Article
Is bevacizumab more effective in combination with re-irradiation for salvage treatment of malignant gliomas?
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Authors
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Jun Thorsteinsdottir
- Neurochirurgische Klinik und Poliklinik, Klinikum der Ludwig-Maximilians-Universität München
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Maximilian Niyazi
- Klinik und Poliklinik für Strahlentherapie und Radioonkologie, Klinikum der Ludwig-Maximilians-Universität München
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Daniel Felix Fleischmann
- Klinik und Poliklinik für Strahlentherapie und Radioonkologie, Klinikum der Ludwig-Maximilians-Universität München
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Jörg-Christian Tonn
- Neurochirurgische Klinik und Poliklinik, Klinikum der Ludwig-Maximilians-Universität München
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Friedrich Wilhelm Kreth
- Neurochirurgische Klinik und Poliklinik, Klinikum der Ludwig-Maximilians-Universität München
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Oliver Schnell
- Neurochirurgische Klinik und Poliklinik, Klinikum der Ludwig-Maximilians-Universität München
| Published: | June 2, 2015 |
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Outline
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Objective: Bevacizumab (BEV) either alone or in combination with irinotecan has been reported to be effective for recurrent glioblastomas. A few retrospective data have indicated that BEV in combination with re-irradiation (Re-RT) might further improve outcome measurements. However, no comparative analysis of patients' characteristics for BEV- and combined-treated patients exists and treatment results were not adjusted accordingly. For clarification the current study was conducted: we compared treatment results after BEV alone and Re-RT plus BEV after adjustment for the effects of other patient- and tumor-related factors.
Method: 110 consecutively treated adult patients with a histologically proven recurrent malignant glioma (WHO°III n=19, WHO°IV n=91) previously undergoing standard treatment (RT; with/ without temozolomide) were considered eligible for this retrospective analysis. All patients gave informed consent. According to the interdisciplinary tumorboard suggestions, the following salvage treatment strategies were initiated: 1. BEV alone (10mg/kg, 33 pat.), 2. Re-RT (36 Gy) with concomitant and adjuvant BEV (10mg/kg, 29 pat.), and 3. Re-RT with concomitant BEV alone (48 pat.). Re-RT was considered possible 6 months after the initial RT. Post-recurrence survival (PRS) and overall survival (OS) were estimated with the Kaplan-Meier method. Prognostic factors were obtained from proportional hazards models.
Results: Treatment groups did not differ in terms of age (median age: 50yrs). Patients undergoing Re-RT had more often WHO°III tumors (p<0.008) and higher performance scores (KPS) at the time of recurrence (p<0.03). Time to salvage treatment and OS was shorter in the BEV group (9.7months, 21months, p<0.0001) than in the Re-RT groups (20.6months, 30months, p<0.0001). Median PRS was longer in the Re-RT groups (9.3months vs. 6.6months, p<0.02). Multivariate models indicate a favorable prognostic role of a prolonged latency time between initial treatment and recurrence (p<0.01) and a KPS>70 on PRS (p<0.02). Salvage treatment strategies did not gain prognostic relevance. No influence on PRS was seen for age, gender, MGMT promoter methylation, IDH1/2 mutations and WHO grade.
Conclusions: Re-RT in combination with BEV might be an attractive salvage treatment strategy for highly selected patients. Whether Re-RT plus BEV is superior to BEV alone is unclear and deserves further prospective evaluation.
