Malignant glioma--a nemesis which requires clinical and basic investigation in radiation oncology

Malignant gliomas account for 40% of all central nervous system malignancies. These are essentially localized neoplastic tumors that have defied most treatment. In spite of improved techniques, surgery is unlikely to increase survival further since true cancer operations cannot be performed. Radiation therapy has made a significant difference in outcome. Investigation in radiation oncology is essential for further improvement in the treatment of these tumors. The pattern of failure is local tumor recurrence, but the method to overcome this resistance to treatment is not clear. Radiation therapy techniques and inherent radio-resistance have been considered as possible reasons for failure. With newer imaging procedures, the extent of tumor can be more accurately defined allowing improved treatment planning. Identifying an effective treatment program is more difficult. Studies have documented the beneficial effect of radiation therapy, but the optimal dose or fractionation schedule has not been determined. Whereas some studies have reported improved survival using higher radiation doses, others have reported no benefit. More recently, studies of multiple daily fractionation schedules have been conducted using two or three daily fractions. Equally confusing results have been reported. Histologically, these tumors have necrotic areas and may be radioresistant due to hypoxic cells. Treatment methods designed to overcome the radioprotective effect of hypoxia have yielded disappointing results. The addition of hypoxic cell sensitizers has not produced the expected improvement in outcome. Studies using neutron radiation therapy report tumor control but not improved survival. Radiobiologic information is now available which may contribute to our understanding of the response of these tumors to radiation. Further laboratory and clinical investigation is required. Carefully designed clinical trials are needed to test new treatment concepts, and all radiation oncologists should be prepared to participate in such clinical studies.