It was with great interest that we reviewed the recent report by Back et al. regarding re-irradiation with bevacizumab (BEV) in refectory high-grade glioma.1 We recently reported on a series of 23 patients with glioblastoma refractory to BEV.2 Our review of the literature (n = 995) found that this cohort of patients had a median overall survival (OS) of only 3.8 months with the continuation of systemic therapies.2 It is noteworthy that by utilizing pulsed-reduced dose rate radiotherapy (PRDR) we were able to treat volumes significantly larger [median planning target volume (PTV) 424 cm3] than those reported by Back et al (median PTV 133 cm3). Patients were treated to a dose of 54 Gray in 27 fractions and BEV (10 mg/kg) was only given on weeks 1 and 4 of radiotherapy. There was a strong suggestion of an OS benefit, as the median OS and 6-month OS after BEV failure were 6.9 months and 65%, respectively. In the Back series, the OS in BEV refractory patients (n = 7) was only 3 months. Treatment with PRDR radiotherapy was well tolerated with no grade 3–5 toxicities.
We hypothesize that PRDR improves the therapeutic index by allowing the normal tissue to repair sublethal damage with greater efficacy than adjacent malignant cells while simultaneously taking advantage of low-dose rate hypersensitivity.2 We are currently partnering with several other institutions in an ongoing prospective clinical trial to further delineate the aforementioned findings.
Funding
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Conflict of interest statement. None declared.
References
- 1. Back M, Gzell CE, Kastelan M et al. Large volume re-irradiation with bevacizumab is a feasible salvage option for patients with refractory high-grade glioma. Neuro Oncol Pract. 2015;1:48–53. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2. Magnuson W, Robins HI, Mohindra P et al. Large volume reirradiation as salvage therapy for glioblastoma after progression on bevacizumab. J Neurooncol. 2014;117:133–139. [DOI] [PubMed] [Google Scholar]