We conducted a single-institutional randomized trial on the use of fractionated radiosurgery versus chemotherapy for recurrent malignant glioma after second-line chemotherapy.

High-grade glioma patients with tumor progression after two previous treatment regimens were enrolled. They were randomized to FSRS with bevacizumab or bevacizumab with irinotecan, temozolomide, or carboplatin (discretion of the treating provider). FSRS was delivered as 32 Gy (8 Gy x 4 treatments within 2 weeks) to the gross target volume (gadolinium enhancing lesion and DWI abnormality), and 24 Gy (6 Gy x 4) to the clinical target volume (FLAIR abnormality). The primary endpoints were local tumor control (LC) at 2 months and progression-free survival (PFS). The study planned to accrue 78 patients total, but was closed early due to slow accrual.

34 patients were enrolled from February 2012 to December 2016. Twenty-seven patients had glioblastoma (WHO IV) and 7 had anaplastic glioma (WHO III). The median number of prior recurrences was 3. Patients on the FSRS arm had an improved PFS (5.3 vs 1.8 months, p<0.001) and improved LC at 2 months (2/16 patients progressing at 2 months compared to 11/15 on chemotherapy alone) (p=0.001).  The overall median survival was 6.4 months (7.1 months in the FSRS arm, 4.8 months in the chemotherapy arm, p=0.24).  Five patients on the chemotherapy alone arm subsequently received FSRS at time of progression.

Findings of our study suggest that FSRS in heavily pretreated patients with recurrent malignant glioma is feasible and improves LC and PFS when compared to treatment with next line chemotherapy alone.