Oncology Flashcards
1
Q
Give 3 examples of common paraneoplastic syndromes
A
- Cachexia
- Thromboses
- Haemorrhage
- Hypercalcaemia
- Lymphocyte level changes
2
Q
What is a histiocytoma
A
A benign tumour from histiocytes (Langerhan’s cells) in the skin - more common i young animals
3
Q
Well differentiated neoplasms are more likely to be benign - T/F?
A
True
Malignant tumours ofte have poor cellular differentiation
4
Q
What is the growth fraction of a tumour?
A
This is the number of cells undergoing division (how many are cycling)
5
Q
Which part of the cell cycle is primarily targeted by:
- radiation
- chemotherapy
A
- The M phase (mitosis)
- S phase
6
Q
What are heterogenous clones
A
These are the cancer cells that develop the ability for metastasis
Links to protease production which dissolves basement membranes of vessels to allow intravasation (lymphatic vessels don’t have a BM so are easier to invade)
7
Q
Which breeds are associated with:
- Localised and disseminated histiocytic sarcomas
- Haemangiosarcomas
- Mast cell tumours
- Osteosarcoma of appendicular skeleton
A
- Flat coated retreivers and Bernese mountain dogs
- GSDs and retrievers
- Boxers, pugs and golden retrievers
- Giant breeds
8
Q
Give 3 examples of oncogenic viruses
A
- FeLV - lymphoma/leukaemia complex
- FSV - fibrosarcomas
- Sheep pulmonary adenomatosis virus
- Marek’s disease in chickens (lymphoma of feather follicle)
- Myxo in rabbits
- Benign papilloma (may become a carcinoma in dogs)
- Equine sarcoids
9
Q
Draw a table to compare and contrast benign and malignant tumours
A
See notes page 4
10
Q
What is the cell origin of sarcomas?
A
Mesenchymal
11
Q
What is the pathogenesis of feline injection site sarcomas
A
They are the result of chronic inflammation (usually after a vaccine)
Leading to osteopathy as a paraneoplastic lesion
12
Q
What stain is commonly used for histopath of mast cell tumours?
A
Toludine blue - stains the granules (but tumours can be without them and still be MCT)
13
Q
What are the standard names for tumours of:
- Endothelium
- Smooth muscle
- Skeletal muscle
- Dendritic cells
A
- Haemangio-
- Rhabdomyo-
- Leiomyo-
- Histio-
14
Q
What are the most common visceral sites for metastasis
A
Lungs, liver, kidney and spleen
after LNs
15
Q
Which cell origin type of tumours often locally invade an then metastasise to internal organs late in disease
A
Mesenchymal
16
Q
Which cell origin type of tumours often locally invade and then metastasise via lymphatic routes to local LNs
A
Epithelial
17
Q
What are the 4 clinical stages of tumour invasion
A
T(is) - in situ - so hasn’t invaded the basement membrane yet
T(1) - superficial tumour of <2cm depth
T(3) - Tumour >5cm diameter or with invasion of the subcutis
T(4) - invading other structures
18
Q
Draw a diagram of the basic lymphatic drainage in the dog
A
Notes pg 9
19
Q
Which tumour types have a particular predilection for lung metastases
A
Carcinomas and sarcomas
20
Q
What are the minimum sizes of tumour generally detected in radiograph and CT
A
Radiograph - 5mm
CT - 2mm
21
Q
What the most common sites for MCT metastases
A
Liver and spleen
22
Q
What are the 6 main capabilities that cancer cells acquire through mutations
A
- Self sufficiency in growth signals
- insensitivity to anti-growth systems
- Limitless potential to replicate
- Evasion of apoptosis
- Sustained angiogenesis
- Tissue invasion and metastasis
23
Q
Why is the growth fraction of a tumour so important?
A
Because most cytotoxic drugs act by interfering with the process of cell division and are therefore only active against dividing cells
24
Q
How do vinca alkaloid drugs work?
A
They inhibit the formation of the mitotic spindle
25
What are the 3 main cytological features groups of malignancy
1) Cell population - densely cellular population and degree of pleomorphism
2) Cell size - large cell size, poorly differentiated cells and high nuclear:cytoplasmic ratio
3) Nuclear features - size, shape, number, nucleoli and chromatin appearance
26
What are the main limitations of cytology vs histology
- In many cases cytology will not provide a definitive diagnosis
- You cannot grade a tumour based on it
- Some tumours exfoliate poorly and hence you will get very few cells
- You cannot understand tissue architecture
27
What are the 3 key physical signs of local invasion
- Diffuse, indistinct borders betwee normal tissue and tumour
- Fixation of the tumour mass in one or more planes
- Thickening of adjacent tissue
28
What are the potential consequences of neoplastic invasion of the BM
- Non regenerative anaemia
- Thrombocytopaenia
- Leukopaenia
29
What are some of the potential indirect effects on haematopoeisis by cancer cells?
- Oestrogen producing tumours can suppress BM function
| - Myelofibrosis (fibrotic bone marrow)
30
Why might you get haemorrhage associated with tumours?
- Haemorrhage from the tumour itself (internal or external)
- GI ulcerations due to hyperhistaminaemia or hypergastrinaemia
- Secondary to a bleeding disroder
31
Why might you get hyperviscosity syndromes associated with cancer - and what clinical signs might you expect?
Can be linked to
- Excess numbers of circulating cells such as in forms of leukaemia
- Renal tumour producing EPO
- Hypergammaglobulinaemia (linked to multiple myeloma)
Clinical signs include:
- Lethargy, ataxia, tremors, seizures, weakness, TBE, retinal detachment
32
Give 3 examples of tumours that can directly lead to endocrinopathies
- Adrenal tumpurs can lead to hyper-AC
- Thyroid tumours can lead to hyper-T, and primary hyper-PT if they involve the parathyroid gland
- Pancreatic beta cell tumours can cause hypoglycaemia (insulinoma)
- Pancreatic gastrin producing neoplasms can cause hypergastrinaemia
33
What tumours can lead to hypercalcaemia and what are the clinical signs
Can be caused by:
- Lymphoid tumours, myeloid tumours, anal gland adenocarcinomas, solid tumours with skeletal metastases and other solid tumour
Clinical signs
- PU/PD, anorexia and vomiting (due to slowing down of gut), dehydration, muscle weakness and tremor (due to neuromuscular depression), bradycardia
34
What tumours can lead to hypoglycaemia and what are the clinical signs
Can be caused by:
- Insulinoma, hepatic tumours, especially hepatocellular carcinoma, other tumours, especially large intra-abdominal ones
Clinical signs
- Episodic weakness, collapse, disorientation and seizures
35
What tumour is most likely to cause hyperhistaminaemia and what are the clinical signs
```
Mast cell tumours
Clinical signs:
- GI ulceration
- Anorexia
- Vomiting and haematemesis
- Melaena and anaemia
```
36
Which hormone is key for lowering body calcium
Calcitonin
37
Hypercalcaemia of malignancy is much more common in the dog than the cat - T/F?
True
38
Osteosarcoma is a common cause of hypercalcaemia of malignancy - T/F?
False - it doesn't tend to have a profound effect on calcium
39
What is the common management for hypercalcaemia of malignancy?
- Restore circulating volume with normal saline - corrects deficit and helps slower excretion of calcium
- Diuretics - once properly rehydrated
- Can try bisphosphonates but they are expensive and quite toxic so not first choice
- Then identify and treat inciting cause
40
What substances can be produced by mast cell tumours?
Histamine, heparin, proteases and other vasoactive amines
41
What symptoms can you get associated with MCT?
- Oedema, erythema and pruritus of the tumour and surrounding area
- Tendency to bleed locally (due to heparin)
- Delayed wound healing or wound breakdown following surgery (due to proteases)
42
How can mast cell tumours lead to GI ulceration?
And how can we prevent/treat it?
If there is chronic release of histamine by the tumours, it stimulates the H2 receptors leading to hyperacidity, hypermotility, dilation of gastric blood vessels and increased endothelial permeability
Clinical signs include vomiting and mild anorexia but can progres to haematemesis, anaemia and the gut can even perforate and lead to peritonitis
Give H1 and H2 antagonists as treatment/prevention - e.g. cimetidine and ranitidine
43
What are the 5 major groups of cytotoxic drugs
- Alkylating agents (interfere with DNA replication)
- Anti-metabolites (interfere with DNA or RNA synthesis)
- Anti-tumour antibiotics (interfere with DNA replication)
- Vinca alkaloids (target mitotic spindle)
- Miscellaneous agents (some interfere with DNA replication)
44
Give some examples of alkylating cytotoxic drugs
- Cyclophosphamide
- Mephalan
- Chlorambucil
- (Lomustine)
45
Give some examples of anti-metabolite cytotoxic drugs
They are not as widely used in veterinary medicine
- Azathioprine (often used as an immunosuppressant)
- 5-fluorouracil
- Methotrexate
- Cytarabine
46
Give some examples of anti-tumour antibiotics
- Doxorubicin
- Mitoxantrone
- Epirubicin
- Actinomycin D
47
What 'miscellaneous' cytotoxic drugs are used in veterinary medicine?
- Cisplatin
- Carboplatin
- L-asparaginase
48
Which tumour types have the following sensitivity to chemotherapy?
- High
- Moderate
- Low
High
- Lymphoma, myeloma and some forms of leukaemia
Moderate
- High grade sarcomas (e.g. osteo- and haemangio) and MCTs
Low
- Most slow growing sarcomas, carcinomas and melanoma
49
What is tumour multidrug resistance?
This is usually linked to a transmembrane P-glycoprotein pump which can transport cytotoxic drugs directly from the cell membrane
Allows the tumour to be resistant to drugs it hasn't been treated with before
50
How do cytotoxic drugs kill cells?
According to first order kinetics - a given dose of drug kills a fixed percentage of the total tumour population as opposed to a set number of cells
51
Why are repeated chemotherapy treatments often given with a 21 day gap between them
This allows the bone marrow to recover- the BM suppression is quite rapid and severe after chemotherapy -and the gap allows cells to repopulate and recover
52
Define maximally tolerated dose
This is the level of normal tissue toxicity that limit the maximal dose possible
And need to give the highest dose possible to effect the highest possible fractional kill
53
What are the 3 main stages of chemotherapy?
1) Inductio therapy to reduce tumour burden to minimal levels
2) Maintenance therapy -less intensive therapy that can be continued after remission (not always done)
3) Rescue therapy - if there is a relapse - usually a more aggressive therapy, often with new agents
54
What is the COP protocol
Often used for lymphoma - includes cyclophosphamide, vincristine (oncovin) and prednisolone
55
What are dose calculations for chemotherapy based on
They are based on a fuction of surface area rather than body weight (as this may better represent the blood supply to the liver and kidneys) - not quite so true for animals <10kg
56
What are the 3 main indications for chemotherapy
- Systemic disease that is chemosensitive
- As an adjunct to surgery or radiotherapy for highly aggressive cancers
- Rarely of value as a sole treatment for solid tumours
57
What are the main chemotherapy protocols as adjuncts to surgery for:
- Osteosarcoma
- Haemangiosarcoma
Osteo - carboplatin +/- doxorubicin
| Haemangiosarcoma - doxorubicin maybe with cyclophosphamide and vincristine
58
What are the 3 types of chemotherapy tissue toxicity
- Immediate (drug reactions) -such as hypersensitivty
- Acute (in organs containing a high proportion)
- Late/cumulative
59
Give the specific toxicities associated with:
- Cyclophosphamide
- Doxorubicin
- Cisplatin
- Cyclo = haemorrhagic cystitis (due to acrylin metabolite excreted in urine)
- Doxorubicin - cardiomyopathy
- Cisplatin = nephrotoxicity
60
What are the most common 'side effects' of chemotherapy
- BM toxicity - myelosuppression, neutropaenia and thrombocytopaenia
- GI toxicity - anorexia, v/d
61
What are the 2 chemotherapeutic drugs that don't tend to cause BM suppression
Vincristine and L-asparaginase
62
What are the clinically significant consequences of bone marrow suppression
- Neutropaenia (<2x10^9/L) - at risk of sepsis
- Thrombocytopaenia (<70x10^9) leading to higher risk of bleeding
- Anaemia - less commonly a problem due to longer life span of RBCs
Often seen within 5-10 days of first durg administration
63
What are the consequences of neutropaenia in the cancer patient
- Predisposes them to infection and sepsis
| - Absoprtion of E.coli and Klebsiella through damaged intestinal mucosa most significantly
64
What is the cut off neutrophil level for continuing chemotherapy?
Usually if the levels fall <3 x 10^9 you need to reduce the dosage or stop chemotherapy altogether
65
If neutrophil levels fall below 1 x 10^9 what should you do?
- Stop all cytotoxic treatment
- Administer potentiated sulphonamide or FQ Abs
- Supportive therapy if suspicious of infection - iv fluids, electrolytes, glucose
66
What are the potential direct effects of Abs on the GI tract?
Cause death and desquamation of the alimentary epithelium (often within 5-10 days) - leads to stomatitis, vomiting and mucoid or haemorrhagic diarrhoea
Often self limiting
67
Which chemotherapeutics can cause nausea and vomiting due to stimulating the CTZ?
Cisplatin and doxorubicin
68
What supportive therapy can be given to combat the GI side effects of chemotherapy?
- Anti-emetics (maropitant and metaclopramide)
- Antacids and ulcer healing drugs
- IV fluids if necessary (if prolonged or severe v/d)
- Appetite stimulant (e.g mirtazapine)
- Abs if suspicious of an infection
69
Which chemotherapeutics have reports of hypersensitivity and anaphylaxis
- L-asparaginase
- Doxorubicin (directly degranulates mast cells)
- Cisplatin
- Cytarabine
70
How can you prevent the anaphylactic/hypersensitive effects of some chemotherapeutic agents
- Route of administration (L-asparaginase is better given i.m than i.v)
- Can premedicate with anti-histamines
- Use an iv catheter to reduce risk of extravasation
71
How would you treat an anaphylactic/hypersensitive reaction to chemotherapy?
- Immediately stop drug administration
| - Give i.v fluids, soluble corticosteroids, adrenaline and antihistamine
72
Give examples of cytotoxic drugs that are:
- Vesicants (cause blisters)
- Irritants
Vesicants - cisplatin, doxorubicin, vinca alkaloids
Irritants - carboplatin and mitoxantrone
Can be prevented by using an i.v catheter to administer and good restraint of the patient
73
How would you manage a perivasular leakage of cytotoxic drugs
- Stop infusion but don't remove catheter
- Aspirate any drug you can - helped with a s/c injection of saline
- Remove catheter
- Give systemic iv corticosteroids
- Cold compresses may help reduce the inflammatory response
74
What is the specific toxicity o cyclophosphamide and why does it occur?
One of the metabolites, acrylin, is excreted in the urine and irritates the urothelium, causing an inflammatory fibrotic response with profuse bleeding
More common following high doses or with long term therapy
Ensuring good fluid intake and urine output (even adding furosemide) can help prevent it
75
What is the specific toxicity of doxorubicin and how can it be avoided?
It causes cardiotoxicity due to actions on myocardial calcium metabolism
This can lead to acute tachycardia and arrhythmias or long term can cause cardiomyopathy
Should be given as a slow rate infusion to reduce the risk of it
All dogs should have a heart assessment before starting treatment
76
What is the specific toxicity of cisplatin and how can it be avoided?
It leads to nephrotoxicity due to platinum coordination compounds accumulating in the renal tubular epithelial cells where they block oxidative phosphorylation and cause necrosis (may also have impacts on renal blood flow)
Minimise these effects by giving with fluid diuresis and monitoring renal parameters carefully during treatment course
77
What are MDR-1 mutations
These are mutations in the ABCB-1 gene which encodes for a p-glycoprotein transport protein
When the protein is not functional - as found in many breeds of dog but most commonly Collie and Australian Shepherd dogs -it can leads to increased drug exposure in the brain and toxicity
It can now be tested for
78
What are the chemotherapeutic drugs that are substrates for P-glycoprotein transporters
- Vinca alkaloids
- Doxorubicin
- Actinomycin D
- Taxanes
79
What new drugs have been developed for MCTs (non-resectable) in dogs
Tyrosine kinase inhibitors
| Palladia and Masivet
80
How does radiation therapy work?
The X-ray photons induce free radical formation - these radical cause chemical changes within the cells, which can have biological effects on DNA (although this may take days, weeks or months to become apparent)
81
What are the 3 main factors than influence tissue sensitivity to radiation?
- Growth fraction - dividing cells are much more sensitive
- Cell cycle -M phase is most sensitive (S is most resistant)
- Oxygenation - hypoxic cells are less sensitive to radiation because free radical formation is oxygen dependent
Therefore small, fast growing and well perfused tumours are the most sensitive
82
What are the ways yu can reduce toxicity from radiation
- Brachytherapy or proton beam therapy instead of conventional radiotherapy - can give a greater degree of selectivity
- Collimation to mould to shape of tumour
- Radioactive implants
83
What is teletherapy and what are its pros and cons
Teletherapy is when radiation is applied in the form of an external beam
Tends to be safer for the operator but the equipment is expensive
Requires multiple treatment and there is limited penetration and the x-rays are preferentially absorbed by bone
84
What is brachytherapy and what are its pros and cons
This is where radioactive substances that emit gamma or beta rays are applied to or implanted into the tumour (or given systemically)
For example iodine 131 for cats with hyperthyroidism
Has the benefit of being a single treatment - but you have a radioactive patient that must be hospitalised
85
What are the benefits/cons of the following teletherapy types:
- Linear accelerator
- Orthovoltage
LA - produce high energy, deeply penetrating radiation which spares the skin and superficial tissues
Orthovoltage - produces lower voltage radiation that is preferentially absorbed by bone - used for superficial tumours
86
What is radiotherapy fractionation and why is it beneficial?
This is giving radiation in multiple small doses over a long period of time
It allows normal tissues to repair ad repopulate (they do this faster than most tumours)
And the redistribution and reoxygenation of tumours also increases their sensitivity to future radiation
It also helps provide pain relief and shrink the tumour (palliation)
87
What is the standard fraction treatment for animals - why is it different than humans
The animal treatment is 10-12 fractions every other day, this is more aggressive than the human course as the animal has to be brought in and anaesthetised
88
What are the key things to consider about fractionation
- The same dose given in a shorter time or fewer fractions has a greater effect
- But, smaller fraction size minimises normal tissue effects
- Overall treatment time is important in achieving tumour control
89
Which tumour types have the following sensitivity to radiotherapy:
- High
- Sensitive
- Moderate
- Low
High
- Lymphoproliferative disorders, myeloproliferative disorders, TVT
Sensitive
- SCC, BCC, adenocarcinoma
Moderate
- MCT (variable), oral melanoma
Low
- Fibrosarcoma, osteosarcoma, chondrosarcoma
Tends to take 6-8 weeks to achieve maximum tumour response
90
Give some examples of acute radiation reactions
Can range from mild reddening or erythema of the skin to vesiculation, desquamation and severe exfoliative dermatitis
May see necrotic tissue
Localised hair loss due to hair follicle epithelium damage - but often not severe alopecia
91
Moist areas of the body suffer more from radiation toxicity than dry ones - T/F?
True
Radiation sickness and severe morbidity only tend to arise when large areas of the body or vital organs are exposed to high doses
92
What are some late effects of radiation toxicity and how do they arise?
They are less predictable and more serious (often irreversible) - linked to loss of stem cell recovery potential and progressive damage to small blood vessels
Examples:
- Skin - fibrosis in dermal connective tissue and vascular changes - can lead to slow healing
- Bone - osteonecrosis
- Nervous tissue (try and avoid irradiation of the spine if possible
93
What are the main tumours in animals treated by radiotherapy?
- SCCs and melanomas in the oral cavity
- Adenocarcinoma in the nasal cavity
- SCC and MCTs and occasionally soft tissue sarcomas elsewhere on the body (often as an adjunct to surgery)
94
Discuss the use of radiation and surgery
Radiation is often used as an adjunct for solid but invasive tumours where not all tissue can be removed
Cytoreductive surgery reduces tumour burden to microscoptic levels - the cells remaining tend to be more sensitive to radiation
But radiation will delay healing of the surgical wound so must either be done after healing or immediately after surgery
95
What is photodynamic therapy?
This involves a light activated drug/chemical teamed with a source of light to activate it
It gives off a lot of free radicals to cause oxidative damage, vascular collapse and tumour cell death
Can have drugs that accumulate specifically in tumour cells - such as porphyrins and 5-ALA cream
96
Platelet consumption can occur with tumours of which organs?
Liver and spleen
97
Which cancer can lead to DIC?
Haemangiosarcoma - be aware if planning surgery
98
Why does the first surgery have the best chance of a cure?
- There is decreased time for metastasis to occur
- The anatomy is near normal
- No seeding of previously non-involved tissue planes
99
When would you use incisional biopsies vs excisional biopsies
Incisional are good for soft tissue sarcomasa, oral tumours and those that are lcerated or necrotic where deeper samples can be obtained
Excisional ones are used when treatment wouldn't be altered by the knowledge of tumour type - e.g. small skin masses, solitary lung tumours, spleen or ovarian tumours etc.
100
What are the classic thoracic metastatic patterns for:
- Mesenchymal tumours
- Adenocarcinomas
- Haemangiosarcomas and epithelial tumours
- Mesenchymal = cannonball
- Adenocarcinoma = typically solitary nodules
- H + ET = typically miliary
101
What is marginal excision and when is it used?
Surgery when you take no extra margins of surrounding tissue - often used for benign tumours, or tumours with discreet origins such as the spleen, ovaries, anal sac etc.
102
Which tumour types require:
- 1cm margins
- 2cm margins
```
1cm
- Small grade 1 MCT
- Oral BCC
- Oral fibromatous epulides
2cm
- Most MCTs
-Oral fibrosarcoma
- Oral SCC
- Other SCCs
```
103
What is radical excision
This is removal of the tumour and the entire tissue compartment with margins that extends into adjacent fascial planes
104
What is compartmental/supraradical excision
This is removal of the tumour with extensive margins that extend into undisturbed tissue planes (e.g. hemipelvectomy)
105
What is a secure surgical margin?
This is ensuring that you place barriers against the spread of tumour cells - fat is a poor barrier to tumour cells, you need something like fascia, cartilage or bone
