Rodney C. Straw, BVSc, DACVS
Radiation therapy (RT) uses high energy radiation to kill or shrink cancer cells by trying to target fast-dividing cancer cells and disrupts or destroys their genetic material, preventing the cells from continuing to grow. It is a modality generally used to treat primary cancer sites but has also been useful to alleviate pain and problems associated with some metastatic lesions.
The types of radiation and methods of delivery can be grouped in two general categories:
External radiation: The most widely used method involves a radiation beam that comes from an outside machine and is directed at the cancer site or tumor.
Internal radiation: This uses radioisotopes that emit forms of ionizing radiation (interstitial or brachytherapy) as radiopharmaceuticals that are injected or as rods, applicators or bead inserted into cavities or the tumours themselves.
Radiation therapy is sometimes used alone to treat cancer. In other instances, it is combined with other cancer treatments such as chemotherapy or surgery. Radiation may be used before or after surgery, depending on the type of cancer, the animal's treatment plan and the clinician's preference (surgeons like operating first and radiation oncologists generally like to give the RT first).
While RT often is effective at treating and controlling cancer, it can also damage normal cells. While this damage usually is temporary, it can cause serious side effects for some animals. The potential side effects vary with the type and amount of radiation received in treatment. This will in turn depend on the goal of the treatment. The animal's general health, tolerance for radiation and goals are considered when balancing the risks of radiation therapy with the potential benefits. We will be talking about external beam RT or telotherapy.
External Beam Radiation Therapy
This type of radiation is a non-invasive, non-surgical treatment which delivers high energy x-rays. It is performed on usually five days a week for about three weeks. External radiation is essentially painless and can be delivered in relatively short sessions requiring short daily anaesthetic episodes (15 to 20 minutes). It can be used to treat many types of cancers. External beam RT is usually classified as orthovoltage or megavoltage RT based on the energy of the photon. Orthovoltage machines produce x-rays with an energy of 150 to 500 kVp; megavoltage radiation emits photons with an average energy greater than 1 million electron volts. (Our linear accelerator produces 6 MV). Although some veterinary radiation oncology centres continue to treat with orthovoltage machines, megavoltage radiation, which is used almost exclusively in human centres, is becoming more common. Megavoltage radiation for therapy can be obtained from cobalt machines or linear accelerators. Megavoltage radiation from linear accelerators can allow radiation of deep seated tumours and have a skin sparing effect because the photons need to interact with tissue to allow the dose to build up before the maximum dose is reached. If orthovoltage units are used to produce the same dose in deep tissue there would be horrendous skin necrosis from the skin receiving a full dose. Tissue equivalent bolus material may be used with megavoltage radiation to allow the surface to receive higher doses if this is required. Also many linear accelerators (such as ours) can also deliver electron beam irradiation which is excellent for surface tumours and somewhat spares the deeper tissue.
Once a veterinarian has determined that radiation therapy is appropriate, the animal will be referred to a radiation oncologist and a series of planning decisions will be made. The oncologist will receive information from the primary care veterinarian, including the results from any scans, pathology reports, surgeries or procedures. The oncologist may also consult with other professionals involved in the treatment who are a part of the animal's cancer care team.
After reviewing information, the radiation oncologist will decide which method of radiation will be best. The choice to use external radiation therapy will lead to a process called simulation (sometimes called a marking session). With the help of a specialized radiation technician, the veterinarian will: check tumor size (if present), identify areas where the cancer may have spread, identify normal tissues in the treatment area, take measurements and mark the area to be radiated
After this, the veterinarian will determine the amount of radiation to be delivered. A clinical physicist might suggest advice on technical matters regarding the radiation therapy, and a dosimetrist will help design the treatment plan so that it is specialized to the individual needs of the animal.
Radiation dosage is delivered in units known as Gray. A Gy is 1 Joule/kg and is equal to 100 rad. The total dose administered to a patient should have a low probability of causing late normal tissue reactions in the region of therapy. However the response of these tissues depends on the fraction size. For example, 48 Gy administered in 4 Gy fractions has a much higher probability of causing late effects than 48 Gy administered in 3 Gy fractions. The probability of tumour control is fairly similar. There is therefore a benefit in protocols that use doses per fraction. There are, however, no perfect RT protocols and all commonly used in Veterinary radiation therapy have advantages and disadvantages. The veterinarian will use a therapeutic ratio in calculating the most effective dosage level. The therapeutic ratio compares the damage inflicted on cancer cells with the damage likely to occur to normal cells. Once a total dosage amount has been selected, it is divided into smaller amounts that are administered over individual treatment sessions. This is called the fractionation schedule, and it allows the veterinarian to maximize the treatment's ability to kill cancer cells while minimizing any incidental damage to normal cells by giving the body rest periods to recover.
Animals also may receive a long-lasting tattoo mark at the spot where the radiation is to be delivered. This will ensure that the radiation is precisely directed at the appropriate spot during each treatment session. The tattoo also provides important placement information should any future radiation be necessary. It is important that animals remain very still and in the same position during a treatment session. This can be achieved by general anaesthesia and placing the animal in a custom mold and bite cast. This ensures that only the proper area is treated.
As the radiation is delivered, the machine being used for the procedure may be rotated around the animal's body to deliver radiation to the cancer from different angles. A treatment session typically lasts for 15 to 20 minutes, although the actual radiation exposure time is much less.
External radiation treatments typically are scheduled on a daily basis, five days a week over a period of about 3 weeks. In some cases, animals will be treated with coarse fractions, which is one large fraction weekly for 3 to 4 weeks for palliation of bone pain from cancer or for malignant melanoma for instance.
Potential Side Effects of RT
While radiation therapy can be highly beneficial to cancer animals, it also often results in significant side effects. These are the result of damage to normal cells incurred during treatment. They usually will disappear once treatment has ended. Side effects are most likely to occur in the area being treated and include:
Fatigue: This is a symptom generally associated with radiation, but its cause is unknown. There is no single treatment for fatigue, but veterinarians can sometimes offer relief by treating the underlying causes of symptoms. For example, if an animal has anemia, blood transfusions or medications may be ordered to stimulate production of red blood cells.
Skin problems: Early in treatment, a faint redness may develop, followed by dryness and peeling. The skin may also become darker and itchy. In some animals, extreme weeping and peeling may eventually develop, or thinning or hardening of the skin.
Mouth problems: Inflammation of the mouth lining (mucositis) may occur with radiation in the head and neck area. Dryness and loss of taste in the mouth also can occur, and can be permanent in the worst cases. Care should be careful to keep their mouths clean to reduce the chance of infection. Finally, radiation can sometimes increase the chance of getting dental disease. A dental is often performed prior to starting radiation of the head and neck.
A rare and serious late effect of radiation to the brain or cord is radiation necrosis. This occurs months to years after radiation treatments. In rare cases it can be fatal. It is avoided by careful radiation planning, fractionation and portal selection.
Lung problems: Radiation treatments of the chest area can cause a decrease in surfactant, the substance that keeps the air passages open. This may result in coughing and shortness of breath. Steroids are sometimes prescribed to reduce inflammation. Fibrosis (stiffening and scarring) can occur later, significantly reducing breathing capacity.
Gastrointestinal tract: Radiation in the abdomen may result in swelling or inflammation of the esophagus or intestines. This can cause nausea, vomiting or diarrhea. Antacids can help, as can a GI diet. In severe cases, dehydration may require administration of intravenous fluids.
Reproductive organs: Radiation of the testicles can cause permanent loss of sperm production, while radiation of the abdomen in intact bitches or queens can damage the ovaries. In most cases, only one ovary will be involved in radiation therapy, which lessens the likelihood of infertility.
Pelvic radiation can cause the vagina, urethra, penis and rectum to be tender and inflamed for weeks following radiation. Scarring can narrow these tubular organs with chronic consequences.
Secondary cancers: Radiation therapy now targets cancers more precisely, which makes the development of second cancers less of a problem than in the past. The risk remains, but it is low and should be weighed against the potentially life-saving benefits of radiation therapy. It takes over 12 months for new cancers to develop in the radiation fields and is extremely rare in veterinary radiation therapy cases.
Ongoing RT Research
Three-dimensional (3-D) conformal radiation therapy: This builds upon the traditional two-dimensional planning of radiation treatments, which has involved just width and height. Computer technology creates three-dimensional images that also add depth. This allows veterinarians to more precisely target tumors with beams of radiation that actually conform to the shape of the tumor. The 3-D image of the tumor can be generated using computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET) or single photon emission computed tomography (SPECT). Because this technique is so precise, it largely spares healthy tissues surrounding the tumor from being damaged. Three-dimensional conformal radiation therapy reportedly has been particularly effective in treating nasopharyngeal, prostate, lung, liver and brain cancers in humans.
Intensity-modulated radiation therapy (IMRT): A new type of three-dimensional conformal radiation therapy that uses radiation beams of varying intensities to deliver different doses of radiation to small areas of tissue at the same time. This results in even greater precision, allowing the veterinarian to deliver higher doses of radiation inside the tumor and lower doses to nearby healthy tissue. A linear accelerator delivers the radiation, and the equipment can be rotated around the animal to ensure that radiation beams are sent from optimal angles. The technology has been used to treat cancers of the brain, head and neck, nasopharynx, breast, liver, lung, prostate, and uterus in humans.
Stereotactic radiation therapy: Delivers a large dose of radiation precisely to a small tumor area. This is most often used in cancers of the brain, but is also being tried on other types of cancer. Linear accelerators or other machines called gamma knives are used to deliver this treatment.