A Review of the Principles of Veterinary Radiation Therapy
World Small Animal Veterinary Association World Congress Proceedings, 2011
Donald E. Thrall, DVM, PhD, DACVR (Radiology, Radiation Oncology)
North Carolina State University, Raleigh, NC, USA

Veterinary radiation therapy (RT) began as a relatively disorganized treatment, prescribed and administered primarily by diagnostic radiologists. As the field of veterinary oncology developed, it was clear that a more organized approach to veterinary RT was needed. Also, there was competition between internists, surgeons and radiologists with regard to the treatment to be administered; this was counterproductive with regard to optimal therapy for the individual patient. A need for a more organized approach to veterinary RT was realized. After much debate between the AVMA, ACVR and ACVIM, a specialty of veterinary radiation oncology was formed in 1994, under the auspices of the ACVR. There are now over 70 board veterinary radiation oncologists certified by the ACVR. The ECVDI is also considering establishment of a radiation oncology specialty in Europe.

In the early days, RT equipment was ineffective. Orthovoltage x-ray machines were common and only superficial tumors could be treated effectively. Orthovoltage x-ray units were nearly uniformly replaced by cobalt machines, which has better radiation dose distribution characteristics but these became difficult to maintain as the bureaucracy associated with large radiation sources increased following the terrorist attack in New York City on September 11, 2001. Also, cobalt machines are not ideal for treatment of very superficial tumors. Currently, nearly all cobalt units have been replaced with linear accelerators that generate high energy x-rays and electrons. These modalities are useful for treatment of both superficial and deeply seated tumors and there is no inherent radioactivity to deal with.

Patient selection is a very important part of the treatment process. Many times some form of therapy is implemented before a comprehensive plan has been developed. This can jeopardize the curability of a tumor. A common mistake is to excise a tumor without having a histologic diagnosis; this is suboptimal as the type of tumor can play a role in selection of the treatment modality. Tumors should be biopsied prior to resection. Also, large tumors should not be considered untreatable as there are many large tumors that can be managed effectively.

The method used for tumor biopsy is very important. A disposable trephine works well for superficial tumors or tumors that are immediately subcutaneous. The sample is large and not traumatized once the technique is learned. An incisional wedge biopsy is also a good technique but care must be exercised to avoid biopsying too superficially. Also, if performing an incisional biopsy the location and length of the incision are critical because if the incision is misplaced or too long, the subsequent radiation field may have to be enlarged. Tru-Cut® needles are a popular biopsy tool. These are good for deeper lesions but the exact site of biopsy location is not known, unless done under ultrasound guidance, and the tissue sample may be traumatized.

When deciding whether to use RT for a patient, many health care providers are most concerned about the type of tumor that is present. Although tumor type is important, the location and volume of the tumor may ultimately be more important in deciding whether RT will be of use as these factors will influence how effectively the tumor can be treated and will also influence outcome.

Tumor volume is the biggest factor that limits the radiation response of gross disease; the effect of tumor volume is huge. For example, the disease free interval may be 3x shorter for a mast cell tumor with a volume of only 1–9 cubic centimeters compared to a microscopic mast cell tumor. As a result of this significant volume effect, there are few indications for irradiation of macroscopic tumors. These include acanthomatous adamantinoma, small oral carcinomas, small grade II mast cell tumors, transmissible venereal tumors, and solitary lymphomas. Also, by necessity, brain and pituitary tumors are often irradiated without prior resection due to their inaccessibility, though it is realized that the response might be improved if the tumor volume could be reduced.

Combining surgery with RT is one of the most effective cancer treatment methods available. Effective use of this combination requires judicious preplanning.

Postoperative RT is an effective approach for mast cell tumor, soft tissue sarcomas and oral melanoma. If postoperative RT is being considered, the direction and size of the incision is critical. This will influence the probability of subsequent normal tissue complications. RT can begin shortly after surgery has been performed, but usually it is delayed until the incision has healed.

Preoperative RT is a standard therapy for human soft tissue sarcoma, but few canine and feline sarcomas are treated with preoperative RT because most of the time the tumor has already been excised when the patient is examined by a radiation oncologist. This eliminates one of the most effective approaches to dealing with soft tissue sarcomas. Preoperative RT can result in downstaging of a tumor so that the subsequent resection is less challenging technically and the chance for tumor-free margins is optimized. Preoperative RT is an effective way of treating feline vaccine associated sarcomas.

Concurrent chemotherapy and RT is the standard of care for head and neck carcinoma in humans. Improved disease control and survival have been proven in multiple randomized trials. However, there are no scenarios where concurrent chemotherapy and RT is the standard of care in dogs or cats. This pertains to the increased toxicity associated with this combination compared to RT alone. Chemotherapy is often used prior to or following RT for some animal tumors but concurrent chemoirradiation has not been optimized in veterinary medicine.

RT can be administered with either curative (definitive) or palliative intent. Definitive RT is reserved for those tumors where the chance of permanent local control is good and the discomfort of the acute normal tissue reactions that accompany definitive RT doses is justified. For definitive RT, a dose of radiation, termed a fraction, is given daily for 3+ weeks. Most prescriptions call for a total dose of 55–60Gy given in 3Gy or smaller fractions. For various reasons, there are many animals presenting for treatment that have tumors too large to be cured with surgery alone, RT alone or with surgery combined with RT. However, in many of these animals the symptoms alleviated temporarily with palliative irradiation. Palliative radiation involves a smaller number of fractions given over a shorter time leading to a smaller total radiation dose. The treatment is completed quickly without acute normal tissue reactions. It is not uncommon for an unexpectedly good response to be observed. If the original dose prescription was chosen wisely, the treatment can be repeated safely and the palliation prolonged.

One of the biggest advances of radiation therapy technology was the multileaf collimator (MLC). Rather than having to use a fixed rectangular treatment field, as would occur with four large opposing collimator blades, as present in a diagnostic x-ray machine, the MLC is comprised of leaflets that allow nearly an infinite combination of field shapes to be used. These irregularly shaped fields can be made more conformal to the volume to be treated, thereby reducing side effects in adjacent normal tissue. It may also be possible to give a higher radiation dose to the more conformal field to increase the chance of tumor control without increasing toxicity.

Another advantage of the MLC is the potential to use multiple beams with varying intensity of each beam to create highly specialized dose distributions. This takes normal tissue sparing to another level, and also provides more opportunity for tumor dose escalation. Powerful computing software is needed to identify the optimal beam configuration after constraints for tumor and normal tissue dose are defined.

These technical advances come at a price with the cost of sophisticated linear accelerators and treatment planning software escalating regularly. It is important that veterinary radiation oncologists not become too enamored with the technology and lose focus on the biologic modifications that may ultimately be more effective in improving tumor response than technologic advances.

In summary, veterinary RT has evolved into a highly specialized modality. Though sometimes expensive for the pet owner, it can provide cure of many tumors once thought incurable. What is important to realize that an incompletely thought out treatment plan at the outset can render a curable tumor non-curable. As the number of highly trained veterinary radiation oncologists expands, consultation prior to treatment is recommended as this will assure the optimal approach for an individual patient.

  

Speaker Information
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Donald E. Thrall, DVM, PhD, DACVR (Radiology, Radiation Oncology)
North Carolina State University
Raleigh, NC, USA


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