Bevacizumab and re-irradiation for recurrent high grade gliomas: does sequence matter?

Purpose/objectives: We report the outcomes of the largest cohort to date of patients receiving both bevacizumab (BEV) and fractionated stereotactic radiotherapy (FSRT) for progressive or recurrent high grade glioma (HGG). Furthermore, the sequence of these two treatment regimens was analyzed to determine an optimal treatment paradigm for recurrent HGG. Materials/methods: After Institutional Review Board approval, patients with pathologically confirmed WHO grade III anaplastic astrocytoma (AA) or IV glioblastoma multiforme (GBM) glioma who subsequently underwent re-irradiation at recurrence with FSRT were retrospectively reviewed. Patients from this group who had received BEV were also identified. Survival from initial diagnosis, as well as from recurrence and re-irradiation, were analyzed as study endpoints. Date of recurrence was defined as the date of radiographic evidence of progressive/recurrent disease. Kaplan–Meier curves were generated utilizing a log-rank test with a p-value ≤ 0.05 considered significant to compare treatment sequences in terms of survival outcomes. Results: A total of 118 patients with recurrent/progressive HGG (GBM = 87, AA = 31) had received both BEV and FSRT. Patient characteristics were as follows: median KPS at recurrence was 80 (range 50–100); median age at recurrence was 57 years; median time to radiographic recurrence/progression was 10.8 months (mo) and 33.1% of patients had surgery for recurrence. The median time from the start of BEV to FSRT was 6.4 months and from FSRT to the start of BEV was 5.1 months. For the entire cohort, median overall survival (OS) was 26.7 months and median survival time (MST) from recurrence was 13.8 months (24.4 months and 11.9 months for GBM only). In patients that received BEV prior to FSRT (n = 50), median OS and MST from recurrence were 25.2 and 13.3 months respectively. In patients receiving FSRT first (n = 56), median OS and MST from recurrence were 28.8 months and 13.9 months, respectively. Sequencing of BEV and FSRT at recurrence was not significantly associated with OS (p = 0.08) or median survival from recurrence (p = 0.75). Conclusions: The combination of FSRT and BEV for recurrent/progressive HGG provides promising results in terms of overall survival and survival from recurrence. Combining these treatment modalities appears to improve upon the historic outcomes of either treatment alone. The outcomes data from this study support the ongoing RTOG trial exploring the combination of BEV and FSRT for recurrent HGG.