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Stacy Santoro Binstock DVM, DACVIM (Oncology)
Cancer in General Practice

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Language of cancer
- Benign/malignant
- Grade
- How abnormal are the cells
- Measure of aggressive behavior
- Stage
- Has it spread?
- TNM
- Metastasis
- Regional
- Distant

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What is cancer?
-Abnormal cell growth
-Benign vs. malignant
-Benign tumors more closely resemble normal tissue
-Sometimes orderly progression
-Benign -->premalignant -->malignant
-Invades into surrounding tissue
-Potential to spread

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Cancer
- Genetically unstable
- Mutant cells
- BRCA – tumor suppressor gene
- Clonal populations
- Sometimes differ within a tumor
- More aggressive, difficult to treat
- Autonomous

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How does it spread?
- Normal conditions
- Cell to cell recognition, physical barriers
- Cancer
- Breakdown of protective barriers like the extracellular matrix
- Invasion and metastasis

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How does it spread?
- Normal conditions
- Cell to cell recognition, physical barriers
- Cancer
- Breakdown of protective barriers like the extracellular matrix
- Invasion and metastasis

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How does cancer spread?
- Lymphatics
- Regional LNS
- Carcinomas
- Blood
- Distant organs
- Sarcomas
- Does not correlate with size
- Anal gland adenocarcinoma
- Inefficient process

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Metastasis
- Seed & Soil hypothesis
- Cancer: seeds
- Specific organ microenvironment: soil
- Adhesion molecules, endothelium, dynamics of blood flow, chemokines
- Organ preference
- Mesenteric circulation of bowels to liver (colon)
- OSA from bone to lungs
- Estimated that <1% tumor cells results in metastasis
- Inefficient process

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a In situ cancer
b Invasion of the tumour border
c Lymphatic spread
d Intravasion of the circulatory system Survival, transport
e Arrest Extravasion
f Solitary dormant cells Occult micrometastases
g Progressive colonization Angiogenesis
Nature Reviews | Cancer

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What causes cancer?
- Genetic instability
- Age
- Specific genetic mutations
- Dark coated dogs and nail bed SCC
- Golden Retrievers and LSA, HSA
- Bernese Mt Dogs and histiocytic disease
- Viruses
- FeLV
- Environmental
- Random

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What are the symptoms of cancer?
- Signs & symptoms
- Lump
- Especially if recent/rapid change
- Acute lethargy
- Weight loss
- Anorexia/V/D
- Depends on location

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Now that?
-Clinical assessment
-Breed, age
-Recent change
-Bleeding/bruised
-Size
-Record in medical record
-Location
-Feel regional lymph nodes
-Other symptoms
-Diagnostics
-Blood work
-Cytology
-Primary mass
-Draining lymph node
-Even if feels normal
-Imaging
-Thoracic radiographs
-Ultrasound

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Cytology
- Simple
- Inexpensive
- Fast
- Non-invasive
- Treatment planning
- Especially for mast cell tumors, STS

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How to get a good sample

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- Various needle gauge, length
- If bloody - smaller gauge (259)
- If large - longer needle (1 1/2"")
- Syringe
- 6 cc
- Clean slides
- Check your sample - make sure it's cellular
- Send it out
- Different stains
- Especially if worried about MCT

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Diff Quick
Wright stain

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How to look at cytology
- Low -> medium -> high power (oil)
- Use low/medium power to scan and find a good spot
- High power/oil for the details
- Criteria of malignancy

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Cellular sample
Inflammatory
(neutrophils, macrophages, eosinophils)
Looks for organisms
Non-inflammatory
Round Epithelial Mesenchymal
Criteria of malignancy
Anisocytosis/karyosis, multinucleated cells, multiple nucleoli, mitotic figures, N:C ratio, etc

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Cytology samples

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Patient Name
Last Name
Date
Canine body map
Date
Size
Description/Appearance
www.DrSueCancer Vet.com
CANCER VET

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Histopathology
- How to interpret
- Read the details
- Margins - is it only 1 mm?
- Mitotic index
- Lymphatic/vascular invasion
- Comments
- Rely on your clinical judgment
- If it doesn't make sense, call the pathologist!
- EX: histologically low grade, biologically high grade FSA in dogs
- Use special stains if necessary
- Weeks for results
- $$$

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Microscopic Description: Mammary gland mass (left groin region): This sample is compatible with mammary gland that contains a multilobular neoplastic mass with a regional lymph node. There is a non encapsulated mass characterized by proliferation of columnar, cuboidal to polygonal cells with differentiation to mammary ducts, tubules and acini. Individual cells show moderate eosinophilic cytoplasm with centrally to basally located vesicular ovoid nuclei with one or two nucleoli. There is moderate nuclear and cellular pleomorphism and increased mitotic activity (20 mitosis per 10 hpf/mitotic index). Tumor cell necrosis and fibrosis are also evident. The tumor cells are also evident in the lumina of some lymphatics and in the parenchyma of the surrounding lymph node.
Microscopic Findings: Mammary gland mass (left groin region): Mammary adenocarcinoma with lymphatic invasion and metastasis to regional lymph node.

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SOURCE: Kidney
DESCRIPTION/MICROSCOPIC FINDINGS/COMMENTS:
MICROSCOPIC DESCRIPTION
Effacing the outer cortex is a interstitial mass that percolates around pre-existing tubules and glomeruli. It is composed of round cells with fairly ample, frothy cytoplasm. These cells have distinct, polygonal borders and large, round nuclei with vesicular chromatin and 1-2 large nucleoli. There is marked anisokaryosis. Mitoses average 7 per high power field. The neoplastic infiltrate is associated with cortical infarcts. Angioinvasion cannot be found. The neoplasm appears totally excised on the renal capsular margins.
MICROSCOPIC FINDINGS: PROBABLE ROUND CELL MALIGNANCY WITH CORTICAL INFARCTS - KIDNEY
COMMENTS: This most closely resembles a pleomorphic round cell tumor. Given the mitotic index, I suspect that these cells are neoplastic lymphocytes, despite the abundant cytoplasm and degree of pleomorphism (renal lymphoma). Secondary differentials include histiocytic sarcoma, clear cell carcinoma, pleomorphic oncocytoma and rhabdomyosarcoma. I have requested in house PAS and Alcian blue stains to rule out chromophobe carcinoma and pleomorphic oncocytoma. I also recommend lymphoid and round cell immunohistochemical stains ( CD20, CD3 and CD18 on BLOCK 1). If these immunohistochemical stains are desired, please contact the lab. An addendum will follow.
REFERENCES:

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Chemotherapy
CHEMOTHERAPY IS A SYSTEMIC THERAPY
meaning that the drugs travel in the bloodstream throughout the entire body

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Intent of chemo
- Chemo sensitive tumor
- LSA, TVT, myeloma
- Micrometastasis
- OSA
- Local recurrrence
- VAS, MCT
- Downstage
- MCT
- Palliation
- TCC, metastatic disease

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Dosing chemo
- Based on body surface area
- Calculated based on kg body weight
- Potential for error
- Not in animals < 10-15 lbs
- mg/kg
- Maximal tolerated dose

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Handling & giving chemo

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How is it different in dogs/cats?
- Dose
- Intensity
- Combinations
- Duration
- Translates to better tolerance in pets
- 10-20% mild side effect
- 5% severe
- <1% chance of death

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Chemo drugs
- Like antibiotics, some are stronger
- Doxorubicin
- CCNU (lomustine)
- Know what drugs cause specific side effects
- Cytoxan
- Sterile hemorrhagic cystitis
- Doxorubicin
- Cardiotoxic
- CCNU
- Hepatotoxic
Lomustine Capsules 100 mg per capsule
Lomustine Capsules 40 mg per capsule
Lomustine Capsules 10 mg per capsule

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Types of chemo
- MTD/conventional
- Metronomic
- Targeted

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Conventional/MTD chemo
- Target dividing cells
- Interferes with progression through cell cycle
- Non specific
- Allow for recovery of normal cells
- Higher dose, less often
- EX: carboplatin for OSA

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Metronomic chemo
- Low dose daily chemotherapy
- Oral
- Not liquid
- Cyclophosphamide
- incidence of sterile hemorrhagic cystitis
- Chlorambucil
- NSAID
- How does it work?
- Antiangiogenic
- Inhibits Treg
- Treo - prevents autoimmunity and immune response to cancer

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Small avascular tumor
tumor
Blood vessels
Large, highly vascularized tumor
Growth factors

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Why choose metronomic?
- Well tolerated
- Inexpensive
- Used to maintain current condition
- Best used in microscopic setting or non-clinical cancer
- Soft tissue sarcoma
- Delays local tumor recurrence in incompletely resected STS
- Hemangiosarcoma
- May prolong outcome after MTD chemo
- TCC
- Maintain stable disease
- PFI 119 days
- MST 221 d

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Targeted therapy - Palladia
- Tumor types
- Mast cell tumors
- Carcinomas
- Inhibits c-kit
- Best for tumors that have a kit mutation
- Run the test at MSU!
- Oral
- $$ for large dogs

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Handling a pet on chemo
- True level of risk unknown
- Handle with caution 48-72 hours
- Some drugs up to 7 days or longer
- Wear gloves
- Double bag
- Avoid high pressure sprays
- Use disposable towels
- Blot dry
- Hand washing
- Elimination in a low traffic area

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Chemo in GP
- Be safe & prepared
- New safety regulations to consider
- USP 800
- PPE
- Closed system device
- Spill kits
- Monitoring
- Separate area for handling hazardous drugs
- Oral chemotherapy

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Radiation therapy
- Local treatment
- Used to treat residual disease when more surgery is not possible
- Tumor types
- Mast cell tumors
- STS
- Melanoma
- VAS
- Brain
- OSA
- Requires anesthesia
- Multiple visits (15-20 if definitive)
- Cost

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How to approach treatment
- Identify goals of owners
- Palliative
- ""Curative""
- How do owners decide?
- Cost
- Emotional connection with pet
- Ease of treatment/feasablilty
- Lifestyle
- Past experience
_ Humans or animals
- Life events
- Birth, death, illness, new job, moving, etc

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Things to consider...
- Growing population of senior pets
- Strongest pet-owner relationship/bond
- Neoplasia most common cause of death in dogs >1-2 years
- Estimated 1 in 4 dogs die of cancer
- Unified health care team
- DVM and staff / pet owner / specialist(s)
- Patient's QOL
- Client's situation
- Emotional, financial, past experiences, etc.

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Living with cancer
- Quality of life
- Symptom management
- Anorexia
- Pain
- Consider alternative options
- Acupuncture, herbal medications, supplements
- Guide the owner when concerns are present