Common Terminology Criteria for Adverse Events (CTCAE)

1. CTCAE 4.03

Common Terminology Criteria for

Adverse Events (CTCAE)

Version 4.0

Published: May 28, 2009 (v4.03: June 14, 2010)

U.S.DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health

National Cancer Institute

__________

† CTCAE v4.0 incorporates certain elements of the MedDRA terminology. For further details on MedDRA refer to the MedDRA MSSO Web site (http://www.meddramsso.com).

Common Terminology Criteria for Adverse Events v4.0 (CTCAE)

Publish Date: May 28, 2009

Quick Reference

The NCI Common Terminology Criteria for

Adverse Events is a descriptive terminology which

can be utilized for Adverse Event (AE) reporting.

A grading (severity) scale is provided for each AE

term.

Components and Organization

SOC

System Organ Class, the highest level of the

MedDRA hierarchy, is identified by anatomical or

physiological system, etiology, or purpose (e.g.,

SOC Investigations for laboratory test results).

CTCAE terms are grouped by MedDRA Primary

SOCs. Within each SOC, AEs are listed and

accompanied by descriptions of severity (Grade).

CTCAE Terms

An Adverse Event (AE) is any unfavorable and

unintended sign (including an abnormal

laboratory finding), symptom, or disease

temporally associated with the use of a medical

treatment or procedure that may or may not be

considered related to the medical treatment or

procedure. An AE is a term that is a unique

representation of a specific event used for

medical documentation and scientific analyses.

Each CTCAE v4.0 term is a MedDRA LLT (Lowest

Level Term).

Definitions

A brief definition is provided to clarify the

meaning of each AE term.

Grades

Grade refers to the severity of the AE. The CTCAE

displays Grades 1 through 5 with unique clinical

descriptions of severity for each AE based on this

general guideline:

Grade 1 Mild; asymptomatic or mild

symptoms; clinical or diagnostic

observations only; intervention not

indicated.

Grade 2 Moderate; minimal, local or

noninvasive intervention indicated;

limiting age-appropriate

instrumental ADL*.

Grade 3 Severe or medically significant but

not immediately life-threatening;

hospitalization or prolongation of

hospitalization indicated; disabling;

limiting self care ADL**.

Grade 4 Life-threatening consequences;

urgent intervention indicated.

Grade 5 Death related to AE.

A Semi-colon indicates ‘or’ within the description

of the grade.

A single dash (-) indicates a grade is not available.

Not all Grades are appropriate for all AEs.

Therefore, some AEs are listed with fewer than

five options for Grade selection.

Grade 5

Grade 5 (Death) is not appropriate for some AEs

and therefore is not an option.

Activities of Daily Living (ADL)

*Instrumental ADL refer to preparing meals,

shopping for groceries or clothes, using the

telephone, managing money, etc.

**Self care ADL refer to bathing, dressing and

undressing, feeding self, using the toilet, taking

medications, and not bedridden.

CONTENTS

SOC

Page

Blood and lymphatic system disorders 3

Cardiac disorders 4

Congenital, familial and genetic disorders 7

Ear and labyrinth disorders 8

Endocrine disorders 9

Eye disorders 10

Gastrointestinal disorders 12

General disorders and administration site conditions 22

Hepatobiliary disorders 24

Immune system disorders 26

Infections and infestations 27

Injury, poisoning and procedural complications 34

Investigations 41

Metabolism and nutrition disorders 44

Musculoskeletal and connective tissue disorders 46

Neoplasms benign, malignant and unspecified (incl cysts and polyps) 50

Nervous system disorders 51

Pregnancy, puerperium and perinatal conditions 56

Psychiatric disorders 57

Renal and urinary disorders 59

Reproductive system and breast disorders 61

Respiratory, thoracic and mediastinal disorders 65

Skin and subcutaneous tissue disorders 71

Social circumstances 75

Surgical and medical procedures 76

Vascular disorders 77

CTCAE 4.03 - June 14, 2010 : Blood and lymphatic system disorders

2. Blood and lymphatic system disorders

Blood and lymphatic system disorders

Grade

Adverse Event 1 2 3 4 5

Anemia Hemoglobin (Hgb) <LLN - 10.0

g/dL; <LLN - 6.2 mmol/L; <LLN -

100 g/L

Hgb <10.0 - 8.0 g/dL; <6.2 - 4.9

mmol/L; <100 - 80g/L

Hgb <8.0 g/dL; <4.9 mmol/L;

<80 g/L; transfusion indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an reduction in the amount of hemoglobin in 100 ml of blood. Signs and symptoms of anemia may include pallor of the skin and mucous

membranes, shortness of breath, palpitations of the heart, soft systolic murmurs, lethargy, and fatigability.

Bone marrow hypocellular Mildly hypocellular or <=25%

reduction from normal cellularity

for age

Moderately hypocellular or >25 -

<50% reduction from normal

cellularity for age

Severely hypocellular or >50 -

<=75% reduction cellularity from

normal for age

Aplastic persistent for longer

than 2 weeks

Death

Definition: A disorder characterized by the inability of the bone marrow to produce hematopoietic elements.

Disseminated intravascular

coagulation

- Laboratory findings with no

bleeding

Laboratory findings and

bleeding

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by systemic pathological activation of blood clotting mechanisms which results in clot formation throughout the body. There is an increase in the

risk of hemorrhage as the body is depleted of platelets and coagulation factors.

Febrile neutropenia - - ANC <1000/mm3 with a single

temperature of >38.3 degrees C

(101 degrees F) or a sustained

temperature of >=38 degrees C

(100.4 degrees F) for more than

one hour.

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an ANC <1000/mm3 and a single temperature of >38.3 degrees C (101 degrees F) or a sustained temperature of >=38 degrees C (100.4

degrees F) for more than one hour.

Hemolysis Laboratory evidence of

hemolysis only (e.g., direct

antiglobulin test; DAT; Coombs';

schistocytes; decreased

haptoglobin)

Evidence of hemolysis and >=2

gm decrease in hemoglobin.

Transfusion or medical

intervention indicated (e.g.,

steroids)

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by laboratory test results that indicate widespread erythrocyte cell membrane destruction.

Hemolytic uremic syndrome Evidence of RBC destruction

(schistocytosis) without clinical

consequences

- Laboratory findings with clinical

consequences (e.g., renal

insufficiency, petechiae)

Life-threatening consequences,

(e.g., CNS hemorrhage or

thrombosis/embolism or renal

failure)

Death

Definition: A disorder characterized by a form of thrombotic microangiopathy with renal failure, hemolytic anemia, and severe thrombocytopenia.

Leukocytosis - - >100,000/mm3 Clinical manifestations of

leucostasis; urgent intervention

indicated

Death

Definition: A disorder characterized by laboratory test results that indicate an increased number of white blood cells in the blood.

Lymph node pain Mild pain Moderate pain; limiting

instrumental ADL

Severe pain; limiting self care

ADL

- -

Definition: A disorder characterized by a sensation of marked discomfort in a lymph node.

Spleen disorder Incidental findings (e.g., Howell-

Jolly bodies); mild degree of

thrombocytosis and

leukocytosis

Prophylactic antibiotics

indicated

- Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder of the spleen.

Thrombotic thrombocytopenic

purpura

Evidence of RBC destruction

(schistocytosis) without clinical

consequences

- Laboratory findings with clinical

consequences (e.g., renal

insufficiency, petechiae)

Life-threatening consequences,

(e.g., CNS hemorrhage or

thrombosis/embolism or renal

failure)

Death

Definition: A disorder characterized by the presence of microangiopathic hemolytic anemia, thrombocytopenic purpura, fever, renal abnormalities and neurological abnormalities such

as seizures, hemiplegia, and visual disturbances. It is an acute or subacute condition.

Blood and lymphatic system

disorders - Other, specify

Asymptomatic or mild

symptoms; clinical or diagnostic

observations only; intervention

not indicated

Moderate; minimal, local or

noninvasive intervention

indicated; limiting age-

appropriate instrumental ADL

Severe or medically significant

but not immediately life-

threatening; hospitalization or

prolongation of existing

hospitalization indicated;

disabling; limiting self care ADL

Life-threatening consequences;

urgent intervention indicated

Death

CTCAE 4.03 - June 14, 2010 : Cardiac disorders

3. Cardiac disorders

Cardiac disorders

Grade

Adverse Event 1 2 3 4 5

Acute coronary syndrome - Symptomatic, progressive

angina; cardiac enzymes

normal; hemodynamically stable

Symptomatic, unstable angina

and/or acute myocardial

infarction, cardiac enzymes

abnormal, hemodynamically

stable

Symptomatic, unstable angina

and/or acute myocardial

infarction, cardiac enzymes

abnormal, hemodynamically

unstable

Death

Definition: A disorder characterized by signs and symptoms related to acute ischemia of the myocardium secondary to coronary artery disease. The clinical presentation covers a

spectrum of heart diseases from unstable angina to myocardial infarction.

Aortic valve disease Asymptomatic valvular

thickening with or without mild

valvular regurgitation or

stenosis by imaging

Asymptomatic; moderate

regurgitation or stenosis by

imaging

Symptomatic; severe

regurgitation or stenosis by

imaging; symptoms controlled

with medical intervention

Life-threatening consequences;

urgent intervention indicated

(e.g., valve replacement,

valvuloplasty)

Death

Definition: A disorder characterized by a defect in aortic valve function or structure.

Asystole Periods of asystole; non-urgent

medical management indicated

- - Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by a dysrhythmia without cardiac electrical activity. Typically, this is accompanied by cessation of the pumping function of the heart.

Atrial fibrillation Asymptomatic, intervention not

indicated

Non-urgent medical intervention

indicated

Symptomatic and incompletely

controlled medically, or

controlled with device (e.g.,

pacemaker), or ablation

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by a dysrhythmia without discernible P waves and an irregular ventricular response due to multiple reentry circuits. The rhythm disturbance

originates above the ventricles.

Atrial flutter Asymptomatic, intervention not

indicated

Non-urgent medical intervention

indicated

Symptomatic and incompletely

controlled medically, or

controlled with device (e.g.,

pacemaker), or ablation

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by a dysrhythmia with organized rhythmic atrial contractions with a rate of 200-300 beats per minute. The rhythm disturbance originates in the

atria.

Atrioventricular block complete - Non-urgent intervention

indicated

Symptomatic and incompletely

controlled medically, or

controlled with device (e.g.,

pacemaker)

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by a dysrhythmia with complete failure of atrial electrical impulse conduction through the AV node to the ventricles.

Atrioventricular block first

degree

Asymptomatic, intervention not

indicated

Non-urgent intervention

indicated

- - -

Definition: A disorder characterized by a dysrhythmia with a delay in the time required for the conduction of an electrical impulse through the atrioventricular (AV) node beyond 0.2

seconds; prolongation of the PR interval greater than 200 milliseconds.

Cardiac arrest - - - Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by cessation of the pumping function of the heart.

Chest pain - cardiac Mild pain Moderate pain; limiting

instrumental ADL

Pain at rest; limiting self care

ADL

- -

Definition: A disorder characterized by substernal discomfort due to insufficient myocardial oxygenation.

Conduction disorder Mild symptoms; intervention not

indicated

Moderate symptoms Severe symptoms; intervention

indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by pathological irregularities in the cardiac conduction system.

Constrictive pericarditis - - Symptomatic heart failure or

other cardiac symptoms,

responsive to intervention

Refractory heart failure or other

poorly controlled cardiac

symptoms

Death

Definition: A disorder characterized by a thickened and fibrotic pericardial sac; these fibrotic changes impede normal myocardial function by restricting myocardial muscle action.

Heart failure Asymptomatic with laboratory

(e.g., BNP [B-Natriuretic

Peptide ]) or cardiac imaging

abnormalities

Symptoms with mild to

moderate activity or exertion

Severe with symptoms at rest or

with minimal activity or exertion;

intervention indicated

Life-threatening consequences;

urgent intervention indicated

(e.g., continuous IV therapy or

mechanical hemodynamic

support)

Death

Definition: A disorder characterized by the inability of the heart to pump blood at an adequate volume to meet tissue metabolic requirements, or, the ability to do so only at an elevation

in the filling pressure.

CTCAE 4.03 - June 14, 2010 : Cardiac disorders

Cardiac disorders

Grade

Adverse Event 1 2 3 4 5

Left ventricular systolic

dysfunction

- - Symptomatic due to drop in

ejection fraction responsive to

intervention

Refractory or poorly controlled

heart failure due to drop in

ejection fraction; intervention

such as ventricular assist

device, intravenous vasopressor

support, or heart transplant

indicated

Death

Definition: A disorder characterized by failure of the left ventricle to produce adequate output despite an increase in distending pressure and in end-diastolic volume. Clinical

manifestations mayinclude dyspnea, orthopnea, and other signs and symptoms of pulmonary congestion and edema.

Mitral valve disease Asymptomatic valvular

thickening with or without mild

valvular regurgitation or

stenosis by imaging

Asymptomatic; moderate

regurgitation or stenosis by

imaging

Symptomatic; severe

regurgitation or stenosis by

imaging; symptoms controlled

with medical intervention

Life-threatening consequences;

urgent intervention indicated

(e.g., valve replacement,

valvuloplasty)

Death

Definition: A disorder characterized by a defect in mitral valve function or structure.

Mobitz (type) II atrioventricular

block

Asymptomatic, intervention not

indicated

Symptomatic; medical

intervention indicated

Symptomatic and incompletely

controlled medically, or

controlled with device (e.g.,

pacemaker)

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by a dysrhythmia with relatively constant PR interval prior to the block of an atrial impulse. This is the result of intermittent failure of atrial electrical

impulse conduction through the atrioventricular (AV) node to the ventricles.

Mobitz type I Asymptomatic, intervention not

indicated

Symptomatic; medical

intervention indicated

Symptomatic and incompletely

controlled medically, or

controlled with device (e.g.,

pacemaker)

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by a dysrhythmia with a progressively lengthening PR interval prior to the blocking of an atrial impulse. This is the result of intermittent failure of

atrial electrical impulse conduction through the atrioventricular (AV) node to the ventricles.

Myocardial infarction - Asymptomatic and cardiac

enzymes minimally abnormal

and no evidence of ischemic

ECG changes

Severe symptoms; cardiac

enzymes abnormal;

hemodynamically stable; ECG

changes consistent with

infarction

Life-threatening consequences;

hemodynamically unstable

Death

Definition: A disorder characterized by gross necrosis of the myocardium; this is due to an interruption of blood supply to the area.

Myocarditis Asymptomatic with laboratory

(e.g., BNP [B-Natriuretic

Peptide ]) or cardiac imaging

abnormalities

Symptoms with mild to

moderate activity or exertion

Severe with symptoms at rest or

with minimal activity or exertion;

intervention indicated

Life-threatening consequences;

urgent intervention indicated

(e.g., continuous IV therapy or

mechanical hemodynamic

support)

Death

Definition: A disorder characterized by inflammation of the muscle tissue of the heart.

Palpitations Mild symptoms; intervention not

indicated

Intervention indicated - - -

Definition: A disorder characterized by an unpleasant sensation of irregular and/or forceful beating of the heart.

Paroxysmal atrial tachycardia Asymptomatic, intervention not

indicated

Symptomatic; medical

management indicated

IV medication indicated Life-threatening consequences;

incompletely controlled

medically; cardioversion

indicated

Death

Definition: A disorder characterized by a dysrhythmia with abrupt onset and sudden termination of atrial contractions with a rate of 150-250 beats per minute. The rhythm disturbance

originates in the atria.

Pericardial effusion - Asymptomatic effusion size

small to moderate

Effusion with physiologic

consequences

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by fluid collection within the pericardial sac, usually due to inflammation.

Pericardial tamponade - - - Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an increase in intrapericardial pressure due to the collection of blood or fluid in the pericardium.

Pericarditis Asymptomatic, ECG or physical

findings (e.g., rub) consistent

with pericarditis

Symptomatic pericarditis (e.g.,

chest pain)

Pericarditis with physiologic

consequences (e.g., pericardial

constriction)

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by irritation to the layers of the pericardium (the protective sac around the heart).

CTCAE 4.03 - June 14, 2010 : Cardiac disorders

Cardiac disorders

Grade

Adverse Event 1 2 3 4 5

Pulmonary valve disease Asymptomatic valvular

thickening with or without mild

valvular regurgitation or

stenosis by imaging

Asymptomatic; moderate

regurgitation or stenosis by

imaging

Symptomatic; severe

regurgitation or stenosis by

imaging; symptoms controlled

with medical intervention

Life-threatening consequences;

urgent intervention indicated

(e.g., valve replacement,

valvuloplasty)

Death

Definition: A disorder characterized by a defect in pulmonary valve function or structure.

Restrictive cardiomyopathy - - Symptomatic heart failure or

other cardiac symptoms,

responsive to intervention

Refractory heart failure or other

poorly controlled cardiac

symptoms

Death

Definition: A disorder characterized by an inability of the ventricles to fill with blood because the myocardium (heart muscle) stiffens and loses its flexibility.

Right ventricular dysfunction Asymptomatic with laboratory

(e.g., BNP [B-Natriuretic

Peptide ]) or cardiac imaging

abnormalities

Symptoms with mild to

moderate activity or exertion

Severe symptoms, associated

with hypoxemia, right heart

failure; oxygen indicated

Life-threatening consequences;

urgent intervention indicated

(e.g., ventricular assist device);

heart transplant indicated

Death

Definition: A disorder characterized by impairment of right ventricular function associated with low ejection fraction and a decrease in motility of the right ventricular wall.

Sick sinus syndrome Asymptomatic, intervention not

indicated

Non-urgent intervention

indicated

Severe, medically significant;

medical intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by a dysrhythmia with alternating periods of bradycardia and atrial tachycardia accompanied by syncope, fatigue and dizziness.

Sinus bradycardia Asymptomatic, intervention not

indicated

Symptomatic, medical

intervention indicated

Severe, medically significant,

medical intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by a dysrhythmia with a heart rate less than 60 beats per minute that originates in the sinus node.

Sinus tachycardia Asymptomatic, intervention not

indicated

Symptomatic; non-urgent

medical intervention indicated

Urgent medical intervention

indicated

- -

Definition: A disorder characterized by a dysrhythmia with a heart rate greater than 100 beats per minute that originates in the sinus node.

Supraventricular tachycardia Asymptomatic, intervention not

indicated

Non-urgent medical intervention

indicated

Medical intervention indicated Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by a dysrhythmia with a heart rate greater than 100 beats per minute that originates above the ventricles.

Tricuspid valve disease Asymptomatic valvular

thickening with or without mild

valvular regurgitation or

stenosis

Asymptomatic; moderate

regurgitation or stenosis by

imaging

Symptomatic; severe

regurgitation or stenosis;

symptoms controlled with

medical intervention

Life-threatening consequences;

urgent intervention indicated

(e.g., valve replacement,

valvuloplasty)

Death

Definition: A disorder characterized by a defect in tricuspid valve function or structure.

Ventricular arrhythmia Asymptomatic, intervention not

indicated

Non-urgent medical intervention

indicated

Medical intervention indicated Life-threatening consequences;

hemodynamic compromise;

urgent intervention indicated

Death

Definition: A disorder characterized by a dysrhythmia that originates in the ventricles.

Ventricular fibrillation - - - Life-threatening consequences;

hemodynamic compromise;

urgent intervention indicated

Death

Definition: A disorder characterized by a dysrhythmia without discernible QRS complexes due to rapid repetitive excitation of myocardial fibers without coordinated contraction of the

ventricles.

Ventricular tachycardia - Non-urgent medical intervention

indicated

Medical intervention indicated Life-threatening consequences;

hemodynamic compromise;

urgent intervention indicated

Death

Definition: A disorder characterized by a dysrhythmia with a heart rate greater than 100 beats per minute that originates distal to the bundle of His.

Wolff-Parkinson-White

syndrome

Asymptomatic, intervention not

indicated

Non-urgent medical intervention

indicated

Symptomatic and incompletely

controlled medically or

controlled with procedure

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by the presence of an accessory conductive pathway between the atria and the ventricles that causes premature ventricular activation.

Cardiac disorders - Other,

specify

Asymptomatic or mild

symptoms; clinical or diagnostic

observations only; intervention

not indicated

Moderate; minimal, local or

noninvasive intervention

indicated; limiting age-

appropriate instrumental ADL

Severe or medically significant

but not immediately life-

threatening; hospitalization or

prolongation of existing

hospitalization indicated;

disabling; limiting self care ADL

Life-threatening consequences;

urgent intervention indicated

Death

CTCAE 4.03 - June 14, 2010 : Congenital, familial and genetic disorders

4. Congenital, familial and genetic disorders

Congenital, familial and genetic disorders

Grade

Adverse Event 1 2 3 4 5

Congenital, familial and genetic

disorders - Other, specify

Asymptomatic or mild

symptoms; clinical or diagnostic

observations only; intervention

not indicated

Moderate; minimal, local or

noninvasive intervention

indicated; limiting age-

appropriate instrumental ADL

Severe or medically significant

but not immediately life-

threatening; hospitalization or

prolongation of existing

hospitalization indicated;

disabling; limiting self care ADL

Life-threatening consequences;

urgent intervention indicated

Death

CTCAE 4.03 - June 14, 2010 : Ear and labyrinth disorders

5. Ear and labyrinth disorders

Ear and labyrinth disorders

Grade

Adverse Event 1 2 3 4 5

Ear pain Mild pain Moderate pain; limiting

instrumental ADL

Severe pain; limiting self care

ADL

- -

Definition: A disorder characterized by a sensation of marked discomfort in the ear.

External ear inflammation External otitis with erythema or

dry desquamation

External otitis with moist

desquamation, edema,

enhanced cerumen or

discharge; tympanic membrane

perforation; tympanostomy

External otitis with mastoiditis;

stenosis or osteomyelitis;

necrosis of soft tissue or bone

Urgent operative intervention

indicated

Death

Definition: A disorder characterized by inflammation, swelling and redness to the outer ear and ear canal.

External ear pain Mild pain Moderate pain; limiting

instrumental ADL

Severe pain; limiting self care

ADL

- -

Definition: A disorder characterized by a sensation of marked discomfort in the external ear region.

Hearing impaired Adults enrolled on a Monitoring

Program (on a 1, 2, 3, 4, 6 and

8 kHz audiogram): Threshold

shift of 15 - 25 dB averaged at 2

contiguous test frequencies in at

least one ear.

Adults not enrolled in Monitoring

Program: subjective change in

hearing in the absence of

documented hearing loss.

Pediatric (on a 1, 2, 3, 4, 6 and

8 kHz audiogram): Threshold

shift >20 dB at 8 kHz in at least

one ear.

Adults enrolled in Monitoring

Program (on a 1, 2, 3, 4, 6 and

8 kHz audiogram): Threshold

shift of >25 dB averaged at 2

contiguous test frequencies in at

least one ear.

Adults not enrolled in Monitoring

Program: hearing loss but

hearing aid or intervention not

indicated; limiting instrumental

ADL.

Pediatric (on a 1, 2, 3, 4, 6 and

8 kHz audiogram): Threshold

shift >20 dB at 4 kHz and above

in at least one ear.

Adults enrolled in Monitoring

Program (on a 1, 2, 3, 4, 6 and

8 kHz audiogram): Threshold

shift of >25 dB averaged at 3

contiguous test frequencies in at

least one ear; therapeutic

intervention indicated.

Adults not enrolled in Monitoring

Program: hearing loss with

hearing aid or intervention

indicated; limiting self care ADL.

Pediatric (on a 1, 2, 3, 4, 6 and

8 kHz audiogram): hearing loss

sufficient to indicate therapeutic

intervention, including hearing

aids; threshold shift >20 dB at 3

kHz and above in at least one

ear; additional speech-language

related services indicated.

Adults: Decrease in hearing to

profound bilateral loss (absolute

threshold >80 dB HL at 2 kHz

and above); non-servicable

hearing.

Pediatric: Audiologic indication

for cochlear implant and

additional speech-language

related services indicated.

Definition: A disorder characterized by partial or complete loss of the ability to detect or understand sounds resulting from damage to ear structures.

Middle ear inflammation Serous otitis Serous otitis, medical

intervention indicated

Mastoiditis; necrosis of canal

soft tissue or bone

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by inflammation (physiologic response to irritation), swelling and redness to the middle ear.

Tinnitus Mild symptoms; intervention not

indicated

Moderate symptoms; limiting

instrumental ADL

Severe symptoms; limiting self

care ADL

- -

Definition: A disorder characterized by noise in the ears, such as ringing, buzzing, roaring or clicking.

Vertigo Mild symptoms Moderate symptoms; limiting

instrumental ADL

Severe symptoms; limiting self

care ADL

- -

Definition: A disorder characterized by a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective

vertigo).

Vestibular disorder - Symptomatic; limiting

instrumental ADL

Severe symptoms; limiting self

care ADL

- -

Definition: A disorder characterized by dizziness, imbalance, nausea, and vision problems.

Ear and labyrinth disorders -

Other, specify

Asymptomatic or mild

symptoms; clinical or diagnostic

observations only; intervention

not indicated

Moderate; minimal, local or

noninvasive intervention

indicated; limiting age-

appropriate instrumental ADL

Severe or medically significant

but not immediately life-

threatening; hospitalization or

prolongation of existing

hospitalization indicated;

disabling; limiting self care ADL

Life-threatening consequences;

urgent intervention indicated

Death

CTCAE 4.03 - June 14, 2010 : Endocrine disorders

6. Endocrine disorders

Endocrine disorders

Grade

Adverse Event 1 2 3 4 5

Adrenal insufficiency Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Moderate symptoms; medical

intervention indicated

Severe symptoms;

hospitalization indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder that occurs when the adrenal cortex does not produce enough of the hormone cortisol and in some cases, the hormone aldosterone. It may be due to a disorder

of the adrenal cortex as in Addison's disease or primary adrenal insufficiency.

Cushingoid Mild symptoms; intervention not

indicated

Moderate symptoms; medical

intervention indicated

Severe symptoms, medical

intervention or hospitalization

indicated

- -

Definition: A disorder characterized by signs and symptoms that resemble Cushing's disease or syndrome: buffalo hump obesity, striations, adiposity, hypertension, diabetes, and

osteoporosis, usually due to exogenous corticosteroids.

Delayed puberty - No breast development by age

13 yrs for females; testes

volume of <3 cc or no Tanner

Stage 2 development by age

14.5 yrs for males

No breast development by age

14 yrs for females; no increase

in testes volume or no Tanner

Stage 2 by age 16 yrs for

males; hormone replacement

indicated

- -

Definition: A disorder characterized by unusually late sexual maturity.

Growth accelerated - >= +2 SD (standard deviation)

above mid parental height or

target height

- - -

Definition: A disorder characterized by greater growth than expected for age.

Hyperparathyroidism Mild symptoms; intervention not

indicated

Moderate symptoms; medical

intervention indicated

- - -

Definition: A disorder characterized by an increase in production of parathyroid hormone by the parathyroid glands. This results in hypercalcemia (abnormally high levels of calcium in

the blood).

Hyperthyroidism Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; thyroid

suppression therapy indicated;

limiting instrumental ADL

Severe symptoms; limiting self

care ADL; hospitalization

indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by excessive levels of thyroid hormone in the body. Common causes include an overactive thyroid gland or thyroid hormone overdose.

Hypoparathyroidism Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Moderate symptoms; medical

intervention indicated

Severe symptoms; medical

intervention or hospitalization

indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by a decrease in production of parathyroid hormone by the parathyroid glands.

Hypothyroidism Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; thyroid

replacement indicated; limiting

instrumental ADL

Severe symptoms; limiting self

care ADL; hospitalization

indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by a decrease in production of thyroid hormone by the thyroid gland.

Precocious puberty Physical signs of puberty with

no biochemical markers for

females <8 years and males <9

years

Physical signs and biochemical

markers of puberty for females

<8 years and males <9 years

- - -

Definition: A disorder characterized by unusually early development of secondary sexual features; the onset of sexual maturation begins usually before age 8 for girls and before age

9 for boys.

Virilization Mild symptoms; intervention not

indicated

Moderate symptoms; medical

intervention indicated

- - -

Definition: A disorder characterized by inappropriate masculinization occurring in a female or prepubertal male.

Endocrine disorders - Other,

specify

Asymptomatic or mild

symptoms; clinical or diagnostic

observations only; intervention

not indicated

Moderate; minimal, local or

noninvasive intervention

indicated; limiting age-

appropriate instrumental ADL

Severe or medically significant

but not immediately life-

threatening; hospitalization or

prolongation of existing

hospitalization indicated;

disabling; limiting self care ADL

Life-threatening consequences;

urgent intervention indicated

Death

CTCAE 4.03 - June 14, 2010 : Eye disorders

7. Eye disorders

Eye disorders

Grade

Adverse Event 1 2 3 4 5

Blurred vision Intervention not indicated Symptomatic; limiting

instrumental ADL

Limiting self care ADL - -

Definition: A disorder characterized by visual perception of unclear or fuzzy images.

Cataract Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; moderate

decrease in visual acuity

(20/40 or better)

Symptomatic with marked

decrease in visual acuity

(worse than 20/40 but better

than 20/200); operative

intervention indicated (e.g.,

cataract surgery)

Blindness (20/200 or worse)

in the affected eye

Definition: A disorder characterized by partial or complete opacity of the crystalline lens of one or both eyes. This results in a decrease in visual acuity and eventual blindness if

untreated.

Conjunctivitis Asymptomatic or mild

symptoms; intervention not

indicated

Symptomatic; topical

intervention indicated (e.g.,

antibiotics); limiting

instrumental ADL

Limiting self care ADL - -

Definition: A disorder characterized by inflammation, swelling and redness to the conjunctiva of the eye.

Corneal ulcer - Symptomatic; medical

intervention indicated (e.g.,

topical agents); limiting

instrumental ADL

Limiting self care ADL;

declining vision (worse than

20/40 but better than 20/200)

Perforation or blindness

(20/200 or worse) in the

affected eye

Definition: A disorder characterized by an area of epithelial tissue loss on the surface of the cornea. It is associated with inflammatory cells in the cornea and anterior chamber.

Dry eye Asymptomatic; clinical or

diagnostic observations only;

mild symptoms relieved by

lubricants

Symptomatic; multiple

agents indicated; limiting

instrumental ADL

Decrease in visual acuity

(<20/40); limiting self care

ADL

- -

Definition: A disorder characterized by dryness of the cornea and conjunctiva.

Extraocular muscle paresis Asymptomatic; clinical or

diagnostic observations only

Symptomatic; limiting

instrumental ADL

Limiting self care ADL;

disabling

- -

Definition: A disorder characterized by incomplete paralysis of an extraocular muscle.

Eye pain Mild pain Moderate pain; limiting

instrumental ADL

Severe pain; limiting self

care ADL

- -

Definition: A disorder characterized by a sensation of marked discomfort in the eye.

Eyelid function disorder Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; nonoperative

intervention indicated;

limiting instrumental ADL

Limiting self care ADL;

operative intervention

indicated

- -

Definition: A disorder characterized by impaired eyelid function.

Flashing lights Symptomatic but not limiting

ADL

Limiting instrumental ADL Limiting self care ADL - -

Definition: A disorder characterized by a sudden or brief burst of light.

Floaters Symptomatic but not limiting

ADL

Limiting instrumental ADL Limiting self care ADL - -

Definition: A disorder characterized by an individual seeing spots before their eyes. The spots are shadows of opaque cell fragments in the vitreous humor or lens.

Glaucoma Elevated intraocular

pressure (EIOP) with single

topical agent for intervention;

no visual field deficit

EIOP causing early visual

field deficits; multiple topical

or oral agents indicated;

limiting instrumental ADL

EIOP causing marked visual

field deficits (e.g., involving

both superior and inferior

visual fields); operative

intervention indicated;

limiting self care ADL

Blindness (20/200 or worse)

in the affected eye

Definition: A disorder characterized by an increase in pressure in the eyeball due to obstruction of the aqueous humor outflow.

Keratitis - Symptomatic; medical

intervention indicated (e.g.,

topical agents); limiting

instrumental ADL

Decline in vision (worse than

20/40 but better than

20/200); limiting self care

ADL

Perforation or blindness

(20/200 or worse) in the

affected eye

Definition: A disorder characterized by inflammation to the cornea of the eye.

Night blindness Symptomatic but not limiting

ADL

Limiting instrumental ADL Limiting self care ADL Blindness (20/200 or worse)

in the affected eye

Definition: A disorder characterized by an inability to see clearly in dim light.

CTCAE 4.03 - June 14, 2010 : Eye disorders

Eye disorders

Grade

Adverse Event 1 2 3 4 5

Optic nerve disorder Asymptomatic; clinical or

diagnostic observations only

Limiting vision of the affected

eye (20/40 or better)

Limiting vision in the affected

eye (worse than 20/40 but

better than 20/200)

Blindness (20/200 or worse)

in the affected eye

Definition: A disorder characterized by involvement of the optic nerve (second cranial nerve).

Papilledema Asymptomatic; no visual field

defects

Symptomatic decline in

vision; visual field defect

present sparing the central

20 degrees

Marked visual field defect

(worse than 20/40 but better

than 20/200)

Blindness (20/200 or worse)

in the affected eye

Definition: A disorder characterized by swelling around the optic disc.

Photophobia Symptomatic but not limiting

ADL

Limiting instrumental ADL Limiting self care ADL - -

Definition: A disorder characterized by fear and avoidance of light.

Retinal detachment Asymptomatic Exudative and visual acuity

20/40 or better

Rhegmatogenous or

exudative detachment;

operative intervention

indicated; decline in vision

(worse than 20/40 but better

than 20/200)

Blindness (20/200 or worse)

in the affected eye

Definition: A disorder characterized by the separation of the inner retina layers from the underlying pigment epithelium.

Retinal tear - Laser therapy or

pneumopexy indicated

Vitroretinal surgical repair

indicated

Blindness (20/200 or worse)

in the affected eye

Definition: A disorder characterized by a small laceration of the retina, this occurs when the vitreous separates from the retina. Symptoms include flashes and floaters.

Retinal vascular disorder - Topical medication indicated Intravitreal medication;

operative intervention

indicated

- -

Definition: A disorder characterized by pathological retinal blood vessels that adversely affects vision.

Retinopathy Asymptomatic; clinical or

diagnostic observations only

Symptomatic with moderate

decrease in visual acuity

(20/40 or better); limiting

instrumental ADL

Symptomatic with marked

decrease in visual acuity

(worse than 20/40);

disabling; limiting self care

ADL

Blindness (20/200 or worse)

in the affected eye

Definition: A disorder involving the retina.

Scleral disorder Asymptomatic; clinical or

diagnostic observations only

Symptomatic, limiting

instrumental ADL; moderate

decrease in visual acuity

(20/40 or better)

Symptomatic, limiting self

care ADL; marked decrease

in visual acuity (worse than

20/40)

Blindness (20/200 or worse)

in the affected eye

Definition: A disorder characterized by involvement of the sclera of the eye.

Uveitis Asymptomatic; clinical or

diagnostic observations only

Anterior uveitis; medical

intervention indicated

Posterior or pan-uveitis Blindness (20/200 or worse)

in the affected eye

Definition: A disorder characterized by inflammation to the uvea of the eye.

Vitreous hemorrhage Asymptomatic or mild

symptoms; clinical or

diagnostic observations only

Symptomatic; limiting

instrumental ADL

Limiting self care ADL;

vitrectomy indicated

Blindness (20/200 or worse)

in the affected eye

Definition: A disorder characterized by blood extravasation into the vitreous humor.

Watering eyes Intervention not indicated Intervention indicated Operative intervention

indicated

- -

Definition: A disorder of excessive tearing in the eyes; it can be caused by overproduction of tears or impaired drainage of the tear duct.

Eye disorders - Other,

specify

Asymptomatic or mild

symptoms; clinical or

diagnostic observations only;

intervention not indicated

Moderate; minimal, local or

noninvasive intervention

indicated; limiting age-

appropriate instrumental

ADL

Severe or medically

significant but not

immediately sight-

threatening; hospitalization

or prolongation of existing

hospitalization indicated;

disabling; limiting self care

ADL

Sight-threatening

consequences; urgent

intervention indicated;

blindness (20/200 or worse)

in the affected eye

CTCAE 4.03 - June 14, 2010 : Gastrointestinal disorders

8. Gastrointestinal disorders

Gastrointestinal disorders

Grade

Adverse Event 1 2 3 4 5

Abdominal distension Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; limiting

instrumental ADL

Severe discomfort; limiting self

care ADL

- -

Definition: A disorder characterized by swelling of the abdomen.

Abdominal pain Mild pain Moderate pain; limiting

instrumental ADL

Severe pain; limiting self care

ADL

- -

Definition: A disorder characterized by a sensation of marked discomfort in the abdominal region.

Anal fistula Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; altered GI

function

Severely altered GI function;

tube feeding, TPN or

hospitalization indicated;

elective operative intervention

indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an abnormal communication between the opening in the anal canal to the perianal skin.

Anal hemorrhage Mild; intervention not indicated Moderate symptoms; medical

intervention or minor

cauterization indicated

Transfusion, radiologic,

endoscopic, or elective

operative intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by bleeding from the anal region.

Anal mucositis Asymptomatic or mild

symptoms; intervention not

indicated

Symptomatic; medical

intervention indicated; limiting

instrumental ADL

Severe symptoms; limiting self

care ADL

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by inflammation of the mucous membrane of the anus.

Anal necrosis - - TPN or hospitalization indicated;

radiologic, endoscopic, or

operative intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by a necrotic process occurring in the anal region.

Anal pain Mild pain Moderate pain; limiting

instrumental ADL

Severe pain; limiting self care

ADL

- -

Definition: A disorder characterized by a sensation of marked discomfort in the anal region.

Anal stenosis Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; altered GI

function

Symptomatic and severely

altered GI function; non-

emergent operative intervention

indicated; TPN or hospitalization

indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by a narrowing of the lumen of the anal canal.

Anal ulcer Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; altered GI

function

Severely altered GI function;

TPN indicated; elective

operative or endoscopic

intervention indicated; disabling

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by a circumscribed, inflammatory and necrotic erosive lesion on the mucosal surface of the anal canal.

Ascites Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; medical

intervention indicated

Severe symptoms; invasive

intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by accumulation of serous or hemorrhagic fluid in the peritoneal cavity.

Bloating No change in bowel function or

oral intake

Symptomatic, decreased oral

intake; change in bowel function

- - -

Definition: A disorder characterized by subject-reported feeling of uncomfortable fullness of the abdomen.

Cecal hemorrhage Mild; intervention not indicated Moderate symptoms; medical

intervention or minor

cauterization indicated

Transfusion, radiologic,

endoscopic, or elective

operative intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by bleeding from the cecum.

Cheilitis Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Moderate symptoms; limiting

instrumental ADL

Severe symptoms; limiting self

care ADL; intervention indicated

- -

Definition: A disorder characterized by inflammation of the lip.

CTCAE 4.03 - June 14, 2010 : Gastrointestinal disorders

Gastrointestinal disorders

Grade

Adverse Event 1 2 3 4 5

Colitis Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Abdominal pain; mucus or blood

in stool

Severe abdominal pain; change

in bowel habits; medical

intervention indicated;

peritoneal signs

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by inflammation of the colon.

Colonic fistula Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; altered GI

function

Severely altered GI function;

bowel rest, TPN or

hospitalization indicated;

elective operative intervention

indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an abnormal communication between the large intestine and another organ or anatomic site.

Colonic hemorrhage Mild; intervention not indicated Moderate symptoms; medical

intervention or minor

cauterization indicated

Transfusion, radiologic,

endoscopic, or elective

operative intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by bleeding from the colon.

Colonic obstruction Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; altered GI

function

Hospitalization indicated;

elective operative intervention

indicated; disabling

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by blockage of the normal flow of the intestinal contents in the colon.

Colonic perforation - Symptomatic; medical

intervention indicated

Severe symptoms; elective

operative intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by a rupture in the colonic wall.

Colonic stenosis Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; altered GI

function

Severely altered GI function;

tube feeding or hospitalization

indicated; elective operative

intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by a narrowing of the lumen of the colon.

Colonic ulcer Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; altered GI

function

Severely altered GI function;

TPN indicated; elective

operative or endoscopic

intervention indicated; disabling

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by a circumscribed, inflammatory and necrotic erosive lesion on the mucosal surface of the colon.

Constipation Occasional or intermittent

symptoms; occasional use of

stool softeners, laxatives,

dietary modification, or enema

Persistent symptoms with

regular use of laxatives or

enemas; limiting instrumental

ADL

Obstipation with manual

evacuation indicated; limiting

self care ADL

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by irregular and infrequent or difficult evacuation of the bowels.

Dental caries One or more dental caries, not

involving the root

Dental caries involving the root Dental caries resulting in pulpitis

or periapical abscess or

resulting in tooth loss

- -

Definition: A disorder characterized by the decay of a tooth, in which it becomes softened, discolored and/or porous.

Diarrhea Increase of <4 stools per day

over baseline; mild increase in

ostomy output compared to

baseline

Increase of 4 - 6 stools per day

over baseline; moderate

increase in ostomy output

compared to baseline

Increase of >=7 stools per day

over baseline; incontinence;

hospitalization indicated; severe

increase in ostomy output

compared to baseline; limiting

self care ADL

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by frequent and watery bowel movements.

Dry mouth Symptomatic (e.g., dry or thick

saliva) without significant dietary

alteration; unstimulated saliva

flow >0.2 ml/min

Moderate symptoms; oral intake

alterations (e.g., copious water,

other lubricants, diet limited to

purees and/or soft, moist foods);

unstimulated saliva 0.1 to 0.2

ml/min

Inability to adequately aliment

orally; tube feeding or TPN

indicated; unstimulated saliva

<0.1 ml/min

- -

Definition: A disorder characterized by reduced salivary flow in the oral cavity.

CTCAE 4.03 - June 14, 2010 : Gastrointestinal disorders

Gastrointestinal disorders

Grade

Adverse Event 1 2 3 4 5

Duodenal fistula Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; altered GI

function

Severely altered GI function;

tube feeding, TPN or

hospitalization indicated;

elective operative intervention

indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an abnormal communication between the duodenum and another organ or anatomic site.

Duodenal hemorrhage Mild; intervention not indicated Moderate symptoms; medical

intervention or minor

cauterization indicated

Transfusion, radiologic,

endoscopic, or elective

operative intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by bleeding from the duodenum.

Duodenal obstruction Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; altered GI

function

Hospitalization or elective

operative intervention indicated;

disabling

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by blockage of the normal flow of stomach contents through the duodenum.

Duodenal perforation - Symptomatic; medical

intervention indicated

Severe symptoms; elective

operative intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by a rupture in the duodenal wall.

Duodenal stenosis Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; altered GI

function

Severely altered GI function;

tube feeding; hospitalization

indicated; elective operative

intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by a narrowing of the lumen of the duodenum.

Duodenal ulcer Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Moderate symptoms; medical

intervention indicated; limiting

instrumental ADL

Severely altered GI function;

TPN indicated; elective

operative or endoscopic

intervention indicated; limiting

self care ADL; disabling

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by a circumscribed, inflammatory and necrotic erosive lesion on the mucosal surface of the duodenal wall.

Dyspepsia Mild symptoms; intervention not

indicated

Moderate symptoms; medical

intervention indicated

Severe symptoms; surgical

intervention indicated

- -

Definition: A disorder characterized by an uncomfortable, often painful feeling in the stomach, resulting from impaired digestion. Symptoms include burning stomach, bloating,

heartburn, nausea and vomiting.

Dysphagia Symptomatic, able to eat

regular diet

Symptomatic and altered

eating/swallowing

Severely altered

eating/swallowing; tube feeding

or TPN or hospitalization

indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by difficulty in swallowing.

Enterocolitis Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Abdominal pain; mucus or blood

in stool

Severe or persistent abdominal

pain; fever; ileus; peritoneal

signs

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by inflammation of the small and large intestines.

Enterovesical fistula Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; noninvasive

intervention indicated

Severe, medically significant;

medical intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an abnormal communication between the urinary bladder and the intestine.

Esophageal fistula Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; altered GI

function

Severely altered GI function;

tube feeding, TPN or

hospitalization indicated;

elective operative intervention

indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an abnormal communication between the esophagus and another organ or anatomic site.

Esophageal hemorrhage Mild; intervention not indicated Moderate symptoms; medical

intervention or minor

cauterization indicated

Transfusion, radiologic,

endoscopic, or elective

operative intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by bleeding from the esophagus.

CTCAE 4.03 - June 14, 2010 : Gastrointestinal disorders

Gastrointestinal disorders

Grade

Adverse Event 1 2 3 4 5

Esophageal necrosis - - Inability to aliment adequately

by GI tract; radiologic,

endoscopic, or operative

intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by a necrotic process occurring in the esophageal wall.

Esophageal obstruction Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; altered GI

function; limiting instrumental

ADL

Hospitalization indicated;

elective operative intervention

indicated; limiting self care ADL;

disabling

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by blockage of the normal flow of the contents in the esophagus.

Esophageal pain Mild pain Moderate pain; limiting

instrumental ADL

Severe pain; limiting self care

ADL

- -

Definition: A disorder characterized by a sensation of marked discomfort in the esophageal region.

Esophageal perforation - Symptomatic; medical

intervention indicated

Severe symptoms; elective

operative intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by a rupture in the wall of the esophagus.

Esophageal stenosis Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; altered GI

function

Severely altered GI function;

tube feeding; hospitalization

indicated; elective operative

intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by a narrowing of the lumen of the esophagus.

Esophageal ulcer Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; altered GI

function; limiting instrumental

ADL

Severely altered GI function;

TPN indicated; elective

operative or endoscopic

intervention indicated; limiting

self care ADL; disabling

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by a circumscribed, inflammatory and necrotic erosive lesion on the mucosal surface of the esophageal wall.

Esophageal varices

hemorrhage

- Self-limited; intervention not

indicated

Transfusion, radiologic,

endoscopic, or elective

operative intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by bleeding from esophageal varices.

Esophagitis Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; altered

eating/swallowing; oral

supplements indicated

Severely altered

eating/swallowing; tube feeding,

TPN or hospitalization indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by inflammation of the esophageal wall.

Fecal incontinence Occasional use of pads required Daily use of pads required Severe symptoms; elective

operative intervention indicated

- -

Definition: A disorder characterized by inability to control the escape of stool from the rectum.

Flatulence Mild symptoms; intervention not

indicated

Moderate; persistent;

psychosocial sequelae

- - -

Definition: A disorder characterized by a state of excessive gas in the alimentary canal.

Gastric fistula Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; altered GI

function

Severely altered GI function;

bowel rest; tube feeding, TPN or

hospitalization indicated;

elective operative intervention

indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by an abnormal communication between the stomach and another organ or anatomic site.

Gastric hemorrhage Mild; intervention not indicated Moderate symptoms; medical

intervention or minor

cauterization indicated

Transfusion, radiologic,

endoscopic, or elective

operative intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by bleeding from the gastric wall.

Gastric necrosis - - Inability to aliment adequately

by GI tract; radiologic,

endoscopic, or operative

intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by a necrotic process occurring in the gastric wall.

CTCAE 4.03 - June 14, 2010 : Gastrointestinal disorders

Gastrointestinal disorders

Grade

Adverse Event 1 2 3 4 5

Gastric perforation - Symptomatic; medical

intervention indicated

Severe symptoms; elective

operative intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by a rupture in the stomach wall.

Gastric stenosis Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; altered GI

function

Severely altered GI function;

tube feeding; hospitalization

indicated; elective operative

intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by a narrowing of the lumen of the stomach.

Gastric ulcer Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; altered GI

function; medical intervention

indicated; limiting instrumental

ADL

Severely altered GI function;

TPN indicated; elective

operative or endoscopic

intervention indicated; limiting

self care ADL; disabling

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by a circumscribed, inflammatory and necrotic erosive lesion on the mucosal surface of the stomach.

Gastritis Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; altered GI

function; medical intervention

indicated

Severely altered eating or

gastric function; TPN or

hospitalization indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by inflammation of the stomach.

Gastroesophageal reflux

disease

Mild symptoms; intervention not

indicated

Moderate symptoms; medical

intervention indicated

Severe symptoms; surgical

intervention indicated

- -

Definition: A disorder characterized by reflux of the gastric and/or duodenal contents into the distal esophagus. It is chronic in nature and usually caused by incompetence of the lower

esophageal sphincter, and may result in injury to the esophageal mucosal. Symptoms include heartburn and acid indigestion.

Gastrointestinal fistula Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; altered GI

function

Severely altered GI function;

tube feeding, TPN or

hospitalization indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by an abnormal communication between any part of the gastrointestinal system and another organ or anatomic site.

Gastrointestinal pain Mild pain Moderate pain; limiting

instrumental ADL

Severe pain; limiting self care

ADL

- -

Definition: A disorder characterized by a sensation of marked discomfort in the gastrointestinal region.

Gastroparesis Mild nausea, early satiety and

bloating, able to maintain caloric

intake on regular diet

Moderate symptoms; able to

maintain nutrition with dietary

and lifestyle modifications; may

need pharmacologic

intervention

Weight loss; refractory to

medical intervention; unable to

maintain nutrition orally

- -

Definition: A disorder characterized by an incomplete paralysis of the muscles of the stomach wall resulting in delayed emptying of the gastric contents into the small intestine.

Gingival pain Mild pain Moderate pain interfering with

oral intake

Severe pain; inability to aliment

orally

- -

Definition: A disorder characterized by a sensation of marked discomfort in the gingival region.

Hemorrhoidal hemorrhage Mild; intervention not indicated Moderate symptoms; medical

intervention or minor

cauterization indicated

Transfusion, radiologic,

endoscopic, or elective

operative intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by bleeding from the hemorrhoids.

Hemorrhoids Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; banding or

medical intervention indicated

Severe symptoms; radiologic,

endoscopic or elective operative

intervention indicated

- -

Definition: A disorder characterized by the presence of dilated veins in the rectum and surrounding area.

Ileal fistula Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; altered GI

function

Severely altered GI function;

TPN or hospitalization indicated;

elective operative intervention

indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an abnormal communication between the ileum and another organ or anatomic site.

Ileal hemorrhage Mild; intervention not indicated Moderate symptoms; medical

intervention or minor

cauterization indicated

Transfusion, radiologic,

endoscopic, or elective

operative intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by bleeding from the ileal wall.

CTCAE 4.03 - June 14, 2010 : Gastrointestinal disorders

Gastrointestinal disorders

Grade

Adverse Event 1 2 3 4 5

Ileal obstruction Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; altered GI

function; limiting instrumental

ADL

Hospitalization indicated;

elective operative intervention

indicated; limiting self care ADL;

disabling

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by blockage of the normal flow of the intestinal contents in the ileum.

Ileal perforation - Symptomatic; medical

intervention indicated

Severe symptoms; elective

operative intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by a rupture in the ileal wall.

Ileal stenosis Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; altered GI

function

Severely altered GI function;

tube feeding or hospitalization

indicated; elective operative

intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by a narrowing of the lumen of the ileum.

Ileal ulcer Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; altered GI

function

Severely altered GI function;

TPN indicated; elective

operative or endoscopic

intervention indicated; disabling

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by a circumscribed, inflammatory and necrotic erosive lesion on the mucosal surface of the ileum.

Ileus - Symptomatic; altered GI

function; bowel rest indicated

Severely altered GI function;

TPN indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by failure of the ileum to transport intestinal contents.

Intra-abdominal hemorrhage - Medical intervention or minor

cauterization indicated

Transfusion, radiologic,

endoscopic, or elective

operative intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by bleeding in the abdominal cavity.

Jejunal fistula Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; altered GI

function

Severely altered GI function;

TPN or hospitalization indicated;

elective operative intervention

indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an abnormal communication between the jejunum and another organ or anatomic site.

Jejunal hemorrhage Mild; intervention not indicated Moderate symptoms; medical

intervention or minor

cauterization indicated

Transfusion, radiologic,

endoscopic, or elective

operative intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by bleeding from the jejunal wall.

Jejunal obstruction Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; altered GI

function; limiting instrumental

ADL

Hospitalization indicated;

elective operative intervention

indicated; limiting self care ADL;

disabling

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by blockage of the normal flow of the intestinal contents in the jejunum.

Jejunal perforation - Symptomatic; medical

intervention indicated

Severe symptoms; elective

operative intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by a rupture in the jejunal wall.

Jejunal stenosis Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; altered GI

function

Severely altered GI function;

tube feeding or hospitalization

indicated; elective operative

intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by a narrowing of the lumen of the jejunum.

Jejunal ulcer Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; altered GI

function

Severely altered GI function;

TPN indicated; elective

operative or endoscopic

intervention indicated; disabling

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by a circumscribed, inflammatory and necrotic erosive lesion on the mucosal surface of the jejunum.

Lip pain Mild pain Moderate pain; limiting

instrumental ADL

Severe pain; limiting self care

ADL

- -

Definition: A disorder characterized by a sensation of marked discomfort of the lip.

CTCAE 4.03 - June 14, 2010 : Gastrointestinal disorders

Gastrointestinal disorders

Grade

Adverse Event 1 2 3 4 5

Lower gastrointestinal

hemorrhage

Mild; intervention not indicated Moderate symptoms; medical

intervention or minor

cauterization indicated

Transfusion, radiologic,

endoscopic, or elective

operative intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by bleeding from the lower gastrointestinal tract (small intestine, large intestine, and anus).

Malabsorption - Altered diet; oral intervention

indicated

Inability to aliment adequately;

TPN indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by inadequate absorption of nutrients in the small intestine. Symptoms include abdominal marked discomfort, bloating and diarrhea.

Mucositis oral Asymptomatic or mild

symptoms; intervention not

indicated

Moderate pain; not interfering

with oral intake; modified diet

indicated

Severe pain; interfering with oral

intake

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by inflammation of the oral mucosal.

Nausea Loss of appetite without

alteration in eating habits

Oral intake decreased without

significant weight loss,

dehydration or malnutrition

Inadequate oral caloric or fluid

intake; tube feeding, TPN, or

hospitalization indicated

- -

Definition: A disorder characterized by a queasy sensation and/or the urge to vomit.

Obstruction gastric Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; altered GI

function; limiting instrumental

ADL

Hospitalization indicated;

elective operative intervention

indicated; limiting self care ADL;

disabling

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by blockage of the normal flow of the contents in the stomach.

Oral cavity fistula Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; altered GI

function

Severely altered GI function;

TPN or hospitalization indicated;

elective operative intervention

indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an abnormal communication between the oral cavity and another organ or anatomic site.

Oral dysesthesia Mild discomfort; not interfering

with oral intake

Moderate pain; interfering with

oral intake

Disabling pain; tube feeding or

TPN indicated

- -

Definition: A disorder characterized by a burning or tingling sensation on the lips, tongue or entire mouth.

Oral hemorrhage Mild; intervention not indicated Moderate symptoms; medical

intervention or minor

cauterization indicated

Transfusion, radiologic,

endoscopic, or elective

operative intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by bleeding from the mouth.

Oral pain Mild pain Moderate pain; limiting

instrumental ADL

Severe pain; limiting self care

ADL

- -

Definition: A disorder characterized by a sensation of marked discomfort in the mouth, tongue or lips.

Pancreatic duct stenosis Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; altered GI

function

Severely altered GI function;

tube feeding or hospitalization

indicated; elective operative

intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by a narrowing of the lumen of the pancreatic duct.

Pancreatic fistula Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; altered GI

function

Severely altered GI function;

tube feeding or TPN or

hospitalization indicated;

elective operative intervention

indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by an abnormal communication between the pancreas and another organ or anatomic site.

Pancreatic hemorrhage Mild; intervention not indicated Moderate symptoms; medical

intervention or minor

cauterization indicated

Transfusion, radiologic,

endoscopic, or elective

operative intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by bleeding from the pancreas.

Pancreatic necrosis - - Tube feeding or TPN indicated;

radiologic, endoscopic, or

operative intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by a necrotic process occurring in the pancreas.

Pancreatitis - Enzyme elevation or radiologic

findings only

Severe pain; vomiting; medical

intervention indicated (e.g.,

analgesia, nutritional support)

Life-threatening consequences;

urgent intervention indicated

Death

CTCAE 4.03 - June 14, 2010 : Gastrointestinal disorders

Gastrointestinal disorders

Grade

Adverse Event 1 2 3 4 5

Definition: A disorder characterized by inflammation of the pancreas.

Periodontal disease Gingival recession or gingivitis;

limited bleeding on probing; mild

local bone loss

Moderate gingival recession or

gingivitis; multiple sites of

bleeding on probing; moderate

bone loss

Spontaneous bleeding; severe

bone loss with or without tooth

loss; osteonecrosis of maxilla or

mandible

- -

Definition: A disorder in the gingival tissue around the teeth.

Peritoneal necrosis - - Tube feeding or TPN indicated;

radiologic, endoscopic, or

operative intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by a necrotic process occurring in the peritoneum.

Proctitis Rectal discomfort, intervention

not indicated

Symptoms (e.g., rectal

discomfort, passing blood or

mucus); medical intervention

indicated; limiting instrumental

ADL

Severe symptoms; fecal

urgency or stool incontinence;

limiting self care ADL

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by inflammation of the rectum.

Rectal fistula Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; altered GI

function

Severely altered GI function;

TPN or hospitalization indicated;

elective operative intervention

indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an abnormal communication between the rectum and another organ or anatomic site.

Rectal hemorrhage Mild; intervention not indicated Moderate symptoms; medical

intervention or minor

cauterization indicated

Transfusion, radiologic,

endoscopic, or elective

operative intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by bleeding from the rectal wall and discharged from the anus.

Rectal mucositis Asymptomatic or mild

symptoms; intervention not

indicated

Symptomatic; medical

intervention indicated; limiting

instrumental ADL

Severe symptoms; limiting self

care ADL

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by inflammation of the mucous membrane of the rectum.

Rectal necrosis - - Tube feeding or TPN indicated;

radiologic, endoscopic, or

operative intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by a necrotic process occurring in the rectal wall.

Rectal obstruction Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; altered GI

function; limiting instrumental

ADL

Hospitalization indicated;

elective operative intervention

indicated; limiting self care ADL;

disabling

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by blockage of the normal flow of the intestinal contents in the rectum.

Rectal pain Mild pain Moderate pain; limiting

instrumental ADL

Severe pain; limiting self care

ADL

- -

Definition: A disorder characterized by a sensation of marked discomfort in the rectal region.

Rectal perforation - Symptomatic; medical

intervention indicated

Severe symptoms; elective

operative intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by a rupture in the rectal wall.

Rectal stenosis Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; altered GI

function

Severely altered GI function;

tube feeding or hospitalization

indicated; elective operative

intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by a narrowing of the lumen of the rectum.

Rectal ulcer Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; altered GI

function (e.g. altered dietary

habits, vomiting, diarrhea)

Severely altered GI function;

TPN indicated; elective

operative or endoscopic

intervention indicated; disabling

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by a circumscribed, inflammatory and necrotic erosive lesion on the mucosal surface of the rectum.

CTCAE 4.03 - June 14, 2010 : Gastrointestinal disorders

Gastrointestinal disorders

Grade

Adverse Event 1 2 3 4 5

Retroperitoneal hemorrhage - Self-limited; intervention

indicated

Transfusion, medical, radiologic,

endoscopic, or elective

operative intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by bleeding from the retroperitoneal area.

Salivary duct inflammation Slightly thickened saliva; slightly

altered taste (e.g., metallic)

Thick, ropy, sticky saliva;

markedly altered taste;

alteration in diet indicated;

secretion-induced symptoms;

limiting instrumental ADL

Acute salivary gland necrosis;

severe secretion-induced

symptoms (e.g., thick saliva/oral

secretions or gagging); tube

feeding or TPN indicated;

limiting self care ADL; disabling

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by inflammation of the salivary duct.

Salivary gland fistula Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; altered GI

function; tube feeding indicated

Severely altered GI function;

hospitalization indicated;

elective operative intervention

indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by an abnormal communication between a salivary gland and another organ or anatomic site.

Small intestinal mucositis Asymptomatic or mild

symptoms; intervention not

indicated

Symptomatic; medical

intervention indicated; limiting

instrumental ADL

Severe pain; interfering with oral

intake; tube feeding, TPN or

hospitalization indicated; limiting

self care ADL

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by inflammation of the mucous membrane of the small intestine.

Small intestinal obstruction Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; altered GI

function; limiting instrumental

ADL

Hospitalization indicated;

elective operative intervention

indicated; limiting self care ADL;

disabling

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by blockage of the normal flow of the intestinal contents.

Small intestinal perforation - Symptomatic; medical

intervention indicated

Severe symptoms; elective

operative intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by a rupture in the small intestine wall.

Small intestinal stenosis Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; altered GI

function

Symptomatic and severely

altered GI function; tube

feeding, TPN or hospitalization

indicated; non-emergent

operative intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by a narrowing of the lumen of the small intestine.

Small intestine ulcer Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; altered GI

function; limiting instrumental

ADL

Severely altered GI function;

TPN indicated; elective

operative or endoscopic

intervention indicated; limiting

self care ADL; disabling

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by a circumscribed, inflammatory and necrotic erosive lesion on the mucosal surface of the small intestine.

Stomach pain Mild pain Moderate pain; limiting

instrumental ADL

Severe pain; limiting self care

ADL

- -

Definition: A disorder characterized by a sensation of marked discomfort in the stomach.

Tooth development disorder Asymptomatic; hypoplasia of

tooth or enamel

Impairment correctable with oral

surgery

Maldevelopment with

impairment not surgically

correctable; disabling

- -

Definition: A disorder characterized by a pathological process of the teeth occurring during tooth development.

Tooth discoloration Surface stains - - - -

Definition: A disorder characterized by a change in tooth hue or tint.

Toothache Mild pain Moderate pain; limiting

instrumental ADL

Severe pain; limiting self care

ADL

- -

Definition: A disorder characterized by a sensation of marked discomfort in the tooth.

CTCAE 4.03 - June 14, 2010 : Gastrointestinal disorders

Gastrointestinal disorders

Grade

Adverse Event 1 2 3 4 5

Typhlitis - - Symptomatic (e.g., abdominal

pain, fever, change in bowel

habits with ileus); peritoneal

signs

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by inflammation of the cecum.

Upper gastrointestinal

hemorrhage

Mild; intervention not indicated Moderate symptoms; medical

intervention or minor

cauterization indicated

Transfusion, radiologic,

endoscopic, or elective

operative intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by bleeding from the upper gastrointestinal tract (oral cavity, pharynx, esophagus, and stomach).

Vomiting 1 - 2 episodes (separated by 5

minutes) in 24 hrs

3 - 5 episodes (separated by 5

minutes) in 24 hrs

>=6 episodes (separated by 5

minutes) in 24 hrs; tube feeding,

TPN or hospitalization indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by the reflexive act of ejecting the contents of the stomach through the mouth.

Gastrointestinal disorders -

Other, specify

Asymptomatic or mild

symptoms; clinical or diagnostic

observations only; intervention

not indicated

Moderate; minimal, local or

noninvasive intervention

indicated; limiting age-

appropriate instrumental ADL

Severe or medically significant

but not immediately life-

threatening; hospitalization or

prolongation of existing

hospitalization indicated;

disabling; limiting self care ADL

Life-threatening consequences;

urgent intervention indicated

Death

CTCAE 4.03 - June 14, 2010 : General disorders and administration site conditions

9. General disorders and administration site conditions

General disorders and administration site conditions

Grade

Adverse Event 1 2 3 4 5

Chills Mild sensation of cold;

shivering; chattering of teeth

Moderate tremor of the entire

body; narcotics indicated

Severe or prolonged, not

responsive to narcotics

- -

Definition: A disorder characterized by a sensation of cold that often marks a physiologic response to sweating after a fever.

Death neonatal - - - - Death

Definition: A disorder characterized by cessation of life occurring during the first 28 days of life.

Death NOS - - - - Death

Definition: A cessation of life that cannot be attributed to a CTCAE term associated with Grade 5.

Edema face Localized facial edema Moderate localized facial

edema; limiting instrumental

ADL

Severe swelling; limiting self

care ADL

- -

Definition: A disorder characterized by swelling due to excessive fluid accumulation in facial tissues.

Edema limbs 5 - 10% inter-limb discrepancy

in volume or circumference at

point of greatest visible

difference; swelling or

obscuration of anatomic

architecture on close inspection

>10 - 30% inter-limb

discrepancy in volume or

circumference at point of

greatest visible difference;

readily apparent obscuration of

anatomic architecture;

obliteration of skin folds; readily

apparent deviation from normal

anatomic contour; limiting

instrumental ADL

>30% inter-limb discrepancy in

volume; gross deviation from

normal anatomic contour;

limiting self care ADL

- -

Definition: A disorder characterized by swelling due to excessive fluid accumulation in the upper or lower extremities.

Edema trunk Swelling or obscuration of

anatomic architecture on close

inspection

Readily apparent obscuration of

anatomic architecture;

obliteration of skin folds; readily

apparent deviation from normal

anatomic contour; limiting

instrumental ADL

Gross deviation from normal

anatomic contour; limiting self

care ADL

- -

Definition: A disorder characterized by swelling due to excessive fluid accumulation in the trunk area.

Facial pain Mild pain Moderate pain; limiting

instrumental ADL

Severe pain; limiting self care

ADL

- -

Definition: A disorder characterized by a sensation of marked discomfort in the face.

Fatigue Fatigue relieved by rest Fatigue not relieved by rest;

limiting instrumental ADL

Fatigue not relieved by rest,

limiting self care ADL

- -

Definition: A disorder characterized by a state of generalized weakness with a pronounced inability to summon sufficient energy to accomplish daily activities.

Fever 38.0 - 39.0 degrees C (100.4 -

102.2 degrees F)

>39.0 - 40.0 degrees C (102.3 -

104.0 degrees F)

>40.0 degrees C (>104.0

degrees F) for <=24 hrs

>40.0 degrees C (>104.0

degrees F) for >24 hrs

Death

Definition: A disorder characterized by elevation of the body's temperature above the upper limit of normal.

Flu like symptoms Mild flu-like symptoms present Moderate symptoms; limiting

instrumental ADL

Severe symptoms; limiting self

care ADL

- -

Definition: A disorder characterized by a group of symptoms similar to those observed in patients with the flu. It includes fever, chills, body aches, malaise, loss of appetite and dry

cough.

Gait disturbance Mild change in gait (e.g., wide-

based, limping or hobbling)

Moderate change in gait (e.g.,

wide-based, limping or

hobbling); assistive device

indicated; limiting instrumental

ADL

Disabling; limiting self care ADL - -

Definition: A disorder characterized by walking difficulties.

Hypothermia - 35 - >32 degrees C; 95 - >89.6

degrees F

32 - >28 degrees C; 89.6 -

>82.4 degrees F

<=28 degrees C; 82.4 degrees

F; life-threatening

consequences (e.g., coma,

hypotension, pulmonary edema,

acidemia, ventricular fibrillation)

Death

Definition: A disorder characterized by an abnormally low body temperature. Treatment is required when the body temperature is 35C (95F) or below.

CTCAE 4.03 - June 14, 2010 : General disorders and administration site conditions

General disorders and administration site conditions

Grade

Adverse Event 1 2 3 4 5

Infusion related reaction Mild transient reaction; infusion

interruption not indicated;

intervention not indicated

Therapy or infusion interruption

indicated but responds promptly

to symptomatic treatment (e.g.,

antihistamines, NSAIDS,

narcotics, IV fluids); prophylactic

medications indicated for <=24

hrs

Prolonged (e.g., not rapidly

responsive to symptomatic

medication and/or brief

interruption of infusion);

recurrence of symptoms

following initial improvement;

hospitalization indicated for

clinical sequelae

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by adverse reaction to the infusion of pharmacological or biological substances.

Infusion site extravasation - Erythema with associated

symptoms (e.g., edema, pain,

induration, phlebitis)

Ulceration or necrosis; severe

tissue damage; operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by leakage of a pharmacologic or a biologic substance from the infusion site into the surrounding tissue. Signs and symptoms include induration,

erythema, swelling, burning sensation and marked discomfort at the infusion site.

Injection site reaction Tenderness with or without

associated symptoms (e.g.,

warmth, erythema, itching)

Pain; lipodystrophy; edema;

phlebitis

Ulceration or necrosis; severe

tissue damage; operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an intense adverse reaction (usually immunologic) developing at the site of an injection.

Irritability Mild; easily consolable Moderate; limiting instrumental

ADL; increased attention

indicated

Severe abnormal or excessive

response; limiting self care ADL;

inconsolable

- -

Definition: A disorder characterized by an abnormal responsiveness to stimuli or physiological arousal; may be in response to pain, fright, a drug, an emotional situation or a medical

condition.

Localized edema Localized to dependent areas,

no disability or functional

impairment

Moderate localized edema and

intervention indicated; limiting

instrumental ADL

Severe localized edema and

intervention indicated; limiting

self care ADL

- -

Definition: A disorder characterized by swelling due to excessive fluid accumulation at a specific anatomic site.

Malaise Uneasiness or lack of well being Uneasiness or lack of well

being; limiting instrumental ADL

- - -

Definition: A disorder characterized by a feeling of general discomfort or uneasiness, an out-of-sorts feeling.

Multi-organ failure - - Shock with azotemia and acid-

base disturbances; significant

coagulation abnormalities

Life-threatening consequences

(e.g., vasopressor dependent

and oliguric or anuric or

ischemic colitis or lactic

acidosis)

Death

Definition: A disorder characterized by progressive deterioration of the lungs, liver, kidney and clotting mechanisms.

Neck edema Asymptomatic localized neck

edema

Moderate neck edema; slight

obliteration of anatomic

landmarks; limiting instrumental

ADL

Generalized neck edema (e.g.,

difficulty in turning neck);

limiting self care ADL

- -

Definition: A disorder characterized by swelling due to an accumulation of excessive fluid in the neck.

Non-cardiac chest pain Mild pain Moderate pain; limiting

instrumental ADL

Severe pain; limiting self care

ADL

- -

Definition: A disorder characterized by discomfort in the chest unrelated to a heart disorder.

Pain Mild pain Moderate pain; limiting

instrumental ADL

Severe pain; limiting self care

ADL

- -

Definition: A disorder characterized by the sensation of marked discomfort, distress or agony.

Sudden death NOS - - - - Death

Definition: An unexpected cessation of life that cannot be attributed to a CTCAE term associated with Grade 5.

General disorders and

administration site conditions -

Other, specify

Asymptomatic or mild

symptoms; clinical or diagnostic

observations only; intervention

not indicated

Moderate; minimal, local or

noninvasive intervention

indicated; limiting age-

appropriate instrumental ADL

Severe or medically significant

but not immediately life-

threatening; hospitalization or

prolongation of existing

hospitalization indicated;

disabling; limiting self care ADL

Life-threatening consequences;

urgent intervention indicated

Death

CTCAE 4.03 - June 14, 2010 : Hepatobiliary disorders

10. Hepatobiliary disorders

Hepatobiliary disorders

Grade

Adverse Event 1 2 3 4 5

Bile duct stenosis Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; altered GI

function; IV fluids indicated <24

hrs

Severely altered GI function;

radiologic, endoscopic or

elective operative intervention

indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by a narrowing of the lumen of the bile duct.

Biliary fistula - Symptomatic and intervention

not indicated

Severely altered GI function;

TPN indicated; endoscopic

intervention indicated; elective

operative intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by an abnormal communication between the bile ducts and another organ or anatomic site.

Cholecystitis - Symptomatic; medical

intervention indicated

Severe symptoms; radiologic,

endoscopic or elective operative

intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by inflammation involving the gallbladder. It may be associated with the presence of gallstones.

Gallbladder fistula Asymptomatic clinical or

diagnostic observations only;

intervention not indicated

Symptomatic and intervention

not indicated

Symptomatic or severely altered

GI function; TPN indicated;

radiologic, endoscopic or

elective operative intervention

indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by an abnormal communication between the gallbladder and another organ or anatomic site.

Gallbladder necrosis - - - Life-threatening consequences;

urgent radiologic or operative

intervention indicated

Death

Definition: A disorder characterized by a necrotic process occurring in the gallbladder.

Gallbladder obstruction Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; altered GI

function; IV fluids indicated <24

hrs

Symptomatic and severely

altered GI function; tube

feeding, TPN or hospitalization

indicated; non-emergent

operative intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by blockage of the normal flow of the contents of the gallbladder.

Gallbladder pain Mild pain Moderate pain; limiting

instrumental ADL

Severe pain; limiting self care

ADL

- -

Definition: A disorder characterized by a sensation of marked discomfort in the gallbladder region.

Gallbladder perforation - - - Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by a rupture in the gallbladder wall.

Hepatic failure - - Asterixis; mild encephalopathy;

limiting self care ADL

Moderate to severe

encephalopathy; coma; life-

threatening consequences

Death

Definition: A disorder characterized by the inability of the liver to metabolize chemicals in the body. Laboratory test results reveal abnormal plasma levels of ammonia, bilirubin, lactic

dehydrogenase, and alkaline phosphatase.

Hepatic hemorrhage Mild; intervention not indicated Symptomatic; medical

intervention indicated

Transfusion indicated Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by bleeding from the liver.

Hepatic necrosis - - - Life-threatening consequences;

urgent radiologic or operative

intervention indicated

Death

Definition: A disorder characterized by a necrotic process occurring in the hepatic parenchyma.

Hepatic pain Mild pain Moderate pain; limiting

instrumental ADL

Severe pain; limiting self care

ADL

- -

Definition: A disorder characterized by a sensation of marked discomfort in the liver region.

Perforation bile duct - - Radiologic, endoscopic or

elective operative intervention

indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by a rupture in the wall of the extrahepatic or intrahepatic bile duct.

CTCAE 4.03 - June 14, 2010 : Hepatobiliary disorders

Hepatobiliary disorders

Grade

Adverse Event 1 2 3 4 5

Portal hypertension - Decreased portal vein flow Reversal/retrograde portal vein

flow; associated with varices

and/or ascites

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an increase in blood pressure in the portal venous system.

Portal vein thrombosis - Intervention not indicated Medical intervention indicated Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by the formation of a thrombus (blood clot) in the portal vein.

Hepatobiliary disorders - Other,

specify

Asymptomatic or mild

symptoms; clinical or diagnostic

observations only; intervention

not indicated

Moderate; minimal, local or

noninvasive intervention

indicated; limiting age-

appropriate instrumental ADL

Severe or medically significant

but not immediately life-

threatening; hospitalization or

prolongation of existing

hospitalization indicated;

disabling; limiting self care ADL

Life-threatening consequences;

urgent intervention indicated

Death

CTCAE 4.03 - June 14, 2010 : Immune system disorders

11. Immune system disorders

Immune system disorders

Grade

Adverse Event 1 2 3 4 5

Allergic reaction Transient flushing or rash, drug

fever <38 degrees C (<100.4

degrees F); intervention not

indicated

Intervention or infusion

interruption indicated; responds

promptly to symptomatic

treatment (e.g., antihistamines,

NSAIDS, narcotics);

prophylactic medications

indicated for <=24 hrs

Prolonged (e.g., not rapidly

responsive to symptomatic

medication and/or brief

interruption of infusion);

recurrence of symptoms

following initial improvement;

hospitalization indicated for

clinical sequelae (e.g., renal

impairment, pulmonary

infiltrates)

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an adverse local or general response from exposure to an allergen.

Anaphylaxis - - Symptomatic bronchospasm,

with or without urticaria;

parenteral intervention

indicated; allergy-related

edema/angioedema;

hypotension

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an acute inflammatory reaction resulting from the release of histamine and histamine-like substances from mast cells, causing a hypersensitivity

immune response. Clinically, it presents with breathing difficulty, dizziness, hypotension, cyanosis and loss of consciousness and may lead to death.

Autoimmune disorder Asymptomatic; serologic or

other evidence of autoimmune

reaction, with normal organ

function; intervention not

indicated

Evidence of autoimmune

reaction involving a non-

essential organ or function (e.g.,

hypothyroidism)

Autoimmune reactions involving

major organ (e.g., colitis,

anemia, myocarditis, kidney)

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder resulting from loss of function or tissue destruction of an organ or multiple organs, arising from humoral or cellular immune responses of the individual to his own

tissue constituents.

Cytokine release syndrome Mild reaction; infusion

interruption not indicated;

intervention not indicated

Therapy or infusion interruption

indicated but responds promptly

to symptomatic treatment (e.g.,

antihistamines, NSAIDS,

narcotics, IV fluids); prophylactic

medications indicated for <=24

hrs

Prolonged (e.g., not rapidly

responsive to symptomatic

medication and/or brief

interruption of infusion);

recurrence of symptoms

following initial improvement;

hospitalization indicated for

clinical sequelae (e.g., renal

impairment, pulmonary

infiltrates)

Life-threatening consequences;

pressor or ventilatory support

indicated

Death

Definition: A disorder characterized by nausea, headache, tachycardia, hypotension, rash, and shortness of breath; it is caused by the release of cytokines from the cells.

Serum sickness Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Moderate arthralgia; fever, rash,

urticaria, antihistamines

indicated

Severe arthralgia or arthritis;

extensive rash; steroids or IV

fluids indicated

Life-threatening consequences;

pressor or ventilatory support

indicated

Death

Definition: A disorder characterized by a delayed-type hypersensitivity reaction to foreign proteins derived from an animal serum. It occurs approximately six to twenty-one days

following the administration of the foreign antigen. Symptoms include fever, arthralgias, myalgias, skin eruptions, lymphadenopathy, chest marked discomfort and dyspnea.

Immune system disorders -

Other, specify

Asymptomatic or mild

symptoms; clinical or diagnostic

observations only; intervention

not indicated

Moderate; minimal, local or

noninvasive intervention

indicated; limiting age-

appropriate instrumental ADL

Severe or medically significant

but not immediately life-

threatening; hospitalization or

prolongation of existing

hospitalization indicated;

disabling; limiting self care ADL

Life-threatening consequences;

urgent intervention indicated

Death

CTCAE 4.03 - June 14, 2010 : Infections and infestations

12. Infections and infestations

Infections and infestations

Grade

Adverse Event 1 2 3 4 5

Abdominal infection - - IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic or operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving the abdominal cavity.

Anorectal infection Localized; local intervention

indicated

Oral intervention indicated (e.g.,

antibiotic, antifungal, antiviral)

IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic, endoscopic, or

operative intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving the anal area and the rectum.

Appendicitis - - IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic or operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by acute inflammation to the vermiform appendix caused by a pathogenic agent.

Appendicitis perforated - Symptomatic; medical

intervention indicated

Severe symptoms; elective

operative intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by acute inflammation to the vermiform appendix caused by a pathogenic agent with gangrenous changes resulting in the rupture of the

appendiceal wall. The appendiceal wall rupture causes the release of inflammatory and bacterial contents from the appendiceal lumen into the abdominal cavity.

Arteritis infective - - IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic or operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving an artery.

Biliary tract infection - - IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic or operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving the biliary tract.

Bladder infection - Oral intervention indicated (e.g.,

antibiotic, antifungal, antiviral)

IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic, endoscopic, or

operative intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving the bladder.

Bone infection - - IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic or operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving the bones.

Breast infection - Local infection with moderate

symptoms; oral intervention

indicated (e.g., antibiotic,

antifungal, antiviral)

Severe infection; axillary

adenitis; IV antibacterial,

antifungal, or antiviral

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving the breast.

Bronchial infection - Moderate symptoms; oral

intervention indicated (e.g.,

antibiotic, antifungal, antiviral)

IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic, endoscopic, or

operative intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving the bronchi.

Catheter related infection - Localized; local intervention

indicated; oral intervention

indicated (e.g., antibiotic,

antifungal, antiviral)

IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic or operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process that arises secondary to catheter use.

Cecal infection - - IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic, endoscopic, or

operative intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

CTCAE 4.03 - June 14, 2010 : Infections and infestations

Infections and infestations

Grade

Adverse Event 1 2 3 4 5

Definition: A disorder characterized by an infectious process involving the cecum.

Cervicitis infection - Localized; local intervention

indicated (e.g., topical antibiotic,

antifungal, or antiviral)

IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic or operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving the uterine cervix.

Conjunctivitis infective - Localized; local intervention

indicated (e.g., topical antibiotic,

antifungal, or antiviral)

IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic or operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving the conjunctiva. Clinical manifestations include pink or red color in the eyes.

Corneal infection - Localized; local intervention

indicated (e.g., topical antibiotic,

antifungal, or antiviral)

IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic or operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving the cornea.

Cranial nerve infection - - IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic or operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving a cranial nerve.

Device related infection - - IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic or operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving the use of a medical device.

Duodenal infection - Moderate symptoms; medical

intervention indicated (e.g., oral

antibiotics)

IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic or operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving the duodenum.

Encephalitis infection - - IV antibiotic, antifungal, or

antiviral intervention indicated;

severe changes in mental

status; self-limited seizure

activity; focal neurologic

abnormalities

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving the brain tissue.

Encephalomyelitis infection - - IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic or operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving the brain and spinal cord tissues.

Endocarditis infective - - IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic or operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving the endocardial layer of the heart.

Endophthalmitis - Local intervention indicated Systemic intervention or

hospitalization indicated

Blindness (20/200 or worse) -

Definition: A disorder characterized by an infectious process involving the internal structures of the eye.

CTCAE 4.03 - June 14, 2010 : Infections and infestations

Infections and infestations

Grade

Adverse Event 1 2 3 4 5

Enterocolitis infectious - Passage of >3 unformed stools

per 24 hrs or duration of illness

>48 hrs; moderate abdominal

pain

IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic, endoscopic, or

operative intervention indicated;

profuse watery diarrhea with

signs of hypovolemia; bloody

diarrhea; fever; severe

abdominal pain; hospitalization

indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving the small and large intestines.

Esophageal infection - Local intervention indicated

(e.g., oral antibiotic, antifungal,

antiviral)

IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic or operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving the esophagus.

Eye infection - Localized; local intervention

indicated (e.g., topical antibiotic,

antifungal, or antiviral)

IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic or operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated;

enucleation

Death

Definition: A disorder characterized by an infectious process involving the eye.

Gallbladder infection - - IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic, endoscopic, or

operative intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving the gallbladder.

Gum infection Local therapy indicated (swish

and swallow)

Moderate symptoms; oral

intervention indicated (e.g.,

antibiotic, antifungal, antiviral)

IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic or operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving the gums.

Hepatic infection - - IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic or operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving the liver.

Hepatitis viral Asymptomatic, treatment not

indicated

- Symptomatic liver dysfunction;

fibrosis by biopsy; compensated

cirrhosis; reactivation of chronic

hepatitis

Decompensated liver function

(e.g., ascites, coagulopathy,

encephalopathy, coma)

Death

Definition: A disorder characterized by a viral pathologic process involving the liver parenchyma.

Infective myositis - Localized; local intervention

indicated (e.g., topical antibiotic,

antifungal, or antiviral)

IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic or operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving the skeletal muscles.

Joint infection - Localized; local intervention

indicated; oral intervention

indicated (e.g., antibiotic,

antifungal, antiviral); needle

aspiration indicated (single or

multiple)

Arthroscopic intervention

indicated (e.g., drainage) or

arthrotomy (e.g., open surgical

drainage)

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving a joint.

Kidney infection - - IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic, endoscopic, or

operative intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving the kidney.

CTCAE 4.03 - June 14, 2010 : Infections and infestations

Infections and infestations

Grade

Adverse Event 1 2 3 4 5

Laryngitis - Moderate symptoms; oral

intervention indicated (e.g.,

antibiotic, antifungal, antiviral)

IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic or operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an inflammatory process involving the larynx.

Lip infection Localized, local intervention

indicated

Oral intervention indicated (e.g.,

antibiotic, antifungal, antiviral)

IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic or operative

intervention indicated

- -

Definition: A disorder characterized by an infectious process involving the lips.

Lung infection - Moderate symptoms; oral

intervention indicated (e.g.,

antibiotic, antifungal, antiviral)

IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic, endoscopic, or

operative intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving the lungs.

Lymph gland infection - Localized; local intervention

indicated (e.g., topical antibiotic,

antifungal, or antiviral)

IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic or operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving the lymph nodes.

Mediastinal infection - - IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic or operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving the mediastinum.

Meningitis - - IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic or operative

intervention indicated; focal

neurologic deficit

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by acute inflammation of the meninges of the brain and/or spinal cord.

Mucosal infection Localized, local intervention

indicated

Oral intervention indicated (e.g.,

antibiotic, antifungal, antiviral)

IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic or operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving a mucosal surface.

Nail infection Localized, local intervention

indicated

Oral intervention indicated (e.g.,

antibiotic, antifungal, antiviral)

IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic or operative

intervention indicated

- -

Definition: A disorder characterized by an infectious process involving the nail.

Otitis externa - Localized; local intervention

indicated (e.g., topical antibiotic,

antifungal, or antiviral)

IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic or operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving the outer ear and ear canal. Contributory factors include excessive water exposure (swimmer's ear infection)

and cuts in the ear canal. Symptoms include fullness, itching, swelling and marked discomfort in the ear and ear drainage.

Otitis media - Localized; local intervention

indicated (e.g., topical antibiotic,

antifungal, or antiviral)

IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic or operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving the middle ear.

Ovarian infection - Localized; local intervention

indicated (e.g., topical antibiotic,

antifungal, or antiviral)

IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic or operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving the ovary.

CTCAE 4.03 - June 14, 2010 : Infections and infestations

Infections and infestations

Grade

Adverse Event 1 2 3 4 5

Pancreas infection - - IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic or operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving the pancreas.

Papulopustular rash Papules and/or pustules

covering <10% BSA, which may

or may not be associated with

symptoms of pruritus or

tenderness

Papules and/or pustules

covering 10-30% BSA, which

may or may not be associated

with symptoms of pruritus or

tenderness; associated with

psychosocial impact; limiting

instrumental ADL

Papules and/or pustules

covering >30% BSA, which may

or may not be associated with

symptoms of pruritus or

tenderness; limiting self-care

ADL; associated with local

superinfection with oral

antibiotics indicated

Papules and/or pustules

covering any % BSA, which

may or may not be associated

with symptoms of pruritus or

tenderness and are associated

with extensive superinfection

with IV antibiotics indicated; life-

threatening consequences

Death

Definition: A disorder characterized by an eruption consisting of papules (a small, raised pimple) and pustules (a small pus filled blister), typically appearing in face, scalp, and upper

chest and back Unlike acne, this rash does not present with whiteheads or blackheads, and can be symptomatic, with itchy or tender lesions.

Paronychia Nail fold edema or erythema;

disruption of the cuticle

Localized intervention indicated;

oral intervention indicated (e.g.,

antibiotic, antifungal, antiviral);

nail fold edema or erythema

with pain; associated with

discharge or nail plate

separation; limiting instrumental

ADL

Surgical intervention or IV

antibiotics indicated; limiting self

care ADL

- -

Definition: A disorder characterized by an infectious process involving the soft tissues around the nail.

Pelvic infection - Moderate symptoms; oral

intervention indicated (e.g.,

antibiotic, antifungal, antiviral)

IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic or operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving the pelvic cavity.

Penile infection - Localized; local intervention

indicated (e.g., topical antibiotic,

antifungal, or antiviral)

IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic or operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving the penis.

Periorbital infection - Localized; local intervention

indicated (e.g., topical antibiotic,

antifungal, or antiviral)

IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic or operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving the orbit of the eye.

Peripheral nerve infection - Localized; local intervention

indicated (e.g., topical antibiotic,

antifungal, or antiviral)

IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic or operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving the peripheral nerves.

Peritoneal infection - - IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic, endoscopic, or

operative intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving the peritoneum.

Pharyngitis - Localized; local intervention

indicated (e.g., topical antibiotic,

antifungal, or antiviral)

IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic or operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by inflammation of the throat.

Phlebitis infective - Localized; local intervention

indicated (e.g., topical antibiotic,

antifungal, or antiviral)

IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic or operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

CTCAE 4.03 - June 14, 2010 : Infections and infestations

Infections and infestations

Grade

Adverse Event 1 2 3 4 5

Definition: A disorder characterized by an infectious process involving the vein. Clinical manifestations include erythema, marked discomfort, swelling, and induration along the course

of the infected vein.

Pleural infection - Localized; local intervention

indicated (e.g., topical antibiotic,

antifungal, or antiviral)

IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic, endoscopic, or

operative intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving the pleura.

Prostate infection - Moderate symptoms; oral

intervention indicated (e.g.,

antibiotic, antifungal, antiviral)

IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic, endoscopic, or

operative intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving the prostate gland.

Rash pustular - Localized; local intervention

indicated (e.g., topical antibiotic,

antifungal, or antiviral)

IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic or operative

intervention indicated

- -

Definition: A disorder characterized by a circumscribed and elevated skin lesion filled with pus.

Rhinitis infective - Localized; local intervention

indicated (e.g., topical antibiotic,

antifungal, or antiviral)

- - -

Definition: A disorder characterized by an infectious process involving the nasal mucosal.

Salivary gland infection - Moderate symptoms; oral

intervention indicated (e.g.,

antibiotic, antifungal, antiviral)

IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic or operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving the salivary gland.

Scrotal infection - Localized; local intervention

indicated (e.g., topical antibiotic,

antifungal, or antiviral)

IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic or operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving the scrotum.

Sepsis - - - Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by the presence of pathogenic microorganisms in the blood stream that cause a rapidly progressing systemic reaction that may lead to shock.

Sinusitis - Localized; local intervention

indicated (e.g., topical antibiotic,

antifungal, or antiviral)

IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic, endoscopic, or

operative intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving the mucous membranes of the paranasal sinuses.

Skin infection Localized, local intervention

indicated

Oral intervention indicated (e.g.,

antibiotic, antifungal, antiviral)

IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic or operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving the skin.

Small intestine infection - Moderate symptoms; oral

intervention indicated (e.g.,

antibiotic, antifungal, antiviral)

IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic or operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving the small intestine.

Soft tissue infection - Localized; local intervention

indicated (e.g., topical antibiotic,

antifungal, or antiviral)

IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic or operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving soft tissues.

Splenic infection - - IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic or operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

CTCAE 4.03 - June 14, 2010 : Infections and infestations

Infections and infestations

Grade

Adverse Event 1 2 3 4 5

Definition: A disorder characterized by an infectious process involving the spleen.

Stoma site infection Localized, local intervention

indicated

Oral intervention indicated (e.g.,

antibiotic, antifungal, antiviral)

IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic, endoscopic, or

operative intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving a stoma (surgically created opening on the surface of the body).

Tooth infection - Localized; local intervention

indicated (e.g., topical antibiotic,

antifungal, or antiviral)

IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic or operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving a tooth.

Tracheitis - Moderate symptoms; oral

intervention indicated (e.g.,

antibiotic, antifungal, antiviral)

IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic, endoscopic, or

operative intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving the trachea.

Upper respiratory infection - Moderate symptoms; oral

intervention indicated (e.g.,

antibiotic, antifungal, antiviral)

IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic, endoscopic, or

operative intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving the upper respiratory tract (nose, paranasal sinuses, pharynx, larynx, or trachea).

Urethral infection - Localized; local intervention

indicated (e.g., topical antibiotic,

antifungal, or antiviral)

IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic, endoscopic, or

operative intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving the urethra.

Urinary tract infection - Localized; local intervention

indicated (e.g., topical antibiotic,

antifungal, or antiviral)

IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic or operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving the urinary tract, most commonly the bladder and the urethra.

Uterine infection - Moderate symptoms; oral

intervention indicated (e.g.,

antibiotic, antifungal, antiviral)

IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic or operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving the endometrium. It may extend to the myometrium and parametrial tissues.

Vaginal infection - Localized; local intervention

indicated (e.g., topical antibiotic,

antifungal, or antiviral)

IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic or operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving the vagina.

Vulval infection Localized, local intervention

indicated

Oral intervention indicated (e.g.,

antibiotic, antifungal, antiviral)

IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic or operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving the vulva.

Wound infection - Localized; local intervention

indicated (e.g., topical antibiotic,

antifungal, or antiviral)

IV antibiotic, antifungal, or

antiviral intervention indicated;

radiologic or operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an infectious process involving the wound.

Infections and infestations -

Other, specify

Asymptomatic or mild

symptoms; clinical or diagnostic

observations only; intervention

not indicated

Moderate; minimal, local or

noninvasive intervention

indicated; limiting age-

appropriate instrumental ADL

Severe or medically significant

but not immediately life-

threatening; hospitalization or

prolongation of existing

hospitalization indicated;

disabling; limiting self care ADL

Life-threatening consequences;

urgent intervention indicated

Death

CTCAE 4.03 - June 14, 2010 : Injury, poisoning and procedural complications

13. Injury, poisoning and procedural complications

Injury, poisoning and procedural complications

Grade

Adverse Event 1 2 3 4 5

Ankle fracture Mild; non-surgical intervention

indicated

Limiting instrumental ADL;

operative intervention indicated

Limiting self care ADL; elective

surgery indicated

- -

Definition: A finding of damage to the ankle joint characterized by a break in the continuity of the ankle bone. Symptoms include marked discomfort, swelling and difficulty moving the

affected leg and foot.

Aortic injury - - Severe symptoms; limiting self

care ADL; disabling; repair or

revision indicated

Life-threatening consequences;

evidence of end organ damage;

urgent operative intervention

indicated

Death

Definition: A finding of damage to the aorta.

Arterial injury Asymptomatic diagnostic

finding; intervention not

indicated

Symptomatic (e.g.,

claudication); repair or revision

not indicated

Severe symptoms; limiting self

care ADL; disabling; repair or

revision indicated

Life-threatening consequences;

evidence of end organ damage;

urgent operative intervention

indicated

Death

Definition: A finding of damage to an artery.

Biliary anastomotic leak Asymptomatic diagnostic

observations only; intervention

not indicated

Symptomatic; medical

intervention indicated

Severe symptoms; radiologic,

endoscopic or elective operative

intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A finding of leakage of bile due to breakdown of a biliary anastomosis (surgical connection of two separate anatomic structures).

Bladder anastomotic leak Asymptomatic diagnostic

observations only; intervention

not indicated

Symptomatic; medical

intervention indicated

Severe symptoms; radiologic,

endoscopic or elective operative

intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A finding of leakage of urine due to breakdown of a bladder anastomosis (surgical connection of two separate anatomic structures).

Bruising Localized or in a dependent

area

Generalized - - -

Definition: A finding of injury of the soft tissues or bone characterized by leakage of blood into surrounding tissues.

Burn Minimal symptoms; intervention

not indicated

Medical intervention; minimal

debridement indicated

Moderate to major debridement

or reconstruction indicated

Life-threatening consequences Death

Definition: A finding of impaired integrity to the anatomic site of an adverse thermal reaction. Burns can be caused by exposure to chemicals, direct heat, electricity, flames and

radiation. The extent of damage depends on the length and intensity of exposure and time until provision of treatment.

Dermatitis radiation Faint erythema or dry

desquamation

Moderate to brisk erythema;

patchy moist desquamation,

mostly confined to skin folds

and creases; moderate edema

Moist desquamation in areas

other than skin folds and

creases; bleeding induced by

minor trauma or abrasion

Life-threatening consequences;

skin necrosis or ulceration of full

thickness dermis; spontaneous

bleeding from involved site; skin

graft indicated

Death

Definition: A finding of cutaneous inflammatory reaction occurring as a result of exposure to biologically effective levels of ionizing radiation.

Esophageal anastomotic leak Asymptomatic diagnostic

observations only; intervention

not indicated

Symptomatic; medical

intervention indicated

Severe symptoms; radiologic,

endoscopic or elective operative

intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A finding of leakage due to breakdown of an esophageal anastomosis (surgical connection of two separate anatomic structures).

Fall Minor with no resultant injuries;

intervention not indicated

Symptomatic; noninvasive

intervention indicated

Hospitalization indicated - -

Definition: A finding of sudden movement downward, usually resulting in injury.

Fallopian tube anastomotic leak Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; medical

intervention indicated

Severe symptoms; radiologic,

endoscopic or elective operative

intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A finding of leakage due to breakdown of a fallopian tube anastomosis (surgical connection of two separate anatomic structures).

Fallopian tube perforation Asymptomatic diagnostic

observations only; intervention

not indicated

Symptomatic and intervention

not indicated

Severe symptoms; elective

operative intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated (e.g., organ resection)

Death

Definition: A finding of rupture of the fallopian tube wall.

Fracture Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic but non-displaced;

immobilization indicated

Severe symptoms; displaced or

open wound with bone

exposure; disabling; operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A finding of traumatic injury to the bone in which the continuity of the bone is broken.

CTCAE 4.03 - June 14, 2010 : Injury, poisoning and procedural complications

Injury, poisoning and procedural complications

Grade

Adverse Event 1 2 3 4 5

Gastric anastomotic leak Asymptomatic diagnostic

observations only; intervention

not indicated

Symptomatic; medical

intervention indicated

Severe symptoms; radiologic,

endoscopic or elective operative

intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A finding of leakage due to breakdown of a gastric anastomosis (surgical connection of two separate anatomic structures).

Gastrointestinal anastomotic

leak

Asymptomatic diagnostic

observations only; intervention

not indicated

Symptomatic; medical

intervention indicated

Severe symptoms; radiologic,

endoscopic or elective operative

intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A finding of leakage due to breakdown of a gastrointestinal anastomosis (surgical connection of two separate anatomic structures).

Gastrointestinal stoma necrosis - Superficial necrosis;

intervention not indicated

Severe symptoms;

hospitalization or elective

operative intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A finding of a necrotic process occurring in the gastrointestinal tract stoma.

Hip fracture - Hairline fracture; mild pain;

limiting instrumental ADL; non-

surgical intervention indicated

Severe pain; hospitalization or

intervention indicated for pain

control (e.g., traction); operative

intervention indicated

Life-threatening consequences;

symptoms associated with

neurovascular compromise

Definition: A finding of traumatic injury to the hip in which the continuity of either the femoral head, femoral neck, intertrochanteric or subtrochanteric regions is broken.

Injury to carotid artery - - Severe symptoms; limiting self

care ADL (e.g., transient

cerebral ischemia); repair or

revision indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A finding of damage to the carotid artery.

Injury to inferior vena cava - - - Life-threatening consequences;

urgent intervention indicated

Death

Definition: A finding of damage to the inferior vena cava.

Injury to jugular vein - - Symptomatic limiting self care

ADL; disabling; repair or

revision indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A finding of damage to the jugular vein.

Injury to superior vena cava Asymptomatic diagnostic

finding; intervention not

indicated

Symptomatic; repair or revision

not indicated

Severe symptoms; limiting self

care ADL; disabling; repair or

revision indicated

Life-threatening consequences;

evidence of end organ damage;

urgent operative intervention

indicated

Death

Definition: A finding of damage to the superior vena cava.

Intestinal stoma leak Asymptomatic diagnostic

observations only; intervention

not indicated

Symptomatic; medical

intervention indicated

Severe symptoms; radiologic,

endoscopic or elective operative

intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A finding of leakage of contents from an intestinal stoma (surgically created opening on the surface of the body).

Intestinal stoma obstruction - Self-limited; intervention not

indicated

Severe symptoms; IV fluids,

tube feeding, or TPN indicated

>=24 hrs; elective operative

intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A finding of blockage of the normal flow of the contents of the intestinal stoma.

Intestinal stoma site bleeding Minimal bleeding identified on

clinical exam; intervention not

indicated

Moderate bleeding; medical

intervention indicated

Severe bleeding; transfusion

indicated; radiologic or

endoscopic intervention

indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A finding of blood leakage from the intestinal stoma.

Intraoperative arterial injury Primary repair of injured

organ/structure indicated

Partial resection of injured

organ/structure indicated

Complete resection or

reconstruction of injured

organ/structure indicated;

disabling

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A finding of damage to an artery during a surgical procedure.

Intraoperative breast injury Primary repair of injured

organ/structure indicated

Partial resection of injured

organ/structure indicated

Complete resection or

reconstruction of injured

organ/structure indicated;

disabling

Life-threatening consequences;

urgent intervention indicated

Death

CTCAE 4.03 - June 14, 2010 : Injury, poisoning and procedural complications

Injury, poisoning and procedural complications

Grade

Adverse Event 1 2 3 4 5

Definition: A finding of damage to the breast parenchyma during a surgical procedure.

Intraoperative cardiac injury - - Primary repair of injured

organ/structure indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A finding of damage to the heart during a surgical procedure.

Intraoperative ear injury Primary repair of injured

organ/structure indicated

Partial resection of injured

organ/structure indicated

Complete resection of injured

organ/structure indicated;

disabling (e.g., impaired

hearing; impaired balance)

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A finding of damage to the ear during a surgical procedure.

Intraoperative endocrine injury Primary repair of injured

organ/structure indicated

Partial resection of injured

organ/structure indicated

Complete resection or

reconstruction of injured

organ/structure indicated;

disabling

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A finding of damage to the endocrine gland during a surgical procedure.

Intraoperative gastrointestinal

injury

Primary repair of injured

organ/structure indicated

Partial resection of injured

organ/structure indicated

Complete resection or

reconstruction of injured

organ/structure indicated;

disabling

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A finding of damage to the gastrointestinal system during a surgical procedure.

Intraoperative head and neck

injury

Primary repair of injured

organ/structure indicated

Partial resection of injured

organ/structure indicated

Complete resection or

reconstruction of injured

organ/structure indicated;

disabling

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A finding of damage to the head and neck during a surgical procedure.

Intraoperative hemorrhage - - Postoperative radiologic,

endoscopic, or operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A finding of uncontrolled bleeding during a surgical procedure.

Intraoperative hepatobiliary

injury

Primary repair of injured

organ/structure indicated

Partial resection of injured

organ/structure indicated

Complete resection or

reconstruction of injured

organ/structure indicated;

disabling

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A finding of damage to the hepatic parenchyma and/or biliary tract during a surgical procedure.

Intraoperative musculoskeletal

injury

Primary repair of injured

organ/structure indicated

Partial resection of injured

organ/structure indicated

Complete resection or

reconstruction of injured

organ/structure indicated;

disabling

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A finding of damage to the musculoskeletal system during a surgical procedure.

Intraoperative neurological

injury

Primary repair of injured

organ/structure indicated

Partial resection of injured

organ/structure indicated

Complete resection or

reconstruction of injured

organ/structure indicated;

disabling

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A finding of damage to the nervous system during a surgical procedure.

Intraoperative ocular injury Primary repair of injured

organ/structure indicated

Partial resection of injured

organ/structure indicated

Complete resection or

reconstruction of injured

organ/structure indicated;

disabling

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A finding of damage to the eye during a surgical procedure.

Intraoperative renal injury Primary repair of injured

organ/structure indicated

Partial resection of injured

organ/structure indicated

Complete resection or

reconstruction of injured

organ/structure indicated;

disabling

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A finding of damage to the kidney during a surgical procedure.

Intraoperative reproductive tract

injury

Primary repair of injured

organ/structure indicated

Partial resection of injured

organ/structure indicated

Complete resection or

reconstruction of injured

organ/structure indicated;

disabling

Life-threatening consequences;

urgent intervention indicated

Death

CTCAE 4.03 - June 14, 2010 : Injury, poisoning and procedural complications

Injury, poisoning and procedural complications

Grade

Adverse Event 1 2 3 4 5

Definition: A finding of damage to the reproductive organs during a surgical procedure.

Intraoperative respiratory injury Primary repair of injured

organ/structure indicated

Partial resection of injured

organ/structure indicated

Complete resection or

reconstruction of injured

organ/structure indicated;

disabling

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A finding of damage to the respiratory system during a surgical procedure.

Intraoperative skin injury Primary repair of injured

organ/structure indicated

Partial resection of injured

organ/structure indicated

Complete resection or

reconstruction of injured

organ/structure indicated;

disabling

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A finding of damage to the skin during a surgical procedure.

Intraoperative splenic injury - Primary repair of injured

organ/structure indicated

Resection or reconstruction of

injured organ/structure

indicated; disabling

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A finding of damage to the spleen during a surgical procedure.

Intraoperative urinary injury Primary repair of injured

organ/structure indicated

Partial resection of injured

organ/structure indicated

Complete resection or

reconstruction of injured

organ/structure indicated;

disabling

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A finding of damage to the urinary system during a surgical procedure.

Intraoperative venous injury Primary repair of injured

organ/structure indicated

Partial resection of injured

organ/structure indicated

Complete resection or

reconstruction of injured

organ/structure indicated;

disabling

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A finding of damage to a vein during a surgical procedure.

Kidney anastomotic leak Asymptomatic diagnostic

observations only; intervention

not indicated

Symptomatic; medical

intervention indicated

Severe symptoms; radiologic,

endoscopic or elective operative

intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A finding of leakage of urine due to breakdown of a kidney anastomosis (surgical connection of two separate anatomic structures).

Large intestinal anastomotic

leak

Asymptomatic diagnostic

observations only; intervention

not indicated

Symptomatic; medical

intervention indicated

Severe symptoms; radiologic,

endoscopic or elective operative

intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A finding of leakage due to breakdown of an anastomosis (surgical connection of two separate anatomic structures) in the large intestine.

Pancreatic anastomotic leak Asymptomatic diagnostic

observations only; intervention

not indicated

Symptomatic; medical

intervention indicated

Severe symptoms; radiologic,

endoscopic or elective operative

intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A finding of leakage due to breakdown of a pancreatic anastomosis (surgical connection of two separate anatomic structures).

Pharyngeal anastomotic leak Asymptomatic diagnostic

observations only; intervention

not indicated

Symptomatic; medical

intervention indicated

Severe symptoms; radiologic,

endoscopic or elective operative

intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A finding of leakage due to breakdown of a pharyngeal anastomosis (surgical connection of two separate anatomic structures).

Postoperative hemorrhage Minimal bleeding identified on

clinical exam; intervention not

indicated

Moderate bleeding; radiologic,

endoscopic, or operative

intervention indicated

Transfusion indicated of >=2

units (10 cc/kg for pediatrics)

pRBCs beyond protocol

specification; urgent radiologic,

endoscopic, or operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A finding of bleeding occurring after a surgical procedure.

Postoperative thoracic

procedure complication

- Extubated within 24 - 72 hrs

postoperatively

Extubated >72 hrs

postoperatively, but before

tracheostomy indicated

Life-threatening airway

compromise; urgent intervention

indicated (e.g., tracheotomy or

intubation)

Death

Definition: A finding of a previously undocumented problem that occurs after a thoracic procedure.

Prolapse of intestinal stoma Asymptomatic; reducible Recurrent after manual

reduction; local irritation or stool

leakage; difficulty to fit

appliance; limiting instrumental

ADL

Severe symptoms; elective

operative intervention indicated;

limiting self care ADL

Life-threatening consequences;

urgent operative intervention

indicated

Death

CTCAE 4.03 - June 14, 2010 : Injury, poisoning and procedural complications

Injury, poisoning and procedural complications

Grade

Adverse Event 1 2 3 4 5

Definition: A finding of protrusion of the intestinal stoma (surgically created opening on the surface of the body) above the abdominal surface.

Prolapse of urostomy Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Local care or maintenance;

minor revision indicated

Dysfunctional stoma; elective

operative intervention or major

stomal revision indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A finding of displacement of the urostomy.

Radiation recall reaction

(dermatologic)

Faint erythema or dry

desquamation

Moderate to brisk erythema;

patchy moist desquamation,

mostly confined to skin folds

and creases; moderate edema

Moist desquamation in areas

other than skin folds and

creases; bleeding induced by

minor trauma or abrasion

Life-threatening consequences;

skin necrosis or ulceration of full

thickness dermis; spontaneous

bleeding from involved site; skin

graft indicated

Death

Definition: A finding of acute skin inflammatory reaction caused by drugs, especially chemotherapeutic agents, for weeks or months following radiotherapy. The inflammatory reaction

is confined to the previously irradiated skin and the symptoms disappear after the removal of the pharmaceutical agent.

Rectal anastomotic leak Asymptomatic diagnostic

observations only; intervention

not indicated

Symptomatic; medical

intervention indicated

Severe symptoms; radiologic,

endoscopic or elective operative

intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A finding of leakage due to breakdown of a rectal anastomosis (surgical connection of two separate anatomic structures).

Seroma Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; simple aspiration

indicated

Symptomatic, elective radiologic

or operative intervention

indicated

- -

Definition: A finding of tumor-like collection of serum in the tissues.

Small intestinal anastomotic

leak

Asymptomatic diagnostic

observations only; intervention

not indicated

Symptomatic; medical

intervention indicated

Severe symptoms; radiologic,

endoscopic or elective operative

intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A finding of leakage due to breakdown of an anastomosis (surgical connection of two separate anatomic structures) in the small bowel.

Spermatic cord anastomotic

leak

Asymptomatic diagnostic

observations only; intervention

not indicated

Symptomatic; medical

intervention indicated

Severe symptoms; radiologic,

endoscopic or elective operative

intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A finding of leakage due to breakdown of a spermatic cord anastomosis (surgical connection of two separate anatomic structures).

Spinal fracture Mild back pain; nonprescription

analgesics indicated

Moderate back pain;

prescription analgesics

indicated; limiting instrumental

ADL

Severe back pain;

hospitalization or intervention

indicated for pain control (e.g.,

vertebroplasty); limiting self care

ADL; disability

Life-threatening consequences;

symptoms associated with

neurovascular compromise

Death

Definition: A finding of traumatic injury to the spine in which the continuity of a vertebral bone is broken.

Stenosis of gastrointestinal

stoma

- Symptomatic; IV fluids indicated

<24 hrs; manual dilation at

bedside

Severely altered GI function;

tube feeding, TPN or

hospitalization indicated;

elective operative intervention

indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A finding of narrowing of the gastrointestinal stoma (surgically created opening on the surface of the body).

Stomal ulcer Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; medical

intervention indicated

Severe symptoms; elective

operative intervention indicated

- -

Definition: A disorder characterized by a circumscribed, inflammatory and necrotic erosive lesion on the jejunal mucosal surface close to the anastomosis site following a

gastroenterostomy procedure.

Tracheal hemorrhage Minimal bleeding identified on

clinical or diagnostic exam;

intervention not indicated

Moderate bleeding; medical

intervention indicated

Severe bleeding; transfusion

indicated; radiologic or

endoscopic intervention

indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A finding of bleeding from the trachea.

Tracheal obstruction Partial asymptomatic

obstruction on examination

(e.g., visual, radiologic or

endoscopic)

Symptomatic (e.g., noisy airway

breathing), no respiratory

distress; medical intervention

indicated (e.g., steroids); limiting

instrumental ADL

Stridor; radiologic or endoscopic

intervention indicated (e.g.,

stent, laser); limiting self care

ADL

Life-threatening airway

compromise; urgent intervention

indicated (e.g., tracheotomy or

intubation)

Death

Definition: A finding of blockage of the lumen of the trachea.

CTCAE 4.03 - June 14, 2010 : Injury, poisoning and procedural complications

Injury, poisoning and procedural complications

Grade

Adverse Event 1 2 3 4 5

Tracheostomy site bleeding Minimal bleeding identified on

clinical exam; intervention not

indicated

Moderate bleeding; medical

intervention indicated

Severe bleeding; transfusion

indicated; radiologic or

endoscopic intervention

indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A finding of blood leakage from the tracheostomy site.

Ureteric anastomotic leak Asymptomatic diagnostic

observations only; intervention

not indicated

Symptomatic; medical

intervention indicated

Severe symptoms; radiologic,

endoscopic or elective operative

intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A finding of leakage due to breakdown of a ureteral anastomosis (surgical connection of two separate anatomic structures).

Urethral anastomotic leak Asymptomatic diagnostic

observations only; intervention

not indicated

Symptomatic; medical

intervention indicated

Severe symptoms; radiologic,

endoscopic or elective operative

intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A finding of leakage due to breakdown of a urethral anastomosis (surgical connection of two separate anatomic structures).

Urostomy leak Asymptomatic diagnostic

observations only; intervention

not indicated

Symptomatic; medical

intervention indicated

Severe symptoms; radiologic,

endoscopic or elective operative

intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A finding of leakage of contents from a urostomy.

Urostomy obstruction Asymptomatic diagnostic

observations only; intervention

not indicated

Symptomatic; dilation or

endoscopic repair or stent

placement indicated

Altered organ function (e.g.,

sepsis or hydronephrosis, or

renal dysfunction); elective

operative intervention indicated

Life-threatening consequences;

organ failure; urgent operative

intervention indicated

Death

Definition: A finding of blockage of the urostomy.

Urostomy site bleeding Minimal bleeding identified on

clinical exam; intervention not

indicated

Moderate bleeding; medical

intervention indicated

Severe bleeding; transfusion

indicated; radiologic or

endoscopic intervention

indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A finding of bleeding from the urostomy site.

Urostomy stenosis - Symptomatic but no

hydronephrosis, no sepsis or no

renal dysfunction; dilation or

endoscopic repair or stent

placement indicated

Symptomatic (e.g.,

hydronephrosis, or renal

dysfunction); elective operative

intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A finding of narrowing of the opening of a urostomy.

Uterine anastomotic leak Asymptomatic diagnostic

observations only; intervention

not indicated

Symptomatic; medical

intervention indicated

Severe symptoms; radiologic,

endoscopic or elective operative

intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A finding of leakage due to breakdown of a uterine anastomosis (surgical connection of two separate anatomic structures).

Uterine perforation Asymptomatic diagnostic

observations only; intervention

not indicated

Symptomatic and intervention

not indicated

Severe symptoms; elective

operative intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by a rupture in the uterine wall.

Vaginal anastomotic leak Asymptomatic diagnostic

observations only; intervention

not indicated

Symptomatic; medical

intervention indicated

Severe symptoms; radiologic,

endoscopic or elective operative

intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A finding of leakage due to breakdown of a vaginal anastomosis (surgical connection of two separate anatomic structures).

Vas deferens anastomotic leak Asymptomatic diagnostic

observations only; intervention

not indicated

Symptomatic; medical

intervention indicated

Severe symptoms; radiologic,

endoscopic or elective operative

intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A finding of leakage due to breakdown of a vas deferens anastomosis (surgical connection of two separate anatomic structures).

Vascular access complication - Device dislodgement, blockage,

leak, or malposition; device

replacement indicated

Deep vein or cardiac

thrombosis; intervention

indicated (e.g., anticoagulation,

lysis, filter, invasive procedure)

Embolic event including

pulmonary embolism or life-

threatening thrombus

Death

Definition: A finding of a previously undocumented problem related to the vascular access site.

CTCAE 4.03 - June 14, 2010 : Injury, poisoning and procedural complications

Injury, poisoning and procedural complications

Grade

Adverse Event 1 2 3 4 5

Venous injury Asymptomatic diagnostic

finding; intervention not

indicated

Symptomatic (e.g.,

claudication); repair or revision

not indicated

Severe symptoms; limiting self

care ADL; repair or revision

indicated; disabling

Life-threatening consequences;

evidence of end organ damage;

urgent operative intervention

indicated

Death

Definition: A finding of damage to a vein.

Wound complication Incisional separation of <=25%

of wound, no deeper than

superficial fascia

Incisional separation >25% of

wound; local care indicated

Hernia without evidence of

strangulation; fascial

disruption/dehiscence; primary

wound closure or revision by

operative intervention indicated

Hernia with evidence of

strangulation; major

reconstruction flap, grafting,

resection, or amputation

indicated

Death

Definition: A finding of development of a new problem at the site of an existing wound.

Wound dehiscence Incisional separation of <=25%

of wound, no deeper than

superficial fascia

Incisional separation >25% of

wound with local care;

asymptomatic hernia or

symptomatic hernia without

evidence of strangulation

Fascial disruption or dehiscence

without evisceration; primary

wound closure or revision by

operative intervention indicated

Life-threatening consequences;

symptomatic hernia with

evidence of strangulation;

fascial disruption with

evisceration; major

reconstruction flap, grafting,

resection, or amputation

indicated

Death

Definition: A finding of separation of the approximated margins of a surgical wound.

Wrist fracture Mild; non-surgical intervention

indicated

Limiting instrumental ADL;

operative intervention indicated

Limiting self care ADL; elective

surgery indicated

- -

Definition: A finding of traumatic injury to the wrist joint in which the continuity of a wrist bone is broken.

Injury, poisoning and procedural

complications - Other, specify

Asymptomatic or mild

symptoms; clinical or diagnostic

observations only; intervention

not indicated

Moderate; minimal, local or

noninvasive intervention

indicated; limiting age-

appropriate instrumental ADL

Severe or medically significant

but not immediately life-

threatening; hospitalization or

prolongation of existing

hospitalization indicated;

disabling; limiting self care ADL

Life-threatening consequences;

urgent intervention indicated

Death

CTCAE 4.03 - June 14, 2010 : Investigations

14. Investigations

Investigations

Grade

Adverse Event 1 2 3 4 5

Activated partial thromboplastin

time prolonged

>ULN - 1.5 x ULN >1.5 - 2.5 x ULN >2.5 x ULN; hemorrhage - -

Definition: An abnormal laboratory test result in which the partial thromboplastin time is found to be greater than the control value. As a possible indicator of coagulopathy, a prolonged

partial thromboplastin time (PTT) may occur in a variety of diseases and disorders, both primary and related to treatment.

Alanine aminotransferase

increased

>ULN - 3.0 x ULN >3.0 - 5.0 x ULN >5.0 - 20.0 x ULN >20.0 x ULN -

Definition: A finding based on laboratory test results that indicate an increase in the level of alanine aminotransferase (ALT or SGPT) in the blood specimen.

Alkaline phosphatase increased >ULN - 2.5 x ULN >2.5 - 5.0 x ULN >5.0 - 20.0 x ULN >20.0 x ULN -

Definition: A finding based on laboratory test results that indicate an increase in the level of alkaline phosphatase in a blood specimen.

Aspartate aminotransferase

increased

>ULN - 3.0 x ULN >3.0 - 5.0 x ULN >5.0 - 20.0 x ULN >20.0 x ULN -

Definition: A finding based on laboratory test results that indicate an increase in the level of aspartate aminotransferase (AST or SGOT) in a blood specimen.

Blood antidiuretic hormone

abnormal

Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; medical

intervention indicated

Hospitalization indicated - -

Definition: A finding based on laboratory test results that indicate abnormal levels of antidiuretic hormone in the blood specimen.

Blood bilirubin increased >ULN - 1.5 x ULN >1.5 - 3.0 x ULN >3.0 - 10.0 x ULN >10.0 x ULN -

Definition: A finding based on laboratory test results that indicate an abnormally high level of bilirubin in the blood. Excess bilirubin is associated with jaundice.

Blood corticotrophin decreased Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; medical

intervention indicated

Hospitalization indicated - -

Definition: A finding based on laboratory test results that indicate an decrease in levels of corticotrophin in a blood specimen.

Blood gonadotrophin abnormal Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; medical

intervention indicated; limiting

instrumental ADL

Severe symptoms; limiting self

care ADL

- -

Definition: A finding based on laboratory test results that indicate abnormal levels of gonadotrophin hormone in a blood specimen.

Blood prolactin abnormal Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Moderate symptoms; limiting

instrumental ADL

- - -

Definition: A finding based on laboratory test results that indicate abnormal levels of prolactin hormone in a blood specimen.

Carbon monoxide diffusing

capacity decreased

3 - 5 units below LLN; for follow-

up, a decrease of 3 - 5 units

(ml/min/mm Hg) below the

baseline value

6 - 8 units below LLN; for follow-

up, an asymptomatic decrease

of >5 - 8 units (ml/min/mm Hg)

below the baseline value

Asymptomatic decrease of >8

units drop; >5 units drop along

with the presence of pulmonary

symptoms (e.g. , >Grade 2

hypoxia or >Grade 2 or higher

dyspnea)

- -

Definition: A finding based on lung function test results that indicate a decrease in the lung capacity to absorb carbon monoxide.

Cardiac troponin I increased Levels above the upper limit of

normal and below the level of

myocardial infarction as defined

by the manufacturer

- Levels consistent with

myocardial infarction as defined

by the manufacturer

- -

Definition: A laboratory test result which indicates increased levels of cardiac troponin I in a biological specimen.

Cardiac troponin T increased Levels above the upper limit of

normal and below the level of

myocardial infarction as defined

by the manufacturer

- Levels consistent with

myocardial infarction as defined

by the manufacturer

- -

Definition: A laboratory test result which indicates increased levels of cardiac troponin T in a biological specimen.

CD4 lymphocytes decreased <LLN - 500/mm3; <LLN - 0.5 x

10e9 /L

<500 - 200/mm3; <0.5 - 0.2 x

10e9 /L

<200 - 50/mm3; <0.2 x 0.05 -

10e9 /L

<50/mm3; <0.05 x 10e9 /L -

Definition: A finding based on laboratory test results that indicate an decrease in levels of CD4 lymphocytes in a blood specimen.

Cholesterol high >ULN - 300 mg/dL; >ULN - 7.75

mmol/L

>300 - 400 mg/dL; >7.75 - 10.34

mmol/L

>400 - 500 mg/dL; >10.34 -

12.92 mmol/L

>500 mg/dL; >12.92 mmol/L -

Definition: A finding based on laboratory test results that indicate higher than normal levels of cholesterol in a blood specimen.

CPK increased >ULN - 2.5 x ULN >2.5 x ULN - 5 x ULN >5 x ULN - 10 x ULN >10 x ULN -

Definition: A finding based on laboratory test results that indicate an increase in levels of creatine phosphokinase in a blood specimen.

CTCAE 4.03 - June 14, 2010 : Investigations

Investigations

Grade

Adverse Event 1 2 3 4 5

Creatinine increased >1 - 1.5 x baseline; >ULN - 1.5

x ULN

>1.5 - 3.0 x baseline; >1.5 - 3.0

x ULN

>3.0 baseline; >3.0 - 6.0 x ULN >6.0 x ULN -

Definition: A finding based on laboratory test results that indicate increased levels of creatinine in a biological specimen.

Ejection fraction decreased - Resting ejection fraction (EF) 50

- 40%; 10 - 19% drop from

baseline

Resting ejection fraction (EF) 39

- 20%; >20% drop from baseline

Resting ejection fraction (EF)

<20%

Definition: The percentage computed when the amount of blood ejected during a ventricular contraction of the heart is compared to the amount that was present prior to the

contraction.

Electrocardiogram QT corrected

interval prolonged

QTc 450 - 480 ms QTc 481 - 500 ms QTc >= 501 ms on at least two

separate ECGs

QTc >= 501 or >60 ms change

from baseline and Torsade de

pointes or polymorphic

ventricular tachycardia or

signs/symptoms of serious

arrhythmia

Definition: A finding of a cardiac dysrhythmia characterized by an abnormally long corrected QT interval.

Fibrinogen decreased <1.0 - 0.75 x LLN or <25%

decrease from baseline

<0.75 - 0.5 x LLN or 25 - <50%

decrease from baseline

<0.5 - 0.25 x LLN or 50 - <75%

decrease from baseline

<0.25 x LLN or 75% decrease

from baseline or absolute value

<50 mg/dL

Definition: A finding based on laboratory test results that indicate an decrease in levels of fibrinogen in a blood specimen.

Forced expiratory volume

decreased

FEV1% (percentages of

observed FEV1 and FVC

related to their respective

predicted values) 99 - 70%

predicted

FEV1 60 - 69% 50 - 59% <= 49% -

Definition: A finding based on test results that indicate a relative decrease in the fraction of the forced vital capacity that is exhaled in a specific number of seconds.

GGT increased >ULN - 2.5 x ULN >2.5 - 5.0 x ULN >5.0 - 20.0 x ULN >20.0 x ULN -

Definition: A finding based on laboratory test results that indicate higher than normal levels of the enzyme gamma-glutamyltransferase in the blood specimen. GGT (gamma-

glutamyltransferase ) catalyzes the transfer of a gamma glutamyl group from a gamma glutamyl peptide to another peptide, amino acids or water.

Growth hormone abnormal Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; medical

intervention indicated; limiting

instrumental ADL

- - -

Definition: A finding based on laboratory test results that indicate abnormal levels of growth hormone in a biological specimen.

Haptoglobin decreased <LLN - - - -

Definition: A finding based on laboratory test results that indicate an decrease in levels of haptoglobin in a blood specimen.

Hemoglobin increased Increase in >0 - 2 gm/dL above

ULN or above baseline if

baseline is above ULN

Increase in >2 - 4 gm/dL above

ULN or above baseline if

baseline is above ULN

Increase in >4 gm/dL above

ULN or above baseline if

baseline is above ULN

- -

Definition: A finding based on laboratory test results that indicate increased levels of hemoglobin in a biological specimen.

INR increased >1 - 1.5 x ULN; >1 - 1.5 times

above baseline if on

anticoagulation

>1.5 - 2.5 x ULN; >1.5 - 2.5

times above baseline if on

anticoagulation

>2.5 x ULN; >2.5 times above

baseline if on anticoagulation

- -

Definition: A finding based on laboratory test results that indicate an increase in the ratio of the patient's prothrombin time to a control sample in the blood.

Lipase increased >ULN - 1.5 x ULN >1.5 - 2.0 x ULN >2.0 - 5.0 x ULN >5.0 x ULN -

Definition: A finding based on laboratory test results that indicate an increase in the level of lipase in a biological specimen.

Lymphocyte count decreased <LLN - 800/mm3; <LLN - 0.8 x

10e9 /L

<800 - 500/mm3; <0.8 - 0.5 x

10e9 /L

<500 - 200/mm3; <0.5 - 0.2 x

10e9 /L

<200/mm3; <0.2 x 10e9 /L -

Definition: A finding based on laboratory test results that indicate a decrease in number of lymphocytes in a blood specimen.

Lymphocyte count increased - >4000/mm3 - 20,000/mm3 >20,000/mm3 - -

Definition: A finding based on laboratory test results that indicate an abnormal increase in the number of lymphocytes in the blood, effusions or bone marrow.

Neutrophil count decreased <LLN - 1500/mm3; <LLN - 1.5 x

10e9 /L

<1500 - 1000/mm3; <1.5 - 1.0 x

10e9 /L

<1000 - 500/mm3; <1.0 - 0.5 x

10e9 /L

<500/mm3; <0.5 x 10e9 /L -

Definition: A finding based on laboratory test results that indicate a decrease in number of neutrophils in a blood specimen.

Pancreatic enzymes decreased <LLN and asymptomatic Increase in stool frequency,

bulk, or odor; steatorrhea

Sequelae of absorption

deficiency

- -

Definition: A finding based on laboratory test results that indicate an decrease in levels of pancreatic enzymes in a biological specimen.

CTCAE 4.03 - June 14, 2010 : Investigations

Investigations

Grade

Adverse Event 1 2 3 4 5

Platelet count decreased <LLN - 75,000/mm3; <LLN -

75.0 x 10e9 /L

<75,000 - 50,000/mm3; <75.0 -

50.0 x 10e9 /L

<50,000 - 25,000/mm3; <50.0 -

25.0 x 10e9 /L

<25,000/mm3; <25.0 x 10e9 /L -

Definition: A finding based on laboratory test results that indicate a decrease in number of platelets in a blood specimen.

Serum amylase increased >ULN - 1.5 x ULN >1.5 - 2.0 x ULN >2.0 - 5.0 x ULN >5.0 x ULN -

Definition: A finding based on laboratory test results that indicate an increase in the levels of amylase in a serum specimen.

Urine output decreased - - Oliguria (<80 ml in 8 hr) Anuria (<240 ml in 24 hr) -

Definition: A finding based on test results that indicate urine production is less relative to previous output.

Vital capacity abnormal 90 - 75% of predicted value <75 - 50% of predicted value;

limiting instrumental ADL

<50% of predicted value;

limiting self care ADL

- -

Definition: A finding based on pulmonary function test results that indicate an abnormal vital capacity (amount of exhaled after a maximum inhalation) when compared to the predicted

value.

Weight gain 5 - <10% from baseline 10 - <20% from baseline >=20% from baseline - -

Definition: A finding characterized by an increase in overall body weight; for pediatrics, greater than the baseline growth curve.

Weight loss 5 to <10% from baseline;

intervention not indicated

10 - <20% from baseline;

nutritional support indicated

>=20% from baseline; tube

feeding or TPN indicated

- -

Definition: A finding characterized by a decrease in overall body weight; for pediatrics, less than the baseline growth curve.

White blood cell decreased <LLN - 3000/mm3; <LLN - 3.0 x

10e9 /L

<3000 - 2000/mm3; <3.0 - 2.0 x

10e9 /L

<2000 - 1000/mm3; <2.0 - 1.0 x

10e9 /L

<1000/mm3; <1.0 x 10e9 /L -

Definition: A finding based on laboratory test results that indicate an decrease in number of white blood cells in a blood specimen.

Investigations - Other, specify Asymptomatic or mild

symptoms; clinical or diagnostic

observations only; intervention

not indicated

Moderate; minimal, local or

noninvasive intervention

indicated; limiting age-

appropriate instrumental ADL

Severe or medically significant

but not immediately life-

threatening; hospitalization or

prolongation of existing

hospitalization indicated;

disabling; limiting self care ADL

Life-threatening consequences;

urgent intervention indicated

Death

CTCAE 4.03 - June 14, 2010 : Metabolism and nutrition disorders

15. Metabolism and nutrition disorders

Metabolism and nutrition disorders

Grade

Adverse Event 1 2 3 4 5

Acidosis pH <normal, but >=7.3 - pH <7.3 Life-threatening consequences Death

Definition: A disorder characterized by abnormally high acidity (high hydrogen-ion concentration) of the blood and other body tissues.

Alcohol intolerance - Present Severe symptoms; limiting self

care ADL

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an increase in sensitivity to the adverse effects of alcohol, which can include nasal congestion, skin flushes, heart dysrhythmias, nausea,

vomiting, indigestion and headaches.

Alkalosis pH >normal, but <=7.5 - pH >7.5 Life-threatening consequences Death

Definition: A disorder characterized by abnormally high alkalinity (low hydrogen-ion concentration) of the blood and other body tissues.

Anorexia Loss of appetite without

alteration in eating habits

Oral intake altered without

significant weight loss or

malnutrition; oral nutritional

supplements indicated

Associated with significant

weight loss or malnutrition (e.g.,

inadequate oral caloric and/or

fluid intake); tube feeding or

TPN indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by a loss of appetite.

Dehydration Increased oral fluids indicated;

dry mucous membranes;

diminished skin turgor

IV fluids indicated <24 hrs IV fluids or hospitalization

indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by excessive loss of water from the body. It is usually caused by severe diarrhea, vomiting or diaphoresis.

Glucose intolerance Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; dietary

modification or oral agent

indicated

Severe symptoms; insulin

indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an inability to properly metabolize glucose.

Hypercalcemia Corrected serum calcium of

>ULN - 11.5 mg/dL; >ULN - 2.9

mmol/L; Ionized calcium >ULN

- 1.5 mmol/L

Corrected serum calcium of

>11.5 - 12.5 mg/dL; >2.9 - 3.1

mmol/L; Ionized calcium >1.5 -

1.6 mmol/L; symptomatic

Corrected serum calcium of

>12.5 - 13.5 mg/dL; >3.1 - 3.4

mmol/L; Ionized calcium >1.6 -

1.8 mmol/L; hospitalization

indicated

Corrected serum calcium of

>13.5 mg/dL; >3.4 mmol/L;

Ionized calcium >1.8 mmol/L;

life-threatening consequences

Death

Definition: A disorder characterized by laboratory test results that indicate an elevation in the concentration of calcium (corrected for albumin) in blood.

Hyperglycemia Fasting glucose value >ULN -

160 mg/dL; Fasting glucose

value >ULN - 8.9 mmol/L

Fasting glucose value >160 -

250 mg/dL; Fasting glucose

value >8.9 - 13.9 mmol/L

>250 - 500 mg/dL; >13.9 - 27.8

mmol/L; hospitalization

indicated

>500 mg/dL; >27.8 mmol/L; life-

threatening consequences

Death

Definition: A disorder characterized by laboratory test results that indicate an elevation in the concentration of blood sugar. It is usually an indication of diabetes mellitus or glucose

intolerance.

Hyperkalemia >ULN - 5.5 mmol/L >5.5 - 6.0 mmol/L >6.0 - 7.0 mmol/L;

hospitalization indicated

>7.0 mmol/L; life-threatening

consequences

Death

Definition: A disorder characterized by laboratory test results that indicate an elevation in the concentration of potassium in the blood; associated with kidney failure or sometimes with

the use of diuretic drugs.

Hypermagnesemia >ULN - 3.0 mg/dL; >ULN - 1.23

mmol/L

- >3.0 - 8.0 mg/dL; >1.23 - 3.30

mmol/L

>8.0 mg/dL; >3.30 mmol/L; life-

threatening consequences

Death

Definition: A disorder characterized by laboratory test results that indicate an elevation in the concentration of magnesium in the blood.

Hypernatremia >ULN - 150 mmol/L >150 - 155 mmol/L >155 - 160 mmol/L;

hospitalization indicated

>160 mmol/L; life-threatening

consequences

Death

Definition: A disorder characterized by laboratory test results that indicate an elevation in the concentration of sodium in the blood.

Hypertriglyceridemia 150 mg/dL - 300 mg/dL; 1.71

mmol/L - 3.42 mmol/L

>300 mg/dL - 500 mg/dL; >3.42

mmol/L - 5.7 mmol/L

>500 mg/dL - 1000 mg/dL; >5.7

mmol/L - 11.4 mmol/L

>1000 mg/dL; >11.4 mmol/L;

life-threatening consequences

Death

Definition: A disorder characterized by laboratory test results that indicate an elevation in the concentration of triglyceride concentration in the blood.

Hyperuricemia >ULN - 10 mg/dL (0.59 mmol/L)

without physiologic

consequences

- >ULN - 10 mg/dL (0.59 mmol/L)

with physiologic consequences

>10 mg/dL; >0.59 mmol/L; life-

threatening consequences

Death

Definition: A disorder characterized by laboratory test results that indicate an elevation in the concentration of uric acid.

Hypoalbuminemia <LLN - 3 g/dL; <LLN - 30 g/L <3 - 2 g/dL; <30 - 20 g/L <2 g/dL; <20 g/L Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by laboratory test results that indicate a low concentration of albumin in the blood.

CTCAE 4.03 - June 14, 2010 : Metabolism and nutrition disorders

Metabolism and nutrition disorders

Grade

Adverse Event 1 2 3 4 5

Hypocalcemia Corrected serum calcium of

<LLN - 8.0 mg/dL; <LLN - 2.0

mmol/L; Ionized calcium <LLN -

1.0 mmol/L

Corrected serum calcium of

<8.0 - 7.0 mg/dL; <2.0 - 1.75

mmol/L; Ionized calcium <1.0 -

0.9 mmol/L; symptomatic

Corrected serum calcium of

<7.0 - 6.0 mg/dL; <1.75 - 1.5

mmol/L; Ionized calcium <0.9 -

0.8 mmol/L; hospitalization

indicated

Corrected serum calcium of

<6.0 mg/dL; <1.5 mmol/L;

Ionized calcium <0.8 mmol/L;

life-threatening consequences

Death

Definition: A disorder characterized by laboratory test results that indicate a low concentration of calcium (corrected for albumin) in the blood.

Hypoglycemia <LLN - 55 mg/dL; <LLN - 3.0

mmol/L

<55 - 40 mg/dL; <3.0 - 2.2

mmol/L

<40 - 30 mg/dL; <2.2 - 1.7

mmol/L

<30 mg/dL; <1.7 mmol/L; life-

threatening consequences;

seizures

Death

Definition: A disorder characterized by laboratory test results that indicate a low concentration of glucose in the blood.

Hypokalemia <LLN - 3.0 mmol/L <LLN - 3.0 mmol/L;

symptomatic; intervention

indicated

<3.0 - 2.5 mmol/L;

hospitalization indicated

<2.5 mmol/L; life-threatening

consequences

Death

Definition: A disorder characterized by laboratory test results that indicate a low concentration of potassium in the blood.

Hypomagnesemia <LLN - 1.2 mg/dL; <LLN - 0.5

mmol/L

<1.2 - 0.9 mg/dL; <0.5 - 0.4

mmol/L

<0.9 - 0.7 mg/dL; <0.4 - 0.3

mmol/L

<0.7 mg/dL; <0.3 mmol/L; life-

threatening consequences

Death

Definition: A disorder characterized by laboratory test results that indicate a low concentration of magnesium in the blood.

Hyponatremia <LLN - 130 mmol/L - <130 - 120 mmol/L <120 mmol/L; life-threatening

consequences

Death

Definition: A disorder characterized by laboratory test results that indicate a low concentration of sodium in the blood.

Hypophosphatemia <LLN - 2.5 mg/dL; <LLN - 0.8

mmol/L

<2.5 - 2.0 mg/dL; <0.8 - 0.6

mmol/L

<2.0 - 1.0 mg/dL; <0.6 - 0.3

mmol/L

<1.0 mg/dL; <0.3 mmol/L; life-

threatening consequences

Death

Definition: A disorder characterized by laboratory test results that indicate a low concentration of phosphates in the blood.

Iron overload - Moderate symptoms;

intervention not indicated

Severe symptoms; intervention

indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by accumulation of iron in the tissues.

Obesity - BMI 25 - 29.9 kg/m2 BMI 30 - 39.9 kg/m2 BMI >=40 kg/m2 -

Definition: A disorder characterized by having a high amount of body fat.

Tumor lysis syndrome - - Present Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by metabolic abnormalities that result from a spontaneous or therapy-related cytolysis of tumor cells.

Metabolism and nutrition

disorders - Other, specify

Asymptomatic or mild

symptoms; clinical or diagnostic

observations only; intervention

not indicated

Moderate; minimal, local or

noninvasive intervention

indicated; limiting age-

appropriate instrumental ADL

Severe or medically significant

but not immediately life-

threatening; hospitalization or

prolongation of existing

hospitalization indicated;

disabling; limiting self care ADL

Life-threatening consequences;

urgent intervention indicated

Death

CTCAE 4.03 - June 14, 2010 : Musculoskeletal and connective tissue disorders

16. Musculoskeletal and connective tissue disorders

Musculoskeletal and connective tissue disorders

Grade

Adverse Event 1 2 3 4 5

Abdominal soft tissue necrosis - Local wound care; medical

intervention indicated (e.g.,

dressings or topical

medications)

Operative debridement or other

invasive intervention indicated

(e.g. tissue reconstruction, flap

or grafting)

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by a necrotic process occurring in the soft tissues of the abdominal wall.

Arthralgia Mild pain Moderate pain; limiting

instrumental ADL

Severe pain; limiting self care

ADL

- -

Definition: A disorder characterized by a sensation of marked discomfort in a joint.

Arthritis Mild pain with inflammation,

erythema, or joint swelling

Moderate pain associated with

signs of inflammation,

erythema, or joint swelling;

limiting instrumental ADL

Severe pain associated with

signs of inflammation,

erythema, or joint swelling;

irreversible joint damage;

disabling; limiting self care ADL

- -

Definition: A disorder characterized by inflammation involving a joint.

Avascular necrosis Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; limiting

instrumental ADL

Severe symptoms; limiting self

care ADL; elective operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by necrotic changes in the bone tissue due to interruption of blood supply. Most often affecting the epiphysis of the long bones, the necrotic

changes result in the collapse and the destruction of the bone structure.

Back pain Mild pain Moderate pain; limiting

instrumental ADL

Severe pain; limiting self care

ADL

- -

Definition: A disorder characterized by marked discomfort sensation in the back region.

Bone pain Mild pain Moderate pain; limiting

instrumental ADL

Severe pain; limiting self care

ADL

- -

Definition: A disorder characterized by marked discomfort sensation in the bones.

Buttock pain Mild pain Moderate pain; limiting

instrumental ADL

Severe pain; limiting self care

ADL

- -

Definition: A disorder characterized by marked discomfort sensation in the buttocks.

Chest wall pain Mild pain Moderate pain; limiting

instrumental ADL

Severe pain; limiting self care

ADL

- -

Definition: A disorder characterized by marked discomfort sensation in the chest wall region.

Exostosis Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; limiting

instrumental ADL

Severe symptoms; limiting self

care ADL; elective operative

intervention indicated

- -

Definition: A disorder characterized by non-neoplastic overgrowth of bone.

Fibrosis deep connective tissue Mild induration, able to move

skin parallel to plane (sliding)

and perpendicular to skin

(pinching up)

Moderate induration, able to

slide skin, unable to pinch skin;

limiting instrumental ADL

Severe induration; unable to

slide or pinch skin; limiting joint

or orifice movement (e.g.

mouth, anus); limiting self care

ADL

Generalized; associated with

signs or symptoms of impaired

breathing or feeding

Death

Definition: A disorder characterized by fibrotic degeneration of the deep connective tissues.

Flank pain Mild pain Moderate pain; limiting

instrumental ADL

Severe pain; limiting self care

ADL

- -

Definition: A disorder characterized by marked discomfort sensation on the lateral side of the body in the region below the ribs and above the hip.

Generalized muscle weakness Symptomatic; weakness

perceived by patient but not

evident on physical exam

Symptomatic; weakness evident

on physical exam; weakness

limiting instrumental ADL

Weakness limiting self care

ADL; disabling

- -

Definition: A disorder characterized by a reduction in the strength of muscles in multiple anatomic sites.

Growth suppression Reduction in growth velocity by

10 - 29% ideally measured over

the period of a year

Reduction in growth velocity by

30 - 49% ideally measured over

the period of a year or 0 - 49%

reduction in growth from the

baseline growth curve

Reduction in growth velocity of

>=50% ideally measured over

the period of a year

- -

Definition: A disorder characterized by of stature that is smaller than normal as expected for age.

CTCAE 4.03 - June 14, 2010 : Musculoskeletal and connective tissue disorders

Musculoskeletal and connective tissue disorders

Grade

Adverse Event 1 2 3 4 5

Head soft tissue necrosis - Local wound care; medical

intervention indicated (e.g.,

dressings or topical

medications)

Operative debridement or other

invasive intervention indicated

(e.g., tissue reconstruction, flap

or grafting)

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by a necrotic process occurring in the soft tissues of the head.

Joint effusion Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; limiting

instrumental ADL

Severe symptoms; limiting self

care ADL; elective operative

intervention indicated; disabling

- -

Definition: A disorder characterized by excessive fluid in a joint, usually as a result of joint inflammation.

Joint range of motion decreased <=25% loss of ROM (range of

motion); decreased ROM

limiting athletic activity

>25 - 50% decrease in ROM;

limiting instrumental ADL

>50% decrease in ROM; limiting

self care ADL; disabling

- -

Definition: A disorder characterized by a decrease in joint flexibility of any joint.

Joint range of motion decreased

cervical spine

Mild restriction of rotation or

flexion between 60 - 70 degrees

Rotation <60 degrees to right or

left; <60 degrees of flexion

Ankylosed/fused over multiple

segments with no C-spine

rotation

- -

Definition: A disorder characterized by a decrease in flexibility of a cervical spine joint.

Joint range of motion decreased

lumbar spine

Stiffness; difficulty bending to

the floor to pick up a very light

object but able to do athletic

activity

Pain with range of motion

(ROM) in lumbar spine; requires

a reaching aid to pick up a very

light object from the floor

<50% lumbar spine flexion;

associated with symptoms of

ankylosis or fused over multiple

segments with no L-spine

flexion (e.g., unable to reach to

floor to pick up a very light

object)

- -

Definition: A disorder characterized by a decrease in flexibility of a lumbar spine joint.

Kyphosis Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Moderate accentuation; limiting

instrumental ADL

Severe accentuation; operative

intervention indicated; limiting

self care ADL

- -

Definition: A disorder characterized by an abnormal increase in the curvature of the thoracic portion of the spine.

Lordosis Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Moderate accentuation; limiting

instrumental ADL

Severe accentuation; operative

intervention indicated; limiting

self care ADL

- -

Definition: A disorder characterized by an abnormal increase in the curvature of the lumbar portion of the spine.

Muscle weakness left-sided Symptomatic; perceived by

patient but not evident on

physical exam

Symptomatic; evident on

physical exam; limiting

instrumental ADL

Limiting self care ADL; disabling - -

Definition: A disorder characterized by a reduction in the strength of the muscles on the left side of the body.

Muscle weakness lower limb Symptomatic; perceived by

patient but not evident on

physical exam

Symptomatic; evident on

physical exam; limiting

instrumental ADL

Limiting self care ADL; disabling - -

Definition: A disorder characterized by a reduction in the strength of the lower limb muscles.

Muscle weakness right-sided Symptomatic; perceived by

patient but not evident on

physical exam

Symptomatic; evident on

physical exam; limiting

instrumental ADL

Limiting self care ADL; disabling - -

Definition: A disorder characterized by a reduction in the strength of the muscles on the right side of the body.

Muscle weakness trunk Symptomatic; perceived by

patient but not evident on

physical exam

Symptomatic; evident on

physical exam; limiting

instrumental ADL

Limiting self care ADL; disabling - -

Definition: A disorder characterized by a reduction in the strength of the trunk muscles.

Muscle weakness upper limb Symptomatic; perceived by

patient but not evident on

physical exam

Symptomatic; evident on

physical exam; limiting

instrumental ADL

Limiting self care ADL; disabling - -

Definition: A disorder characterized by a reduction in the strength of the upper limb muscles.

CTCAE 4.03 - June 14, 2010 : Musculoskeletal and connective tissue disorders

Musculoskeletal and connective tissue disorders

Grade

Adverse Event 1 2 3 4 5

Musculoskeletal deformity Cosmetically and functionally

insignificant hypoplasia

Deformity, hypoplasia, or

asymmetry able to be

remediated by prosthesis (e.g.,

shoe insert) or covered by

clothing

Significant deformity,

hypoplasia, or asymmetry,

unable to be remediated by

prosthesis or covered by

clothing; disabling

- -

Definition: A disorder characterized by of a malformation of the musculoskeletal system.

Myalgia Mild pain Moderate pain; limiting

instrumental ADL

Severe pain; limiting self care

ADL

- -

Definition: A disorder characterized by marked discomfort sensation originating from a muscle or group of muscles.

Myositis Mild pain Moderate pain associated with

weakness; pain limiting

instrumental ADL

Pain associated with severe

weakness; limiting self care

ADL

- -

Definition: A disorder characterized by inflammation involving the skeletal muscles.

Neck pain Mild pain Moderate pain; limiting

instrumental ADL

Severe pain; limiting self care

ADL

- -

Definition: A disorder characterized by marked discomfort sensation in the neck area.

Neck soft tissue necrosis - Local wound care; medical

intervention indicated (e.g.,

dressings or topical

medications)

Operative debridement or other

invasive intervention indicated

(e.g., tissue reconstruction, flap

or grafting)

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by a necrotic process occurring in the soft tissues of the neck.

Osteonecrosis of jaw Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; medical

intervention indicated (e.g.,

topical agents); limiting

instrumental ADL

Severe symptoms; limiting self

care ADL; elective operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by a necrotic process occurring in the bone of the mandible.

Osteoporosis Radiologic evidence of

osteoporosis or Bone Mineral

Density (BMD) t-score -1 to -2.5

(osteopenia); no loss of height

or intervention indicated

BMD t-score <-2.5; loss of

height <2 cm; anti-osteoporotic

therapy indicated; limiting

instrumental ADL

Loss of height >=2 cm;

hospitalization indicated; limiting

self care ADL

- -

Definition: A disorder characterized by reduced bone mass, with a decrease in cortical thickness and in the number and size of the trabeculae of cancellous bone (but normal chemical

composition), resulting in increased fracture incidence.

Pain in extremity Mild pain Moderate pain; limiting

instrumental ADL

Severe pain; limiting self care

ADL

- -

Definition: A disorder characterized by marked discomfort sensation in the upper or lower extremities.

Pelvic soft tissue necrosis - Local wound care; medical

intervention indicated (e.g.,

dressings or topical

medications)

Operative debridement or other

invasive intervention indicated

(e.g., tissue reconstruction, flap

or grafting)

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by a necrotic process occurring in the soft tissues of the pelvis.

Scoliosis <20 degrees; clinically

undetectable

>20 - 45 degrees; visible by

forward flexion; limiting

instrumental ADL

>45 degrees; scapular

prominence in forward flexion;

operative intervention indicated;

limiting self care ADL; disabling

- -

Definition: A disorder characterized by a malformed, lateral curvature of the spine.

Soft tissue necrosis lower limb - Local wound care; medical

intervention indicated (e.g.,

dressings or topical

medications)

Operative debridement or other

invasive intervention indicated

(e.g., tissue reconstruction, flap

or grafting)

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by a necrotic process occurring in the soft tissues of the lower extremity.

Soft tissue necrosis upper limb - Local wound care; medical

intervention indicated (e.g.,

dressings or topical

medications)

Operative debridement or other

invasive intervention indicated

(e.g., tissue reconstruction, flap

or grafting)

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by a necrotic process occurring in the soft tissues of the upper extremity.

CTCAE 4.03 - June 14, 2010 : Musculoskeletal and connective tissue disorders

Musculoskeletal and connective tissue disorders

Grade

Adverse Event 1 2 3 4 5

Superficial soft tissue fibrosis Mild induration, able to move

skin parallel to plane (sliding)

and perpendicular to skin

(pinching up)

Moderate induration, able to

slide skin, unable to pinch skin;

limiting instrumental ADL

Severe induration; unable to

slide or pinch skin; limiting joint

or orifice movement (e.g.,

mouth, anus); limiting self care

ADL

Generalized; associated with

signs or symptoms of impaired

breathing or feeding

Death

Definition: A disorder characterized by fibrotic degeneration of the superficial soft tissues.

Trismus Decreased ROM (range of

motion) without impaired eating

Decreased ROM requiring small

bites, soft foods or purees

Decreased ROM with inability to

adequately aliment or hydrate

orally

- -

Definition: A disorder characterized by lack of ability to open the mouth fully due to a decrease in the range of motion of the muscles of mastication.

Unequal limb length Mild length discrepancy <2 cm Moderate length discrepancy 2 -

5 cm; shoe lift indicated; limiting

instrumental ADL

Severe length discrepancy >5

cm; limiting self care ADL;

disabling; operative intervention

indicated

- -

Definition: A disorder characterized by of a discrepancy between the lengths of the lower or upper extremities.

Musculoskeletal and connective

tissue disorder - Other, specify

Asymptomatic or mild

symptoms; clinical or diagnostic

observations only; intervention

not indicated

Moderate; minimal, local or

noninvasive intervention

indicated; limiting age-

appropriate instrumental ADL

Severe or medically significant

but not immediately life-

threatening; hospitalization or

prolongation of existing

hospitalization indicated;

disabling; limiting self care ADL

Life-threatening consequences;

urgent intervention indicated

Death

CTCAE 4.03 - June 14, 2010 : Neoplasms benign, malignant and unspecified (incl cysts and polyps)

17. Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Grade

Adverse Event 1 2 3 4 5

Leukemia secondary to

oncology chemotherapy

- - - Present Death

Definition: A disorder characterized by leukemia arising as a result of the mutagenic effect of chemotherapy agents.

Myelodysplastic syndrome - - - Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by insufficiently healthy hematapoietic cell production by the bone marrow.

Treatment related secondary

malignancy

- - Non life-threatening secondary

malignancy

Acute life-threatening secondary

malignancy; blast crisis in

leukemia

Death

Definition: A disorder characterized by development of a malignancy most probably as a result of treatment for a previously existing malignancy.

Tumor pain Mild pain Moderate pain; limiting

instrumental ADL

Severe pain; limiting self care

ADL

- -

Definition: A disorder characterized by marked discomfort from a neoplasm that may be pressing on a nerve, blocking blood vessels, inflamed or fractured from metastasis.

Neoplasms benign, malignant

and unspecified (incl cysts and

polyps) - Other, specify

Asymptomatic or mild

symptoms; clinical or diagnostic

observations only; intervention

not indicated

Moderate; minimal, local or

noninvasive intervention

indicated; limiting age-

appropriate instrumental ADL

Severe or medically significant

but not immediately life-

threatening; hospitalization or

prolongation of existing

hospitalization indicated;

disabling; limiting self care ADL

Life-threatening consequences;

urgent intervention indicated

Death

CTCAE 4.03 - June 14, 2010 : Nervous system disorders

18. Nervous system disorders

Nervous system disorders

Grade

Adverse Event 1 2 3 4 5

Abducens nerve disorder Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Moderate symptoms; limiting

instrumental ADL

Severe symptoms; limiting self

care ADL

- -

Definition: A disorder characterized by involvement of the abducens nerve (sixth cranial nerve).

Accessory nerve disorder Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Moderate symptoms; limiting

instrumental ADL

Severe symptoms; limiting self

care ADL

- -

Definition: A disorder characterized by involvement of the accessory nerve (eleventh cranial nerve).

Acoustic nerve disorder NOS Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Moderate symptoms; limiting

instrumental ADL

Severe symptoms; limiting self

care ADL

- -

Definition: A disorder characterized by involvement of the acoustic nerve (eighth cranial nerve).

Akathisia Mild restlessness or increased

motor activity

Moderate restlessness or

increased motor activity; limiting

instrumental ADL

Severe restlessness or

increased motor activity; limiting

self care ADL

- -

Definition: A disorder characterized by an uncomfortable feeling of inner restlessness and inability to stay still; this is a side effect of some psychotropic drugs.

Amnesia Mild; transient memory loss Moderate; short term memory

loss; limiting instrumental ADL

Severe; long term memory loss;

limiting self care ADL

- -

Definition: A disorder characterized by systematic and extensive loss of memory.

Aphonia - - Voicelessness; unable to speak - -

Definition: A disorder characterized by the inability to speak. It may result from injuries to the vocal cords or may be functional (psychogenic).

Arachnoiditis Mild symptoms Moderate symptoms; limiting

instrumental ADL

Severe symptoms; limiting self

care ADL

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by inflammation of the arachnoid membrane and adjacent subarachnoid space.

Ataxia Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Moderate symptoms; limiting

instrumental ADL

Severe symptoms; limiting self

care ADL; mechanical

assistance indicated

- -

Definition: A disorder characterized by lack of coordination of muscle movements resulting in the impairment or inability to perform voluntary activities.

Brachial plexopathy Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Moderate symptoms; limiting

instrumental ADL

Severe symptoms; limiting self

care ADL

- -

Definition: A disorder characterized by regional paresthesia of the brachial plexus, marked discomfort and muscle weakness, and limited movement in the arm or hand.

Central nervous system

necrosis

Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Moderate symptoms;

corticosteroids indicated

Severe symptoms; medical

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by a necrotic process occurring in the brain and/or spinal cord.

Cerebrospinal fluid leakage Post-craniotomy: asymptomatic;

Post-lumbar puncture: transient

headache; postural care

indicated

Post-craniotomy: moderate

symptoms; medical intervention

indicated; Post-lumbar

puncture: persistent moderate

symptoms; blood patch

indicated

Severe symptoms; medical

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by loss of cerebrospinal fluid into the surrounding tissues.

Cognitive disturbance Mild cognitive disability; not

interfering with work/school/life

performance; specialized

educational services/devices

not indicated

Moderate cognitive disability;

interfering with work/school/life

performance but capable of

independent living; specialized

resources on part time basis

indicated

Severe cognitive disability;

significant impairment of

work/school/life performance

- -

Definition: A disorder characterized by a conspicuous change in cognitive function.

Concentration impairment Mild inattention or decreased

level of concentration

Moderate impairment in

attention or decreased level of

concentration; limiting

instrumental ADL

Severe impairment in attention

or decreased level of

concentration; limiting self care

ADL

- -

Definition: A disorder characterized by a deterioration in the ability to concentrate.

CTCAE 4.03 - June 14, 2010 : Nervous system disorders

Nervous system disorders

Grade

Adverse Event 1 2 3 4 5

Depressed level of

consciousness

Decreased level of alertness Sedation; slow response to

stimuli; limiting instrumental

ADL

Difficult to arouse Life-threatening consequences Death

Definition: A disorder characterized by a decrease in ability to perceive and respond.

Dizziness Mild unsteadiness or sensation

of movement

Moderate unsteadiness or

sensation of movement; limiting

instrumental ADL

Severe unsteadiness or

sensation of movement; limiting

self care ADL

- -

Definition: A disorder characterized by a disturbing sensation of lightheadedness, unsteadiness, giddiness, spinning or rocking.

Dysarthria Mild slurred speech Moderate impairment of

articulation or slurred speech

Severe impairment of

articulation or slurred speech

- -

Definition: A disorder characterized by slow and slurred speech resulting from an inability to coordinate the muscles used in speech.

Dysesthesia Mild sensory alteration Moderate sensory alteration;

limiting instrumental ADL

Severe sensory alteration;

limiting self care ADL

- -

Definition: A disorder characterized by distortion of sensory perception, resulting in an abnormal and unpleasant sensation.

Dysgeusia Altered taste but no change in

diet

Altered taste with change in diet

(e.g., oral supplements);

noxious or unpleasant taste;

loss of taste

- - -

Definition: A disorder characterized by abnormal sensual experience with the taste of foodstuffs; it can be related to a decrease in the sense of smell.

Dysphasia Awareness of receptive or

expressive characteristics; not

impairing ability to communicate

Moderate receptive or

expressive characteristics;

impairing ability to communicate

spontaneously

Severe receptive or expressive

characteristics; impairing ability

to read, write or communicate

intelligibly

- -

Definition: A disorder characterized by impairment of verbal communication skills, often resulting from brain damage.

Edema cerebral - - - Life-threatening consequences;

urgent intervention indicated

Definition: A disorder characterized by swelling due to an excessive accumulation of fluid in the brain.

Encephalopathy Mild symptoms Moderate symptoms; limiting

instrumental ADL

Severe symptoms; limiting self

care ADL

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by a pathologic process involving the brain.

Extrapyramidal disorder Mild involuntary movements Moderate involuntary

movements; limiting

instrumental ADL

Severe involuntary movements

or torticollis; limiting self care

ADL

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by abnormal, repetitive, involuntary muscle movements, frenzied speech and extreme restlessness.

Facial muscle weakness Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Moderate symptoms; limiting

instrumental ADL

Severe symptoms; limiting self

care ADL

- -

Definition: A disorder characterized by a reduction in the strength of the facial muscles.

Facial nerve disorder Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Moderate symptoms; limiting

instrumental ADL

Severe symptoms; limiting self

care ADL

- -

Definition: A disorder characterized by involvement of the facial nerve (seventh cranial nerve).

Glossopharyngeal nerve

disorder

Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Moderate symptoms; limiting

instrumental ADL

Severe symptoms; limiting self

care ADL

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by involvement of the glossopharyngeal nerve (ninth cranial nerve).

Headache Mild pain Moderate pain; limiting

instrumental ADL

Severe pain; limiting self care

ADL

- -

Definition: A disorder characterized by a sensation of marked discomfort in various parts of the head, not confined to the area of distribution of any nerve.

Hydrocephalus Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Moderate symptoms;

intervention not indicated

Severe symptoms or

neurological deficit; intervention

indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an abnormal increase of cerebrospinal fluid in the ventricles of the brain.

Hypersomnia Mild increased need for sleep Moderate increased need for

sleep

Severe increased need for

sleep

- -

Definition: A disorder characterized by characterized by excessive sleepiness during the daytime.

CTCAE 4.03 - June 14, 2010 : Nervous system disorders

Nervous system disorders

Grade

Adverse Event 1 2 3 4 5

Hypoglossal nerve disorder Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Moderate symptoms; limiting

instrumental ADL

Severe symptoms; limiting self

care ADL

- -

Definition: A disorder characterized by involvement of the hypoglossal nerve (twelfth cranial nerve).

Intracranial hemorrhage Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Moderate symptoms; medical

intervention indicated

Ventriculostomy, ICP

monitoring, intraventricular

thrombolysis, or operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by bleeding from the cranium.

Ischemia cerebrovascular Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Moderate symptoms - - -

Definition: A disorder characterized by a decrease or absence of blood supply to the brain caused by obstruction (thrombosis or embolism) of an artery resulting in neurological

damage.

IVth nerve disorder Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Moderate symptoms; limiting

instrumental ADL

Severe symptoms; limiting self

care ADL

- -

Definition: A disorder characterized by involvement of the trochlear nerve (fourth cranial nerve).

Lethargy Mild symptoms; reduced

alertness and awareness

Moderate symptoms; limiting

instrumental ADL

- - -

Definition: A disorder characterized by a decrease in consciousness characterized by mental and physical inertness.

Leukoencephalopathy Asymptomatic; small focal

T2/FLAIR hyperintensities;

involving periventricular white

matter or <1/3 of susceptible

areas of cerebrum +/- mild

increase in subarachnoid space

(SAS) and/or mild

ventriculomegaly

Moderate symptoms; focal

T2/FLAIR hyperintensities,

involving periventricular white

matter extending into centrum

semiovale or involving 1/3 to 2/3

of susceptible areas of

cerebrum +/- moderate increase

in SAS and/or moderate

ventriculomegaly

Severe symptoms; extensive

T2/FLAIR hyperintensities,

involving periventricular white

matter involving 2/3 or more of

susceptible areas of cerebrum

+/- moderate to severe increase

in SAS and/or moderate to

severe ventriculomegaly

Life-threatening consequences;

extensive T2/FLAIR

hyperintensities, involving

periventricular white matter

involving most of susceptible

areas of cerebrum +/- moderate

to severe increase in SAS

and/or moderate to severe

ventriculomegaly

Death

Definition: A disorder characterized by diffuse reactive astrocytosis with multiple areas of necrotic foci without inflammation.

Memory impairment Mild memory impairment Moderate memory impairment;

limiting instrumental ADL

Severe memory impairment;

limiting self care ADL

- -

Definition: A disorder characterized by a deterioration in memory function.

Meningismus Mild symptoms Moderate symptoms; limiting

instrumental ADL

Severe symptoms; limiting self

care ADL

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by neck stiffness, headache, and photophobia resulting from irritation of the cerebral meninges.

Movements involuntary Mild symptoms Moderate symptoms; limiting

instrumental ADL

Severe symptoms; limiting self

care ADL

- -

Definition: A disorder characterized by uncontrolled and purposeless movements.

Myelitis Asymptomatic; mild signs (e.g.,

Babinski's reflex or Lhermitte's

sign)

Moderate weakness or sensory

loss; limiting instrumental ADL

Severe weakness or sensory

loss; limiting self care ADL

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by inflammation involving the spinal cord. Symptoms include weakness, paresthesia, sensory loss, marked discomfort and incontinence.

Neuralgia Mild pain Moderate pain; limiting

instrumental ADL

Severe pain; limiting self care

ADL

- -

Definition: A disorder characterized by intense painful sensation along a nerve or group of nerves.

Nystagmus - Moderate symptoms; limiting

instrumental ADL

Severe symptoms; limiting self

care ADL

- -

Definition: A disorder characterized by involuntary movements of the eyeballs.

Oculomotor nerve disorder Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Moderate symptoms; limiting

instrumental ADL

Severe symptoms; limiting self

care ADL

- -

Definition: A disorder characterized by involvement of the oculomotor nerve (third cranial nerve).

Olfactory nerve disorder - Moderate symptoms; limiting

instrumental ADL

Severe symptoms; limiting self

care ADL

- -

Definition: A disorder characterized by involvement of the olfactory nerve (first cranial nerve).

CTCAE 4.03 - June 14, 2010 : Nervous system disorders

Nervous system disorders

Grade

Adverse Event 1 2 3 4 5

Paresthesia Mild symptoms Moderate symptoms; limiting

instrumental ADL

Severe symptoms; limiting self

care ADL

- -

Definition: A disorder characterized by functional disturbances of sensory neurons resulting in abnormal cutaneous sensations of tingling, numbness, pressure, cold, and warmth that

are experienced in the absence of a stimulus.

Peripheral motor neuropathy Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Moderate symptoms; limiting

instrumental ADL

Severe symptoms; limiting self

care ADL; assistive device

indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by inflammation or degeneration of the peripheral motor nerves.

Peripheral sensory neuropathy Asymptomatic; loss of deep

tendon reflexes or paresthesia

Moderate symptoms; limiting

instrumental ADL

Severe symptoms; limiting self

care ADL

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by inflammation or degeneration of the peripheral sensory nerves.

Phantom pain Mild pain Moderate pain; limiting

instrumental ADL

Severe pain; limiting self care

ADL

- -

Definition: A disorder characterized by marked discomfort related to a limb or an organ that is removed from or is not physically part of the body.

Presyncope - Present (e.g., near fainting) - - -

Definition: A disorder characterized by an episode of lightheadedness and dizziness which may precede an episode of syncope.

Pyramidal tract syndrome Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Moderate symptoms; limiting

instrumental ADL

Severe symptoms; limiting self

care ADL

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by dysfunction of the corticospinal (pyramidal) tracts of the spinal cord. Symptoms include an increase in the muscle tone in the lower extremities,

hyperreflexia, positive Babinski and a decrease in fine motor coordination.

Radiculitis Mild symptoms Moderate symptoms; limiting

instrumental ADL; medical

intervention indicated

Severe symptoms; limiting self

care ADL

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by inflammation involving a nerve root. Patients experience marked discomfort radiating along a nerve path because of spinal pressure on the

connecting nerve root.

Recurrent laryngeal nerve palsy Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Moderate symptoms Severe symptoms; medical

intervention indicated (e.g.,

thyroplasty, vocal cord injection)

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by paralysis of the recurrent laryngeal nerve.

Reversible posterior

leukoencephalopathy syndrome

Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Moderate symptoms; abnormal

imaging studies; limiting

instrumental ADL

Severe symptoms; very

abnormal imaging studies;

limiting self care ADL

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by headaches, mental status changes, visual disturbances, and seizures associated with imaging findings of posterior leukoencephalopathy. It has

been observed in association with hypertensive encephalopathy, eclampsia, and immunosuppressive and cytotoxic drug treatment. It is an acute or subacute reversible condition.

Seizure Brief partial seizure; no loss of

consciousness

Brief generalized seizure Multiple seizures despite

medical intervention

Life-threatening; prolonged

repetitive seizures

Death

Definition: A disorder characterized by a sudden, involuntary skeletal muscular contractions of cerebral or brain stem origin.

Sinus pain Mild pain Moderate pain; limiting

instrumental ADL

Severe pain; limiting self care

ADL

- -

Definition: A disorder characterized by marked discomfort in the face, between the eyes, or upper teeth originating from the sinuses.

Somnolence Mild but more than usual

drowsiness or sleepiness

Moderate sedation; limiting

instrumental ADL

Obtundation or stupor Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by characterized by excessive sleepiness and drowsiness.

Spasticity Mild or slight increase in muscle

tone

Moderate increase in muscle

tone and increase in resistance

through range of motion

Severe increase in muscle tone

and increase in resistance

through range of motion

Life-threatening; unable to move

active or passive range of

motion

Death

Definition: A disorder characterized by increased involuntary muscle tone that affects the regions interfering with voluntary movement. It results in gait, movement, and speech

disturbances.

Stroke Asymptomatic or mild

neurologic deficit; radiographic

findings only

Moderate neurologic deficit Severe neurologic deficit Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by a sudden loss of sensory function due to an intracranial vascular event.

Syncope - - Fainting; orthostatic collapse - -

Definition: A disorder characterized by spontaneous loss of consciousness caused by insufficient blood supply to the brain.

CTCAE 4.03 - June 14, 2010 : Nervous system disorders

Nervous system disorders

Grade

Adverse Event 1 2 3 4 5

Transient ischemic attacks Mild neurologic deficit with or

without imaging confirmation

Moderate neurologic deficit with

or without imaging confirmation

- - -

Definition: A disorder characterized by a brief attack (less than 24 hours) of cerebral dysfunction of vascular origin, with no persistent neurological deficit.

Tremor Mild symptoms Moderate symptoms; limiting

instrumental ADL

Severe symptoms; limiting self

care ADL

- -

Definition: A disorder characterized by the uncontrolled shaking movement of the whole body or individual parts.

Trigeminal nerve disorder Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Moderate symptoms; limiting

instrumental ADL

Severe symptoms; limiting self

care ADL

- -

Definition: A disorder characterized by involvement of the trigeminal nerve (fifth cranial nerve).

Vagus nerve disorder Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Moderate symptoms; limiting

instrumental ADL

Severe symptoms; limiting self

care ADL

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by involvement of the vagus nerve (tenth cranial nerve).

Vasovagal reaction - - Present Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by a sudden drop of the blood pressure, bradycardia, and peripheral vasodilation that may lead to loss of consciousness. It results from an

increase in the stimulation of the vagus nerve.

Nervous system disorders -

Other, specify

Asymptomatic or mild

symptoms; clinical or diagnostic

observations only; intervention

not indicated

Moderate; minimal, local or

noninvasive intervention

indicated; limiting age-

appropriate instrumental ADL

Severe or medically significant

but not immediately life-

threatening; hospitalization or

prolongation of existing

hospitalization indicated;

disabling; limiting self care ADL

Life-threatening consequences;

urgent intervention indicated

Death

CTCAE 4.03 - June 14, 2010 : Pregnancy, puerperium and perinatal conditions

19. Pregnancy, puerperium and perinatal conditions

Pregnancy, puerperium and perinatal conditions

Grade

Adverse Event 1 2 3 4 5

Fetal death - - - - Fetal loss at

any

gestational

age

Definition: A disorder characterized by death in utero; failure of the product of conception to show evidence of respiration, heartbeat, or definite movement of a voluntary muscle after

expulsion from the uterus, without possibility of resuscitation.

Fetal growth retardation - <10% percentile of weight for

gestational age

<5% percentile of weight for

gestational age

<1% percentile of weight for

gestational age

Definition: A disorder characterized by inhibition of fetal growth resulting in the inability of the fetus to achieve its potential weight.

Premature delivery Delivery of a liveborn infant at

>34 to 37 weeks gestation

Delivery of a liveborn infant at

>28 to 34 weeks gestation

Delivery of a liveborn infant at

24 to 28 weeks gestation

Delivery of a liveborn infant at

24 weeks of gestation or less

Definition: A disorder characterized by delivery of a viable infant before the normal end of gestation. Typically, viability is achievable between the twentieth and thirty-seventh week of

gestation.

Unintended pregnancy - - Unintended pregnancy - -

Definition: A disorder characterized by an unexpected pregnancy at the time of conception.

Pregnancy, puerperium and

perinatal conditions - Other,

specify

Asymptomatic or mild

symptoms; clinical or diagnostic

observations only; intervention

not indicated

Moderate, local or noninvasive

intervention indicated; limiting

instrumental ADL

Severe or medically significant

but not immediately life-

threatening; hospitalization or

prolongation of existing

hospitalization indicated;

disabling; limiting self care ADL

Life-threatening consequences;

urgent intervention indicated

Death

CTCAE 4.03 - June 14, 2010 : Psychiatric disorders

20. Psychiatric disorders

Psychiatric disorders

Grade

Adverse Event 1 2 3 4 5

Agitation Mild mood alteration Moderate mood alteration Severe agitation; hospitalization

not indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by a state of restlessness associated with unpleasant feelings of irritability and tension.

Anorgasmia Inability to achieve orgasm not

adversely affecting relationship

Inability to achieve orgasm

adversely affecting relationship

- - -

Definition: A disorder characterized by an inability to achieve orgasm.

Anxiety Mild symptoms; intervention not

indicated

Moderate symptoms; limiting

instrumental ADL

Severe symptoms; limiting self

care ADL; hospitalization not

indicated

Life-threatening; hospitalization

indicated

Death

Definition: A disorder characterized by apprehension of danger and dread accompanied by restlessness, tension, tachycardia, and dyspnea unattached to a clearly identifiable

stimulus.

Confusion Mild disorientation Moderate disorientation; limiting

instrumental ADL

Severe disorientation; limiting

self care ADL

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by a lack of clear and orderly thought and behavior.

Delayed orgasm Delay in achieving orgasm not

adversely affecting relationship

Delay in achieving orgasm

adversely affecting relationship

- - -

Definition: A disorder characterized by sexual dysfunction characterized by a delay in climax.

Delirium Mild acute confusional state Moderate and acute confusional

state; limiting instrumental ADL

Severe and acute confusional

state; limiting self care ADL;

hospitalization indicated

Life-threatening consequences,

threats of harm to self or others;

hospitalization indicated

Death

Definition: A disorder characterized by the acute and sudden development of confusion, illusions, movement changes, inattentiveness, agitation, and hallucinations. Usually, it is a

reversible condition.

Delusions - Moderate delusional symptoms Severe delusional symptoms;

hospitalization not indicated

Life-threatening consequences,

threats of harm to self or others;

hospitalization indicated

Death

Definition: A disorder characterized by false personal beliefs held contrary to reality, despite contradictory evidence and common sense.

Depression Mild depressive symptoms Moderate depressive

symptoms; limiting instrumental

ADL

Severe depressive symptoms;

limiting self care ADL;

hospitalization not indicated

Life-threatening consequences,

threats of harm to self or others;

hospitalization indicated

Death

Definition: A disorder characterized by melancholic feelings of grief or unhappiness.

Euphoria Mild mood elevation Moderate mood elevation Severe mood elevation (e.g.,

hypomania)

- -

Definition: A disorder characterized by an exaggerated feeling of well-being which is disproportionate to events and stimuli.

Hallucinations Mild hallucinations (e.g.,

perceptual distortions)

Moderate hallucinations Severe hallucinations;

hospitalization not indicated

Life-threatening consequences,

threats of harm to self or others;

hospitalization indicated

Death

Definition: A disorder characterized by a false sensory perception in the absence of an external stimulus.

Insomnia Mild difficulty falling asleep,

staying asleep or waking up

early

Moderate difficulty falling

asleep, staying asleep or

waking up early

Severe difficulty in falling

asleep, staying asleep or

waking up early

- -

Definition: A disorder characterized by difficulty in falling asleep and/or remaining asleep.

Libido decreased Decrease in sexual interest not

adversely affecting relationship

Decrease in sexual interest

adversely affecting relationship

- - -

Definition: A disorder characterized by a decrease in sexual desire.

Libido increased Mild increase in sexual interest

not adversely affecting

relationship

Moderate increase in sexual

interest adversely affecting

relationship

Severe increase in sexual

interest leading to dangerous

behavior

- -

Definition: A disorder characterized by an increase in sexual desire.

Mania Mild manic symptoms (e.g.,

elevated mood, rapid thoughts,

rapid speech, decreased need

for sleep)

Moderate manic symptoms

(e.g., relationship and work

difficulties; poor hygiene)

Severe manic symptoms (e.g.,

hypomania; major sexual or

financial indiscretions);

hospitalization not indicated

Life-threatening consequences,

threats of harm to self or others;

hospitalization indicated

Death

Definition: A disorder characterized by excitement of psychotic proportions manifested by mental and physical hyperactivity, disorganization of behavior and elevation of mood.

Personality change Mild personality change Moderate personality change Severe personality change;

hospitalization not indicated

Life-threatening consequences,

threats of harm to self or others;

hospitalization indicated

Death

CTCAE 4.03 - June 14, 2010 : Psychiatric disorders

Psychiatric disorders

Grade

Adverse Event 1 2 3 4 5

Definition: A disorder characterized by a conspicuous change in a person's behavior and thinking.

Psychosis Mild psychotic symptoms Moderate psychotic symptoms

(e.g., disorganized speech;

impaired reality testing)

Severe psychotic symptoms

(e.g., paranoid; extreme

disorganization); hospitalization

not indicated

Life-threatening consequences,

threats of harm to self or others;

hospitalization indicated

Death

Definition: A disorder characterized by personality change, impaired functioning, and loss of touch with reality. It may be a manifestation of schizophrenia, bipolar disorder or brain

tumor.

Restlessness Mild symptoms; intervention not

indicated

Moderate symptoms; limiting

instrumental ADL

Severe symptoms; limiting self

care ADL

- -

Definition: A disorder characterized by an inability to rest, relax or be still.

Suicidal ideation Increased thoughts of death but

no wish to kill oneself

Suicidal ideation with no specific

plan or intent

Specific plan to commit suicide

without serious intent to die

which may not require

hospitalization

Specific plan to commit suicide

with serious intent to die which

requires hospitalization

Definition: A disorder characterized by thoughts of taking one's own life.

Suicide attempt - - Suicide attempt or gesture

without intent to die which may

not require hospitalization

Suicide attempt with intent to

die which requires

hospitalization

Death

Definition: A disorder characterized by self-inflicted harm in an attempt to end one's own life.

Psychiatric disorders - Other,

specify

Asymptomatic or mild

symptoms; clinical or diagnostic

observations only; intervention

not indicated

Moderate; minimal, local or

noninvasive intervention

indicated; limiting age-

appropriate instrumental ADL

Severe or medically significant

but not immediately life-

threatening; disabling; limiting

self care ADL

Life-threatening consequences;

hospitalization or urgent

intervention indicated

Death

CTCAE 4.03 - June 14, 2010 : Renal and urinary disorders

21. Renal and urinary disorders

Renal and urinary disorders

Grade

Adverse Event 1 2 3 4 5

Acute kidney injury Creatinine level increase of >0.3

mg/dL; creatinine 1.5 - 2.0 x

above baseline

Creatinine 2 - 3 x above

baseline

Creatinine >3 x baseline or >4.0

mg/dL; hospitalization indicated

Life-threatening consequences;

dialysis indicated

Death

Definition: A disorder characterized by the acute loss of renal function and is traditionally classified as pre-renal (low blood flow into kidney), renal (kidney damage) and post-renal

causes (ureteral or bladder outflow obstruction).

Bladder perforation - Extraperitoneal perforation,

indwelling catheter indicated

Intraperitoneal perforation;

elective radiologic, endoscopic

or operative intervention

indicated

Life-threatening consequences;

organ failure; urgent operative

intervention indicated

Death

Definition: A disorder characterized by a rupture in the bladder wall.

Bladder spasm Intervention not indicated Antispasmodics indicated Hospitalization indicated - -

Definition: A disorder characterized by a sudden and involuntary contraction of the bladder wall.

Chronic kidney disease eGFR (estimated Glomerular

Filtration Rate) or CrCl

(creatinine clearance) <LLN - 60

ml/min/1.73 m2 or proteinuria

2+ present; urine

protein/creatinine >0.5

eGFR or CrCl 59 - 30

ml/min/1.73 m2

eGFR or CrCl 29 - 15

ml/min/1.73 m2

eGFR or CrCl <15 ml/min/1.73

m2; dialysis or renal transplant

indicated

Death

Definition: A disorder characterized by gradual and usually permanent loss of kidney function resulting in renal failure.

Cystitis noninfective Microscopic hematuria; minimal

increase in frequency, urgency,

dysuria, or nocturia; new onset

of incontinence

Moderate hematuria; moderate

increase in frequency, urgency,

dysuria, nocturia or

incontinence; urinary catheter

placement or bladder irrigation

indicated; limiting instrumental

ADL

Gross hematuria; transfusion, IV

medications or hospitalization

indicated; elective endoscopic,

radiologic or operative

intervention indicated

Life-threatening consequences;

urgent radiologic or operative

intervention indicated

Death

Definition: A disorder characterized by inflammation of the bladder which is not caused by an infection of the urinary tract.

Hematuria Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; urinary catheter

or bladder irrigation indicated;

limiting instrumental ADL

Gross hematuria; transfusion, IV

medications or hospitalization

indicated; elective endoscopic,

radiologic or operative

intervention indicated; limiting

self care ADL

Life-threatening consequences;

urgent radiologic or operative

intervention indicated

Death

Definition: A disorder characterized by laboratory test results that indicate blood in the urine.

Hemoglobinuria Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

- - - -

Definition: A disorder characterized by laboratory test results that indicate the presence of free hemoglobin in the urine.

Proteinuria 1+ proteinuria; urinary protein

<1.0 g/24 hrs

Adults: 2+ proteinuria; urinary

protein 1.0 - 3.4 g/24 hrs;

Pediatric: urine P/C

(Protein/Creatinine) ratio 0.5 -

1.9

Adults: urinary protein >=3.5

g/24 hrs;

Pediatric: urine P/C >1.9

- -

Definition: A disorder characterized by laboratory test results that indicate the presence of excessive protein in the urine. It is predominantly albumin, but also globulin.

Renal calculi Asymptomatic or mild

symptoms; occasional use of

nonprescription analgesics

indicated

Symptomatic; oral antiemetics

indicated; around the clock

nonprescription analgesics or

any oral narcotic analgesics

indicated

Hospitalization indicated; IV

intervention (e.g., analgesics,

antiemetics); elective

endoscopic or radiologic

intervention indicated

Life-threatening consequences;

urgent radiologic, endoscopic or

operative intervention indicated

Death

Definition: A disorder characterized by the formation of crystals in the pelvis of the kidney.

Renal colic Mild pain not interfering with

activity; nonprescription

medication indicated

Moderate pain; limiting

instrumental ADL; prescription

medication indicated

Hospitalization indicated;

limiting self care ADL

- -

Definition: A disorder characterized by paroxysmal and severe flank marked discomfort radiating to the inguinal area. Often, the cause is the passage of kidney stones.

CTCAE 4.03 - June 14, 2010 : Renal and urinary disorders

Renal and urinary disorders

Grade

Adverse Event 1 2 3 4 5

Renal hemorrhage Mild symptoms; intervention not

indicated

Analgesics and hematocrit

monitoring indicated

Transfusion, radiation, or

hospitalization indicated;

elective radiologic, endoscopic

or operative intervention

indicated

Life-threatening consequences;

urgent radiologic or operative

intervention indicated

Death

Definition: A disorder characterized by bleeding from the kidney.

Urinary fistula - Noninvasive intervention

indicated; urinary or suprapubic

catheter placement indicated

Limiting self care ADL; elective

radiologic, endoscopic or

operative intervention indicated;

permanent urinary diversion

indicated

Life-threatening consequences;

urgent radiologic or operative

intervention indicated

Death

Definition: A disorder characterized by an abnormal communication between any part of the urinary system and another organ or anatomic site.

Urinary frequency Present Limiting instrumental ADL;

medical management indicated

- - -

Definition: A disorder characterized by urination at short intervals.

Urinary incontinence Occasional (e.g., with coughing,

sneezing, etc.), pads not

indicated

Spontaneous; pads indicated;

limiting instrumental ADL

Intervention indicated (e.g.,

clamp, collagen injections);

operative intervention indicated;

limiting self care ADL

- -

Definition: A disorder characterized by inability to control the flow of urine from the bladder.

Urinary retention Urinary, suprapubic or

intermittent catheter placement

not indicated; able to void with

some residual

Placement of urinary,

suprapubic or intermittent

catheter placement indicated;

medication indicated

Elective operative or radiologic

intervention indicated;

substantial loss of affected

kidney function or mass

Life-threatening consequences;

organ failure; urgent operative

intervention indicated

Death

Definition: A disorder characterized by accumulation of urine within the bladder because of the inability to urinate.

Urinary tract obstruction Asymptomatic; clinical or

diagnostic observations only

Symptomatic but no

hydronephrosis, sepsis or renal

dysfunction; urethral dilation,

urinary or suprapubic catheter

indicated

Symptomatic and altered organ

function (e.g., hydronephrosis,

or renal dysfunction); elective

radiologic, endoscopic or

operative intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by blockage of the normal flow of contents of the urinary tract.

Urinary tract pain Mild pain Moderate pain; limiting

instrumental ADL

Severe pain; limiting self care

ADL

- -

Definition: A disorder characterized by a sensation of marked discomfort in the urinary tract.

Urinary urgency Present Limiting instrumental ADL;

medical management indicated

- - -

Definition: A disorder characterized by a sudden compelling urge to urinate.

Urine discoloration Present - - - -

Definition: A disorder characterized by a change in the color of the urine.

Renal and urinary disorders -

Other, specify

Asymptomatic or mild

symptoms; clinical or diagnostic

observations only; intervention

not indicated

Moderate, local or noninvasive

intervention indicated; limiting

instrumental ADL

Severe or medically significant

but not immediately life-

threatening; hospitalization or

prolongation of existing

hospitalization indicated;

disabling; limiting self care ADL

Life-threatening consequences;

urgent intervention indicated

Death

CTCAE 4.03 - June 14, 2010 : Reproductive system and breast disorders

22. Reproductive system and breast disorders

Reproductive system and breast disorders

Grade

Adverse Event 1 2 3 4 5

Azoospermia - - Absence of sperm in ejaculate - -

Definition: A disorder characterized by laboratory test results that indicate complete absence of spermatozoa in the semen.

Breast atrophy Minimal asymmetry; minimal

atrophy

Moderate asymmetry; moderate

atrophy

Asymmetry >1/3 of breast

volume; severe atrophy

- -

Definition: A disorder characterized by underdevelopment of the breast.

Breast pain Mild pain Moderate pain; limiting

instrumental ADL

Severe pain; limiting self care

ADL

- -

Definition: A disorder characterized by marked discomfort sensation in the breast region.

Dysmenorrhea Mild symptoms; intervention not

indicated

Moderate symptoms; limiting

instrumental ADL

Severe symptoms; limiting self

care ADL

- -

Definition: A disorder characterized by abnormally painful abdominal cramps during menses.

Dyspareunia Mild discomfort or pain

associated with vaginal

penetration; discomfort relieved

with use of vaginal lubricants or

estrogen

Moderate discomfort or pain

associated with vaginal

penetration; discomfort or pain

partially relieved with use of

vaginal lubricants or estrogen

Severe discomfort or pain

associated with vaginal

penetration; discomfort or pain

unrelieved by vaginal lubricants

or estrogen

- -

Definition: A disorder characterized by painful or difficult coitus.

Ejaculation disorder Diminished ejaculation Anejaculation or retrograde

ejaculation

- - -

Definition: A disorder characterized by problems related to ejaculation. This category includes premature, delayed, retrograde and painful ejaculation.

Erectile dysfunction Decrease in erectile function

(frequency or rigidity of

erections) but intervention not

indicated (e.g., medication or

use of mechanical device,

penile pump)

Decrease in erectile function

(frequency/rigidity of erections),

erectile intervention indicated,

(e.g., medication or mechanical

devices such as penile pump)

Decrease in erectile function

(frequency/rigidity of erections)

but erectile intervention not

helpful (e.g., medication or

mechanical devices such as

penile pump); placement of a

permanent penile prosthesis

indicated (not previously

present)

- -

Definition: A disorder characterized by the persistent or recurrent inability to achieve or to maintain an erection during sexual activity.

Fallopian tube obstruction Diagnostic observations only;

intervention not indicated

Mild symptoms; elective

intervention indicated

Severe symptoms; elective

operative intervention indicated

- -

Definition: A disorder characterized by blockage of the normal flow of the contents in the fallopian tube.

Fallopian tube stenosis Asymptomatic clinical or

diagnostic observations only;

intervention not indicated

Symptomatic and intervention

not indicated

Severe symptoms; elective

operative intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated (e.g., organ resection)

Death

Definition: A disorder characterized by a narrowing of the fallopian tube lumen.

Female genital tract fistula Asymptomatic clinical or

diagnostic observations only;

intervention not indicated

Symptomatic and intervention

not indicated

Severe symptoms; elective

operative intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an abnormal communication between a female reproductive system organ and another organ or anatomic site.

Feminization acquired Mild symptoms; intervention not

indicated

Moderate symptoms; medical

intervention indicated

- - -

Definition: A disorder characterized by the development of secondary female sex characteristics in males due to extrinsic factors.

Genital edema Mild swelling or obscuration of

anatomic architecture on close

inspection

Readily apparent obscuration of

anatomic architecture;

obliteration of skin folds; readily

apparent deviation from normal

anatomic contour

Lymphorrhea; gross deviation

from normal anatomic contour;

limiting self care ADL

- -

Definition: A disorder characterized by swelling due to an excessive accumulation of fluid in the genitals.

Gynecomastia Asymptomatic breast

enlargement

Symptomatic (e.g., pain or

psychosocial impact)

Severe symptoms; elective

operative intervention indicated

- -

Definition: A disorder characterized by excessive development of the breasts in males.

Hematosalpinx Minimal bleeding identified on

imaging study or laparoscopy;

intervention not indicated

Moderate bleeding; medical

intervention indicated

Severe bleeding; transfusion

indicated; radiologic or

endoscopic intervention

indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

CTCAE 4.03 - June 14, 2010 : Reproductive system and breast disorders

Reproductive system and breast disorders

Grade

Adverse Event 1 2 3 4 5

Definition: A disorder characterized by the presence of blood in a fallopian tube.

Irregular menstruation Intermittent menses with

skipped menses for no more

than 1 to 3 months

Intermittent menses with

skipped menses for more than 4

to 6 months

Persistent amenorrhea for more

than 6 months

- -

Definition: A disorder characterized by irregular cycle or duration of menses.

Lactation disorder Mild changes in lactation, not

significantly affecting production

or expression of breast milk

Changes in lactation,

significantly affecting breast

production or expression of

breast milk

- - -

Definition: A disorder characterized by disturbances of milk secretion. It is not necessarily related to pregnancy that is observed in females and can be observed in males.

Menorrhagia Mild; iron supplements indicated Moderate symptoms; medical

intervention indicated (e.g.,

hormones)

Severe; transfusion indicated;

surgical intervention indicated

(e.g., hysterectomy)

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by abnormally heavy vaginal bleeding during menses.

Nipple deformity Asymptomatic; asymmetry with

slight retraction and/or

thickening of the nipple areolar

complex

Symptomatic; asymmetry of

nipple areolar complex with

moderate retraction and/or

thickening of the nipple areolar

complex

- - -

Definition: A disorder characterized by a malformation of the nipple.

Oligospermia Sperm concentration >48

million/mL or motility >68%

Sperm concentration 13 - 48

million/mL or motility 32 - 68%

Sperm concentration <13

million/mL or motility <32%

- -

Definition: A disorder characterized by a decrease in the number of spermatozoa in the semen.

Ovarian hemorrhage Minimal bleeding identified on

imaging study or laproscopy;

intervention not indicated

Moderate bleeding; medical

intervention indicated

Severe bleeding; transfusion

indicated; radiologic or

endoscopic intervention

indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by bleeding from the ovary.

Ovarian rupture Asymptomatic clinical or

diagnostic observations only;

intervention not indicated

Symptomatic and intervention

not indicated

Transfusion, radiologic,

endoscopic, or elective

operative intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by tearing or disruption of the ovarian tissue.

Ovulation pain Mild pain Moderate pain; limiting

instrumental ADL

Severe pain; limiting self care

ADL

- -

Definition: A disorder characterized by marked discomfort sensation in one side of the abdomen between menstrual cycles, around the time of the discharge of the ovum from the

ovarian follicle.

Pelvic floor muscle weakness Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic, not interfering

with bladder, bowel, or vaginal

function; limiting instrumental

ADL

Severe symptoms; limiting self

care ADL

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by a reduction in the strength of the muscles of the pelvic floor.

Pelvic pain Mild pain Moderate pain; limiting

instrumental ADL

Severe pain; limiting self care

ADL

- -

Definition: A disorder characterized by marked discomfort sensation in the pelvis.

Penile pain Mild pain Moderate pain; limiting

instrumental ADL

Severe pain; limiting self care

ADL

- -

Definition: A disorder characterized by marked discomfort sensation in the penis.

Perineal pain Mild pain Moderate pain; limiting

instrumental ADL

Severe pain; limiting self care

ADL

- -

Definition: A disorder characterized by a sensation of marked discomfort in the area between the genital organs and the anus.

Premature menopause - - Present - -

Definition: A disorder characterized by ovarian failure before the age of 40. Symptoms include hot flashes, night sweats, mood swings and a decrease in sex drive.

Prostatic hemorrhage Minimal bleeding identified on

imaging study; intervention not

indicated

Moderate bleeding; medical

intervention indicated

Severe bleeding; transfusion

indicated; radiologic or

endoscopic intervention

indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

CTCAE 4.03 - June 14, 2010 : Reproductive system and breast disorders

Reproductive system and breast disorders

Grade

Adverse Event 1 2 3 4 5

Definition: A disorder characterized by bleeding from the prostate gland.

Prostatic obstruction Diagnostic observations only;

intervention not indicated

Mild symptoms; elective

intervention indicated

Severe symptoms; elective

operative intervention indicated

- -

Definition: A disorder characterized by compression of the urethra secondary to enlargement of the prostate gland. This results in voiding difficulties (straining to void, slow urine

stream, and incomplete emptying of the bladder).

Prostatic pain Mild pain Moderate pain; limiting

instrumental ADL

Severe pain; limiting self care

ADL

- -

Definition: A disorder characterized by a sensation of marked discomfort in the prostate gland.

Scrotal pain Mild pain Moderate pain; limiting

instrumental ADL

Severe pain; limiting self care

ADL

- -

Definition: A disorder characterized by marked discomfort sensation in the scrotal area.

Spermatic cord hemorrhage Minimal bleeding identified on

imaging study; intervention not

indicated

Moderate bleeding; medical

intervention indicated

Severe bleeding; transfusion

indicated; radiologic or

endoscopic intervention

indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by bleeding from the spermatic cord.

Spermatic cord obstruction Diagnostic observations only;

intervention not indicated

Mild symptoms; elective

intervention indicated

Severe symptoms; elective

operative intervention indicated

- -

Definition: A disorder characterized by blockage of the normal flow of the contents of the spermatic cord.

Testicular disorder Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic but not interfering

with urination or sexual

activities; intervention not

indicated; limiting instrumental

ADL

Severe symptoms; interfering

with urination or sexual function;

limiting self care ADL;

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by involvement of the testis.

Testicular hemorrhage Minimal bleeding identified on

imaging study; intervention not

indicated

Moderate bleeding; medical

intervention indicated

Severe bleeding; transfusion

indicated; radiologic or

endoscopic intervention

indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by bleeding from the testis.

Testicular pain Mild pain Moderate pain; limiting

instrumental ADL

Severe pain; limiting self care

ADL

- -

Definition: A disorder characterized by a sensation of marked discomfort in the testis.

Uterine fistula Asymptomatic clinical or

diagnostic observations only;

intervention not indicated

Symptomatic and intervention

not indicated

Severe symptoms; elective

operative intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an abnormal communication between the uterus and another organ or anatomic site.

Uterine hemorrhage Minimal bleeding identified on

imaging study; intervention not

indicated

Moderate bleeding; medical

intervention indicated

Severe bleeding; transfusion

indicated; radiologic or

endoscopic intervention

indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by bleeding from the uterus.

Uterine obstruction Diagnostic observations only;

intervention not indicated

Mild symptoms; elective

intervention indicated

Severe symptoms; elective

operative intervention indicated

- -

Definition: A disorder characterized by blockage of the uterine outlet.

Uterine pain Mild pain Moderate pain; limiting

instrumental ADL

Severe pain; limiting self care

ADL

- -

Definition: A disorder characterized by a sensation of marked discomfort in the uterus.

Vaginal discharge Mild vaginal discharge (greater

than baseline for patient)

Moderate to heavy vaginal

discharge; use of perineal pad

or tampon indicated

- - -

Definition: A disorder characterized by vaginal secretions. Mucus produced by the cervical glands is discharged from the vagina naturally, especially during the childbearing years.

Vaginal dryness Mild vaginal dryness not

interfering with sexual function

Moderate vaginal dryness

interfering with sexual function

or causing frequent discomfort

Severe vaginal dryness

resulting in dyspareunia or

severe discomfort

- -

Definition: A disorder characterized by an uncomfortable feeling of itching and burning in the vagina.

CTCAE 4.03 - June 14, 2010 : Reproductive system and breast disorders

Reproductive system and breast disorders

Grade

Adverse Event 1 2 3 4 5

Vaginal fistula Asymptomatic clinical or

diagnostic observations only;

intervention not indicated

Symptomatic and intervention

not indicated

Severe symptoms; elective

operative intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an abnormal communication between the vagina and another organ or anatomic site.

Vaginal hemorrhage Minimal bleeding identified on

clinical exam or imaging study;

intervention not indicated

Moderate bleeding; medical

intervention indicated

Severe bleeding; transfusion

indicated; radiologic or

endoscopic intervention

indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by bleeding from the vagina.

Vaginal inflammation Mild discomfort or pain, edema,

or redness

Moderate discomfort or pain,

edema, or redness; limiting

instrumental ADL

Severe discomfort or pain,

edema, or redness; limiting self

care ADL; small areas of

mucosal ulceration

Widespread areas of mucosal

ulceration; life-threatening

consequences; urgent

intervention indicated

Death

Definition: A disorder characterized by inflammation involving the vagina. Symptoms may include redness, edema, marked discomfort and an increase in vaginal discharge.

Vaginal obstruction Diagnostic observations only;

intervention not indicated

Mild symptoms; elective

intervention indicated

Severe symptoms; elective

operative intervention indicated

- -

Definition: A disorder characterized by blockage of vaginal canal.

Vaginal pain Mild pain Moderate pain; limiting

instrumental ADL

Severe pain; limiting self care

ADL

- -

Definition: A disorder characterized by a sensation of marked discomfort in the vagina.

Vaginal perforation Asymptomatic clinical or

diagnostic observations only;

intervention not indicated

Symptomatic and intervention

not indicated

Severe symptoms; elective

operative intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by a rupture in the vaginal wall.

Vaginal stricture Asymptomatic; mild vaginal

shortening or narrowing

Vaginal narrowing and/or

shortening not interfering with

physical examination

Vaginal narrowing and/or

shortening interfering with the

use of tampons, sexual activity

or physical examination

- Death

Definition: A disorder characterized by a narrowing of the vaginal canal.

Vaginismus Mild discomfort or pain

associated with vaginal

spasm/tightening; no impact

upon sexual function or physical

examination

Moderate discomfort or pain

associated with vaginal

spasm/tightening; disruption in

sexual function and physical

examination

Severe discomfort or pain

associated with vaginal

spasm/tightening; unable to

tolerate vaginal penetration or

physical examination

- -

Definition: A disorder characterized by involuntary spasms of the pelvic floor muscles, resulting in pathologic tightness of the vaginal wall during penetration such as during sexual

intercourse.

Reproductive system and breast

disorders - Other, specify

Asymptomatic or mild

symptoms; clinical or diagnostic

observations only; intervention

not indicated

Moderate; minimal, local or

noninvasive intervention

indicated; limiting age-

appropriate instrumental ADL

Severe or medically significant

but not immediately life-

threatening; hospitalization or

prolongation of existing

hospitalization indicated;

disabling; limiting self care ADL

Life-threatening consequences;

urgent intervention indicated

Death

CTCAE 4.03 - June 14, 2010 : Respiratory, thoracic and mediastinal disorders

23. Respiratory, thoracic and mediastinal disorders

Respiratory, thoracic and mediastinal disorders

Grade

Adverse Event 1 2 3 4 5

Adult respiratory distress

syndrome

- - Present with radiologic findings;

intubation not indicated

Life-threatening respiratory or

hemodynamic compromise;

intubation or urgent intervention

indicated

Death

Definition: A disorder characterized by progressive and life-threatening pulmonary distress in the absence of an underlying pulmonary condition, usually following major trauma or

surgery.

Allergic rhinitis Mild symptoms; intervention not

indicated

Moderate symptoms; medical

intervention indicated

- - -

Definition: A disorder characterized by an inflammation of the nasal mucous membranes caused by an IgE-mediated response to external allergens. The inflammation may also

involve the mucous membranes of the sinuses, eyes, middle ear, and pharynx. Symptoms include sneezing, nasal congestion, rhinorrhea and itching.

Apnea - - Present; medical intervention

indicated

Life-threatening respiratory or

hemodynamic compromise;

intubation or urgent intervention

indicated

Death

Definition: A disorder characterized by cessation of breathing.

Aspiration Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Altered eating habits; coughing

or choking episodes after eating

or swallowing; medical

intervention indicated (e.g.,

suction or oxygen)

Dyspnea and pneumonia

symptoms (e.g., aspiration

pneumonia); hospitalization

indicated; unable to aliment

orally

Life-threatening respiratory or

hemodynamic compromise;

intubation or urgent intervention

indicated

Death

Definition: A disorder characterized by inhalation of solids or liquids into the lungs.

Atelectasis Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic (e.g., dyspnea,

cough); medical intervention

indicated (e.g., chest

physiotherapy, suctioning);

bronchoscopic suctioning

Oxygen indicated;

hospitalization or elective

operative intervention indicated

(e.g., stent, laser)

Life-threatening respiratory or

hemodynamic compromise;

intubation or urgent intervention

indicated

Death

Definition: A disorder characterized by the collapse of part or the entire lung.

Bronchial fistula Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; tube

thoracostomy or medical

management indicated; limiting

instrumental ADL

Severe symptoms; limiting self

care ADL; endoscopic or

operative intervention indicated

(e.g., stent or primary closure)

Life-threatening consequences;

urgent operative intervention

with thoracoplasty, chronic open

drainage or multiple

thoracotomies indicated

Death

Definition: A disorder characterized by an abnormal communication between the bronchus and another organ or anatomic site.

Bronchial obstruction Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic (e.g., mild

wheezing); endoscopic

evaluation indicated;

radiographic evidence of

atelectasis/lobar collapse;

medical management indicated

(e.g., steroids, bronchodilators)

Shortness of breath with stridor;

endoscopic intervention

indicated (e.g., laser, stent

placement)

Life-threatening respiratory or

hemodynamic compromise;

intubation or urgent intervention

indicated

Death

Definition: A disorder characterized by blockage of a bronchus passage, most often by bronchial secretions and exudates.

Bronchial stricture Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic (e.g., rhonchi or

wheezing) but without

respiratory distress; medical

intervention indicated (e.g.,

steroids, bronchodilators)

Shortness of breath with stridor;

endoscopic intervention

indicated (e.g., laser, stent

placement)

Life-threatening respiratory or

hemodynamic compromise;

intubation or urgent intervention

indicated

Death

Definition: A disorder characterized by a narrowing of the bronchial tube.

Bronchopleural fistula Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; tube

thoracostomy or medical

intervention indicated; limiting

instrumental ADL

Severe symptoms; limiting self

care ADL; endoscopic or

operative intervention indicated

(e.g., stent or primary closure)

Life-threatening consequences;

urgent operative intervention

with thoracoplasty, chronic open

drainage or multiple

thoracotomies indicated

Death

Definition: A disorder characterized by an abnormal communication between a bronchus and the pleural cavity.

Bronchopulmonary hemorrhage Mild symptoms; intervention not

indicated

Moderate symptoms; medical

intervention indicated

Transfusion, radiologic,

endoscopic, or operative

intervention indicated (e.g.,

hemostasis of bleeding site)

Life-threatening respiratory or

hemodynamic compromise;

intubation or urgent intervention

indicated

Death

Definition: A disorder characterized by bleeding from the bronchial wall and/or lung parenchyma.

CTCAE 4.03 - June 14, 2010 : Respiratory, thoracic and mediastinal disorders

Respiratory, thoracic and mediastinal disorders

Grade

Adverse Event 1 2 3 4 5

Bronchospasm Mild symptoms; intervention not

indicated

Symptomatic; medical

intervention indicated; limiting

instrumental ADL

Limiting self care ADL; oxygen

saturation decreased

Life-threatening respiratory or

hemodynamic compromise;

intubation or urgent intervention

indicated

Death

Definition: A disorder characterized by a sudden contraction of the smooth muscles of the bronchial wall.

Chylothorax Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; thoracentesis or

tube drainage indicated

Severe symptoms; elective

operative intervention indicated

Life-threatening respiratory or

hemodynamic compromise;

intubation or urgent intervention

indicated

Death

Definition: A disorder characterized by milky pleural effusion (abnormal collection of fluid) resulting from accumulation of lymph fluid in the pleural cavity.

Cough Mild symptoms; nonprescription

intervention indicated

Moderate symptoms, medical

intervention indicated; limiting

instrumental ADL

Severe symptoms; limiting self

care ADL

- -

Definition: A disorder characterized by sudden, often repetitive, spasmodic contraction of the thoracic cavity, resulting in violent release of air from the lungs and usually accompanied

by a distinctive sound.

Dyspnea Shortness of breath with

moderate exertion

Shortness of breath with

minimal exertion; limiting

instrumental ADL

Shortness of breath at rest;

limiting self care ADL

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an uncomfortable sensation of difficulty breathing.

Epistaxis Mild symptoms; intervention not

indicated

Moderate symptoms; medical

intervention indicated (e.g.,

nasal packing, cauterization;

topical vasoconstrictors)

Transfusion, radiologic,

endoscopic, or operative

intervention indicated (e.g.,

hemostasis of bleeding site)

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by bleeding from the nose.

Hiccups Mild symptoms; intervention not

indicated

Moderate symptoms; medical

intervention indicated; limiting

instrumental ADL

Severe symptoms; interfering

with sleep; limiting self care

ADL

- -

Definition: A disorder characterized by repeated gulp sounds that result from an involuntary opening and closing of the glottis. This is attributed to a spasm of the diaphragm.

Hoarseness Mild or intermittent voice

change; fully understandable;

self-resolves

Moderate or persistent voice

changes; may require

occasional repetition but

understandable on telephone;

medical evaluation indicated

Severe voice changes including

predominantly whispered

speech

- -

Definition: A disorder characterized by harsh and raspy voice arising from or spreading to the larynx.

Hypoxia - Decreased oxygen saturation

with exercise (e.g., pulse

oximeter <88%); intermittent

supplemental oxygen

Decreased oxygen saturation at

rest (e.g., pulse oximeter <88%

or PaO2 <=55 mm Hg)

Life-threatening airway

compromise; urgent intervention

indicated (e.g., tracheotomy or

intubation)

Death

Definition: A disorder characterized by a decrease in the level of oxygen in the body.

Laryngeal edema Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; medical

intervention indicated (e.g.,

dexamethasone, epinephrine,

antihistamines)

Stridor; respiratory distress;

hospitalization indicated

Life-threatening airway

compromise; urgent intervention

indicated (e.g., tracheotomy or

intubation)

Death

Definition: A disorder characterized by swelling due to an excessive accumulation of fluid in the larynx.

Laryngeal fistula Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; tube

thoracostomy or medical

management indicated; limiting

instrumental ADL

Severe symptoms; limiting self

care ADL; endoscopic or

operative intervention indicated

(e.g., stent or primary closure)

Life-threatening consequences;

urgent operative intervention

indicated (e.g., thoracoplasty,

chronic open drainage or

multiple thoracotomies)

Death

Definition: A disorder characterized by an abnormal communication between the larynx and another organ or anatomic site.

Laryngeal hemorrhage Mild cough or trace hemoptysis;

laryngoscopic findings

Moderate symptoms; medical

intervention indicated

Transfusion, radiologic,

endoscopic, or operative

intervention indicated (e.g.,

hemostasis of bleeding site)

Life-threatening airway

compromise; urgent intervention

indicated (e.g., tracheotomy or

intubation)

Death

Definition: A disorder characterized by bleeding from the larynx.

Laryngeal inflammation Mild sore throat; raspy voice Moderate sore throat;

analgesics indicated

Severe throat pain; endoscopic

intervention indicated

- -

Definition: A disorder characterized by an inflammation involving the larynx.

CTCAE 4.03 - June 14, 2010 : Respiratory, thoracic and mediastinal disorders

Respiratory, thoracic and mediastinal disorders

Grade

Adverse Event 1 2 3 4 5

Laryngeal mucositis Endoscopic findings only; mild

discomfort with normal intake

Moderate discomfort; altered

oral intake

Severe pain; severely altered

eating/swallowing; medical

intervention indicated

Life-threatening airway

compromise; urgent intervention

indicated (e.g., tracheotomy or

intubation)

Death

Definition: A disorder characterized by an inflammation involving the mucous membrane of the larynx.

Laryngeal obstruction Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic (e.g., noisy airway

breathing), but causing no

respiratory distress; medical

management indicated (e.g.,

steroids); limiting instrumental

ADL

Limiting self care ADL; stridor;

endoscopic intervention

indicated (e.g., stent, laser)

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by blockage of the laryngeal airway.

Laryngeal stenosis Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic (e.g., noisy airway

breathing), but causing no

respiratory distress; medical

management indicated (e.g.,

steroids)

Limiting self care ADL; stridor;

endoscopic intervention

indicated (e.g., stent, laser)

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by a narrowing of the laryngeal airway.

Laryngopharyngeal dysesthesia Mild symptoms; no anxiety;

intervention not indicated

Moderate symptoms; mild

anxiety, but no dyspnea; short

duration of observation and or

anxiolytic indicated; limiting

instrumental ADL

Severe symptoms; dyspnea and

swallowing difficulty; limiting self

care ADL

Life-threatening consequences Death

Definition: A disorder characterized by an uncomfortable persistent sensation in the area of the laryngopharynx.

Laryngospasm - Transient episode; intervention

not indicated

Recurrent episodes;

noninvasive intervention

indicated (e.g., breathing

technique, pressure point

massage)

Persistent or severe episodes

associated with syncope; urgent

intervention indicated (e.g.,

fiberoptic laryngoscopy,

intubation, botox injection)

Death

Definition: A disorder characterized by paroxysmal spasmodic muscular contraction of the vocal cords.

Mediastinal hemorrhage Radiologic evidence only;

minimal symptoms; intervention

not indicated

Moderate symptoms; medical

intervention indicated

Transfusion, radiologic,

endoscopic, or elective

operative intervention indicated

(e.g., hemostasis of bleeding

site)

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by bleeding from the mediastinum.

Nasal congestion Mild symptoms; intervention not

indicated

Moderate symptoms; medical

intervention indicated

Associated with bloody nasal

discharge or epistaxis

- -

Definition: A disorder characterized by obstruction of the nasal passage due to mucosal edema.

Pharyngeal fistula Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; tube

thoracostomy or medical

intervention indicated; limiting

instrumental ADL

Severe symptoms; limiting self

care ADL; endoscopic or

operative intervention indicated

(e.g., stent or primary closure)

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an abnormal communication between the pharynx and another organ or anatomic site.

Pharyngeal hemorrhage Mild symptoms; intervention not

indicated

Moderate symptoms; medical

intervention indicated

Transfusion, radiologic,

endoscopic, or operative

intervention indicated (e.g.,

hemostasis of bleeding site)

Life-threatening respiratory or

hemodynamic compromise;

intubation or urgent intervention

indicated

Death

Definition: A disorder characterized by bleeding from the pharynx.

Pharyngeal mucositis Endoscopic findings only;

minimal symptoms with normal

oral intake; mild pain but

analgesics not indicated

Moderate pain and analgesics

indicated; altered oral intake;

limiting instrumental ADL

Severe pain; unable to

adequately aliment or hydrate

orally; limiting self care ADL

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an inflammation involving the mucous membrane of the pharynx.

Pharyngeal necrosis - - Inability to aliment adequately

by GI tract; tube feeding or TPN

indicated; radiologic,

endoscopic, or operative

intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

CTCAE 4.03 - June 14, 2010 : Respiratory, thoracic and mediastinal disorders

Respiratory, thoracic and mediastinal disorders

Grade

Adverse Event 1 2 3 4 5

Definition: A disorder characterized by a necrotic process occurring in the pharynx.

Pharyngeal stenosis Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic (e.g., noisy airway

breathing), but causing no

respiratory distress; medical

management indicated (e.g.,

steroids); limiting instrumental

ADL

Limiting self care ADL; stridor;

endoscopic intervention

indicated (e.g., stent, laser)

Life-threatening airway

compromise; urgent intervention

indicated (e.g., tracheotomy or

intubation)

Death

Definition: A disorder characterized by a narrowing of the pharyngeal airway.

Pharyngolaryngeal pain Mild pain Moderate pain; limiting

instrumental ADL

Severe pain; limiting self care

ADL

- -

Definition: A disorder characterized by marked discomfort sensation in the pharyngolaryngeal region.

Pleural effusion Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; intervention

indicated (e.g., diuretics or

limited therapeutic

thoracentesis)

Symptomatic with respiratory

distress and hypoxia; surgical

intervention including chest tube

or pleurodesis indicated

Life-threatening respiratory or

hemodynamic compromise;

intubation or urgent intervention

indicated

Death

Definition: A disorder characterized by an increase in amounts of fluid within the pleural cavity. Symptoms include shortness of breath, cough and marked chest discomfort.

Pleural hemorrhage Asymptomatic; mild hemorrhage

confirmed by thoracentesis

Symptomatic or associated with

pneumothorax; chest tube

drainage indicated

>1000 ml of blood evacuated;

persistent bleeding (150-200

ml/hr for 2 - 4 hr); persistent

transfusion indicated; elective

operative intervention indicated

Life-threatening respiratory or

hemodynamic compromise;

intubation or urgent intervention

indicated

Death

Definition: A disorder characterized by bleeding from the pleural cavity.

Pleuritic pain Mild pain Moderate pain; limiting

instrumental ADL

Severe pain; limiting self care

ADL

- -

Definition: A disorder characterized by marked discomfort sensation in the pleura.

Pneumonitis Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; medical

intervention indicated; limiting

instrumental ADL

Severe symptoms; limiting self

care ADL; oxygen indicated

Life-threatening respiratory

compromise; urgent intervention

indicated (e.g., tracheotomy or

intubation)

Death

Definition: A disorder characterized by inflammation focally or diffusely affecting the lung parenchyma.

Pneumothorax Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; intervention

indicated (e.g., tube placement

without sclerosis)

Sclerosis and/or operative

intervention indicated;

hospitalization indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by abnormal presence of air in the pleural cavity resulting in the collapse of the lung.

Postnasal drip Mild symptoms; intervention not

indicated

Moderate symptoms; medical

intervention indicated

- - -

Definition: A disorder characterized by excessive mucous secretion in the back of the nasal cavity or throat, causing sore throat and/or coughing.

Productive cough Occasional/minimal production

of sputum with cough

Moderate sputum production;

limiting instrumental ADL

Persistent or copious production

of sputum; limiting self care ADL

- -

Definition: A disorder characterized by expectorated secretions upon coughing.

Pulmonary edema Radiologic findings only;

minimal dyspnea on exertion

Moderate dyspnea on exertion;

medical intervention indicated;

limiting instrumental ADL

Severe dyspnea or dyspnea at

rest; oxygen indicated; limiting

self care ADL

Life-threatening respiratory

compromise; urgent intervention

or intubation with ventilatory

support indicated

Death

Definition: A disorder characterized by accumulation of fluid in the lung tissues that causes a disturbance of the gas exchange that may lead to respiratory failure.

Pulmonary fibrosis Mild hypoxemia; radiologic

pulmonary fibrosis <25% of lung

volume

Moderate hypoxemia; evidence

of pulmonary hypertension;

radiographic pulmonary fibrosis

25 - 50%

Severe hypoxemia; evidence of

right-sided heart failure;

radiographic pulmonary fibrosis

>50 - 75%

Life-threatening consequences

(e.g., hemodynamic/pulmonary

complications); intubation with

ventilatory support indicated;

radiographic pulmonary fibrosis

>75% with severe

honeycombing

Death

Definition: A disorder characterized by the replacement of the lung tissue by connective tissue, leading to progressive dyspnea, respiratory failure or right heart failure.

Pulmonary fistula Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; tube

thoracostomy or medical

management indicated; limiting

instrumental ADL

Limiting self care ADL;

endoscopic stenting or

operative intervention indicated

Life-threatening consequences;

urgent operative intervention

indicated

Death

CTCAE 4.03 - June 14, 2010 : Respiratory, thoracic and mediastinal disorders

Respiratory, thoracic and mediastinal disorders

Grade

Adverse Event 1 2 3 4 5

Definition: A disorder characterized by an abnormal communication between the lung and another organ or anatomic site.

Pulmonary hypertension Minimal dyspnea; findings on

physical exam or other

evaluation

Moderate dyspnea, cough;

requiring evaluation by cardiac

catheterization and medical

intervention

Severe symptoms, associated

with hypoxemia, right heart

failure; oxygen indicated

Life-threatening airway

consequences; urgent

intervention indicated (e.g.,

tracheotomy or intubation)

Death

Definition: A disorder characterized by an increase in pressure within the pulmonary circulation due to lung or heart disorder.

Respiratory failure - - - Life-threatening consequences;

urgent intervention, intubation,

or ventilatory support indicated

Death

Definition: A disorder characterized by impaired gas exchange by the respiratory system resulting in hypoxemia and a decrease in oxygenation of the tissues that may be associated

with an increase in arterial levels of carbon dioxide.

Retinoic acid syndrome Fluid retention; <3 kg of weight

gain; intervention with fluid

restriction and/or diuretics

indicated

Moderate signs or symptoms;

steroids indicated

Severe symptoms;

hospitalization indicated

Life-threatening consequences;

ventilatory support indicated

Death

Definition: A disorder characterized by weight gain, dyspnea, pleural and pericardial effusions, leukocytosis and/or renal failure originally described in patients treated with all-trans

retinoic acid.

Sinus disorder Asymptomatic mucosal crusting;

blood-tinged secretions

Symptomatic stenosis or

edema/narrowing interfering

with airflow; limiting instrumental

ADL

Stenosis with significant nasal

obstruction; limiting self care

ADL

Necrosis of soft tissue or bone;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by involvement of the paranasal sinuses.

Sleep apnea Snoring and nocturnal sleep

arousal without apneic periods

Moderate apnea and oxygen

desaturation; excessive daytime

sleepiness; medical evaluation

indicated; limiting instrumental

ADL

Oxygen desaturation;

associated with hypertension;

medical intervention indicated;

limiting self care ADL

Cardiovascular or

neuropsychiatric symptoms;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by cessation of breathing for short periods during sleep.

Sneezing Mild symptoms; intervention not

indicated

Moderate symptoms; medical

intervention indicated

- - -

Definition: A disorder characterized by the involuntary expulsion of air from the nose.

Sore throat Mild pain Moderate pain; limiting

instrumental ADL

Severe pain; limiting self care

ADL; limiting ability to swallow

- -

Definition: A disorder characterized by of marked discomfort in the throat

Stridor - - Respiratory distress limiting self

care ADL; medical intervention

indicated

Life-threatening airway

compromise; urgent intervention

indicated (e.g., tracheotomy or

intubation)

Death

Definition: A disorder characterized by a high pitched breathing sound due to laryngeal or upper airway obstruction.

Tracheal fistula Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; tube

thoracostomy or medical

intervention indicated; limiting

instrumental ADL

Severe symptoms; limiting self

care ADL; endoscopic or

operative intervention indicated

(e.g., stent or primary closure)

Life-threatening consequences;

urgent operative intervention

indicated (e.g., thoracoplasty,

chronic open drainage or

multiple thoracotomies)

Death

Definition: A disorder characterized by an abnormal communication between the trachea and another organ or anatomic site.

Tracheal mucositis Endoscopic findings only;

minimal hemoptysis, pain, or

respiratory symptoms

Moderate symptoms; medical

intervention indicated; limiting

instrumental ADL

Severe pain; hemorrhage or

respiratory symptoms; limiting

self care ADL

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an inflammation involving the mucous membrane of the trachea.

Tracheal stenosis Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic (e.g., noisy airway

breathing), but causing no

respiratory distress; medical

management indicated (e.g.,

steroids)

Stridor or respiratory distress

limiting self care ADL;

endoscopic intervention

indicated (e.g., stent, laser)

Life-threatening airway

compromise; urgent intervention

indicated (e.g., tracheotomy or

intubation)

Death

Definition: A disorder characterized by a narrowing of the trachea.

CTCAE 4.03 - June 14, 2010 : Respiratory, thoracic and mediastinal disorders

Respiratory, thoracic and mediastinal disorders

Grade

Adverse Event 1 2 3 4 5

Voice alteration Mild or intermittent change from

normal voice

Moderate or persistent change

from normal voice; still

understandable

Severe voice changes including

predominantly whispered

speech; may require frequent

repetition or face-to-face contact

for understandability; may

require assistive technology

- -

Definition: A disorder characterized by a change in the sound and/or speed of the voice.

Wheezing Detectable airway noise with

minimal symptoms

Moderate symptoms; medical

intervention indicated; limiting

instrumental ADL

Severe respiratory symptoms

limiting self care ADL; oxygen

therapy or hospitalization

indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by a high-pitched, whistling sound during breathing. It results from the narrowing or obstruction of the respiratory airways.

Respiratory, thoracic and

mediastinal disorders - Other,

specify

Asymptomatic or mild

symptoms; clinical or diagnostic

observations only; intervention

not indicated

Moderate; minimal, local or

noninvasive intervention

indicated; limiting age-

appropriate instrumental ADL

Severe or medically significant

but not immediately life-

threatening; hospitalization or

prolongation of existing

hospitalization indicated;

disabling; limiting self care ADL

Life-threatening consequences;

urgent intervention indicated

Death

CTCAE 4.03 - June 14, 2010 : Skin and subcutaneous tissue disorders

24. Skin and subcutaneous tissue disorders

Skin and subcutaneous tissue disorders

Grade

Adverse Event 1 2 3 4 5

Alopecia Hair loss of <50% of normal for

that individual that is not

obvious from a distance but only

on close inspection; a different

hair style may be required to

cover the hair loss but it does

not require a wig or hair piece to

camouflage

Hair loss of >=50% normal for

that individual that is readily

apparent to others; a wig or hair

piece is necessary if the patient

desires to completely

camouflage the hair loss;

associated with psychosocial

impact

- - -

Definition: A disorder characterized by a decrease in density of hair compared to normal for a given individual at a given age and body location.

Body odor Mild odor; physician intervention

not indicated; self care

interventions

Pronounced odor; psychosocial

impact; patient seeks medical

intervention

- - -

Definition: A disorder characterized by an abnormal body smell resulting from the growth of bacteria on the body.

Bullous dermatitis Asymptomatic; blisters covering

<10% BSA

Blisters covering 10 - 30% BSA;

painful blisters; limiting

instrumental ADL

Blisters covering >30% BSA;

limiting self care ADL

Blisters covering >30% BSA;

associated with fluid or

electrolyte abnormalities; ICU

care or burn unit indicated

Death

Definition: A disorder characterized by inflammation of the skin characterized by the presence of bullae which are filled with fluid.

Dry skin Covering <10% BSA and no

associated erythema or pruritus

Covering 10 - 30% BSA and

associated with erythema or

pruritus; limiting instrumental

ADL

Covering >30% BSA and

associated with pruritus; limiting

self care ADL

- -

Definition: A disorder characterized by flaky and dull skin; the pores are generally fine, the texture is a papery thin texture.

Erythema multiforme Target lesions covering <10%

BSA and not associated with

skin tenderness

Target lesions covering 10 -

30% BSA and associated with

skin tenderness

Target lesions covering >30%

BSA and associated with oral or

genital erosions

Target lesions covering >30%

BSA; associated with fluid or

electrolyte abnormalities; ICU

care or burn unit indicated

Death

Definition: A disorder characterized by target lesions (a pink-red ring around a pale center).

Erythroderma - Erythema covering >90% BSA

without associated symptoms;

limiting instrumental ADL

Erythema covering >90% BSA

with associated symptoms (e.g.,

pruritus or tenderness); limiting

self care ADL

Erythema covering >90% BSA

with associated fluid or

electrolyte abnormalities; ICU

care or burn unit indicated

Death

Definition: A disorder characterized by generalized inflammatory erythema and exfoliation. The inflammatory process involves > 90% of the body surface area.

Fat atrophy Covering <10% BSA and

asymptomatic

Covering 10 - 30% BSA and

associated with erythema or

tenderness; limiting instrumental

ADL

Covering >30% BSA;

associated with erythema or

tenderness; limiting self-care

ADL

- -

Definition: A disorder characterized by shrinking of adipose tissue.

Hirsutism In women, increase in length,

thickness or density of hair in a

male distribution that the patient

is able to camouflage by

periodic shaving, bleaching, or

removal of hair

In women, increase in length,

thickness or density of hair in a

male distribution that requires

daily shaving or consistent

destructive means of hair

removal to camouflage;

associated with psychosocial

impact

- - -

Definition: A disorder characterized by the presence of excess hair growth in women in anatomic sites where growth is considered to be a secondary male characteristic and under

androgen control (beard, moustache, chest, abdomen)

Hyperhidrosis Limited to one site (palms,

soles, or axillae); self care

interventions

Involving >1 site; patient seeks

medical intervention; associated

with psychosocial impact

Generalized involving sites

other than palms, soles, or

axillae; associated with

electrolyte/hemodynamic

imbalance

- -

Definition: A disorder characterized by excessive perspiration.

CTCAE 4.03 - June 14, 2010 : Skin and subcutaneous tissue disorders

Skin and subcutaneous tissue disorders

Grade

Adverse Event 1 2 3 4 5

Hypertrichosis Increase in length, thickness or

density of hair that the patient is

either able to camouflage by

periodic shaving or removal of

hairs or is not concerned

enough about the overgrowth to

use any form of hair removal

Increase in length, thickness or

density of hair at least on the

usual exposed areas of the

body [face (not limited to

beard/moustache area)

plus/minus arms] that requires

frequent shaving or use of

destructive means of hair

removal to camouflage;

associated with psychosocial

impact

- - -

Definition: A disorder characterized by hair density or length beyond the accepted limits of normal in a particular body region, for a particular age or race.

Hypohidrosis - Symptomatic; limiting

instrumental ADL

Increase in body temperature;

limiting self care ADL

Heat stroke Death

Definition: A disorder characterized by reduced sweating.

Lipohypertrophy Asymptomatic and covering

<10% BSA

Covering 10 - 30% BSA and

associated tenderness; limiting

instrumental ADL

Covering >30% BSA and

associated tenderness and

narcotics or NSAIDs indicated;

lipohypertrophy; limiting self

care ADL

- -

Definition: A disorder characterized by hypertrophy of the subcutaneous adipose tissue at the site of multiple subcutaneous injections of insulin.

Nail discoloration Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

- - - -

Definition: A disorder characterized by a change in the color of the nail plate.

Nail loss Asymptomatic separation of the

nail bed from the nail plate or

nail loss

Symptomatic separation of the

nail bed from the nail plate or

nail loss; limiting instrumental

ADL

- - -

Definition: A disorder characterized by loss of all or a portion of the nail.

Nail ridging Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

- - - -

Definition: A disorder characterized by vertical or horizontal ridges on the nails.

Pain of skin Mild pain Moderate pain; limiting

instrumental ADL

Severe pain; limiting self care

ADL

- -

Definition: A disorder characterized by marked discomfort sensation in the skin.

Palmar-plantar

erythrodysesthesia syndrome

Minimal skin changes or

dermatitis (e.g., erythema,

edema, or hyperkeratosis)

without pain

Skin changes (e.g., peeling,

blisters, bleeding, edema, or

hyperkeratosis) with pain;

limiting instrumental ADL

Severe skin changes (e.g.,

peeling, blisters, bleeding,

edema, or hyperkeratosis) with

pain; limiting self care ADL

- -

Definition: A disorder characterized by redness, marked discomfort, swelling, and tingling in the palms of the hands or the soles of the feet.

Periorbital edema Soft or non-pitting Indurated or pitting edema;

topical intervention indicated

Edema associated with visual

disturbance; increased

intraocular pressure, glaucoma

or retinal hemorrhage; optic

neuritis; diuretics indicated;

operative intervention indicated

- -

Definition: A disorder characterized by swelling due to an excessive accumulation of fluid around the orbits of the face.

Photosensitivity Painless erythema and

erythema covering <10% BSA

Tender erythema covering 10 -

30% BSA

Erythema covering >30% BSA

and erythema with blistering;

photosensitivity; oral

corticosteroid therapy indicated;

pain control indicated (e.g.,

narcotics or NSAIDs)

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by an increase in sensitivity of the skin to light.

CTCAE 4.03 - June 14, 2010 : Skin and subcutaneous tissue disorders

Skin and subcutaneous tissue disorders

Grade

Adverse Event 1 2 3 4 5

Pruritus Mild or localized; topical

intervention indicated

Intense or widespread;

intermittent; skin changes from

scratching (e.g., edema,

papulation, excoriations,

lichenification, oozing/crusts);

oral intervention indicated;

limiting instrumental ADL

Intense or widespread;

constant; limiting self care ADL

or sleep; oral corticosteroid or

immunosuppressive therapy

indicated

- -

Definition: A disorder characterized by an intense itching sensation.

Purpura Combined area of lesions

covering <10% BSA

Combined area of lesions

covering 10 - 30% BSA;

bleeding with trauma

Combined area of lesions

covering >30% BSA;

spontaneous bleeding

- -

Definition: A disorder characterized by hemorrhagic areas of the skin and mucous membrane. Newer lesions appear reddish in color. Older lesions are usually a darker purple color

and eventually become a brownish-yellow color.

Rash acneiform Papules and/or pustules

covering <10% BSA, which may

or may not be associated with

symptoms of pruritus or

tenderness

Papules and/or pustules

covering 10 - 30% BSA, which

may or may not be associated

with symptoms of pruritus or

tenderness; associated with

psychosocial impact; limiting

instrumental ADL

Papules and/or pustules

covering >30% BSA, which may

or may not be associated with

symptoms of pruritus or

tenderness; limiting self care

ADL; associated with local

superinfection with oral

antibiotics indicated

Papules and/or pustules

covering any % BSA, which

may or may not be associated

with symptoms of pruritus or

tenderness and are associated

with extensive superinfection

with IV antibiotics indicated; life-

threatening consequences

Death

Definition: A disorder characterized by an eruption of papules and pustules, typically appearing in face, scalp, upper chest and back.

Rash maculo-papular Macules/papules covering

<10% BSA with or without

symptoms (e.g., pruritus,

burning, tightness)

Macules/papules covering 10 -

30% BSA with or without

symptoms (e.g., pruritus,

burning, tightness); limiting

instrumental ADL

Macules/papules covering

>30% BSA with or without

associated symptoms; limiting

self care ADL

- -

Definition: A disorder characterized by the presence of macules (flat) and papules (elevated). Also known as morbillform rash, it is one of the most common cutaneous adverse

events, frequently affecting the upper trunk, spreading centripetally and associated with pruritus.

Scalp pain Mild pain Moderate pain; limiting

instrumental ADL

Severe pain; limiting self care

ADL

- -

Definition: A disorder characterized by marked discomfort sensation in the skin covering the top and the back of the head.

Skin atrophy Covering <10% BSA;

associated with telangiectasias

or changes in skin color

Covering 10 - 30% BSA;

associated with striae or

adnexal structure loss

Covering >30% BSA;

associated with ulceration

- -

Definition: A disorder characterized by the degeneration and thinning of the epidermis and dermis.

Skin hyperpigmentation Hyperpigmentation covering

<10% BSA; no psychosocial

impact

Hyperpigmentation covering

>10% BSA; associated

psychosocial impact

- - -

Definition: A disorder characterized by darkening of the skin due to excessive melanin deposition.

Skin hypopigmentation Hypopigmentation or

depigmentation covering <10%

BSA; no psychosocial impact

Hypopigmentation or

depigmentation covering >10%

BSA; associated psychosocial

impact

- - -

Definition: A disorder characterized by loss of skin pigment.

Skin induration Mild induration, able to move

skin parallel to plane (sliding)

and perpendicular to skin

(pinching up)

Moderate induration, able to

slide skin, unable to pinch skin;

limiting instrumental ADL

Severe induration, unable to

slide or pinch skin; limiting joint

movement or orifice (e.g.,

mouth, anus); limiting self care

ADL

Generalized; associated with

signs or symptoms of impaired

breathing or feeding

Death

Definition: A disorder characterized by an area of hardness in the skin.

Skin ulceration Combined area of ulcers <1 cm;

nonblanchable erythema of

intact skin with associated

warmth or edema

Combined area of ulcers 1 - 2

cm; partial thickness skin loss

involving skin or subcutaneous

fat

Combined area of ulcers >2 cm;

full-thickness skin loss involving

damage to or necrosis of

subcutaneous tissue that may

extend down to fascia

Any size ulcer with extensive

destruction, tissue necrosis, or

damage to muscle, bone, or

supporting structures with or

without full thickness skin loss

Death

Definition: A disorder characterized by circumscribed, inflammatory and necrotic erosive lesion on the skin.

CTCAE 4.03 - June 14, 2010 : Skin and subcutaneous tissue disorders

Skin and subcutaneous tissue disorders

Grade

Adverse Event 1 2 3 4 5

Stevens-Johnson syndrome - - Skin sloughing covering <10%

BSA with associated signs (e.g.,

erythema, purpura, epidermal

detachment and mucous

membrane detachment)

Skin sloughing covering 10 -

30% BSA with associated signs

(e.g., erythema, purpura,

epidermal detachment and

mucous membrane

detachment)

Death

Definition: A disorder characterized by less than 10% total body skin area separation of dermis. The syndrome is thought to be a hypersensitivity complex affecting the skin and the

mucous membranes.

Telangiectasia Telangiectasias covering <10%

BSA

Telangiectasias covering >10%

BSA; associated with

psychosocial impact

- - -

Definition: A disorder characterized by local dilatation of small vessels resulting in red discoloration of the skin or mucous membranes.

Toxic epidermal necrolysis - - - Skin sloughing covering >=30%

BSA with associated symptoms

(e.g., erythema, purpura, or

epidermal detachment)

Death

Definition: A disorder characterized by greater than 30% total body skin area separation of dermis. The syndrome is thought to be a hypersensitivity complex affecting the skin and the

mucous membranes.

Urticaria Urticarial lesions covering <10%

BSA; topical intervention

indicated

Urticarial lesions covering 10 -

30% BSA; oral intervention

indicated

Urticarial lesions covering >30%

BSA; IV intervention indicated

- -

Definition: A disorder characterized by an itchy skin eruption characterized by wheals with pale interiors and well-defined red margins.

Skin and subcutaneous tissue

disorders - Other, specify

Asymptomatic or mild

symptoms; clinical or diagnostic

observations only; intervention

not indicated

Moderate; minimal, local or

noninvasive intervention

indicated; limiting age-

appropriate instrumental ADL

Severe or medically significant

but not immediately life-

threatening; hospitalization or

prolongation of existing

hospitalization indicated;

disabling; limiting self care ADL

Life-threatening consequences;

urgent intervention indicated

Death

CTCAE 4.03 - June 14, 2010 : Social circumstances

25. Social circumstances

Social circumstances

Grade

Adverse Event 1 2 3 4 5

Menopause Menopause occurring at age 46

- 53 years of age

Menopause occurring at age 40

- 45 years of age

Menopause occurring before

age 40 years of age

- -

Definition: A disorder characterized by the permanent cessation of menses, usually defined by 12 consecutive months of amenorrhea in a woman over 45 years of age.

Social circumstances - Other,

specify

Asymptomatic or mild

symptoms; clinical or diagnostic

observations only; intervention

not indicated

Moderate; minimal, local or

noninvasive intervention

indicated; limiting age-

appropriate instrumental ADL

Severe or medically significant

but not immediately life-

threatening; hospitalization or

prolongation of existing

hospitalization indicated;

disabling; limiting self care ADL

Life-threatening consequences;

urgent intervention indicated

Death

CTCAE 4.03 - June 14, 2010 : Surgical and medical procedures

26. Surgical and medical procedures

Surgical and medical procedures

Grade

Adverse Event 1 2 3 4 5

Surgical and medical

procedures - Other, specify

Asymptomatic or mild

symptoms; clinical or diagnostic

observations only; intervention

not indicated

Moderate; minimal, local or

noninvasive intervention

indicated; limiting age-

appropriate instrumental ADL

Severe or medically significant

but not immediately life-

threatening; hospitalization or

prolongation of existing

hospitalization indicated;

disabling; limiting self care ADL

Life-threatening consequences;

urgent intervention indicated

Death

CTCAE 4.03 - June 14, 2010 : Vascular disorders

27. Vascular disorders

Vascular disorders

Grade

Adverse Event 1 2 3 4 5

Capillary leak syndrome - Symptomatic; medical

intervention indicated

Severe symptoms; intervention

indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by leakage of intravascular fluids into the extravascular space. This syndrome is observed in patients who demonstrate a state of generalized

leaky capillaries following shock syndromes, low-flow states, ischemia-reperfusion injuries, toxemias, medications, or poisoning. It can lead to generalized edema and multiple organ

failure.

Flushing Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Moderate symptoms; medical

intervention indicated; limiting

instrumental ADL

Symptomatic, associated with

hypotension and/or tachycardia;

limiting self care ADL

- -

Definition: A disorder characterized by episodic reddening of the face.

Hematoma Mild symptoms; intervention not

indicated

Minimally invasive evacuation or

aspiration indicated

Transfusion, radiologic,

endoscopic, or elective

operative intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by a localized collection of blood, usually clotted, in an organ, space, or tissue, due to a break in the wall of a blood vessel.

Hot flashes Mild symptoms; intervention not

indicated

Moderate symptoms; limiting

instrumental ADL

Severe symptoms; limiting self

care ADL

- -

Definition: A disorder characterized by an uncomfortable and temporary sensation of intense body warmth, flushing, sometimes accompanied by sweating upon cooling.

Hypertension Prehypertension (systolic BP

120 - 139 mm Hg or diastolic

BP 80 - 89 mm Hg)

Stage 1 hypertension (systolic

BP 140 - 159 mm Hg or

diastolic BP 90 - 99 mm Hg);

medical intervention indicated;

recurrent or persistent (>=24

hrs); symptomatic increase by

>20 mm Hg (diastolic) or to

>140/90 mm Hg if previously

WNL; monotherapy indicated

Pediatric: recurrent or persistent

(>=24 hrs) BP >ULN;

monotherapy indicated

Stage 2 hypertension (systolic

BP >=160 mm Hg or diastolic

BP >=100 mm Hg); medical

intervention indicated; more

than one drug or more intensive

therapy than previously used

indicated

Pediatric: Same as adult

Life-threatening consequences

(e.g., malignant hypertension,

transient or permanent

neurologic deficit, hypertensive

crisis); urgent intervention

indicated

Pediatric: Same as adult

Death

Definition: A disorder characterized by a pathological increase in blood pressure; a repeatedly elevation in the blood pressure exceeding 140 over 90 mm Hg.

Hypotension Asymptomatic, intervention not

indicated

Non-urgent medical intervention

indicated

Medical intervention or

hospitalization indicated

Life-threatening and urgent

intervention indicated

Death

Definition: A disorder characterized by a blood pressure that is below the normal expected for an individual in a given environment.

Lymph leakage - Symptomatic; medical

intervention indicated

Severe symptoms; radiologic,

endoscopic or elective operative

intervention indicated

Life-threatening consequences;

urgent intervention indicated

Death

Definition: A disorder characterized by the loss of lymph fluid into the surrounding tissue or body cavity.

Lymphedema Trace thickening or faint

discoloration

Marked discoloration; leathery

skin texture; papillary formation;

limiting instrumental ADL

Severe symptoms; limiting self

care ADL

- -

Definition: A disorder characterized by excessive fluid collection in tissues that causes swelling.

Lymphocele Asymptomatic; clinical or

diagnostic observations only;

intervention not indicated

Symptomatic; medical

intervention indicated

Severe symptoms; radiologic,

endoscopic or elective operative

intervention indicated

- -

Definition: A disorder characterized by a cystic lesion containing lymph.

Peripheral ischemia - Brief (<24 hrs) episode of

ischemia managed non-

surgically and without

permanent deficit

Recurring or prolonged (>=24

hrs) and/or invasive intervention

indicated

Life-threatening consequences;

evidence of end organ damage;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by impaired circulation to an extremity.

Phlebitis - Present - - -

Definition: A disorder characterized by inflammation of the wall of a vein.

Superficial thrombophlebitis - Present - - -

Definition: A disorder characterized by a blood clot and inflammation involving a superficial vein of the extremities.

CTCAE 4.03 - June 14, 2010 : Vascular disorders

Vascular disorders

Grade

Adverse Event 1 2 3 4 5

Superior vena cava syndrome Asymptomatic; incidental finding

of SVC thrombosis

Symptomatic; medical

intervention indicated (e.g.,

anticoagulation, radiation or

chemotherapy)

Severe symptoms; multi-

modality intervention indicated

(e.g., anticoagulation,

chemotherapy, radiation,

stenting)

Life-threatening consequences;

urgent multi-modality

intervention indicated (e.g.,

lysis, thrombectomy, surgery)

Death

Definition: A disorder characterized by obstruction of the blood flow in the superior vena cava. Signs and symptoms include swelling and cyanosis of the face, neck, and upper arms,

cough, orthopnea and headache.

Thromboembolic event Venous thrombosis (e.g.,

superficial thrombosis)

Venous thrombosis (e.g.,

uncomplicated deep vein

thrombosis), medical

intervention indicated

Thrombosis (e.g.,

uncomplicated pulmonary

embolism [venous], non-embolic

cardiac mural [arterial]

thrombus), medical intervention

indicated

Life-threatening (e.g.,

pulmonary embolism,

cerebrovascular event, arterial

insufficiency); hemodynamic or

neurologic instability; urgent

intervention indicated

Death

Definition: A disorder characterized by occlusion of a vessel by a thrombus that has migrated from a distal site via the blood stream.

Vasculitis Asymptomatic, intervention not

indicated

Moderate symptoms, medical

intervention indicated

Severe symptoms, medical

intervention indicated (e.g.,

steroids)

Life-threatening; evidence of

peripheral or visceral ischemia;

urgent intervention indicated

Death

Definition: A disorder characterized by inflammation involving the wall of a vessel.

Visceral arterial ischemia - Brief (<24 hrs) episode of

ischemia managed medically

and without permanent deficit

Prolonged (>=24 hrs) or

recurring symptoms and/or

invasive intervention indicated

Life-threatening consequences;

evidence of end organ damage;

urgent operative intervention

indicated

Death

Definition: A disorder characterized by a decrease in blood supply due to narrowing or blockage of a visceral (mesenteric) artery.

Vascular disorders - Other,

specify

Asymptomatic or mild

symptoms; clinical or diagnostic

observations only; intervention

not indicated

Moderate; minimal, local or

noninvasive intervention

indicated; limiting age-

appropriate instrumental ADL

Severe or medically significant

but not immediately life-

threatening; hospitalization or

prolongation of existing

hospitalization indicated;

disabling; limiting self care ADL

Life-threatening consequences;

urgent intervention indicated

Death

28. Publication Information

NIH Publication No. 09-5410

Revised June 2010

Reprinted June 2010