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How computers help in cancer treatment…

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01 October 2015, at 1:00am

MARION McCULLAGH reports from last month’s congress of the British Equine Veterinary Association on sessions dealing with cancer and a treatment with a promising future

THE British Equine Veterinary Association (BEVA) held its 54th congress beside the Mersey at the Liverpool Arena and Congress Centre. About 1,200 delegates brought equine expertise from around the world.

Derek Knottenbelt of the Liverpool and Glasgow veterinary schools chaired the session on “Surgical treatment of neoplasia”, when James Kinross, of the department of Biosurgery and Surgical Technology at Imperial College London and St Mary’s Hospital, explained how molecular tools are revolutionising the handling of cancer in humans.

Since Halstead performed the first radical mastectomy as a treatment for breast cancer the surgeon has needed to balance patient safety with effective tumour resection. One in 10 women in the UK get breast cancer and 20% of cancer cells can be left after surgery as the surgeon does not know where the cancer margin is.

Cancer is the result of the interaction between genes and the environment. Both are dynamic, constantly changing. The use of molecular tools has refined clinical diagnosis, prognosis and treatment selection and given a far more detailed appreciation of the cancers and the biology of the individual patient.

Metabolic phenotyping allows far better understanding of the unique composition of each patient by using predictive modelling of deep biological information. This allows far more precision in disease management.

Metabolic phenotypes (metabotypes) can be measured from tissue samples and body fluids. Each person’s metabotype is the result of interaction between phenotype, environment, lifestyle, diet and gut microbes. There is wide variation between individuals and populations.

These techniques have surgical application in the iKnife: by using conventional surgical electro-cautery and analysing the smoke it produces in a mass spectrometer, the surgeon is given sophisticated information at the time when he is deciding where to cut.

This method, known as Rapid Evaporative Ionisation Mass Spectrometry (REIMS), is coupled with multivariate statistical methods to compare the molecular composition of the patient’s tissue with a large scale database of prevalidated tissue mass spectral signatures.

This technology has been used in the treatment of human breast, bowel and brain cancers. As a simple example of its use, we were shown how the technique can determine the composition of a beefburger. The diathermy probe is first put into a sample of horse muscle and then the burger is probed. Analysis of the molecules of the two smoke samples by mass spectrometry can prove the identity of the muscle tissue in the burger at the time of sampling.

Radiation therapy

Derek Knottenbelt continued the cancer theme on Friday when Meredith Smith of Image Equine, Newmarket, gave her views on “High dose radiation therapy (HDR) – a new treatment option?”.

She explained that the use of radiation therapy in equine oncology was lagging far behind its use in humans and pets partly because horses are large and expensive to treat.

Radiation therapy was used for solid tumours in horses as long ago as the early 1900s, using the isotope radium Ra-226. At present there are two ways of getting the radioactivity into the tumour: brachytherapy where the source of radiation is applied directly within the mass, or teletherapy where the source of radioactivity is stored away from the horse and the dose is delivered with all humans behind a screen so that they are not exposed to the radiation.

Treatment is carried out in short bursts, with high activity radiation being present in the mass for minutes rather than the days which are needed for brachytherapy. The main time content is involved in imaging the lesion and calculating the dose, though the whole system relies on software already regularly in use for small animals at the Animal Health Trust’s facility at Newmarket where Meredith is pioneering equine treatment.

The tumours most commonly being treated by radiation therapy are sarcoids and squamous cell carcinomas. Periocular tumours are particularly appropriate for radiotherapy because of the need to preserve the eye and keep the periorbital tissues intact so that the horse can blink and maintain the tear film over the cornea.

As with tumours elsewhere, the dilemma is to destroy the cancer while preserving a functional animal. Bracytherapy using iridium (Ir- 192) beads or wire was long used at Leahurst.*

Wires or beads were inserted into the tumour after the application of local anaesthetic to a sedated horse. Keeping them in place for two to six days was not always easy. One horse ate his iridium wire; he had to be kept isolated until he had passed it in his faeces and was no longer regarded as a source of radioactivity. This method was demanding in terms of health and safety for the horse’s attendants.

In humans, HDR has largely taken over from the direct method. The source of radiation, in this case iridium-192 of high activity, is stored outside the operating area in its own lead-proofed environment and is delivered to the tumour in short bursts.

In this remote “after loading” technique the source is attached to a motorised guide wire and it is delivered through pre-placed catheters. The horse is prepared for treatment by being sedated and stood in stocks in the treatment room, where the tumour is infiltrated with local anaesthetic.

The perimeter of the area to be treated is marked with skin staples; then the catheters are placed. They are colour-coded so that the right dose goes to each place and the catheters contain radio-opaque markers to assist the imaging.

Cross-sectional imaging (and CT scanning in humans) means that the radiation delivery can be calculated precisely. The horse will have short treatments at daily or weekly intervals and in between sedation for treatment it can live a normal life.

Peri-ocular tumours are the most likely candidates for HDR but it has worked well for invasive tumours within the mandible, maxilla and sinuses. As with all cancer treatment the aim is to kill off the tumour while leaving the surrounding tissue viable. Meredith has carried out a series of HDR treatments at Newmarket and is ready to take on more patients this autumn.

The highly complicated HDR system appears to be offering huge advances in accuracy and efficacy: it should have a bright future.

*Knottenbelt, D. C. and Kelly, D. F. (2000) The diagnosis and treatment of periocular sarcoid in the horse: 445 cases from 1974-1999. Vet. Ophthalmol. 3: 169-191.