Daniel Felix Fleischmann1, Johanna Jenn2, Stefanie Corradini2, Viktoria Ruf3, Jochen Herms3, Robert Forbrig4, Marcus Unterrainer5, Niklas Thon6, Friedrich Wilhelm Kreth6, Claus Belka7, Maximilian Niyazi8. 1. Department of Radiation Oncology, University Hospital, LMU Munich, Germany; German Cancer Consortium (DKTK), Munich, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany. 2. Department of Radiation Oncology, University Hospital, LMU Munich, Germany. 3. Institute of Neuropathology, Faculty of Medicine, LMU Munich, Germany. 4. Institute of Neuroradiology, University Hospital, LMU Munich, Germany. 5. Department of Nuclear Medicine, University Hospital, LMU Munich, Germany. 6. German Cancer Consortium (DKTK), Munich, Germany; Department of Neurosurgery, University Hospital, LMU Munich, Germany. 7. Department of Radiation Oncology, University Hospital, LMU Munich, Germany; German Cancer Consortium (DKTK), Munich, Germany. 8. Department of Radiation Oncology, University Hospital, LMU Munich, Germany; German Cancer Consortium (DKTK), Munich, Germany. Electronic address: maximilian.niyazi@med.uni-muenchen.de.
Abstract
PURPOSE: The role of bevacizumab (BEV) in the setting of reirradiation (reRT) of malignant glioma recurrences is poorly defined. At our institution, reRT plus BEV was routinely used until its disapproval for glioma treatment by the European Medical Agency. Accordingly, reRT was applied without the addition of BEV since 2017. Here we present for the first time outcome and toxicity profiles of reRT plus BEV and reRT alone for malignant glioma recurrences. PATIENTS AND METHODS: All adult patients consecutively undergoing reRT of a recurrent malignant glioma (37 anaplastic astrocytoma, WHO III; 124 glioblastoma, WHO IV) between 2007 and 2017 were included. In one group of patients, BEV (10 mg/kg bodyweight) was applied concomitantly on days 1 and 15 of reRT. Radiation toxicity referred to clinically significant toxicities of proven symptomatic radionecrosis (RN) and symptomatic oedema (SE) requiring steroid treatment for more than six weeks after reRT. Post-recurrence survival (PRS) and freedom from RN/SE were estimated with the Kaplan-Meier method. Prognostic factors were obtained from proportional hazards models. RESULTS: BEV plus reRT was applied in 124 and reRT alone in 37 patients. Both groups were comparable in terms of their patient-, tumour-, and RT/reRT-related variables. PRS was independent from the applied reRT protocols. RN/SE was less frequently seen after reRT plus BEV absolutely (27/124 (21.8%) vs. 14/37 (37.8%) patients; p = 0.025) and over time (1-year RN/SE rate: 23.9% vs. 54.1%; p = 0.013). The unadjusted and adjusted hazard ratio for RN/SE was doubled in case of reRT alone. Absence of BEV remained the only risk factor for RN/SE in multivariate models (p = 0.026). CONCLUSION: Concomitant BEV effectively reduces treatment toxicity of reRT and should be reconsidered in future reRT protocols.
PURPOSE: The role of bevacizumab (BEV) in the setting of reirradiation (reRT) of malignant glioma recurrences is poorly defined. At our institution, reRT plus BEV was routinely used until its disapproval for glioma treatment by the European Medical Agency. Accordingly, reRT was applied without the addition of BEV since 2017. Here we present for the first time outcome and toxicity profiles of reRT plus BEV and reRT alone for malignant glioma recurrences. PATIENTS AND METHODS: All adult patients consecutively undergoing reRT of a recurrent malignant glioma (37 anaplastic astrocytoma, WHO III; 124 glioblastoma, WHO IV) between 2007 and 2017 were included. In one group of patients, BEV (10 mg/kg bodyweight) was applied concomitantly on days 1 and 15 of reRT. Radiation toxicity referred to clinically significant toxicities of proven symptomatic radionecrosis (RN) and symptomatic oedema (SE) requiring steroid treatment for more than six weeks after reRT. Post-recurrence survival (PRS) and freedom from RN/SE were estimated with the Kaplan-Meier method. Prognostic factors were obtained from proportional hazards models. RESULTS:BEV plus reRT was applied in 124 and reRT alone in 37 patients. Both groups were comparable in terms of their patient-, tumour-, and RT/reRT-related variables. PRS was independent from the applied reRT protocols. RN/SE was less frequently seen after reRT plus BEV absolutely (27/124 (21.8%) vs. 14/37 (37.8%) patients; p = 0.025) and over time (1-year RN/SE rate: 23.9% vs. 54.1%; p = 0.013). The unadjusted and adjusted hazard ratio for RN/SE was doubled in case of reRT alone. Absence of BEV remained the only risk factor for RN/SE in multivariate models (p = 0.026). CONCLUSION: Concomitant BEV effectively reduces treatment toxicity of reRT and should be reconsidered in future reRT protocols.
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