I&TP Veterinary radiotherapy Veterinary radiotherapy Veterinary radiotherapy at Glasgow University’s Small Animal Hospital: Two case studies. 20 September 2014 Veterinary radiotherapy I&TP Radiotherapy has been used to treat veterinary patients since the 1970s and veterinary radiation oncology became a recognised specialty of the American College of Veterinary Radiology in 19941. Although radiotherapy has been available at Cambridge Veterinary School in the UK since last century, other centres for veterinary radiotherapy are becoming increasingly available as more owners are prepared to seek cancer treatment for their pets. Liverpool and Edinburgh Veterinary Schools and a private practice in Essex (VRCC Veterinary Referrals) now offer radiotherapy treatments and most recently in 2014, the Animal Health Trust in Newmarket also started treating patients. In September 2010, the oncology service at Glasgow University’s Small Animal Hospital opened its new radiotherapy unit, employing one therapeutic radiographer to work alongside the existing veterinary oncology team. Four veterinary oncologists and a specialist veterinary oncology nurse also work in this department, which deals with all aspects of diagnosis and tumour staging, and prescribes treatment, including chemotherapy and immunotherapy, as well as radiotherapy. The radiographer’s role within the small animal hospital involves all aspects of radiotherapy, from making beam directional shells and electron cut outs, to manual and 3D conformal treatment planning, as well as the treatment of the animals and the quality control of the machine. The hospital installed a reconditioned linear accelerator (ex NHS), a Siemens September 2014 Oncor Impression Plus which was only one year old. The machine has 6MV and 10MV photons and six electron energy options, 80 leaf MLC and portal imaging and complemented the existing Siemens CT and MRI facility. How long have we been treating patients? Although patients have been treated with radiotherapy since the unit opened three and a half years ago, the service has had a gradual build up of cases since opening. With increased publicity and experience, there has been an increase in cases referred to the hospital for radiotherapy from local veterinary practices, and internal referrals from other services such as internal medicine or neurology; we have now treated over 160 patients since 2010. Limiting factors for uptake of treatment are mostly financial, although owner time commitment, anticipated survival time and fear for patient quality of life during treatment also contribute. What sort of cases do we treat? A variety of different tumour types can be treated in animals, depending on the technical capabilities of the centre and whether treatment is definitive or palliative. For brain, nasal and oral tumours, 3D conformal CT planning is usually used, with the aim of treatment being to shrink the tumour volume since most of these tumours (particularly brain and nasal) would not have had any previous surgery. For other more superficial tumours, such as skin and subcutaneous tumour types, eg sarcomas and mast cell tumours, adjunctive treatment of microscopic disease at the surgical scar site is common if histopathology has shown unclear margins2,3. Many such tumours in animals present late on and are large in size and infiltrative, and therefore difficult to excise completely, especially on the limbs, hence surgical excision alone is inadequate. Scar treatments are usually manually calculated with dose tables and are therefore very quick treatments to do. Electron beam treatment is widely used for scars over the thorax or abdomen, to avoid irradiation of underlying organs. Generally, treatments to the thoracic or abdominal cavities or pelvic area are avoided in animals, as it is considered unfair to cause excessive side effects in the internal organs such as lungs, intestines, rectum or bladder. Electron beam treatment of anal sac tumours adjacent to the anus is well tolerated, however, as side effects to the anal sphincter and rectum can be minimised by using the appropriate energy of electrons. This ensures the animal will have no problems passing faeces after treatment. Increasing use of more precise dose techniques such as IMRT and IGRT at some veterinary centres in the USA, means that treatment of pelvic areas is now being considered more routine since side-effects are far fewer4. Whole body radiation is often avoided because of excessive bone marrow suppression and internal organ side-effects, although half-body radiation combined with chemotherapy is reported in some centres for treatment of canine lymphoma5. 21 I&TP Veterinary radiotherapy Figure 7. Figure 1: Protocols that are used within small animal radiotherapy. SEMI - RADICAL PROTOCOLS PALLIATIVE PROTOCOLS 48Gy in 12# Monday,Wednesday, Friday for four weeks 40Gy in 8# Twice weekly (gross tumour) 48Gy in 16# Mon – Fri, for three weeks (usually brain tumours) 36Gy in 4# once weekly for four weeks 40Gy in 8# Twice a week (scars) 20Gy in 5# daily for one week Treatment delivery When animal patients are being treated with radiotherapy they require a general anaesthetic each visit to ensure that they remain still during treatment delivery and can be positioned with sandbags and foam wedges or vacuum bags. The intravenous drugs and inhaled gas that are used are very fast acting so that the patient can have their treatment and be recovered within an hour, but the treatment length obviously limits the number of cases that can be treated each day, and the animals must be healthy enough to undergo multiple repeated anaesthetics. Most of the pet owners come to the Small Animal Hospital on an outpatient basis but the hospital has the facilities to board the animals if they are coming from far away or if the owners are working. The animals that board within the hospital receive lots of attention from all the staff and they are always taken out to walk around the hospital grounds to try and make it a pleasant experience for them. Palliative and radical treatment differences The main aim of veterinary radiotherapy is to give the animal a good quality of extended life, both during treatment and when it finishes. Although life extension is important, it is 22 essential to minimise side effects as much as possible and provide medication when side effects do occur, to prevent further patient deterioration. Side-effects are monitored and scored using radiation toxicity standard guidelines6. Treatment may be delivered with more curative intent (definitive protocols) where the animal is expected to live for a year or more and the temporary discomfort of acute side-effects is therefore considered acceptable or with more palliative intent for pain relief without an expectation of extended life expectancy or with the aim of partial tumour shrinkage and some slightly increased life expectancy1. Doses/ protocols vary accordingly (see figure 1). Cost of treatment and owner commitment as well as the general health status of the patient with regard to number of anaesthetics, influence greatly which protocols are selected. When the owner comes to the hospital with their pet, the oncologist discusses all appropriate treatment options with them and they make a decision as to how to proceed, taking into account estimated survival times, potential side effects and costs of the treatment. Cost of treatments The cost of veterinary radiotherapy treatments vary depending on which protocol is chosen, but palliative protocols are approximately £2000 and radical protocols are approximately £4000 (including anaesthesia), with another £1000 needed for diagnosis and staging prior to embarking on treatment. Treatment of brain tumours is more expensive as they require an MRI for diagnosis (in the region of £2000 for full diagnostic tests) and treatment with daily fractions (£5000 approximately). Many patients are insured and radiotherapy is covered by most pet insurance policies, although diagnostic investigations often consume much of the insurance, leaving limited amounts for treatment procedures in many cases. Nasal tumour case study History Harvey presented as a male, neutered, five year old, very excitable Labrador when he was referred to the Small Animal Hospital oncology service by his general practice vet in June 2012. He had a three month history of difficulty breathing and wheezing, and a congested nose with persistent blood-tinged nasal discharge from the left nostril. On clinical examination he had reduced airflow in the left nostril and slight discharge, but no other clinical signs. Investigations Several investigations were performed whilst Harvey was in the hospital. After routine bloods (haematology and biochemistry) ensured he was fit and well enough to undergo a general anaesthetic, he had a CT of his thorax to check that he did not have metastases in his lungs, and a CT of his nose. Although the chest was clear, the CT of his nose showed a 2x2.5cm soft tissue mass in the mid left nasal chamber, which was suspected to be a tumour because of associated turbinate destruction. Nasal biopsies followed the CT and these confirmed that the mass was a chondrosarcoma. The treatment of choice with the best survival time for Harvey was radiotherapy, with a dose of 48Gy in 12#, three times a week7. Despite living in Aberdeen, his owners decided to go ahead with the treatment and leave Harvey boarding in Glasgow. Planning Harvey had a beam directional shell (BDS) and head cushion made before his CT scan and while in prone position. The CT images of Harvey’s head (figure 2) were transferred to the planning software (Prowess September 2014 Veterinary radiotherapy I&TP Figure 2. 5.1). Four radiation fields gave the best dose distribution: beam directions were left lateral and left posterior oblique with the couch at 0 degrees and then two further beams (superior posterior oblique and an inferior posterior oblique) with the couch at 90 degree. Wedges were used to improve the dose distribution and had 95% dose around the PTV with a maximum dose of 105%. MLC was used to give minimal dose to the eyes. Treatment Harvey coped well with the four week treatment with minimal side effects, which included some snorting and sneezing as the tumour shrank, ocular discharge and mild ulcers in his mouth. These were controlled with low dose anti-inflammatory corticosteroids and antibiotics. Harvey boarded at the hospital for the whole treatment and got to know all the staff in the hospital very well. Two weeks after finishing the course of treatment, his owner updated us on his progress and sent a photograph (figure 3). At this stage radiotherapy damage to the tear ducts had produced tear overspill from the eyes, causing the area around the eye to become moist which encouraged the hair loss. Restage Harvey came back to the hospital for a check up and a full restage three months post radiotherapy. He was very well in himself, with no nasal discharge and he was still very excitable! Clinical examination revealed good airflow in both nostrils and white patches below both eyes where the hair had regrown without September 2014 pigment. A CT of his nose at this visit revealed a dramatic decrease in size of the left nasal mass and also turbinate destruction in the left nostril where the tumour had been (figure 4). Harvey returned for a further CT of his nose six months post radiotherapy (Figure 5) and this showed no regrowth of the tumour. Figure 3. July 2013 A year after initial presentation, Harvey started sneezing and having nose bleeds again. CT of his nose at this time revealed that the tumour had started regrowing, but was still 50% smaller than before radiotherapy (figure 6). Since the owners were reluctant to go through a four week radiotherapy protocol again, a palliative course of radiotherapy was offered, combined with a non-steroidal anti-inflammatory drug (NSAID) Meloxicam. Harvey’s owners were not able to bring him for treatment until September 2013, when his protocol this time was 20Gy in 5# Monday to Friday8. As the tumour was smaller it meant it was easier to plan as the eyes were not included in the field. Three beams, a left lateral, left posterior oblique and a right posterior oblique gave the best dose distribution. Harvey coped well with the second course of radiotherapy and had no side effects as the dose was smaller. Figure 4. Figure 5. Outcome June 2014 Two years after initial presentation, Harvey continues to do well. The loss of turbinates in the nose means there is reduced filtration of dust particles and a tendency for the nose mucosa to be more inflamed, although Figure 6. 23 I&TP Veterinary radiotherapy Figure 9. Figure 8. long term use of Meloxicam helps this. When Harvey gets too excited he sneezes repeatedly and he has a nose bleed, due to his increased blood pressure and more inflamed vessels in his nose. Starting medication to keep his blood pressure low has stopped him from having these nose bleeds. Harvey’s owner is happy with his quality of life and the outcome of the treatment and says he’s as excitable as ever. Harvey now has a very distinct appearance after his radiotherapy treatment since leukotrichia of the hair in the treatment field has left him with a white stripe over his nose (figure 7). Discussion Although historically, surgical debulking of nasal tumours followed by orthovoltage radiation was used1,9, most nasal tumours are usually now treated with megavoltage radiation alone, since most studies have not shown a survival advantage of surgery and radiotherapy combined3, Median survival times of over one year are frequently achieved (8-12.5 months for carcinomas and 12-15 months for chondrosarcomas4), although protocols can vary from hypofractionated four times once weekly fractions (total 32-36Gy) to 15-20 times daily fraction protocols (total 44-55Gy). Palliative five times 4Gy daily fractions are also possible and can achieve a median response duration of approximately six months10. Reirradiation of recurrent tumours is possible, both with definitive protocols11 or coarsely fractionated protocols12 and can extend survival further without causing life-threatening side–effects. The 24 main problem with irradiation of nasal tumours is delivery of adequate dose to the tumour, without side-effects to the eyes. The introduction of IMRT to veterinary patients to spare the eyes should improve treatment outcomes in future13,14, although the introduction of more sophisticated and expensive techniques will invariably increase the cost of treatment to the patients. Harvey has survived 24 months after two courses of radiotherapy and had good quality of life throughout. This is in good agreement with the expected outcome in the veterinary literature and has had the advantage of very few side-effects. Brain tumour case study History Pebbles was a nine year old female neutered boxer when she was referred to the small animal hospital neurology service by her general practice vet, after having three seizures in close succession in February 2011. Clinical examination On clinical examination by the neurology service Pebbles was mildly ataxic in all limbs, her mentation and cranial nerve examination was unremarkable, hopping reactions were reduced in all limbs and spinal palpation and spinal reflexes were unremarkable. Investigations After routine bloods (haematology and biochemistry) were shown to be normal, Pebbles was anaesthetised and had chest radiographs which showed no abnormalities or metastatic spread. An MRI scan of her brain showed a large intra-axial heterogeneous mass affecting the right olfactory bulb, (figure 8). The mass was isointense on T1w, hyperintense but heterogeneous on T2w, contrast enhancing and was associated with oedema on FLAIR. There was no dural tail or meningeal enhancement making a glioma most likely. Pebbles was started on anti seizure medication (phenobarbitone) and anti-inflammatory corticosteroids to reduce oedema and inflammation in her brain. Pebbles’ owners were given the option of radiotherapy to shrink the tumour or palliative care with medication only. They decided to go ahead with the radiotherapy, but to have the shortest boarding time in Glasgow. Her prescribed radiation dose was 45Gy in 15# Monday to Friday over three weeks, whilst continuing with her medications. CT planning Pebbles returned to the hospital 10 days later to have a CT scan of her head for radiotherapy planning. Under general anaesthesia, she was in prone position with a vacuum cushion to support her neck and mandible, and had a BDS made for immobilisation. Using the CT images, but with reference to the MRI images, a treatment plan was devised with planning software. This involved 6MV photons, delivered as three beams of radiation: a direct posterior, right posterior oblique and a right lateral. Wedges were used on all beams to improve the dose distribution and 95% dose coverage was achieved around the PTV with a maximum dose 102% (figure 9). September 2014 Veterinary radiotherapy I&TP Figure 12. Figure 11. Figure 10. Treatment During her treatment Pebbles boarded at the hospital from Monday to Friday and went home at weekends. She coped well with the daily general anaesthetics and had no side effects from the treatment (figure 10) so her owners were happy with how the treatment had gone Restage Pebbles returned to the Oncology service three months after finishing her treatment for a re-imaging of the tumour. At this point she had no clinical signs and was doing well at home. The MRI scan of her brain showed 50% reduction in tumour size (figure 11). Pebbles’ owners were really pleased with the outcome of the radiotherapy, and elected for further imaging six months after end of treatment (figure 12) which showed that the tumour had remained stable since the three month post radiotherapy MRI scans. Fourteen months after finishing her treatment Pebbles returned for a further MRI scan (figure 13), which unfortunately showed that the tumour had grown back to its original size, although it was asymptomatic (Pebbles was still on antiepileptic medication). A CT scan of her lungs and abdominal scan of her abdomen did not detect any other sign of metastatic spread at this point. Low dose anti-inflammatory corticosteroids were restarted and Pebbles continued on anti -seizure medication, so that one and a half years after treatment had finished she was still clinically asymptomatic and had a good quality of life (figure 14). Pebbles was sadly euthanised in May 2013, 26 months after finishing radiotherapy, due to her clinical September 2014 signs returning. Her owners were really pleased with the outcome of radiotherapy and never expected to get an extra two years of good quality life with Pebbles. Discussion Since the introduction of 3D conformal planning to veterinary radiotherapy, it has become the treatment of choice for most primary brain tumours (other than surgically resectable meningiomas) with median survival times varying widely from approximately 5-23 months15,16. Dogs with pituitary macroadenomas may have median survival over two years, however, this is closer to 12 months for those with neurological signs at presentation5,17. Diagnosis for most brain tumour cases is based on CT/MRI findings rather than biopsy and histopathology, with post-mortem confirmation in some cases. Although hypofractionated protocols have been tried18, most centres nowadays would use smaller fractions on a daily or three times weekly protocol to a higher total dose (45-54Gy). Pebbles survived more than two years, having been treated with daily fractions to a moderate total dose and so her outcome was comparable to what is reported in the literature. offering treatment to small companion animals • The main aim of treatment is to prolong survival where possible but to maintain a good quality of life for the animal • Radical and palliative options are available and each animal is individually assessed to decide on the best protocol for them • A general anaesthetic is needed to deliver each treatment • Treatment costs range from £2000 to £5000 approximately but is generally covered by pet insurance Figure 13. Acknowledgements Thank you to the owners of Harvey and Pebbles for allowing us to use their pets as case studies. Figure 14. About the Authors Author: Shona Burnside BSc (Hons), PG Dip, MSc, Therapeutic Radiographer, Glasgow University Small Animal Hospital. Joanna Morris BSc, BVSc, PhD, FRCVS, DipECVIM-CA (oncology), Senior Lecturer in Veterinary Oncology, Glasgow University Small Animal Hospital. References for this article can be found at http://www.sor.org//learning/library-publications/itp This article has been prepared following local guidance relating to the use of patient data and medical images. To comment on this article, please write to editorial@itpmagazine.co.uk Summary Radiotherapy is now an accepted and established treatment for many tumour types in animals, either as a sole modality or combined with surgery and /or chemotherapy. • Glasgow University Small Animal Hospital is one of six radiotherapy units in the UK How to use this article for CPD How do you feel about animals being treated with radiotherapy, with regards to side effects, cost and the repeated anaesthetics? Which radiotherapy treatment protocols do you think are the best options for animal treatments? 25 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
