Oncology Flashcards
When preparing, administering, or disposing of chemotherapeutics, or when cleaning up waste from patients that have received chemo, what PPE is recommended?
- Chemotherapy rated double gloving
- Long sleeved, coated impermeable gowns with back closure
- Eye/face shield
- Shoe and hair coverings to maintain sterility (if needed)
- Respirator if there is potential for aerosolization
Animals receiving chemo at home should not be allowed to urinate/defecate in community areas, areas where children may be exposed, or areas that are difficult to clean for how many hours after administration?
48 hours
What is the mechanism of action of alkylating agents?
- Bind to DNA strands and insert an alkyl group, which creates cross links in DNA => strand breaks
- Act in all phases of the cell cycle
Name 5 alkylating agents
- Cyclophosphamide
- Chlorambucil
- Melphalan
- Lomustine (CCNU)
- Mustargen
- Procarbazine
- Dacarbazine
What is the mechanism of action of mitotic inhibitors? Name 3
- Inhibit the assembly (vinca alkaloids) or disassembly (paclitaxel) of the mitotic spindle - arrest cell division in metaphase
- Vincristine, vinblastine, vinorelbine
What is the mechanism of action of platinum compounds? Name 2
- Create cross links in DNA (like alkylating agents)
- Cisplatin, carboplatin
Why is cisplatin fatal when given to cats?
Causes pulmonary edema
What is metronomic chemotherapy?
Uses small doses of chemotherapy drugs frequently (daily or EOD) rather than conventional chemotherapy, which uses maximum tolerated doses at intervals of weeks
What is the mechanism of action of metronomic chemotherapy?
- Anti-angiogenic (targets tumor endothelial cells)
- Immunomodulatory (inhibits Tregs)
- NOT cytotoxic, like conventional chemo
After giving chemotherapy, the patient’s neutrophil count should be checked at the expected nadir or before the next dose of myelosuppressive chemotherapy. If the neutrophil count is <1,000, what should be done?
Patient is afebrile, healthy
- Consider prophylactic antibiotics at home
- Reduce future dose by 25%
Patient is febrile or sick
- Hospitalize for IV antibiotics, fluids - treat for sepsis
If the neutrophil count is 1,000-3,000, what should be done?
Delay scheduled chemotherapy until the neutrophil count is >3,000. Recheck CBC in 3-7 days
One common mechanism of tumor resistance to chemotherapy is the P-glycoprotein transmembrane pump, which can efflux chemo out of the tumor cells. What chemo drugs are NOT substrates for this pump and will still be effective?
Alkylating agents - mainstay of treatment for patients with this type of resistance
What oral chemotherapy drug is used for the treatment of multiple myeloma?
Melphalan
If vincristine is given outside of the vein, what should be done?
Dilute and WARM compress
What is the mechanism of action of doxorubicin and mitoxantrone?
Inhibit topoisomerase II => inhibition of DNA synthesis
S phase specific
If doxorubicin is given outside of the vein, what should be done?
COLD compress
What chemotherapeutic can cause a red color in the urine up to 2 days post-administration?
Doxorubicin
What chemotherapy drug can cause anaphylaxis within 30 minutes of administration and the patient should be pretreated with dexamethasone and/or Benadryl?
L-asparaginase
Name 3 chemotherapeutics that cross the blood brain barrier
CCNU, procarbazine, cytarabine
What drug can be given to reduce cardiotoxicty from doxorubicin? How does it work?
Dexrazocane (Zinecard)
What is the mechanism of action of L-asparaginase?
Catalyzes the conversion of L-asparagine to aspartic acid and ammonia. This deprives myeloproiferative cells of circulating asparagine because they cannot synthesize it on their own, which leads to cell death
What detoxification system is upregulated by many cancer cells to remove chemotherapeutic drugs?
Glutathione system
What is multidrug resistance-related protein?
Protein that excretes detoxified products of the glutathione system - unregulated in some cancer cells
What cell type expresses CD1?
Antigen presenting cells - useful for diagnosing histioproliferative disorders
Describe the staging system for lymphoma
- Stage 1: single LN
- Stage 2: multiple LNs in a regional area
- Stage 3: generalized LN involvement
- Stage 4: Liver and/or spleen involvement (with OR without LN involvement)
- Stage 5: bone marrow or blood involvement and/or any non-lymphoid organ (with OR without any of the other stages)
Substage a: no clinical signs
Substage b: clinical signs
Describe acute radiation toxicity. What types of tissue are most affected?
- Affects rapidly proliferating tissues (skin, mucous membranes)
- Generally reversible changes that occur during or shortly after therapy
- Increase with dose, dose rate, and dose per fraction
Describe late radiation toxicity
- Affects tissues that have limited to no renewing capabilities (bone, nerve, muscle)
- Occurs 3-6 months after radiation
- Severity dependent on dose per fraction
- Progressive and irreversible changes
What radiation protocols are more likely to cause acute toxicity? Late toxicity?
Acute toxicity - definitive intent protocols
Late toxicity - palliative intent protocols
What is the typical schedule and dosing for definitive intent radiation?
- Large number of fractions with a low dose/fraction
- Goal is to achieve long term control while limiting late toxicity
What is the typical schedule and dosing for palliative intent radiation?
- Fewer number of fractions, but a high dose per fraction
- Intent is to improve QOL (improve function, decrease pain/bleeding)
In a study of malignant solid tumors treated with palliative intent radiation, what tumor types had the best overall response rate? What was the overall response rate?
- Sarcoma (87%), primary bone tumors (85%), melanoma (73%)
- Overall response rate 75%
In a study of malignant solid tumors treated with palliative intent radiation, what was the MST? What factors influenced MST?
134 days - did not vary with tumor location, but dogs that had a positive clinical response or maintained stable disease after radiation had longer MSTs
In a study of malignant solid tumors treated with palliative intent radiation, what percent of dogs developed acute toxicity? Late toxicity?
- Acute - 55% (dermatitis, alopecia, mucositis most common)
- Chronic - 12% in dogs that lived at least 3 months - neuropathy, blindness, laryngeal paralysis, etc
What is thought to cause feline injection site sarcomas?
Pathogenesis not fully known, but it is thought that local irritation (especially from adjuvants) stimulates fibroblasts - chronic inflammation leads to malignant transformation
What vaccines are more at risk of inducing feline injection site sarcomas?
Adjuvanted, killed vaccines (rabies, FeLV), although any vaccine and injections of long acting drugs (glucocorticoids, etc) can
What temperature of vaccine is more likely to induce feline injection site sarcomas?
Cold vaccines - bring to room temperature for 15 minutes before injection
What are the most common presenting characteristics of dogs with B cell CLL?
Peripheral lymphadenopathy or splenomegaly (50%)
Anemia (26%)
English bulldogs are at increased risk of B cell CLL and have a unique presentation. What is it?
- Younger (6 yrs vs 11 yrs)
- Lower class II MHC and CD25
Over 50% of gliomas occur in what dog breeds?
Brachycephalics
What are the diagnostic criteria for B cell CLL?
- Usually >5000 to 6000 lymphocytes/uL in the blood
- B cell expansion by immunophenotyping
- Small cell morphology
What dog breed has a shorter survival time with B cell CLL than other breeds? Why?
Boxers - BCLL in these dogs preferentially rearrange unmated immunoglobulin heavy variable region genes - poorer outcome in people
What are negative prognostic indicators in B cell CLL cases?
- Ki67 - greater than 40% of Ki67 expression had a shorter MST (173 days vs not reached)
- High lymphocyte count: >60,000 lymphocytes
- Clinical signs at presentation
Describe the staging scheme for canine splenic hemangiosarcoma
- Stage I: <5 cm diameter tumor, no mets
- Stage II: >5cm diameter tumor OR evidence of rupture, +/- regional LN involvement
- Stage III: distant mets
In dogs with stage II splenic hemangiosarcoma, what histologically determined score correlated with survival?
Mitotic index: <11 mitoses/10 hpf did better
Of dogs undergoing splenectomy for nonruptured splenic masses or nodules (no hemoperitoneum), what percent were benign?
70%
Are thoracic radiographs sensitive or specific for heart base masses?
Specific, but not very sensitive
What percent of cats treated for small cell GI lymphoma develop large cell GI lymphoma? When does it occur?
10% - developed large cell 540 days after small cell diagnosis
What clinicopathologic findings were more common in cats with large cell vs small cell GI lymphoma?
Lower hematocrit, albumin, and total protein - cats with small cell lymphoma that develop these signs should be screened for large cell
What was the MST for feline large cell GI lymphoma?
25 days
What subset of dogs with mammary carcinoma benefit from OHE at the time of tumor removal?
Dogs with high peri-surgical serum estradiol concentrations or expression of estrogen receptors on tumor IHC
What dog breed may be more predisposed to pulmonary histiocytic sarcoma?
Miniature schnauzers
What are the clinical findings in dogs with doxorubicin induced cardiotoxicity?
- Decreased systolic function, resembling DCM
- Arrhythmias
What factors were associated with doxorubicin induced cardiotoxicity in the JVIM paper?
- Higher cumulative dose (144 vs 121 mg/m2)
- Higher body weight
- Decreases in fractional shortening after 5 doses
- Development of VPCs
- Boxers
In dogs with previously untreated, peripheral nodal lymphoma treated with prednisone alone, what was the MST? What factors were associated with survival
- 50 days
- Substage (a vs b) and immunophenotype
In dogs with lymphoma, what tumor mutation was associated with decreased survival time?
p53 mutation: 67 days vs 264 days
What sample type yielded the best sensitivity and specificity for PARR in canine lymphoma?
FNA (100% S&S) > FFPE > flow cytometry pellets
Bernese Mountain dogs with what other condition were at increased risk of developing histiocytic sarcoma? What decreased their risk?
- Orthopedic condition = increased risk
- Administration of anti-inflammatory meds = lower risk
Inflammation may be a risk factor?
In dogs with genitourinary carcinoma treated with NSAIDs, mitoxantrone, and RT, what factors influenced survival?
- Shorter survival in dogs with moderate to severe clinical signs
- Shorter in dogs with prostatic involvement
n dogs with genitourinary carcinoma treated with NSAIDs, mitoxantrone, and RT, what percent developed permanent urinary incontinence? When did it develop?
31% - median of 70 days post-irradiation