It's All About the Energy: What Nuclear Medicine and Radiation Therapy Offer the General Practitioner
Kim A. Selting1, DVM, MS, DACVIM (Oncology), DACVR (Radiation oncology)
Because of the high overhead involved in building and maintaining a radiation facility, this subspecialty service is only provided by veterinarians with additional training in radiation therapy. However, any veterinarian from general to specialty practice will encounter patients for whom radiation can significantly improve both quality and quantity of life. In addition to radiation therapy using a traditional external beam, radiation can be delivered to a tumor in a variety of novel ways including targeted radioisotopes (such as radioiodine) and brachytherapy. This talk will cover how radiation works, cases for which diagnostic or therapeutic radiation are indicated, and management of side effects which often occur after completion of radiation and may be handled by general practitioners.
Radiation therapy works by damaging the DNA of tumor cells, causing strand breaks. Because cancer cells may either divide or lay dormant, effects of radiation can be seen at various times. When a cell eventually attempts mitosis, the damaged cell undergoes a mitotic catastrophe and death. Because of this, tumors can shrink slowly over weeks to months, or sometimes simply stop growing. Lymphocytes are unusual in that they can undergo an intermitotic death.
Radiation is divided into smaller treatments called fractions. This allows the normal tissues to tolerate the radiation, and slowly dividing cells have time to execute DNA repair.
Radiation can be administered in a definitive protocol or a palliative protocol. With definitive protocols, the goal is to give as much radiation to the tumor as the normal surrounding tissue will tolerate. Treatments are divided into small daily fractions for a total of 18–20 treatments in most cases. With palliative protocols, the goal is to administer a total dose of radiation that will provide some relief from the pain or other effects of the tumor. These protocols typically consist of a larger dose per fraction and given less often and to a lower total dose (often once or twice weekly for a total of 4–6 treatments). The benefits of definitive protocols include a better chance for tumor control and less risk of permanent late side effects. Palliative protocols involve fewer trips to the hospital, achieving pain relief, and less risk of short-term side effects. Newer machines can also perform stereotactic body radiation therapy which uses precise and rigid positioning with CT-guided confirmation and sophisticated software to allow the equivalent effects of many smaller fractions to be delivered in a few, larger fractions.
Cancer therapy should parallel the predicted behavior of the disease. For tumors that are locally aggressive such as low-grade soft-tissue sarcomas and mast cell tumors, radiation therapy offers excellent long-term control and presumed cure in many patients. In brief, radiation does whatever surgery can't. Ideally, surgery is used to cytoreduce a tumor to a microscopic tumor burden, then radiation is used to sterilize any remaining cells (a notable exception is nasal tumors). The advantage of radiation over surgery is the ability to treat a greater volume of tissue than could be removed surgically. If tumors are non-resectable, either because of size or location (such as brain or thyroid tumors), radiation can be considered as a sole therapy or as a neoadjuvant therapy in which radiation is used to shrink the tumor to allow later resection. Another important goal of radiation is palliation of clinical signs, even if tumor control is not expected to be durable. Radiation can also be used to palliate clinical signs associated with lymphoma, or as consolidation of remission that has been achieved with chemotherapy.
When considering side effects, short-term (acute or early) and long-term (chronic or late) effects can be considered. Early effects will happen in all animals to some extent and will heal in all animals (i.e., they are temporary). Early effects begin during the second half of a course of radiation treatment and will be at their peak (worst) toward the end or just after completion of a course of radiation therapy. Healing occurs over the following few weeks. Late effects are uncommon or rare but are permanent, and occur more than one year following radiation treatment. In any location, late effects can include osteonecrosis and secondary cancers (risk ~3%). Occasionally, side effects are seen between one and 12 months after radiation either as a consequence of early effects or as a delayed effect due to a particular organ's response to radiation.
Common acute effects that are clinically relevant include moist desquamation of the skin and mucositis if mucous membranes are in the treatment field. Late effects of most concern include osteonecrosis, cataracts, and demyelination, depending on which critical structures are in the treatment field.
In general, time is the most important factor in healing. Other measures that can ensure proper healing of affected tissues include prevention of self-trauma, pain medication, and topical gels. To prevent self-trauma, it is critical to use an Elizabethan collar when skin side effects begin.
For topical care of skin effects, do not apply oil or petroleum-based products as these will slow healing. If topical preparations seem soothing (such as water-based aloe vera gels, which should be alcohol-free), then they may be applied 2–3 times per day. If the application of topical gels causes the pet to focus on the area and be more inclined to lick, then they should be avoided altogether. The area should be kept clean and dry and open to the air whenever possible. Do not remove scabs that are attached because they are acting as natural Band-Aids while healing occurs beneath them. For mucositis, decaffeinated black tea rinses can provide tannins and medicated mouth rinses can be used.
Radioisotopes offer a sensitive way to diagnose cancer by exploiting the metabolism of the cancer cell, and a specific way to treat cancer because the cancer cell can be targeted using the properties of the radioisotope. Because facilities that work with radioactive diagnostic and therapeutic isotopes are sparse, it is important to identify appropriate applications for nuclear medicine for veterinary patients. This will help the upper-level practitioner identify patients that may benefit from these resources so that this can be offered to the appropriate patient and owner, and justify the benefit of traveling to a facility that performs scintigraphy, and in some cases radioisotope therapy.
Radioisotopes emit energy (decay) until they are energetically stable. With a knowledge of the strength and kind of energy that is emitted from a radioisotope, these properties can be exploited for diagnostic testing. Scintigraphy using Tc-99m-MDP identifies osteoblastic activity and is a common application of diagnostic nuclear medicine for assessing bone pathology in dogs, cats, and horses. Positron emission tomography (PET) scanning is another method of assessing the function of a population of cells. When glucose is labeled with a radioisotope of fluorine, F-18 labeled FDG is produced and will detect any population of cells in the body with an unusually high metabolism for sugar, such as cancer cells. The F-18 emits a positron which travels a very short distance before being annihilated by its electrical counterpart, an electron, and the result is two gamma rays that are emitted at 180 degree angle, to be detected and traced back to their origin. Limitations include cancer cells that use alternate pathways of metabolism. Other PET radioisotopes can be used to detect proliferating cells (FLT) or areas of hypoxia.
Therapeutic applications of nuclear medicine include the well-known use of radioactive iodine for the treatment of hyperfunctional thyroid disorders. In addition, dogs with non-functional malignant thyroid tumors can also take up radioiodine and results have been promising. Dogs with thyroid carcinoma treated with radioiodine have median survival times of 2½ to 3 years with locoregional disease even if nonresectable, and one year with metastatic disease.
Another radioisotope used in the treatment of metastatic and primary bone cancer is samarium-153-EDTMP (Sm-153-EDTMP) which was developed at the University of Missouri (trade name Quadramet). Diagnostic bone scans using Tc-99m-MDP are used to determine optimal candidates for this treatment. Sm-153-EDTMP causes myelosuppression that occurs 2–4 weeks after treatment and can cause a transient anemia and increased ALP. The myelosuppression recovers over a 2–4-week period. A single dose can be effective at palliating pain associated with bone lesions, especially those with significant bone production. A new compound, samarium-153-DOTMP is currently being developed to be safer and more effective.
Intralesional brachytherapy has traditionally been accomplished using radioactive seeds, needles, or ribbons. One common application is prostate cancer in men, for which dogs are an excellent translational model. Liquid brachytherapy with radioactive gold nanoparticles injected directly into prostatic tumors in dogs is being explored at the University of Missouri. Additionally, intralesional yttrium-90 in a colloidal suspension is being explored for direct injection into appendicular osteosarcoma lesions in dogs.
Time, distance, and shielding are the most important aspects of keeping radiation exposure as low as is reasonably achievable (ALARA). Radiation exposure decreases exponentially with distance so moving a small distance further away can result in a great decrease in radiation exposure.
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