Accelerated radiotherapy in glioblastoma multiforme: a dose searching prospective study

Abstract

The EORTC Radiotherapy Cooperative Group performed a prospective phase II study in glioblastoma multiforme using accelerated radiotherapy in escalating doses. The aims of the study were to investigate acute and late toxicity as well as tumor response and survival. Only the CT-enhanced tumor zone plus a margin of 2–3 cm were treated (mean volume, 1034 ± 477 cm 3). Radiotherapy was administered with 5–18 MV photons. The radiation schedule consisted of 3 fractions of 2 Gy/day, separated with at least 4 h. The first group of patients was scheduled to receive a total dose of 42 Gy, 21 fractions in 9 days. The total dose was then escalated up to 48 Gy (24 fractions in 10 days), 54 Gy (27 fractions in 11 days) and 60 Gy (30 fractions in 12 days). The numbers of patients entered in each dose-level group were 15, 17, 18 and 16, respectively. Acute toxicity was mild, nausea/vomiting was absent in 91% of the patients. In 80% of the patients the neurological condition improved or remained stable compared with the start of radiotherapy but in 58% of the patients steroids were necessary, either increased in dose or initiated. Acute toxicity did not increase with increasing radiation doses although patients treated with 60 Gy more often required steroids than the other groups. Late toxicity was strongly suspected in 2 patients receiving 52 Gy and 56 Gy, respectively. Within the whole group of 66 patients only one recurrence outside the primary site was found. Median survival was 8.7 ± 0.7 months and no statistically significant differences were found for the four different dose-level groups. As compared with other published series, no substantial gain in either median or overall survival was achieved by a considerable shortening of the overall treatment time (less than 2 weeks in the present study as compared with 6 weeks in conventionally fractionated radiation schedules). This could be an indication that repopulation during treatment did not explain the well-known radioresistance of glioblastoma multiforme.