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新诊断胶质母细胞瘤的低分割大剂量强度调制放疗同期和辅助替莫唑胺治疗的 2 期临床试验。

Phase 2 trial of hypofractionated high-dose intensity modulated radiation therapy with concurrent and adjuvant temozolomide for newly diagnosed glioblastoma.

机构信息

Division of Neurological Surgery, Chiba Cancer Center, Chiba, Japan.

Division of Radiation Oncology, Chiba Cancer Center, Chiba, Japan.

出版信息

Int J Radiat Oncol Biol Phys. 2014 Mar 15;88(4):793-800. doi: 10.1016/j.ijrobp.2013.12.011. Epub 2014 Feb 1.

Abstract

PURPOSE/OBJECTIVES: To assess the effect and toxicity of hypofractionated high-dose intensity modulated radiation therapy (IMRT) with concurrent and adjuvant temozolomide (TMZ) in 46 patients with newly diagnosed glioblastoma multiforme (GBM).

METHODS AND MATERIALS

All patients underwent postsurgical hypofractionated high-dose IMRT. Three layered planning target volumes (PTVs) were contoured. PTV1 was the surgical cavity and residual tumor on T1-weighted magnetic resonance images with 5-mm margins, PTV2 was the area with 15-mm margins surrounding the PTV1, and PTV3 was the high-intensity area on fluid-attenuated inversion recovery images. Irradiation was performed in 8 fractions at total doses of 68, 40, and 32 Gy for PTV1, PTV2, and PTV3, respectively. Concurrent TMZ was given at 75 mg/m(2)/day for 42 consecutive days. Adjuvant TMZ was given at 150 to 200 mg/m(2)/day for 5 days every 28 days. Overall and progression-free survivals were evaluated.

RESULTS

No acute IMRT-related toxicity was observed. The dominant posttreatment failure pattern was dissemination. During a median follow-up time of 16.3 months (range, 4.3-80.8 months) for all patients and 23.7 months (range, 12.4-80.8 months) for living patients, the median overall survival was 20.0 months after treatment. Radiation necrosis was diagnosed in 20 patients and was observed not only in the high-dose field but also in the subventricular zone (SVZ). Necrosis in the SVZ was significantly correlated with prolonged survival (hazard ratio, 4.08; P=.007) but caused deterioration in the performance status of long-term survivors.

CONCLUSIONS

Hypofractionated high-dose IMRT with concurrent and adjuvant TMZ altered the dominant failure pattern from localized to disseminated and prolonged the survival of patients with GBM. Necrosis in the SVZ was associated with better patient survival, but the benefit of radiation to this area remains controversial.

摘要

目的

评估 46 例新诊断的多形性胶质母细胞瘤(GBM)患者接受术后短疗程大剂量强度调制放疗(IMRT)联合辅助替莫唑胺(TMZ)的疗效和毒性。

方法和材料

所有患者均接受术后短疗程大剂量 IMRT。勾画了三个分层的计划靶区(PTV)。PTV1 为 T1 加权磁共振成像上的手术腔和残留肿瘤,加 5mm 边界;PTV2 为 PTV1 周围 15mm 边界区;PTV3 为液体衰减反转恢复图像上的高信号区。PTV1、PTV2 和 PTV3 的照射剂量分别为 68、40 和 32Gy,共 8 个分次。TMZ 同步给予 75mg/m2/天,共 42 天。辅助 TMZ 于每 28 天的 5 天内给予 150-200mg/m2/天。评估总生存期和无进展生存期。

结果

未观察到急性 IMRT 相关毒性。治疗后主要的失败模式是播散。所有患者的中位随访时间为 16.3 个月(范围,4.3-80.8 个月),存活患者的中位随访时间为 23.7 个月(范围,12.4-80.8 个月),治疗后中位总生存期为 20.0 个月。20 例患者诊断为放射性坏死,不仅在高剂量区,而且在侧脑室下区(SVZ)也观察到坏死。SVZ 中的坏死与延长生存时间显著相关(风险比,4.08;P=.007),但导致长期存活者的生存状态恶化。

结论

短疗程大剂量 IMRT 联合辅助 TMZ 改变了 GBM 患者的局部失败模式,延长了患者的生存时间。SVZ 中的坏死与患者更好的生存相关,但对该区域的放疗获益仍存在争议。

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