Radiotherapy versus combination radiotherapy-bevacizumab for the treatment of recurrent high-grade glioma: a systematic review

Abstract

Background High-grade gliomas (HGG) comprise the most common primary adult brain cancers and universally recur. Combination of re-irradiation therapy (reRT) and bevacizumab (BVZ) therapy for recurrent HGG is common, but its reported efficacy is mixed. Objective To assess clinical outcomes after reRT ± BVZ in recurrent HGG patients receiving stereotactic radiosurgery (SRS), hypofractionated radiosurgery (HFSRT), or fully fractionated radiotherapy (FFRT). Methods We performed a systematic review of PubMed, Web of Science, Scopus, Embase, and Cochrane databases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We identified studies reporting outcomes for patients with recurrent HGG treated via reRT ± BVZ. Cohorts were stratified by BVZ treatment status and re-irradiation modality (SRS, HFSRT, and FFRT). Outcome variables were overall survival (OS), progression-free survival (PFS), and radiation necrosis (RN). Results Data on 1399 patients was analyzed, with 954 patients receiving reRT alone and 445 patients receiving reRT + BVZ. All patients initially underwent standard-of-care therapy for their primary HGG. In a multivariate analysis that adjusted for median patient age, WHO grade, RT dosing, reRT fractionation regimen, time between primary and re-irradiation, and re-irradiation target volume, BVZ therapy was associated with significantly improved OS (2.51, 95% CI [0.11, 4.92] months, P = .041) but no significant improvement in PFS (1.40, 95% CI [− 0.36, 3.18] months, P = .099). Patients receiving BVZ also had significantly lower rates of RN (2.2% vs 6.5%, P < .001). Conclusions Combination of reRT + BVZ may improve OS and reduce RN rates in recurrent HGG, but further controlled studies are needed to confirm these effects.

Boron neutron capture therapy and add-on bevacizumab in patients with recurrent malignant glioma

“…Linear-accelerator SRS with adjuvant bevacizumab results in signi cantly longer PFS and OS (5.2 and 11.2 months, respectively) than SRS alone (2.1 and 3.9 months, respectively) for recurrent glioblastoma [19]. A systematic review of radiotherapies, including fully or hypo fractionated SRT and SRS with or without bevacizumab for recurrent MG also found that a combination of radiotherapy and bevacizumab results in longer PFS and OS (5.6 ± 1.0 and 11.2 ± 2.1 months, respectively) than radiotherapy alone (5.2 ± 1.6 and 9.9 ± 2.1 months, respectively), but the difference was not statistically signi cant [20]. In a subanalysis of radiation modalities, only fractionated SRT showed signi cantly longer OS in the bevacizumab group than in the non-bevacizumab group (11.3 ± 1.6 and 9.4 ± 1.6 months, respectively), but not PFS (6.4 ± 0.9 and 5.2 ± 1.4 months, respectively).…”

Glioblastoma Treatment: State-of-the-Art and Future Perspectives

“…Particularly in the recurrence setting, BEV presented response rates of approximately 30% in uncontrolled phase II trials [43]. About co-adjuvant chemotherapy with BEV, a randomized phase III trial tested the combination of BEV + lomustine versus lomustine alone, and results showed an improvement in PFS without OS changes in the combination group [44][45][46].…”

Intraoperative MR Imaging during Glioma Resection

“…Following 6 weeks of radiation and oral temozolomide, followed by six cycles of adjuvant temozolomide (150-200 mg per square meter for 5 days during each 28-day cycle) 187 , bevacizumab is administered intravenously at a dose of 10 mg/kg once every 2 weeks for high-grade glioma. [188][189][190][191][192][193] The newly developed U.S. Food and Drug Administration-approved Optune transducer array (Novocure, Haifa, Israel) is an noninvasive regional therapy that aims to inhibit the growth of glioblastoma multiforme cells via the use of alternating electric fields. [194][195][196][197][198][199]…”