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Large volume reirradiation as salvage therapy for glioblastoma after progression on bevacizumab

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Abstract

Outcomes after bevacizumab failure for recurrent glioblastoma (GBM) are poor. Our analysis of 16 phase II trials (n = 995) revealed a median overall survival (OS) of 3.8 months (±1.0 month SD) after bevacizumab failure with no discernible activity of salvage chemotherapy. Thus, the optimal treatment for disease progression after bevacizumab has yet to be elucidated. This study evaluated the efficacy of reirradiation for patients with GBM after progression on bevacizumab. An IRB approved retrospective (2/2008–5/2013) analysis was performed of 23 patients with recurrent GBM (after standard radiotherapy/temozolomide) treated with bevacizumab (10 mg/kg) every 2 weeks until progression (median age 53 years; median KPS 80; median progression free survival on bevacizumab 3.7 months). Within 7–14 days of progression on bevacizumab, patients initiated reirradiation to a dose of 54 Gy in 27 fractions using pulsed-reduced dose rate (PRDR) radiotherapy. The median planning target volume was 424 cm3. At the start of reirradiation, bevacizumab (10 mg/kg) was given every 4 weeks for two additional cycles. The median OS and 6 month OS after bevacizumab failure was 6.9 months and 65 %, respectively. Reirradiation was well tolerated with no symptomatic grade 3–4 toxicities. Favorable outcomes of reirradiation after bevacizumab failure in patients with recurrent GBM suggest its role as a treatment option for large volume recurrences not amenable to stereotactic radiosurgery. As PRDR is easily accomplished from a technological standpoint, we are in the process of expanding this approach to a multi-institutional cooperative group trial.

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Notes

  1. Rationale for CTV: During the first course of radiotherapy, the CTV for the initial field recommended by the radiation therapy oncology group (RTOG) is the contrast enhancing lesion and adjacent T2-weighted or FLAIR irregularity with a 2.0 cm margin. This recommendation is based upon two studies, one of which demonstrated that the isolated tumor cell infiltration extended at least as far as the T2 prolongation on MRI and another which showed that 90 % of recurrences were within 2 cm of the contrast enhancing lesion [30, 31].

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Acknowledgments

Kathleen Reader Neuro-oncology Fund.

Conflict of interest

HIR has served as a consultant to Novocure and Genentech

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Authors and Affiliations

  1. Department of Radiation Oncology, University of Wisconsin, Madison, WI, USA

    William Magnuson, Pranshu Mohindra & Steven Howard

  2. Departments of Medicine, Human Oncology and Neurology, K4/534 Clinical Science Center, University of Wisconsin, 600 Highland Avenue, Madison, WI, 53792, USA

    H. Ian Robins

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  1. William Magnuson
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Correspondence to H. Ian Robins.

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Magnuson, W., Ian Robins, H., Mohindra, P. et al. Large volume reirradiation as salvage therapy for glioblastoma after progression on bevacizumab. J Neurooncol 117, 133–139 (2014). https://doi.org/10.1007/s11060-014-1363-z

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  • DOI: https://doi.org/10.1007/s11060-014-1363-z

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