A Systematic Overview of Radiation Therapy Effects in Head and Neck Cancer

A systematic review of radiation therapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on radiation therapy for head and neck cancer is based on data from 39 randomized trials and 1 meta-analysis. In total, 40 scientific articles are included, involving 20 893 patients. The results were compared with those of a similar overview from 1996 including 79 174 patients. The conclusions reached can be summarized as follows: General, non-nasopharynx <list id="l1" type="5"> <item>Substantial evidence indicates that the tumour effect of radiotherapy can be increased by the concomitant administration of chemotherapeutic agents, particularly cisplatin and 5-fluorouracil. </item><item>There is moderate evidence of a survival benefit of radiation combined with concomitant chemotherapy compared to radiation alone. However, the results are equivocal. </item><item>There is substantial evidence in published studies for an increased frequency of severe acute side effects as a result of concomitant chemotherapy and radiotherapy. </item><item>There are very few studies that allow any estimates of the risk for serious late side effects. There is a weak indication of an increased risk for serious fibrosis. </item></list> Comment: The general quality of studies and the lack of information on serious side effects indicate a need for large, well-designed clinical studies with a reasonable follow-up. Larynx preservation studies <list id="l2" type="5"> <item>There is strong evidence that larynx preservation is possible in 50% of the patients surviving for 5 years with hypopharyngeal cancers when treated with neoadjuvant chemotherapy and radical radiotherapy. </item><item>There is a non-significant trend for the overall survival being lower in non-surgically treated patients than in those treated with primary surgery and postoperative radiotherapy. </item></list> Nasopharynx <list id="l3" type="5"> <item>There is moderate evidence that patients with nasopharyngeal carcinomas of the endemic type benefit from therapy with a combination of chemotherapy and radical radiotherapy. However, the results from the reported studies are equivocal. </item><item>There is some indication that the acute side effects of radiation are more severe in the concomitant setting than in the neoadjuvant. </item></list> Comment: There are no data on serious late toxicity. Dose, fractionation schedules <list id="l4" type="5"> <item>There is some evidence that certain schedules of altered fractionation improve tumour control without increasing severe late side effects. </item><item>There is some evidence that nervous tissues are more susceptible to damage by altered fractionation. </item><item>Solid data shows that altered fractionation increases acute side effects. </item><item>There is moderate evidence that accelerated hyperfractionation may reduce the frequency of serious late side effects while retaining a similar tumour effect as conventional radiotherapy. </item></list> Hypoxic cell sensitizers <list id="l5" type="5"> <item>Most reported trials reject the usefulness of nitroimidazole derivatives for sensitization of hypoxic tumour cells. </item><item>There is some evidence that patients with tumours in the pharynx and larynx may benefit from sensitization by nimorazole. </item></list> Prophylactic treatment of side effects <list id="l6" type="5"> <item>There is weak evidence that local antibiotics have a clinically significant effect in preventing acute radiotherapy side effects. </item><item>There is insufficient evidence that radioprotective agents offer clinically significant protection of parotid glands (one study in two publications). </item><item>There is insufficient evidence that radioprotective agents do not spare tumour tissue. </item></list> Since the previous report no randomized studies comparing the effectiveness of external beam radiotherapy and brachytherapy have been performed. Both methods are well established and have independently proved to be effective in the treatment of certain head and neck cancers. No conclusion can be drawn regarding their relative effectiveness. Since the previous report no data to guide the use of intraoperative radiotherapy have been identified.