Oncology Flashcards
what is the spectrum of behaviour shown by tumours?
truly benign to highly malignant
some may have local characteristics of malignancy but do not metastasise
what are the 6 features necessary for the development of cancer?
self-sufficiency in growth signals
insensitivity to anti-growth signals
tissue invasion and metastasis
limitless replicative potential
sustained angiogenesis
evasion of apoptosis
what is the hallmark of cancer?
alterations in genes
different from hereditary disease
what are overactive oncogens?
tumour-promoting genes (secondary to mutation)
what is the other genetic component of cancer?
loss of tumour suppressor genes
e.g. alteration to P53 checkpoint gene
what is neoplasia defined as?
“new growth” - but inferring abnormal growth
what is a tumour?
a swelling (but inferred to be a neoplasm)
what does benign mean?
a neoplasm that forms a solid cohesive tumour and does not metastasise
what does malignant mean?
a neoplasm with the capacity for local invasion and metastasis
what is a cancer?
a malignant tumour
what does metastasis mean?
development of a secondary tumour remotely from the primary tumour
tumours are described according to…
the tissue of origin (epithelial/mesenchymal/round cell)
status (benign/malignant)
what suffix do benign tumours end in?
-oma
what is a benign squamous epithelial tumour called?
papilloma
what is a benign glandular tissue tumour called?
adenoma
what is a benign bone tissue tumour called?
osteoma
what is a benign blood vessel tumour called?
haemangioma
what is a malignant squamous epithelial tissue called?
squamous cell carcinoma
what is a malignant glandular tissue tumour called?
adenocarcinoma
what is a malignant bone tissue tumour called?
osteosarcoma
what is a malignant blood vessel tissue tumour called?
haemangiosarcoma
what is malignant caner of the lymphocytes called?
lymphoma
what is malignant cancer of the mast cells called?
mast cell tumour
what are the epithelial tissues most prone to tumour formation?
squamous
glandular
what are the mesenchymal tissues most prone to tumour formation?
bone
blood vessels
what are the round cells most prone to tumour formation?
lymphocytes
mast cells
what are the 2 important clinical features of a cancer?
effect on the host
response to treatment
what factors will affect the effect on the host and the response to treatment of a cancer?
tumour growth (how actively the cancer is developing)
tumour grade (how severe the neoplasm is on histopathological analysis)
tumour behaviour (local behaviour, metastatic potential, paraneoplastic effects)
when does a tumour do most of its growing?
before detection
what size/weight does a tumour have to be to be detectable by palpation or radiography?
1cm diameter
0.5-1 gram in weight
10^9 cells
what is the growth fraction?
the proportion of actively dividing cells in a tumour
what does the “tumour doubling time” refer to?
the time taken for a tumour to double in size
a reflection of the growth fraction
what happens to the tumour doubling time as the tumour grows?
tendency to lengthen
how receptive are tumours to treatment in the early stages of growth?
dividing and growing rapidly - sensitive to chemotherapy and radiation therapy
how receptive are tumours to treatment by the time they are detectable?
growth fraction is reaching plateau - less susceptible than healthy tissues to therapy
why are treatments that attack rapidly dividing cells likely to be toxic to the body?
proportion of dividing cells is often less than that in normal, rapidly dividing body tissues such as the intestinal epithelium and bone marrow (by the time the tumour can be detected by palpation)
which types of tumours are still susceptible to treatment even when palpable?
tumours which maintain a high growth fraction despite a large tumour burden (e.g. lymphoma)
are tumours homogenous?
no - a tumour cell population is quite heterogenous
Cancer cells modify their properties as they grow, mainly by small sequential mutations
what does the grade of a tumour depend on?
mitotic rate
cellular and nuclear characteristics
with respect to benign and malignant tumours, describe: rate of growth manner of growth effects on adjacent tissues effects of surgery metastasis effect on host paraneoplastic effects
what factors have an impact on tumour behaviour?
rate and manner of growth
effects on adjacent tissues
surgery
metastasis
effect on host
paraneoplastic effects
how do malignant tumours grow?
local invasion
what are the physical clues of local invasion?
diffuse, indistinct boundaries
fixation of the tumour in one or more planes
thickening of adjacent tissue
spontaneous bleeding
how do malignant cancers spread?
via the blood, producing secondary tumours in any body organ
via lymphatics, to local and regional lymph nodes
transcoelomic across the pleural or peritoneal space
iatrogenic e.g. seeding by FNA or tru-cut biopsy
where is the most common site for the development of haematogenous secondary tumours?
lungs - primary lung tumours are rarer, but will metastasise to peripheral sites
which other sites are prone to development of haematogenous secondary tumours?
those with high blood flow e.g. liver, spleen, kidneys, bone and CNS
which tumour is usually the largest?
the primary tumour
what are paraneoplastic syndromes (PNS)?
signs arising from the indirect effect of tumours’ production and release of biologically active substances
what do PNS affect?
distant organs - may be the first evidence of neoplastic disease
what are the haematologic PNS?
anaemia (weakness, lethargy, tachypnoea)
thrombocytopaenia (bleeding)
leukopenia (susceptibility to infection)
what is hyperviscosity syndrome (HS)?
increased blood cell numbers with sludging blood and poor circulation
what are the physiological effects of hyperviscosity syndrome?
leukaemia
primary polycythaemia
secretion of excess erythropoietin causing secondary polycythaemia
excess gammaglobulins (especially IgM) secreted by multiple myeloma (plasma cell tumour)
what are the clinical signs of HS syndrome?
lethargy episodic weakness thromboembolism disorientation bleeding tremors, ataxia, seizures retinal haemorrhage and detachment
what causes hyperhistaminaemia?
mast cell tumours - often release histamine and vasoactive amines (especially when handled for FNA/surgery)
what are the local effects of hyperhistaminaemia?
oedematous swelling with erythema and pruritus
tendency for localised bleeding
delayed wound healing or dehiscence after surgery (released proteases)
what are the systemic effects of hyperhistaminaemia?
anaphylactic shock due to massive sudden release of histamine (vasodilation and hypotension)
gastroduodenal ulcer (can perforate)
how do you avoid anaphylactic shock due to hyperhistaminaemia?
premedication with H1 antagonist (diphenhydramine) prior to surgical manipulation of tumour
how do you avoid gastroduodenal ulcer due to hyperhistaminaemia?
Treat with H2 antagonist (cimetidine or ranitidine)
or proton pump inhibitor (omeprazole)
what are the common immune-mediated reactions associated with neoplasia?
immune-mediated haemolytic anaemia and/or thrombocytopaenia
neuropathies - insulinoma
myasthenia gravis
feline paraneoplastic alopecia (shiny skin disease)
why do immune-mediated reactions occur alongside neoplasia?
cross-reactivity between cancer cells and healthy cells leading to dysregulation of the immune system
what are the main 2 resulting issues of endocrine-related PNS?
hypercalcaemia
hypoglycaemia
what is the most common neoplastic syndrome in dogs?
hypercalcaemia
how does hypercalcaemia occur in oncology?
tumours release parathyroid hormone-related peptide
increases total and ionised calcium concentrations
which type of cancer most commonly causes neoplasia?
lymphoma
but also anal sac adenocarcinoma, multiple myeloma and carcinoma/sarcoma with skeletal metastasis
what are the clinical signs of hypercalcaemia?
renal effects are of greatest importance: dehydration and renal failure
PUPD anorexia and vomiting lethargy, depression (neuro depression) muscular weakness (NM depression) bradycardia (CVS depression)
what causes hypogylcaemia in oncology?
pancreatic insulinoma
excessive consumption of glucose by the body (hepatoma, hepatocellular carcinoma, large intra-abdominal masses, chronic lymphocytic leukaemia)
release of an insulin-like factor
what causes cancer cachexia?
muscle and fat loss
enhanced catabolism
reduced food intake
what commonly causes fever during cancer?
pyrogens cytokins (IL-1, IL-6)
what are the aims of investigation into a cancer?
make a histological diagnosis of the type and grade
determine the extent of the disease (stage)
investigate and treat any tumour-related or concurrent complications
what is required to make an accurate diagnosis of cancer?
microscopic examination of representative tissues or cells - cannot diagnose via palpation
all excised masses should be…
submitted for histology
fixed and stored, just in case the owners change their mind or the patient deteriorates
what types of cytology samples can be made?
touch/impression preparations
FNAs
analysis of body fluids/effusions
how do you prep for an FNA?
no need to prep of clip skin
no need for sedation or GA
use 21G or 23G needle
what can cytology tell us?
nature of the tumour i.e.
type of cell (epithelial/mesenchymal/round cell)
cytological features
what can cytology not tell us?
the definitive diagnosis
false negatives may occur (sarcoma)
can be difficult to differentiate inflammation from neoplasia, especially if tumour outgrows blood supply or is necrotic
what types of histological sampling can be performed?
surgical biopsy
needle (tru-cut)
punch biopsy
why is surgical biopsy the best histological sampling method?
can tell us: cellular features of malignancy tumour architecture invasion of adjacent tissues evidence of metastatic behaviour (presence in blood vessels/lymphatics)
what types of surgical biopsy are there?
incisional - part of tumour along with a part of healthy tissue
excisional - removal of the entire tumour and a margin of healthy-looking tissue
what are the rules for taking a biopsy?
avoid superficial ulceration/inflammation/necrosis
ensure adequate depth
try to include a boundary between tumour and normal tissue
in which cases might we not obtain a biopsy?
where the risk of obtaining a biopsy may be too great (e.g. brain tumour)
where performing a biopsy does not alter what is done to the patient (e.g. splenectomy)
what does clinical staging of a tumour aim to identify?
cytological or histological grade
local invasion
metastatic spread
what is the TNM staging system?
Tumour - assessing size and invasiveness
Nodes - assessing local draining lymph nodes for evidence of spread
Metastasis - assessing spread to other organs
what are the grades of T in the TNM staging system?
T0 - no evidence of primary tumour
T1-4 - size and/or extent of primary tumour
what are the grades of N in the TNM staging system?
N0 - no regional lymph node involvement
N1-4 - degree of involvement of regional lymph nodes
what are the grades of M in the TNM staging system?
M0 - no distant metastasis
M1, M2 - distant metastasis is present (single/multiple)
which tests can be performed to assess the distant spread of a tumour?
history and physical exam
thoracic radiographs (3 views) or CT
abdominal radiographs and US
FNA of lymph nodes/liver/spleen
bone marrow aspiration (if haematological abnormalities)
how can you evaluate the local/regional lymph nodes?
palpation of size and texture
imaging of deeper nodes
FNAs to distinguish tumour spread from reactive hyperplasia due to tumour necrosis
why is clinical staging never exact?
differences between clinical stage and true pathological state may occur because of microscopic tumour extensions or deposits that are impossible to detect in vivo
which factors play a role in deciding the best treatment for cancer?
nature of the disease
options and side effects
prognosis with/without treatment
cost
tumour biology/histology/grade/stage
what is considered ‘cured’ cancer?
all cells that have the capacity for tumour regeneration eradicated
what is considered remission?
all clinical evidence of cancer has disappeared, but occult cancer cells remain and relapse will occur at some point
what is palliation?
reduction of pain/improved sense of well-being and/or correcting physiological malfunction
cancer still clinically identifiable
what are the three main methods of cancer treatments in animals?
surgical excision
radiation
anti-cancer/cytotoxic drugs (chemotherapy)
what is the most effective treatment?
surgery is the most effective treatment for the majority of solid tumours, and offers the best chance of a cure, as the primary objective is to remove all tumour cells
what is a surgical excision suitable for?
truly benign tumours - fibroma, lipoma, benign mammary tumours
what is a wide local excision?
wide margins (1-2cm) and two tissue planes of apparently normal tissue excised to ensure that all tumour is removed so that growth doesn’t occur
what type of tumours is wide local excision suitable for?
locally invasive tumours e.g. basal cell carcinoma, squamous cell carcinoma, mast cell tumours
when might wide local excision be challenging?
if there is insufficient normal tissue to be able to close the wound
e.g. chest wall, distal limbs, head, oral cavity
often requires local excision of underlying bone
what is compartmental resection?
resection involves removing every tissue compartment which the tumour involves
‘en bloc’
reconstructive procedures often needed to close the wound
which tumours often require compartmental resection?
soft tissue sarcomas - fibrosarcoma, haemangiopericytoma
when does failure of surgery occur?
when the tumour grows at the primary site due to incomplete resection
when the tumour has already metastasised
when the cancer is systemic, e.g. multicentric lymphoma
what is surgical debulking?
partial removal of the tumour without curative intent
followed by subsequent therapy with drugs, radiation or other adjunctive measure
what type of tumour is surgical debulking used for?
surgically incurable malignant neoplasms
what are the general rules for surgical excision of a tumour?
mark out margins (include a margin of normal tissue)
cut large and deep
use two sets of instruments?
why should you use two set of instruments for surgery?
one for excision and one for closure
to avoid iatrogenic seeding of cancerous cells
what are the considerations when filling out the form for a laboratory sample?
provide a clinical history
if concerned about a particular margin, mark it and inform pathologist
identify and orientate samples (labels)
submit all the samples and the entire tumour
what are the general considerations post-op?
nutrition
analgesia
wound care/management
functionality
what can excessive tension at wound closure result in?
compromise to circulation ischaemia oedema slow wound healing wound breakdown necrosis distortion of anatomic areas e.g. anus, eyelid
what are the patient factors involved in wound breakdown (intrinsic and extrinsic)?
intrinsic = concurrent disease, poor nutrition
extrinsic = chemotherapy, steroids, radiotherapy
what are the wound factors which contribute to wound breakdown?
neoplasia tissue handling/haemostasis excessive tension motion poor suturing infection patient interference
how should a wound be managed after it has broken down/re-opened?
do not re-suture - considered dirty/contaminated
allow to heal via second intention
what is a seroma?
accumulation of fluid at the level of a wound
how can seroma formation be prevented?
limit formation of dead space - drain placement
rest - limit motion
leave alone
pressure bandage
how should a wound be managed if it becomes infected?
provide drainage
allow to heal via second intention
antibiotics based on culture and sensitivity
exploration of wound if necessary
what is radiation therapy?
the medical use of ionizing radiation as an integral part of cancer treatment by killing or controlling malignant cells
when might radiation be used?
it is the most effective and least toxic local treatment if surgery is incomplete
what is the main principle of radiation therapy?
radiation interacts with biological material by removing an orbiting electron, a process termed ionisation
what are the 2 methods of application of radiotherapy?
brachytherapy
external beam radiation therapy/teletherapy (most common)
what are the 2 types of radiation used in radiation therapy?
electrons (beta particles) - absorbed by tissue or easily shielded
high - energy x-rays - penetrating and harmful
how is brachytherapy administered (3 ways)?
applied to the surface of a tumour
implanted within the tumour (gold seeds)
administered systemically but concentrated in the tumour
what is external beam radiation therapy?
radiation therapy given by an external radiation source at a distance from the body
why is use of teletherapy limited?
because of restricted availability of a fixed radiation source or a linear accelerator (LINAC)
what are the acute reactions to radiotherapy?
skin reddening vesiculation desquamation severe exfoliative dermatitis localised heat loss
what are the signs of late toxicity after radiation therapy?
depigmentation
dermal fibrosis
osteonecrosis
neural necrosis (blindness, neurological signs)
what is the response to chemotherapy dependent on?
the growth fraction
drug resistance
are tumours in their early stages sensitive to chemotherapy?
yes - sensitive to chemotherapy and radiation
are tumours receptive chemotherapy by the time they are detectable?
less susceptible to chemotherapy than healthy tissues
growth fraction is reaching plateau
which healthy tissues are most susceptible to chemotherapy?
bone marrow
gut epithelium
how do chemotherapy drugs work?
act upon processes in cell growth and division - DNA replication, mitotic spindle, metabolic activities
what is the main principle of chemotherapy treatment?
efficacy vs toxicity
using the highest possible dose to effect maximum fractional kill with minimum side effects
when is chemotherapy most effective?
when tumour burden is at its lowest and growth fraction highest, i.e. early or after surgical ‘debulking’
how can you maximise efficacy and minimise toxicity?
use repeated cycles of a range of drugs, allowing recovery time (typically 3 week cycles)
how is dosing calculated?
as a function of surface area (m^2)
which types of cancer are highly sensitive to chemotherapy?
lymphoma
myeloma
some forms of leukaemia
which types of cancer are moderately sensitive to chemotherapy?
high grade sarcomas
mast cell tumours
which types of cancer are poorly sensitive to chemotherapy?
most slow-growing sarcomas
most carcinomas
melanomas
what is combination therapy?
the combination of different classes of chemotherapy agents with different mechanisms of action
what is the favoured approach in chemotherapy?
combination therapy - more effective than a single agent
why is combination therapy more effective than a single agent?
greater tumour cell kill achieved
less resistance
fewer side effects
what are the common chemotherapy protocols for cats and dogs with lymphoma?
COP for cats
CHOP for dogs
is chemotherapy used as a first-line treatment for solid tumours?
rarely of value as sole therapy - best treated with surgical resection and/or radiotherapy
why might chemotherapy be used as an adjunct to surgical and/or radiotherapy?
to reduce tumour mass to enable surgical resection
to try to prevent/delay metastasis
what is metronomic chemotherapy?
palliative low doses of chemotherapy drugs, given daily
why is metronomic chemotherapy given?
anti-angiogenic - targets the endothelium or tumour stroma
designed to minimize toxicity and palliative only
what is chemoembolisation?
local, directed delivery of chemotherapy drug and embolisation to treat inoperable solid tumours
how is chemoembolisation performed?
chemotherapy drug injected in blood vessel supplying the tumour
synthetic material (embolic) placed inside the blood vessel trapping the chemotherapy in the tumour
what is involved in safe use of chemotherapy?
use of protective equipment (gloves, mark, glasses, apron)
use of a sealed closed system for admin of injectable chemo
cleaning procedures
use of a chemo room
clear protocol for disposal with allocated bins
pregnant women should not handle any chemo drugs
what is involved in safe handling of cytotoxic drugs?
chemo room locked
use of a cabinet with vertical flow containment hood
use of a plastic pad, the drug is never in direct contact with a surface
use of luer-lock syringes for administration
how should chemotherapy material be disposed of?
all material used is gathered in a sealed plastic bag and disposed in bin for chemo wastes
what is involved in nursing care of chemotherapy patients?
designated kennel with clear ID of agents used
PPE for those caring for patient (gloves, gown, eye protection)
all materials that have been in contact with the animal should be regarded as potentially contaminated - use a dedicated cytotoxic waste bin
what is the average period of risk to humans after chemo drug administration?
3-7 days
how should cleaning of materials be handled when the dog is at home?
wash any food bowls/toys/bedding separately from other household items
use latex gloves when cleaning up urine/faeces/bodily fluids, disinfect area with household bleach, wash hands
dispose of gloves in trash, double bagged
what is the inherent toxicity of chemotherapy agents due to?
effect on dividing cells, including normal tissues with a high cell turnover (bone marrow, intestinal)
why does chemotherapy cause GI toxicity?
direct toxic effects on the GI tract through death and loss of intestinal epithelial cells
how long after chemotherapy admin do GI side effects start to occur?
5-10 days
what are the GI side effects of chemotherapy?
stomatitis
vomiting
mucoid/haemorrhagic diarrhoea
some drugs (e.g. doxorubicin) also induce early nausea and vomiting by stimulation of the CRTZ
how are signs of GI toxicity due to chemotherapy treated?
treatment is symptomatic
IV fluid therapy
ant-emetics
gastroprotectants for GI ulceration
parenteral antibiotics (if immunosuppressed or haemorrhagic diarrhoea)
what coat changes can occur in an animal undergoing chemotherapy?
cats usually only lose their whiskers
not a major problem in most dogs but some breeds are susceptible to significant patchy hair loss
what is myelosuppression?
a decrease in bone marrow activity that results in reduced production of blood cells
why is routine haematology performed before cytotoxic agents are given?
most cytotoxic drugs are myelosuppressive - treatment is delayed and/or reduced if there is myelosuppression
what does myelosuppression cause?
neutropenia (can be life-threatening)
thrombocytopaenia
anaemia (rarely clinically significant)
at what neutrophil count is the patient at risk of sepsis and/or pyrexia?
<2 x 10⁹/L
why are patients with myelosuppression at risk of sepsis?
due to translocation of enteric bacteria across the mucosa into the bloodstream
what does management of neutropenia depend on?
absolute cell count
clinical signs
at what myelosuppression grade should chemotherapy be stopped?
moderate (<2 x 10⁹/L)
why might neutropenia grade be associated with a better prognosis?
neutropenia is an indicator of maximum tolerated dose being reached/approached
which cytotoxic drug may cause hypersensitivity/anaphylaxis?
rare but reported in dogs with doxorubicin
what should be done if a hypersensitivity/anaphylaxis reaction occurs?
stop the drug admin
give IV fluids, soluble corticosteroids, adrenaline and antihistamines
what can happen if a cytotoxic drugs extravasates?
can cause phlebitis or tissue necrosis
what can occur if a vesicant drug (e.g. doxorubicin) moves peri-vascularly?
severe and/or irreversible tissue injury and necrosis
how can risks of extravasation be reduced?
using drugs in a sealed system
adequate restraint of the patient
“clean stick” - don’t re-arrange catheter after it is placed
catheter flushed with saline before and after
how is perivascular leakage of doxorubicin treated?
stop infusion but do not remove the catheter
aspirate extravasated drug through catheter and give intralesional saline to dilute drug
draw back blood and remove catheter
IV hydrocortisone and cold compress
?antidote - dexrazosane
what are the signs of sterile haemorrhagic cystitis?
profuse haematuria - sometimes irreversible
how is sterile haemorrhagic cystitis treated?
no specific treatment - an irritant effect of the drug
MESNA may be protective
how can you minimise the risk of sterile haemorrhagic cystitis?
administer drug early in morning so not retained in bladder overnight
ensure good fluid intake
encourage frequent urination
concurrent steroids of furosemide will assist diuresis
monitor urine for blood/protein (urine dipstick before each administration)
what is a sign of acute doxorubicin toxicity?
tachyarrhythmias
what is a sign of chronic doxorubicin toxicity?
dose-dependent cardiomyopathy
irreversible
what other specific toxicities are associated with chemotherapy drugs?
hepatotoxicity (increase in liver enzymes)
nephrotoxicity (monitor urea/creatinine)
