Oncology (1-6) Flashcards
a group of cells whose proliferation is uncontrolled and, under certain circumstances, can metastasis to distant sites
cancer
what is the dominant type of cancer in cats
FeLV infection
name the 7 alterations in cellular physiology that collectively dictate malignant growth
- a self sufficiency in growth
- an insensitivity to anti-growth signals
- an ability to evade programmed death (apoptosis)
- limitless replicative potential (mainly through reactivation of telomerase)
- an ability to sustain angiogenesis
- an ability to invade and metastasize
- an ability to evade host immunity
name 4 mechanisms of oncogene activation
- chromosomal translocation
- gene amplification
- point mutations
- viral insertions
cause a stimulatory effect on cell growth and proliferation; produce positive signals leading to uncontrolled growth
oncogene
cause tumor formation as a result from loss of inhibitory functions; has an inhibitory effect on cell growth and proliferation
tumor suppressor genes
name 3 treatment modalities of cancer
- surgery
- radiotherapy
- chemotherapy
this is the most important treatment modality of cancer; majority can be treated this way
surgery
this treatment modality of cancer is very important for primary tumors
radiotherapy
this is a systemic treatment important for secondary disease and ‘liquid tumors’ like leukemia
chemotherapy
this describes the severity of a patient’s cancer based on size and/or extent (reach) of the original (primary) tumor and whether or not cancer has spread in the body
staging
name 3 reasons why staging in cancer is important
- helps plan appropriate treatment
- can be used to determine prognosis
- helps vets and researchers exchange info about the patients
name 5 common elements considered in most cancer staging systems
- site of primary tumor and cell type
- tumor size and extent (reach)
- presence of metastasis
- tumor grade
what is the TNM staging system based on
T ‐ size and invasiveness of tumor
N ‐ status of nodal metastasis
M ‐ status of distant metastasis
this stage of cancer means the carcinoma is in situ
stage 0
this stage of cancer means the cancer has spread to distant tissues or organs
stage IV
this is a means of detecting disease early in asymptomatic individuals
screening
name 4 types of tumors diagnostic imaging is required for
- deep tumors
- tumors involving vital structures
- tumors involving bones
- tumors adjacent to bone
this type of imaging is useful for assessing parenchymatous organs and internal lymph nodes
ultrasound
this type of imaging is great for bony lesions, pulmonary lesions, and radiation planning
CT
this type of imaging is best for CNS lesions; many more shades of grey in soft tissue
MRI
name the type of biopsy
used to remove small cores of tumor tissue from solid lesions
tru-cut biopsy
name the type of biopsy
excellent for skin and superficial soft-tissue tumors; recover substantially more tissue than needle aspirates
skin punch biopsy
name the type of biopsy
surgical removal of a solid piece of tissue from a tumor for histopathological examination
incisional biopsy
name the type of biopsy
complete surgical extirpation of a tumor following which tissue samples are removed for histopathological examination
excisional biopsy
name the type of biopsy
often indicated in the diagnosis of conditions affecting lymphoid and myeloid systems - may take form of an aspirate or a core biopsy
bone marrow biopsy
name 3 possible sites for bone marrow biopsy
- humerus
- femur
- iliac crest
this is defined as one or more clinical signs induced by a tumor distant from its primary site; often due to production of a hormone, cytokine, enzyme/peptide, or homone-like substance
paraneoplastic syndrome (PNS)
what are the 2 ways factors causing PNS can be secreted?
- othotopically / topically
- ectopically
what 3 forms of calcium are included in the total serum calcium?
- active ionized calcium
- inactive protein-bound calcium
- complexed calcium
low albumin will have what effect on total calcium
reduce total calcium
high albumin will have what effect on total calcim
increase total calcium
what 3 things is calcium homeostasis tightly regulated by
- parathyroid hormone (PTH)
- active vitamin D (calcitriol)
- calcitonin
what is the most common cause of hypercalcemia in the dog?
cancer
what are the most common initial signs of hypercalcemia
primary polyuria with secondary polydipsia
name 4 tumors associated with hypercalcemia of malignancy
- lymphoproliferatice disease
- apocrine gland neoplasia
- parathyroid gland neoplasia
- other carcinomas
list the 8 investigations that should be made to diagnose hypercalcemia of malignancy
- clinical exam (lymph nodes, rectal)
- hematology/chemistry/UA
- ionized calcium
- radiography
- U/S
- FNA/biopsy abnormalities
- PTH/PTHrP
- bone marrow biopsy
name 5 differential diagnoses for hypercalcemia
- malignancy
- primary hyperparathyroidism
- primary renal disease
- hypervitaminosis D
- hyperthyroidism
what happens to PTH when there is hypercalcemia?
(except in cases of primary hyperparathyroidism)
reduced
what is the treatment for patients midly affected by hypercalcemia
2-3x maintenance IV isotonic fluid
(for subclinical dehydration)
what is the treatment for patients moderately affected by hypercalcemia
loop diuretics
(for non-azotemic patients)
what is the treatment for patients severely affected by hypercalcemia
salmon calcitonin
(oncologic emergency)
these are commonly co-administered with calcitonin because their peak effect can be delayed for a few days after administration but persists for weeks;
ideal for management of chronic hypercalcemia
biophosphonates
what are the clinical signs of hypoglycemia
neurological sgns and catecholamine effects
name 6 differential diagnoses of hypoglycemia
- neonatal
- breed-related
- sepsis
- liver failure
- insulinoma
- other paraneoplastic
list the 6 investigations that should be made to diagnose paraneoplastic hypocalcemia
- history
- physical exam
- biochemistry/hematology
- diagnositc imaging
- advanced imaging (CT/MRI)
- serum insulin
what is the treatment of choice for hypocalcemia caused by insulinoma
surgery
what is hyperhistaminemia (can be caused by mast cell tumors) treated with
- diphenhydramine, loratadine (H1 receptor blockade)
- ranitide, cimetidine or famotidine (H2 receptor blockade)
this is acquired due to an immune response against acetylcholine receptors of the motor nerve end-plates in skeletal muscle;
commonest PNS (paraneoplastic syndrome) in cats and dogs with thymoma
myasthenia gravis
this paraneoplastic syndrome (PNS) is associated with phaeochromacytoma (tumor of the adrenal medulla), secreting catecholamines
hypertension
what can hyperviscosity be associated with
- increased plasma proteins
- increased cell numbers (WBCs or RBCs)
name 5 clinical signs of hyperviscosity
- CNS
- polyuria/polydipsia
- cardiac compromise
- hemorrhage
- ocular changes
this is a syndrome characterized by periosteal proliferation of new bone
hypertrophic osteopathy
what type of tumor is hypertrophic osteopathy associated with
thoracic neoplasia
(or other space occupying lesions in chest/abdomen)
name some risks of oncology surgery
- non-diagnostic sample
- seeding
- incr. contamination field
- infection
- wound breakdown
- hemorrhage
- pain
what is the surgical dose for oncology surgery?
- remove adequate margin of tissue around tumor gross edge
- preserve as much healthy tissue as possible
what is the general rule for numerical margins for a mast cell tumor
2 cm
what is the general rule for numerical margins for STS
3-5 cm
what is the general rule for numerical margins for a melanoma
2-3 cm
what is the general rule for numerical margins for a carcioma
1-2 cm
name the 6 basic principles of surgical oncology - involving removing the tumor without seeding/spreading
- plan resection
- look but don’t touch
- protect wound from seeding
- ensure wound heals as planned
- orientate the scar
- extirpate the nodes?
what are the 4 options for closure following tumor removal
- primary, local closure
- local flaps
- axial pattern flaps
- free skin grafts
name 4 important roles that make up a surgical oncology team
- carer
- oncologist
- nurse
- anaesthesia team
name 4 ways oncology surgery can be classified
- debulking
- marginal
- wide
- radical
name the oncology surgery classification
definition is variable and may result in remaining macroscopic or microscopic disease;
piecemeal and intrascapular removal is classified as this;
this type of surge ymay improce patient function/comfort but where macroscopic disease remains the efficacy of subsequent adjuvant therapy may be reduced
debulking
name the oncology surgery classification
removal of tissue just peripheral to the gross mass, excising narrow ‘piece’ of normal tissue;
may be all that is required with benign lesions; microscopic neoplasia may remain with malignancies
marginal
name the oncology surgery classification
curative intent surgery and incorporates a prescribed margin of normal tissue
wide
name the oncology surgery classification
curative intent surgery removes the entire body compartment which contains the tumor
radical
how should lateral (numerical) margins be measured
using a ruler
name some considerations when decision-making for surgical margins
- tumor type
- tumor site
- metastases
- co-morbidities
- owner preference
- availability of neo-adjuvant or adjuvant therapies
once surgery is complete, what should be done to all cut margins on the excised mass before sending to pathology
all cut margins should be inked
what are the 3 best colors for inking cut margins on excised masses for pathology
yellow, blue, green
what do most chemotherapy or “cytotoxic” drugs act upon
(which provides some specificity/sparing of normal cells)
cell division
what kind of tumor cells are generally resistant to chemotherapy and act as a reservoir to repopulate tumors
non-dividing cells (G0)
this is the time taken for a tumor to physically double in size; much shorter during early tumor growth
Mass Doubling Time (MDT)
name three factors affecting Mass Doubling Time (MDT) of tumors
- proportion of total cells which are actively dividing
- duration of cell cycle
- number of cells being lost by cell death
this is the proportion of total cells which are actively dividing
growth fraction (GF)
name 6 factors affecting tumor response to chemotherapy
- growth raction and mass doubling time
- inherent tumor cell sensitivity
- inherent or acquired drug resistance
- drug dosage
- tumor cell heterogeneity
- tumor blood supply
name 8 basic mechanisms by which drug resistance occurs
- less drug entering cell (binding and uptake)
- defective drug activation
- increased drug inactivation
- increased target molecules
- altered target molecules
- enhanced DNA repair
- inability to undergo apoptosis
- enhanced export of drug from the cells
what does the tumor cell kill hypothesis state?
cytotoxic drugs kill tumor cells according to first order kinetics
what inaccurate assumption does the Tumor Cell Kill Hypothesis make to help us understand responses
tumor is homogenous in terms of chemosensitivity
for most cytotoxic drugs, what is the dose based on
body surface area (BSA) of the patient
what is the equation for BSA (body surface area)
surface area (m^2) = (k x body weight)^0.66 / 10^4
k = 10.1 (dogs), 10 (cats)
what are the 2 most common dose limiting toxicities of chemotherapy drugs
- myelosuppression
- GI side effects
what is a chemotherapy dose schedule
chemotherapy administered at intervals during which normal tissues recover fully but tumor does not
what three ways can chemotherapy be used
- sole treatment for highly chemosensitive tumors
- post-operatively
- neo-adjunctively prior to surgery
what are the 6 main categories of chemotherapy agents based on their mechanisms of action
- alkylating agents
- mitotic spindle inhibitors/toxins
- antimetabolites
- antitumor antibiotic
- glucocorticoids
- miscellaneous
name the chemotherapy agent category
cause cross-linking and breaking of DNA molecules, interfering with DNA replication and RNA transcription
(cyclophosphamide, chlorambucil, melphalan, lomustine)
alkylating agents
name the chemotherapy agent category
bind to cytoplasmic microtubular proteins and arrest mitosis in metaphase
(vincristine, vinblastine, vinorelbine, paclitaxel)
Mitotic spindle inhibitors/toxins
name the chemotherapy agent category
mimic normal substrates for nucleic acid synthesis; inhibit cellular enzymes or cause production of non-functional molecules
(methotrexate and cytosine arabinoside)
antimetabolites
name the chemotherapy agent category
bind to DNA and inhibit DNA and RNA synthesis through various mechanisms
(doxorubicin, epirubicin, mitoxantrone)
antitumor antibiotics
name the chemotherapy agent category
cytolytic for lymphoid tissues and therefore useful in treatment of lymphoproliferative diseases;
mechanism of action unclear
glucocorticoids
are alkylating agents cell cycle specific?
no, non-specific
are anti-tumor antibiotics cell cycle specific?
no, but more active in S phase
are antimetabolites cell cycle specific?
yes, S phase specific
what is the major drug in glucocorticoid class of chemotherapy agents
prednisolone
are mitotic spindle inhibitors (vinca alkaloids) cell cycle specific?
yes, M phase specific
name 5 drug toxicities that can occur with chemotherapy delivery
- GI adverse effects
- myelosuppression
- anaphylaxis
- drug extravasation
- specific adverse effects
how to manage anaphylaxis as a side effect of chemotherapy
premedication with antihistamines
how to manage cardiac dysrhythmias as a side effect of chemotherapy
stop infusion then restart at reduced rate
drug that causes soft tissue damage following inadvertant perivascular administration;
self-limiting inflammation, erythema, discomfort
ex: vinca alkaloids
irritant
drug that causes soft tissue damage following inadvertant perivascular administration;
catastrophic progressive soft tissue necrosis
ex: doxorubicin
vesicant
how to manage drug extravasation as a side effect of chemotherapy
stop drug administration immediately and attempt to withdraw as much drug as possible through the cannula in place
how to treat drug extravasation of vincristine (irritant)
HOT compress;
hyaluronidase diluted with 0.9% saline
how to treat drug extravasation of doxorubicin/epirubicin (vesicants)
COLD compress;
hyaluronidase diluted with 0.9% saline
this side effect of chemotherapy is the killing of rapidly dividing bone marrow stem cells
myelosuppression
how to manage febrile neutropenia (myelosupression) as a side effect of chemotherapy
assume patient is septic! hospitilize, broad spectrum IV antibiotics, etc
how to manage asymptomatic neutropenic patients (myelosuppression) as a side effect of chemotherapy
chemotherapy dose ddelat and reduction
name 4 specific adverse effects (related to specific chemotherapeutic agents)
- cardiotoxicity
- sterile hemorrhagic cystitis
- nephrotoxicity
- hepatotoxicity
this is a low dose oral form of chemotherapy which targets angiogenesis;
usually low dose cyclophosphamide + prioxicam or meloxicam
metronomic chemotherapy
name 6 receptor tyrosine kinases (RTKs) which can be dysregulated in cancer
- FGFR (fibroblast growth factor receptor)
- VEGFR (vascular endothelial)
- PDGFR (platelet derived)
- EGFR (epidermal)
- MET (hepatocyte GFR)
- KIT (hematopoietic GFR)
name the two tyrosine kinase inhibitors (TKIs) that have been approved in veterinary medicine for treatment of mast cell tumors
toceranib & masitinib
this is a key treatment modality for cancer that is based on the use of high energy rays to kill neoplastic cells
radiation therapy (RT)
how is radiotherapy prescribed? (what units?)
Gray (J/kg)
this is when the total dose is divided into multiple smaller doses over the course of several days to weeks (common with radiotherapy)
fractionation
this is the amount of energy (radiation) absorbed by the patient (tissue); unit used in radiation therapy treatment
Gray (J/kg)
this is the particular dose and number of fractions to be given to a particular tumor (radiotherapy)
RT protocol
what is the rationale behind fractionation of radiotherapy
- helps normal tissues tolerate treatment better
- potentiates efficiency
this type of radiation toxicity typically develops during or just after treatment
early (acute) toxicity
how long after completion of treatment are acute toxicities from radiotherapy expected to resolve
1-4 weeks
what tissues do early toxicities from radiotherapy affect
rapidly proliferating tissues (skin and mucus membranes)
what do early toxicities from radiotherapy depend on
dose intensity & total dose
name 5 things that should be considered when managing a patient with acute radiation induced toxicities
- manage discomfort
- protect from external damage
- keep site clean (but do not rub or cover)
- do not use prophylactic antibiotics
- consider topical ointments/medications
this type of radiation toxicity typically occurs months-years after RT
late (chronic) toxicity
what tissues does late toxicity from radiotherapy damage
with low turn-over rates (connective tissue or neuronal tissue)
what increases the risk of late toxicity from radiotherapy
larger dose per fraction
this refers to protocols that use a higher number of fractions (10-20) using a relatively low dose per fraction & a high total dose; often administered on a daily basis
definitive/curative intent protocols
name 3 advantages of definitive intent protocols for radiotherapy
- improves therapeutic index
- optimizes chance of long term tumor control
- risks of late toxicities low
name 2 disadvantages of definitive intent protocols for radiotherapy
- more demanding (vet visits, cost, etc)
- higher risk of acute toxicities
these protocols consist of 3-6 fractions typically 1-2 times weekly for 3-4 weeks OR daily for 1 week;
higher dose per fraction & lower total dose
aim is to quality of life in dog with advanced cancer
palliative protocols
name 1 disadvantage of palliative protocols for radiotherapy
- risk of late toxicity
name 2 advantages of palliative protocols for radiotherapy
- less acute toxicities seen
- lower cost (fewer vet visits)
these protocols consist of very few treatments (1-3 fractions) given within a few days (1-5);
high dose intensity & high dose fraction;
used for well delineated, non-infiltrative and small tumors
stereotactic protocols
name 1 advantage of sterotactic protocols for radiotherapy
good tumor control rate with fewer treatments
name 1 disadvantage of sterotactic protocols for radiotherapy
risk of late complications
name 3 indications of radiotherapy in veterinary oncology
- sole therapy
- in combination with surgery
- benign conditions
this is the most common form of administering radiation to dogs and cats;
source of radiation is at distance from body of patient;
ionizing radiation can be human made or obtained from natural decay
teleradiotherapy (external beam radiotherapy)
this is voltage in the. range of 100-500kV (x-rays);
best for superficial/shallow tumors (<2-3cm)
orthovoltage (kV)
name 3 disadvantages of orhtovoltage (kV) for radiotherapy
- low penetration
- higher bone absorption
- limited small field size
this is voltage over 1 million volts (x-rays or gamma rays)
Megavoltage (MV)
name 3 advantages of megavoltage for radiotherapy
- high penetration
- homogenous tissue absorption
- large field size
these rays are from radioactive decay;
decay of cobalt 60
gamma rays
these rays are man-made;
electrons are produced by heating the filament (cathode, C), then accelerated in a straight line in accelerating waveguide; Electrons strike a target (anode, A) to produce these high-energy rays
x-rays
this is a form of radiotherapy in which the source of radiation is applied in or on the patient in one prolonged dose, using surface applicators, needles or seeds
Brachytherapy
name 3 advantages of brachytherapy
- deliver continuous radiation
- minimizes dose to surrounding tissue
- maximizes dose to tumor
this is a form of brachytherapy where the source is applied to the surface of the lesion;
only for superficial lesions (2-3mm)
plesiotherapy
this is when radiation is targeted to a specific tissue by using a radionuclide;
routes of administration are oral, IV, and intraperitoneal
systemic radiation
name the type of ionization
a secondary electron resulting from absorption of an x-ray interacts with the DNA to produce an effect (damage)
direct ionization
name the type of ionization
secondary electron interacts with water molecules to produce a hydroxyl radical which produces damage to DNA;
oxygen is needed to then attach to damaged ends of DNA so that DNA cannot repair
indirect action/ionization