Radiation oncology for equine tumors

Radiation was first used on horses in 1906. Today, finer, more sophisticated therapeutic techniques, procedures and equipment can be used to treat the relatively uncommon cancerous tumors in horses.

What's important to a successful outcome is delivery of the radiation dose to eradicate the tumor while sparing surrounding healthy tissues. Fortunately for horses (and people), healthy tissue is more resilient, and current individualized techniques can deliver radiation to the tumor site with fairly good precision. Prognosis, of course, depends on tumor size, type and location.

"The large size of equine patients can make radiation therapy difficult, but it's a valuable tool for treating cancer and should not be overlooked when treating horses," says Janean Fidel, BS, MS, DVM, Dipl. ACVIM (medical oncology), Dipl. ACVR (radiation oncology), associate professor at Washington State University's College of Veterinary Medicine. The basis for the procedure entails damaging tumor tissues with ionizing radiation through the use of electromagnetic X-rays and gamma ray photons or corpuscular radiation (streams of electrons).

Radiation therapy's effectiveness is accomplished by destroying the cellular DNA, damaging one of the two strands, thereby rendering cells unable to divide so that they die attempting mitosis. Therefore, a tumor's growth rate plays a role in its demise. Only a portion of the cancer cells are killed with each dose. Although radiation damages both cancer and normal cells, the healthy cells can repair to a greater extent and survive by accelerating their division of the surviving cells, while cancer cells are more vulnerable. Healthy cells' ability to survive while cancer cells succumb is noted as the selective effect of irradiation. Furthermore, "Survival of normal tissue can be improved when radiation is administered over a prolonged period of time or fractionated into many small doses," says Fidel.

Equine radiation therapy can attack cancerous tissue, with radiation energy directed on the tumor cells in the area being treated. Radiation is ineffective for treating distant metastasized cells. The therapy is best indicated for solid tumors confined to a limited anatomical area and for those that are locally invasive. The most common tumors that are curable are, in descending order, squamous cell carcinoma or papilloma, sarcoid, soft tissue sarcoma and melanoma.

Radiation therapy is tailored to the particular tumor. "For deep-seated tumors that require imaging for assessment, computerized treatment plans based on the images are most accurate for predicting what the treatment will deliver to the tumor and normal tissue," says Fidel. Tumors of the same histologic type may respond differently depending on where they're located.

In addition to radiation therapy, initial accompanying surgery to debulk and minimize tumor size is important to a good outcome. Radiation before surgery improves resectability by reducing the tumor size and sterilizing tumor margins, thus making for easier surgical removal. Or radiation may be used postsurgically to eradicate tumor cells left behind after an incomplete excision.

Radiation dose, procedure type

For tumor management, the radiation dose is determined by radiosensitivity and the tolerance of nearby normal tissues. Connective, osseous, muscular and nerve tissues are most tolerant to the early effects of radiation injury; the ovaries, testes and hematopoietic and lymphoid tissues are the most vulnerable. Glandular tissue and squamous epithelium are intermediary in their sensitivity.

"When fractionated radiation is used, a total dose of radiation is chosen based on what is needed to kill the tumor," says Fidel. "A time interval is chosen based on the tumor and the normal surrounding tissue, and a fraction size is chosen based on the tissue in the field with the least ability to cope with large doses of radiation."

Radiation is measured in Grays (Gy), which vary with the type of treatment. Fraction size for curative treatments usually is 3 to 4 Gy. For palliative treatments, the dose is often 6 to 10 Gy.

Technique variation is based on tissue type (soft tissue vs. bone), the tumor's location (superficial vs. deep or inaccessible) and tumor size. The procedure is either teletherapy, in which the source of radiation is some distance (80 to 100 cm) from the target tissue, or brachytherapy, in which sealed radioactive sources are applied directly to the area of treatment.

Teletherapy allows for delivery of radiation to large and deep-seated tumors. Unfortunately, it also exposes surrounding normal tissue within the delivery path. With brachytherapy, high doses of radiation can be delivered directly to the tumor, which limits the dose to affecting adjacent normal tissues.

Although not commonly used in horses, teletherapy uses machines that emit high-energy x-rays or gamma rays, with treatment units in the megavoltage range (> 1 million eV). The high energy allows for precise treatment of large and deep-seated tumors, especially bone or soft tissue-invading bone tumors. Low-energy units are not suited for horses since they produce limited tissue penetration and may induce complications such as skin and bone necrosis. The tumor's size, depth and anatomical location direct the teletherapy treatment plan. Precise, high-radiation dosing must be accurately positioned to attack the cancer with minimal damage to normal cells. To accomplish this, the horse must be anesthetized.

Brachytherapy is better suited for use in horses because a high radiation dose can be delivered precisely and safely during a short duration. It's best for soft-tissue tumors. It cannot be used for bone tumors or tumors invading bone because of the limitations of implantation. Brachytherapy is most suitable for squamous cell carcinoma, sarcoid and soft-tissue tumors of the head, distal extremities and genitalia.

Iridium-192 and iodine-125 are commonly used. They emit gamma rays in the form of "seeds" or wire that are implanted under local or general anesthesia. It's best to use temporary implants that are left within the tumor for a specified time and removed once the prescribed radiation dose has been administered.

With brachytherapy, "sources generally deliver a low-dose rate, but because they're left in place and exposure is constant, a relatively high total dose of radiation is delivered over a short time (i.e., six days to two weeks, depending on the source and its activity)," Fidel says.

Although brachytherapy is highly successful, it's not without complications and poses a hazard to equine (and human) patients, says Fidel. "For eyelid squamous cell carcinoma, the radiation may affect the eye tissue, which cannot be shielded during treatment," she says. "Also, equine patients implanted with radiation seeds may rub the tumor, dislodging the seeds and contaminating the stall."

Brachytherapy may be used in combination with surgery. For some tumors, debulking is helpful before radiation, but for others, this process can create additional problems. It is critical to determine the extent of the tumor and tumor type before surgery.

Treatment options outlined

Clinicians at The Ohio State University (OSU) Veterinary Medical Center radiation therapy facility treat horses with a linear accelerator. Brachytherapy is not available. During the past five to seven years, the center has treated about 40 horses.

"I think radiation therapy is most useful for the management of head and nasal tumors in horses," says Eric Green, DVM, Dipl. ACVR (radiology and radiation oncology), clinical associate professor in the Department of Veterinary Clinical Sciences.

OSU clinic officials also use radiation therapy to treat sarcoids and squamous cell carcinomas—at least for those they can get to with the limitations of the machine, which is generally the head, extremities and some of the neck. "I think it plays a very useful role in the management of these tumors, often after surgery in many cases," Green says. "In my experience, we've treated a lot of sarcoids that have been refractory to all other forms of therapy with great success."

Most cases treated at the OSU facility have been quite successful. "Unfortunately, there is very little literature to determine what to expect in a lot of cases," Green says. "We're extrapolating a lot of the information we have from dogs, cats and people. I think we might have better responses in horses than one might expect for a dog or a cat, as the tumors may behave somewhat differently to the radiation therapy in horses."

Fidel notes that at Washington State University (WSU), squamous cell carcinomas are most commonly treated. For eyelid squamous cell carcinomas, radiation therapy works quite well, as opposed to genital squamous cell carcinomas that are harder to treat, though it is possible.

Officials at WSU do a novel protocol compared with other facilities. Horses are treated twice a day. "Radiation therapy works very well," says Fidel, "and I often think it's sort of foolish that people don't consider the option a little sooner. Some horses have had a variety of treatments, each of which last only for a short time. But a horse is going to live for 20 years, so why don't you cure the problem with radiation therapy?"

Regardless of success rates, there are limitations, especially dictated by cost and the small number of available treatment centers with proper radiation therapy equipment. There are only six locations across the country where practitioners can send their patients for radiation therapy. Keeping a copy of the contact information for those equine radiation therapy centers is key.

"As an oncologist, we always tell people to just call and we'll discuss the case and let them know the feasibility of doing the procedure," says Fidel. "If you think you have a horse that's a candidate for radiation therapy, you should not only talk to one of the radiation therapy facilities, but also send photographs and digital images of the tumor area to assist the radiation oncologist in making the proper determination. Almost immediately, we can give an idea of whether it's treatable and what side effects there may be, etc."

At WSU, oncologists consult with surgeons because not every eyelid squamous cell carcinoma is a good candidate. "If it's a fairly localized tumor, the horse has a fair amount of value and the horse is going to live several more years, (owners) should seriously consider the treatment," Fidel says. "It's curative. It makes the horse not just better for a short while—it can cure the horse."

The future

"I think the advances in the field are going to be limited, in that there are very few of us who can do radiation therapy with linear accelerators," says Green. "If people wanted to, they could purposely build a radiation therapy vault in their practices to accommodate horses. But radiation therapy is not going to be a lucrative venture, so unless someone wanted to subsidize that, it probably wouldn't be the best idea to deliberately build a vault for horses, unless you could also use it to treat small animals. Ninety-five percent of what I do is small animals. This is due simply to the fact that horses don't get a lot of tumors."

However, there are advances in human radiotherapy, including intensity-modulated radiation therapy (IMRT), radiosurgery and TomoTherapy.

IMRT is a procedure that uses multiple radiation beams from multiple angles. The beam shape changes during treatment to allow more precise delivery of radiation dose to the tumor with better avoidance of normal tissues. Like conventional radiation protocols, it requires multiple anesthetized treatment sessions. IMRT can be done with a conventional linear accelerator equipped with a multileaf collimator. It also requires cross-sectional imaging of the body part and a 3-D computerized treatment planning system to determine radiation dose delivery.

IMRT is being investigated in small-animal patients, but it has not been reported in horses. Auburn University's College of Veterinary Medicine has onsite computed tomography (CT), magnetic resonance imaging (MRI) and a linear accelerator with a multileaf collimator accessible for horses and can accommodate IMRT for horses, but it has not yet used the procedure, according to William Brawner, DVM, PhD, Dipl. ACVR (radiology and radiation oncology), a professor at Auburn's College of Veterinary Medicine. The challenge of doing IMRT in horses is that their body sizes limit the precise and repeatable positioning required and also make it difficult to allow the linear accelerator gantry to rotate around the patient to deliver the multiple beam angles. Linear accelerators are designed for people; none are designed for animals, and especially not for large animals. The tumor's location and size, the ability to obtain cross-sectional images and the ability to position the patient for gantry rotation will be important considerations in case selection. It's likely that only tumors of the head and extremities of horses will be accessible for IMRT.

A new equine radiation oncology unit is being built at Texas A&M College of Veterinary Medicine and Biomedical Sciences (TAMU CVM). The Diagnostic Imaging and Cancer Treatment Center (DICTC) is a state-of-the-art research and clinical facility that will contain about 9,000 square feet dedicated to advanced diagnostics, radiotherapeutics and translational research. The DICTC includes a 40-slice configuration SOMATOM Sensation Open CT scanner (Siemens), a wide-bore MAGNETOM Verio 3T MRI scanner (Siemens) and a TomoTherapy Hi·Art treatment system (TomoTherapy).

Michael Deveau, DVM, Dipl. ACVR (radiation oncology), a clinical assistant professor at TAMU CVM, says, "The facility signals a major new material and intellectual commitment on the part of TAMU CVM toward advancing research and improving veterinary patient health care."

TAMU CVM purchased a helical TomoTherapy system and has exclusively dedicated it for veterinary patient image-guided radiotherapy. The ring-based TomoTherapy platform combines integrated CT imaging with conformal IMRT to deliver sophisticated and unmatched radiation treatments with speed and precision while reducing radiation exposure to surrounding healthy tissue. "It's a flagship product in veterinary radiation oncology," says Deveau. Access to a TomoTherapy system for veterinary patients is limited to only two institutions worldwide: TAMU CVM and the University of Wisconsin-Madison Veterinary Medical Teaching Hospital. Only Texas A&M intends to treat large animals, says Deveau.

"Ring-style gantry systems like the Hi·Art treatment system aren't specifically designed for large animal use," says Deveau. "Of course, the same can be said for any of the linear accelerators. The systems are designed for attributes encompassing the human silhouette. It's fortunate we're able to translate the use to such a wide range of species and clinical presentations in veterinary medicine."

The DICTC is scheduled to start treating small-animal patients in September. Integration of large animals will be limited initially to the weight limit of the system's couch (425 to 450 lbs.). Active research and development is under way to integrate an independent couch system for large animals weighing more than 450 lb, but it's currently not ready for clinical implementation.

Ed Kane, PhD, is a researcher and consultant in animal nutrition. He is an author and editor on nutrition, physiology and veterinary medicine with a background in horses, pets and livestock. Kane is based in Seattle.