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* This is the Veterinary Version. *

Overview of Radiation Therapy

By Jimmy C. Lattimer, DVM, MS, DACVR, DACVRO, Associate Professor (Radiology and Radiation Oncology), Veterinary Medicine and Surgery, Veterinary Medical Teaching Hospital, University of Missouri

Radiation therapy has seen dramatic increases in demand and sophistication in recent years, which has led to creation of a board specialty in radiation oncology, granted by the American College of Veterinary Radiology. The sophistication and scope of both veterinary imaging and radiation therapy has advanced to the point that only a few radiologists now actively practice in both the fields of imaging and therapy.

Historically, radiation therapy was delivered using orthovoltage x-ray machines or very large activities of 64-cobalt and 137-cesium. Except for a few specialized instances, orthovoltage x-ray machines have fallen from favor because of the intensity of adverse radiation reactions associated with their use and their limited flexibility. Cobalt and cesium are no longer used because as long-lived isotopes they are extremely dangerous and heavily regulated in most of the world. Today, it is virtually impossible to purchase these sources because of public safety concerns.

Veterinary radiation therapy practices today almost exclusively use linear accelerators as the source of the ionizing radiation used to treat neoplasia and occasionally specific benign diseases. These machines produce powerful x-rays and electron beams with energies of 4–20 million electron volts. The x-rays are used to treat deep-seated tumors, whereas electron beams are generally used to treat tumors of the skin and subcutis. Linear accelerators are complex machines that require the support of a medical physicist to maintain safe and effective use. This increased support load is offset by the machine’s flexibility and speed, which is necessary as treatment techniques become more sophisticated and complex.

Computerized treatment planning systems are now used by veterinary radiation oncologists to improve the localization and distribution of the therapeutic beam within the patient. This reduces the dose to healthy tissues relative to the dose to the neoplastic tissue being treated, increasing cure or control rates and reducing the severity of healthy tissue complications. These programs are best used in conjunction with CT or MRI images, which determine the position and extent of the tumor within the body and its relative position to healthy structures. Many hours of work may be required to generate a treatment plan for a large, complex tumor.

Patients are then treated in precisely the same position as they were in for the CT or MRI. Repeatability of positioning is of paramount importance and can be achieved by using special positioning devices in conjunction with careful landmarking. Proper patient positioning is then confirmed using an imaging system integrated with the linear accelerator. Once proper positioning is confirmed, the treatment can be administered. Great attention to detail is necessary during this part of the treatment, because even small changes in position can have profound effects on the distribution of the radiation dose delivered. This is especially true in CNS tumors, in which the lesion diameter may be only 1 cm.

Except in rare instances, all radiation therapy treatments using external sources of radiation must be delivered with the patient immobilized by general anesthesia. Because the plane of anesthesia required is light and the procedures are typically of a relatively short duration, this repeated anesthesia is well tolerated, and complications are few with proper observation and monitoring. This requirement for anesthesia is rarely if ever a contraindication for implementing a course of radiation therapy.

A typical course of radiation therapy consists of multiple doses of radiation delivered on different days. This is done to allow healthy tissues to heal somewhat between doses. Healthy tissues have a greater ability to repair radiation damage than neoplastic tissues; therefore, use of multiple small doses of radiation, although it has a cumulative effect, favors survival of healthy over neoplastic tissues. Most radiation therapy regimens designed with curative intent use 15–20 individual doses (fractions) of radiation. Each dose of radiation may be delivered using several different fractions of radiation of differing size, shape, and intensity. In cases when the tumor is too advanced to be controlled by radiation, palliative therapy using larger doses and fewer fractions of radiation may be used to retard the tumor's growth or reduce associated pain. Such a palliative approach may also be used when mandated by owner finances.

Whenever possible, removal of a tumor by surgery is preferred. However, in many instances, large neoplasms, or those in critical areas such as the brain, are not amenable to complete or even partial surgical removal. Even when a tumor is grossly removed, microscopic foci of neoplastic cells often extend beyond the limits of the surgical field. This is more common for some tumor types than for others. In all of these instances, radiation therapy, often in combination with chemotherapy, is useful in treating the remaining cancer. Radiation therapy is often the treatment of choice for brain tumors, nasal tumors, and other neoplasms of the head and neck in which even partial resection may be extremely disfiguring or carry a high risk of mortality. It may be the only treatment option for cancer of the vertebral column and pelvic canal. Radiotherapy is also used to treat tumors in the mediastinum and soft tissues of the skin and subcutis either before or after surgery. It is seldom used in the treatment of lung neoplasia or in the treatment of neoplastic disease of the abdominal cavity because of the mobility of tumors in these areas. However, treatment of mediastinal tumors and those of the pelvic canal, such as thymoma and prostatic carcinoma, are possible and may well be indicated. As the sophistication of radiotherapy techniques increases, more and more types of neoplasia are being treated at least in part by radiation therapy.

In many instances, radiation therapy, especially when combined with surgery and chemotherapy, may be curative. However, radiation therapy can delay the development of disease or control its expansion in many instances. Radiation oncologists typically talk in terms of control rate rather than cure. Sometimes, the control may be relatively short lived, and recrudescence of the tumor occurs within months after completion of the treatment regimen. In other cases, control may last several years or even until other disease processes supersede the neoplastic disease. Unfortunately, it is seldom possible to predict even within an individual tumor type which patients will experience good control and which ones will not. Continual advances in the evaluation of genetic markers within tumors hold the promise of being able to predict this in the future.

Because of the risk of serious and potentially life-threatening complications associated with this treatment modality, the complexity of the equipment and sophistication of the radiation therapy procedures should only be prescribed by and administered under the supervision of a veterinarian with special training, experience, and certification in the field of veterinary radiation oncology. A veterinary radiation oncologist should also be consulted any time further treatment is contemplated for neoplasia that has been treated by radiation therapy. This is particularly important if surgery within the radiation field is being considered.

Brachytherapy is the implantation of radioactive sources into the tumor to achieve radiation therapy. It is seldom used for treatment of cancers in animals because of the difficulties associated with maintenance of the sources and keeping the sources in place within the tumor. The notable exception to this is the use of radioiodine to treat thyroid adenomas in cats and adenocarcinomas in dogs. Radioisotopes developed for treatment of metastatic osseous neoplasia in people are also useful in the treatment of primary and metastatic bone cancer in dogs and cats. Such "nuclear oncology" treatments are being continually developed for use in human medicine and are directly applicable to veterinary patients as well. In fact, these treatments are typically developed in veterinary patients before being introduced into human medicine.

Implantable radiation sources that are so small (microns or even nanometers) that they are permanently implanted within the body blur the margins between radiation therapy and nuclear medicine. The implantation of such sources comes under the heading interventional radiology. Interventional radiology procedures such as catheter placement and CT guidance of source implantation are used to introduce both macroscopic and microscopic scale brachytherapy sources into neoplasms located deep within the body. Targeting of such agents is accomplished either by using sources of sufficient size to be locally retained within the tissue or capillaries of the tumor or by targeting them specifically to tumor cells using monoclonal antibody labeling. These techniques have been around for many years but have not received widespread attention in veterinary medicine because of the cost of both the agents and the equipment required for their implantation. However, in recent years there has been a marked upswing in the interest in such interventional radiology procedures for both treatment and diagnosis, not only of cancer but also of many other conditions. Such techniques may well increase the interest in and availability of brachytherapy procedures. Because of the risk of excessive radiation exposure and contamination of the patient or hospital, these procedures should be performed only by veterinarians with appropriate training, experience, and support in a properly licensed facility.

A full list of appropriately trained and accredited veterinarians as well as a list of radiation therapy facilities can be obtained through the American College of Veterinary Radiology or the American Veterinary Medical Association.

The radiosensitivity of virtually any neoplasm is higher in minimal or microscopic disease. Some neoplasms respond well initially but tend to recur at some time after radiation therapy. The time to recrudescence is highly variable between and within tumor types.

Selected Common Neoplasms that Can Be Treated with Radiation Therapy

Tumor Type

Radiosensitivity

Comments

Nasal adenocarcinoma

Intermediate

Usually respond well but often recur

Nasal squamous cell carcinoma

Low

Response is often minimal

Nasal chondrosarcoma

Intermediate to high

Some subtypes respond better than others

Nasal osteosarcoma

Low

Response may be better if after surgery

Oral melanoma

Low to intermediate

Poor response usually unless after surgery

Oral squamous cell carcinoma

Low

Especially poor in cats; aggressive treatment required

Osteosarcoma

Low

Metastatic disease in >90%; pain palliation

Chondrosarcoma

Intermediate

Best when small; metastasis a problem

Fibrosarcoma

Low to intermediate

Depends on tissue of origin

Injection-related fibrosarcoma

Low to intermediate

Best if done after first surgery, poor later

Thyroid carcinoma

Intermediate to high

Usually respond very well; 131I possible

Thyroid adenoma

High

Treat with 131I (>95% cure)

Salivary adenocarcinoma

Intermediate

Usually respond well, especially in cats

Brain tumor – meningioma

Intermediate to high

Usually stabilizes mass; good clinical result

Brain tumor – glioma

Low to intermediate

Depends on size, location, and clinical signs

Brain tumor – lymphoma

High

Most effective treatment for CNS lymphoma

Brain tumor – metastasis

Intermediate

Effective but short term due to other disease

Spinal cord mesenchymal tumor

Intermediate

Reasonable response but dose limited by cord

Spinal neurofibrosarcoma

Low to intermediate

Short-term response good but commonly recur

Lymphosarcoma

High

Excellent response but can only treat locally

Cutaneous lymphoma

High

Often curative

Nasal lymphoma

High

Good response, often very durable

Thymoma

Low to high

Low for scirious form, high for lymphocytic

Mediastinal chemodectoma

Low

Large masses, dose limited by heart and lungs

Adrenal neoplasias

Low

Difficult to accurately localize treatment

Transitional cell carcinoma

Intermediate

May respond well initially but recur

Prostatic adenocarcinoma

Low to intermediate

Data available on response is quite variable

Mast cell tumors

Intermediate to high

Very good for low grade, less for high grade

Peripheral nerve sheath tumor

Intermediate to high

Strongly recommended after surgery

Soft-tissue sarcoma

Low to high

Improves control after surgery, not alone

Lick granuloma

Intermediate to high

Treatment of last resort, often works well

Transmissible venereal tumor

High

Very good control even for large tumors

Equine sarcoid

High

Used in refractory tumors, brachytherapy

Equine nasal carcinoma

Intermediate to high

Beam treatment effective, very few sites

Equine ocular squamous cell carcinoma

Intermediate to high

Best treatment when bone involved

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* This is the Veterinary Version. *