Validation of the prognostic Heidelberg re-irradiation score in an independent mono-institutional patient cohort.

PURPOSE: Re-irradiation has been shown to be a valid option with proven efficacy for recurrent high-grade glioma patients. Overall, up to now it is unclear which patients might be optimal candidates for a second course of irradiation. A recently reported prognostic score developed by Combs et al. may guide treatment decisions and thus, our mono-institutional cohort served as validation set to test its relevance for clinical practice. PATIENTS AND METHODS: The prognostic score is built upon histology, age (< 50 vs. ≥ 50 years) and the time between initial radiotherapy and re-irradiation (≤ 12 vs. > 12 months). This score was initially introduced to distinguish patients with excellent (0 points), good (1 point), moderate (2 points) and poor (3-4 points) post-recurrence survival (PRS) after re-irradiation. Median prescribed radiation dose during re-treatment of recurrent malignant glioma was 36 Gy in 2 Gy single fractions. A substantial part of the patients was additionally treated with bevacizumab (10 mg/kg intravenously at d1 and d15 during re-irradiation). RESULTS: 88 patients (initially 61 WHO IV, 20 WHO III, 7 WHO II) re-irradiated in a single institution were retrospectively analyzed. Median follow-up was 30 months and median PRS of the entire patient cohort 7 months. Seventy-one patients (80.7%) received bevacizumab. PRS was significantly increased in patients receiving bevacizumab (8 vs. 6 months, p = 0.027, log-rank test). KPS, age, MGMT methylation status, sex, WHO grade and the Heidelberg score showed no statistically significant influence on neither PR-PFS nor PRS. CONCLUSION: In our cohort which was mainly treated with bevacizumab the usefulness of the Heidelberg score could not be confirmed probably due to treatment heterogeneity; it can be speculated that larger multicentric data collections are needed to derive a more reliable score.

Re-irradiation and bevacizumab in recurrent high-grade glioma: an effective treatment option.

Re-irradiation has been shown to be a meaningful option for recurrent high-grade glioma (HGG) patients. Furthermore, bevacizumab exerts certain activity in combination with chemotherapy/as monotherapy and was safely tested in combination with radiotherapy in several previous studies. To our knowledge, this is the largest cohort of patients treated with both re-irradiation and bevacizumab to date. After receiving standard radiotherapy (with or without TMZ) patients with recurrent HGG were treated with bevacizumab (10 mg/kg intravenously at d1 and d15) during re-irradiation. Median prescribed radiation dose during re-treatment was 36 Gy, conventionally fractionated. Datasets of 71 re-irradiated patients were retrospectively analyzed. Patients either received bevacizumab (N = 57) or not (N = 14; other substances (N = 4) and sole radiation (N = 10)). In patients receiving bevacizumab, both post-recurrence survival (PRS) (median 8.6 vs. 5.7 months; p = 0.003, log-rank test) and post-recurrence progression-free survival (PR-PFS, 5.6 vs. 2.5 months; p = 0.005, log-rank test; PFS-6 42.1 % for the bevacizumab group) were significantly increased which was confirmed by multivariate analysis. KPS, re-surgery, MGMT methylation status, sex, WHO grade, tumor volume and age were no significant predictors for neither PR-PFS nor PRS (univariate analysis). Re-irradiation with bevacizumab remains a feasible and highly effective treatment schedule. Studies on further salvage strategies and timing of sequential treatment options versus observation are warranted.