Klinik für Strahlentherapie, Leopoldina Krankenhaus Schweinfurt, MVZ Leopoldina Krankenhaus, Robert-Koch-Straße 10, 97422, Schweinfurt, Germany.
Klinik für Radio-Onkologie, Universitätsspital Zürich, Universität Zürich, 8006, Zurich, Switzerland.
J Neurooncol. 2022 Jan;156(2):407-417. doi: 10.1007/s11060-021-03926-0. Epub 2021 Dec 23.
The standard treatment of glioblastoma patients consists of surgery followed by normofractionated radiotherapy (NFRT) with concomitant and adjuvant temozolomide chemotherapy. Whether accelerated hyperfractionated radiotherapy (HFRT) yields comparable results to NFRT in combination with temozolomide has only sparsely been investigated. The objective of this study was to compare NFRT with HFRT in a multicenter analysis.
A total of 484 glioblastoma patients from four centers were retrospectively pooled and analyzed. Three-hundred-ten and 174 patients had been treated with NFRT (30 × 1.8 Gy or 30 × 2 Gy) and HFRT (37 × 1.6 Gy or 30 × 1.8 Gy twice/day), respectively. The primary outcome of interest was overall survival (OS) which was correlated with patient-, tumor- and treatment-related variables via univariable and multivariable Cox frailty models. For multivariable modeling, missing covariates were imputed using multiple imputation by chained equations, and a sensitivity analysis was performed on the complete-cases-only dataset.
After a median follow-up of 15.7 months (range 0.8-88.6 months), median OS was 16.9 months (15.0-18.7 months) in the NFRT group and 14.9 months (13.2-17.3 months) in the HFRT group (p = 0.26). In multivariable frailty regression, better performance status, gross-total versus not gross-total resection, MGMT hypermethylation, IDH mutation, smaller planning target volume and salvage therapy were significantly associated with longer OS (all p < 0.01). Treatment differences (HFRT versus NFRT) had no significant effect on OS in either univariable or multivariable analysis.
Since HFRT with temozolomide was not associated with worse OS, we assume HFRT to be a potential option for patients wishing to shorten their treatment time.
胶质母细胞瘤患者的标准治疗包括手术，随后进行常规分割放疗（NFRT），同时联合替莫唑胺化疗。加速超分割放疗（HFRT）与 NFRT 联合替莫唑胺的疗效是否相当，这方面的研究还很少。本研究的目的是在多中心分析中比较 NFRT 和 HFRT。
回顾性汇总并分析了来自四个中心的 484 名胶质母细胞瘤患者。其中 310 名患者接受 NFRT（30×1.8 Gy 或 30×2 Gy）治疗，174 名患者接受 HFRT（37×1.6 Gy 或 30×1.8 Gy 每日 2 次）治疗。主要观察终点是总生存（OS），通过单变量和多变量 Cox 脆弱性模型，将其与患者、肿瘤和治疗相关变量进行相关性分析。对于多变量建模，使用链方程的多重插补法对缺失的协变量进行插补，并对完整病例数据集进行敏感性分析。
中位随访 15.7 个月（范围 0.8-88.6 个月）后，NFRT 组中位 OS 为 16.9 个月（15.0-18.7 个月），HFRT 组为 14.9 个月（13.2-17.3 个月）（p=0.26）。在多变量脆弱性回归中，更好的表现状态、大体全切除与非大体全切除、MGMT 甲基化、IDH 突变、较小的计划靶区和挽救性治疗与更长的 OS 显著相关（均 p<0.01）。在单变量和多变量分析中，治疗差异（HFRT 与 NFRT）对 OS 均无显著影响。
由于 HFRT 联合替莫唑胺治疗与 OS 无明显相关，我们假设 HFRT 可能是希望缩短治疗时间的患者的潜在选择。
