1. Cancer Care in Pets (Veterinary Oncology)
Orna Kristal, DVM
Dip. American College of Vet Internal Medicine (oncology)
Chavat Daat, Beit Berl

2. Veterinary Specialty Training
Requirements: DVM degree and internship
Began in the US
Today in Europe as well
3 yrs of working under supervision of specialists in different fields
Tumor biology studies
Publication, presentations
Specialty examination

4. Specialty in Veterinary Medicine
Large Animals (horses, ruminants)
Internal medicine, Surgery, reproduction
Small Animals
Internal Medicine, oncology, cardiology, neurology
Surgery
Imaging
Emergency medicine
Ophthalmology, Dermatology, anesthesia
Exotic animals (birds, reptiles, ferrets, rodents)
Pathology – clinical and histopathology
In Israel The Vet school in Beit Dagan qualifies specialists in most areas in the European colleges programs.

5. Cancer in dogs and cats No accurate incidence rates (IR)
Dorn et al – new cancer cases a yr in 2 counties in CA
Dogs – 382/100,000
Cats – 156/100,000
IR today probably much higher
Estimated lifetime risk of cancer
Dogs – 50%
Cats – 30%
IR probably much higher today due to longer life expectancy as a result of better nutrition and improved health care. Also, more advanced diagnostics are being used.
Cancer is therefore the leading cause of death in older animals.

6. Comparative aspects Humans Dogs Cats Breast/prostate Breast* Lymphoid
Lung
Skin
(non-melanoma)
Colorectal
Sarcoma
Testicular (intact)
Lymphoid, oral tumors
Most female dogs are spayed at a young age at least in the US so breast cancer is actually uncommon. In cats similar association exists but only if spayed before one yr of age. Same for testicular cancer and males but not here!
This order of frequency is based on Dorn’s studies and some has probably changed. Lymphoid in cats has probably declined with the control of FeLV. Probably increased in dogs due to environmental contamination.

7. Genetic factors Golden Retriever Boxer Bernese Mountain Dogs
1 in 5 – Hemangiosarcoma
1 in 8 - Lymphoma
Boxer
Lymphoma (T-cell)
Bernese Mountain Dogs
Histiocytic Sarcoma
Scottish Terriers
Transitional Cell Carcinoma
Sharpei
High grade Mast Cell Tumors
Scottish terriers have about 18 times the risk of bladder cancer compared with MB.

8. Hormonal factors Ovariohysterectomy Castration
Before 2.5 yrs of age in dogs and 1 yr in cats is protective of mammary tumors
Castration
Reduces risk of testicular cancer
Esp. in cryptorchids
Increases risk of prostate cancer (still uncommon)
OVH has a stronger effect in dogs and is lost earlier in cats.
Neutering at a young age has been found to increase risk of OSA in male Rottweilers only, and possibly in females with MCT and HSA.

9. Environmental factors - Dogs
Exposure may be higher in indoor pets
Exposure to passive smoke
 risk for lung cancer – short and medium length nose (weak)
 risk for nasal cancer – long-nosed breeds
Insecticides in shampoos or dips  risk of TCC, esp. if obese
But not spot-ons like Frontline or Advantage
Herbicides and insecticides on lawns  risk of TCC in Scottish terriers
Exposure to EF may be higher in pets that spend most or all their time indoors compared with humans who go out often.
No dose response relationship in the ETS respiratory cancer risk study.
In obese animals increased risk - thought is inert lypohilic ingredients accumulate in body fat and may be carcinogenic.
Fipronil and imidacloprid spot-ons did not increase risk.
TCC Scotish – herbicides – mainly phenoxy acids
One study from Italy found that residence near industrial areas and exposure to paints and solvents increased risk OR were 8.5 and 5.5 respectively (Gavazza A, JVIM 2001). Median age of dogs exposed to chemicals was also younger (from 7.5 to 6.1 yrs) which strengthens the relationship.
3) Pastor – French study found Association with waste incinerators, polluted sites and radioactive waste

10. Environmental factors - Cats
Oral Squamous Cell CA (SCC)
 risk with:
High intake of canned food (RR – 3.6) and canned tuna fish (RR – 4.7)
Flea collar use (RR – 5.3)
 risk with flea shampoo use
Lymphoma
 risk with exposure to passive smoking
Oral SCC is a common malignancy in older cats. Subjectively seen more commonly in the US than here. Therapy is relatively ineffective.
Bertone et al looked for carcinogenic substances that the cat may eat or lick from fur while grooming, that can lead to this cancer. Controls was a population of cats with CKD.
Risk of SCC was higher in smoking households but NS.
Significant association with high intake of canned food and canned tuna fish
Increased risk with canned food and tuna may be due to nutritional difference between them and dry food, or it is possible that cats that eat primarily canned food have more tartar buildup and worse oral hygiene that increases the risk for SCC. In humans poor oral hygiene is associated with a 2-fold increase in risk for oral SCC. To counter that, teeth brushing and Hx of dental problems was N.S.
She did not try to explain the canned tuna separately from canned food. Maybe the heavy metals?
Increased risk with collars – close to head? Decreased risk with shampoos – wash off carcinogenic substances?
As for ETS, the connection is not strong, and may or may not exist. Interestingly the same author has shown an increase in risk of LSA in cats exposed to household ETS, with evidence of a strong dose-response relationship. – longer duration and higher quantity increased risk with a linear trend.

11. Why treat pets with cancer?
Cancer is perceived by many to be a serious and often fatal disease
Treatment in people is commonly associated with side effects leading to poor QOL
Therefore treating pets with similar treatment is perceived as cruel and selfish
This perception represents total misunderstanding of the treatment of cancer in animals
The main goal of treating animals with cancer is to extend a good quality of life for the patient (and family) for as long as possible.

12. What is QOL in animals? Life without pain & daily normal activity
Happy when owners come home, plays
Wants to eat and drink
Has control of eliminations
Quality is more important than quantity
Life without QOL means prolonging unnecessary suffering of the animal

13. How do we maintain QOL? We try to prevent treatment’s side effects
Before treatment is begun risk vs. benefit is considered
Often animals treated for cancer live longer and better than animals treated for other chronic disease (i.e - diabetes, chronic renal or heart disease)

14. Maintaining QOL If the animal develops significant treatment toxicity
We can lower drug dosages
Use other drugs
Consider stopping treatment
Treatment can be with a curative intent or palliative
Know when to quit
Treatment with a curative intent is usually more aggressive.
In other cases we and owners choose treatment that is more palliative just to try and slow down the disease and/or improve symptoms.
When treatment is no longer effective or in cases that are too advanced it is our duty to tell the owners it is time to let go.

15. Treatment modalities Treatment options depend on Tumor type
Location in body
Tumor stage (TNM)
Comorbidities

16. Treatment modalities Surgery Radiation therapy (not in Israel)
Chemotherapy
Small molecule inhibitors (TKI’s)
Cancer Vaccines
Melanoma
Multimodality Tx
Symptomatic Tx
Surgery is still the main modality for local tumors. If the tumor can be completely excised and has a low metastatic potential, it is the most likely treatment modality to cause a cure.

17. Choosing the treatment
Owners ultimately choose the treatment after hearing
Different options
Prognosis for each option
Possible side effects
Cost
Should they choose not to treat, they are making an educated decision
Very different from humans
Today I consulted on a dog with advanced MCT. Tumor is huge and disseminated. Owner NI in chemo d/t finance limitations and poor Px. He mainly wanted to know if and when to euthanize and anything palliative he can still do like prednisone.

18. Common signs of cancer in small animals
Abnormal swellings that persist or continue to grow
Sores that do not heal
Weight loss
Loss of appetite
Bleeding or discharge from an opening
Abnormal swellings that persist or continue to grow
Sores that do not heal
Weight loss
Loss of appetitie
Bleeding or discharge from any body opening
Offensive odor
Difficulty eating or swallowing

19. סימנים שכיחים של סרטן בחיות קטנות
Offensive odor
Loss of energy, tire easily
Persistent lameness
Difficulty breathing, chewing, urinating, defecating
Hesitation to exercise or loss of stamina
Persistent lameness or stiffness
Difficulty breathing, urinating, or defecating

20. Aural SCC

21. Baaci
7 yr old spayed female Golden Retriever

22. Baaci
Presented with enlarged lymph nodes, fever, unwell and diagnosed with lymphoma on cytology

23. Baaci
With no treatment median survival is 4-6 weeks and QOL is poor most of this time.
With CHOP based chemotherapy median survival is extended to 12 months and about 25% are 2 yrs.
Drug dosages is lower than in humans. Only 20% develop grade 3-4 toxicity.
Baaci’s owner chose to treat with chemo.

24. Baaci Achieved complete remission Treatment continued for one yr
One episode of vomiting & diarrhea requiring supportive care.
Still alive and happy today > 4 yrs from diagnosis.

25. Chaos 4 yr old female Great Dane Diagnosed with osteosarcoma (OSA)
Distal radius - LFL

26. Osteosarcoma Many similarities to human OSA Two main differences
Affects large to giant breed dogs
Metaphyses of long bones most affected
Most stage negative at presentation
90% are high grade
Common hematogenous lung metastases
Two main differences
10 times more prevalent in dogs
Mean age
Dog – 7rs human – 14 yrs
Heavy people
Rare nodal mets.
ALKP is prognostic in both

27. Osteosarcoma
Dogs
Are an outbred species
Have innate immune system
Their cancer progresses more rapidly
Combined with similarities in tumor behavior they can serve as an excellent model for research of this disease
Dr. Steve Withrow - pioneer in the field
Clinical trials in dogs serve a dual purpose
Cancer progresses more rapidly due to accelerated aging process
Research in dogs showed that in both species ionizing RT and metalic implants can lead to OSA.
Withrow has developed limb sparing technology in dogs, showed IA cisplatin is safe and that pre-op chemo increases percent necrosis in tumor which in turn increases number of limb spare resections. Much of his research was applied to human medicine.
Clinical trials help us improve standard of care for our patients and may also provide valuable data for therapies destined for use in people.

28. Chaos Had forequarter amputation
To control primary tumor and relieve pain
Post-operatively entered into a clinical trial
5 treatments with doxorubicin
Followed by the oral trial drug vs. placebo
No side effects at all
Enjoyed an excellent QOL for 18 months after treatment
Median survival with amputation and chemo is 10 months
Sponsored by Bayer company

30. Slim, 7 yr old male Whippet
Presented with unilateral nose bleed from the left nostril (Sept 2008)
CT and biopsy – left nasal adenocarcinoma
Unilateral nose bleeds in middle age to older long nosed dog – primary DD is nasal tumor.

31. Slim Treated with Radiation
12 X 4 Gy, 3 days a week
Tumor shrunk by 30%, was stable for 2 yrs then started growing very slowly
Receives low dose prednisone permanently for nasal congestion

32. Canine Mast Cell Tumors
Common skin cancer
Can be benign to malignant
May swell up and shrink due to surges of histamine release

33. Mast cell tumors Fairly easy to diagnose by cytology
Biologic behavior highly correlated with histologic grade
Treatment depends on tumor grade and stage

34. Targeted therapy for canine MCT
33% of MCT express mutation in c-kit
Toceranib Phosphate
(Palladia™)
KIT
PDGFRβ
VEGFR2
Flt3
Masitinib Mesylate
(Masivet®)
KIT
PDGFR
FGFR3
FAK (focal adhesion
kinase)
2 dedicated veterinary products that are TKIs
Palladia through inhibition of VEGFR2 and PDGFR inhibits angiogenesis and through KIT has direct inhibition on MCT.
Blocking both R is more effective than blocking either alone.
Potential for efficacy in other tumor types

35. In summary
The main goal in treating animals with cancer is good QOL for as long as possible
Every case should be evaluated individually
Owners should be given all options
The decision is theirs to make after weighing risk vs. benefit and cost