Department of Oncology, McMaster University, ON, Canada.
Department of Surgery, McMaster University, ON, Canada.
Onco Targets Ther. 2014 Mar 24;7:485-90. doi: 10.2147/OTT.S60358. eCollection 2014.
Local recurrence represents a significant challenge in the management of patients with glioblastoma multiforme. Salvage treatment options are limited by lack of clinical efficacy. Recent studies have demonstrated a significant response rate and acceptable toxicity with the use of fractionated stereotactic radiosurgery in this patient population. Our primary objective was to determine the efficacy and toxicity of fractionated stereotactic radiosurgery combined with concurrent temozolomide chemotherapy as a salvage treatment for recurrent glioblastoma multiforme. We prospectively collected treatment and outcome data for patients having fractionated stereotactic radiosurgery for locally recurrent glioblastoma multiforme after radical radiotherapy. Eligible patients had a maximum recurrence diameter of 60 mm without causing significant mass effect. The gross tumor volume was defined as the enhancing lesion on an enhanced fine-slice T1 (spin-lattice) magnetic resonance imaging, and a circumferential setup margin of 1 mm was used to define the planning target volume. All patients were treated using robotic radiosurgery with three dose/fractionation schedules ranging from 25 to 35 Gy in five fractions, depending on the maximum tumor diameter. Concurrent temozolomide 75 mg/m(2) was prescribed to all patients. Tumor response was judged using the Macdonald criteria, and toxicity was assessed using the CTCAE (Common Terminology Criteria for Adverse Events). A total of 31 patients were enrolled in this study. The median overall survival was 9 months, and progression-free survival was 7 months. The 6-month progression-free survival was 60% with a 95% confidence interval of 43%-77%. The a priori stratification factor of small tumor diameter was shown to predict overall survival, while time to recurrence was not predictive of progression-free or overall survival. Three patients experienced grade 3 acute toxicity that responded to increased steroid dosing. One patient experienced a grade 4 acute toxicity that did not respond to increased steroids but did respond to anti-angiogenic therapy. Fractionated stereotactic radiosurgery with concurrent temozolomide has shown good short-term clinical and radiologic control with manageable acute toxicity. This regimen appears to provide superior efficacy to either temozolomide or fractionated radiosurgery alone. The results of this study support the continued evaluation of this regimen.
局部复发是多形性胶质母细胞瘤患者治疗的重大挑战。挽救性治疗方案因临床疗效有限而受到限制。最近的研究表明，在这种患者人群中，分次立体定向放射外科治疗具有显著的反应率和可接受的毒性。我们的主要目标是确定分次立体定向放射外科联合替莫唑胺化疗作为局部复发性多形性胶质母细胞瘤挽救性治疗的疗效和毒性。我们前瞻性地收集了接受分次立体定向放射外科治疗局部复发性多形性胶质母细胞瘤的患者的治疗和结果数据。接受治疗的患者在接受根治性放疗后，最大复发直径为 60mm，且未引起明显的肿块效应。大体肿瘤体积定义为增强精细切片 T1（自旋晶格）磁共振成像上的增强病变，使用 1mm 的环形设置边界来定义计划靶区。所有患者均采用机器人放射外科治疗，根据最大肿瘤直径，采用 25-35Gy 的 3 个剂量/分次方案，分为 5 次。所有患者均接受替莫唑胺 75mg/m2 同期治疗。根据 Macdonald 标准判断肿瘤反应，根据 CTCAE（不良事件通用术语标准）评估毒性。本研究共纳入 31 例患者。中位总生存期为 9 个月，无进展生存期为 7 个月。6 个月无进展生存率为 60%，95%置信区间为 43%-77%。小肿瘤直径的预先分层因素表明可预测总生存期，而复发时间与无进展生存期或总生存期无关。3 例患者出现 3 级急性毒性，增加类固醇剂量后得到缓解。1 例患者出现 4 级急性毒性，增加类固醇剂量后无反应，但对抗血管生成治疗有反应。替莫唑胺同期分次立体定向放射外科治疗具有良好的短期临床和影像学控制效果，急性毒性可管理。与单独使用替莫唑胺或分次放射外科相比，该方案似乎具有更好的疗效。该研究结果支持继续评估该方案。
