Department of Radiosurgery and Neurooncology, Prof. Franciszek Lukaszczyk Memorial Oncology Center, Bydgoszcz, Poland.
Department of Oncology and Brachytherapy, Nicolaus Copernicus University, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland.
Clin Cancer Res. 2022 Jul 15;28(14):3011-3020. doi: 10.1158/1078-0432.CCR-22-0171.
Dual timepoint fluoro-ethyl-tyrosine (FET)-PET acquisition (10 and 60 minutes after FET injection) improves the definition of glioblastoma (GBM) location and shape. Here we evaluated the safety and efficacy of simultaneous integrated boost (SIB) planned using dual FET-PET for postoperative GBM treatment.
In this prospective pilot study (March 2017-December 2020), 17 patients qualified for FET-PET-based SIB intensity-modulated radiotherapy after resection. The prescribed dose was 78 and 60 Gy (2.6 and 2.0 Gy per fraction, respectively) for the FET-PET- and magnetic resonance (MR)-based target volumes. Eleven patients had FET-PET within 9 months to precisely define biological responses. Progression-free survival (PFS), overall survival (OS), toxicities, and radiation necrosis were evaluated. Six patients (35%) had tumors with MGMT promoter methylation.
The 1- and 2-year OS and PFS rates were 73% and 43% and 53% and 13%, respectively. The median OS and PFS were 24 [95% confidence interval (CI), 9-26] and 12 (95% CI, 6-18) months, respectively. Two patients developed uncontrolled seizures during radiotherapy and could not receive treatment per protocol. In patients treated per protocol, 7 of 15 presented with new or increased neurologic deficits in the first month after irradiation. Radiation necrosis was diagnosed by MRI 3 months after SIB in 5 patients and later in another 2 patients. In 2 patients, the tumor was larger in FET-PET images after 6 months.
Survival outcomes using our novel dose-escalation concept (total 78 Gy) were promising, even within the MGMT unmethylated subgroup. Excessive neurotoxicity was not observed, but radionecrosis was common and must be considered in future trials.
氟乙基酪氨酸（FET）的双时相 PET 采集（注射 FET 后 10 和 60 分钟）可提高胶质母细胞瘤（GBM）位置和形状的定义。在此，我们评估了使用双 FET-PET 进行术后 GBM 治疗的同步整合推量（SIB）计划的安全性和有效性。
在这项前瞻性的初步研究（2017 年 3 月至 2020 年 12 月）中，17 例患者在切除后符合 FET-PET 指导的 SIB 调强放疗标准。规定的剂量分别为 FET-PET 和磁共振（MR）靶区的 78 和 60 Gy（分别为 2.6 和 2.0 Gy/次）。11 例患者在 9 个月内进行 FET-PET 检查以准确确定生物学反应。评估无进展生存期（PFS）、总生存期（OS）、毒性和放射性坏死。6 例患者（35%）肿瘤有 MGMT 启动子甲基化。
1 年和 2 年 OS 和 PFS 率分别为 73%和 43%以及 53%和 13%。中位 OS 和 PFS 分别为 24 个月（95%可信区间[CI]，9-26）和 12 个月（95% CI，6-18）。2 例患者在放疗期间出现无法控制的癫痫发作，无法按方案进行治疗。按方案治疗的 15 例患者中，有 7 例在照射后 1 个月出现新的或加重的神经功能缺损。5 例患者在 SIB 后 3 个月通过 MRI 诊断为放射性坏死，另外 2 例患者随后诊断为放射性坏死。在 2 例患者中，肿瘤在 FET-PET 图像上在 6 个月后增大。
即使在 MGMT 未甲基化亚组中，使用我们新的剂量递增概念（总剂量 78 Gy）的生存结果是有希望的。未观察到过度的神经毒性，但放射性坏死很常见，在未来的试验中必须考虑。
