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Surgery, chemotherapy and radiation therapy all have the potential to provide tremendous benefit to the cancer patient when recommended appropriately. However, all of these treatment modalities, when used inappropriately, can do tremendous harm. When a treatment plan consisting of surgery and/or chemotherapy is developed for our cancer patients, we spend much time considering the potential gain to the patient vs. the probability of short and long term side effects. Many issues are considered and discussed with the pet owner when developing the treatment plan. These issues include the patient’s current quality of life; potential gain in quality of life and length of life from the treatment; incidence and severity of side effects from the treatment; cost of the treatment and philosophical goals of the pet owner. When these factors are considered collectively, we might choose to develop a treatment plan that is actually suboptimal in regards to long term survival for the patient but is absolutely optimal in regards to overall quality of life of the patient. As with surgery and chemotherapy, the limiting factor in the use of radiation therapy is tolerance of normal tissue to the applied treatment. The response of normal tissue of various locations of the body to radiation therapy is well studied and documented. This information allows us to understand and predict which locations of the body will recover smoothly from the effects of radiation treatment and which locations will experience potentially unacceptable short-term and/or long-term side effects. The effectiveness of radiation for killing cancer is also well documented. This information allows us to predict the probability of local tumor control in the short term and long term based on histologic diagnosis of the cancer (tumor type and grade), and volume of disease being treated. We can then balance the dose of radiation needed to effectively control the tumor with the dose of radiation that should not be exceeded in a given area to achieve our goals regarding patient quality of life. In some cases, a compromise in dose may be decided upon so that our philosophy regarding patient care can be respected. By combining radiation therapy with other treatment modalities (surgery, chemotherapy, gene therapy) we can capitalize on the synergistic effects of these therapies while minimizing side effects of each.
Indications of Radiation therapy in the Veterinary Cancer Patient
Soft Tissue Sarcoma: This is by far the most common use of radiation therapy in both dogs and cats. Tumors that cannot be completely excised but can be surgically or medically reduced down to microscopic disease can often be cured with radiation therapy. Effectiveness of irradiation to control (cure) these cancers is highest when the tumor is located on the limbs, with average time to recurrence of greater than 5 years. Irradiation is particularly effective when the tumor is low to moderate grade (1 or 2). Radiation therapy allows us to preserve the function of a limb that might otherwise require amputation to eliminate the disease. Grade 3 tumors often require combination with chemotherapy to achieve long-term control or cure. The size of the soft tissue sarcoma and/or the surgical incision influences the amount of normal tissue that must be irradiated (size of radiation field) which in turn influences dose to normal tissue and side effects.Mast Cell Tumors: This cancer is also one of the most common indications for the use of radiation therapy, as they are very radiosensitive. In this case, we have the added benefit of being able to irradiate regional draining lymph nodes for all mast cell tumors that may metastasize. Just as with soft tissue sarcomas, tumors on the limbs are the most successfully treated with the least side effects. Effectiveness of irradiation does depend on tumor grade and volume of disease undergoing treatment. Median duration of local tumor control exceeds 4 years when microscopic disease is irradiated. Grade 3 tumors remain a challenge and require multi-modality therapy (surgery, radiation therapy and chemotherapy) for long term control or cure.
Lymphoma: This cancer is extremely sensitive to the effects of radiation therapy allowing for effective control of the cancer in the field of treatment. Because most lymphomas in dogs are systemic and in cats are intestinal, radiation is not used routinely. Radiation is very beneficial for patients with lymphoma localized to one lymph node or one extra-nodal site (e.g. nasal cavity, cranial mediastinum). Radiation can be used in combination with chemotherapy to assist in the treatment of patients that have one lymph node or one region of lymph nodes that is refractory to chemotherapy. Sites that are amenable to treatment with radiation either alone or in combination with chemotherapy include intra-nasal, oral cavity, retrobulbar (after enucleation), retropharyngeal/ cervical, cranial mediastinum, bone, cutaneous, and solitary peripheral lymph node. Whole body radiation, after a complete remission is achieved with chemotherapy, is currently under investigation at numerous centers around the country.
Skin carcinomas (sweat gland, basal cell, and squamous cell): Most of these skin tumors can be controlled successfully with surgery. From time to time however, we are faced with a large and invasive skin cancer that can only be resected down to microscopic disease. Radiation therapy is highly effective for achieving long term tumor control in these circumstances. Radiation therapy has the added benefit of being used in these cases to treat regional draining lymph nodes to prevent metastatic disease.
Acanthomatous epulis: This cancer is one of four most common canine malignancies of the mouth. It is extremely invasive into bone but does not metastasize. The effectiveness of radiation for cure of this cancer is almost as effective as radical surgery. Because many pet owners have fears about the disfiguring effects of maxillectomy or mandibulectomy, irradiation is a great alternative to surgery. It is particularly beneficial in cases where the tumor is large enough that a viable surgical option is not available. While the mouth will blister from the effects of the radiation, healing is generally complete within 2 weeks following completion of treatment and the patient will experience years of tumor control.
Oral Melanoma: surgery remains the treatment of choice for this cancer but all too often we find ourselves faced with unresectable tumors. Unresected and unresectable melanomas bleed and are often painful for the patient. Treatment with radiation therapy alone will partially reduce tumor size so that the bleeding stops and pain is alleviated. There is exciting early evidence that combination of radiation therapy with chemotherapy and autologous genetic tumor vaccines can result in complete remissions, and dramatically improved quality of life and survival times.
Oral Fibrosarcoma and Squamous Cell Carcinoma: Squamous cell carcinoma in dogs responds very favorably to radiation therapy if the tumor can be cytoreduced to a microscopic level. Radiation following surgery is indicated to achieve long term tumor control when complete resection is not achieved. In cats with squamous cell carcinoma, radiation therapy is reserved for tumors on the rostral mandible, in which case it can be somewhat effective, in combination with chemotherapy, at stabilizing the tumor . In general, squamous cell carcinoma of the oral cavity of cats is poorly responsive to radiation. Fibrosarcoma remains a challenge as effective surgical cytoreduction is generally not feasible and microscopic disease is typically very extensive. Local control for one year or longer may be achieved with a combination of radiation therapy and surgery when surgical cytoreduction is effective.
Salivary Carcinoma: The greatest challenge when treating patients with this cancer is the large size of the tumor at presentation. This large size invariably prevents complete surgical resection of the tumor. Radiation therapy applied to the tumor site before or after surgery significantly prolongs patient survival time and time to recurrence. Cure of the tumor can occur when treating low to moderate grade tumors. High-grade salivary carcinomas require treatment with chemotherapy in addition to the surgery and radiation regimen for long term (> 1 year) tumor control.
Thyroid carcinoma: Historically, we have considered dogs with large, fixed thyroid cancers to have untreatable disease. Surgical resection is typically not done due to the high morbidity and mortality from bleeding. Patients typically have tremendous stridor, inappetance and lethargy from their bulky disease. Treatment with radiation therapy has been reported to be of tremendous palliative benefit in these patients. Survival times are significantly prolonged, with 75% of patients living greater than 3 years.
Fibrosarcoma in Cats: This cancer continues to be very challenging to control long term. The most important part of long term tumor control is aggressive surgical resection resulting in wide clean surgical margins. Surgery alone, even in this circumstance, is associated with a time to recurrence of not more than 1 year. When the surgery site is irradiated, the time to recurrence (disease free survival) increases to 2 years.
Appendicular Osteosarcoma: Amputation and limb-sparing surgery (for distal radius tumors) remain the treatment of choice for controlling local disease and pain. However, pet owners are increasingly declining surgery for their pets due to concerns of progressive arthritis and associated immobility. Radiation therapy offers a terrific option for palliation. Patients are treated with only 3 treatments of radiation on days 0, 7 and 21. Pain relief occurs in 75% of patients for approximately 2 and 1/2 months. This often gives pet owners the time they need to come to terms with losing their pet while still enjoying some quality time. Full course radiation is currently being investigated at numerous sites around the country. Preliminary results indicate that this approach, in combination with chemotherapy, may be as effective as the combination of amputation and chemotherapy. Future studies will focus on combining radiation therapy with chemotherapy and novel bio-therapeutics to prolong quality survival time in these patients.
Bone tumors: Treatment of osteosarcoma of the axial skeleton is often limited by the inability to achieve wide surgical resection of the disease. Radiation therapy can offer palliative benefit in this situation as well as in the case of bone metastasis from a variety of tumors (transitional cell carcinoma, mammary carcinoma, hemangiosarcoma, and multiple myeloma).
Sublumbar lymph nodes: This is a common location for development of metastatic disease from malignancies of the caudal abdomen and perineum (anal sac carcinoma, perianal adenocarcinoma, anal and rectal carcinoma, mammary carcinoma, bladder/prostate carcinoma, mast cell tumor, lymphoma). Surgical resection of enlarged sublumbar lymph nodes followed by treatment with chemotherapy in many cases (anal sac carcinoma, perianal carcinoma) will result in prolonged palliation and survival time. Unfortunately, progression of disease occurs cranially along the sublumbar lymphatic chain. Radiation therapy following surgery has the benefit over chemotherapy of providing direct treatment to the draining sublumbar lymphatic chain. A recent report indicated that irradiation of sublumbar lymph nodes in patients with anal sac carcinoma metastasis to this site was as effective as surgical resection of lymph nodes. While irradiation following surgery is still optimal for long-term control, irradiation in lieu of surgery would be recommended when resection of markedly vascularized sublumbar lymph node metastases would be associated with high morbidity/mortality.
Brain tumors: While many brain tumors in dogs and cats are benign and amenable to surgery, some are deep seated and therefore pose significant surgical risks (e.g. pituitary macroadenomas). Radiation therapy in these patients can result in dramatic and rapid improvement of symptoms. Consultation with a neurologist is recommended when considering the treatment of choice for a patient with a brain tumor
Nasal tumors: While radiation therapy is still considered to be the treatment of choice for cancers in this location, normal tissue is this area experiences substantial short term (blistering of nasal and oral mucosa, conjunctivitis) and some long term (cataracts and retinal degeneration) side effects. The probability of achieving long term tumor control based on the histologic tumor type, tumor grade and extent of disease must be balanced with the side effects to normal tissue from the treatment. In some cases, such as with intra-nasal lymphoma, cures are possible and therefore the side effects are often justifiable. However, when the tumor type is very resistant to irradiation (ie intra-nasal squamous cell carcinoma or osteosarcoma), treatment with radiation therapy is not encouraged.
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