Oncology Flashcards
What 6 features are 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 Evading apoptosis
How does alteration in genes cause cancer?
Overactive oncogens (tumour-promoting genes) - secondary to mutation Loss of tumour suppressor genes
Define neoplasia/neoplasm.
‘New growth’, but inferring abnormal growth
Define benign.
Neoplasm that forms a solid cohesive tumour and does not metastasise
Define malignant.
Neoplasm with the capacity for local invasion and metastasis
What are the important clinical features of a cancer?
Effect on the host
Response to treatment
Reflection of tumour growth/grade/behaviour
When is it possible to detect a tumour by palpation/radiography?
When approx. 1cm in diameter / 1g in weight / 10^9 cells
Tumour does most of its growing before detection
Define ‘growth fraction’.
Growth of a tumour is a function of the proportion of actively dividing cells.
Describe ‘tumour doubling time’.
Time for a tumour to double in size
A reflection of the ‘growth fraction’
Tends to lengthen as the tumour grows
Do early or late tumours respond best to chemotherapy/radiation therapy?
Early ones! Tumour cells divide and grow rapidly
By the time they are detectable - growth fraction is reaching plateau, less susceptible to destruction than rapidly-dividing healthy cells
What does the grade of a tumour depend on?
Mitotic rate
Cellular and nuclear characteristics
What are some physical clues of local invasion by malignant tumours?
Diffuse, indistinct boundaries
Fixation of the tumour in one or more planes
Thickening of adjacent tissue
Spontaneous bleeding
How can a malignant tumour spread?
Via the blood, producing secondary tumours in any body organ
Via lymphatics, first to local and regional lymph nodes
Transcoelomic across the pleural or peritoneal space
Iatrogenic e.g. seeding by FNA or biopsy
What are paraneoplastic syndromes (PNS)?
Signs arising from the indirect effect of tumours’ production and release of biologically active substances
Affect distant organs and may be the first evidence of neoplastic disease
These effects may be life-threatening before cancer directly kills patient
What are some haematological paraneoplastic syndromes?
Anaemia - weakness, lethargy, tachypnoea
Thrombocytopenia - bleeding
Leukopenia - susceptibility to infection
Hyperviscosity syndrome
What are the two main causes of hyperviscosity syndrome?
Increased blood cell numbers with sludging blood and poor circulation - leukaemia, primary polycthaemia, secretion of excess erythropoietin causing secondary polycthaemia (EPO-secreting renal tumour/EPO-secreting leiomyoma) Excess gammaglobulins (especially IgM) secreted by multiple myeloma (plasma cell tumour)
What are the clinical signs of hyperviscosity syndrome?
Lethargy Tremors Thromboembolism Disorientation Episodic weakness Bleeding Ataxia Seizures Retinal haemorrhage and detachment
What are the local effects of PNS hyperhistaminaemia?
Oedematous swelling with erythema and pruritus
Tendency for localised bleeding due to heparin release
Delayed wound healing or dehiscence after surgery due to released proteases
What are the systemic effects of PNS hyperhistaminaemia?
Anaphylactic shock due to massive sudden release of histamine (vasodilation and hypotension) - premed with H1 antagonist (diphenhydramine) prior to surgical manipulation of tumour Gastroduodenal ulcer (can perforate) - treat with H2 antagonist (cimetidine/ranitidine) or proton pump inhibitor (omeprazole)
What immune-mediated PNS reactions might a patient show?
Immune-mediated haemolytic anaemia and/or thrombocytopenia (haematopoietic tumours)
Immune-mediated neuropathies (insulinoma)
Myasthenia Gravis - secondary to thymoma
Feline paraneoplastic alopecia (‘shiny skin disease’) (secondary to pancreatic and biliary carcinoma)
Pemphigus foliaceous (secondary to thymoma)
Describe PNS hypercalcaemia.
Most common PNS in dogs, relatively rare in cats
Tumours release a parathormone-like substance, called parathyroid hormone-related peptide (PTHrp)
Increases total and ionised calcium concentrations
Most commonly lymphoma
What are the clinical signs of PNS hypercalcaemia?
PUPD Anorexia Vomiting Lethargy, depression Muscular weakness Bradycardia
Describe PNS hypoglycaemia.
Pancreatic insulinoma - production of insulin
Excessive consumption of glucose - hepatoma, hepatocellular carcinoma, large intra-abdominal mass, chronic lymphocytic leukaemia
Release of an insulin-like factor - leiomyoma/GI stromal tumour (GIST)
Describe cancer cachexia.
Weight loss - muscle and fat loss
Abnormal metabolism - enhanced catabolism
Reduced food intake
What are the main aims of investigations into a tumour?
Make a histological/cytological diagnosis of type and grade
Determine extent of disease (stage) - local/distant spread
Investigate and treat any tumour-related/concurrent complications
How can we obtain a diagnosis of a tumour?
History Physical examination Laboratory testing Imaging Biopsy - cytology / histopathology
What should we do with all excised masses?
Submit for histology / fix and store in case owner changes their mind or the patient deteriorates
How can we collect cytology samples?
Touch/impression preparations
Fine needle aspirates (FNAs)
Analysis of body fluids/effusions
What can cytology samples tell us?
Nature of tumour, i.e. epithelial/mesenchymal/round cell
Cytological features
How can we collect a sample for histological exam?
Surgical/needle/punch biopsy
Surgical - incisional/excisional
What can a histological sample tell us?
Cellular features of malignancy
Tumour architecture
Invasion of adjacent tissues
Evidence of metastatic behaviour e.g. presence in blood vessels and/or lymphatics
How should we take a biopsy?
Procure a representative sample
Avoid superficial ulceration, inflammation or necrosis
Ensure adequate depth
Try to include a boundary between tumour and normal tissue
What are the aims of clinical staging?
Identify cytological or histological spread
Identify local invasion
Identify metastatic spread
Describe the TNM staging system.
T (0/1/2/3/4) = tumour, assessing size and invasiveness
N (0/1/2/3/4) = nodes, assessing local draining lymph nodes for evidence of spread
M (0/1/2) = metastasis, assessing spread to other organs
How can we test for metastatic disease?
History
Physical examination
Thoracic radiographs (3 views) or CT
Abdominal radiographs and ultrasound
FNA of lymph nodes (local/draining) and liver/spleen
Bone marrow aspiration (if haematological abnormalities)
How do we choose the best treatment option?
Decision made by owner, counselled by vet about: nature of disease, treatment options, potential side-effects, prognosis with and without treatment, cost
Tailored to individual patient, taking into account: tumour biology, histology, grade, stage
What are the three possible aims of treatment?
Cure (all cells that have the capacity for tumour regeneration eradicated)
Remission - more achievable (all clinical evidence of cancer has disappeared, occult cancer cells remain and relapse will occur at some point)
Palliation (reduce pain/improve sense of wellbeing and/or correct physiological malfunction)
What are the three main methods of cancer treatment in animals?
Surgical excision
Radiation
Anti-cancer/cytotoxic drugs (‘chemotherapy’)
Except for systemic cancers, modalities are often combined
Describe a local excision (lumpectomy).
Suitable for truly benign tumour e.g. fibroma/lipoma/benign mammary tumour
Simple procedure when lesions are small
Not so simple if tumour has been left to enlarge
Describe wide local excision.
Wider margins (1-2cm) and two planes of apparently normal tissue excised
Suitably for locally invasive tumours e.g. basal/squamous cell carcinoma/mast cell tumour
May be challenging if there is insufficient normal tissue to be able to close the wound, e.g. the mass is on chest wall/distal limbs/head/oral cavity
Often require local excision of underlying bone
Describe compartmental excision.
Certain solid soft tissue tumours infiltrate adjacent tissues more widely than 1-2cm margins e.g. soft tissue sarcomas
Resection involves removing every tissue compartment which the tumour involves, termed ‘en bloc’
Reconstructive procedures often needed to close the wound
For distal limbs, en bloc resection may be possible but amputation is available as a salvage procedure
When does failure of surgery occur?
When tumour regrows at primary site due to incomplete resection
When tumour has already metastasised
When tumour is systemic, e.g. multicentric lymphoma
What is surgical debulking?
Used for surgically incurable malignant neoplasm
Partially removed without curative intent
Followed by subsequent therapy with drugs/radiation/other adjunctive measure
What are the general rules of surgical excision?
Margin of normal tissue
Mark out margins
Cut large and deep
Two sets of instruments (excision + closure)
How do we submit an excised tumour to a laboratory for analysis?
Fill out form comprehensively Provide a clinical history If concerned about a particular margin mark it (ink) and inform pathologist Identify and orientate samples (labels) Submit all samples and entire tumour
What general considerations should we have for post-op management of surgical excision patients?
Nutrition
Analgesia
Wound care/management
Functionality (physio?)
What post-op complications can occur?
Tension and wound closure
Wound breakdown
Seroma
Wound infection
Describe tension and wound closure.
Excessive tension
Compromise to circulation
Artery = ischaemia, veins/lymphatics = oedema
Slow wound healing, wound breakdown
Necrosis
Distortion of anatomic areas, e.g. anus/eyelid
Describe wound breakdown.
Patient factors (rare) - intrinsic e.g. concurrent disease, nutrition / extrinsic e.g. chemotherapy, steroids, radiotherapy Wound factors - neoplasia, tissue handling/haemostasis, tension, motion, sutures, infection, patient interference Do not re-suture, allow to heal via second intention
Describe seroma.
Prevention = dead space, placement of drains, rest
Leave alone
Pressure bandage
Provide further drainage
Describe wound infection.
Drainage
Allow to heal via second intention
Antibiotics based on culture and sensitivity
Exploration of wound if necessary
How can we deliver radiation therapy?
Brachytherapy
External beam radiation therapy/teletherapy (most common form in vet med)
What two types of radiation are used in radiation therapy?
Electrons (beta particles) - absorbed by tissue or easily shielded
High energy X-rays - penetrating and harmful
Describe brachytherapy.
Radioactive substance emits gamma rays/beta particles close to tumour
Admin - applied to surface of tumour / implanted within tumour (gold ‘seeds’) / administered systemically but concentrated in tumour
E.g. radioiodine treatment for hyperthyroid cats
Describe external beam radiation therapy.
Radiation therapy given by external radiation source at distance from body Linear accelerator (LINAC) most commonly used Multiple doses (fractions) given over 4-6 weeks Use of teletherapy limited because of restricted availability of fixed radiation source or LINAC (only 4 veterinary centres in UK)
What acute side-effects can we see after radiation therapy?
Skin reddening Vesiculation Desquamation Severe exfoliative dermatitis Localised hair loss
What late toxicity side-effects can we see with radiation therapy?
Depigmentation
Dermal fibrosis
Osteonecrosis
Neural necrosis (blindness, neurologic signs)
How do chemotherapy drugs act on dividing cells?
Act upon processes in cell growth and division - DNA replication, mitotic spindle, metabolic activities
What does the cellular response to chemotherapy depend on?
Tumour growth rate
Drug resistance
How do we decide the dosage for chemotherapy drugs?
Efficacy vs toxicity - use the highest possible dose (i.e. the dose that has maximum acceptable side effects) to effect maximum fractional kill with minimum side effects
Use repeated doses of range of drugs allowing recovery time - typically 3-week cycles
Dosing calculated as function of surface area (m2)
How sensitive are different types of tumours to chemotherapy?
Highly sensitive = lymphoma, myeloma, some forms of leukaemia
Moderately sensitive = high grade sarcomas, mast cell tumours
Poorly sensitive = most slow-growing sarcomas, most carcinomas, melanomas
What are the benefits of combination chemotherapy?
Greater tumour cell kill achieve
Less resistance
Fewer side effects
What is the common feline chemotherapy regime for lymphoma?
COP:
C = cyclophosphamide
O = Oncovin (contains vincristine)
P = prednisolone
What is the common canine chemotherapy regime for lymphoma?
CHOP C = cyclophosphamide H = hydroxydaunorubicin (doxorubicin) O = Oncovin (contains vincristine) P = prednisolone
When do we use chemotherapy as a first-line treatment?
Diseases that are systemic in nature
Usually respond well to cytotoxic drugs because of high growth fraction
E.g. lymphoma, some forms of leukaemia, multiple myeloma (plasma cell tumour)
When do we use adjunctive chemotherapy?
Solid tumours - chemotherapy solely is rarely of value, best treated with surgical resection and/or radiotherapy
Chemotherapy as ‘adjunct’ to reduce tumour mass to enable surgical resection / to try and prevent/delay metastases
What is metronomic chemotherapy?
Palliative low doses of chemotherapy drugs. given daily
Targets endothelium/tumour stroma (anti-angiogenic)
Designed to minimise toxicity, palliative only
What is chemoembolisation?
Interventional radiology
Local, directed delivery of chemotherapy drug and embolization to treat inoperable solid tumour
Chemotherapy drug injected in blood vessel supplying tumour, synthetic embolic placed inside blood vessels trapping the chemotherapy in the tumour
What safety protocols should practices using chemotherapy have?
All employees aware of use of cytotoxic drugs
Use of PPE - gloves, mask, glasses, apron
Use of sealed/closed system for admin of injectable chemotherapy
Cleaning procedures
Use of a chemo room
Clear protocol for disposal with allocated bins
Pregnant women should not handle any chemo drugs
What safety precautions should we have for handling cytotoxic drugs?
Chemo room locked
Use of a cabinet with vertical flow containment hood
Use of a plastic pad - drug never in direct contact with a surface
Use of Luer-Lock syringes for administration
All material used is gathered in a sealed plastic bag and disposed in bin for chemo wastes
What nursing care can we provide for chemotherapy patients?
Excreta from treated animals may contain traces of drugs or metabolites
Have a designated kennel, with clear ID of agents used
PPE should be used by those caring for patient (vinyl gloves, gown, eye protection)
All materials that have been in contact with animal should be regarded as potentially contaminated
Use a dedicated cytotoxic waste bin
How should chemotherapy patients be managed at home?
Keep children and other pets away
Wash food bowls, toys and bedding separately from household items
Use latex gloves when cleaning up bodily fluids
Double bag trash
Always wash hands after removing and disposing of used gloves
After cleaning soiled areas, disinfect it with household bleach (1 part bleach to 10 parts water)
Describe GI toxicity from chemotherapy.
Direct toxic effects on GI tract through death and loss of intestinal epithelial cells
Usually occurs 5-10 days after drug admin - stomatitis, vomiting, mucoid/haemorrhagic diarrhoea
How can we treat chemotherapy-related GI toxicity?
Symptomatic
IV fluid therapy
Anti-emetics (maropitant)
Gastroprotectants for any gastric ulceration (acid blockers, sucralfate)
Parenteral antibiotics if haemorrhagic diarrhoea/immunosuppressed
How can chemotherapy affect the patient’s coat?
Cats usually only lose their whiskers
Not a major problem in most dogs - some breeds susceptible to significant hair loss, hair of Old English sheepdogs may regrow in different colour, other breeds lose their ‘beard’
Describe myelosuppression from chemotherapy.
Routine haematology performed before cytotoxic agent given
Treatment delayed and/or reduced if there is myelosuppression
Neutropenia is indicator of max. tolerated dose being reached/approached, may be associated with better prognosis
What can myelosuppression from chemotherapy cause?
Neutropenia - can be life-threatening
Thrombocytopenia - rarely severe enough to cause bleeding
Anaemia - rarely clinical significant
How do we manage any hypersensitive/anaphylactic reactions from chemotherapy?
Stop drug admin and give: IV fluids Soluble corticosteroids Epinephrine (adrenaline) Antihistamines
How can we reduce the risk of extravasation from chemotherapy?
Drugs in a sealed system
Adequate restraint of patient
Administered through IV catheter - ‘clean stick’
Catheter flushed with saline before and after
How can we treat perivascular leakage of chemotherapy drugs?
Stop infusion but do not remove catheter Aspirate extravasated drug through catheter and give intralesional saline to dilute drug Draw back blood and then remove catheter IV hydrocortisone Cold compress Antidote (Dexrazoxane)
What are some specific chemotherapy drug toxicities?
Sterile haemorrhagic cystitis
Cardiotoxicity
Hepatotoxicity
Nephrotoxicity
Describe sterile haemorrhagic cystitis.
Metabolites of cyclophosphamide (e.g. acrolein) in urine
Irritant effect on bladder - cystitis (profuse haematuria, sometimes irreversible)
No specific treatment, MESNA may be protective
How can we minimise the risk of sterile haemorrhagic cystitis from chemotherapy?
Administer drug in early morning so not retained in bladder overnight
Ensure good fluid intake
Encourage frequent urination
Concurrent steroids or furosemide will assist diuresis
Monitor urine for blood/protein - urine dipstick before and after each admin
Describe the two types of cardiotoxicity from chemotherapy drugs.
Acute toxicity - tachyarrhythmias (infusion over at least 15mins, pulse should be monitored)
Chronic toxicity - cardiomyopathy (dose-dependent, irreversible, monitor cardiac function with ECG)
Describe hepatotoxicity from chemotherapy drugs.
Cumulative and often irreversible effect
Increase in liver enzymes > 3x upper reference range = delay/discontinue treatment
Co-administration with SAMe
Monitor biochemistry before each treatment
Describe nephrotoxicity from chemotherapy drugs.
Platinum compounds cause necrosis of proximal tubular cells
Administered slowly with IV fluid diuresis
Urea/creatinine monitored
