Head and neck cancers Radiation Therapy

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Radiotherapy plays an integral role in the treatment of most head and neck cancers. Used as the sole modality for the treatment of select early-stage disease (T1 and T2), it gives comparable results to a surgical resection, often with less morbidity. For tumors arising in the larynx, it may be preferred to surgery because it maintains organ function. For intermediate sized lesions, it is used as an adjuvant to surgery in order to improve locoregional control.

When used as an adjuvant, it is important that there be good communication between the surgeon and the radiation oncologist in order to avoid inadvertent delays that can compromise outcome. For example, Vikram and colleagues have noted that the rate of locoregional tumor recurrence was greater if there was more than a 6-week delay between surgery and the initiation of adjuvant radiotherapy. The adverse impact of a delay in beginning treatment has been confirmed by Mackillop and colleagues, who found an approximate 10% lowering of local control in patients with advanced tonsillar carcinoma per month of delay in beginning radiotherapy. For advanced inoperable lesions and for tumors arising in certain sites such as the nasopharynx, radiation therapy may be the only potentially curative modality. Its effectiveness has been increased by the concomitant use of chemotherapy and by using more optimal treatment fractionation schemas (discussed below).

Ionizing radiation (high-energy photons, electrons, neutrons, protons, and other charged particles) interacts with matter in subtle ways and should not be thought of as simply a form of cautery. Tumors and normal tissues can vary dramatically in their ability to repair the cellular damage caused by ionizing radiation. This makes it possible to use treatments such as chemotherapy and hyperthermia to reduce the repair capability of tumors and to design fractionation schemes that effectively widen the therapeutic window between tumor control and normal tissue damage.

HNSCCs are generally characterized as being “moderately radiosensitive,” meaning that fairly large amounts of radiation must be delivered in order to achieve a high probability of tumor control. Fortunately, the required doses are within the tolerance range of most tissues in the head and neck.

The effectiveness of a given dose of radiation depends upon how it is given. Over the past 30 years, various “standard” treatment regimens have evolved to treat head and neck cancer. In the United States the traditional “curative” treatment regimen consists of giving 180 to 200 cGy once a day for 5 days a week to a total dose of 6,500 to 7,400 cGy; in England and Canada, higher daily doses of 220 to 250 cGy are given once a day for 5 days a week to a total dose of 5,000 to 5,500 cGy. These two schemas have evolved empirically, and a review of the literature seems to indicate that they provide comparable tumor control with the main debate relating to differences in complications. Various altered fractionation regimens have been compared to the standard regimens in clinical trials and some of these appear to be evolving into new “standards.”

Radiation kills the stem cells in the basal layer of the skin and mucosa, and several weeks later, the cells in the more superficial protective layers are not adequately replaced when they are lost through normal physiologic processes. This denudes the epithelium, giving rise to a mucosal reaction that can greatly inhibit a patient’s ability to swallow solids and liquids. This does not occur immediately but is progressive after several weeks of radiotherapy. The use of concomitant chemotherapy and/or altered fractionation treatment regimens can make this reaction occur sooner and be more severe. Patients must be monitored closely to ensure that they maintain adequate nutrition during therapy and often a feeding tube is required. Placement of such a tube is preferable to giving the patient a break in therapy, which can lower the tumor control probability due to repopulation. A similar reaction can occur in the skin in the treatment portals, giving rise to a severe sunburnlike reaction. Amifostine, a radioprotective agent, has been shown to reduce the incidence and severity of these side effects but is itself associated with nausea as a side effect. Thus far, it appears that this agent does not impart any radioprotective effect to patients with HNSCCs.

Radiation to the head and neck area can cause significant changes in salivary gland function and taste perception. The severity and duration of these changes are dose dependent. In the absence of amifostine, there is transient loss of saliva and taste after doses of 1,000 to 1,500 cGy; doses of 4,000 to 5,000 cGy cause permanent changes. Pilocarpine (Salagen) is effective in maximizing any residual salivary gland output. Both the decrease in the amount of saliva and the changes in its chemical composition allow changes in the distribution of microorganisms inhabiting the mouth, which in turn can markedly increase the risk of dental caries. Aggressive dental prophylaxis prior to beginning radiotherapy is mandatory in the dentulous patient as the incidence of osteoradionecrosis can be considerably reduced if the necessary repairs and/or extractions are done prior to treatment rather than in heavily irradiated tissues after treatment. If extractions are necessary, a delay of 2 to 3 weeks between the extractions and the initiation of radiotherapy is necessary in order to allow for adequate healing. If extractions or other invasive procedures are required after high-dose radiotherapy, hyperbaric oxygen treatments are helpful in reducing the risk of osteoradionecrosis, particularly if the mandible is involved.

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