Vet Times The website for the veterinary profession https://www.vettimes.co.uk Radiotherapy and tumours in veterinary practice: part one Author : Aleksandra Marcinowska, Jane Dobson Categories : Companion animal, Vets Date : September 28, 2015 ABSTRACT Radiotherapy is an increasingly used treatment in veterinary medicine. It remains the second most important treatment option for people and dogs with cancer, after surgery. More than half of cancer patients will be treated with radiotherapy. Similarly to surgery, it is a loco-regional treatment, therefore it is inappropriate for widespread disease. It may be used in a neo and/or adjuvant setting, alongside surgery and some chemotherapeutics, and, depending on the tumour type, the intent of the radiotherapy treatment may be radical (curative) or palliative. Radical treatment aims at curing the patient so the side effects are unavoidable. The role of palliative radiation therapy is to alleviate the distressing symptoms, providing a good quality of life with minimal side effects. In veterinary medicine a number of neoplasms are treated with radiotherapy, achieving very good loco-regional control of the disease and providing good quality of life, minimal side effects and prolonged survival times. This article aims to familiarise veterinary clinicians with the most commonly seen tumours in veterinary practice that may significantly benefit from radiation therapy, either as a sole treatment, or in combination with other treatment modalities. Radiotherapy uses electromagnetic and particle radiation for the treatment of mainly malignant tumours 1. Radiotherapy remains the second most important treatment option for human cancer patients, after surgery, and more than 50% of patients will receive radiation at some point during the management of their disease 2. Like surgery, radiotherapy is loco-regional and is not suitable for treatment of systemic malignant disease. Tumours treated in the early stages, without metastatic disease, may be cured or high success rates can be achieved. Depending on the tumour type the treatment intent can be either 1 / 8
radical/curative or palliative. Radical treatment can be further defined as definitive therapy (either if there are no plans to perform surgery, or in a presence of a recurrent disease after previous curative intent surgical excision), neo-adjuvant prior to definitive surgery to reduce the bulk of the tumour, or adjuvant following definitive treatment in the event of any confirmed or potential microscopic disease 3. Radical radiotherapy treatment is delivered with high total doses of radiation, therefore side effects are unavoidable, but these are accepted as an inevitable part of the cure. Palliative radiotherapy is aimed at relieving distressing symptoms in advanced diseases and does not require high doses of radiotherapy. Instead, it is delivery of a sufficient dose to enable symptom control. Animal cancer patients may also be treated radically or palliatively depending on the tumour, its location, prognosis and the owners wishes. Palliative radiation therapy is most commonly applied in the treatment of nasal and brain tumours, where, even with more fractionated and radical approaches, cure cannot be achieved. Curative intent radiotherapy is most common in the postoperative setting, in the treatment of incompletely excised soft tissue sarcomas, mast cell tumours and similar, where the chances of cure are high and prognosis is thought to be good. Radiotherapy may be delivered by photons or electrons, depending on the desired treatment depth. Most radiotherapy treatments are delivered by means of photons using linear accelerators as common sources of high energy x-ray beams, which enable delivery of the dose to the deepestseated tumours in the largest of patients. Four to eight megavoltage (MV) beams are the most commonly used in the clinical setting and provide an adequate distribution of the dose between deep structures and the skin surface. 2 / 8
Figure 1. Percentage dose depth for 6MV x-rays. The main advantage of the MV linear accelerator is the ability to spare the skin (Figure 1), but this can be a disadvantage when treating superficial, cutaneous tumours, as they may not receive the required dose. However, with modern, highly sophisticated machines, a dose delivery precision of 2% to 3% can be achieved. To achieve this, several methods may be implemented. A multileaf collimator provides complex beam shaping that enables precise radiation delivery to the tumour and sparing of normal tissue. Dynamic wedges are another way of normal tissue sparing, by adjusting the beam and the dose delivered to the desired place. They change the angle of the isodose curve relative to the beam axis at a specified depth 4. Radiotherapy works by interaction between photons or electrons with the target material/tissue. Tumours may vary in their sensitivity to radiation; some tumours (for example, mast cell tumour or lymphoma) are more radiosensitive than others and the dose prescribed for their treatment can be lower. In comparison, radioresistant tumours (for example, melanoma) will require much higher dose for their treatment. One of the secondary effects of radiotherapy is exposure of normal, healthy tissue, which may result in killing quickly dividing, healthy cells, such as those in the skin or gut mucosa. If the treatment is well planned (that is, the radiation dose is higher for the tumour compared to the surrounding healthy tissue), the tumour may be effectively treated and eradicated. Different tissues in the body vary in their response to the radiotherapy and some organs are more sensitive to radiation than others. The eyes, kidneys and spinal cord are the most sensitive organs, therefore the dose to these organs must be kept to a minimum. Whole lung, whole liver, thyroid gland, ovary and testes are also sensitive with a minimal normal tissue tolerance and radiotherapy of these is rarely performed, especially in veterinary medicine. In general, all radiotherapy treatments are prescribed to the limit of the normal tissue tolerance, and any reduction in the radiotherapy dose may result in inadequate control of the tumour 1. The effect of the radiotherapy on both tumour and normal tissue depends on several factors: fractionation overall time the treatment is delivered volume irradiated patient and biological factors 3 / 8
The principle of fractionation is to divide the total dose into several, smaller doses over a period of days/weeks, which maximises the effect of radiotherapy on the tumour, but minimises the side effects in normal tissue. Generally speaking, normal tissue toxicity depends on the total time over which the dose is given and the fraction size. Dividing the total dose into smaller and frequent fractions reduces the risk of side effects and allows for the total dose to be higher to a particular area, compared to treatment with one large dose. If a patient misses a prescribed dose, complications may arise, which subsequently reduces the effectiveness of the radiotherapy treatment. This is particularly important for head and neck tumours where any treatment breaks can result in cancer cell repopulation and treatment failure 1. The irradiated volume is also very important for dose prescription and planning the treatment. The smaller the volume to be irradiated the higher the total dose that may be tolerated by that irradiated field. Various types of radiation treatment are used in human and veterinary patients. Photons are able to penetrate deep into the body, sparing skin at the same time. Electrons can penetrate up to a few centimetres deep from the skin surface, which makes this type of therapy effective in treatment of superficial tumours. Protons are able to deposit their energy with very high precision and are most often used for paediatric, skull or spinal tumours; they are not used in veterinary medicine. Brachytherapy involves radioactive sources temporarily or permanently inserted into the tumour. This type of treatment has been used in veterinary medicine; however, apart from treatment of horses it is not commonly used now 5. Photons and electrons are used most commonly in veterinary medicine. Treatment planning and delivery 4 / 8
Figure 2. GTV, CTV and PTV drawn on the CT image of the dog s head. The radiotherapy process comprises three main steps: imaging, to define the gross tumour volume (GTV), clinical target volume (CTV) and planning target volume (PTV) treatment planning treatment set up, verification and delivery Before the radiation treatment begins, planning imaging must be performed. A planning CT scan is used to define the area to be treated with the patient in the treatment position. The immobilisation procedure is very important at this stage as it will determine the patient s position throughout the full course of radiation therapy. This may be achieved by means of cushions, bite blocks and/or thermoplastic shells. Once the CT images are obtained, three volumes are drawn on them. GTV represents the actual tumour dimensions. In some instances where the primary tumour has been surgically excised, the GTV cannot be defined. CTV accounts for the tumour itself with a margin of a microscopic disease around it. In other words, this is a gross tumour plus subclinical disease, and it is advised to describe this volume by anatomic-topographic terms. PTV is a geometrical concept, used for selection of appropriate beam sizes and their arrangements. It takes into account the net effect of all possible geometrical variations to ensure the prescribed 5 / 8
dose is actually absorbed in the CTV. PTV includes the CTV and the margin that accounts for potential daily variation in tumour position, which can be a result of slight differences in daily position and internal organ motion (Figure 2). Treatment planning is one of the final processes before the actual treatment can be delivered. It takes into account GTV, CTV, PTV, treated volume, irradiated volume and organs at risk. Figure 3. Treatment planning creating patient s contours, especially of the body outlines, CTV and critical structures. The first stage of the planning process is to produce an isodose distribution. This is achieved by collecting all the tumour localisation information, mostly from CT or MR images. These are then input into the treatment planning computer, which is followed by creating the patient s contours, especially of the body outlines, CTV and critical structures (brain, eyes, spinal cord and so on; Figure 3). In recent years, significant advances have been made in human and animal radiotherapy planning and treatment delivery. New radiotherapy techniques allow precise dose delivery/distribution and sparing of normal tissue, reducing potential side effects. They also allow dose escalation, which can improve tumour control and result in increased cure rates 3. Intensity modulated radiotherapy (IMRT) uses the concept of conformal avoidance, which is an everything but treatment approach. The main goal is definition and avoidance of critical structures rather than precise delineation of the target organs. In people, IMRT is especially important in the treatment of head and neck, prostatic and anal cancers 6. 6 / 8
IMRT is rarely used in veterinary medicine, but has been reported for intranasal tumours where the dose to the tumour is limited by the tolerance of the surrounding critical structures eyes and brain so the dose cannot be safely increased without increasing serious complications 7,8. The main advantage of IMRT is improved PTV coverage and sparing of normal tissues as it can achieve complex concave shaped treatments with steep dose gradients 9. Image-guided radiotherapy allows accurate delivery of radiotherapy by using imaging before and during treatment. It checks for any movement during treatment delivery and allows for the smaller safety margins to be used in treatment planning. It is especially important in IMRT where steep dose gradients are used. Stereotactic radiosurgery (SRS) is a very precise method of radiation delivery. It was originally designed to treat functional disorders of the brain; however, it is now indicated for tumours, vascular lesions, and pain syndromes, including but not exclusive to the brain and spine 10. The principle of SRS is the delivery of many finely collimated beams, which are focused on a specific target to deliver a very high dose to a small target with minimal radiotherapy doses to surrounding tissues. Treatment delivery can be linac-based or by means of gamma knife. In veterinary medicine, this type of radiation delivery is very rare and has only been described in two reports 11,12. Conformal radiotherapy is similar to conventional 3D planning. The difference is in the conformal radiotherapy planning, multiple beam angles and conformal blocks are used to shape the dose as closely to the target volume as possible, sparing normal tissues. This is achieved with the use of treatment planning software performing thousands of calculations in a short space of time. This radiotherapy planning requires the treated volume to match the PTV as accurately as possible. To assess this, interpretation of dose volume histograms, inspection of 3D dose distribution and calculation of the conformity index that describes the fraction of the planned target volume covered by the treated volume must be performed. Conclusion In conclusion, radiation therapy is a loco-regional treatment using either photon or electron beams. The effect of radiotherapy depends on fractionation schedule, overall time the treatment is delivered, irradiated volume and patient factors. Various new radiotherapy techniques allow precise dose delivery/distribution and sparing of normal tissue, therefore reducing potential side effects. These techniques are increasingly commonly prescribed in veterinary medicine. 7 / 8
Powered by TCPDF (www.tcpdf.org) References In the second part of this article, application of radiotherapy in certain malignancies in veterinary patients will be discussed. 1. Griffiths S and Short C (1994). About radiotherapy. In Radiotherapy: Principles to Practice, Longman, Singapore. 2. Hoskin P (2006). Introduction. In External Beam Therapy (Radiotherapy in Practice), Oxford University Press, Oxford. 3. Owadally W and Staffurth J (2015). Principles of cancer treatment by radiotherapy, Surgery 33(3): 127-130. 4. Coleman A M (2004). Treatment procedures. In Washington C M and Leaver D (eds), Principles and Practice of Radiation Therapy (2nd edn), Elsevier, St Louis. 5. Surjan Y, Warren-Forward H and Milross C (2011). Is there a role for radiation therapist within veterinary oncology? Radiography 17(3): 250-253. 6. Chao K S, Ozyigit G, Blanco A I et al (2005). Intensity-modulated radiation therapy for oropharyngeal carcinoma: impact of tumour volume, International Journal of Radiation Oncology, Biology, Physics 62(4): 1,055-1,069. 7. Lawrence J A, Forrest L J, Turek M M et al (2010). Proof of principle of ocular sparing in dogs with sinusoidal tumours treated with intensity-modulated radiation therapy, Veterinary Radiology and Ultrasound 51(5): 561-570. 8. Kaser-Hotz B, Sumova A, Lomax A et al (2002). A comparison of normal tissue complication probability of brain for proton and photon therapy of canine nasal tumors, Veterinary Radiology and Ultrasound 43(5): 480-486. 9. Staffurth J A (2010). Review of the clinical evidence for intensity-modulated radiotherapy, Clinical Oncology 22(8): 643-657. 10. Gordon I K and Kent M S (2008). Veterinary radiation oncology: technology, imaging, intervention and future applications, Cancer Therapy 6: 167-176. 11. Farese J P, Milner R, Thompson M S et al (2004). Stereotactic radiosurgery for treatment of osteosarcoma involving the distal portions of the limbs in dogs, Journal of American Veterinary Medical Association 225(10): 1,567-1,572. 12. Lester N V, Hopkins A L, Bova F J et al (2001). Radiosurgery using a stereotactic headframe system for irradiation of brain tumours in dogs, Journal of American Veterinary Medical Association 219(11): 1,562-1,567. 8 / 8