Initial Results of a Phase 2 Trial of 18F-DOPA PET-Guided Dose-Escalated Radiation Therapy for Glioblastoma
Initial Results of a Phase 2 Trial of 18F-DOPA PET-Guided Dose-Escalated Radiation Therapy for Glioblastoma
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DOI：
10.1016/j.ijrobp.2021.03.032
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发表时间：
2021-07-14
影响因子：
7
通讯作者：
Brinkmann, Debra
中科院分区：
文献类型：
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作者：
Laack, Nadia Nicole;Pafundi, Deanna;Brinkmann, Debra
目的：我们以前的工作表明，3，4-二羟基-6-[18 F]-氟-L-苯丙氨酸（F-18-DOPA）正电子发射断层扫描（PET）对识别高密度和生物侵袭性胶质母细胞瘤区域是敏感和特异的。本前瞻性2期研究的目的是确定生物导向的，剂量递增的放射治疗（DERT）的安全性和有效性，使用F-18-DOPA PET在胶质母细胞瘤patients with glioblastoma.Methods和Materials：新诊断的，组织学证实的胶质母细胞瘤患者年龄>= 18岁，无F-18-DOPA禁忌症是合格的。靶体积包括51、60和76戈伊，分30次，同时进行整合加强，同时进行替莫唑胺辅助治疗6个月。18 F-DOPA PET成像用于引导DERT。该研究旨在检测O 6-甲基鸟嘌呤甲基转移酶（MGMT）未甲基化患者（DE-Un）的6个月（PFS 6）真实无进展生存率（PFS）≥ 72.5%，总体显著性水平（α）为0.20，把握度为80%。对PFS和总生存期（OS）进行Kaplan-Meier分析。历史对照（HC）包括139例患者（82例未甲基化）在前瞻性临床试验或标准RT在我们的机构。采用不良事件通用术语标准v4.0评价毒性。结果：2014年1月至2018年12月，75例可评价患者入组（39例DE-Un，24例甲基化[DE-Mth]，12例不确定）。DE-Un的PFS 6为79.5%（95%置信区间，63.1%-90.1%）。与历史对照组相比，DE-Un患者的中位PFS更长（8.7个月vs 6.6个月; P = 0.017）。OS同样更长，但差异不显着（16.0 vs 13.5个月; P = 0.13）。与HC-Mth患者相比，DE-Mth患者的OS显著改善（35.5 vs 23.3个月; P = 0.049），尽管PFS无显著改善（10.7 vs 9.0个月; P = 0.26）。13%的患者发生3级中枢神经系统坏死，但贝伐单抗治疗改善了所有cases.Conclusions的症状：F-18-DOPA PET引导的DERT似乎是安全的，它显着提高PFS MGMT非甲基化胶质母细胞瘤。MGMT甲基化患者的OS显著改善。18F-DOPA PET生物引导DERT治疗胶质母细胞瘤的进一步研究是必要的。(C)2021爱思唯尔公司All rights reserved.
Purpose: Our previous work demonstrated that 3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine (F-18-DOPA) positron emissiontomography (PET) is sensitive and specific for identifying regions of high density and biologically aggressive glioblastoma. The purpose of this prospective phase 2 study was to determine the safety and efficacy of biologic-guided, dose-escalated radiation therapy (DERT) using F-18-DOPA PET in patients with glioblastoma.Methods and Materials: Patients with newly diagnosed, histologically confirmed glioblastoma aged >= 18 years without contraindications to F-18-DOPA were eligible. Target volumes included 51, 60, and 76 Gy in 30 fractions with a simultaneous integrated boost, and concurrent and adjuvant temozolomide for 6 months. 18F-DOPA PET imaging was used to guide DERT. The study was designed to detect a true progression-free survival (PFS) at 6 months (PFS6) rate >= 72.5% in O6-methylguanine methyltransferase (MGMT) unmethylated patients (DE-Un), with an overall significance level (alpha) of 0.20 and a power of 80%. Kaplan-Meier analysis was performed for PFS and overall survival (OS). Historical controls (HCs) included 139 patients (82 unmethylated) treated on prospective clinical trials or with standard RT at our institution. Toxicities were evaluated with Common Terminology Criteria for Adverse Events v4.0.Results: Between January 2014 and December 2018, 75 evaluable patients were enrolled (39 DE-Un, 24 methylated [DE-Mth], and 12 indeterminate). PFS6 for DE-Un was 79.5% (95% confidence interval, 63.1%-90.1%). Median PFS was longer for DE-Un patients compared with historical controls (8.7 months vs 6.6 months; P =.017). OS was similarly longer, but the difference was not significant (16.0 vs 13.5 months; P =.13). OS was significantly improved for DE-Mth patients compared with HC-Mth (35.5 vs 23.3 months; P =.049) despite nonsignificant improvement in PFS (10.7 vs 9.0 months; P =.26). Grade 3 central nervous system necrosis occurred in 13% of patients, but treatment with bevacizumab improved symptoms in all cases.Conclusions: F-18-DOPA PET-guided DERT appears to be safe, and it significantly improves PFS in MGMT unmethylated glioblastoma. OS is significantly improved in MGMT methylated patients. Further investigation of 18F-DOPA PET biologic guided DERT for glioblastoma is warranted. (C) 2021 Elsevier Inc. All rights reserved.