Oncology (Intro)

Question 1

Multistep Carcinogenesis: what is the mechanism?

Answer 1

Initiation (rapid DNA damage) – Promotion (reversible tissue and cellular changes) – Progression (slow and irreversible conversion to malignancy)

Question 2

What are the six essential alterations that dictate malignant growth of a cancer cell?

Answer 2

Self-sufficiency in growth signals
Insensitive to anti-growth signals
Tissue invasion and metastasis
Limitless replicative potential 
Sustained angiogenesis
Evading apoptosis

Question 3

List the DDx for Round cell tumor.

Answer 3

Lymphoma, MCT, Plasmacytoma, Histiocytoma, TVT, and sometimes Melanoma

Question 4

What are the microscopic characteristics of Sarcomas?

Answer 4

Spindle-shaped cells arranged individually (mesenchymal)

Question 5

What are the microscopic characteristics of Carcinomas?

Answer 5

Round, cuboidal, columnar, or polygonal cells arranged in cohesive sheets or clusters (epithelial)

Question 6

What are the characteristics of malignancy?

Answer 6

Homogenous (one cell type), Pleomorphic (variable morphology), anisocytosis (cellular/cytoplasmic variation in size), and anisokaryosis (nuclear variation in size)

Question 7

What are the advantages and disadvantages of dx cytopathology (needle biopsy/cytology)?

Answer 7

Pro: highly specific (+ = +)
Con: low sensitivity (FN)

Question 8

Never perform a needle tract implantation (cytopathology) with what tumor?

Answer 8

Urogenital carcinomas (can seed off the needle and implant into the body wall)

Question 9

T/F: Needle bx specimens of liver are most accurate and reliable.

Answer 9

False. Studies report accuracy of 50% or less.

Question 10

What is the purpose of staging testing?

Answer 10

To establish a tumor specific dx (differentiated between B9 and malignant); non-invasive way of answering if the tumor is localized, spread regionally, or diffusely

Question 11

How is Grading different from Staging?

Answer 11

Grading: requires block of tissue to establish inherent aggressiveness of tumor in Grade I (least aggressive) to III (most) to allow prognostication and alter therapeutic recommendations
Staging: non-invasive testing based on a WHO TNM system (0-IV)

Question 12

What do classic staging tests include (name 5)?

Answer 12

MDB (CBC, Chem, UA), Regional LN cytology (based on sentinel node), 3-view thoracic mets check (i.e. rads), abdominal u/s (+/- image guided FNA), and CT/MRI

Question 13

T/F: Never assume normal sized LN’s are not metastatic.

Answer 13

True. Local LN mets when lymphadenomegaly was not present in 40% dogs.

Question 14

T/F: Distant mets can still be present if the SLN does not have evidence of tumor.

Answer 14

False. Distant mets is possible if the SLN is (+).

Question 15

What are the steps of mapping SLN?

Answer 15

A 4-quadrant injection around the tumor w/ lipiodol (lipid soluble contrast agent like poppyseed oil)– has a slow transit time and therefore regional rads (always 3-views) are taken 24h later to determine which node it drained to = SLN

Question 16

What is the minimum threshold size of pulmonary nodules to be detected on rads?

Answer 16

7-9 mm (otherwise, CT is needed)

Question 17

What organ is the most common receptacle of blood-borne mets?

Answer 17

Liver

Question 18

What are the classic Paraneoplastic syndromes (often the first sign of malignancy?

Answer 18

Hypercalcemia (anal sac ACA, LSA, multiple myeloma, mammary tumor), Hypoglycemia (intestinal leiomyosarcoma), Neurologic, Cutaneous, or Bone (i.e. hypertrophic osteopathy)

Question 19

T/F: Treating the tumor will resolved both tumor and its PNS signs.

Answer 19

True

Question 20

What does conventional chemotherapy target?

Answer 20

Drugs target all rapidly dividing cells including tumor cells and cell populations of the gut, BM, and hair follicles.

Question 21

Why are certain breeds (name 2) tested for ABCB-1 gene mutation prior to chemo dosing?

Answer 21

All susceptible breeds like Collie and Australian Shepherds should be tested before tx with known problematic drugs (increased risk with Vincristine, Vinblastine, Paclitaxel, and Doxorubicin) because they cannot remove drugs as effectively. Hence, if MDR-1 gene mutation is present, dose must be reduced by 30-40%.

Question 22

What is required for chemotherapy handling/safety?

Answer 22

Need both Biological Safety Cabinets and Closed-system Drug-transfer Devices.

Question 23

What are the common adverse events of cytotoxic chemotherapy?

Answer 23

Bone marrow suppression (most common), Alopecia in non-shedding breeds only, and Gastrointestinal crypt cells destroyed resulting in vomiting and diarrhea.

Question 24

What is required before giving chemo?

Answer 24

Prior to giving chemo: neutrophils ≥ 3000/µL and platelets ≥ 100,000/µL (if too low, no tx and recheck CBC in 3-7d)
If the neutrophil count at the nadir (7d post chemo) is <1,500 neutrophils/μL or the platelet count <60,000 platelets/μL, then subsequent doses should be decreased by 20-25% (the efficacy is reduced by 50%)

Question 25

What are the key drug players for GI toxicity?

Answer 25

Cisplatin and Doxorubicin

Question 26

Name the chemotherapy MOA and specific toxicities of Vincristine (Antimitotic).

Answer 26

Cell-cycle-phase specific

Vesicant, neuropathy and mostly GI signs

Question 27

What is the protocol for Vincristine/blastine extravasation?

Answer 27

Aspirate any fluid into IV catheter prior to removal – dry, warm compress 20-30 min at a time Q6 x 24-48h – administer Hyaluronidase (dose of 1:1) to disperse and dilute

Question 28

Name the chemotherapy MOA and specific toxicities of Cyclophosphamide (Alkylating agent).

Answer 28

Cell-cycle-phase nonspecific
Sterile hemorrhagic cystitis (formation of Acrolein) and mostly BM suppression
Commonly used in Metronomic chemotherapy; SHC can be avoided with environmental control and concurrent glucocorticoid/furosemide administration.

Question 29

Name the chemotherapy MOA and specific toxicities of Iomustine/CCNU (Alkylating agent).

Answer 29

Cell-cycle-phase nonspecific
Liver toxicity (give with Denamarin) and mostly BM suppression

Question 30

Name the chemotherapy MOA and specific toxicities of Chlorambucil (Alkylating agent).

Answer 30

Cell-cycle-phase nonspecific

Mostly BM suppression

Question 31

Name the chemotherapy MOA and specific toxicities of Doxorubicin (Antibiotic agent).

Answer 31

Cell-cycle-phase nonspecific
Vesicant, dose-related cardiotoxicity (prescreen Boxers/Dobies), and mostly GI signs
Mitoxantrone: cardiac sparing

Question 32

What is the protocol for Doxorubicin extravasation?

Answer 32

Dexrazoxane (Zinecard) reduces cardiac toxicity and should be given (10x dose IV)
via new catheter in different leg w/in 3h of extravasation and again w/ 24 and 48h. Do not disperse in case of extravasation, localize and neutralize; apply cold pack.

Question 33

Name the chemotherapy MOA and specific toxicities of Cisplatin (Platinum agent).

Answer 33

Cell-cycle-phase nonspecific

Species-specific, dose-related, primary pulmonary toxicity (fatal pulmonary edema) in cats and nephrotoxicity in dogs.

Question 34

Name the chemotherapy MOA and specific toxicities of Carboplatin (Platinum agent).

Answer 34

Cell-cycle-phase nonspecific
BM suppression only (no nephrotoxicity and okay in cats)
indicated for OSA and other sarcomas.

Question 35

What is the MOA for Tanovea-CA1.

Answer 35

Inhibits the proliferation of lymphocytes and LSA cell lines by inhibiting DNA synthesis; 1st FDA conditionally approved lymphoma tx for dogs (after standard chemo fails).

Question 36

How is Metronomic Chemo different from MTD Chemo?

Answer 36

All MTD chemo requires a break period (may result in recurrence) whereas MC revolves around concept of eliminating break period by giving low dose continuous chemotherapy

Question 37

What is the MOA for Metronomic chemo?

Answer 37

Antiangiogenesis (blocks COX and circulating endothelial progenitor cells), Immuomodulation (reduces regulatory T cells), and direct targeting (cytotoxic effect on cancer cells)