Split course multiple daily fractionated radiotherapy schedule combined with misonidazole for the management of grade III and IV gliomas A pilot feasibility study of the Radiotherapy Group of the EORTC

The effect of a fractionated radiotherapy on tissue is not only determined by the total dose; but also by the dose per fraction and the overall time of treatment. Recent experimental data have demonstrated that with the overall treatment time of 6 or 7 weeks, as is usually the case in the clinical practice, the late tolerance of the central nervous system (CNS) is only determined by the fraction size. Based on these premises a totally new fractionation schedule for the treatment of malignant gliomas was developed. The interval between irradiation is reduced to 4 hr, which makes it practical and possible to give 3 fractions a day. Thus, 15 fractions of 2 Gy can be given in 5 days; this scheme can be repeated after a rest period of 2 weeks. In this way, a dose of 60 Gy can be delivered in an overall treatment time of 4 weeks. As the total number of treatment days is reduced this schedule reduces the burden on the patient, and renders a more efficient combination with misonidazoLe possible. The shortening of the overall time could enhance the efficacy of radiotherapy on a rapidly proliferating tumor. A total of 122 patients have been treated according to this schedule. The acute tolerance has been found to be very good. Only 18% of the patients experienced transient severe side effects, such as nausea, vomiting, somnolence and headache. Thus, it has been proven that this treatment schedule reduces the burden on the patients. The preliminary survival data are encouraging. The median survival time of patients treated after tumor resection is over a year. These results warrant further study. A randomized trial exploring this treatment modality has been started.