Radiotherapy Versus Combination Radiotherapy-bevacizumab for the Treatment of Recurrent High-grade Glioma: a Systematic Review

Overview

Journal Acta Neurochir (Wien)

Specialty Neurosurgery

Date 2021 Apr 2

PMID 33796887

Citations 19

Authors

Daniel P Kulinich

John P Sheppard

Thien Nguyen

Aditya M Kondajji

Ansley Unterberger

Courtney Duong

Adam Enomoto

Kunal Patel

Isaac Yang

Affiliations

Soon will be listed here.

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.

Citing Articles

Aberrant choroid plexus formation drives the development of treatment-related brain toxicity.

Bender T, Schickel E, Schielke C, Debus J, Grosshans D, Durante M Commun Biol. 2025; 8(1):276.

PMID: 39987290 PMC: 11846864. DOI: 10.1038/s42003-025-07736-2.

The efficacy of stereotactic radiotherapy followed by bevacizumab and temozolomide in the treatment of recurrent glioblastoma: a case report.

Zhong W, Mao J, Wu D, Peng J, Ye W Front Pharmacol. 2024; 15:1401000.

PMID: 39295944 PMC: 11408163. DOI: 10.3389/fphar.2024.1401000.

Is add-on Bevacizumab therapy to Temozolomide and radiotherapy associated with clinical utility for newly diagnosed Glioblastoma? A systematic review and meta-analysis.

Habibi M, Shad N, Mirjnani M, Fasihi S, Sadeghi S, Karami S Neurosurg Rev. 2024; 47(1):445.

PMID: 39162874 DOI: 10.1007/s10143-024-02667-8.

Glioblastoma microenvironment-from biology to therapy.

Read R, Tapp Z, Rajappa P, Hambardzumyan D Genes Dev. 2024; 38(9-10):360-379.

PMID: 38811170 PMC: 11216181. DOI: 10.1101/gad.351427.123.

Feedback loop between hypoxia and energy metabolic reprogramming aggravates the radioresistance of cancer cells.

Shi Z, Hu C, Zheng X, Sun C, Li Q Exp Hematol Oncol. 2024; 13(1):55.

PMID: 38778409 PMC: 11110349. DOI: 10.1186/s40164-024-00519-1.

References

Amelio D, Amichetti M . Radiation therapy for the treatment of recurrent glioblastoma: an overview. Cancers (Basel). 2013; 4(1):257-80. PMC: 3712688. DOI: 10.3390/cancers4010257. View

Auffinger B, Spencer D, Pytel P, Ahmed A, Lesniak M . The role of glioma stem cells in chemotherapy resistance and glioblastoma multiforme recurrence. Expert Rev Neurother. 2015; 15(7):741-52. PMC: 4830899. DOI: 10.1586/14737175.2015.1051968. View

Bao S, Wu Q, McLendon R, Hao Y, Shi Q, Hjelmeland A . Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 2006; 444(7120):756-60. DOI: 10.1038/nature05236. View

Bao S, Wu Q, Sathornsumetee S, Hao Y, Li Z, Hjelmeland A . Stem cell-like glioma cells promote tumor angiogenesis through vascular endothelial growth factor. Cancer Res. 2006; 66(16):7843-8. DOI: 10.1158/0008-5472.CAN-06-1010. View

Bir S, Connor Jr D, Ambekar S, Wilden J, Nanda A . Factors predictive of improved overall survival following stereotactic radiosurgery for recurrent glioblastoma. Neurosurg Rev. 2015; 38(4):705-13. DOI: 10.1007/s10143-015-0632-4. View

Biswas T, Okunieff P, Schell M, Smudzin T, Pilcher W, Bakos R . Stereotactic radiosurgery for glioblastoma: retrospective analysis. Radiat Oncol. 2009; 4:11. PMC: 2662864. DOI: 10.1186/1748-717X-4-11. View

Cabrera A, Cuneo K, Desjardins A, Sampson J, McSherry F, Herndon 2nd J . Concurrent stereotactic radiosurgery and bevacizumab in recurrent malignant gliomas: a prospective trial. Int J Radiat Oncol Biol Phys. 2013; 86(5):873-9. DOI: 10.1016/j.ijrobp.2013.04.029. View

Chamberlain M, Barba D, Kormanik P, Shea W . Stereotactic radiosurgery for recurrent gliomas. Cancer. 1994; 74(4):1342-7. DOI: 10.1002/1097-0142(19940815)74:4<1342::aid-cncr2820740426>3.0.co;2-y. View

Chaudhry I, ODonovan D, Brenchley P, Reid H, Roberts I . Vascular endothelial growth factor expression correlates with tumour grade and vascularity in gliomas. Histopathology. 2001; 39(4):409-15. DOI: 10.1046/j.1365-2559.2001.01230.x. View

10.

Ciammella P, Podgornii A, Galeandro M, DAbbiero N, Pisanello A, Botti A . Hypofractionated stereotactic radiation therapy for recurrent glioblastoma: single institutional experience. Radiat Oncol. 2013; 8:222. PMC: 3852333. DOI: 10.1186/1748-717X-8-222. View

11.

Clarke J, Neil E, Terziev R, Gutin P, Barani I, Kaley T . Multicenter, Phase 1, Dose Escalation Study of Hypofractionated Stereotactic Radiation Therapy With Bevacizumab for Recurrent Glioblastoma and Anaplastic Astrocytoma. Int J Radiat Oncol Biol Phys. 2017; 99(4):797-804. PMC: 5654655. DOI: 10.1016/j.ijrobp.2017.06.2466. View

12.

Combs S, Gutwein S, Thilmann C, Huber P, Debus J, Schulz-Ertner D . Stereotactically guided fractionated re-irradiation in recurrent glioblastoma multiforme. J Neurooncol. 2005; 74(2):167-71. DOI: 10.1007/s11060-004-2463-y. View

13.

Combs S, Widmer V, Thilmann C, Hof H, Debus J, Schulz-Ertner D . Stereotactic radiosurgery (SRS): treatment option for recurrent glioblastoma multiforme (GBM). Cancer. 2005; 104(10):2168-73. DOI: 10.1002/cncr.21429. View

14.

Combs S, Bischof M, Welzel T, Hof H, Oertel S, Debus J . Radiochemotherapy with temozolomide as re-irradiation using high precision fractionated stereotactic radiotherapy (FSRT) in patients with recurrent gliomas. J Neurooncol. 2008; 89(2):205-10. DOI: 10.1007/s11060-008-9607-4. View

15.

Cuneo K, Vredenburgh J, Sampson J, Reardon D, Desjardins A, Peters K . Safety and efficacy of stereotactic radiosurgery and adjuvant bevacizumab in patients with recurrent malignant gliomas. Int J Radiat Oncol Biol Phys. 2011; 82(5):2018-24. PMC: 3690566. DOI: 10.1016/j.ijrobp.2010.12.074. View

16.

Dincoglan F, Beyzadeoglu M, Sager O, Demiral S, Gamsiz H, Uysal B . Management of patients with recurrent glioblastoma using hypofractionated stereotactic radiotherapy. Tumori. 2015; 101(2):179-84. DOI: 10.5301/tj.5000236. View

17.

Elliott R, Parker E, Rush S, Kalhorn S, Moshel Y, Narayana A . Efficacy of gamma knife radiosurgery for small-volume recurrent malignant gliomas after initial radical resection. World Neurosurg. 2011; 76(1-2):128-40. DOI: 10.1016/j.wneu.2010.12.053. View

18.

Fleischmann D, Jenn J, Corradini S, Ruf V, Herms J, Forbrig R . Bevacizumab reduces toxicity of reirradiation in recurrent high-grade glioma. Radiother Oncol. 2019; 138:99-105. DOI: 10.1016/j.radonc.2019.06.009. View

19.

Garcia-Barros M, Paris F, Cordon-Cardo C, Lyden D, Rafii S, Haimovitz-Friedman A . Tumor response to radiotherapy regulated by endothelial cell apoptosis. Science. 2003; 300(5622):1155-9. DOI: 10.1126/science.1082504. View

20.

Gigliotti M, Hasan S, Karlovits S, Ranjan T, Wegner R . Re-Irradiation with Stereotactic Radiosurgery/Radiotherapy for Recurrent High-Grade Gliomas: Improved Survival in the Modern Era. Stereotact Funct Neurosurg. 2018; 96(5):289-295. DOI: 10.1159/000493545. View