Radiation Therapy in Animals

Oncological treatment goals are often specified as "definitive" or "palliative" intent. Oncologists typically do not use the word "cure," which implies that the cancer can be completely eradicated with no chance of the original tumor returning or metastasizing. True "cure" is uncommon.

An understanding of the underlying biology and clinical disease process based on the literature available will provide a level of prognostication to veterinary oncologists when deciding what treatment procedure to elect and how aggressively to pursue it. Patient factors, such as the presence of concurrent diseases (diabetes, myxomatous mitral valve disease, varying stages of chronic kidney disease, etc) as well as the owners' goals, play a role in the decision to pursue definitive or palliative intent treatment as well as the ultimate treatment modality.

Treatments administered with definitive intent are expected, based on evaluation of the patient as well the specific diagnosis of their cancer (biopsy report), to give the pet the best chance for durable survival time without recurrence or metastasis of their cancer for a period of time.

A typical example of this would be a pet dog with a grade I soft tissue sarcoma on the antebrachium that was removed with dirty margins and has recurred multiple times. This patient could be prescribed conventionally fractionated definitive intent radiation therapy (total radiation dose administered in 18 to 19 fractions on consecutive weekdays) to the scar after surgical removal, with the goal of keeping the tumor from growing back, hopefully within that patient's lifetime. Based on the known literature of this tumor type and its expected biological behavior, the prognosis for such a patient would be excellent, and the risks of multiple anesthetic episodes as well as the expected radiotherapy adverse effects are outweighed by this excellent prognosis.

Treatments administered with palliative intent have the goal of helping to alleviate pain and discomfort. Palliative intent treatments do not imply "giving up" or substandard treatments. In the context of radiation therapy, palliative intent treatments are powerful tools for alleviating pain, discomfort, and clinical signs associated with the tumor.

Once a given tumor type becomes very advanced or the patient has been treated for their cancer with a variety of modalities before receiving palliative radiation therapy, prognosticating survival time can be difficult. The goal of palliative radiation therapy is to alleviate pain and discomfort while avoiding adverse effects from radiation therapy. The total dose is lower, while the dose per fraction is typically higher.

Stereotactic treatments, while more intensive and administered in higher doses, are not expected to cause immediate adverse effects. For this reason, stereotactic treatments may be administered with palliative intent depending on the patient's condition and expected prognosis. A dog with a nasal carcinoma that is small and confined to the rostral nasal cavity may be administered stereotactic radiotherapy with definitive intent (3 treatments of 10 Gy/fraction on consecutive weekdays; Gy denotes a unit of absorbed radiation dose equal to 100 rads). A dog with a nasal carcinoma, chronic renal failure, and a tumor that is invading into the brain causing seizures may be prescribed the same stereotactic protocol after discussion with the owners; however, due to the stage of the disease, clinical signs, and comorbidities, the goal is of more palliative intent, even though the protocol is the same.

Palliative intent treatments and, in some cases, definitive intent treatments are typically about optimizing the patient's ability to live with their cancer rather than die from it. In many cases cancer can be manged like any other chronic disease while maintaining good quality of life with treatments that are optimized toward avoiding adverse effects.

In most veterinary practices offering radiation therapy, linear accelerators are the source of the ionizing radiation used to treat neoplasia and occasionally specific benign diseases. Linear accelerators are complex machines that require the support of a medical physicist to maintain safe and effective use.

Linear accelerators produce high-energy x-rays and electron beams with energies of 4–20 MeV. X-rays are used to treat deep-seated tumors, whereas electron beams are generally used to treat tumors of the skin and subcutis.

Contemporary teletherapy techniques incorporate image guidance via cone beam CT (CBCT), which is integrated into the treatment delivery system (see cone beam CT system image). Image-guided radiotherapy (IGRT) allows for delivery of radiation therapy to tumors anywhere on the body.

Linear accelerator, cone beam CT system

Image

Courtesy of Dr. Nicholas Rancilio.

Computerized treatment-planning systems that accurately model the deposition of radiation energy within the body are used by veterinary radiation oncologists to improve the localization and distribution of the therapeutic beam within the patient. This decreases the dose to normal tissues relative to the dose delivered to neoplastic tissue, improving control rates while decreasing the severity of complications in normal tissues.

These programs are used in conjunction with CT images to calculate dose and determine the position and extent of the tumor within the body and its position in relation to normal structures. MRI, especially for CNS tumors, is frequently used in conjunction with CT to localize the tumor. Images obtained by MRI cannot typically be used for dose calculation, so additional imaging with CT is required for radiation therapy planning.

Hours of work on a computer by a radiation oncologist or dosimetrist may be required to carefully delineate the tumor and each of the normal structures at risk to generate a treatment plan for a large, complex tumor. The computer system is able to quickly generate dose profiles for proposed treatment configurations and determine whether the plan meets certain treatment constraints set by the radiation oncologist.

Once the treatment plan is set, the patient is then treated in precisely the same position they were in for the CT and MRI. Repeatability of positioning is of paramount importance, and special positioning devices are used in conjunction with careful landmarking to achieve this. This requires that the patient be scanned in exactly the same position in which it will be treated, requiring close communication between the diagnostic radiologist and radiation oncologist.

The integration of image guidance into the treatment delivery system (linear accelerator/teletherapy) using CBCT allows for robotic control of the treatment-positioning table while comparing the original planning CT scan to the treatment position. The treatment beam can be aligned to match the anatomy with submillimeter precision and to avoid normal tissues as much as possible by adjusting the positioning of the robotic treatment table.

To achieve this, a CT is performed with the patient set up in the exact position in which they will be treated. Proper patient positioning is then confirmed using the imaging system integrated with the linear accelerator before a treatment is administered. Close attention to detail is necessary during this part of the process because even small changes in position can have profound effects on the distribution of the radiation dose delivered. This is especially true in stereotactic radiotherapy or stereotactic body radiotherapy, where the target positioning must be determined with submillimeter accuracy.

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 relatively short duration, this repeated anesthesia is well tolerated, and complications are few with proper observation and monitoring by trained and experienced technologists. 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 therapeutic technique is termed conventionally fractionated definitive intent radiation therapy. This schedule allows 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, which have a cumulative effect, favors survival of healthy over neoplastic tissues.

Conventionally fractionated definitive intent radiation therapy regimens use 10–20 individual doses (fractions) of radiation. Each dose of radiation may be delivered using several beams of radiation of differing size, shape, and intensity.

Intensity-modulated radiation therapy (IMRT) is a newer adaptation of radiation therapy in which each of the primary radiation treatment beams is broken down into a number of smaller beams to tightly control the deposition of radiation injury in the tissue, thereby improving not only tumor control but normal tissue complication rates.

Doses of radiation therapy using teletherapy are measured in a unit called gray (Gy) and administered in fractions (individual treatment sessions). An example dose and fractionation scheme would be 3 Gy/fraction administered on 19 consecutive weekdays to a total dose of 57 Gy, which may be variously denoted (eg, 3 Gy x 19 fx or 57 Gy/19 fx).

Stereotactic radiotherapy (SRT) and stereotactic body radiation therapy (SBRT) are techniques that incorporate IGRT, rigid and reproducible patient immobilization, and treatment planning using sharp dose falloff to deliver an ablative dose of radiation to only the tumor. These techniques may also be referred to as stereotactic radiosurgery (SRS) or stereotactic ablative radiotherapy (SABR). 

In this type of radiation therapy, a definitive intent, intense dose of radiation therapy is delivered to the tumor in 1–5 fractions on consecutive or alternating days in a single week. This markedly decreases the hospital stay for the patient and the inconvenience for the owner, but often not the cost. Use of these techniques should be reserved for grossly visible tumors.

Administration of ablative doses of radiation to normal tissue, such as a scar where only microscopic disease exists, may result in treatment failure because microscopic foci of cancer cells may be missed and injury to normal tissue may occur. There is no image-guidance system that can detect a foci of microscopic cancer cells that would enable this modality to target microscopic disease while avoiding injury to normal tissue (see stereotactic radiotherapy images).

CT scans, stereotactic radiotherapy, dog

Image

Courtesy of Dr. Nicholas Rancilio.

Stereotactic radiotherapy requires extreme precision in the administration of the radiation beam to avoid normal tissues and to irradiate only the neoplastic tissue. The equipment required to do this is both delicate and expensive.

Although SRT has a number of advantages, it also has the potential to result in severe normal tissue adverse effects if an inappropriate administration occurs or if large amounts of tumor undergo acute necrosis. For these and a number of other reasons related to the physics of radiation, SRT may not be appropriate for very large tumors.

In cases where the tumor is very advanced or prolonged survival time is not expected, palliative therapy with smaller total doses of radiation may be used to slow the tumor's growth or decrease associated pain. This is done to improve the patient’s quality of life or to give the owner more time with their animal. Palliative protocols are intended to be therapeutic, not curative. While fewer fractions are administered, similar to SRT, the dose intensity is much milder. Thus, inclusion of normal tissues (eg, skin or oral mucosa) is permissible, whereas in SRT, irradiating the skin should be avoided.

Palliative treatments with most linear accelerators do not always require a CT scan and can be administered by manual calculation, which may help to save costs for a patient with a poorer prognosis. Palliative intent protocols are completed in a short period of time (once daily for a week and once weekly for 4 to 6 weeks are typical palliative intent protocols). Such treatments have a low likelihood of resulting in durable control of the cancer, and they carry a greater risk for late radiation effects if a durable control does occur, which happens in some cases.

The potential late effects from palliative intent protocols can be moderated by using a smaller total dose and fraction size (4 Gy/fraction administered on 5 consecutive weekdays) to account for uncertainty in predicting survival time in patients with advanced but potentially radiation-responsive cancers (see CT scan, teletherapy image). Similar to stereotactic radiotherapy, palliative intent protocols are not typically administered to microscopic foci of tumor because there is no gross tumor to palliate or the microscopic foci of neoplastic cells may be missed.

CT scan, sagittal slice, teletherapy, dog

Image

Courtesy of Dr. Nicholas Rancilio.

Radiation therapy is able to control tumors for prolonged periods of time, depending on the type of cancer being treated as well as the protocol that is administered.

When treated with radiation therapy, patients with nasal tumors and brain tumors may have prolonged survival times of 8 months to a year or longer. The bulk of the data for brain tumors and nasal tumors focuses on conventionally fractionated definitive intent radiation therapy. Survival times for stereotactic radiotherapy approach what would be expected for more conventional radiotherapy techniques for brain tumors and nasal tumors in dogs and cats.

In some cases, patients can be treated with a second course of radiation therapy if the duration of response is long enough (typically greater than 6 months).

See the table for a list of tumors and expected survival times after various types of radiation therapy.

Because of the risk of serious and potentially life-threatening complications associated with radiation therapy, the complexity of the equipment, and the sophistication of procedures, radiation therapy 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 when 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 or scar bed to administer radiation. It is widely used in human medicine, but seldom 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.

Radiation safety is also a concern in that the patients must be monitored and confined until the sources are removed or decay to a nonradioactive state. However, implantation of the radiation source directly into the tumor results in very high doses of radiation to the tumor with minimal dose to surrounding tissue. This can improve the control rate in many instances, with a decrease in normal tissue complications as compared with external beam radiation therapy.

Brachytherapy treatment times are on par with those observed with SRT and results may be similar. The implantation of the sources is, however, a surgical procedure and carries with it some amount of risk. One of the major barriers to this type of treatment is cost, in that the sources are expensive to purchase and maintain and may require frequent replacement or even be single use if they are to be a permanent implant.

Use of brachytherapy in veterinary medicine has been limited due to the cost of both the radioactive sources and the equipment required for their implantation. 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. Very few veterinary radiation oncologists focus on this treatment modality, and only a few facilities have the capability to administer brachytherapy to veterinary patients.

Biologically targeted radiotherapy, or nuclear oncology, involves administration of a radioactive therapeutic agent to a patient and having the radioisotope localize within the tumor by one of a variety of physiological processes. When deemed appropriate by pretreatment testing, this can be a very effective and efficient way to treat these conditions in animals.

An example is the use of radioiodine to treat thyroid cancer. In veterinary medicine, this has become a mainstay of treatment of thyroid adenomas in cats (ie, treatment of feline hyperthyroidism with iodine 131) and occasionally to treat thyroid adenocarcinomas in dogs. 

Bone-seeking radioisotopes developed for treatment of metastatic osseous neoplasia in humans are also useful in the treatment of primary and metastatic bone cancer in dogs and cats. Cancer-seeking mononuclear antibody and small-molecule isotope carriers are currently available for treatment of a variety of neoplasias in humans, such as neuroendocrine and mammary carcinomas.

Biologically targeted radiotherapy may also be effective in the treatment of metastasis distant from the primary tumor, which is another advantage over conventional radiation therapy in which the treatment of metastasis is usually limited to treatment of regional lymph nodes or, on rare occasions, up to 3 distant metastases. As the number of agents grows, more tumor types may potentially be treated in this way.

There are many facilities in the US dedicated to radioiodine treatment of cats with hyperthyroidism using iodine 131 because the dose of radiation administered is much lower and the duration the patient will remain radioactive is short. The use of biologically targeted treatments for cancer treatment (eg, thyroid or bone cancer) is limited to a few facilities with the capability to safely isolate patients that are highly radioactive for a period of time after treatment. Radiation doses of biologically targeted agents for malignancies such as thyroid carcinoma are typically orders of magnitude higher than those needed to treat benign thyroid adenoma in cats.

Regardless of the way in which the radiation is delivered, the goal of radiation therapy is to eradicate or severely damage the tumor cells to prevent further growth or regrowth. It is inevitable that some normal cells and tissues will be irradiated at the same time, and it is the damage to these normal structures that limits the radiation dose that can be delivered.

There is often a narrow therapeutic index separating the dose that will control the tumor and the dose that the normal tissues cannot tolerate or recover from. The way radiation therapy is currently practiced, there is almost always a therapeutic effect on the tumor. This results in either tumor regression or cessation of growth that lasts for a variable period of time. Adverse effects on normal tissues may occur either immediately after the radiation therapy or later.

The short-term adverse effects are managed medically and, unless very severe, generally heal 4–6 weeks after the end of the course of treatment. Short-term adverse effects typically occur in rapidly proliferating normal tissues such as the skin, oral mucosa, and GI epithelium. These are tissues of self-renewal and are the colloquially noted tissues, such as the mouth or skin, where a radiation "burn" will occur. These adverse effects are termed desquamation or mucositis, depending on their location, and are typically completely reversible with time, pain medication, and appropriate patient management such as e-collars, fluid therapy, and feeding assistance (see soft tissue sarcoma image).

Soft tissue sarcoma, dog

Image

Courtesy of Dr. Nicholas Rancilio.

In many cases, with image-guidance and intensity-modulated radiation therapy, these types of acute adverse effects can be avoided completely. Late effects may result in loss of function and fibrosis or even necrosis of normal tissues, and these are the effects that dictate the design of radiation therapy plans. Late effects of radiation therapy are irreversible adverse effects that can occur in slowly proliferating normal tissues such as bone, smooth muscle, and CNS. The probability of late adverse effects is mediated by the fraction size and total dose of radiation administered.

With careful planning and management of normal tissue adverse effects, most radiation therapy patients will have positive effects of varying duration.

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.

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. More information on the management of cancer in general is available from the Veterinary Cancer Society.

• American College of Veterinary Radiology

• American College of Veterinary Internal Medicine

• Veterinary Cancer Society

• Also see pet health content regarding radiation therapy.

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