Randomized prospective trial of fractionated stereotactic radiosurgery with chemotherapy versus chemotherapy alone for bevacizumab-resistant high-grade glioma.

Abstract

Outcomes for patients with recurrent high-grade glioma (HGG) progressing on bevacizumab (BEV) are dismal. Fractionated stereotactic radiosurgery (FSRS) has been shown to be feasible and safe when delivered in this setting, but prospective evidence is lacking. This single-institution randomized trial compared FSRS plus BEV-based chemotherapy versus BEV-based chemotherapy alone for BEV-resistant recurrent malignant glioma. HGG patients on BEV with tumor progression after 2 previous treatments were randomized to 1) FSRS plus BEV-based chemotherapy or 2) BEV-based chemotherapy with irinotecan, etoposide, temozolomide, or carboplatin. FSRS was delivered as 32Gy (8Gy × 4 fractions within 2weeks) to the gross target volume and 24Gy (6Gy × 4 fractions) to the clinical target volume (fluid-attenuated inversion recovery abnormality). The primary endpoints were local control (LC) at 2months and progression-free survival (PFS). Of the 35 patients enrolled, 29 had glioblastoma (WHO IV) and 6 had anaplastic glioma (WHO III). The median number of prior recurrences was 3. Patients treated with FSRS had significantly improved PFS (5.1 vs 1.8months, P < .001) and improved LC at 2months (82% [14/17] vs 27% [4/15], P = .002). The overall median survival was 6.6months (7.2months with FSRS vs 4.8months with chemotherapy alone, P = .11). FSRS combined with BEV-based chemotherapy in recurrent HGG patients progressing on BEV is feasible and improves LC and PFS when compared to treatment with BEV-based chemotherapy alone.