Exam 7 Flashcards

Question

Understand the mechanisms of resistance to chemotherapy

Answer 1

-Impaired cellular uptake -Intracellular metabolism -Multi-drug resistance (EFFUX PUMPS): P-glycoprotein, Certain breed are born with mutations in this protein = predisposition to toxicity. -Decreased cell death

Answer 2

Anti-microtubule agents -MOA: Cell cycle (M) inhibition by binding to microtubules -Eliminated via hepatic metabolism: **MDR-1 substrates** -IV or IP -Toxicity: perivascular damage outside vein. Hepatic **Vincristine, Vinblastine** Alkylating agents -MOA: Binds to DNA carbon atoms, and halt replication -Oral and IV -Carcinogenic -Immunosuppressive -Toxicity: Bone marrow, Alopecia (Hair), GI. ~ 7 days to enter bone marrow -CYCLOPHOSPHAMIDE: metabolite ACROLEIN = Sterile hemorrhagic cystitis. But, Stem cell sparing -CHLORAMBUCIL & MELPHALAN: Leukeran substitute for cytoxan. **Neurotoxic, platelets and neutrophils toxic** -LOMUSTINE (CNNU or CeeNu) : hepatotoxic, Denamarin may reduce toxicity Anti-tumor antibiotics -IV only -MDR substrate -Hepatic metabolism and urinary excretion **Doxorubicin, Mitoxantrone, Actinomycin-D** -DOXORUBICIN: **Cardiotoxic (dog>human>cat), nephrotoxic - cats, anaphylaxis, vesicant** Platinum agents -Bind, DNS, RNA, protein, lipids -Similar to alkylating agents -Toxicity: BAG, double nadir ~14 days. Can be toxic to nervous tissue -CISPLATIN: IV or intra-lesional. High grade sarcomas, carcinomas. -Toxicity: nephrotoxic, emetogenic, capillary leak syndrome and fatal pulmonary edema in cats. Prepare with diuretic drugs -CARBOPLATIN: safer, ok in cats, renal disease requires dosage modifications Anti-metabolites -Mimic normal cellular metabolites and interfere with DNA, RNA, or protein synthesis. **Not considered carcinogenic** -Oral and IV and topical -Renal and hepatic clearance -5-FU: Large animal tumors, carcinoma in dogs, **neurotoxic in cats** -CYTOSAR: used for GME Ganulomatous meningeoencephalitis -METHOTREXATE -5-FLUOROUCIL -CYSTOSINE ARABINOSIDE (CYTOSTAR) -GEMCITABINE -L-ASPARAGINASE: non-traditional antimetabolite. -Depletion of circulating pools of amino acid asparagine = inhibition of protein synthesis -Works on lymphoid tissue = selectively toxic to lymphocytes. -Use as adjunct drug in lymphoma cats and dogs -Toxicity: Rare anaphylaxis, NO IV, delays hepatic clearance of vincristine. Hypersensitivity, impairs protein production.

Answer 3

Use of beams of energy to kill cancer cells Photons, electrons and others (human med) Secondary charged particles are created, usually electrons. Results A. Direct Action -Radiation -DNA damage -Cell death B. Indirect Action -Free radicals -DNA damage -Cell death The 4 Rs of Radiation Repair of cellular damage Reoxygenation of the tumor Redistribution within cell cycle Repopulation of cells

Answer 4

**Normal tissue is better at repairing than tumor tissue** **Big tumors are resistant because they don't have much oxygen, and they have less actively growing cells** Repair of sublethal injury -Most normal tissues repair in 3 hours to 24 hours -Tumors lack ability to repair or repair slowly Reoxygenation -Hypoxic cells require more radiation to be killed -Large tumors often hypoxic -Tumor shrinkage decreases hypoxic areas Redistribution -Cell cycle position determines sensitivity of cells -G2/M phase is most sensitive bc cell is locked into dividing -Breaking total dosages into smaller fractions allows for redistribution within tumor population Repopulation -Rapidly proliferating tumors regenerate faster Dose-Response Relations -Tumor size -Radiation dose -Tumor histologic type -Small well vascularized, homogenous tumors = favorable response curve -Large, bulky, hypoxic, heterogenous, variable cell number tumors that have stem cells = Unfavorable response curves Fraction Schedules (Gy) -Conventional: 2.0-3.0 5x/week -Total 4-6 weeks -Minimize long term side effects Palliative -4.0-8.0 daily -Lower total dose -Minimize short term side effects, pain

Answer 5

-Photons vs. electrons have dramatically different depth-dose distributions -Modifying type of ionizing particle and its energy you can optimize dosage to tumor and minimal normal tissue dosing -Collimators -Dividing radiation dosage into multiple fields

Answer 6

Acute tissue Reactions -Happen right away -Skin, hair, mucosa, and TUMOR TISSUE -Typically reversible Examples: mucositis, moist desquamation, erythema, etc. Late tissue Reaction -Delayed side effects by weeks or months to years -Bone, lung tumors **Unacceptable side effects is ~5%** Example: non-healing skin wounds, secondary tumor formation -Xerostomia, KCS, fibrosis, soft-tissue necrosis, nerve tissue damage

Answer 7

Cutaneous SCC Orange/White Cats -Low metastatic potential -DFI (disease free interval) 3-9 mts for T3 -DFI 5 years for T1 tumors Nasal Tumors -Adenocarcinoma>SCC>Sarcoma in Dogs -T1>T2>T3 -surgery and chemotherapy have no survival impact -Radiation only modality -MST 8-18 mts Soft Tissue Sarcomas -Most common SQ tumor in dogs/cats -Vaccine related cats>dogs -Large tumors resistant -Control radiation therapy: 70-80% at 3 years low grade dog 50-60% at 3 years high grade dog 50% at 1 year for a cat

Answer 8

-Usually papilla virus -Most common skin/sq tumor in horses -Sensitive to surgery, chemotherapy, and radiation -Radiation usually reserved for peri-ocular and or large tumors Mast Cell Tumors -Most common skin tumor -Locally invasive, < 30% metastatic -Marginal resection curative 60-70% of cases -Radiation therapy useful for extremities, head, neck, urogenital, >90% curative for low grade -Chemotherapy indicated for metastatic, high grade non-resectable tumors

Answer 9

Bening vs. Malignant tumor Growth -Maximum diameter of tumor correlated with prognosis -Friable, discolored -Bulk mass -Benign: grow by expansile/compressive growth -Malign: grow by invasion Pseudocapsule -Solid tumors often surrounded by pseudo capsule, fibrous tissue -Contains benign tumors, but it does not contain neoplastic cells Microscopic Tumor -Tumor extent that can not be visualized but it is known to be present -Typically found within surrounding reactive zone

Answer 10

Biopsy: used to obtain diagnosis, prognostic information, histologic grade -Type: malignant vs bening -Grade FNA: easiest way to obtain sample of mass -Can differentiate between benign and malignant -Significant inflammation can impair differentiation -Gives major tumor category for malignancies -Subcategory for round cell tumors: MCT, Lymphoma, Melanoma, Histiocytic sarcoma. Tru-cut biosy: not common Incisional biopsy: Great for very large tumors in bad locations (limbs, head/face, near anus or genitalia) -Location very important: NOT central (avoid necrosis of large tumors). Within confines of tumor tissue -Poorly planned can lead to neoplastic cells to normal tissue Lumpectomy or excision biopsy -Removes all Gross disease and small barrier of normal tissue, remove pseudo capsule Surgical Biopsy -Gold standard -Bigger the biopsy the more information gained -Use when FNA inconclusive or not possible

Answer 11

Occasionally a tumor-free surgical margin is not attempted -Quality of life -Disfiguring or non-cosmetic -No advantage for treatment -Not compatible with life Curative intent tumor surgery -Achieve tumor-free margin -Not possible if metastatic -Also referred as radical resection -Lateral margin -Deep margin -Always have a plan in case "dirty" margin Marginal Excision/Resection -Benign can be curative -Microscopic disease may remain -Ex: perianal adenoma -Sometimes to avoid curative intent surgery due to cosmetics, metastasis, etc. -Curative may be achieve by adding other modalities, usually radiation Palliative Intent Surgery -When lower than curative -Goal: improve quality of life, improve function, pain relief -Ex: amputation, bleeding tumors, etc. -May delay euthanasia -Debulking: considered a form of palliative surgery. Only indicated if symptoms need palliation. Necrotic, bleeding tumors, CNS, pelvic, neck

Answer 12

MCT, STS, Feline FSA, Mammary tumors High grade: Curative intents > 3cm lateral and 3cm deep, smaller if low grade Low grade curative: >/= 3mm Recurrence 5cm and 2 fascial planes: 80% (only can achieve distal extremities)

Answer 13

Predisposition: Boxer, Boston terriers, Pugs -Surgery treatment of choice -Curative sx 80-100% for low grade if >1cm margin -Aggressive require >3cm -Recurrence dirty margin: 30-40% for low grade

Answer 14

-Fibrosarcoma, Peripheral nerver sheeth tumor PNST, hemangiopericytoma, liposarcoma, myxosarcoma -Recurrence low grade: 30% and >3 years DFI -Curative: >3cm margin -May not need Amputation for SA in distal limb -Radical excision recommended for high grade, can combine with radiation

Answer 15

Anal Sac Tumors -50% malignant have calcium increased -Local resection: 1 year local control -Margins typically dirty -Fecal incontinence is concern -Adjunct therapy, radiation and chemotherapy -Moderate metastasis rate

Answer 16

1. Canine Lymphoma 2. Canine Osteosarcoma 3. Canine Hemangiosarcoma

Answer 17

1. Breed at risk -Middle aged -Healthy dogs -Crocker spaniels, Labs, Goldens, Boxers, Danes, Scotties, etc -No gender predilection -Further presenting c/s clinical stage paraneoplastic syndromes 2. Standard locations -Multicentric = generalized 80-85% of cases ->50% of cases have liver and or splenic involvement -50-75% healthy presentation 3. Staging diagnostics Primary tier -CBC, low grade anemia, thrombocytopenia -Chemistry, ALP elevation Second tier -Thoracic imaging 34% involvement -Abdominal imaging 50% splenic/liver involvement Tertiary -Biopsy -Flow cytometry -Bone marrow analysis -MDR analysis -Diagnosis by clinical history, exam, and cytology. -Round cell tumor, >50% lymphoblasts from nodal sample. Can be difficult if neoplastic cell is small or intermediate lymphocyte, and only a portion of the LN is affected. -Subtype B. or T. -B-cell 68% and easiest to treat 4. Treatment options -Chemotherapy: most common -Radiation -General palliative -CHOP protocol: most common UW-Madison. -Vincristine, L-asparaginase, Prednisone, Adriamycin, Cyclophosphamide 5. Prognosis -Medial survival 12-16 months -Monitor response to therapy

Answer 18

1. Breed at risk -Scottish Deerhound -Irish Wolfhound -Rotweiller -Great Dane -St. Bernard -Middle age to older patients -Giant breeds >75% appendicular skeleton **Bad genes #1 cause** -Previous fracture -Ionizing radiation 2. Standard locations -Away from elbow -Towards the knee -Distal radius, Proximal humerus -Distal femur, Proximal tibia. -Other sites -Rare: mammary gland, soft tissue, mandibular, maxillary, vertebral, ribs, scapula 3. Staging diagnostics -Highly malignant -Hematogenous spread -95% predictably metastatic -<10% of cases cured by surgery -Lungs appear to be the most common metastatic site: chemotherapy alters the pattern -Thoracic radiographs, LN aspirate, Abdominal ultrasound, Nuclear scintigraphy - monostatic or polyostatic 4. Treatment options -Surgical amputation: forequarter or hemipelvectomy -Chemotherapy: effective adjuvant ineffective as sole treatment -Doxorubicin -Cisplatin -Carboplatin: most commonly used 5. Prognosis -Carboplatin: 40% 1 year survival, 20% 2 year survival Median DFI 8-9 months

Answer 19

1. Breed at risk -Golden -GSD -Boxer -Schnauzer -Grey hounds -Labs -BMD -Middle to older pure-bred dogs Etiology -cutaneous, thought to be solar. Inguinal area -Genetic 2. Standard locations -Spleen -Heart -Liver -Kidneys -Metastatic 30-50% of splenic cases 3. Staging diagnostics -Hemorrhagic effusion -Pericardial -Peritoneal -Cavitary masses -Blood work: anemia, thrombocytopenia, SCHISTOCYTOSIS almost always, DIC. -Minimum database -Thoracic radiographs -Pulmonary metastasis 5-10% -Abdominal ultrasound: visceral metastasis 30-50% -Cardiac ultrasound -Troponin I levels 4. Treatment options -Surgical removal if isolated -Chemotherapy: Doxorubicin drug of choice -Alkylating agents: Cytoxan, DTIC, Temozalamine -Rapamyacin -Palladia 5. Prognosis -Cutaneous 6-12 mts -Splenic/liver palliative care/surgery: days-5 weeks -Kidney surgery: 4-6 mts -Splenectomy and chemotherapy 4-11 mts

Answer 20

age: 10 yo Breed: DSH Species: feline Sex: Female, spayed c/s: anorexia, weight loss, cachexia, ocular changes, neurologic changes

Answer 21

Dx: Hit 29.5% Chem: BUN 35 Creat 1.6 USG 1.035 Ultrasound: enlarged kidney Cytology: renal lymphoma, mitotic figure Risk factors -FIV: 5 fold -FIV/FeLV 80 fold -FeLV: 60 fold -Tabacco

Answer 22

-Systemic disease -Doxorubicin -CHOP-type protocols #1 option -CCNU/Prednisolone #2 -Chlorambucil and prednisolone for low grade

Answer 23

-Histologic grade/type: small cell low-grade vs. Large cell high-grade -Anatomic location -Treatment regimen -Response to therapy -NOT phenotype -FeLV status: CD4 T cells challenging to treat

Answer 24

Age: 15 yo Breed: DSH Species: feline Sex: Male, neutered -Vaccine induced mutations -Rabies FeLV vaccines -20-25% metastatic -Rapidly growing tumor c/s: flank mass Next step: cytology FNA Staging -Minimum database -FeLV/FIV FeSV -Thoracic radiographs -CT scan -/+ abdominal ultrasound Treatment -Surgery -3cm 50-70% recurrence rate within 2-3 years -5cm and 2 fascial planes 11% recurrence at >3 years -<1cm 80% recurrence 5-6 mts -1 cm 80% recurrence 12-24 mts Adjuvant Radiation -<1cm 60% recurrence PFS 12 mts -3cm 30% Chemotherapy -Palliative purposes -Doxorubicin -Costly, early detection is critical Pathology reports: Type, margins, grade

Answer 25

Age: 10 yo Breed: Britanny spaniel Sex: F, intact Species: canine c/s: mammary mass, firm, increased RR Intact females: 7 fold increased risk OHE: before 1st heat best 0.05% risk OHE: after second heat 26% OHE later in life does not reduce risk 50% malignant 50% metastatic 15 LNs -PE -Radiographs -FNA -Ultrasound -Cytology Treatment -Surgery: mammectomy, regional mammectomy unilateral or bilateral (uncommon) -No difference in survival radical vs. local Treatment -Doxorubicin -Carboplatin -5-Fluorouracil -Palladia -Paclitaxel Prognosis Stage 0: 0-19% recurrence within 2 years Stage 1: 60% Stage 2: 97% **Overall 48% of dogs die or are euthanized due to disease at 1 year**

Answer 26

Age: History: 2 mts of right axillary mass Rapidly grew 10 cm 50-60% trunk, extremities, 25% head/neck 10% **Can visually look like anything** **Mutations in the c-kit protocols-oncogene 30-50% of cases** c-kit is a transmembrane receptor tyrosine kinase: functions as signal transducer, mutations provide growth advantage for tumor cells Mean age: 9 yo NO gender predilection -Labrador, Weimaraners, Brachiocephalic breeds -Aggressive: young Sharpeis Staging -MDB -Blood work: anemia, increased BUN, peripheral eosinophilia, basophilia mastocytosis, liver enzyme elevation. -FNA of lymph node -Radiographs thoracic to assess draining lymph nodes if front of the limb -Abdominal ultrasound Treatment -Surgery if resectable and no evidence of metastasis -Often Benaryl and Omeprazole prior to surgery -Radiation if incomplete resected and not amenable to curative surgery -Chemotherapy: for high grade, metastatic, too many to resect. Palladia, Presisone, Viblastine Prognostic -Grade I: 83% -Grade II: 44% -Grade III: 6% Low 24 mts, 12 mts PFS High 6 mts, 6 mts PFS

Exam 7 Flashcards

(56 cards)