Hyperfractionated and accelerated radiation therapy in central nervous system tumors (malignant gliomas, pediatric tumors, and brain metastases).

The authors review the main contributions of the international literature concerning the role of hyperfractionation (HF), accelerated fractionation (AF), and accelerated hyperfractionation (AHF) of the dose in radiation therapy (RT) of central nervous system tumors. Basic rationales, clinical results, acute/late toxicity, and current prospectives are summarized in three sections focusing on malignant gliomas, pediatric brainstem tumors, and brain metastases. In supratentorial malignant gliomas the superiority of AHF (0.89 Gy x 3 fractions/day; total dose 61.4 Gy) over conventional fractionation ((CF) total dose 58 Gy) was demonstrated by a randomized trial. However, the gain in median survival time was less than 6 months. No other randomized trials support the preferential choice of non-CF schedules outside clinical trials. Ongoing trials are exploring the role of AHF in combination with chemotherapy, hypoxic cell and radiosensitizing agents. As for pediatric brainstem tumors, there are no data to support the routine use of HF that should be preferably used in an investigative setting. As late sequelae have been reported in the few long-term survivors, patients should be carefully selected. Regarding brain metastases AF RT and AHF RT, with their faster treatment course, may represent a convenient alternative to CF RT for the palliation of brain metastases. In carefully selected patients with solitary brain metastases non-CF RT may be part of aggressive treatment approaches.