Hypofractionated Stereotactic Radiotherapy for Malignant Glioma: A Phase I/II Study

In order to shorten treatment time for patients with newly diagnosed supratentorial malignant glioma, a phase I study of LINAC-based hypofractionated stereotactic radiotherapy (SRT) was initiated in September 1991. Nineteen adult patients entered the study. They were treated with 23 MV photons using a single-isocenter arc technique. Six patients received 5 × 5 Gy, 11 received 5 × 6 Gy, and 2 received 5 × 7 Gy over 1 week. Treatment plans were normalized to 100% at the isocenter. Target volume encompassed the tumor with a margin of 1.5–2 cm and was surrounded by the 80% isodose. Five patients had anaplastic astrocytoma and 14 had glioblastoma multiforme. Median tumor volume before SRT was 20.4 cm³. A matching group of 19 patients who received conventionally fractionated radiotherapy (CFRT) was selected in order to compare time to progression and survival. CFRT was applied with daily fractions of 2 Gy up to 60 Gy in 6 weeks. No chemotherapy was given. Seven of 19 patients developed acute grade III or IV toxicity (RTOG central nervous system toxicity criteria) and had to be treated with high-dose steroids and/or mannitol within 8 weeks after SRT (1 of 6 after 5 × 5 Gy, 5 of 11 after 5 × 6 Gy, and 1 of 2 after 5 × 7 Gy). In contrast, only 2 patients had signs of late toxicity. No radionecrosis was observed. Median time to progression was 5 months, median survival 7 months (CFRT: 7 and 11 months, p>0.1). One-year survival rate was 32% versus 37%. However, it was 0% after 5 × 5 Gy, but 40% after 5 × 6 or 7 Gy (p = 0.06). In conclusion, toxicity of SRT with 5 × 6 or 7 Gy was not acceptable. The 5 × 5 Gy regimen was tolerable, but not effective with regard to time to progression and overall survival.