12- Clinical Oncology Flashcards
What techniques are used to determine the “what”?
Cytology > examination of cell types from bodily fluids
- obtained by fine needle aspiration (FNA)
- important to rule out benign lesions (most are)
Histopathology > microscopic examination of tissue
- the gold standard
- requires tissue biopsy
- provides architecture information
What lymph nodes are usually palpable in a normal healthy dog?
- Mandibular/ Prescapular/ Popliteal
Why is FNA (fine needle aspiration) for cytology done in lymph nodes?
- drainage of tumor > often 1st site of metastasis
What are the most common cancers in vet med vs humans?
Humans- carcinomas (epithelial)
Vet med- sarcomas (mesenchymal)/ hematopoietic)
What is a very common tumor in vet med (dogs)?
Mast cell tumor
- C-kit is a marker for canine mast cell tumors
What are the 5 criteria of malignancy?
- Anisocytosis (cell size differences)
- Anisokaryosis (nucleus size differences)
- Lack of cell-cell contact (epithelial tumors)
- Abundant mitotic figures
- General reversion to a less mature phenotype
What are some specialized staining techniques?
ICC = Immunocytochemistry
IHC = Immunohistochemistry
Why are specialized staining techniques used?
- to more definitively identify cell of origin > cancer type
- to identify cell subtypes within a type of cancer (T vs B cell lymphoma)
What is done if cytology is inconclusive?
- Histology (histopathology)
- Immunohistochemistry (IHC)
- Flow Cytometry > test multiple markers
- PCR of antigen receptor rearrangements of lymphocytes
What is the difference between grading/ staging?
Grading- classify cancer cells by appearance (how undifferentiated)
Staging- classify cancer cells by extent in body/ spread
What is the WHO criteria for cancer staging?
TNM (tumor, node, metastasis)/ 0,1,2
T- depends on of mass
N- (0-no LN/ 1-few regional LN/ 2-many regional LN)
M- 0-no metastasis/ 1-yes metastasis
How is cancer staging obtained?
- physical examination
- laboratory analysis
- imaging (CT is more sensitive/ definitive than x-ray)
- abdominal ultrasound
How does a PET scan work? (imaging for staging)
- glucose metabolize measured (fluorescent dye)
- Warburg effect > tumor take up glucose at higher rate
What is paraneoplastic syndrome?
- cancer cells secrete substances with distant effects (symptoms)
ex) mast cell degranulation > release of mast cell mediators - can lead to difficulty closing wounds/ anaphylaxis
Why are biomarkers important for clinical oncology?
- identification of potential responders to treatment
- monitoring treatment response
- pharmacologic biomarkers for drug optimization
What is the WHO classification for canine MCT?
Stage 1 > 1 tumor confined to dermis/ no lymph node involvement
Stage 2 > 1 tumor confined to dermis/ regional lymph node involvment
Stage 3 > multiple tumors or 1 large infiltrating/ lymph node
Stage 4 > distant metastasis
Substage > a/b > based on outlook of patient (a = good/ b = problems)
How does staging impact treatment?
- local disease > local therapy > surgery/ radiation
- systemic disease > systemic therapy > chemo
= Oncology Dogma
What are important considerations for surgery?
- Margins
- Fascial planes (may need to remove)
- separate surgical teams > surgeon removes tumor, trauma/ plastics close and repair
- not all wounds are closed > heal by scarring/ second intention
What is a pre-surgery treatment?
- Neoadjuvant therapy > to ↓ surgical field
- assess response of primary tumor to chemotherapy
- early treatment of micrometastasis
What is adjuvant therapy?
- follow up after treatment
- surgical complication (dirty margins)/ metastatic disease
What are the types of radiation therapy?
- Orthovoltage/ Megavoltage/ Brachytherapy/ Systemic
What is the mechanism of radiation therapy?
- double-stranded DNA damage
- direct action > DNA damage > cell death
- indirect action > free radicals > DNA damage > cell death
What is an important protocol of radiation therapy?
Fractionation- smaller doses over time
- palliative, coarse-fractioned
What are the 4 R’s of radiation therapy?
Repair- allow normal cells to repair between treatments
Reoxygenation- more O2 > more sensitive to radiation > target
Redistribution- at any one time, cells in different stages of cell cycle (DNA damage best in G2-M phase of cell cycle)
Repopulation- working against you > proliferation between cycles
What are the side effects of radiation therapy?
Early > within days/ weeks/ completely repairable/ harsh
Late > months-years/ irreversible damage
- VRTOG scoring system used to assess extent of side effects in tissues
What is the general mechanism of chemotherapy?
- targets rapidly dividing cells > therapeutic index
What are the side effects of chemotherapy?
- generalized side effect profile since target rapidly proliferating cells (GIT/ hair/ bone marrow)
- neutropenia (↓ neutrophils)/ thrombocytopenia (↓ platelets)
- HSC lineage affected > susceptible to infections
What are some chemotherapies?
Alkylating agents > covalently bonding alkyl groups ex)nitrogen mustard
- induce dsDNA breaks
Antimetabolites > interfere with DNA synthesis (purine/ pyrimidine analogs)
Anthracyclines > Topoisomerase II inhibitors/ generate free radicals
What are chemotherapy principles?
MTD = max tolerated dose (without killing patient)
Metronomic Chemotherapy > smaller doses more often/ for longer
What are the 3 rules of combination chemotherapy protocols?
- Different mechanisms of action
- No overlapping side effect profiles
- Drugs do not impact each other
What are the therapeutic considerations of targeted drugs?
- monoclonal antibodies VS small molecule RTK inhibitors
- target specificity (↑ MAb/ ↓ RTKI)
- target trafficking > MAb extracellular/ RTKI intracellular
- administration > IV (MAb) vs oral (RTKI)
- frequency > MAb less often/ RTKI more often
- mechanism of action
What is the goal of personalized medicine?
- knowledge of molecular composition > specific therapies
- prognostic information
- predictive information
