Abstract

Background

Pulsed radiation therapy (PRT) has shown effective tumor control and superior normal-tissue sparing ability compared with standard radiotherapy (SRT) in preclinical models and retrospective clinical series. This is the first prospective trial to investigate PRT in the treatment of patients with newly diagnosed glioblastoma (GBM).

Methods

This is a single-arm, prospective study. Patients with newly diagnosed GBM underwent surgery, followed by 60 Gy of PRT with concurrent temozolomide (TMZ). Each day, a 2-Gy fraction was divided into ten 0.2-Gy pulses, separated by 3-minute intervals. Patients received maintenance TMZ. Neurocognitive function (NCF) and quality of life (QoL) were monitored for 2 years using the Hopkins Verbal Learning Test‒Revised and the European Organisation for Research and Treatment of Cancer QLQ-C30 QoL questionnaire. Change in NCF was evaluated based on a minimal clinically important difference (MCID) threshold of 0.5 standard deviation.

Results

Twenty patients were enrolled with a median follow-up of 21 months. Median age was 60 years. Forty percent underwent subtotal resection, and 60% underwent gross total resection. One patient had an isocitrate dehydrogenase (IDH)–mutated tumor. Median progression-free survival (PFS) and overall survival (OS) were 10.7 and 20.9 months, respectively. In a post-hoc comparison, median OS for the prospective cohort was longer, compared with a matched cohort receiving SRT (20.9 vs 14 mo, P = 0.042). There was no decline in QoL, and changes in NCF scores did not meet the threshold of an MCID.

Conclusions

Treatment of newly diagnosed GBM with PRT is feasible and produces promising effectiveness while maintaining neurocognitive function and QoL. Validation of our results in a larger prospective trial warrants consideration.

中文翻译：

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脉冲放射疗法治疗新诊断的胶质母细胞瘤

摘要

背景

在临床前模型和回顾性临床系列研究中，与标准放射疗法（SRT）相比，脉冲放射疗法（PRT）已显示出有效的肿瘤控制和优异的正常组织保留能力。这是研究PRT治疗新诊断的胶质母细胞瘤（GBM）患者的首项前瞻性试验。

方法

这是一项单臂的前瞻性研究。新诊断为GBM的患者接受了手术，随后进行了60 Gy的PRT并发替莫唑胺（TMZ）治疗。每天，将2-Gy馏分分成十个0.2-Gy脉冲，每3分钟间隔一次。患者接受了TMZ维护。使用Hopkins语言学习测试修订版和欧洲癌症研究和治疗组织QLQ-C30 QoL问卷对神经认知功能（NCF）和生活质量（QoL）进行了2年的监测。根据0.5的标准差的最小临床重要差异（MCID）阈值评估NCF的变化。

结果

20名患者入组，中位随访时间为21个月。中位年龄为60岁。40％的患者进行了大部切除，60％的患者进行了总切除。一名患者患有异柠檬酸脱氢酶（IDH）突变的肿瘤。中位无进展生存期（PFS）和总体生存期（OS）分别为10.7和20.9个月。在事后比较中，与接受SRT的匹配队列相比，预期队列的中位OS更长（20.9 vs 14 mo，P = 0.042）。QoL没有下降，并且NCF分数的变化不符合MCID的阈值。

结论

用PRT治疗新诊断的GBM是可行的，并在维持神经认知功能和QoL的同时产生有希望的疗效。在更大范围的前瞻性试验中验证我们的结果值得考虑。