Oncology 1.0 Flashcards
what is cancer?
uncontrolled proliferation of abnormal cells independent of normal homeostatic mechanisms and the requirement for new cells
what are the reasons a patient may die of cancer?
delayed/incorrect diagnosis
failure of treatment
owner decided not to treat
what are the AVMAs signs of cancer?
abnormal swelling that persists/continuously grows
sores that don’t heal
unexplained weight loss
loss of appetite
bleeding/discharge from any body opening
bad odour (especially halitosis)
difficulty eating/swallowing
reluctance to exercise/loss of stamina
difficulty breathing, urinating, defecating
change in behaviour
what is the most common neoplasia seen in dogs?
mast cell
what is the use of cytology for neoplasia?
guiding diagnostics and treatment planning particularly prior to surgery
what is the use of histopathology for neoplasia?
making a final diagnosis and guiding post surgical treatment
when is needle off FNA used?
lymph nodes
suspected round cell tumours
when is needle on FNA used?
suspected solid tumours
needle off gave a poor yield
what are some tips for needle on FNA?
don’t go through lesion
be vigorous
release suction before taking needle out
what are some contraindications of sampling/biopsy of neoplasms ?
risk of bleeding - evidence of coagulopathy
risk of pneumothorax, urine, abscess leakage after sampling
risk of tumour transplantation deeper into tissue (seeding)
damage adjacent structures
what are some issues associated with FNAs?
not always diagnostic
not always representative - heterogenous or healing lesions
what are the advantages of needle core biopsies?
larger sample than aspirates
inaccessible tissue can be assessed percutaneously
can evaluate some architecture
can do conscious but sedated
what is the most commonly used technique for an incisional biopsy?
inverted wedge
what are the general rules for incisional biopsies?
avoid major structures
avoid necrotic, haemorrhagic, infected areas
should be able to remove entire biopsy tract in subsequent surgery
general rules of surgery
ensure adequate fixation when removed
include normal tissue if able to
what tumours are surface pinch/grab biopsies often used for?
nasal tumours
what is the technique point to note when doing a punch biopsies?
rotate punch continuously the same direction to ensure you don’t shear the layers
what cases is excision biopsy appropriate without pre-treatment diagnosis?
haemorrhagic splenic mass
mammary tumours
pulmonary tumours
what are some contraindications for excision biopsies?
rapidly growing masses
ill-defined/poorly demarcated lesions
peritumoural oedema or erythema
skin ulceration
injection site mass in cats
suspicious of MCT or STS after FNA
non-diagnostic FNA
when is the only time active monitoring should be considered?
if a diagnosis has been made and owners have been made aware of this
what system is usually used to stage solid tumours?
TNM classification
what is the TNM classification for staging solid tumours?
T - primary tumour
N - metastatic disease in local lymph nodes
M - distant metazoic disease
how is clinical staging of T (primary tumour) carried out?
clinical examination
location and palpability
fixation - deeper tissue, skin…
is ulceration present
imaging (plain/contrast radiograph…)
advanced imaging (CT, MRI…)
what are the two categories of metastatic patterns?
haematogenous
lymphatic
what two tumours commonly metastasis haematogenously?
sarocomas
malignant melanoma
how is clinical staging of N (nodal metastasis) carried out?
palpation (lymph node size, texture…)
imaging (radiography, ultrasound, lymphangiography…)
cytology/histology (FNA, biopsy…)
what is lymphangiography?
injecting contrast into a tumour to determine which node it drains to (CT based)
what lymph node do cranial abdomen tumours metastasise to?
sternal lymph node
what lymph node do thyroid carcinomas metastasise to?
retropharyngeal lymph nodes
what are common sites of metastatic disease?
lung
parenchymatous organs
bone
skin
CNS
distant nodes
what is a cause of mineralised opacities in the lungs that look like metastasis?
pulmonary osteoma
what are the indications for cytology?
lesion - palpable or seen on imaging
organomegaly
cavitary effusion
cancer staging - lymph nodes, liver, spleen
pyrexia of unknown origin
what is usually used to stain cytology slides for analysis of tumours?
diff quik (wear gloves and dip 10 times in each)
what are the stages of analysis a cytology slide of a tumour?
assess with naked eye
low magnification
what is assessed by the naked eye on cytology slides of tumours?
is it labeled
macroscopic appearance - good staining, even distribution
what is assessed on low magnification of tumour cytology slides?
intact cells
cellular populations
thin regions with good nuclear/cytoplasmic detail
what do lots of ruptured cells suggest about the cytology slide?
incorrect sampling/smearing (repeat sampling procedure)
why might a cytology slide have inadequate staining?
insufficient time in stain
inadequate drying time
layer of cells is too thick
exposed to formulin fumes
what are the predominant cell types seen with inflammation?
neutrophils, macrophages, lymphocytes, plasma cells, eosinophils
(can also see microorganisms)
what are the three types of cells seen with neoplasia?
epithelial (skin, gut, glandular…)
mesenchymal (connective tissue, muscle…)
round cells (immune system)
once you have identified neoplasia on cytology what should be assessed next, starting from low power?
cell arrangement - cohesive, cytoarchitecture…
cell shape - round, spindle, polygonal…
how can the cell arrangement/shape of epithelial cell neoplasms be described?
cohesive - adhere in clumps/clusters
well define cell-cell junction
polygonal, cuboid, columnar with round nucleus
how can the cell arrangement/shape of round cell neoplasms be described?
non-adherent and individualised
round with round/oval nuclei
how can the cell arrangement/shape of mesenchymal cell neoplasms be described?
non-adherent but can be loosely aggregated
fusiform to stellate shape with elongated nuclei
wispy cytoplasmic projections
indistinct cell borders
are most skin tumours in dogs and cats benign or malignant?
cats - malignant
dogs - benign
what are some examples of round cell tumours?
histiocytoma
plasma cell tumour
mast cell tumour
lymphoma
(transmissible venereal tumour)
what are some non-neoplastic non-inflammatory lesions?
keratinising cysts (sebaceous cysts)
sebaceous hyperplasia
what are the two groups of criteria of malignancy?
nuclear criteria (stronger indication)
cytoplasmic criteria
what are the nuclear criteria of malignancy?
mulitnucleation
karyomegaly
mitoses
nuclear moulding
large, angular, variably sized nucleoli
what is the minimum number of criteria of malignancy to suggest a malignant neoplasm?
minimum of three throughout the smear (take into account organ/cell type)
what are the two main categories of radiotherapy?
brachytherapy (radiation close to tumour)
tele therapy (radiation far from tumour)
what are the types of brachytherapy?
direct application
implantation
systemic administration
what is the main type of teletherapy?
external beam (linear accelerator)
what are the ways radiation is produced for teletherapy?
linear accelerator
natural radioactive decay
what are the main forms of therapy used in teletherapy?
photon and electrons produced by linear accelerators
what is the Compton effect?
when a photon interacts with another molecule (usually electron) there will be release of energy from the electron and the photon will have slightly more energy (hence the maximum dose isn’t absorbed at the skin but builds up)
what piece of equipment is needed to treat the skin with teletherapy?
bolus (allow compton effect before it hits the skin) - skin can achieve maximum dose
what is the indirect way high energy electromagnetic radiation damages DNA?
water molecules are ionised which generates free radicals which cause damage to DNA
why do photons not cause much direct damage to the DNA?
DNA is very small so chances of photon hitting it is very small
what inhibits the rapid repair of DNA?
oxygen (hypoxic cells DNA repaired quicker)
how much more radiation is required to kill a hypoxic cell than a well oxygenated cell?
3 times
how can high energy electromagnetic radiation cause cell death?
induce apoptosis
permanent cll cycle arrest
mitotic catastrophe
why might the full effects of high energy electromagnetic radiation therapy not be seen until weeks later?
cell damage often isn’t expressed until the cell tries to divide, at this point the damage becomes apparent and the cell dies
is single or multiple beam radiation therapy generally better?
multiple - increase tumour dose while sparing surrounding tissue
what type of tumours are electrons usually used to treat?
superficial tumours (skin) - lose energy rapidly as it passes through tissue
what are the four Rs of response radiotherapy?
repair
repopulation
redistribution/reassortment
reoxygenation
what is fractionation in relation to radiotherapy?
total dose of radiation required to kill cells is less if a few larger doses is given rather than lots of smaller doses
what tissues is repopulation in response to radiotherapy seen most commonly in?
rapidly dividing tissues (slightly protects normal tissues)
what is the redistribution response to radiotherapy?
certain stages of the cell cycle are more sensitive to radiation than others (late G2 and M sensitive) so cell cycle can become synchronised after one treatment (use multiple treatments)
how can redistribution response to radiation therapy be used to our advantage?
cells synchronise there cycle as certain stages are more effected by radiation so can treat a second time to damage more cells
why is one larger radiation dose more effective than multiple smaller doses?
cells have time to repair between therapy
cells can repopulate between therapy
why would fractionation be beneficial?
allows normal cells to repair and repopulate
what are the limitations of fractionation in animals?
requires GA
cost
owner compliance
are cats or dogs better at dealing with radiation therapy side effects?
cats (dogs don’t deal well)
what cell cycle phase is the most resistant to radiotherapy?
S - synthesis phase (new DNA being made)
what cell cycle phase is the least resistant to radiotherapy?
M - mitotic (cell dividing)
why are smaller tumours more sensitive to radiotherapy?
rapidly dividing
high fraction of cells in sensitive growth phase
better oxygenation
can dose evenly and accurately
what are some tumours that are very sensitive to radiotherapy?
lymphoma
transmissible venereal tumour
gingival basal cell carcinoma
what are some tumours that are very resistant to radiotherapy?
fibrosarcoma
haemangiopericytoma
oral SCC (cats)
osteosarcoma
rhinarial SCC (dogs)
what are some acute side effects of radiotherapy?
rapidly dividing cells - skin and MM (erythema or desquamation)
what are the late side effects of radiotherapy?
damage to tissue/microvasculature - ischeamic necrosis, alopecia, skin fibrosis, reduced healing capacity
why should radiotherapy be avoided in young patients?
carcinogenic
why isn’t radiotherapy usually indicated prior to surgery?
delays wound healing
what is the general action of chemotherapy?
genotoxic (damage DNA) treatment of disease using chemical substances
what ways can chemotherapy be used?
primary therapy - sole treatment of tumour
adjuvant therapy - after surgery to mop us residual disease
neoadjuvant therapy - before surgery to shrink tumour
concurrent therapy - simultaneously to radiation to increase sensitivity to radiotherapy
what is adjuvant chemotherapy?
used after surgery to mop up any residual disease
what is neoadjuvant chemotherapy?
before surgery to shrink tumour and increase successful resection
what cells does chemotherapy target?
rapidly proliferating cells
how useful if chemotherapy at treating indolent tumours?
(slow growing tumours) - chemotherapy a poor treatment option
what factors effect the success of chemotherapy?
growth fraction
tumour cell heterogeneity (resistance evolution)
inherent tumour sensitivity
drug dosage
tumour blood supply/oxygenation
intervals between treatments
why are liver cell generally less responsive to chemotherapy?
their job is to process toxins
how can resistance to chemotherapy drugs be minimised?
treat as early as possible
use standard protocols
use correct dose
administer agents properly
act ASAP at relapse
what can induce resistance to chemotherapy drugs in lymphomas or mast cells?
pretreating with steroids
what factors affect the response and side effects of chemotherapy?
administration (ability to treat)
distribution (ability for drug to reach target)
metabolism (drug activation/deactivation)
excretion (how its cleared)
(ADME)
why is single agent chemotherapy generally avoided?
due to rapid selection for drug resistance
what are the two types of polychemotherapy?
sequential
combined
what features should agents of polychemotherapy have?
proven efficacy against tumour
different modes of action
affect different stages of cell cycle
not interfere with each others actions
have non-overlapping dose limiting toxicities
what routes of administration should be avoided for chemotherapy?
topical
intralesions
(due to environmental contamination)
what patients pose problems for chemotherapy dosing?
obese patients
animals with known drug sensitivities (collies…)
animals with hepatic functional compromise
animals with reduced renal function
what is the dosage of the first dose of chemotherapy drug given?
maximum tolerated dose (dose tolerated with minimal side effects in most dogs)
what is dosage of chemotherapy drugs based on?
body surface area (correlates better with liver/kidney blood supply)
what is the dosage interval of chemotherapy designed to do?
allow normal tissues to repair/repopulate but tumour tissue to stay damaged
what is done on a pre-chemotherapy treatment assessment?
determine tolerance of previous treatments
assess patient
tumour status
biochemistry (every few months)
haematology (prior to each treatment)
urinalysis
what is the main thing checked on haematology prior to each dose of chemotherapy?
neutrophil count (should be >3 x10e9/L)
what are some side effects that can be seen immediately on administration of chemotherapies?
anaphylaxis/hypersensitivity
cardiac arrhythmias (doxorubicin)
emesis (platinum compounds)
acute tumour lysis syndrome
what is acute tumour lysis syndrome?
large tumours that are sensitive to chemotherapy causes mass lysis after treatment causing release of tumour content into body
what are the general side effects of chemotherapy?
bone marrow
alopecia
gastrointestinal (anorexia, vomiting, diarrhoea…)
(BAG of side effects)
how can GI toxicity of chemotherapy be managed?
maropitant - prevent vomiting
pre-treatment fasting
smectite - reduce diarrhoea
when may GI toxicity of chemotherapy be considered severe and may need supportive treatment?
prolonged vomiting/diarrhoea (24-48 hours)
unwell and off food
concerned owner
when do neutrophil counts dip after chemotherapy treatment?
2-4 days post treatment (associated with improved outcome) - don’t want too low as can cause sepsis
if a patient is pyrexic and neutropenic following chemotherapy, what may be suspected?
sepsis
if a patient is severely neutropenic following chemotherapy, what actions should be taken?
antibiotics
reduction of subsequent dose (delay subsequent dose)
what must be avoided when administering chemotherapy agents?
extravasation - causes severe tissue reaction
what is metronomic chemotherapy?
using continuous low does chemotherapy to prevent angiogenesis (new vasculature formation) in the tumour
how often do chemotherapy agents need to be administered for metronomic chemotherapy?
daily
what are the functions of tyrosine kinase inhibitors in chemotherapy?
inhibit activation of specific signalling pathways involved in the growth of specific tumours
what neoplasms are tyrosine kinase inhibitors generally used for?
aggressive metastatic tumours
what are possible side effects of tyrosine kinase inhibitors?
diarrhoea, vomiting, anorexia
bone marrow suppression
which chemotherapy agents can induce sterile haemorrhagic cystitis?
cyclophosphamide
what are lymphomas?
group of neoplasms that arise from lymphoreticular cells (T/B cells)
why is canine lymphoma slightly less common in entire females?
oestrogens have a protective effect against it
what are the different presentations of canine lymphoma?
multicentric
craniomediastinal
gastrointestinal
cutaneous
extranodal
what is the most common canine lymphoma?
mulitcentric
what is the main clinical sign of multicentric canine lymphoma?
generalised peripheral lymphadenopathy
what are the clinical signs of multi centric canine lymphoma?
non-specific - weight loss, pyrexia, lethargy…
specific - diarrhoea, vomiting, ocular signs…
regional oedema (lymph drainage impaired)
what are the clinical signs of cranial mediastinal canine lymphoma?
tachypnoea, dyspnoea
hypercalcaemia (PUPD, vomiting, muscle tremor…)
pre-caval syndrome
altered heart sounds
what are the two forms of cutaneous canine lymphoma?
epitheliotrophic and non-epitheliotrophoc
what cell is the origin of epitheliotropic cutaneous canine lymphoma?
T cells
what cell do hepatosplenic extranodal canine lymphomas arise from?
T cells
what is a paraneoplastic syndrome?
set of signs/symptoms that is the consequence of the tumour but not due to the actual presence of the tumour cells in that location
what are some possible paraneoplastic syndromes?
hypercalcaemia
immune mediated disease
monoclonal gammopathies
neuropathies
cachexia
what form of canine lymphoma is hypercalcaemia associated with?
T cell
what are some immune mediated disease paraneoplastic syndomes?
IMHA
immune mediated thrombocytopenia
pemphigus foliaceous
what is the on way to get a definitive diagnosis for canine lymphoma?
cytology and histopathology
what is the main differential diagnosis for multicentric canine lymphoma?
infectious disease
what are the prognostic/clinical indicators for canine lymphoma?
grade
immunophenotype (T or B cell)
what is a stage 1 canine lymphoma?
single node of a single organ effected
what is a stage 2 canine lymphoma?
multiple lymph nodes in a local region effected
what is stage 3 canine lymphoma?
generalised lymph node involvement
what is a stage 4 canine lymphoma?
hepatic/splenic involvement
what is a stage 5 canine lymphoma?
blood and bone marrow involvement
what are the possible treatment options for canine lymphoma?
none (euthanasia)
prednisolone alone
multidrug chemotherapy (gold standard)
what do the owners need to be made aware of if they choose to treat canine lymphoma with just prednisolone?
causes resistance to chemotherapy (less likely to respond to chemo)
what is the median survival time for high dose COP to treat canine lymphoma?
6-9 months
what are some possible chemotherapy regimes for canine lymphoma?
high dose COP
discontinuous CHOP
what drugs are used in the discontinuous CHOP?
prednisolone
vincristine
cyclophosphamide
doxorubicin
what drugs are used in the high dose COP?
prednisolone
vincristine
cyclophosphamide
what is the median survival time for treating canine lymphoma with discontinuous CHOP?
10-12 months
what are the main side effects of chemotherapy?
GI toxicity - vomiting, diarrhoea, nausea
myelosuppression - neutropenia, anaemia
what specific side effect can cyclophosphamide cause?
sterile haemorrhagic cystitis
what specific side effect can doxorubicin cause?
cardiotoxicity
what specific side effect can lomustine cause?
hepatotoxicity
when may radiotherapy be indicated for canine lymphoma?
stage 1 disease
palliative care
mass lesion of CNS
what is the issue with treating CNS canine lymphoma?
many drugs don’t penetrate the blood brain barrier
why is achieving a complete response to canine lymphoma treatment vital?
increases time to relapse
increases survival time
more chance of achieving remission on next treatment
what is the issue with not achieving a complete response to canine lymphoma treatment?
suggests resistant population of tumour cells which them become the dominant population
what are the two rescue protocols for canine lymphoma treatment when complete response isn’t achieved?
DMAC (dexamethasone, melphalan, anctinomycin, citarabine)
LPP (lomustine, procarbazine, prednisolone)
what is one of the main causes of feline lymphoma?
feline leukaemia virus (most cats vaccinated for this now)
why can FIV lead to feline lymphoma?
due to the immune suppression caused by the virus
what is the main clinical sign seen with nodal-multicentric feline lymphoma?
regional lymphadenopathy (generalised lymphadenopathy is rare in cats)
what are the clinical signs of mediastinal feline lymphoma?
respiratory distress
regurgitation/dysphagia
weight loss
lethargy/exercise intolerance
what is the most commonly seen feline lymphoma?
alimentary
what is the general prognosis for renal lymphoma?
poor (low survive time)
how well does cutaneous feline lymphoma respond to chemotherapy?
poor response (poor prognosis)
why is diagnosis of feline lymphoma harder than canine?
cats generally have low grade, small cell or mixed lymphoma
difficult to differentiate from reactive hyperplasia on cytology
what ancillary test can aid diagnosis of feline lymphoma?
PCR for antigen receptor rearrangement (PARR)
is staging, grading and typing of feline lymphoma?
no (not the same prognostic indications as there is in dogs)
what is the main prognostic indicator for feline lymphoma?
how they respond to treatment (if they achieve complete response or not)
what are the treatment options for feline lymphoma?
none (euthanasia)
corticosteroids
mutlidrug chemotherapy - COP, CHOP
what is the median survival time for feline lymphoma without therapy?
4 weeks
what is the best treatment regime for feline lymphoma?
high dose COP
why is doxorubicin use in cats controversial?
nephrotoxicity
what is the risk associated with treated alimentary feline lymphoma that has extensive infiltration?
aggressive treatment can lead to perforation of the GI tract so stagger the induction to the treatment
how is leukaemia classified?
progression (acute/chronic)
cell type (lymphoid/myeloid)
what two leukaemia are rapidly progressive and fatal diseases?
acute lymphoid leukaemia
acute myeloid leukaemia
what cancer is myelodysplastic syndrome a precursor for?
acute leukaemia
what are some treatment options for acute leukaemia?
supportive (blood transfusion, antibiotics…)
multiagent chemotherapy
what is the mean survival time of acute leukaemias when treated with chemotherapy?
120 days
is the prognosis for acute or chronic leukaemia better?
chronic
what is chronic lymphoid leukaemia?
proliferation of mature lymphocytes in bone marrow
what is the best/easiest way to diagnose leukaemia?
haematology with manual differential
what are myeloma related disorders (multiple myeloma)?
systems neoplastic proliferations of plasma cells resulting in overproduction of antibodies
what are the criteria that dogs have to achieve two of to be diagnosed with multiple myeloma?
monoclonal gammopathy
radiographic evidence of osteolytic bone lesions
>5% neoplastic plasma cells or >10% plasmacytosis in bone marrow
bence-jones proteinuria
what are paraneoplastic syndromes?
consequences of cancer but not due to the location of the cancer cells/tumour
what are systemic effects of cancer?
effects seen due the physical location of a cancer
what are some GI paraneoplastic and systemic effects of cancer?
cachexia and anorexia
gastroduodenal ulceration
protein losing enteropathy
why does cancer cachexia happen?
poor appetite
altered metabolism from cytokines/inflammation due to cancer
glucose used up by anaerobic respiration of tumour causes lactate production and insulin sensitivity
what diet is best to try and combat cancer cachexia/anorexia?
low carbohydrate and high fat
how does gastroduodenal ulceration occur as a paraneoplastic effect of cancer?
some tumours produce hormone/metabolites that trigger gastric acid production and hence ulceration
what is a common tumour that causes gasproduodenal ulceration due its paraneoplastic effects?
mast cell tumour (elevated blood histamine)
what are some haematological paraneoplastic and systemic effects of cancers?
loss, reduced production, destruction
cytoses
mono-clonal gammopathies
coagulation disorders
what anaemia is caused by chronic blood loss from cancers?
poorly regenerative microcytic hypo chromic anaemia (due to iron deficiency)
why can cancers cause reduced production cytopenias?
crowding of stem cells in marrow by tumour cells
suppressive cytokines produced by cancer
what is the order of cytopenias seen with reduced production cytopenias?
neutropenia then thrombocytopenia then anaemia
what are some possible causes of reduced production cytopenias?
anaemia of chronic inflammation
myelophthisis
hyperoestrogenism
what tumours cause hyperoestrogenism?
testicular (Sertoli cell)
how does hyperoestrogenism cause a reduced production cytopenia?
causes bone marrow hypoplasia
other than cytopenias, what are some other signs of hyperoestrogenism?
feminisation
symmetrical alopecia
penile atrophy
prostatic metaplasia
gynecomastia
what causes paraneoplastic destruction cytopenias relating to cancer?
immune mediated hypersensitivity (type 2)
microangiopathic anaemia
what must be excluded before diagnosing and treating paraneoplastic destruction cytopenias?
lymphoproliferative disease
what is a key indicator of microangiopathic anaemia as a systemic effect of cancer?
schistocytosis (fragmented/sheared RBCs)