Exam 7 Flashcards
Introduction to Oncology lecture
Number one cause of death in veterinary patients over 10 years of age
> 50% of dogs
30% of cats
Be familiar with the common causes of cancer in veterinary patients
Causes include
-Genetics
-Environment
-Infectious: retrovirus infection
-Dietary: chronic enteropathic diseases, GI lymphoma
-Hormonal: mammary tumors
-Chronic inflammation/trauma: fibrosarcoma vax associated rabies, FeLV
Heritable cancers
Breeds - Cancer
GS -renal
BM -Histio
ScDeer -Osteo
Gold -Hemangio
Shelties, others - Bladder
-German shepherds: renal cystuadenocarcinoma with nodular dermatofibrosis (RCND)
-Bernese Mtn dog - Histiocytic sarcoma
-Scottish Deerhound - Osteosarcoma
-Golden retrievers - Hemangiosarcoma
-Shelties, Scottish, Westies, Beagles, Yorkers: TCC
-Many breeds: Lymphoma
Environmental factors
What type of cancer risk is increased by
-Tabacco smoke
-Pesticides, herbicides, insecticides,
-Sunlight
-Radiation
- Sunlight
-HSA
-SCC - Tabacco smoke
-Many cancers
-Increased risk for Lymphoma and nasal carcinomas in dogs
-Lymphoma and oral SCC in cats - Pesticides, herbicides, and insecticides
-TCC in dogs - Living environment (urban, waste sites)
-Lymphoma - Radiation
-SCC
-OSA - Asbestos
-Mesothelioma
Know the risk factors for development of Transitional cell carcinoma
Environmental factors
A. 2, 4-D dichlorophenoxyacetic acid pesticides
Know the risk factors for development of Squamous cell carcinoma
- Sunlight
- Radiation
- Environmental: tabacco smoke, pesticides, herbicides, insecticides in cats
Infectious causes for cancer - Lymphoma
Retroviruses
- FeLV/FIV co infection
80 fold increase - FeLV
60 fold increased - FIV
4 fold
Others
-Spirocerca Lupi - esophageal
-Schistosomiasis - bladder
-FeSV (Feline Sarcoma Virus): multifocal sarcoma
-Papillomavirus - herpes, Lymphoma
-Bovine Leukemia virus - Lymphoma
-Marek’s disease - Herpes virus in horses and Lymphoma
Trauma/Chronic Inflammation
May lead to
-Feline Ocular Sarcoma
-Feline Injection site sarcoma: ISS
-IBD especially in cats
Know the risk factors for development of Lymphosarcoma
Know the risk factors for development of Mammary tumors
Sex hormones in females
-Intact females = 7x increased risk (26%)
-Spay before 6 month of age
Understand the basic indications for surgery, radiation therapy, and chemotherapy
Considerations: Tumor stage, tumor type, other factors: owner finances, patient comorbidities, etc
- Local therapies
Surgery
**Main indication is solid localized tumors **
-Best Control
-Except: lymphoproliferative and metastasis
-Can be diagnostic and or therapeutic
Radiation
-Useful for highly responsive large tumors
-Some exceptions
-Usually treat small amounts of residual tumor cells
-Can also be used to reduce pain symptoms
-Limitations: cost, availability, localized lesions
- Systemic therapies
Chemotherapy
-Useful for highly responsive large tumors
-Involves the use of cytotoxic drugs with narrow therapeutic indices to treat primary tumors
-Prevent metastasis
-Palliate tumor-related symptoms
-Can be sole, additive, palliative therapy
-Can be intralesional too
Chemotherapy sensitive tumors
-LSA
-Plasmacytomas
-TVT
Neoadjuvant Chemotherapy
-Using chemotherapy in hopes of “downstaging” tumors
-When surgery not feasible or reduce tumor size prior to surgery
-“test” dose
Alternative therapies
-Photodynamic
-Cryotherapy
-Hyperthermia
-Immunotherapy
Understand the different goals of difinitive vs. palliative therapy
Definitive
-Long-term control
-More expensive
-higher morbidity
Palliative
-Improving quality of life
-Less expensive
-Does not directly equate with improved survival
Medial Survival Time (MST)
-Point where 50% of patients have succumbed due to cancer
Disease-free Interval (DFI)
-From disease resolution to recurrence
Cure
-DFI > 3 years
Understand the terminology involved in response evaluation
Complete Remission/Response
-Disappearance of cancer, patient has normal life expectancy
-Minimum 2 dosing intervals
Partial Remission
-50% or greater decrease in tumor burden and no new disease for a minimum of two dosing intervals
Overall response rate (ORR)
-CR+PR
Stable Disease
-<50% decrease and no more than 25% increase in tumor burden minimum 2 dose intervals
Progressive Disease
-25% increase… new lesions.. in spite of therapy
Lecture - General Therapeutic approaches to the cancer patient
Understand the basic concept of staging and how it applies to cancer patient
What are the two basic staging systems?
How is increasing stage generally a negative prognostic finding?
Ideal staging diagnostic are determined by SIGNALMENT, financial concerns, technology availability/limitations, history, biological behavior of tumor
Two common ways to stage
- TNM (Solid Tumors)
T: tumor size/extent
N: Nodal status
M: distant status
-Combinations results in different cancer stages - WHO I-V (Canine Lymphoma)
I: Single lymph node
II: Regional LNs, Mediastinum, same side of diaphragm
III: Generalized LNs
IV: Liver, spleen, +/- stages I-II
V: anywhere else
Standard Staging Example: Anal Sac Adenocarcinoma
First
-Complete Blood work
Second
-Abdominal Radiographs
Third
-Thoracic Radiographs in combo with ultrasound
~50% of dogs have elevated calcium, negative prognostic finding
Behavior of tumor
Carcinomas - Lymphatic route
-Lungs
-LNs
Sarcoma - Hematogenous route
-Liver
-Lungs
-Rarely LNs
Mast Cell Tumor
-Liver
-Spleen
-Regional LNs
Understand the principles of multi-modality therapy
-Multiple therapies allow increased therapeutic intensity without increased clinical toxicity
-Modalities should have non-overlapping toxicities
-Should have proven efficacy
-Should be given over the shortest time interval practical
Examples
-Canine cutaneous MCT: typically localized, goal curative, sensitive to surgery and radiation
-Treatment: surgical and radiation to remove residual disease
-Canine appendicular Osteosarcoma: surgical typically only local option
-Highly metastatic: chemotherapy improves outcome
-Goal: palliative and curative
-Treatment:
Be able to design a rationale treatment plan when give
1. Goal of therapy
2. Tumor behavior
3. Extent of disease
Localized or systemic?
Curative or palliative?
Sensitivity of tumor to specific modalities? Lymphoma = chemo sensitive, Osteosarcoma = Not radiation sensitive
Financial and technology limitations? Radiation is expensive and limited availability
Lecture - Chemotherapy
What is the major determinant for chemotherapy?
-Most agents are generally cytotoxic
->80% specific agents have been developed
Differential growth fraction responsible for specificity of drugs
-Relative low specificity for tumor cells
Dose limiting toxicity
-Cytopenias
-Neutropenia
-Thrombocytopenia
What is the MDR mutation and what breeds are affected?
MDR protein expressed in hepatocytes
Patients with mutations don’t clear the drug appropriately and develop high toxicity at lower doses
What are the predictable side effects of chemotherapy? What is their timing?
BAG
-Nadir ~7 days for bone marrow
-GI: 3-5 days
-Hair: alopecia 1-2 days
Chemotherapy Toxicity
-Replacement of mature cells: 7-14 days
3-4 grades: not acceptable =/> 50-75%
Unique Toxicity
-Can be schedule and or dosage specific
-Include extravasation events
-Not always reversible
-Not related to how rapidly cells are proliferating
-Can be species specific
Understand the different types of chemotherapy
- MOA
- Basic uses
- Most common standard side effects. What is considered unacceptable
- Unique side effects
MOA
- Cell cycle specific (Cell Cycle Active Drugs)
-Work by impairing normal cell processes
-Often analogues of normal cellular substrates
-Typically Plateau effect
-Time dependent
-More actively cycling tumors are typically more sensitive
**Only a few “true” cycle active drugs in use: Cytosar **
a. Cytostatic
b. Cytotoxic
- Non-cell cycle specific
-Great for supplementing cycle active drugs or slow growing tumors
-Effective against cells in resting phase
-DNA breaking, impairing glucose homeostasis, impairing membrane dynamics, etc.
-Exponential dose-response relationship
-Threshold effect
-Vast majority of drugs in common use
a. Cytostatic
b. Cytotoxic
Understand the mechanisms of resistance to chemotherapy
-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
Anti-cancer drugs - Chemotherapy
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.
Mechanism of cellular damage and Critical determinants of tumor responsiveness to radiation therapy
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
Understand the difference between external beam vs. brachytherapy
How to limit normal tissue toxicity?
-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
Examples of tumors treated with radiation
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
Radiation - Sarcoids Horse & Mast Cell Tumors dogs
-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
Lecture - Surgical Oncology
Tumor Anatomy
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
Surgical intent: curative, palliative, marginal resection, radical resection
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
Surgical Concepts Risks & complications
MCT
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
Soft tissue Sarcoma - Dog
-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
Injection Site Sarcoma
-3-5 cm and 2 fascial planes: 80% cure
-1-3cm and 1 facial plane: 60% cure
-<1cm: 20% cure and RECURRENCE rate 80%
-Consider follow up radiation
<25% metastasis
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
Canine Lymphoma (LSA)
- 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 - Standard locations
-Multicentric = generalized 80-85% of cases
->50% of cases have liver and or splenic involvement
-50-75% healthy presentation - 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
- Treatment options
-Chemotherapy: most common
-Radiation
-General palliative
-CHOP protocol: most common UW-Madison.
-Vincristine, L-asparaginase, Prednisone, Adriamycin, Cyclophosphamide - Prognosis
-Medial survival 12-16 months
-Monitor response to therapy
Canine Osteosarcoma
- 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 - 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 - 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 - Treatment options
-Surgical amputation: forequarter or hemipelvectomy
-Chemotherapy: effective adjuvant ineffective as sole treatment
-Doxorubicin
-Cisplatin
-Carboplatin: most commonly used - Prognosis
-Carboplatin: 40% 1 year survival, 20% 2 year survival
Median DFI 8-9 months
Understand the typical presentation for feline Lymphoma
age: 10 yo
Breed: DSH
Species: feline
Sex: Female, spayed
c/s: anorexia, weight loss, cachexia, ocular changes, neurologic changes
Understand the typical presentation, staging, treatment, and prognosis of canine mammary tumors
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
Understand the typical presentation, staging, treatment, and prognosis for canine and feline mast cell tumors
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
