| RADIATION THERAPY - Side Effects and
Complication in Head and Neck Treatment. Abeloff: Clinical Oncology, 2nd ed., 2000 Soft Tissue and Bone Necrosis The soft tissue necrosis of oral cavity mucosa that occurs after high doses of radiation therapy is attributed to the obliteration of small blood vessels. Irradiated epithelium is thinner than normal and clinically appears pale and atrophic. It also has telangiectatic vessels. The irradiated mucosa is more susceptible to mechanical injury and to the noxious effects of alcohol and tobacco. Soft tissue necrosis usually begins with breakdown of damaged mucosa, resulting in a small ulcer. The vast majority of soft tissue necroses will occur within 2 years after radiation therapy. Occurrence after 2 years is generally preceded by mucosal trauma. The risk of soft tissue necrosis is increased with larger fraction sizes, higher total doses, large volumes of irradiated mucosa, and the use of an interstitial implant. Treatment of Necrosis If recurrent cancer is not clinically suspected, biopsy should be avoided, as this may enlarge the area of necrosis. Topical anesthetics can relieve the discomfort associated with soft tissue necrosis and allow the patient to eat normally. Antibiotics often provide pain relief, particularly when the ulceration is deep and infected. It is essential that the patient discontinue the use of alcohol and tobacco. If the area of necrosis is traumatized by dentures, the dentures should not be worn until healing is complete. More than 90 percent of soft tissue necroses will heal with conservative treatment, although in some instances it may take many months. A small trial, consisting of 12 patients with 15 sites of late radiation necrosis of the soft tissues, has been conducted for preliminary evaluation of the effect of pentoxifylline. The average duration of nonhealing before treatment with pentoxifylline was 30.5 weeks. With the institution of pentoxifylline (400 mg PO tid), 13 of 15 necroses healed completely, and one partially healed an average of 9 weeks after starting treatment. All patients had pain relief. These results support further study of pentoxifylline in patients in whom soft tissue necrosis develops after a course of radiation therapy. The Radiation Therapy Oncology Group is currently evaluating the efficacy of pentoxifylline in healing irradiation-related soft tissue necrosis. The mandible and maxilla will tolerate rather high doses of radiation therapy without serious problems, as long as the tissues overlying the bone remain intact. If soft tissue necrosis develops in the mucosa overlying the mandible or maxilla, the underlying bone may become exposed. This can lead to serious injury, resulting in bone necrosis (osteoradionecrosis). Compared with the maxilla, the gingiva of the mandible has a rather tenuous blood supply, placing the mandible at greater risk of exposure and necrosis. Most bone exposures will heal spontaneously after conservative treatment. At one institution, 86 percent of bone exposures healed after conservative treatment. Small areas of bone exposure (<1 cm) generally heal spontaneously after a period of weeks to months. Larger areas of bone exposure may persist for a long period and may lead to bone necrosis, followed by sequestration. If exposed, necrotic bone may become infected. The necrotic process may then extend to involve adjacent bone for a considerable distance. Severe necrosis can then develop and lead to orocutaneous fistulae and pathologic fractures. If the bone is rough or protrudes above the level of the gingiva, the oral surgeon may file it down to promote healing. Local debridement of moderate-size necrosis can be performed by the oral surgeon, if indicated. If the patient wears a denture, it should be withheld or relieved over the site of exposure. Pain is not a common symptom; if present, it can usually be controlled with analgesics. A local anesthetic can be applied with a cotton-tipped applicator, if needed for pain control. Antibiotics frequently reduce infection and discomfort within a few days, but should be continued for 2 to 3 weeks. Hyperbaric oxygen along with antibiotic therapy and local debridement may help promote healing. Mandibular resection should be reserved as the last resort for the patient with intractable pain, recurrence of severe infections, or trismus. Most bone problems develop within 3 to 12 months after radiation therapy, but some risk persists for many years, especially if the patient undergoes dental extractions. Necrosis is most likely after extraction of mandibular teeth, although this is infrequent if special precautions are taken. The edentulous patient has a lower overall risk for bone necrosis compared to the dentulous patient. Patients at highest risk of osteoradionecrosis appear to be those with tumors involving the gingiva or bone; those who continue to smoke or drink, or both, after radiation therapy; and those who receive high doses of radiation therapy, large treatment volumes, large fraction sizes, and/or interstitial implantation. Taste Alterations Loss of taste occurs rapidly early in the course of radiation therapy to the oral cavity. Most patients report that the sense of taste is essentially nonexistent by the third or fourth week of treatment. Following the completion of radiation therapy, most patients report some taste improvement within 1 to 2 months. Full recovery of taste usually requires 2 to 4 months. In some patients, the taste never returns to normal, due at least in part, to xerostomia. Although some have suggested that zinc therapy may be useful in improving taste acuity, no standard treatment can be recommended until further study is undertaken. [100] As discussed above, amifostine may protect against taste loss due to irradiation. Trismus Trismus results after radiation therapy to the oral cavity or to the oropharynx secondary to fibrosis of the muscles of mastication following high doses, or when advanced carcinomas involve the pterygoid musculature. The temporomandibular joint itself is relatively resistant to ankylosis secondary to radiation therapy, but the risk of injury increases if the joint is invaded by tumor. The use of large daily treatment fractions also appears to increase the risk of trismus. Prevention and Treatment of Trismus The use of high-energy x-ray beams and sophisticated multiple field techniques should be utilized whenever possible to reduce the dose of radiation therapy to the temporomandibular joint and to the muscles of mastication. Patients treated with both surgery and radiation therapy are at greater risk of trismus than patients treated with either modality alone. High-risk patients and those in whom trismus has developed before treatment should perform jaw-stretching exercises daily, in an attempt to increase the interarch or interincisor distance. A number of techniques are used, including commercially available jaw-stretching tools and less expensive stacked tongue blades, tapered corks, or clothespins. These devices are inserted between the teeth to increase the interincisor distance, until slight pain is encountered. The exercises should be done for about 30 seconds every 2 hours. Additional tongue blades are added, or a thicker aspect of the cork is placed between the teeth every few days, to increase the interincisor distance and stretch the muscles of mastication. Malignancy The carcinogenic effect of ionizing radiation has long been recognized. The latent interval between radiation therapy and the development of cancer varies from several to many years. Kogelnik reviewed 1,163 patients treated for head and neck cancer at the M.D. Anderson Hospital who had survived a minimum of 5 years after treatment without developing recurrent cancer. Follow-up for these patients ranged from 7.5 to 25.5 years. Patients were treated with surgery alone (337 patients) or radiation therapy with or without surgery (826 patients). The incidence of new cancers in the original disease site (1.8 percent vs. 2.7 percent), within the immediate vicinity of the original cancer (4.2 percent vs. 3.1 percent), or at sites remote from the primary tumor but still within the oral cavity or pharynx (4.7 percent vs. 5.7 percent) was very similar for patients treated with surgery alone versus irradiation with or without surgery, respectively. It was concluded that moderate or high-dose radiation therapy did not produce any new squamous cell carcinomas of the mucous membranes. Similar findings were reported from the Fox Chase Cancer Center and from UCLA. The rarity of radiation-induced sarcomas, the long latent period to their development, and the difficulty in obtaining reliable long-term follow-up data make the task of estimating the true risk of this problem difficult. However, most series report one or two cases of radiation-induced bone sarcoma per 1,000 5-year survivors. If one were to assume malignant induction in 1 patient of every 500 long-term survivors, then with an estimated 5-year survival rate of 40 percent for all irradiated head and neck cancer patients, it is calculated that 1 case would be induced per 1,250 patients treated. A review of the Mayo Clinic experience showed no difference in survival between patients with radiation-induced sarcomas of the mandible or maxilla and nonradiation-induced sarcomas of the same site (45 percent 5-year overall survival). Since some patients with radiation-induced osteogenic sarcomas of the mandible or maxilla can be cured, the risk of dying from a radiation-induced sarcoma after a course of radiation therapy is minimal and is very similar to the risk of death a patient accepts undergoing general anesthesia and major head and neck cancer surgery. An association has also been noted between radiation therapy and thyroid tumors. The latent period is usually 10 to 30 years. Almost all reported cases have followed low doses of radiation therapy well below the doses used for squamous cell carcinomas of the oral cavity (<6 cGy to 1,500 cGy). Doses above 2,000 cGy are associated with a very low risk of induction of thyroid neoplasia compared with lower doses. This is likely because higher doses of radiation therapy either completely destroy follicular cells or at least render the surviving cells incapable of division. Not all thyroid neoplasms that develop after radiation therapy are malignant, and many of the malignant neoplasms that do develop (papillary and follicular carcinomas) are readily curable with surgery. Thus, the risk of radiation-induced carcinoma should not be a major determinant in deciding treatment approaches for the typical patient with head and neck cancer. |