A multi-center prospective study of re-irradiation with bevacizumab and temozolomide in patients with bevacizumab refractory recurrent high-grade gliomas

Karan S. Dixit*, Sean Sachdev, Christina Amidei, Priya Kumthekar, Tim J. Kruser, Vinai Gondi, Sean Grimm, Rimas V. Lukas, Martin Kelly Nicholas, Steven J. Chmura, Angela J. Fought, Minesh Mehta, Jeffrey J. Raizer

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Purpose: Survival is dismal for bevacizumab refractory high-grade glioma patients. We prospectively investigated the efficacy of re-irradiation, bevacizumab, and temozolomide in bevacizumab-naïve and bevacizumab-exposed recurrent high-grade glioma, without volume limitations, in a single arm trial. Methods: Recurrent high-grade glioma patients were stratified based on WHO grade (4 vs. < 4) and prior exposure to bevacizumab (yes vs. no). Eligible patients received radiation using a simultaneous integrated boost technique (55 Gy to enhancing disease, 45 Gy to non-enhancing disease in 25 fractions) with bevacizumab 10 mg/kg every 2 weeks IV and temozolomide 75 mg/m2 daily followed by maintenance bevacizumab 10 mg/kg every 2 weeks and temozolomide 50 mg/m2 daily for 6 weeks then a 2 week holiday until progression. Primary endpoint was overall survival. Quality of life was studied using FACT-Br and FACT-fatigue scales. Results: Fifty-four patients were enrolled. The majority (n = 36, 67%) were bevacizumab pre-exposed GBM. Median OS for all patients was 8.5 months and 7.9 months for the bevacizumab pre-exposed GBM group. Patients ≥ 36 months from initial radiation had a median OS of 13.3 months compared to 7.5 months for those irradiated < 36 months earlier (p < 0.01). FACT-Br and FACT-Fatigue scores initially declined during radiation but returned to pretreatment baseline. Treatment was well tolerated with 5 patients experiencing > grade 3 lymphopenia and 2 with > grade 3 thrombocytopenia. No radiographic or clinical radiation necrosis occurred. Conclusions: Re-irradiation with bevacizumab and temozolomide is a safe and feasible salvage treatment for patients with large volume bevacizumab-refractory high-grade glioma. Patients further from their initial radiotherapy may derive greater benefit with this regimen.

Original languageEnglish (US)
Pages (from-to)297-306
Number of pages10
JournalJournal of Neuro-Oncology
Volume155
Issue number3
DOIs
StatePublished - Dec 2021

Funding

We would like to thank all patients and caregivers. We would like to thank all of the clinical staff at the Robert H. Lurie Cancer Center of Northwestern University. We would like to thank Lyndsey Van for assistance with manuscript preparation. Finally, we would like to thank Dr. Roger Stupp for critical review of the manuscript.

Keywords

  • Bevacizumab
  • Glioblastoma
  • Radiation
  • Re-irradiation
  • Recurrent glioma
  • Temozolomide

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

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