What to irradiate and what not (Proceedings)
Radiation therapy is one of the most powerful tools available in the fight against cancer and can be applied as a primary treatment modality, in combination with surgery and/or chemotherapy in an adjuvant setting, or as a palliative therapy. The dose of radiation therapy administered is limited by the tolerance of normal tissue structures within the treatment field. The theory of fractionation indicates that sublethal radiation injury is repaired more effectively in normal tissues than tumors and allows for the administration of doses high enough to establish long term control safely when small doses are administered repeatedly. The acute side effects are more dramatic in this setting and include desquamation, mucositis, conjunctivitis, keratitis and K-sicca. They will persist for 2-4 weeks and then resolve. Although the acute side effects are amplified, it keeps the late effects, which can be life-threatening down to very low levels. Late side effects include radioosteonecrosis, second malignancies, and myelomalacia.
When administering radiation therapy in the palliative setting, i.e. with the intent of improving the quality of life of the pet and not necessarily the overall survival time, radiation is administered in higher doses per fraction, but a lower total dose. This greatly decreases the incidence of the acute side effects and is still effective in most cases, often for many months.
Tumors with complete, often long term control include transmissible venereal tumors, ameloblastomas, extranodal lymphomas; and mast cell tumors, soft tissue sarcomas and thyroid carcinomas that have been surgically cytoreduced to microscopic disease.Transmissible venereal tumors have control rates of over 90%, even with relatively low doses. Because they are also chemotherapy responsive, radiation therapy is not usually indicated except in the rare chemoresistant, or recurrent case.
Ameloblastomas have control rates reported in the 80-95% range. Surgery is also a good option but may require a mandibulectomy or maxillectomy as bony invasion is always present. Non-resectable masses, the presence of residual microscopic disease after surgery, and recurrent disease are all indications for radiation therapy.
When to add radiation therapy to mast cell tumors can be a difficult decision as not all grade II mast cell tumors with marginal excision will grow back. If the historical literature is reviewed, it appears that about 45-50% of grade II mast cell tumors will die from mast cell tumor related causes in the first three years with surgery alone. The addition of radiation therapy appears to decrease that number down to 10-12% but is associated with additional expense and some acute side effects. Ultimately this is the owner's decision, and one can only present them with the options.
Soft tissue sarcomas that have been narrowly excised have a very high incidence of recurrence and radiation therapy should be strongly considered in that setting. When applied during that window of opportunity, 3 year control rates exceed 50%. Recurrence and/or the presence of bulky disease significantly decrease the chance of long-term control.
Because of their location it is often difficult to completely remove thyroid carcinomas, and because of their high metastatic rate, adjuvant radiation therapy and chemotherapy should be considered. When treated aggressively, with multi-modality therapy, survival rates exceeding three years have been reported in several studies.
Tumors with survival times extended significantly with the addition of radiation therapy include nasal tumors, vaccine associated sarcomas, ceruminous gland carcinomas, apocrine gland adenocarcinomas, pituitary tumors, meningiomas, canine squamous cell carcinomas and canine oral melanomas.
The median survival time is untreated nasal tumor cases is ~3 months. That number is extended to a median of 9-15 months with the addition of radiation therapy. Side effects often can be dramatic in these cases, but the addition of conformal treatment plans and more hypofractionated schedules have made them much more manageable.
Feline vaccine associated sarcomas are very difficult to control with surgery alone. The addition of radiation therapy to aggressive surgical resection has consistently resulted in the longest reported disease-free intervals and survival times. Luckily the incidence of this tumor has decreased significantly.
Ceruminous gland carcinomas in both dogs and cats will respond to radiation therapy and it is often combined with surgical resection. Over half of cases will remain disease free for one year or longer.
Apocrine gland tumors of the anal sac (AGASACA) will live approximately one year with surgery alone. Their median survival time is doubled out to ~2 years when radiation therapy and chemotherapy are added to their treatment regimen.
Pituitary tumors and meningiomas both appear to benefit from radiation therapy. These need to be planned carefully and should be treated in a positioning frame if at all possible. Glial cell tumors tend to be less responsive.
Approximately 60% of canine oral squamous cell carcinomas will be controlled for one year or longer when irradiated. Their location in the mouth makes a difference with tumors more rostral in location having a better prognosis.
Canine oral melanomas will only respond to a coarsely fractionated radiation therapy scheme, usually involving four fractions at weekly intervals. Approximately 50% will have a complete response. The median survival time is 8 months. Addition of the melanoma treatment vaccine will prolong survival times even further in ~55% of cases.
Palliative radiation therapy is used most often for pain relief or to minimize bulky disease. Osteosarcomas will have significant pain relief associated with palliative radiation therapy for a median of 4 months. The addition of chemotherapy increases the percentage of cases that benefit. The biggest risk associated with its application is the development of pathologic fractures. Bisphosphonates are included in their treatment plan to try and minimize this complication in high risk patients.
With the newer technology available at a handful of centers in the United States, carefully selected tumors can be treated with highly conformal, CT driven plans which allow very high doses to be administered to closely defined sites in one application. This is known as stereotactic radiosurgery. Information is now starting to accrue in these patients and may open new opportunities for previously untreatable patients.