Targeted Melanoma Treatment for Inoperable Areas of Horses
Clinical Connections – Summer 2022
In January the RVC Equine Referral Hospital began to offer a novel treatment for equine melanoma using locoregional hyperthermia combined with intratumoral chemotherapy. The treatment specifically targets tumours that cannot be surgically removed, thus enhancing the service that RVC equine specialists can offer and improving the quality of life for horses affected by this disease.
Melanoma is a very common nodular skin disease that affects older grey horses of any breed. The disease is caused by a single gene mutation that increases the activity of melanoblasts. This manifests as a grey coat colour, however over time it also results in malignant transformation of these cells, leading to the development of melanocytic tumours. This gene has been bred into horses over millennia, as the grey horse was venerated by ancient cultures, and consequently it is estimated that up to 80 per cent of grey horses over the age of 15 years will develop melanoma at some point in their lifetime.
Though several treatments are available for equine melanoma, none are 100% effective – and some lesions are not amenable for surgical removal. For example, melanomas affecting the parotid region and other anatomically sensitive areas. Locoregional hyperthermia combined with intratumoral chemotherapy has been specifically developed to target these tumours. Hyperthermia transfers a large volume of electromagnetic energy deep into the patient’s tissue. The absorbed energy causes molecular friction, heating the targeted area to the febrile range (41 - 42⁰C) that has been shown to have a direct killing effect on tumour cells. This is likely due to heat shock induced apoptosis and alterations to the structure of proteins that support DNA metabolism, thus inhibiting repair of damaged tumour cells.
Additional mechanisms that may play a role include direct damage to tumour vasculature and production of heat shock proteins that stimulate an innate and adaptive immune response to the tumour. Importantly, hyperthermia has also been shown to have a synergistic effect with various cytotoxic drugs (e.g. cisplatin or carboplatin) by increasing drug penetration into tumour cells. The equipment is safe, easy to use and can be performed in standing horses without the need for a general anaesthetic.
Although it is not expected to result in complete remission, locoregional hyperthermia and intratumoral chemotherapy is aimed at tumour shrinkage, thus improving function and quality of life in affected horses. In many cases treatment will be performed in concert with diode laser removal of other tumours that are amenable to surgical removal. Prior to embarking on treatment, the horse will be examined, and an individually tailored treatment plan will be devised based upon the size and location of the tumours.
Horses that meet the criteria receive three rounds of treatment, with a week between each. Treatment involves injection of the cytotoxic drug into the melanoma, followed by locoregional hyperthermia using the ThermofieldTM system that utilises microwave energy to heat the tissues. The procedure takes about an hour to complete. A second hyperthermia treatment is performed the following day and the horse is discharged until the second and the third treatment rounds. The treatment is not associated with any side effects and is well tolerated by the horse.
The RVC appears to be the only equine service in the UK currently using this technology to treat melanoma. The Thermofield unit was funded by the RVC Animal Care Trust. Hyperthermia and chemotherapy have been used in human oncology for many years, and the combination has been reported to result in a reduction in tumour size and improved survival rates for a variety of cancers. There is currently no published data on the efficacy of this multidisciplinary treatment for equine melanoma, however, results from preclinical studies have been promising.
Discussing the development and ramifications for patients and their owners, Dr Michael Hewetson, Senior Lecturer in Equine Medicine at the RVC, said: “Although locoregional hyperthermia combined with intratumoral chemotherapy is a relatively new treatment in equine oncology, I have been impressed with the response in the horses that we have treated thus far, and I am optimistic for the future. We will be collecting data over the next few years to report on its effectiveness.”