Henriksson Roger, Capala Jacek, Michanek Annika, Lindahl Sten-Ake, Salford Leif G, Franzén Lars, Blomquist Erik, Westlin Jan-Erik, Bergenheim A Tommy
Department of Radiation Sciences & Oncology, Umeå University, Umeå, Sweden.
Radiother Oncol. 2008 Aug;88(2):183-91. doi: 10.1016/j.radonc.2006.04.015. Epub 2008 Mar 11.
To evaluate the efficacy and safety of boron neutron capture therapy (BNCT) for glioblastoma multiforme (GBM) using a novel protocol for the boronophenylalanine-fructose (BPA-F) infusion.
This phase II study included 30 patients, 26-69 years old, with a good performance status of which 27 have undergone debulking surgery. BPA-F (900 mg BPA/kg body weight) was given i.v. over 6h. Neutron irradiation started 2h after the completion of the infusion. Follow-up reports were monitored by an independent clinical research institute.
The boron-blood concentration during irradiation was 15.2-33.7 microg/g. The average weighted absorbed dose to normal brain was 3.2-6.1 Gy (W). The minimum dose to the tumour volume ranged from 15.4 to 54.3 Gy (W). Seven patients suffered from seizures, 8 from skin/mucous problem, 5 patients were stricken by thromboembolism and 4 from abdominal disturbances in close relation to BNCT. Four patients displayed 9 episodes of grade 3-4 events (WHO). At the time for follow-up, minimum ten months, 23 out of the 29 evaluable patients were dead. The median time from BNCT treatment to tumour progression was 5.8 months and the median survival time after BNCT was 14.2 months. Following progression, 13 patients were given temozolomide, two patients were re-irradiated, and two were re-operated. Patients treated with temozolomide lived considerably longer (17.7 vs. 11.6 months). The quality of life analysis demonstrated a progressive deterioration after BNCT.
Although, the efficacy of BNCT in the present protocol seems to be comparable with conventional radiotherapy and the treatment time is shorter, the observed side effects and the requirement of complex infrastructure and higher resources emphasize the need of further phase I and II studies, especially directed to improve the accumulation of (10)B in tumour cells.
采用一种新的硼苯丙氨酸 - 果糖（BPA - F）输注方案，评估硼中子俘获疗法（BNCT）治疗多形性胶质母细胞瘤（GBM）的疗效与安全性。
本II期研究纳入30例年龄在26 - 69岁、身体状况良好的患者，其中27例接受了肿瘤减积手术。静脉输注BPA - F（900 mg BPA/千克体重），持续6小时。输注结束2小时后开始中子照射。随访报告由一家独立的临床研究机构监测。
照射期间硼血浓度为15.2 - 33.7微克/克。正常脑组织的平均加权吸收剂量为3.2 - 6.1 Gy（W）。肿瘤体积的最小剂量范围为15.4至54.3 Gy（W）。7例患者出现癫痫发作，8例出现皮肤/黏膜问题，5例发生血栓栓塞，4例出现与BNCT密切相关的腹部不适。4例患者出现9次3 - 4级事件（世界卫生组织分级）。在随访时，最短随访时间为10个月，29例可评估患者中有23例死亡。从BNCT治疗到肿瘤进展的中位时间为5.8个月，BNCT后的中位生存时间为14.2个月。病情进展后，13例患者接受了替莫唑胺治疗，2例患者接受了再次照射，2例患者接受了再次手术。接受替莫唑胺治疗的患者存活时间明显更长（17.7个月对11.6个月）。生活质量分析显示BNCT后生活质量逐渐恶化。
尽管本方案中BNCT的疗效似乎与传统放疗相当且治疗时间较短，但观察到的副作用以及对复杂基础设施和更多资源的需求强调了进一步开展I期和II期研究的必要性，特别是旨在提高硼 - 10在肿瘤细胞中的蓄积。
