SA oncology Flashcards
How are solid tumours clinically staged?
TNR classification T: primary tumour - clinical exam - location and palpable extent (well demarcated?) - fixation to deep tissues, skin - ulceration - histological diagnosis (biopsy or FNA) - diagnostic imaging N: metastatic disease in local and regional lymph nodes M: distant metastatic disease
Difference between tumour stage and grade?
Stage: tumour burden and sites involved
Grade: histological features of tumour
What is the gold standard for cancer diagnosis?
Histopathology
Advantages and disadvantages of cytology for cancer diagnosis?
Relatively non-invasive Often requires minimal restraint Minimal tissue disruption Rapidly performed Rapid results Cheaper No architectural detail Small numbers of cells examined- representative? Limited assessment of tumour type/grade
Advantages and disadvantages of histopathology for cancer diagnosis?
More invasive GA (or sedation) required Moderate tissue disruption More time consuming Delay in results More expensive Architecture apparent Larger sample size - more representative More accurate tumour type/grade
Biopsy techniques for cancer diagnosis?
Needle core biopsy Incisional biopsy Surface and pinch biopsies Punch biopsies Excisional biopsy
Risks of biopsy?
Haemmorrhage
Transplantation of tumour cells
Compromise of future surgery
Damage to adjacent structures
Needle core biopsy - how?
Cylinder of tissue is removed from the lesion by a specialised needle
Ultrasound guidance very useful
Adequate restraint
Trucut needles - two handed operation, need assistance, can be cold sterilised
Cook’s/Arnolds biopsy needles - semi automated, can be cold sterilised
Clip, prepare site aseptically
Make small stab incision in skin (essential to not blunt needle)
Immobilise mass and introduce needle
Once embedded, advance central obturator, rotate through 90 degrees, briskly advance outer cannula over central obturator, remove from mass
Flush sample from notch with saline
Advantages and disadvantages of needle core biopsies?
Advs:
- larger sample than aspirate
- comparatively inaccessible tissues can be accessed percutaneously
- multiple samples can easily be taken
- superficial lesions can be biopsied under sedation and local anaesthesia
Disadvs:
- small sample size compared to other biopsies (still might not be sufficient to view architectural change)
- greater risk of complications compared to FNA
- not good for lymph nodes (insensitive to metastatic disease, inadequate for architectural assessment in lymphoma)
What is used for a bone core biopsy? What must be done/not done?
Jamshidi needle
Do not penetrate far cortex - risk of pathological fracture
Take multiple samples
Advantages and disadvantages of incisional biopsies?
Advs: - good evaluation of architecture - histopathological grading - surgical approach allows selection of biopsy site - more tissue - can carry out special stains etc Disadvs: - GA normally required - increased time - both increase costs
What is the most common technique used for incisional biopsies? Rules?
Inverted wedge - easy closure
Plan your site
Sample selection
Avoid major structures
Avoid necrotic, haemorrhagic or infected areas
Position incision and biopsy so that entire biopsy tract can be removed during subsequent surgery
Make the incision large enough to harvest the sample without excessive tissue manipulation
Minimise instrumental manipulation of biopsy
Avoid diathermy, cryosurgery etc
Include a portion of normal tissue only if easy to do so
Ensure adequate fixation - serially section large samples
Surface pinch and grab biopsies - used for? how?
Accessible surfaces - resp tract, GIT, urogenital tract
Direct visualisation
Endoscopy
Blind
Laparoscopy/thoracoscopy
GA often required
Very small biopsies - always take multiple
Punch biopsies - used for/not used for? How?
Cutaneous and other superficial lesions only
Not for lymph nodes
Sedation (+/- local)
Rotate punch continuously in same direction so don’t shear layers apart
What is excision biopsy?
(Attempted) surgical extirpation of a lesion or mass, followed by removal of biopsies from it for histopathological evaluation or submission of whole sample if possible
Often results in inadequate excision
Only used when knowledge of tumour type will not affect surgical dose
Widely used in treatment of skin tumours
All excised tumours should be submitted for histopathology - assess margins
Contraindications for excision biopsy for skin and s/c masses?
Rapidly growing masses Ill defined or poorly demarcated lesion Peritumoural oedema or erythema Skin ulceration Injection site masses in cats FNA suspicious of MCT or STS Non diagnostic FNA
What percentage of bone mineral content must be lost for lysis to be apparent on radiographs?
> 60%
So lack of obvious lysis doesn’t mean no bony involvement
Which lymph node enlargement may be seen on a lateral thorax radiograph?
Suprasternal
Cranial mediastinal
Tracheobronchial
Only moderate-marked enlargement detectable
Which lymph node enlargement may be seen on an abdominal radiograph?
Medial iliac (sub lumbar) Very unlikely to detect enlargement of mesenteric nodes unless massively enlarged
What is lymphangiography used for?
Detection of sentinel nodes
Inject contrast into the tumour to find out which nodes drain it
Doesn’t tell you if they are affected by metastases
Only tells you which are draining nodes
FNA for lymph nodes?
More sensitive than palpation or needle core biopsy
Not infallible - can have negative aspirates from positive node
Use needle only technique
Which lymph nodes do tumours metastasise to?
Most which spread by the lymphatic route go to the nearest node towards the centre of the body (ie towards the thoracic duct)
Cranial abdominal tumours can metastasise to the retropharyngeal lymph nodes
Metastases can skip a node
Lesions on the distal forelimb metastasise to the prescapular rather than the axillary lymph nodes
Lesions on the proximal forearm metastasise to the axillary node
Common sites of distant metastasis?
Lung Parenchymatous organs - liver, spleen, kidney Bone Skin CNS Distant nodes
Detection of pulmonary metastases?
Very difficult to pick up on examination - adventitious sounds uncommon, may pick up if concurrent effusion, cough uncommon
Radiographs
- both lateral inflated views, ideally all 4 views
- do not confuse pleural plaques/pulmonary oesteomas with metastases
CT
- more sensitive but more expensive and less available
Detection of metastases to parenchymatous organs?
Ultrasound generally superior to radiography
NB old dog changes
- nodular hyperplasia in the liver
- nodular hyperplasia, lymphoid hyperplasia, haematomas in the spleen
Confirm by FNA
Are blood tests useful in cancer patients?
Haematology will only give a diagnosis if patient has leukaemia
- lymphoma patients seldom have circulating tumour cells
- required prior to chemo
- paraneoplastic syndromes
Biochemistry never diagnostic
- poorly sensitive to organ infiltration
- paraneoplastic syndromes
- concurrent disease
Infectious disease
- vast majority of feline lymphoma patients are not FeLV positive
What is involved in tumour metastasis?
Vascularisation of tumour - angiogenesis factors
Invasion of tumour cells into vasculature
- enzymes (collagenases, matrix metalloproteinases)
- lack of adhesion
- motility characteristics
Dissemination - evasion host immunity
Arrest - adhesion to normal cells
Extravasation - enzymes
Proliferation - angiogenesis
Which tumours tend to have haematogenous metastases?
Sarcomas
Malignant melanomas
Which tumours tend to have lymphatic metastases?
Local and regional lymph node spread
Mast cell tumours
Carcinomas
Malignant melanomas
Limitations of the TNM system?
Animals do not always present with the primary disease
Metastatic disease
Paraneoplastic syndromes
Biological behaviour of the tumour must be born in mind
Which tumours are highly metastatic?
Oral/mucosal malignant melanoma
Visceral and some other soft tissue haemangiosarcomas
Appendicular osteosarcoma
High grade (Patniak grade III/Kiupel high grade or poorly differentiated) MCTs
Subungual malignant melanoma (dogs)
Poorly differentiated mammary tumours (dogs)
Most mammary carcinomas in cats
(Anal sac adenocarcinomas - often slow)
(Prostatic carcinomas - often slow)
(Digital squamous cell carcinomas - often slow)
Which tumours are variably metastatic?
Oral/axial OSA Thyroid carcinomas (dog) Patnaik intermediate grade MCTs Injection site sarcoma Anaplastic sarcoma Insulinoma (most do) Mammary carcinoma (dog) Apocrine adenocarcinomas GIT carcinomas TCC of bladder Liposarcoma
Which tumours have a lower metastatic potential?
Oral fibrosarcoma
Non-tonsillar oral squamous cell carcinoma
Most ST sarcomas
Sebaceous adenocarcinoma
Low grade MCTs
Multilobular osteoma/osteosarcoma of bone
Intranasal tumours
Which tumours don’t metastasise?
Oral acanthomatous ameloblastomas
Haemangiopericytoma
Schwannoma/neurofibroma
Benign tumours!
What are the aims of oncological surgery?
Prophylaxis Diagnosis and staging Definitive excision Cytoreduction of tumour mass Palliative treatment Treatment of metastatic disease
Which cancers are castration and ovariohysterectomy prophylaxis for?
Castration: testicular neoplasia (not prostatic cancer)
Ovariohysterectomy: ovarian/uterine neoplasia, reduces mammary cancer
What is multimodality therapy for cancer?
Cytoreduction of tumour mass before, at time of or after radio- or chemotherapy
When is palliative treatment for cancer used?
If hopeless prognosis (usually due to early metastasis)
Pointless aggressively treating primary neoplasia if patient will die from diffuse disease
Removal of tumour burden may restore or maintain quality of life until euthanasia is inevitable
Pre-op considerations of oncological surgery?
Type, grade and stage Local and systemic effects of disease Is a cure possible? Is surgical intervention appropriate? Prognosis with/without surgery Anticipated complications Patient's quality of life Cost of (ongoing) treatment
What to be careful of with oncological surgery?
Inappropriate surgery may seed tumour to tissue planes previously unaffected
Most active/invasive parts of tumour are at edges
If tumour recurs there is less normal tissue for closure
Pre-operative nutritional support for oncological surgery?
Provide if:
Anorexia for >5days
>10% acute loss of lean body weight
Disease or surgery will prevent feeding for >3-5 days post-op
Methods to achieve surgical margins for cancers?
Local excision - easiest, often used inappropriately
Wide excision
Radical excision
Preparation for oncological surgery?
Plan reconstruction before tumour excision
Avoid vigorous palpation
Clip and prepare wide area around proposed surgical site
Gentle cleaning using effective skin preparation not vigorous scrubbing
Why does oncological surgery have higher infection rates?
Old age Poor nutritional status Obesity Diabetes/concurrent disease Hypoxaemia Remote infection Corticosteroid therapy Immunocompromise Thrombocytopenia/poor blood supply
When should antibiotic prophylaxis be used for oncological surgery?
If debilitated patient
If clean-contaminated/contaminated/dirty surgery
If surgical procedure >90 mins
In general begin no more than 2h pre-op and continue no more than 24h post-op
Are adhesions between a tumour and adjacent structures a problem?
Represent direct tumour invasion in >50% cases
What to do after tumour excision during oncological surgery?
Saline lavage - allows removal of blood clots, foreign material, necrotic tissue and possibly any unattached tumour fragments
Change gloves, drapes and instruments after tumour excision and lavage - tumours will adhere to inanimate objects and potentially seed to other tissues prior to closing
Vascular occlusion techniques for oncological surgery?
Ligate vascular supply to tumour and venous and lymphatic drainage from it as early as possible
Especially important for tumours of ectodermal origin (e.g. SCC, MCT) where probability of exfoliation is high)
How to avoid wound complications (e.g. haematomas, serums, sepsis) in oncological surgery?
Meticulous haemostasis
Effective closure of dead space
Appropriate use of drains
Appropriate use of perioperative antibiotics
General recommendations for the management of local lymph nodes in oncological surgery?
Non destructive biopsy of grossly normal lymph node
Lymph node removal if:
- histologically proven to contain tumour cells
- appears grossly abnormal at surgery
- intimately associated with tissue being removed and surgical margins dictate its removal
Indications for chemotherapy?
Systemic tumours Risk of metastatic disease Palliative treatment Delay/prevent local tumour recurrence Radiation sensitisation
Types of chemotherapy?
Primary
Adjunctive (used with another treatment)
Neoadjunctive (used before a treatment to help its success)
How does conventional chemotherapy work?
Cytotoxic drugs which are mainly active against highly proliferating cells
So do not specifically target cancer cells
Targets are DNA synthesis, RNA synthesis, protein synthesis and cell cycle progression
Which part of the cell cycle is relatively resistant to the actions of cytotoxic chemotherapy drugs?
G0 - act as a reservoir to repopulate the tumour after therapy
Define growth fraction, mitotic index and mass doubling time of tumours?
Growth fraction - fraction of cells actively dividing at any given time
Mitotic index - % or number of mitoses per high power field on light microscopy
Mass doubling time - time taken for tumour to double in size (affected by GF, cell cycle time, cell loss)
What is Gompertzian growth of tumours? How does this affect chemotherapy sensitivity? Which tumours don’t follow this growth pattern?
Decreasing growth rate with increasing number of cells
Early stages (microscopic):
- rapid growth, high GF, short MDT
- more cells in chemotherapy sensitive phases of cell cycle
Later stages (large bulky disease):
- slower growth, lower GF, longer MDT
- fewer cells in chemotherapy sensitive phases of cell cycle
Not true of leukaemia and lymphoma
Factors affecting chemotherapy success?
Growth fraction and mass doubling time Inherent tumour sensitivity Tumour cell heterogeneity Inherent tumour cell resistance/acquired drug resistance Drug dosage Interval between treatments Tumour blood supply/oxygenation
Are lymphomas and melanomas chemo-sensitive?
Lymphoma: remains relatively sensitive even at large volumes
Melanoma: poorly sensitive even with high GF
What is Nowell’s hypothesis?
Cancer is the result of genetic instability
If a cell develops a genetic mutation this is transferred to further clones
New clones may develop further genetic mutations
Mechanisms of chemotherapy drug resistance of tumours?
Less drug entering cell Defective drug activation Increased drug inactivation Alteration in target molecules Enhanced DNA repair
Intrinsic drug resistance of tumours?
Increased DNA repair
Over expression of anti-apoptotic proteins
Altered expression of oncogenes or tumour suppression genes
P-glycoprotein
Acquired drug resistance of tumours?
Single agent specific resistance
Resistance to drugs which have similar modes of action
Multidrug resistance
How to minimise tumour drug resistance?
Treat as early as possible Use standard protocols Use correct doses Administer agents properly (e.g. don't pretreat lymphoma patients with steroids) At relapse, act sooner rather than later
Drug dosage for chemotherapy?
Narrow therapeutic window
Aim for maximum tolerated dose (MTD) to minimise tumour burden but without toxicity
If no response to first dose, don’t keep trying same dose as won’t work
Dose on the basis of body surface area (BSA) - correlates with blood supply to liver and kidneys (better than weight)
For smaller patients sometimes mg/kg instead (dox, carbo)
Tumour blood supply? Problems for chemotherapy?
Many tumours are poorly vascularised with disorganised sinusoidal blood vessels
Larger tumours tend to outgrow their blood supply
Poor blood supply results in:
- inadequate drug delivery
- inherently low growth fraction
- areas of anoxia -> low pH, build up of toxic metabolites, interference with cytotoxicity
What chemotherapy drugs are there?
Agents that affect DNA replication:
- alkylating agents (cyclophosphamide, melphalan, chlorambucil, lomustine)
- antitumour antibiotics (doxorubicin, epirubicin, mitoxantrone, Actinomycin D)
- platinum compounds (cisplatin, carboplatin)
Agents which affect purine and pyrimidine synthesis
- antimetabolites (cytosine arabinoside, methotrexate, 5-fluorouracil)
Agents which interfere with mitosis
- vinca alkaloids (vincristine, vinblastine)
Enzymes
- e.g. L-asparaginase
Miscellaneous agents
- corticosteroids
- NSAIDs
Disadvantages of single agent chemotherapy? When used?
Tends to select rapidly for drug resistance
Not capable of adequate antineoplastic activity
Used for exquisitely sensitive tumours - transmissible venereal tumour
Or where no other known effective agents:
- platinum compounds in osteosarcoma
- doxorubicin in high grade STS
Polychemotherapy protocol?
Agents should: - have proven efficacy against the tumour - have different modes of action - affect different stages of the cell cycle - have non-overlapping DLT toxicities - not interfere with each others actions Combined or sequential Toxicity: combined > sequential
Chemotherapy routes of administration?
Oral IV IM/SC Intracavitary Intratumoural Intrathecal
Define chemotherapy drug dose intensity and dose density?
Dose intensity = the drug dose delivered per time unit, expressed as mg/m^2 per week
Drug density = how often the drug is administered during the protocol
- interval between doses needed to allow recovery of normal tissues
- rapidly dividing tissue e.g. bone marrow and GIT have tremendous capacity to repair rapidly and tend to repair more rapidly than most tumours
Which patients present chemotherapy drug dosing problems?
Obese patients - should we estimate lean weight?
Collies and others with known drug sensitivity - can test for MDR1 (ABCB1) mutations
Animals with hepatic functional compromise
Animals with reduced renal function
Immediate toxicity (<24hrs) reactions to chemotherapy?
Anaphylaxis/hypersensitivity: - L-asparaginase, antracyclines, cisplatin, cytosine - IVFT, dex IV, H1 blocker, adrenaline Cardiac arrhythmia - doxorubicin (epirubicin) Emesis - platinum compounds, antracyclines
Possible toxicity reactions 1-5 days post chemotherapy treatment?
GI toxicity - most agents
Perivascular reactions - antracyclines, platinums, vinka alkaloids
Pancreatitis - corticosteroids, asparagina, azathioprine, platinum compounds
Why can chemotherapy drugs cause GI toxicity 1-5 days post treatment? Signs? Treatment? Which drugs?
Direct damage to enterocytes
Anorexia, nausea, vomiting, diarrhoea
Syptomatic treatment:
- treat more aggressively than non-chemo patients
- anti-emetics, anti-diarrhoeals, antibiotics, IVFT, gastroprotectants, appetite stimulants
GI toxicity seen before bone marrow toxicity
Disrupted mucosal barrier with neutropenia increases risk of sepsis
Mainly: doxorubicin/epi, vincristine, cyclophosphamide (cats), cytarabine infusion, platinum compounds
Why may dogs/cats get myelosuppression 7-10 days post chemotherapy?
Damage to haematopoietic stem cells
Neutropenia is generally the limiting toxicity (<3x10^9/L dog, <2.5x10^9/L cat)
Thrombocytopenia less common
What to do if pyrexic neutropenic patient 7-10 days post chemotherapy?
- medical emergency as may be septic
- translocation of bacteria from patient’s own GI flora
- hospitalisation
- stop all cytotoxic drugs
- barrier nurse and aseptic technique
- supportive therapy
- bactericidal antibiotics
What to do if asymtpmatic afebrile neutropenic patient: - <1x10^9/L - 1-1.5x10^9/L - 1.5-2x10^9/L 7-10 days post chemotherapy?
<1x10^9/L: - ABs if indicated - drug discontinuation and subsequent dose reduction - check temperature 1-1.5x10^9/L: - dose likely postponement - no Abs unless good reason 1.5-2x10^9/L: - dose may require postponement/modification
Which chemotherapy drug can cause cumulative cardio toxicity (DCM) in dogs?
Doxorubicin
What variable onset toxicities are there of chemotherapy?
Alopecia - rare
Sterile haemorrhagic cystitis - cyclophosphamide
Hepatotoxicity - Iomustine (dogs)
Nephrotoxicity - cisplatin, doxorubicin (cats), Iomustine (dogs)
Peripheral neuropathy - vincristine
Fatal non cariogenic pulmonary oedema - cisplatin (cats)
Fatal CNS signs - 5-FU (cats)
Acute tumour lysis syndrome - large tumour burdens, rapid destruction of cancer cells, ARF
Which chemotherapy drugs can cause extravasation? How to avoid it?
Vincristine and vinblastine are perivascular irritants (but stays local as non DNA binding)
Doxorubicin, epirubicin and Actinomycin D are catastrophic perivascular irritants (DNA binding so will spread)
Always use a cleanly placed first stick catheter
Monitor for any swelling, discomfort, changes in resistance to injection or rate of infusion
Never leave an animal unsupervised on an infusion
Flush catheters appropriately before catheter removal
Treatment for extravasation from chemotherapy?
Doxorubicin/epirubicin/actinomycin D:
- cold packing
- dexrazoxane (expensive)
- topical DMSO (can’t use at same time as dexrazoxane)
- consider (immediate) surgical debridement
Vincristine/vinblastine:
- can try and aspirate drug back out
- hot packing q4h
- topical DMSO for a week
- don’t bandage
- hyaluronidase (unknown efficacy, may mop up free radicals, not recommended)
What is metronomic chemotherapy?
Continuous low dose chemotherapy (usually low dose cyclophosphamide with piroxicam or other NSAIDs) More recently: addition of thalidomide Dose dense chemotherapy strategy Main target is angiogenesis Also inhibition of CEPs Stimulation of immune response Direct action of tumour cells
Tyrosine kinase inhibitors for chemotherapy?
Inhibit the activation of specific signalling pathways involved in specific types of cancer
Two oral drugs targeting the RTK KIT (toceranib and masitinib) licensed for treatment of mast cell tumours in dogs - only in very specific situations
Drugs affect non target tyrosine kinases:
- have an effect on angiogenesis
- other tumour targets
- toxicity
- need regular monitoring
What is immunotherapy?
Patient’s own immune system to target cancer cells
Highly selective
E.g. canine melanoma vaccine (produces anti-tyrosinase antibodies)
Methods of radiotherapy?
Brachytherapy:
- direct application (pleisiotherapy)
- implantation (iridium wires to emit gamma rays)
- systemic administration (iodine 131 in feline hyperthyroidism)
Teletherapy:
- external beam (orthovoltage source, linear accelerator, cobalt 60)
Types of radiation used by teletherapy?
Electromagnetic radiation: - X rays - high energy produced by linear accelerators or low energy produced by orthovoltage sources - Gamma rays - cobalt sources - Electrons Particle beam therapy - heavy particles
What happens with low linear energy transfer of x rays or gamma rays for tele therapy radiation?
Loses energy slowly as passes through tissues
Deep penetration
Must consider effects on deep structures
Indirectly ionising - absorption by the Compton effect, interaction of photons with water molecules important
The maximum dose is not absorbed at the surface - build up effect
What is the critical target for therapeutic radiation? What causes damage?
DNA
Ionised water molecules around DNA -> free radicals generated -> damage DNA
Damage is rapidly reversible unless fixed by oxygen
Oxygen inhibits the repair of free radical induced damage - forms irreversible peroxides
Requires 2/5-3 x more radiation to kill a hypoxic cell (larger tumours more difficult)
Cell death occurs due to:
- induction of apoptosis
- permanent cell cycle arrest
- mitotic catastrophe
Damage often not expressed until cell tries to divide
What is a dual modality Linac? How does it work?
Produces photons and electrons
Couch, collimator and gantry rotate around a fixed point
How to target photons/electrons for radiotherapy?
Photons:
- shape beam with the jaws - rectangle or tumour shaped
- multiple beams can increase tumour dose while sparing surrounding tissue
Electrons:
- directly ionising
- loses energy rapidly as passes through tissue so ionisation only occurs superficially
- can treat superficial tumours
What is fractionation?
= Giving multiple small doses instead of one big one
Aim is to achieve better tumour cell kill
Reduce repair and repopulation, achieve deoxygenation and redistribution
Larger fraction sizes: greater normal tissue damage, especially late responding tissues
Smaller fraction sizes: ideal for most tumours, more treatments required for the same anti-tumour effect
Once weekly, M-W-F or daily
Total dose of radiation required to kill cells is less if a few large doses are given rather than lots of smaller doses
2 doses of radiation given at separate times have less effect than the sum of the 2 doses given as a single treatment
What happens in tissues after radiotherapy that affects the response?
Repair
- between treatments cells can rapidly repair sublethal damage
- tumour cells and normal cells have similar capacities
Repopulation
- seen in rapidly dividing tissues
- cells are recruited from G0
- protects rapidly dividing normal tissues
- rapidly dividing tumours also repopulate effectively
Redistribution/reassortment
- cells are more sensitive to radiation in late G2 and M
- cells may become synchronised in post treatment period but soon lost
Reoxygenation
- changes in tumour vascularity
Limitations of fractionation for animal radiotherapy?
Requirement of GA
Cost
Owner reluctance - inconvenience, frequent visits, long hospitalisation
Tumour features which affect the response to radiotherapy?
Tumour growth characteristics - slowly dividing tissues may be more radio resistant as fewer cells in sensitive phases
Tumour size - smaller tumours more sensitive, less likely to contain large numbers of hypoxic cells, easy to dose accurately and evenly
Inherent sensitivity
Tumour type
Tumour site
Patient species
What tumour types are highly radiosensitive?
Lymphoma
Transmissible venereal tumour
Gingival basal cell carcinoma (acanthomatous epulid)
What tumour types are moderately radiosensitive?
Oral SCC (dogs) Oral malignant melanoma (dogs) Nasal tumours Perianal adenocarcinoma MCTs Rhinarial SCC (cats) Thyroid carcinomas Brain tumours
What tumour types are poorly radiosensitive?
Fibrosarcomas Haemangiopericytomas Oral SCC (cats) Osteosarcomas Rhinarial SCC (dogs)
Side effects of radiotherapy? When seen? What?
Radiation damage not usually apparent until cells try to divide
Acute side effects:
- affect rapidly dividing tissues (skin, mm)
- erythema, desquamation
- develop during or soon after treatment (days-weeks)
- resolve within a few weeks of cessation of therapy
Late side effects:
- affects slowly dividing tissues
- develop many weeks, months or years after treatment
- potentially very serious e.g. necrosis of brain or bone tissue
- many inconsequential/less serious e.g. alopecia, skin fibrosis
- reduced healing capacity
Carcinogenesis of radiotherapy?
Radiation therapy is carcinogenic - DNA damage and mutagenesis
Tends to be a long time period before development of malignancy - usually years in dogs
Avoid irradiating young patients
Avoid irradiation caused by inadequate surgery or poor surgical planning
Radiotherapy post-operatively for tumours?
Commonly used
After radical surgical debulking
First treatment immediately post-op
Remaining tumour has high growth fraction and should be well oxygenated
Radiotherapy intra-operatively for tumours?
Application to unresectable, otherwise inaccessible tumours at the time of surgery
Single large dose - side effects on normal tissues
Prolonged surgical time so greater morbidity
Radiotherapy pre-operatively or neo-adjunctive for tumours?
Reduces tumour burden
Eliminates small numbers of tumour cells at the periphery of the lesion
Can have negative impact on wound healing
Used occasionally for OSA and ST sarcomas
Radiotherapy outcomes?
The effects of radiation on tumour growth are not instantaneous
Residual mass may be left esp mesenchymal tumours
Analgesia may be achieved within hours - very valuable, powerful analgesic for the majority of patients
Clinical signs of oral tumours?
Mass/facial swelling Oral bleeding Dysphagia/pain Loose teeth/proliferative lesions noted at dentals (always biopsy lesions) Halitosis Epistaxis Cervical lymphadenopathy
Diagnosis and staging of oral tumours? Assessment of lymph nodes?
Assessment under GA usually required Diagnosis - FNA or biopsy Local staging: - many are locally invasive - visal assessment underestimates - advanced imaging Distant staging: - thoracic imaging adequate for some, CT greater se - abdominal imaging if melanoma Always assess local lymph nodes: - FNA submandibular lymph nodes - consider imaging retropharyngeal nodes
Treatment for an oral tumour local disease?
Surgery preferred to RT where excision possible
At least 2cm margin required
Surgery well tolerated in dogs
Cats take long time to adjust after mandibulectomy and may need a feeding tube for several months
For FSA and SCC surgery, follow by adjuvant RT - better results than surgery alone
RT alone is reasonable option for oral melanoma - 4 fractions
Complications of surgery for oral tumours?
Bleeding Recurrence Infection Altered cosmetic appearance Difficulty pretending food Salivation Mandibular drift after semi-mandibulectomy
Oral melanoma - which animals generally? Diagnosis? Invasiveness? Metastatic potential?
Generally smaller, older dogs
GRT, cocker spaniel, miniature poodle, chow chow
Diagnosis based upon melanin containing mesenchymal cells
Some tumours don’t contain melanin and IHC required to diagnose
Locally invasive
High metastatic rate (up to 80%) - check both submandibular lymph nodes
Oral melanoma - treatment options
Surgery associated with quite high rates of local recurrence: - maxillectomy 48% - mandibulectomy 22% - higher risk of metastasis if >2cm - lower risk if more complete excision - 1 year survival 35% Radiotherapy: - 4 fractions -> RR >80% - median time to recurrence 5 months - 1 year survival 36% Chemotherapy can induce responses but does not appear to extend survival Plasmid vaccine immunotherapy: - used in stage II and III disease - targets melano-protein (tyrosinase) - injection leads to expression of human tyrosinase in dog cells - stimulates immune response - may help a minority of patients - no side effects
Survival time with oral melanoma if distant metastasis?
<3 months
Oral squamous cell carcinomas - metastatic rate? Treatment options?
Low metastatic rate - LN 10% - distant < 35% Local surgery: - mandible 10% recurrence - maxilla 30% recurrence - rostral mandible lesions have better outcome - MST 19-26 months Radiotherapy: - MST 15 months Surgery and radiotherapy - MST 34 months - good option for incomplete excision Medical therapy - metastatic disease - neoadjuvant - when other therapies not possible - Piroxicam RR 20% - Piroxicam + Carboplatin CR 57% - sustained responses with MST 18 months
Clinical presentation of tonsillar squamous cell carcinoma? Metastatic rate? Treatment options? Prognosis (MST)?
Dysphagia, coughing
Enlarged cervical lymph nodes -> abscessation (FNA yields necrotic debris and sometimes tumour cells)
Oral exam - enlargement of one or both tonsils
Metastatic rate >70%
Local control of tonsillar enlargement - surgery or RT
Surgery or RT for lymph node metastasis
Carboplatin or mitoxantrone chemotherapy for be beneficial
MST 7 months
Patients who receive the most therapy survive longest
Oral fibrosarcoma - Which animals? Invasiveness? Metastatic risk? Treatment options? MST?
Large breed dogs especially GRT and labrador Middle aged dogs (median 7.5years) Invasive Low/moderate metastatic risk - lung and occasionally lymph nodes Surgery single most important therapy: - but RR 40-60% - MST 1y after surgery Multimodal therapy often best outcomes: - surgery and RT: MST 18-26 months - RR 30% RT alone - MST 7 montjs Smaller tumours better outcomes - T1 tumours MST 31 months - T2 and T3 tumours (>2cm) MST 7 months Cats - similar to dogs, successful surgery has better outcome, mandibular more easily addressed, RT can be helpful
Problem with low histological grade high biological grade sarcomas of the mouth? Treatment?
Aggressive, rapidly progressing oral tumour with benign histological appearance even after large biopsy
Tumours reported as low grade, fibroma or even granulation tissue or epulis
Very locally invasive so aggressive local management with surgery and RT required
What are epulides? Types?
Benign lesions arising from gingiva
Acanthomatous - aggressive local behaviour and bone invasion
Peripheral odontogenic fibroma - slow growing firm masses usually not invasive
Oral osteosarcoma - treatment options? MST?
Surgery most important treatment RT does not extend survival Mandibular 14-18 months Maxillary 5-10 months Complete excision vital Local RR >80% Significance of chemotherapy unknown
What less common oral tumours are there? Treatment?
MCT and haemangiosarcoma
Plasmacytoma
Oral lymphoma - generally require multi-agent chemotherapy, some dogs with oral (only) epitheliotrophic lymphoma can do well with RT alone
Undifferentiated tumour of young dogs - rare, grave prognosis
Feline oral squamous cell carcinoma - what increases the risk? Signs? Invasiveness? Metastatic risk? Site?
Most common feline oral tumour
Risk increased by:
- use of flea collars
- exposure to smoking
- canned food including canned tuna
Causes considerable oral discomfort -> anorexia
Locally invasive
Low metastatic risk - higher risk in caudally positioned lesions
Predilection at base of tongue (but can be anywhere in mouth)
Bone invasive
Outcome of feline oral squamous cell carcinomas?
Cats with surgical resectable disease can have a good outcome but recurrence is common
Best outcomes in rostral mandibular SCC - long term feeding tubes often needed for several months
Soft tissue lesions affecting the tongue have a poor prognosis as resections are difficult
RT occasionally helpful
ECT is an emerging therapy
Oral multilobular oesteochondrosarcoma in dogs - appearance?
Popcorn appearance
Usually local problem
Oral viral papillomatosis in dogs - appearance? Prognosis?
Wart like lesions affecting oral soft tissues
Usually resolve in 4-8 weeks
Occasionally persist in immunosuppressed animals
Oral eosinophilic granuloma - which animals? Treatment?
Dogs:
- granuloma affecting ventral and lateral aspect of tongue
- husky and CKCS
- surgery and corticosteroids
Cats:
- typically erosive lesions affecting upper lip near midline
- steroids/hypoallergenic diets, RT, surgery
Transmissible venereal tumours in dogs - transmission? Prognosis?
Proliferative lesion affecting dogs who have been licking place they shoudn’t whilst on hols in southern europe
Spontaneous regression and very responsive to vincristine
Effect of neutering on risk of mammary tumours?
Neutering prior to first oestrus – 0.5 % risk
Neutering prior to second oestrus – 8 % risk
Neutering prior to third oestrus – 26 % risk
No risk reduction if neutering after the second season
Must balance early neutering against risk of urinary incontinence
Progestin, oestrogen use increases risk of tumours
Risk factors for mammary tumours?
Obesity: - reduced sex hormone-binding globulin -> oestrogen levels - underweight at puberty reduces risk Age: - mean age with benign tumours 7-9yo - mean age with malignant tumours 9-11yo - mean age of cats 10-12yo Breed: - poodles, chihuahua, dachshund, maltese, cocker spaniels and yorkshire terriers - siamese cats
Diagnosis and staging of canine and mammary tumours?
> 70% have more than one tumour
30-50% are malignant
Incidence increases after 6yo
Majority of malignant tumours are carcinomas
FNA can be useful to exclude other ddx e.g. mastitis, lipoma, MCT
Excisional biopsy by single or segmental mastectomy reasonable for single lesions without negative prognostic indicators
Staging prior to treatment of suspicious lesions
Tumours >3cm have poorer outcome
Local staging:
- assessment of local lymph nodes
- cranial two glands drain to axillary lymph node
- caudal two glands drain to inguinal lymph node
- middle gland drains either way
Distant staging
- thoracic radiographs
- abdominal ultrasound
- consider bone pain as mammary tumours metastasise to bone
