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CyberKnife 再放疗联合“剂量密集”替莫唑胺治疗复发性脑胶质瘤的疗效和毒性。

Efficacy and toxicity of CyberKnife re-irradiation and "dose dense" temozolomide for recurrent gliomas.

机构信息

Department of Neurosurgery, University of Messina, Messina, Italy.

出版信息

Acta Neurochir (Wien). 2012 Feb;154(2):203-9. doi: 10.1007/s00701-011-1184-1. Epub 2011 Oct 9.

Abstract

BACKGROUND

Stereotactic radiosurgery (SRS) can be a useful adjunct to the treatment of recurrent glioblastoma multiforme (GBM). Its combination with chemotherapy is attractive for the possible radiosensitization effect and cytotoxicity on tumor cells in distant areas. The aim of this study was to evaluate the efficacy and toxicity of CyberKnife SRS alone and combined with a "dose-dense" administration of temozolomide (TMZ) for recurrent GBM.

METHODS

Between July 2007 and July 2010, 23 patients underwent CyberKnife SRS. In 12 patients irradiation was combined with TMZ at 75 mg/m(2)/day for 21 days every 28 days. The median prescription dose in this group was 20 Gy (mean 20.7 ± 4 Gy) with a median number of fractions of 2. The median dose for the 11 patients who underwent SRS alone was 20 Gy (mean 19.9 ± 4.4 Gy; p = NS).

RESULTS

The median survival was 12 months for patients who underwent SRS/TMZ and 7 months for those who received SRS alone (p < 0.01). The 6-month progression-free survival (PFS) of the SRS/TMZ group was 66.7% vs. 18% for those who underwent SRS alone (p = 0.03). The median time to progression (TTP) was 7 months for patients who underwent SRS/TMZ and 4 months for those who underwent SRS alone (p = 0.01). Corticosteroid dependency was developed by most patients; radionecrosis was evident in one patient (4.3%) receiving TMZ. Grade 3 hematological toxicity was recorded in >40% of patients receiving chemotherapy.

CONCLUSIONS

The results suggest that Cyberknife re-treatments are relatively safe using selected dose/fraction schemes. The combination with TMZ improved patients' outcomes with OS and 6-month PFS that favorably compares with alternative treatments, but the incidence of major adverse effects was >40%. Further studies are warranted.

摘要

背景

立体定向放射外科(SRS)可以作为多形性胶质母细胞瘤(GBM)复发的有效辅助治疗手段。由于其可能具有放射增敏作用以及对远处肿瘤细胞的细胞毒性,因此与化疗联合应用很有吸引力。本研究旨在评估单独使用 CyberKnife SRS 以及与替莫唑胺(TMZ)“剂量密集”给药联合治疗复发性 GBM 的疗效和毒性。

方法

2007 年 7 月至 2010 年 7 月,23 例患者接受 CyberKnife SRS 治疗。在 12 例患者中,放疗联合 TMZ 治疗,TMZ 剂量为 75mg/m2/天,每 28 天给药 21 天。该组的中位处方剂量为 20Gy(平均 20.7±4Gy),中位数分割次数为 2 次。11 例仅接受 SRS 治疗的患者的中位剂量为 20Gy(平均 19.9±4.4Gy;p=NS)。

结果

接受 SRS/TMZ 治疗的患者中位生存时间为 12 个月,而仅接受 SRS 治疗的患者为 7 个月(p<0.01)。SRS/TMZ 组的 6 个月无进展生存期(PFS)为 66.7%,而仅接受 SRS 治疗的患者为 18%(p=0.03)。SRS/TMZ 组的中位进展时间(TTP)为 7 个月,而仅接受 SRS 治疗的患者为 4 个月(p=0.01)。大多数患者均出现皮质类固醇依赖,1 例(4.3%)接受 TMZ 治疗的患者出现放射性坏死。接受化疗的患者中,有>40%的患者出现 3 级血液学毒性。

结论

结果表明,采用选定的剂量/分割方案,使用 CyberKnife 进行再治疗相对安全。与其他治疗方法相比,联合 TMZ 可改善患者的生存结局和 6 个月 PFS,但主要不良事件发生率>40%。需要进一步研究。

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