Re-irradiation and bevacizumab in recurrent high-grade glioma: an effective treatment option

Abstract

Re-irradiation has been shown to be a meaningful option for recurrent high-grade glioma (HGG) patients. Furthermore, bevacizumab exerts certain activity in combination with chemotherapy/as monotherapy and was safely tested in combination with radiotherapy in several previous studies. To our knowledge, this is the largest cohort of patients treated with both re-irradiation and bevacizumab to date. After receiving standard radiotherapy (with or without TMZ) patients with recurrent HGG were treated with bevacizumab (10 mg/kg intravenously at d1 and d15) during re-irradiation. Median prescribed radiation dose during re-treatment was 36 Gy, conventionally fractionated. Datasets of 71 re-irradiated patients were retrospectively analyzed. Patients either received bevacizumab (N = 57) or not (N = 14; other substances (N = 4) and sole radiation (N = 10)). In patients receiving bevacizumab, both post-recurrence survival (PRS) (median 8.6 vs. 5.7 months; p = 0.003, log-rank test) and post-recurrence progression-free survival (PR-PFS, 5.6 vs. 2.5 months; p = 0.005, log-rank test; PFS-6 42.1 % for the bevacizumab group) were significantly increased which was confirmed by multivariate analysis. KPS, re-surgery, MGMT methylation status, sex, WHO grade, tumor volume and age were no significant predictors for neither PR-PFS nor PRS (univariate analysis). Re-irradiation with bevacizumab remains a feasible and highly effective treatment schedule. Studies on further salvage strategies and timing of sequential treatment options versus observation are warranted.

Therapeutic options in recurrent glioblastoma—An update

“…Several studies evaluated the combination of bevacizumab with re-irradiation with the hypothesis that vascular normalization results in improved oxygenation of tumor tissue and thereby increases the effect of radiation. With heterogeneous cohorts of WHO grade III (n=6, n=14, n=12) and glioblastomas (n=8, n=43, n=42) treated with re-irradiation with and without bevacizumab a higher median PFS (5.7 vs. 3.7, 5.6 vs. 2.5, and 6 vs. 4 months) and higher median OS (8.3 vs. 14.3, 8.6 vs. 5.7, 11 vs 8.3 months) were reached in 2 of 3 retrospective studies in the bevacizumab cohort [40][41][42]. In the study of Minniti and colleagues the non-bevacizumab group received fotemustine.…”

Re-irradiation for Recurrent Primary Brain Tumors

“…Overall and progressionfree survival were significantly better in the bevacizumab cohort. Combined with conventionally fractionated reirradiation (median dose 36 Gy), median survival was 8.6 months (79). Compared with patients who did not receive bevacizumab (n=44), the patients who received bevacizumab after radiosurgery (n=11) in a case-control study had significantly prolonged progression-free survival (15 months vs. 7 months, p=0.035) and overall survival (18 months vs. 12 months, p=0.005) and were less likely to develop an adverse radiation effect (9 vs. 46%, p=0.037).…”

Therapeutic Options for Recurrent High-Grade Gliomas: A Perspective Statement

“…Several trials have been published with results comparable to microsurgical reresection; reported PRS was in the range of 6-12 months. 18 The major limiting factors of percutaneous re-irradiation are tumor/treatment volume, applied total dose, as well as the time interval to initial radiotherapy. The recommended time interval between initial and re-irradiation should not fall short of 6 months.…”

“…Flieger et al showed that the concomitant administration of bevacizumab (BEV) in patients undergoing re-irradiation for HGGs significantly improved PFS. 18 The armamentarium of systemic approaches for treatment of recurrent HGGs mainly consists of rechallenge regimens comprising established alkylating agents such nitrosoureas (e.g. carmustine, lomustine, imustine) and TMZ.…”