BRITISH VETERINARY ONCOLOGY STUDY GROUP

Proceedings of Inaugural Meeting

28th October 2000

The meeting was attended by thirteen veterinary surgeons from practice, specialist centres and diagnostic pathology laboratories, and was opened by Ron Lowe with a brief history of his experience of Oncology and especially chemotherapy in small animal practice over the past 25 years. This was followed by a discussion of the many aspects of oncology with which the group should concern its activities.

It was agreed that it was possible to consider Carcinogenesis (and this might include pathophysiology), Diagnostic methods, Staging, Surgery, Chemotherapy, Radiotherapy, Immunotherapy, Palliative measures, Client management (including the emotional as well as practical aspects), Ethics, Alternative therapies and Health and Safety issues. The group felt that all these aspects would be considered, but that it would probably not be possible to cover them all at any one meeting. It was also considered that all species normally treated by the veterinary profession should be represented.

Malcolm Brearley, one of only three RCVS recognised specialists in Oncology, then gave an overview of the position of the specialist in current veterinary oncology. He reviewed the history of veterinary oncology and its relations to human oncology such as the dog melanoma model used in early studies of radiotherapy and Glasgow University's work with Retroviruses and the study of HIV.

The differences between veterinary and human oncology start with the proportion of patients treated by specialist oncolgists: 99% of humans and 1% of pets. Thus one role of the group could be to foster excellence in veterinary practitioners. The practice of waiting to see waht a lump does should be discouraged: at least fine needle aspirate biopsy should be carried out on all potential tumours when first seen. The owners should be informed of the full spectrum of possibilities for treatment from euthanasia to specialist intervention to allow them to choose how their pet would be treated. Mr Brearley stressed that the first surgery is always the best and should therefore be carried out in as definitive a manner as possible. He cited the example of so-called 'vaccine-induced' sarcomas in cats as being the most locally aggressive tumours he deals with. The expertise of a specialist surgical oncologist will improve the cure-rate for such tumours.

Radiotherapy which was started at Cambridge University in the 1970's is available only at Cambridge to this day, though this situation might change before too long. The Pets Passport scheme might increase the treatment of animals from continental Europe in this country as radiotherapy facilities are very scattered. In the USA where there are very many more specialists and where referral of oncology patients is the norm it has been suggested that a purpose built radiotherapy unit will pay for itself in 3 years! The enormously greater activity in the field of oncology in the States supports many very large specialist centres and allows clinical trials to be conducted in individual centres.

At the Veterinary Cancer Society congress in the USA earlier this month there were 350 abstracts presented! There were also four keynote papers given. One described enzymes in malignant cells involved in repairing 'frayed' chromosome ends thus delaying death of a cell line. These enzymes (tolomerases) might be a target for chemotherapy. There was a paper on surgical oncology describing multiple (c40) sampling of margins of excision and repeat surgery to extend resection in the light of results. Another discussed angiogenesis, the property of tumours to stimulate increased vascular supply, and the possibilities of targetting this therapeutically. The fourth paper covered tumours in fish, their relationship to pollutants and the possible use of fish fry in testing for for oncogenic effects of substances (very small young fish can be blocked and sectioned whole for complete body searches under the microscope).

After digressions and coffee, Dr Joan Rest of Rest Associates gave a histopathologist's view of the pitfalls of cytological diagnosis. She warned of high error rates, the impossibility of accurate grading of tumours, the disadvantages caused by the lack of tissue structure and failures of technique and preservation. Her informal style invited discussion of points as they were raised, and some useful tips were added by Trevor Whitbread of Abbey Vet Services. To a practitioner, the upshot was that fine needle aspirate biopsy, fluid cytology and exfoliative/wash techniques were of value in selected tumours, but poor sample collection and handling were very common problems to pathologists endeavouring to provide some useful information. A well spread (monolayer) of representative cells with minimal blood contamination is the first requirement. Dr Rest advocated IMMEDIATE spreading of a fine needle specimen (using the same technique as for blood smears). This should be fixed with 70% alcohol before posting as plastic containers leach tiny amounts of formalin into their contents which will preclude use of some commonly used stains. Mr Whitbread suggested an exception to this in the case of alveolar washings wo which a few drops of formailn should be added as long as the request form makes it clear this has been done.

Bloody samples, and marrow samples, can be run down a tilted microscope slide to drain free fluid, and CSF samples should be spun and spread immediately upon collection. Dr Rest advised against FNAB of liver, kidney or mammary tumours as structural detail is vital to interpretation of biopsies from these. Blood filled masses, fat, fibrous and keratinised tissues and areas with significant necrosis or inflammation were poor sources of cells. Mastocytomas in dogs and cats were prime candidates for FNAB but in the horse they are entirely different.

The huge topic of cytology of lymphomas was, Dr Rest ended by saying, the subject for an entire paper in itself.

The final paper of the morning was a discussion of the use of Piroxicam in oncology and was given by Clare Knottenbelt of the University of Glasgow. Observations in humans had suggested that some cancer patients who were given Piroxicam for arthritis had better and longer remissions than others. In particular rectal and colonic tumours regressed. Experimentally, the induction of large bowel tumours in rats and fibrosarcoma in mice is rendered more difficult by the drug. It is surmised that suppression of PGE2 may interfere with tumour progression, and this is borne out by the facts that PGE2 is immunosuppressive and levels are increased in humans with colonic cancer. COX2 inhibitors upregulate the genes regulating apoptosis (programmed cell death). Experimental urinary tract obstruction in embryos leads to high COX2 levels in the bladder wall: these high levels also occur in transitional cell carcinomas in dogs.

There are then reasons to expect some beneficial effects in cancer patients from COX2 suppressive drugs, such as piroxicam. Clare reviewed a study where 34 dogs with spontaneous tumours of several types were treated with Piroxicam at several dose rates. There were toxic effects at doses higher than 0.3mgm/kgm daily (or 0.5mgm/kgm/48hours). There were no complete remissions, but 8 partial remissions were seen. Clare herself has carried out a study (with colleagues at Edinburgh University) which were published in JSAP in Sept/Oct 2000. This study involved dogs with rectal adenomatous polyps and 7/8 dogs showed benefits from Piroxicam administered by suppository. Apparently owner compliance was very good. Clare ahs also treated 3 dogs with transitional cell carcinoma of the trigone area of the bladder. All three showed clinical improvements within 7 days, and survival times (without surgery) were encouraging.

In the discussion which followed it was suggested that we might, as a group, conduct a trial using Meloxicam, which is a better COX2 inhibitor than Piroxicam, and is licensed for use in dogs (and in cats in the short-term). No final decision was made about this, but interested members might contact Malcolm Brearley at Davies White Veterinary Specialists for the state of play.

After lunch Ron Lowe chaired an informal discussion session based on a hypothetical cat with a ileo-colic lymphoma. Whilst most practitioners would have opted for surgery, the specialists were in favour of chemotherapy unless the cat was obstructed. The CHOP regime (Cyclophosphamide, Adriamycin, Vincristine and Prednisolone) was favoured by Malcolm Brearley. There was a lively discussion of various aspects of such cases.

The rest of the day was spent in a business meeting to set up the structure of the group.