VCOG-CTCAE v1.1
1
Veterinary cooperative oncology
group – common terminology criteria for
adverse events (VCOG-CTCAE) following
chemotherapy or biological antineoplastic
therapy in dogs and cats v1.1
PUBLISH DATE: July, 2011
A consensus document from the veterinary
cooperative oncology group (VCOG)
Quick Reference
The VCOG-CTCAE is a descriptive terminology,
which can be used for Adverse Event (AE) reporting
in dogs and cats. A grading (severity) scale is
provided for each AE term.
Components and Organization
Grades
Grade refers to the severity of the AE. The VCOGCTCAE displays Grades 1 through 5 with unique
clinical description of severity for each AE based on
this general guideline:
Grade 1
Grade 2
Grade 3
AE and grades apply to both cats and dogs unless
otherwise stated.
Category
Grade 4
A CATEGORY is a broad classification of AEs based
on anatomy and/or pathophysiology. Within each
CATEGORY, AEs are listed accompanied by their
descriptions of severity (Grade).
Grade 5
Mild; asymptomatic or mild symptoms;
clinical signs or diagnostic observations
only; intervention not indicated.
Moderate; minimal, outpatient or noninvasive intervention indicated; moderate limitation of activities of daily living
(ADL).
Severe or medically significant but not
immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; significantly
limiting ADL.
Life-threatening consequences; urgent
interventions indicated.
Death related to AE.
Further Comments
Adverse Event Terms
An AE is any unfavorable and unintended sign
(including an abnormal clinicopathologic finding),
clinical sign or disease temporally associated with
the use of a medical treatment that may or may not
be considered related to the medical treatment (see
ATTRIBUTION below). An AE is a term that is a
unique representation of a specific event used for
medical documentation and scientific analyses. AEs
are listed alphabetically within CATEGORIES. For
several AEs, a definition is provided and highlighted
in grey within the tables.
• A semi-colon indicates ‘or’ within the
description of the grade. When items within
the description of the grade are separated
by a comma, the ‘,’ means ‘and’. All items
separated by a comma are necessary to
establish that grade level.
• An ‘ – ’ 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 (Death) is not appropriate for some
AEs and therefore is not an option.
© 2011 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, DOI: 10.1111/j.1476-5829.2011.00283.x
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VCOG-CTCAE v1.1
Abbreviations Used
• ADL = activities of daily living (eating, sleep•
•
•
•
•
•
•
•
•
•
•
ing, defecating and urinating)
AV = atrioventricular
BSA = body surface area
CHF = congestive heart failure
EF = ejection fraction
EIOP = elevated intraocular pressure
FS = fractional shortening
LLN = lower limit of normal
NSAID = nonsteroidal anti-inflammatory
drug
PPN = partial parenteral nutrition
TPN = total parenteral nutrition
ULN = upper limit of normal
AE Attribution
There exist several potential causes of AEs, including
the protocol intervention under assessment, preexisting conditions (e.g. liver disease with associated
liver enzyme abnormalities, diabetes), progression
of disease being treated, concomitant medications
(e.g. steroids) and other causes (e.g. transfusion
reactions, accidental injuries). Documenting and
grading an AE simply reports that an event has
occurred and the seriousness of the event. To be
complete the clinician should assign attribution of
the AE, either to the intervention or something else.
Designating an event as treatment related (or not)
can be done in two ways:
(1) By the treating clinician at the time of clinical
evaluation;
(2) By investigators, usually occurring later in
aggregate data review and reporting by the
investigators.
Attribution Standards Are Divided into
Five Categories
(1) Unrelated: The Adverse Event is clearly not
related to the investigational agent(s)
(2) Unlikely: The Adverse Event is doubtfully
related to the investigational agent(s)
(3) Possible: The Adverse Event may be related
to the investigational agent(s)
(4) Probable: The Adverse Event is likely related
to the investigational agent(s)
(5) Definite: The Adverse Event is clearly related
to the investigational agent(s)
TABLE OF CONTENTS:
ADMINISTRATION SITE CONDITIONS . . . . . . 3
ALLERGIC/IMMUNOLOGIC EVENT . . . . . . . . . 4
BLOOD/BONE MARROW . . . . . . . . . . . . . . . . . . . . 5
CARDIAC ARRHYTHMIA . . . . . . . . . . . . . . . . . . . . 6
CARDIAC GENERAL . . . . . . . . . . . . . . . . . . . . . . . . 7
COAGULATION . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
CONSTITUTIONAL CLINICAL SIGNS . . . . . . . . 8
DERMATOLOGIC/SKIN . . . . . . . . . . . . . . . . . . . . . 9
EAR AND LABYRINTH DISORDERS . . . . . . . . . 11
ENDOCRINE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
GASTROINTESTINAL . . . . . . . . . . . . . . . . . . . . . . 13
HAEMORRHAGE/BLEEDING . . . . . . . . . . . . . . . 15
HEPATOBILIARY/PANCREAS . . . . . . . . . . . . . . . 16
METABOLIC/LABORATORY . . . . . . . . . . . . . . . . 17
MUSCULOSKELETAL/SOFT TISSUE . . . . . . . . . 19
NEUROLOGY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
OCULAR/VISUAL . . . . . . . . . . . . . . . . . . . . . . . . . . 22
PAIN . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
PULMONARY/RESPIRATORY . . . . . . . . . . . . . . 24
RENAL/GENITOURINARY . . . . . . . . . . . . . . . . . . 26
NEOPLASMS BENIGN, MALIGNANT AND
UNSPECIFIED (INCL CYSTS AND POLYPS) . 28
SEXUAL/REPRODUCTIVE FUNCTION . . . . . . 29
VASCULAR . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
© 2011 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, doi: 10.1111/j.1476-5829.2011.00283.x
Mild transient reaction;
infusion interruption not
indicated; intervention not
indicated
1
Infusion interruption indicated but
responds promptly to medical
treatment (e.g. antihistamines, NSAIDs,
narcotics, IV fluids); prophylactic
medications indicated for ≤24 h
2
3
4
5
Prolonged (e.g. not rapidly responsive
Life-threatening consequences;
Death
to medication and/or brief
urgent intervention indicated
interruption of infusion); recurrence
of signs following initial
improvement; hospitalization
indicated for clinical sequelae
Definition: A disorder characterized by adverse reaction to the infusion of pharmacological or biological substances.
Infusion site
—
Erythema with associated signs (e.g.
Ulceration or necrosis; severe tissue
Life-threatening consequences;
Death
extravasation
oedema, pain, induration, phlebitis)
damage; operative intervention
urgent intervention indicated
indicated
Definition: A disorder characterized by leakage of a pharmacological or a biological substance from the infusion site into the surrounding tissue. Signs include induration, erythema, swelling and
marked discomfort at the infusion site.
Injection site reaction
Tenderness with or without
Pain; lipodystrophy; oedema; phlebitis
Ulceration or necrosis; severe tissue
Life-threatening consequences;
Death
associated signs (e.g.
damage; operative intervention
urgent intervention indicated
warmth, erythema, itching)
indicated
Definition: A disorder characterized by an intense adverse reaction (usually immunological) developing at the site of an injection.
)
Mild
Moderate
Severe
Life-threatening; disabling
Death
Other (Specify,
Infusion-related reaction
Adverse Event
Grade
ADMINISTRATION SITE CONDITIONS
VCOG-CTCAE v1.1
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© 2011 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, doi: 10.1111/j.1476-5829.2011.00283.x
Transient urticaria or rash, drug
fever <40 ◦ C (<104 ◦ F);
intervention not indicated
1
3
Prolonged (e.g. not rapidly responsive to
medication and/or brief interruption
of infusion); recurrence of signs
following initial improvement;
hospitalization indicated for clinical
sequelae (e.g. renal impairment,
pulmonary infiltrates or oedema)
2
Intervention or infusion interruption
indicated; responds promptly to
treatment (e.g. antihistamines,
NSAIDs, narcotics); prophylactic
medications indicated for ≤24 h
Life-threatening consequences;
urgent intervention indicated
4
Death
5
Bronchospasm, with or without
Life-threatening consequences;
Death
urticaria; parenteral intervention
urgent intervention indicated
indicated; allergy-related oedema/
angiooedema; hypotension
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, hypotension, cyanosis and loss of consciousness and may lead to death.
Autoimmune disorder
Subclinical and serologic or other
Evidence of autoimmune reaction
Reversible reaction involving function of
Autoimmune reaction with
Death
evidence of autoimmune
involving a nonessential organ or
a major organ or other adverse event
life-threatening
reaction, with normal organ
function (e.g. hypothyroidism)
(e.g. transient colitis or anaemia)
consequences
function and intervention not
indicated
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 their own tissue
constituents.
Serum sickness
Clinical or diagnostic observations
Moderate arthralgia; fever, rash,
Severe arthralgia or arthritis; extensive
Life-threatening consequences;
Death
only; intervention not indicated
urticaria, antihistamines indicated
rash; steroids or IV fluids indicated
pressor or ventilatory support
indicated
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. Signs include fever, arthralgias, myalgias, skin eruptions, lymphadenopathy, and dyspneoa.
Vasculitis (Not
Mild, intervention not indicated
Nonsteroidal medical intervention
Steroids indicated
Ischaemic changes; amputation
Death
including
indicated
or surgical debridement
perivascular injection
indicated
of drug)
Definition: A disorder characterized by inflammation involving the wall of a vessel.
)
Mild
Moderate
Severe
Life-threatening; disabling
Death
Other (Specify,
Definition: A disorder characterized by an adverse local or general response from exposure to an allergen.
Anaphylaxis
—
—
Allergic reaction/
hypersensitivity
Adverse Event
Grade
ALLERGIC/IMMUNOLOGIC EVENT
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VCOG-CTCAE v1.1
© 2011 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, doi: 10.1111/j.1476-5829.2011.00283.x
Mildly hypocellular; <25% reduction
from normal cellularity for age
Bone marrow
cellularity
2
3
Thrombocytopenia
Other
)
(Specify,
Neutropenia
Neutrophilia
Haemolysis
1000–1499 μL−1
50 000–100 000 μL−1
50 000–99 000 μL−1
Moderate
1500 μL−1 to <LLN
—
100 000 μL−1 to <LLN
Mild
25 000–49 000 μL−1
Severe
500–999 μL−1
>100 000 μL−1
Laboratory evidence of haemolysis
Evidence of haemolysis and ≥2 g
Transfusion or medical intervention
only (e.g. direct antiglobulin test;
decrease in haemoglobin.
indicated (e.g. steroids)
DAT; Coombs’ test; schistocytes
Definition: A disorder characterized by laboratory test results that indicate widespread erythrocyte cell membrane destruction.
Packed cell volume
Dog:
Dog:
Dog:
30% to <LLN
20 to <30%
15 to <20%
Cat:
Cat:
Cat:
25% to <LLN
20 to <25%
15 to <20%
Moderately hypocellular; >25 to
Severely hypocellular; >50%
<50% reduction from normal
reduction from normal cellularity
cellularity for age
for age
Definition: A disorder characterized by the inability of the bone marrow to produce haematopoietic elements.
Dog:
Haemoglobin
Dog:
Dog:
<8.0–6.5 g dL−1
10 g dL−1 to <LLN
<10–8.0 g dL−1
Cat:
Cat:
Cat:
<8.0–6.5 g dL−1
<6.5–5.0
8.0 g dL−1 to <LLN
1
Adverse Event
Grade
BLOOD/BONE MARROW
<25 000
Life-threatening; disabling
Death
Death
Death
—
Death
Dog:
<15%
Cat:
<15%
<500 μL−1
Clinical manifestations of leucostasis;
urgent intervention indicated
Death
Death
Death
5
Life-threatening consequences;
urgent intervention indicated
Dog:
<6.5 g dL−1
Cat:
<5.0
—
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VCOG-CTCAE v1.1
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© 2011 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, doi: 10.1111/j.1476-5829.2011.00283.x
Non-urgent medical
intervention indicated
Non-urgent medical
intervention indicated
Non-urgent medical
intervention indicated
Moderate
Asymptomatic, intervention
not indicated
Asymptomatic, intervention
not indicated
Mild
Supraventricular and nodal arrhythmia.
Select:
-Atrial fibrillation
-Atrial flutter
-Atrial tachycardia/paroxysmal
-Atrial tachycardia
-Nodal/junctional
-Sinus tachycardia
-Supraventricular extrasystoles
-Supraventricular tachycardia
)
-Other (Specify,
Ventricular arrhythmia. Select:
-Bigeminy
-Idioventricular rhythm
-Premature ventricular contractions
-Torsade de pointes
-Trigeminy
-Ventricular fibrillation
-Ventricular flutter
-Ventricular tachycardia
)
-Other (Specify,
Other Cardiac Arrhythmia
)
(Specify,
2
Asymptomatic, intervention
not indicated
1
Conduction abnormality/atrioventricular
heart block. Select:
-Asystole
-AV block – first degree
-AV block – second degree Mobitz I
-AV block – second degree Mobitz II
-AV block – third degree (complete)
-Sick sinus syndromes
-Other (specify)
Adverse Event
CARDIAC ARRHYTHMIA
3
© 2011 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, doi: 10.1111/j.1476-5829.2011.00283.x
Severe
Symptomatic and incompletely
controlled medically or
controlled with device (e.g.
pacemaker)
Symptomatic and incompletely
controlled medically or
controlled with device (e.g.
pacemaker)
Incompletely controlled medically
or controlled with device (e.g.
pacemaker)
Grade
Life-threatening; disabling
Life-threatening (e.g. arrhythmia
associated with CHF,
hypotension, syncope, shock)
Life-threatening (e.g. arrhythmia
associated with CHF,
hypotension, syncope, shock)
Life-threatening (e.g. arrhythmia
associated with CHF,
hypotension, syncope, shock)
4
Death
Death
Death
Death
5
6
VCOG-CTCAE v1.1
Symptomatic CHF responsive to
intervention
Symptomatic CHF responsive to
intervention; EF < 40–20%,
FS < 15%
Asymptomatic, Intervention indicated
Asymptomatic, resting EF <50–40%;
FS 15–20%
Asymptomatic, resting ejection
fraction (EF) <60–50%; fractional
shortening (FS) 20–25%
Left ventricular
systolic
dysfunction
Moderate
Valvular thickening with or without
mild valvular regurgitation or
stenosis, treatment not indicated
Mild
Valvular heart
disease
Other
(Specify,
)
Moderate regurgitation or stenosis by
imaging
No associated clinical signs without
therapy
Right ventricular
dysfunction (cor
pulmonale)
—
—
Pericardial effusion
(non-malignant)
Absence of associated clinical signs,
however therapy indicated
Effusion without associated clinical
signs
—
Myocarditis
Severe
Severe regurgitation or stenosis; signs
controlled with medical therapy
Cor pulmonale present, responsive to
intervention
Physiological consequences
CHF responsive to intervention
Sustained (>24 h) therapy, resolves
without persisting physiological
consequences
Asymptomatic diagnostic finding
without associated signs;
intervention not indicated
Brief (<24 h) fluid replacement or
other therapy; no physiological
consequences
Left ventricular
diastolic
dysfunction
—
Requiring more than one drug or
more intensive therapy
<30 bpm
Asymptomatic, transient (<24 h),
intervention not indicated
—
Recurrent or persistent (>24 h) or
clinical signs increase; monotherapy
may be indicated
<40 bpm
3
Hypotension
—
2
Asymptomatic, transient (<24 h)
increase, intervention not
indicated
<60 bpm
1
Hypertension
Cardiopulmonary
arrest
Bradycardia
Adverse Event
Grade
CARDIAC GENERAL
<20 bpm
Life-threatening; disabling
Life-threatening; disabling; poorly
responsive to medical therapy
Cor pulmonale, poorly controlled
Life-threatening; emergency
intervention indicated
Severe or refractory CHF
Refractory CHF or poorly controlled;
EF< 20%
Refractory CHF, poorly controlled with
intervention
Shock (e.g. impairment of vital organ
function)
Life-threatening consequences (e.g.
hypertensive crisis)
Life-threatening
4
Death
Death
Death
Death
Death
Death
Death
Death
Death
Death
Death
5
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© 2011 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, doi: 10.1111/j.1476-5829.2011.00283.x
—
Disseminated intravascular
coagulation
Mild lethargy over baseline;
diminished activity from
predisease level, but able to
function as an acceptable pet
Lethargy/fatigue/
general
performance
2
Grade
CONSTITUTIONAL CLINICAL SIGNS
Laboratory findings, evidence of
haemorrhage, non-disabling
3
4
3
4
Moderate lethargy causing some difficulty
Compromised, severely restricted in
Disabled, must be force fed and
with performing ADL; ambulatory only to
ADL; unable to confine urinations
helped to perform ADL
the point of eating, sleeping and
and defecation to acceptable
consistently defecating and urinating in
areas; will consume food if offered
acceptable areas
in place
Definition: Disorders characterized by a state of generalized weakness with a pronounced inability to summon sufficient energy to accomplish daily activities.
>40.0–41 ◦ C
>41–42 ◦ C
>42◦
Fever
39.5–40.0 ◦ C
(>107.6 ◦ F)
(103.5–104 ◦ F)
(>104–105.8 ◦ F), transient (<6 h), not
(>105.8–107.6 ◦ F), prolonged
requiring hospitalization
(>6 h); requiring hospitalization
Hypothermia
—
36 to >33 ◦ C
33 to >28 ◦ C
<28 ◦ C
◦
◦
(96.8 to >91.4 F)
(91.4 to >82.4 F)
(<82.4 ◦ F)
or life-threatening consequences
(e.g. coma, hypotension,
pulmonary oedema)
Weight loss
<10% from baseline;
10–15% from baseline; nutritional dietary
>15% of baseline
—
intervention not indicated
modification indicated
Mild
Moderate
Severe
Life-threatening; disabling
Other
)
(Specify,
1
Adverse Event
Laboratory findings, no
haemorrhage detected
2
Grade
5
© 2011 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, doi: 10.1111/j.1476-5829.2011.00283.x
Death
Death
Death
Death
Death
5
Laboratory findings, life-threatening or disabling consequences (e.g.
Death
CNS haemorrhage, organ damage or haemodynamically
significant blood loss)
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
haemorrhage as the body is depleted of platelets and coagulation factors.
Prothrombin time
>1–1.9× ULN
>2.0–2.9× ULN
>3× ULN
Grades 2–3, Life-threatening bleeding
—
Partial thromboplastin time
>1–1.9× ULN
>2.0–2.9× ULN
>3× ULN
Grades 2–3, Life-threatening bleeding
—
)
Mild
Moderate
Severe
Life-threatening; disabling
Death
Other (Specify,
1
Adverse Event
COAGULATION
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VCOG-CTCAE v1.1
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2
3
Minimal changes or dermatitis (e.g.
erythema) without pain
—
—
Partial or complete loss of nail(s)/claw(s);
pain
Ulcerative dermatitis or skin changes with
pain interfering with function
Skin changes (e.g. peeling, blisters,
bleeding, oedema) or pain, not
interfering with function, easily
managed medically
Definition: A disorder characterized by redness, marked discomfort, swelling, and possible ulceration of the palmar/plantar surfaces of the paws.
Photosensitivity
Painless erythema
Painful erythema
Erythema with desquamation
Definition: A disorder characterized by an increase in sensitivity of the skin to light.
Pruritus
Mild or localized
Moderate or widespread and occurs
Severe and prolonged; continues when
regularly; may occur at night but not
eating, playing, exercising, limits
when eating or playing
sleeping; oral corticosteroid or
immunosuppressive therapy indicated
Definition: A disorder characterized by intense itching.
Combined area of lesions covering
Combined area of lesions covering >30%
Purpura
Combined area of lesions covering <10%
BSA
10–30% BSA; bleeding with trauma
BSA; spontaneous bleeding
Palmar–plantar
erythrodysesthesia
syndrome
Definition: A disorder characterized by target lesions (a pink–red ring around a pale centre).
Hyperpigmentation
Slight or localized
Marked or generalized
Hypopigmentation
Slight or localized
Marked or generalized
Nail/claw changes
Discolouration, pitting
Weakening
Sparse thinning or denuding of hair at
Generalized thinning of hair coat,
—
localized site, patchy alopecia
generalized alopecia
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.
Bruising (in the absence
Localized or in a dependent area
Generalized.
—
of grade 3 or 4
thrombocytopenia)
Definition: A finding of injury of the soft tissues or bone characterized by leakage of blood into surrounding tissues.
Erythema
Limited to localized site
Generalized
—
Definition: Superficial reddening of the skin, usually in patches, as a result of injury or irritation causing dilatation of the blood capillaries.
Target lesions covering 10–30% BSA and
Target lesions covering >30% BSA and
Erythema multiforme
Target lesions covering <10% BSA and
not associated with skin tenderness
associated with skin tenderness
associated with oral or genital erosions
Alopecia
Adverse Event
Grade
DERMATOLOGIC/SKIN
—
Death
—
Target lesions covering >30% BSA;
associated with fluid or
electrolyte abnormalities; ICU
care indicated
—
—
—
Death
Life-threatening; disabling
—
—
—
—
Significantly interfering with
ADL – unwilling to ambulate
—
—
—
—
—
—
5
—
—
4
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© 2011 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, doi: 10.1111/j.1476-5829.2011.00283.x
1
2
3
4
5
Definition: A disorder characterized by haemorrhagic areas of the skin and mucous membrane. Newer lesions appear reddish in colour. Older lesions are usually darker purple in colour and eventually become
brownish-yellow in colour.
Papules and/or pustules covering
Rash: acne/
Papules and/or pustules covering
Papules and/or pustules covering any % BSA,
Papules and/or pustules covering
Death
<10% BSA, which may or may not
>30% BSA, which may or may not be
10–30% BSA, which may or may not
acneiform
which may or may not be associated with
be associated with symptoms of
associated with symptoms of
be associated with symptoms of
symptoms of pruritus or tenderness and are
pruritus or tenderness
pruritus or tenderness; limiting ADL;
pruritus or tenderness
associated with extensive superinfection
associated with local superinfection
with IV antibiotics indicated; life-threatening
with oral antibiotics indicated
consequences
Definition: A disorder characterized by an eruption of papules and pustules.
Rash: maculo-papula
Macules/papules covering <10%
Macules/papules covering 10–30%
—
—
Macules/papules covering >30% BSA
BSA with or without
with or without
BSA with or without symptoms (e.g.
symptoms (e.g. pruritus)
associated symptoms
pruritus);
Definition: A disorder characterized by the presence of macules (flat) and papules (elevated). Also known as morbilliform rash.
Scaling
Fine scaling, noticeable only upon
Scaling easily visible but not exfoliation
Easily visible generalized scaling and
—
—
close examination
in clumps; minimal crusting
crusting with generalized exfoliation
upon examination
Definition: A disorder characterized by flaky and dull skin.
—
—
Skin atrophy
Covering <10% BSA; associated with
Covering 10–30% BSA; associated with
Covering >30% BSA; associated with
telangiectasia or changes in skin
ulceration
striae or adnexal structure loss
colour
Definition: A disorder characterized by the degeneration and thinning of the epidermis and dermis.
Skin ulceration
Combined area of ulcers <1 cm;
Combined area of ulcers 1–2 cm;
Combined area of ulcers >2 cm;
Any size ulcer with extensive destruction, tissue
Death
nonblanchable erythema of intact
full-thickness skin loss involving
partial thickness skin loss involving
necrosis or damage to muscle, bone or
skin with associated warmth or
damage to or necrosis of
skin or subcutaneous fat
supporting structures with or without
oedema
subcutaneous tissue that may
full-thickness skin loss
extend down to fascia
Definition: A disorder characterized by circumscribed, inflammatory and necrotic erosive lesion on the skin.
Toxic epidermal
—
—
—
Skin sloughing covering ≥30% BSA with
Death
associated symptoms (e.g. erythema,
necrolysis
purpura or epidermal
detachment)
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.
Intervention indicated >48 h
—
—
Urticaria (hives, welts,
—
Transient, intervention indicated <48 h
wheals)
Definition: A disorder characterized by a pruritic skin eruption characterized by wheals with pale interiors and well-defined red margins.
Mild
Moderate
Severe
Life-threatening; disabling
Death
Other
)
(Specify,
Adverse Event
Grade
DERMATOLOGIC/SKIN (CONTINUED)
10 VCOG-CTCAE v1.1
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1
2
Grade
3
4
5
Ear pain
Mild pain
Moderate pain; not limiting ADL
Severe pain; limiting ADL
—
—
Definition: A disorder characterized by a sensation of marked discomfort in the ear.
External ear
External otitis with erythema or
External otitis with moist
External otitis with mastoiditis;
Urgent operative intervention indicated
Death
inflammation
dry desquamation
desquamation, oedema,
stenosis or osteomyelitis; necrosis
enhanced cerumen or discharge;
of soft tissue or bone
tympanic membrane perforation;
tympanostomy
Definition: A disorder characterized by inflammation, swelling and redness to the outer ear and ear canal.
External ear pain
Mild pain
Moderate pain; not limiting ADL
Severe pain; limiting ADL
—
—
Definition: A disorder characterized by a sensation of marked discomfort in the external ear region.
Hearing impaired
Slow to respond to auditory
Only responsive to loud auditory
Clinically deaf; severe BAER
—
—
stimuli; mild BAER abnormalities
stimuli; moderate BAER
abnormalities
abnormalities
Definition: A disorder characterized by partial or complete loss of the ability to detect or understand sounds resulting from damage to ear structures. BAER = brainstem auditory evoked potentials.
Middle ear
Serous otitis
Serous otitis, medical intervention
Mastoiditis; necrosis of canal soft
Life-threatening consequences; urgent
Death
inflammation
indicated
tissue or bone
intervention indicated
Definition: A disorder characterized by inflammation, swelling and redness to the middle ear.
Vertigo
—
Symptomatic; not limiting ADL
Severe symptoms; limiting ADL
—
—
Definition: A disorder characterized by dizziness, imbalance, nausea, and vision problems.
Mild
Moderate
Severe
Life-threatening; disabling
Death
Other
)
(Specify,
Adverse Event
EAR AND LABYRINTH DISORDERS
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1
2
Grade
3
4
5
Adrenal
Asymptomatic, intervention not
Symptomatic, intervention indicated
Hospitalization
Life-threatening; disabling
Death
insufficiency
indicated
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.
Pancreatic
Asymptomatic, intervention not
Symptomatic, dietary modification or
Symptoms interfering with ADL;
Life-threatening consequences (e.g.
Death
endocrine:
indicated
oral agent indicated
insulin indicated
ketoacidosis, hyperosmolarity)
glucose
intolerance
Definition: A disorder characterized by insufficient production of pancreatic insulin leading to glucose intolerance.
Pancreatic exocrine:
Asymptomatic, intervention not
Symptomatic, dietary modification or
Symptoms interfering with ADL; grade
Life-threatening consequences;
Death
maldigestion
indicated
oral agents indicated
3 weight loss
cachexia
Definition: A disorder characterized by insufficient production of pancreatic exocrine enzymes leading to maldigestion.
Parathyroid
Asymptomatic, intervention not
Symptomatic, intervention indicated
—
—
Death
function (hyperindicated
parathyroidism)
Definition: A disorder characterized by an increase in production of parathyroid hormone by the parathyroid glands. This results in hypercalcaemia.
Parathyroid
Asymptomatic; clinical or diagnostic
Moderate symptoms; medical
Severe symptoms; medical
Life-threatening consequences;
Death
function
observations only; intervention not
intervention indicated
intervention and hospitalization
urgent
(hypoparathyindicated
indicated
intervention indicated
roidism)
Definition: A disorder characterized by a decrease in the production of parathyroid hormone by the parathyroid glands.
Thyroid function,
Asymptomatic; clinical or diagnostic
Symptomatic; thyroid suppression
Severe symptoms; limiting ADL,
Life-threatening consequences;
Death
hyperthyroidism
observations only; intervention not
therapy indicated; limiting ADL
hospitalization indicated
urgent intervention indicated
indicated
Definition: A disorder characterized by excessive levels of thyroid hormone in the body. Common causes include an overactive thyroid gland or thyroid hormone overdose.
Thyroid function,
Asymptomatic, intervention not
Symptomatic, not interfering with
Symptoms interfering with ADL,
Life-threatening myxoedema; coma
Death
hypothyroidism
indicated
ADL, thyroid replacement indicated
hospitalization indicated
Definition: A disorder characterized by a decrease in production of thyroid hormone by the thyroid gland.
Mild
Moderate
Severe
Life-threatening; disabling
Death
Other
)
(Specify,
Adverse Event
ENDOCRINE
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1
2
Death
Death
Death
Death
Life-threatening consequences
(e.g. obstruction, megacolon)
Life-threatening (e.g.
haemodynamic collapse)
Life-threatening (e.g.
haemodynamic collapse)
Life-threatening (e.g.
obstruction, perforation)
Death
Death
Life-threatening consequences;
urgent operative intervention
indicated
Severe symptoms; invasive intervention
indicated
Death
—
5
Life-threatening consequences
(e.g. perforation, bleeding,
ischaemia, necrosis)
Life-threatening consequences;
TPN indicated; >5 days
duration
—
4
Of >3 days duration; associated with
significant weight loss (≥10%) or
malnutrition; IV fluids, tube feeding or
force feeding indicated
Severe discomfort; limiting ADL; inpatient
management indicated
3
Definition: A disorder characterized by accumulation of serous or haemorrhagic fluid in the peritoneal cavity
Colitis
Asymptomatic, pathological or
Abdominal cramping/pain; mucus or
Abdominal pain, fever, change in bowel
radiological findings only
blood in stool; outpatient medical
habits, ileus, peritoneal signs;
intervention indicated; ≤5 days
hospitalization indicated; >5 days
duration
duration
Definition: A disorder characterized by inflammation of the colon.
Constipation
Occasional or intermittent symptoms;
Persistent symptoms with regular use of
Symptoms interfering with ADL;
occasional use of stool softeners,
laxatives or enemas indicated
obstipation with manual evacuation
laxatives, dietary modification or
indicated
enema
Definition: A disorder characterized by irregular and infrequent or difficult evacuation of the bowels.
Dehydration
Increased oral fluids indicated; dry
Parenteral (IV or SC) fluids indicated
IV fluids indicated >48 h
mucous membranes; <skin turgor
<48 h
Definition: A disorder characterized by excessive loss of water from the body. It is usually caused by severe diarrhoea.
Diarrhoea
Increase of up to 2 stools per day over
Increase of 3–6 stools per day over
Increase of >6 stools per day over
baseline; no increase in frequency,
baseline; medications indicated;
baseline; incontinence >48 h; IV fluids
however, consistency decreased over
parenteral (IV or SC) fluids indicated
>48 h; hospitalization; interfering with
baseline
≤48 h; not interfering with ADL
ADL
Definition: A disorder characterized by frequent and watery bowel movements.
Dysphagia
Symptomatic but able to eat regular diet
Symptomatic and altered
Symptomatic and severely altered
eating/swallowing (e.g. altered dietary
eating/swallowing (e.g. inadequate oral
habits, food consistency); parenteral (IV
caloric or fluid intake); IV fluids >48 h,
or SC) fluids indicated <48 h
tube feeding or PPN/TPN indicated
Abdominal
Clinical or diagnostic observations only;
Clinical signs present; outpatient medical
distention
intervention not indicated
management indicated
Definition: A disorder characterized by swelling of the abdomen.
Anorexia
Coaxing or dietary change required to
Oral intake altered (≤3 days) without
maintain appetite
significant weight loss; oral nutritional
supplements/appetite stimulants may
be indicated
Definition: A disorder characterized by a loss of appetite.
Ascites
Clinical or diagnostic observations only;
Symptomatic; medical intervention
intervention not indicated
indicated
Adverse Event
Grade
GASTROINTESTINAL
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1
2
Severely altered GI function; TPN
indicated; elective
operative or endoscopic
intervention indicated
—
Abdominal pain/cramping, fever,
change in bowel habits with ileus;
peritoneal signs; hospitalization
>48 h indicated
3
Definition: A disorder characterized by a circumscribed, inflammatory and necrotic erosive lesion on the mucosal surface of the stomach.
Ileus, GI
Asymptomatic, radiological finding only
Symptomatic; altered GI function (e.g.
Symptomatic and severely altered GI
altered dietary habits); parenteral (IV or
function; IV fluids, tube feedings or
SC) fluids indicated ≤48 h
PPN/TPN indicated >48 h
Definition: A disorder characterized by failure of the ileum to transport intestinal contents.
Incontinence, anal
Occasional
Daily
Interfering with ADL; operative
intervention indicated
Definition: A disorder characterized by inability to consciously control rectal evacuation.
Mucositis/
Erythema of the mucosa
Patchy ulcerations or pseudomembranes
Confluent ulcerations or
stomatitis
pseudomembranes; bleeding with
minor trauma
Definition: A disorder characterized by inflammation of the oral mucosa.
Nausea/ptyalism
Loss of appetite without alteration in
Salivation or ‘smacking of lips’ <3 days,
Salivation or ‘smacking of lips’
eating habits
grade 2 anorexia
>3–5 days, grade 3 anorexia
Definition: A disorder characterized by hypersalivation and sensation or urge to vomit – difficult to assess in companion species.
Vomiting
<3 episode in 24 h, medical
3–10 episodes in 24 h; <5 episodes/day
Multiple episodes >48 h and IV fluids
intervention not indicated
for ≤48 h; parenteral fluids (IV or SC)
or PPN/TPN indicated >48 h
indicated ≤48 h; medications indicated
Definition: A disorder characterized by the reflexive act of ejecting the contents of the stomach through the mouth.
Mild
Moderate
Severe
Other
)
(Specify,
Abdominal pain/cramping; mucus or
blood in stool); medical management
indicated; hospitalization ≤48 h
indicated
Definition: A disorder characterized by inflammation of the small intestine.
Flatulence
Mild
Moderate
Definition: A disorder characterized by a state of excessive gas in the intestinal tract.
Gastric ulceration
Clinical or diagnostic observations only;
Altered GI function; medical intervention
intervention not indicated
indicated
Definition: A disorder characterized by difficulty in swallowing.
Enteritis
Asymptomatic, pathological or
radiological findings only
Adverse Event
Grade
GASTROINTESTINAL (CONTINUED)
Death
Tissue necrosis; significant
spontaneous bleeding;
life-threatening
© 2011 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, doi: 10.1111/j.1476-5829.2011.00283.x
Death
Death
Life-threatening (e.g.
haemodynamic collapse)
Life-threatening
—
Death
Permanent
Salivation or ‘smacking of lips’
>5 days, grade 4 anorexia
Death
Death
—
Death
5
Life-threatening
consequences
Life-threatening
consequences; urgent
operative intervention
indicated; gastric
perforation
—
Life-threatening (e.g.
perforation, bleeding,
ischaemia, necrosis)
4
14 VCOG-CTCAE v1.1
1
2
3
4
Minimal signs, invasive intervention
Minimally invasive evacuation or
Transfusion or operative intervention
Life-threatening; major urgent
not indicated
aspiration indicated
indicated
intervention indicated
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.
Haemorrhage/bleeding
—
—
Requiring transfusion(s) beyond what is
Life-threatening
associated with surgery,
‘normal’ for that procedure; operative
intraoperative or
intervention
postoperative
Definition: Bleeding associated with an operative procedure
Mild or microscopic, intervention not
Symptomatic, medical or minor
Transfusion, operative intervention
Life-threatening; major urgent
Haemorrhage/bleeding,
indicated
operative intervention indicated
indicated
intervention indicated
spontaneous
Specify site:
Definition: Bleeding occurring spontaneously, without a history of trauma or operative procedure
Petechiae/ecchymoses
Few petechiae
Moderate petechiae; ecchymoses
Generalized petechiae or ecchymoses
—
(skin or mucosa)
Definition: small or patchy red or purple spot caused by bleeding into the skin.
)
Mild
Moderate
Severe
Life-threatening; disabling
Other (Specify,
Haematoma
Adverse Event
Grade
HAEMORRHAGE/BLEEDING
Death
Death
Death
Death
Death
5
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1
2
3
4
5
Asymptomatic, radiologic
Symptomatic, medical
Operative or endoscopic intervention
Life-threatening (e.g. sepsis or
Death
findings only
intervention indicated
required
perforation)
Definition: A disorder characterized by inflammation involving the gallbladder. It may be associated with the presence of gallstones.
Liver
—
—
Jaundice
Encephalopathy or coma
Death
dysfunction/failure
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.
Pancreatic exocrine
—
Increase in stool frequency, bulk or
Sequelae of absorption deficiency (e.g.
Life-threatening
Death
insufficiency
odour; steatorrhoea
weight loss)
Definition: A disorder characterized by insufficient production of pancreatic exocrine enzymes leading to maldigestion.
Pancreatitis
Enzyme elevation; radiological
Grade 1 or 2 vomiting; medical
Severe pain; grade 3 or higher vomiting;
Life-threatening consequences;
Death
findings only
intervention indicated
plasma or other transfusion necessary
urgent intervention indicated
(e.g. analgesia, parenteral
hydration, nutritional support)
Definition: A disorder characterized by inflammation of the pancreas.
)
Mild
Moderate
Severe
Life-threatening; disabling
Death
Other (Specify,
Cholecystitis
Adverse Event
Grade
HEPATOBILIARY/PANCREAS
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Calcium, high
Calcium, low
Amylase
AST
Bile acids
Bilirubin
BUN
ALT
Alkalosis
Acidosis
Albumin, low
Alkaline
phosphatase
Adverse Event
>ULN to 1.5× ULN
>1–1.5× baseline;
>ULN to 1.5× ULN
<LLN–8.0 mg dL−1
Ionized dog: <LLN–1.1 nmol
L−1
Ionized cat: <LLN–0.9 nmol L−1
>ULN to <12.0 mg dL−1
Ionized: >ULN–1.5 nmol L−1
>ULN to 1.5× ULN
>ULN to 1.5× ULN
Dog:
>ULN to 1.5× ULN
Cat:
>ULN to 1.25× ULN
pH > normal, but ≤7.5
pH< normal, but ≥7.3
<LLN–2.0 g dL−1
Dog:
>ULN to 2.5× ULN
Cat:
>ULN to 1.25× ULN
1
≥12.0 − 13.0 mg dL−1
Ionized: >1.5–1.6 nmol L−1 , mild
clinical signs not requiring
immediate intervention
>1.5–3.0× ULN
>1.5–3× baseline;
>1.5–2.0× ULN
<8.0–7.0 mg dL−1
Ionized dog: <1.1–1.0 nmol L−1
Ionized cat: <0.9–0.8 nmol L−1
Dog:
>1.5–4.0× ULN, transient
(<2 weeks)
Cat:
>1.25–1.5× ULN, transient
(<2 weeks)
>1.5–2.0× ULN
>1.5–2.0× ULN
—
<2.0–1.5 g dL−1
Dog:
>2.5–5.0 × ULN, transient
(<2 weeks)
Cat:
>1.25–1.5 × ULN, transient
(<2 weeks)
—
2
>13.0 mg dL−1
Ionized: >1.6–1.8 nmol L−1 with
clinical signs and/or sequela
requiring medical intervention;
hospitalization indicated
Life-threatening, require immediate
patient intervention
<6.0 mg dL−1
Ionized dog: <0.9 nmol L−1
Ionized cat: <0.7 nmol L−1
<7.0–6.0 mg dL−1
Ionized dog: <1.0–0.9 nmol L−1
Ionized cat: <0.8–0.7 nmol L−1
>5× ULN
>10× ULN
Dog:
>10× ULN
Cat:
>2× ULN
Life-threatening consequences
Life-threatening consequences
—
Dog:
>20× ULN
Cat:
>2× ULN
4
>10× ULN
>3× ULN
3
>3.0–10× ULN
>3× baseline; >2.0–3× ULN
>2.0–5× ULN
>2.0–10× ULN
Dog:
>4.0–10× ULN
Cat:
>1.5–2.0× ULN
pH > 7.5
pH <7.3
<1.5 g dL−1
Dog:
>5.0–20× ULN
Cat:
>1.5–2.0× ULN
Grade
METABOLIC/LABORATORY
Death
Death
—
—
—
—
—
Death
Death
—
—
5
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>ULN to 2.5× ULN
>1–1.5× baseline;
>ULN to 1.5× ULN
Dog:
>ULN–160 mg dL−1
Cat:
>ULN–200 mg dL−1
<LLN to 55 mg dL−1
Present
>ULN to 1.5× ULN
>ULN–5.5 mmol L−1
<LLN–3.0 mmol L−1
>ULN–8.9 mg dL−1
Asymptomatic,
clinicopathological finding
1
2
3
>2.5–5× ULN
>5–10× ULN
>1.5–3× baseline;
>3× baseline; >2.0–3× ULN
>1.5–2.0× ULN
Dog:
Dog:
Glucose, high
>160–250 mg dL−1
>250–500 mg dL−1
Cat:
Cat:
>200–250 mg dL−1
>250–500 mg dL−1
Glucose, low
<55–40 mg dL−1
<40–30 mg dL−1
Haemoglobinuria
—
—
Lipase
>1.5–2.0× ULN
>2.0–5× ULN
>5.5–6.0 mmol L−1
>6.0–7.0 mmol L−1
Potassium, high
—
<3.0–2.5
Potassium, low
9.0–12.9 mg dL−1
13.0–18.9 mg dL−1
Phosphorous, high
Tumour lysis syndrome
Mild to moderate clinical signs,
Medical intervention, hospitalization
medical intervention indicated
>48 h indicated
≤48 h
Definition: A disorder characterized by metabolic abnormalities that result from a spontaneous or therapy-related cytolysis of tumour cells.
)
Mild
Moderate
Severe
Other (Specify,
CPK
Creatinine
Adverse Event
Grade
METABOLIC/LABORATORY (CONTINUED)
Life-threatening; disabling
—
Dog:
>500 mg dL−1
Cat:
>500 mg dL−1
<30 mg dL−1
—
>5× ULN
>7.0 mmol L−1
<2.5
>19.0 mg dL−1
Life-threatening consequences;
urgent intervention indicated
Death
Death
Death
Death
Death
Death
—
—
5
>10× ULN
>3× ULN
4
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2
Severe
Definition: A disorder characterized by a necrotic process occurring in the soft tissues.
)
Mild
Moderate
Other (Specify,
Open, ulceration or necrosis
Severe erythema or swelling or
pain
Life-threatening; disabling
Life-threatening; major invasive
intervention indicated (e.g.
reconstruction, graft)
Disabling
Pain interfering with ADL
Operative debridement or other
invasive intervention indicated
Life-threatening; disabling
Symptomatic and interfering with
ADL
—
Non-weight bearing lameness
Stands abnormally, severe
lameness with stride modified,
occasionally weight bears on
involved limb
Severe symptoms; limiting ADL;
operative intervention
indicated; disabling
Disabling
4
Severe pain with inflammation or
joint swelling and interfering
with ADL
3
Definition: A disorder characterized by a tumour-like collection of serum in the tissues.
Soft tissue necrosis
Minor signs of soft tissue damage,
Local wound care; medical
no intervention indicated
intervention indicated
Definition: A disorder characterized by excessive fluid in a joint.
Muscle weakness,
Asymptomatic, weakness on
Symptomatic and interfering with
generalized or specific
physical examination
function, but not interfering with
area
ADL
Definition: A disorder characterized by a reduction in the strength of the muscles.
Myositis (inflammation
Mild pain, not interfering with
Pain interfering with function, but
of muscle)
function
not interfering with ADL
Definition: A disorder characterized by inflammation involving the skeletal muscles.
Seroma
Mild erythema; swelling
Moderate erythema or swelling; pain
Mild pain with inflammation or
joint swelling, but not
interfering with function
1
Moderate pain with inflammation or
joint swelling interfering with
function, but not interfering with
ADL
Definition: A disorder characterized by inflammation involving a joint.
Extremity
Stands normally, slight lameness
Stands normally, noticeable
(gait/ambulation)
when walking
lameness when walking, or
lameness
limitation of limb function, but
able to walk unassisted
Definition: Inability to walk normally because of an injury or illness affecting the limbs.
Joint effusion
Clinical or diagnostic observations
Limiting ADL, medical intervention
only; intervention not indicated
indicated
Arthritis, non-septic
Adverse Event
Grade
MUSCULOSKELETAL/SOFT TISSUE
Death
Death
Death
Death
—
—
—
5
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1
2
Grade
3
4
© 2011 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, doi: 10.1111/j.1476-5829.2011.00283.x
Neuropathy:
Sensory
Neuropathy: Motor
Asymptomatic; weakness on
examination/testing only
Asymptomatic; loss of deep
tendon reflexes or
paresthesia but not
interfering with function
Symptomatic weakness interfering with
function but not ADL
Sensory alteration or paresthesia,
interfering with function but not ADL
Sensory alteration or paresthesia
interfering with ADL
Weakness interfering with ADL
Disabling
Life-threatening; disabling (e.g. paralysis)
Apnea
—
—
Present
Intubation indicated
Definition: A disorder characterized by cessation of breathing.
Ataxia
Asymptomatic
Symptomatic, not interfering with ADL
Symptomatic, interfering with ADL
Disabling
Definition: A disorder characterized by lack of coordination of muscle movements resulting in the impairment or inability to perform voluntary activities.
Cerebral oedema
—
—
—
Life-threatening consequences; urgent
intervention indicated
Definition: A disorder characterized by swelling due to an excessive accumulation of fluid in the brain.
Encephalopathy
—
Mild signs or symptoms; not interfering
Signs or symptoms interfering with
Life-threatening; disabling
with ADL
ADL; hospitalization indicated
Definition: A disorder characterized by a pathological process involving the brain.
Irritability
Mild; easily consolable
Moderate; requiring increased attention
Severe; 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.
Laryngeal nerve
Asymptomatic; clinical
Symptomatic, but not interfering with
Symptomatic, interfering with ADL;
Life-threatening; tracheostomy indicated
dysfunction
examination finding
ADL; intervention not indicated
intervention indicated
Definition: A disorder characterized by abnormal laryngeal function.
Neuropathy :
Asymptomatic, detected on
Symptomatic, not interfering with ADL
Symptomatic, interfering with ADL
Life-threatening; disabling
Cranial nerve
examination/testing only
Select:
CNI CNVII CNIII
CNIV CNV CNVI
CNVII CNVIII
CNIX
CNX CNXI CNXII
Adverse Event
NEUROLOGY
Death
Death
Death
Death
—
Death
Death
Death
Death
5
20 VCOG-CTCAE v1.1
Change noticed but not
adversely affecting patient or
family
—
1
Change, adversely affecting patient or
family
2
Change is harmful to others or self;
affects ADL
3
One brief generalized seizure; well
Seizures in which consciousness is
controlled by anticonvulsants or
altered; poorly controlled seizure
infrequent focal motor seizures not
disorder with breakthrough seizures
interfering with ADL
despite medical intervention
Definition: A disorder characterized by sudden, involuntary skeletal muscular contractions of cerebral or brain stem origin.
Somnolence/depressed
—
Somnolence or sedation interfering with
Obtundation or stupor; difficult to
level of
function but not ADL
arouse; interfering with ADL
consciousness/dullness
Definition: A disorder characterized by excessive sleepiness and drowsiness.
Syncope (fainting)
—
—
Present
Definition: A disorder characterized by spontaneous loss of consciousness caused by insufficient blood supply to the brain.
Tremor
Mild and brief or intermittent
Moderate and brief or intermittent
Severe and/or frequent tremor
but not interfering with
tremor interfering with function, but
interfering with ADL
function
not interfering with ADL
Definition: A disorder characterized by the uncontrolled shaking movement of the whole body or individual parts.
)
Mild
Moderate
Severe
Other (Specify,
Seizure
Personality/behaviour
Adverse Event
Grade
NEUROLOGY (CONTINUED)
Death
Death
Death
—
Death
Coma
Life-threatening
Disabling
Life-threatening; disabling
—
5
Seizures of any kind which are
prolonged, repetitive, or
difficult to control (e.g. status
epilepticus, intractable epilepsy)
—
4
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Asymptomatic, detected on
examination only
1
Symptomatic with moderate
decrease in visual acuity
2
Grade
3
4
Symptomatic with marked decrease
—
in visual acuity; operative
intervention indicated
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/ocular
Asymptomatic or minimally
Symptomatic, significant discharge;
Symptomatic and interfering with
—
surface disease
symptomatic but not interfering
interfering with function but not
ADL; operative intervention
with function
ADL; topical antibiotics or other
indicated
topical intervention indicated
Definition: A disorder characterized by inflammation, swelling and redness to the conjunctiva of the eye.
Dry eye syndrome
Mild, intervention not indicated
Symptomatic, interfering with
Symptomatic or decrease in visual
—
function but not ADL; medical
acuity interfering with ADL
intervention indicated
Definition: A disorder characterized by dryness of the cornea and conjunctiva.
Epiphora
Symptomatic, intervention not
Symptomatic, interfering with
Symptomatic, interfering with ADL
—
indicated
function but not ADL
Definition: A disorder characterized by excessive watering of the eye.
Glaucoma
Elevated intraocular pressure
EIOP causing early visual field deficit;
EIOP causing marked visual deficits;
EIOP resulting in blindness;
(EIOP) with single topical agent
multiple topical or oral agents
operative intervention indicated
enucleation indicated
for intervention; no visual deficit
indicated
Definition: A disorder characterized by an increase in pressure in the eyeball due to obstruction of the aqueous humour outflow.
Keratitis (corneal
Abnormal ophthalmologic
Symptomatic and interfering with
Symptomatic and interfering with
Perforation or blindness
inflammation/corneal
changes only; intervention not
function, but not ADL
ADL; operative intervention
ulceration)
indicated
indicated
Definition: A disorder characterized by inflammation to the cornea of the eye.
Optic disc oedema
Asymptomatic
Symptomatic with moderate
Blindness in one but not both eyes
Bilateral blindness
(papilloedema)
decrease in visual acuity
Definition: A disorder characterized by oedema and swelling of the optic disc.
Retinal detachment
Exudative; no central vision loss;
Exudative and some visual acuity
Rhegmatogenous or exudative
Blindness
intervention not indicated
loss but intervention not
detachment; operative
indicated
intervention indicated
Definition: A disorder characterized by the separation of the inner retina layers from the underlying pigment epithelium.
Retinopathy
Asymptomatic
Symptomatic with moderate
Symptomatic with marked decrease
Blindness
decrease in visual acuity
in visual acuity; disabling;
interfering with ADL
Cataract
Adverse Event
OCULAR/VISUAL
© 2011 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, doi: 10.1111/j.1476-5829.2011.00283.x
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—
—
—
—
—
—
—
—
5
22 VCOG-CTCAE v1.1
1
Symptomatic, interfering with
function but not ADL; moderate
decrease in visual acuity; medical
intervention indicated
2
Mild pain not interfering with function;
manageable with nonsteroidal
anti-inflammatory drug (NSAID)
Pain
Specify site:
Definition: A disorder characterized by marked discomfort.
Mild
Other
)
(Specify,
1
Adverse Event
Moderate
3
Grade
3
Severe
Severe pain; manageable with
systemic analgesics, pain or
analgesics interfering with ADL
Severe
Symptomatic, interfering with ADL;
intervention indicated
Posterior or pan-uveitis; operative
intervention indicated
Symptomatic, interfering with ADL;
operative intervention indicated
Moderate pain; manageable with
standard oral analgesics (NSAIDs,
opiates), pain or analgesics interfering
with function but not ADL
2
PAIN
Anterior uveitis; medical
intervention indicated
Definition: A disorder characterized by inflammation of the uvea of the eye.
Vitreous haemorrhage
Asymptomatic, clinical findings
Symptomatic, interfering with
only
function but not ADL;
intervention not indicated
Definition: A disorder characterized by blood extravasation into the vitreous humour.
)
Mild
Moderate
Other (Specify,
Definition: A disorder characterized by necrosis of the sclera.
Uveitis
Asymptomatic
Definition: A disorder involving the retina.
Scleral necrosis/melt
Asymptomatic or symptomatic
but not interfering with function
Adverse Event
Grade
OCULAR/VISUAL (CONTINUED)
—
Life-threatening; disabling
Disabling or uncontrollable pain
4
Life-threatening; disabling
Blindness
Blindness; painful eye with
enucleation indicated
4
—
5
Death
Death
—
—
—
5
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—
1
—
2
Clinical or radiographic signs of
pneumonia or pneumonitis,
hospitalization indicated
Present; medical intervention
indicated
3
Life-threatening respiratory or
haemodynamic compromise; intubation or
urgent intervention indicated
Life-threatening respiratory or
haemodynamic compromise; intubation or
urgent intervention indicated
4
Death
Death
5
Definition: A disorder characterized by inhalation of solids or liquids into the lungs.
Bronchospasm,
Asymptomatic
Symptomatic, not interfering with
Symptomatic, interfering with
Life-threatening
Death
wheezing
function
function
Definition: A disorder characterized by a sudden contraction of the smooth muscles of the bronchial wall.
Cough
Symptomatic, non-narcotic
Symptomatic and narcotic
Symptomatic and interfering with
—
—
medication only indicated
indicated
sleep or 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.
Dyspnoea
Dyspnoea on exertion, but can
Dyspnoea on exertion and tires
Dyspnoea with ADL
Dyspnoea at rest; intubation/ventilator
Death
walk without tiring
upon ambulating
indicated
Definition: A disorder characterized by discomfort due to difficulty in breathing.
Oedema, larynx
Asymptomatic oedema by
Symptomatic oedema, no
Stridor; respiratory distress;
Life-threatening; tracheotomy, intubation,
Death
examination only
respiratory distress
interfering with ADL
indicated
Definition: A disorder characterized by swelling due to an excessive accumulation of fluid in the larynx.
Life-threatening; intubation or ventilation
Death
<O2 saturation at rest; continuous
Hypoxia
—
<O2 saturation with exercise
required
O2 supplementation required
Definition: A disorder characterized by a decrease in the level of oxygen in the body.
Pleural effusion
Asymptomatic
Symptomatic, intervention with
Symptomatic and requiring
Life-threatening (e.g. haemodynamic
Death
(non-malignant)
diuretics or single
supplemental oxygen, >1
instability or ventilatory support)
thoracocentesis indicated
thoracocenteses, continuous
tube drainage or pleurodesis
indicated
Definition: A disorder characterized by an increase in the amounts of fluid within the pleural cavity. Symptoms include shortness of breath, cough and marked chest discomfort.
Life-threatening; ventilatory support indicated
Death
Pneumonitis/pulmonary
Asymptomatic, radiographic
Symptomatic, not interfering with
Symptomatic, interfering with
infiltrates
findings only
ADL
ADL; O2 indicated
Definition: A disorder characterized by cessation of breathing.
Aspiration
Asymptomatic; radiographic
Symptomatic; medical
findings
intervention indicated
Apnea
Adverse Event
Grade
PULMONARY/RESPIRATORY
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1
2
Grade
3
Life-threatening, haemodynamic
instability; ventilatory support
4
Life-threatening respiratory
compromise; urgent
intervention or intubation with
ventilatory support indicated
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
Minimal, estimated lung volume
Patchy or bilateral changes with
Dense or widespread
Estimated involved lung volume
involved <25%
estimated lung volume 25 to
infiltrates/consolidation with
>75%
<50%
estimated involved lung volume
≥50 to 75%
Definition: A disorder characterized by the replacement of the lung tissue by connective tissue, leading to progressive dyspnoea, respiratory failure or right heart failure.
Respiratory distress
—
—
Present, intubation not indicated
Present, intubation indicated
syndrome (acute
respiratory distress
syndrome)
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.
Life-threatening; ventilatory support
Tachypnoea (not
Respiratory rate up to 60 bpm
>60 bpm; increased abdominal
O2 indicated
indicated
panting)
effort
Definition: A disorder characterized by abnormally rapid breathing.
Mild
Moderate
Severe
Life-threatening; disabling
Other
)
(Specify,
Definition: A disorder characterized by inflammation focally or diffusely affecting the lung parenchyma.
Pneumothorax
Asymptomatic, radiographic
Symptomatic; non-operative
Sclerosis and/or operative
findings only
intervention indicated
intervention indicated
Definition: A disorder characterized by abnormal presence of air in the pleural cavity resulting in the collapse of the lung.
Pulmonary oedema
Radiologic findings only; minimal
Moderate dyspnoea on exertion;
Severe dyspnoea or dyspnoea at rest;
dyspnoea on exertion
medical intervention
oxygen indicated; limiting ADL
indicated
Adverse Event
PULMONARY/RESPIRATORY (CONTINUED)
Death
Death
Death
Death
Death
Death
5
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1
2
3
4
5
Acute kidney injury
Creatinine >2 but <3× above
Creatinine >3× baseline or >4.0 mg
Life-threatening consequences;
Death
Creatinine level increase of >0.3 mg
baseline
dL−1 ; hospitalization indicated
dialysis indicated
dL−1 ; creatinine 1.5–2.0× above
baseline
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 postrenal causes (ureteral or
bladder outflow obstruction).
Mild clinical signs [creatinine
Transitional clinical signs [creatinine
Death
Chronic kidney
Uremic; creatinine >440 mmol L−1
Asymptomatic [creatinine
140–249 μmol L−1 (1.6–2.8 mg
250–439 μmol L−1 (2.9–5.0 mg
[>5.0 mg dL−1 ], chronic dialysis or
disease
<140 μmol L−1 (<1.6 mg dL−1 ) in
cats; <125 μmol L−1 (<1.4 mg
dL−1 ) in cats; 125–179 μmol L−1
dL−1 ) in cats; 180–430 μmol L−1
renal transplant indicated
[International
dL−1 ) in dogs]
(1.4–2.0 mg dL−1 ) in dogs]
(2.1–5.0 mg dL−1 ) in dogs], fluid
Renal Interest
therapy indicated; dialysis not
Society (IRIS)
indicated
stage]
Definition: A disorder characterized by gradual and usually permanent loss of kidney function resulting in renal failure.
Cystitis (haemaAsymptomatic; microscopic
Pollakiuria with dysuria; macroscopic
Transfusion indicated; pain or
Catastrophic bleeding; non-elective
Death
turia/pyuria
haematuria/pyuria, not requiring
haematuria, transient and not
antispasmodic medication; bladder
intervention indicated
included)
attributed drug discontinuation
requiring attributed drug
irrigation indicated; requiring
discontinuation
attributed drug discontinuation
Definition: A disorder characterized by inflammation of the bladder which is not caused by an infection of the urinary tract.
Glucosuria
—
Present but transient (<2 weeks)
Prolonged (>2 weeks)
Permanent
Definition: A disorder characterized by the excretion of glucose in the urine.
Incontinence,
Occasional (with coughing, sneezing,
Spontaneous
Interfering with ADL; medical
Operative intervention indicated
—
urinary
etc.,)
intervention indicated
Definition: A disorder characterized by insufficient voluntary control over urination
Obstruction,
Asymptomatic; radiographic or
Symptomatic without hydronephrosis
Symptomatic, altered organ function;
Life-threatening; organ failure
Death
urinary
endoscopic finding
or renal dysfunction
hydronephrosis; operative
intervention indicated
Definition: A disorder characterized by blockage of the normal flow of contents of the urinary tract.
Proteinuria
Urine protein/creatinine ratio >0.5
Urine protein/creatinine ratio ≥ 1.0
Urine protein/creatinine ratio ≥ 1.0
—
—
but <1.0
but transient (<14 days in duration)
and prolonged (≥14 days duration)
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.
>3 mL kg−1 h−1 urine production
—
Polyuria
Greater in frequency or nocturia up to
>2× normal but < hourly
≥1× h−1 ; >2 mL kg−1 h−1 urine
production
2× normal
Adverse Event
Grade
RENAL/GENITOURINARY
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Adverse Event
1
2
Death
Death
—
Death
Life-threatening consequences; organ
failure
—
Life-threatening; disabling
Life-threatening, urinary obstruction
and postrenal failure result
Excessive straining, makes repeated
attempts to urinate, severely
reduced urine stream, signs
persist >5 days; medical or
surgical intervention required
5
Anuria: absence of urine production
—
4
Pet asks to be let out >10 times/day;
any change in frequency that lasts
>5 days, medical or surgical
intervention required
3
Mild oliguria: <1.0 ml kg−1 h−1 in
Oliguria: <0.5 ml kg−1 h−1 in a well
a well hydrated and well
hydrated and well perfused
perfused patient, responsive to
patient, resistant to medical
medical diuresis
diuresis
Definition: A disorder characterized by diminished production of urine.
Urinary retention
Hesitancy or dribbling, no
Bladder atony requiring transient
Bladder atony requiring indwelling
(including
significant residual volume
indwelling catheter <72 h
catheter ≥72 h; operative
neurogenic bladder)
intervention indicated
Definition: A disorder characterized by accumulation of urine within the bladder because of the inability to urinate.
Urine colour change
Present
—
—
Mild
Moderate
Severe
Other
)
(Specify,
Definition: A disorder characterized by straining to urinate.
Urinary
—
output – diminished
Definition: A disorder characterized by production of abnormally large volumes of dilute urine.
Pollakiuria
Pet asks to be let out more
Pet asks to be let out 6–10
frequently but <6 times/day;
times/day; any change in
any change in frequency that
frequency that lasts 2–5 days
lasts ≤2 days.
Definition: A disorder characterized by frequent daytime urination.
Stranguria
Minimal straining, attempts to
Minimal straining, attempts to
urinate 1–3 times at a urination
urinate >3 times at a urination
event, slightly reduced stream,
event, moderately reduced
signs persist up to 2 days
stream, signs persist 2–5 days
Grade
RENAL/GENITOURINARY (CONTINUED)
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1
2
Present
Life-threatening consequences;
urgent intervention indicated
—
4
—
3
Definition: A disorder characterized by insufficiently healthy haematapoietic cell production by the bone marrow.
—
—
Non-life-threatening benign
Acute life-threatening secondary
Treatment-related secondary
tumour or malignancy
malignancy; blast crisis in
malignancy
)
leukaemia
(Specify,
Definition: A disorder characterized by development of a malignancy most probably as a result of treatment for a previously existing malignancy.
Tumour pain
Mild pain not interfering with
Moderate pain; manageable with
Severe pain; manageable with
Disabling or uncontrollable pain
function; manageable with
standard oral analgesics
systemic analgesics, pain or
nonsteroidal anti-inflammatory
(NSAIDs, opiates), pain or
analgesics interfering with ADL
drug (NSAID)
analgesics interfering with
function but not 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.
Clinical or diagnostic observations
Moderate; minimal, local or
Severe or medically significant but
Neoplasms benign, malignant
Life-threatening consequences;
only; intervention not indicated
noninvasive intervention
not immediately
and unspecified (including
urgent intervention indicated
indicated
life-threatening; hospitalization
cysts
or prolongation of existing
and polyps)
)
hospitalization indicated;
Other (Specify,
limiting ADL
Leukaemia secondary to
—
—
oncology chemotherapy
Definition: A disorder characterized by leukaemia arising as a result of the mutagenic effect of chemotherapy agents.
Myelodysplastic syndrome
—
—
Adverse Event
Grade
NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS)
Death
—
Death
Death
Death
5
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—
Fetal death
—
2
—
3
—
4
5
Foetal 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.
Gynaecomastia
Breast enlargement without
Breast enlargement with clinical effect
—
—
—
clinical effect on patient
on patient
Definition: A disorder characterized by excessive development of the mammary tissue in males.
Infertility/sterility
—
Male: Oligospermia/low sperm count
Male: Sterile/azoospermia
—
—
Female: Diminished fertility/estrus
Female: infertile/anestrous
Definition: A disorder characterized by inability to reproduce.
Mammary gland
Mammary abnormality, not
Mammary abnormality, functionally
—
—
—
function/lactation
functionally significant
significant
Definition: A disorder characterized by disturbances in milk production or secretion.
Vaginal discharge
Mild
Moderate to heavy
—
—
—
(non-infectious)
Definition: A disorder characterized by excess vaginal secretions.
Mild
Moderate
Severe
Life-threatening;
—
Other
)
disabling
(Specify,
1
Adverse Event
Grade
SEXUAL/REPRODUCTIVE FUNCTION
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1
2
3
Grade
4
5
Capillary leak syndrome
—
Symptomatic, fluid support not indicated
Respiratory compromise or pressor support
Life-threatening; ventilatory support 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, ischaemia–reperfusion injuries, toxemias, medications or poisoning. It can lead to generalized oedema and multiple organ failure.
Lymph leakage
—
Symptomatic; medical intervention indicated
Severe symptoms; radiologic, endoscopic or
Life-threatening consequences; urgent
Death
elective operative intervention indicated
intervention indicated
Definition: A disorder characterized by the loss of lymph fluid into the surrounding tissue or body cavity.
Peripheral arterial
—
Brief (<24 h) episode of ischaemia managed
Recurring or prolonged (>24 h) and/or
Life-threatening, disabling and/or associated
Death
ischaemia
nonsurgically and without permanent
invasive intervention indicated
with end-organ damage (e.g. limb loss)
deficit
Definition: A disorder characterized by impaired circulation to an extremity.
Phlebitis
—
Present
—
—
—
Definition: A disorder characterized by inflammation of the wall of a vein.
Thrombosis/thrombus/
—
Deep vein thrombosis or cardiac thrombosis;
Deep vein thrombosis or cardiac thrombosis;
Embolic event including pulmonary embolism
Death
embolism
intervention not indicated
intervention indicated (e.g. anticoagulation,
or life-threatening thrombus
lysis, invasive procedure)
Definition: A disorder characterized by occlusion of a vessel by a thrombus that has migrated from a distal site via the blood stream.
Visceral arterial ischaemia
—
Brief (<24 h) episode of ischaemia managed
Prolonged (>24 h) or recurring clinical signs
Life-threatening; disabling; evidence of
Death
medically and without permanent deficit
and/or invasive intervention indicated
end-organ damage
Definition: A disorder characterized by a decrease in blood supply due to narrowing or blockage of a visceral (mesenteric) artery.
)
Mild
Moderate
Severe
Life-threatening; disabling
Death
Other (Specify,
Adverse Event
VASCULAR
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