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Randomized prospective trial of fractionated stereotactic radiosurgery with chemotherapy versus chemotherapy alone for bevacizumab-resistant high-grade glioma

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Abstract

Purpose

Outcomes for patients with recurrent high-grade glioma (HGG) progressing on bevacizumab (BEV) are dismal. Fractionated stereotactic radiosurgery (FSRS) has been shown to be feasible and safe when delivered in this setting, but prospective evidence is lacking. This single-institution randomized trial compared FSRS plus BEV-based chemotherapy versus BEV-based chemotherapy alone for BEV-resistant recurrent malignant glioma.

Materials and methods

HGG patients on BEV with tumor progression after 2 previous treatments were randomized to 1) FSRS plus BEV-based chemotherapy or 2) BEV-based chemotherapy with irinotecan, etoposide, temozolomide, or carboplatin. FSRS was delivered as 32 Gy (8 Gy × 4 fractions within 2 weeks) to the gross target volume and 24 Gy (6 Gy × 4 fractions) to the clinical target volume (fluid-attenuated inversion recovery abnormality). The primary endpoints were local control (LC) at 2 months and progression-free survival (PFS).

Results

Of the 35 patients enrolled, 29 had glioblastoma (WHO IV) and 6 had anaplastic glioma (WHO III). The median number of prior recurrences was 3. Patients treated with FSRS had significantly improved PFS (5.1 vs 1.8 months, P < .001) and improved LC at 2 months (82% [14/17] vs 27% [4/15], P = .002). The overall median survival was 6.6 months (7.2 months with FSRS vs 4.8 months with chemotherapy alone, P = .11).

Conclusions

FSRS combined with BEV-based chemotherapy in recurrent HGG patients progressing on BEV is feasible and improves LC and PFS when compared to treatment with BEV-based chemotherapy alone.

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Data availability

Data will be available from the authors upon request.

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Funding

Funding was provided by the Hermelin Brain Tumor Center, the Department of Neurosurgery at Henry Ford Health System and funds raised with help of the Head for the Cure Foundation.

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Authors and Affiliations

  1. Department of Neurosurgery, Henry Ford Health System, 2799 W Grand Blvd, Detroit, MI, 48202, USA

    Lonni Schultz, James Snyder, Tom Mikkelsen & Tobias Walbert

  2. Department of Neurology, Henry Ford Health System, 2799 W Grand Blvd, Detroit, MI, 48202, USA

    James Snyder, Tom Mikkelsen & Tobias Walbert

  3. Department of Radiation Oncology, Henry Ford Health System, 2799 W Grand Blvd, Detroit, MI, 48202, USA

    David Bergman, Ankit Modh, Mira Shah & M. Salim Siddiqui

  4. Department of Radiation Oncology, Stony Brook University Hospital, 101 Nicolls Road, Stony Brook, NY, 11794, USA

    Samuel Ryu

  5. Department of Public Health Sciences, Henry Ford Health System, 2799 W Grand Blvd, Detroit, MI, 48202, USA

    Lonni Schultz

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  1. David Bergman
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Contributions

Study design and oversight: SR, MSS, TW, TM. Manuscript composition and editing: DB, TW, SR, TM. Statistical analysis: LS. Collection of data: DB, AM, MS, MSS. Data analysis: TW, JS, SR, DB, AM. Approval and review of submitted manuscript: DB, AM, LS, JS, TM, MS, SR, MSS, TW.

Corresponding author

Correspondence to Tobias Walbert.

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Conflict of interest:

The authors declare there are no conflicts of interest. ICMJE forms have been signed by all authors.

Ethical approval:

This study was approved by our institutional review board (HFHS-C # 11–01).

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Bergman, D., Modh, A., Schultz, L. et al. Randomized prospective trial of fractionated stereotactic radiosurgery with chemotherapy versus chemotherapy alone for bevacizumab-resistant high-grade glioma. J Neurooncol 148, 353–361 (2020). https://doi.org/10.1007/s11060-020-03526-4

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