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ACVIM Specialty Exam (Condensed) > Oncology > Flashcards

Oncology Flashcards

1
Q

What is the staging system for canine lymphoma?

A

Stages I: single LN, II: multiple LNs, III: regional LNs, IV: liver and/or spleen, V: distant metastasis.

Substaging: a - systemically well. b - systemically unwell.

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2
Q

Canine multicentric lymphoma - treatment options and prognosis?

A
  1. Multiagent - CHOP. Remission rate >90%, DFI 12 months. 4-6 week cycles.
  2. Single agent - doxorubicin (+ steroid).
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3
Q

Chronic lymphocytic leukemia (CLL) - criteria for treatment?

A

Lymphocyte count >60K
Organomegaly (infiltrative disease)
Most common form - T cell, granular form.

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4
Q

CLL - treatment and prognostic factors?

A

Chlorambucil and prednisolone - long term
Overall good prognosis
Negative - anemia, immunophenotype (B cell worse than T)

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5
Q

Cell surface markers for vascular neoplasia

A

CD31
Vimentin (spindle cell)
Factor 8

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6
Q

Cell cycle non-specific drugs?

A

Anti-tumor antibiotics (doxo, mitoxantrone)

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7
Q

Cell cycle specific drugs?

A

Alkylating agents (vinc-)

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8
Q

MDR-positive dogs - pathogenesis and considerations?

A

ABCB1 gene mutation (aka Multi Drug Resistance 1 gene) - deletion in 4 base pairs. Gene encodes for p-glycoprotein - affects drug efflux from cells. Most significant implication in epileptic control (often more refractory to conventional anti-epileptic drugs in Collies).
Overall <2% prevalence (UK, presumably Aus).

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9
Q

MDR - which drugs?

A

Alkylating agents (vincristine, vinblastine, vinorelbine), paclitaxel.
NOT cyclophosphamide, CCNU, doxorubicin.

Dose reduction by 40% if MDR positive.

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10
Q

Chemotherapeutic drugs that cross the BBB

A

Lipophilic drugs:
Procarbazine
Alkylating agents - lomustine (CCNU), temozolomide
Cytarabine arabinoside (anti-metabolite)

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11
Q

Multiple myeloma - diagnostic criteria (list 4)

A

1) Neoplastic plasma cells in the BM/tissues
2) Lytic bone lesions
3) Monoclonal gammopathy (serum)
4) Bence Jones proteinuria (urine fLC)

3 & 4 - presence of clonal Ig paraproteins produced by neoplastic cells (M-proteins) - can be complete Ig or free light chains (fLC).

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12
Q

Multiple myeloma - clinical manifestations & mechanisms?

A

Hyperviscosity syndrome - bleeding diathesis (M component interferes with platelet aggregation & platelet factor 3 release)
Systemic hypertension
Renal dysfunction
Lameness/bone pain
Immunosuppression - secondary/acquired infections
Cytopenias (anemia, thrombocytopenia)
Hypercalcemia (D>C)

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13
Q

Multiple myeloma - treatment?

A

Melphalan and prednisolone
Pamidronate (if osteolytic lesions)
Lomustine (CCNU) + hepatoprotectant

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14
Q

Multiple myeloma - prognosis?

A

MST 540-930 days with PO chemotherapy

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15
Q

Soft tissue sarcoma (STS) grading system?

A

Grade I & II: low grade
Grade III: high grade
Histologic grade is PROGNOSTIC

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16
Q

Grading system for neutropenia?

A

Grade 1-4

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17
Q

Cyclophosphamide MOA?

A

Alkylating agent

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18
Q

Cyclophosphamide adverse effects and MOA?

A
  • Haemorrhagic cystitis (via renal excretion of its hepatic metabolite acrolein which is urotoxic)
  • Myelosuppression (neutropenia)
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19
Q

Canine cutaneous epitheliotropic LSA - predilection sites and presentation?

A

Mucocutaneous junctions (perianal, perioral, conjunctiva, paw pads)
GI epithelium - different disease entity

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20
Q

ICC/IHC markers - which?
B or T cell LSA

A

B cell - Pax5, CD79
T cell - CD4, CD8, CD3
Histiocytic sarcoma - Iba1 (macrophage origin)

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21
Q

MCT - prognostic factors?

A

Grading: high grade/grade III MCTs with a high mitotic rate (>5/10hpf) and/or prominent anisokaryosis and/or giant cell formation may have a poor outcome as a result of a high rate of local and distant metastasis or inoperable recurrence.

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22
Q

Oral SCC - dogs - prognostic indicators?

A

Tumor size
Tumor location (rostral more likely surgically resectable than caudal)
LN metastasis (uncommon, 10%) - good to do sentinel lymph node mapping

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23
Q

Hemangiosarcoma - staging system?

A

Stage I: Tumor confined to the spleen.
Stage II: Ruptured splenic tumor with or without regional lymph node involvement.
Stage III: Distant lymph node or other tissue metastases.

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24
Q

Canine HSA - common primary sites?

A

Spleen&raquo_space; right atrium, cutaneous, SQ.

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25
Q

Canine HSA - prognostic factors?

A

Negative prognostic indicators -
Advanced stage - hemoperitoneum or splenic rupture.
Stage I tumors - MST >2yrs survival with sx alone, stage II & III - 6-10mths with sx alone.
Some forms of cutaneous/ subcutaneous HSA appear to have a lower metastatic potential and less aggressive biologic behavior.

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26
Q

Tigilanol tiglate (Stelfonta) - MOA and indications?

A

Intra-lesional injection for non-metastatic canine MCT.
Reported 75% with single injection, 87% with >1 injection.
Indications:
Non-metastatic subcutaneous mast cell tumors located at or distal to the elbow or the hock in dogs
Non-metastatic cutaneous mast cell tumors located all over the body
Tumors must be less than or equal to 10 cm3 in volume, and must be accessible to intratumoral injection
Do not exceed 5 mL per dog, regardless of tumor volume or body weight
The minimum dose of STELFONTA is 0.1 mL, regardless of tumor

Day 1: acute inflammatory response with swelling and erythema noted on the tumor margins and surrounding tissues.
Day 2: necrotic destruction –> blackening, shrinkage and thick discharge

See JVIM 2021 papers:
1) Jones et al. Recurrence-free interval 12 months after local treatment of mast cell tumors in dogs using intratumoral injection of tigilanol tiglate.
2) De Ridder et al. Randomized controlled clinical study evaluating the efficacy and safety of intratumoral treatment of canine mast cell tumors with tigilanol tiglate (EBC-46).
3) Reddell et al. Wound formation, wound size, and progression of wound healing after intratumoral treatment of mast cell tumors in dogs with tigilanol tiglate.

27
Q

Bisphosphonates - MOA and indications?

A

Example drugs - pamidronate, zolendronate.
MOA: synthetic analogs of naturally occurring inorganic pyrophosphate compounds whose therapeutic effect inhibits osteoclasts, reducing pathologic bone resorption without inhibiting bone mineralization. Bind to hydroxyapatite particles in bone and are subsequently released and endocytosed during osteoclastic-mediated resorption, resulting in apoptosis of osteoclasts and inhibition of bone resorption.
Indications - hypercalcemia of malignancy, reduction of skeletal events in the management of bony metastases (humans)
Adverse effects - nephrotoxicity (4.5% for zolendronate in dogs in 1 study)

28
Q

L-asparaginase - differences between native and pergylated (PEG) form?
Indications & disadvantages?

A

PEG L-aspar - prolonged circulation time –> requires less frequent administration. Pergylation also reduces immunogenicity of the enzyme
Rapid acting
Antibody development occurs quickly to enzyme, often after 1 injection - so limited efficacy with multiple injections

29
Q

Modified Adam staging system for nasal tumors in dogs and cats?

A

Stage I - confined to 1 nasal passage, paranasal, and frontal sinus, no bone involvement.
Stage II - any bone involvement with no evidence of involvement of orbit, SQ/submucosal tissue.
Stage III - any involvement of the orbit and/or nasopharyngeal and/or SQ/submucosal tissues.
Stage IV - involvement of the cribriform plate/invasion of the brain

30
Q

Doxorubicin adverse effects and MOA? Cats vs dogs?

A

1) Nephrotoxicity (cats)
2) Cardiotoxicity (dogs?): arrhythmias, DCM? Occurs via myocyte injury from generation of free radicals, which incorporate iron. Histo - loss of myofibrils, sarcoplasmic vacuolar degeneration, and decreasing number of myocytes.
3) Hypersensitivity
4) Extravasation injury

31
Q

Methotrexate MOA, indications?

A

MOA: antifolate drug –> inhibits dihydrofolate reductase (DHFR) = key enzyme in folate synthesis. Folate is needed for production & maintenance of new cells, DNA replication (methyl donor for formation of thymidylate), RNA synthesis. Drug effects - folate accumulation in inactive form - depletes reduced folate substrates.
SE: rapidly proliferating cells most susceptible - neoplastic cells, BM, GI epithelium. Low doses - GI epithelial necrosis, myelosuppression. High doses - hepatocellular tox, nephrotox, CNS damage.
70% renal excretion.
Indications: OSA & LSA most common.
Tx for MTX tox (humans): leucovorin (folinic acid) = reduced active form of folate. Competes with MTX. Used as rescue therapy in high dose MTX therapy.

32
Q

Which LNs can an oral melanoma or SCC metastasize to?

A

Mandibular, retropharyngeal. Can also go to contralateral LN.

33
Q

What is the typical phenotype of CLL in cats?

A

CD4+ (T helper)

34
Q

What is an example of a drug that could theoretically increase the risk of toxicity of some chemotherapeutics?

A

P-glycoprotein inhibiting medications can induce a risk similar to ABCB1 (MDR-1) mutants. E.g. ketoconazole, cyclosporine. Both drugs also inhibit cytochrome p450 metabolism —> thus can also increase vinblastine toxicity.

35
Q

Protocols for which neoplasms may feature carboplatin?
What is its side effect profile?

A

OSA, UCC, AGASACA, Melanoma. Carcinomas in general.
Can be given intra-cavitary.
Platinum, like cisplatin - but not nephrotoxic and doesn’t cause fatal pulmonary oedema (cisplatin - ‘splat’ cats).

SE: GI, myelosuppression (14-28 days in).
Suggest dose adjustment for cats with renal disease, as renal excretion of drug means with reduced GFR > increased risk of myelosuppression.

36
Q

Tx for doxorubicin extra-vasation?
What is a cat-specific doxorubicin adverse effect?

A

Dexrazoxane.
Nephrotoxicity.

37
Q

Cell surface receptors associated with malignant histiocytiosis?

A

CD11c & CD18

Haemophagocytic: CD11d, CD18

38
Q

Cell surface markers for:
- T cell
- B cell
- Haematopoietic stem cells

A
  • CD3, CD5; subtypes CD4 (T helper) & CD8 (cytotoxic T cell)
  • CD21, CD22, CD 25 (if activated)
  • CD34
39
Q

Cytarabine
- MOA
- Indications
- AE

A

Converted intracellularly to aracytidine triphosphate —> competes with deoxycytidine triphosphate to inhibit DNA polymerase —> inhibits DNA synthesis. S-phase specific - blocks cell progress from G1 to S phase.
Drug is incorporated into DNA.

Adjunct tx for:
- Lymphoreticular neoplasia (especially CNS lymphoma) - as rescue agent (poorly effective as single agent, limited data on efficacy as multi agent).
- Myeloproliferative disease (leukemia)
- MUO (dogs/cats) - combo with GCS

AE
- Hematologic - neutropenia (35%), thrombocytopenia (12%) most common. Myelosuppression worse with IV vs SQ.
- GI signs (including oral ulceration), neurotoxicity, hepatotoxicity (increased ALT in 15%), lethargy, pyrexia
- Alopecia, delayed hair regrowth, calcinosis cutis at injection sites reported
- Infiltrative lung disease (case report) following CRI
NB: drug resistance can develop (several mechanisms)

40
Q

Which chemo drugs are contraindicated in MDR 1 (ABCB1) mutant dogs? What aspect of the drug PK is implicated?

A

Vincristine, Vinblastine, Doxorubicin, Paclitaxel.
Reduced biliary excretion so increased risk of SE.
Rare report of neurotoxicity (vincristine).

41
Q

Vinca alkaloids
- Which drugs
- MOA (part of cell cycle affected)

A
  • Vincristine, vinblastine, vinorelbine
  • Inhibit microtubule assembly - so inhibit M phase.
42
Q

Cyclophosphamide
- Drug class
- SE
- Contraindications

A

Alkylating agent

SE:
- Sterile hemorrhagic cystitis (acrolein metabolite) - dogs not cats
- Myelosuppression
-GI upset

Contraindications:
- Caution with hepatic or renal impairment
- Caution in TCC breeds (Scottish terrier)

43
Q

Melphalan
- Drug class
- MOA
- SE

A

Alkylating agent
Effects DNA and RNA - so affects resting cells. Does not require hepatic activation, excreted in the urine unchanged.

SE
- Myelosuppression - onset & recovery from leukopenia can be delayed
- GI signs
- Pulmonary infiltrates/fibrosis.
- Neurotoxicity
- Skin HS (reported in people), dogs - minor hair coat changes (shaggy, lack lustre coat). Breeds with continuous growing hair coats (Poodles etc) more likely to have significant alopecia
- Secondary malignancies (reported in people)

44
Q

Lomustine
- Drug class
- MOA
- AE
- Contraindications

A

Alkylating agent
Non-cell cycle phase specific
Crosses BBB - good for CNS neoplasia.

SE
Myelosuppression (nadir @1-3 weeks)
Hepatotoxicity (LE increase in 29% dogs, 6% clinical) - prophylactic SAME (hepatoadvanced) proven to reduce risk of this
GI upset
Pulmonary infiltrates
Nephrotoxicity

45
Q

What stain can be used to differentiate canine osteosarcoma from others?

A

ALKP stain
100% Sn & 89% Sp.
Caution - reactive bone can stain similar, read cyto first

46
Q

What biochemical/metabolic derangements are noted with tumor lysis syndrome? Which tumors are risk factors for this?

A
  • Acute lysis of tumour cells following chemotherapy. Release of intracellular products & metabolites&raquo_space; hyperK, hyperphos (+ 2’ hypoCa), hyperuricemia (from nucleic acids)
  • Most common tumors: hematologic malignancies (ALL, lymphoblastic leukemia, acute myeloid leukemia, lymphoma), also other bulky or rapidly growing tumors
47
Q

What paraneoplastic manifestations can occur with testicular neoplasia?

A

Oestrogen production (also progesterone, corticosteroids)
Most commonly seen with Sertoli cell tumors (70% intraabdominal testes, less in scrotal & inguinal testes), rare with seminomas & Leydig cell tumors. Related to excessive E2 production.
**- Feminization syndrome **
- BM hypoplasia with myelosuppression > thrombocytopenia, anemia >, granulocytopenia), hemorrhage)
- Symmetrical and squamous metaplasia of the prostate resulting in cystic benign prostatic hyperplasia
- Gynecomastia and galactorrhea
- Attractiveness to other males
- Atrophy of non-neoplastic testicle due to negative feedback of E2 on HP axis etc.

48
Q

What % of dogs with splenic HSA have right atrial involvement?

A

Up to 25%

49
Q

What are potential benefits for hypofractionated external beam RT in canine HSA?

A
  • Palliation for non-resectable SQ or IM HSA - high response rate but not necessarily increase survival.
  • Cardiac HSA - reduce frequency of tamponade
50
Q

Which 3 angiogenic factors were found to be increased in blood & effusions of HSA dogs, with overexpression of receptors in tumor tissues?

A

VCNA review
VEGF, PDGF & endothelin-1

51
Q

What is collagen XXVII peptide? What is its diagnostic & prognostic utility for canine HSA?

A

Mullin VCNA 2019 review
Protein breakdown product, related to invasive & angiogenic processes.
Higher serum [ ] in HSA dogs esp with large metastatic burdens.
Also decreased levels after sx resection, and subsequent increases with tumor recurrence.

52
Q

For the following treatments, what is the drug MOA & outcome when used in dogs with HSA?
1. Thalidomide
2. Ifosfamide

A
53
Q

What paraneoplastic signs occur in dogs with thymoma and how often?
What flow cytometry findings are encountered with neoplastic thymic lymphocytes?

A

2/3 cases.
- MG 40%, megaO & aspiration pneumonia 40%
- Exfoliative dermatitis, erythema multiforme
- HyperCa
- T-cell lymphocytosis
- Anemia
- Polymyositis

Thymic lymphocytes are CD4+CD8+ (T cells). Vs peripheral Lc (<2% CD4+CD8+)

54
Q

Which of the following are positive prognostic factors with thymoma in dogs & cats?
- Age
- Tumor invasiveness
- Significant lymphocytic infiltrate
- Mitotic index
- Cystic thymomas (cats)

A

Only cystic thymomas in cats & significant lymphocytic infiltrate.

55
Q

What infectious organism has been reported with canine transmissible veneral tumor (TVT) cells?

A

Leishmania spp.

56
Q

What markers may be useful to differentiate HSA from other neoplasms?

A
  • FVIII/vWF - differentiate from lymphangiosarcoma
  • CD34 - haematopoietic stem cell marker. Some evidence that HSA may arise from these cells.
57
Q

What markers may be useful to diagnose histiocytic sarcoma?

A

CD204 - macrophages (macrophage scavenger receptor)
CD11c - dendritic cells - HS (vs histiocytoma Ecad+)
CD11d - splenic red pulp Mp - hemophagocytic HS
CD18 - leukocyte adhesion molecule, binds to CD11. Incr expression in Mp & granulocytes

58
Q

Which breed is overrepresented with periarticular HS?

A

Flat coated retrievers

59
Q

How may bisphosphonates be useful in the treatment of histiocytic sarcoma in dogs?

A

E.g. liposomal clodronate - ability to deplete macrophages & potential to increase effectiveness of cytotoxic chemotherapy (increase cell uptake of drug). Induce apoptosis in HS cell lines.

Zoledronate - significantly increases doxo uptake by malignant histiocytic cells & significantly increased cell killing in-vitro

60
Q

What are mechanisms of hypoglycemia as a paraneoplastic syndrome, and commonly associated tumors?

A
  • Excessive insulin pdtn (insulinomas), IGF-I & II, somatomedins (extra-pancreatic tumours)
  • Expression of insulin receptors or glucose utilisation by neoplastic cells
  • Decreased hepatic glycogenolysis and/or gluconeogenesis
  • Binding of insulin by M proteins (multiple myeloma)
61
Q

Treatment options for insulinoma?

A

Surgical excision (partial pancreatectomy) - complications DM, pancreatitis, hypoglycemia (atrophied normal beta cells)

Medical management
- Frequent feeds, complex CHO & fibre, high fat
- Glucocorticoids (incr hepatic gluconeogenesis & glycogenolysis, stimulate glucagon, inhibit insulin pdtn > inhibit tissue glucose uptake)
- Diazoxide (benzothiadiazide diuretic; inhibits insulin secretion & glucose utilization by peripheral tissues, stimulates hepatic gluconeogenesis & glycogenolysis; inhibits closure of ATP-dependent K+ channels in pancreatic beta cells > inhibits opening of voltage-gated Ca2+ channels, Ca2+ influx > decr exocytosis of insulin vesicles)
70% response rate.
- Octreotide (somatostatin analogue) - inhibits insulin, glucagon, GH
- Streptozotocin (cytotoxic tx): selective destruction of pancreatic B-cells, only taken up by GLUT-2 & not other transporters.

62
Q

Clinical response of dogs with multicentric LSA to conventional CHOP chemotherapy?

How does the clinical response & remission time for a reinduction protocol compare with that of an induction CHOP protocol in these dogs?

A

80-95% remission, MST 10-12 months; 20-25% dogs alive at 2 years.

Similar clinical response but 50% remission time with re-induction

63
Q

Negative prognostic factors for canine LSA?

A

Substage b (CSx at presentation)
HyperCa, mediastinal lymphadenopathy - likely reflect T-cell LSA
Significant BM infiltration

ACVIM Specialty Exam (Condensed) (20 decks)

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