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复发性多形性胶质母细胞瘤的再放疗:不同概念的批判性比较。

Re-irradiation for recurrent glioblastoma multiforme: a critical comparison of different concepts.

机构信息

Department of Radiation Oncology, University Hospital Münster, Albert-Schweitzer Campus 1, 48149, Muenster, Germany.

Department of Neurology, University Hospital Münster, Albert-Schweitzer Campus 1, 48149, Muenster, Germany.

出版信息

Strahlenther Onkol. 2020 May;196(5):457-464. doi: 10.1007/s00066-020-01585-0. Epub 2020 Feb 3.

Abstract

PURPOSE

Purpose of this study was to investigate outcome and toxicity of re-irradiation for recurrent primary glioblastoma (rGBM). We evaluated a group of patients with rGBM and identical primary treatment comprising adjuvant radiotherapy (30 × 2 Gy) with concurrent temozolomide (TMZ).

METHODS

In this retrospective study of 46 patients, all received adjuvant or definitive normofractionated radiotherapy to a pretreated area, some with concurrent chemotherapy. Impact of different clinical, histological, or epidemiological factors on survival and radiation toxicity was reviewed.

RESULTS

Of 46 patients, 40 completed the intended therapy. Overall survival (OS) was 20 months (range 6-72 months). Overall survival and progression-free survival after re-irradiation (OS2 and PFS2) were 9.5 and 3.4 months (range 2-40 and 0.7-44 months). Simultaneous systemic therapy improved PFS2 and OS2 (4.3 vs. 2.0, p < 0.001 and 12 vs. 4 months, p = 0.13, respectively). Therapy with TMZ or bevacizumab improved PFS2 vs. nitrosureas (6.6 vs. 2.9, p = 0.03 and 5.1 vs. 2.9 months, p = 0.035, respectively). TMZ also improved PFS2 and OS2 vs. all other systemic therapies (6.6 vs. 4, p < 0.001 and 17 vs. 10 months, p = 0.1). In a subgroup analysis for patients with methylation of the MGMT promoter, doses of >36 Gy as well as TMZ vs. no systemic therapy improved PFS2 (p = 0.045 and p = 0.03, respectively). 27.5% of all patients had no acute toxicity. Three patients with acute and four patients with late grade 3 toxicities were reported.

CONCLUSION

Normofractionated radiotherapy is a feasible option for rGBM with a good toxicity profile. Simultaneously applied systemic therapy was associated with improved outcome. For MGMT promoter-methylated histology, higher radiation doses improved survival.

摘要

目的

本研究旨在探讨复发性原发性胶质母细胞瘤(rGBM)再放疗的疗效和毒性。我们评估了一组接受过辅助放疗(30×2Gy 与替莫唑胺同步治疗)的 rGBM 患者。

方法

在这项 46 例患者的回顾性研究中,所有患者均接受了辅助或标准分割放疗,部分患者接受了同期化疗。我们回顾了不同的临床、组织学或流行病学因素对生存和放射毒性的影响。

结果

46 例患者中,40 例完成了预期治疗。总生存期(OS)为 20 个月(6-72 个月)。再放疗后的总生存期(OS2)和无进展生存期(PFS2)分别为 9.5 个月和 3.4 个月(2-40 个月和 0.7-44 个月)。同期全身治疗改善了 PFS2 和 OS2(4.3 个月比 2.0 个月,p<0.001;12 个月比 4 个月,p=0.13)。TMZ 或贝伐单抗治疗改善了 PFS2 与氮氧脲(6.6 个月比 2.9 个月,p=0.03 和 5.1 个月比 2.9 个月,p=0.035)。TMZ 也改善了 PFS2 和 OS2 与所有其他全身治疗(6.6 个月比 4 个月,p<0.001;17 个月比 10 个月,p=0.1)。在亚组分析中,MGMT 启动子甲基化的患者中,剂量>36Gy 以及 TMZ 与无全身治疗相比,均改善了 PFS2(p=0.045 和 p=0.03)。所有患者中 27.5%无急性毒性。报告了 3 例急性 3 级毒性和 4 例晚期 3 级毒性。

结论

标准分割放疗是 rGBM 的一种可行选择,具有良好的毒性特征。同期应用的全身治疗与改善的预后相关。对于 MGMT 启动子甲基化的组织学,较高的放射剂量改善了生存。

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