O-(2-[18F]fluoroethyl)-L-tyrosine-PET-guided versus contrast-enhanced T1-weighted MRI-guided re-irradiation in patients with recurrent glioblastoma (GLIAA/NOA-10 ARO2013-01): a multicentre, open-label, randomised trial.

We aimed to evaluate whether a FET-PET-based target volume delineation, compared with CE-T1MRI, improves outcomes in patients with recurrent glioblastoma scheduled for re-irradiation.

我们旨在评估与 CE-T1MRI 相比，基于 FET-PET 的靶区体积描绘是否能改善计划接受再放疗的复发性胶质母细胞瘤患者的治疗结果。

Methods

GLIAA was a multicentre, open-label, parallel randomised study done in 15 radiation oncology centres in Germany.

GLIAA 是一项在德国15个放射肿瘤学中心进行的多中心、开放标签、平行随机研究。

Patients aged 18 years or older with a Karnofsky performance score greater than 60% and a macroscopic WHO grade IV recurrent glioblastoma (1-6 cm) were randomly assigned (1:1) to receive either FET-PET-based or CE-T1MRI-based target volume delineation followed by re-irradiation with 39 Gy in 13 fractions.

年龄在18岁或以上的患者，卡氏功能状态评分大于60%，并有宏观世界卫生组织（WHO）四级复发性胶质母细胞瘤（1-6厘米），被随机分配（1:1）接受基于FET-PET或基于CE-T1MRI的目标体积描绘，随后接受39 Gy分13次的再放疗。

Randomisation was performed centrally, using a minimisation technique with a random element and a computer-assisted randomisation tool, stratified by time since first radiotherapy, previous chemotherapy, tumour diameter, MGMT status, and planned chemotherapy.

随机化是通过中心进行的，使用了带有随机元素的最小化技术以及计算机辅助的随机化工具，根据首次放疗后的时间、之前的化疗、肿瘤直径、MGMT状态和计划中的化疗进行分层。

The primary endpoint was progression-free survivalfrom randomisation, assessed in the per-protocol population (patients who initiated treatment per their assigned group).

主要终点是从随机化开始的无进展生存期，在按方案人群（即按照分配组开始治疗的患者）中进行评估。

Adverse events were systematically assessed in all patients who commenced therapy.

所有开始治疗的患者均系统评估了不良事件。

The trial was registered with ClinicalTrials.gov (NCT01252459), German Clinical Trials Registry (DRKS00000634), and European Clinical Trials Database (EudraCT 2012-001121-27), and is completed.

该试验已在ClinicalTrials.gov (NCT01252459)、德国临床试验注册处(DRKS00000634)和欧洲临床试验数据库(EudraCT 2012-001121-27)注册，并已完成。

Results

Between Nov 22, 2013, and Aug 18, 2021, 271 patients were recruited and screened for eligibility, 200 of whom were randomly assigned to re-irradiation based on FET-PET (n=100) or CE-T1MRI (n=100). 85 (43%) participants were female and 115 (58%) were male. 98 patients in the FET-PET group and 97 in the CE-T1MRI group were treated per protocol.

在2013年11月22日至2021年8月18日期间，共有271名患者被招募并进行了资格筛选，其中200名患者被随机分配接受基于FET-PET（n=100）或CE-T1MRI（n=100）的再放疗。85名（43%）参与者为女性，115名（58%）为男性。FET-PET组有98名患者和CE-T1MRI组有97名患者按照方案接受了治疗。

Median follow-up for censored patients was 12·2 months (IQR 6·6-20·7).

被删失患者的中位随访时间为12.2个月（四分位数间距6.6-20.7）。

Median progression-free survivalwas 4·0 months (95% CI 3·7-5·2) in the FET-PET group and 4·9 months (3·7-6·0) in the CE-T1MRI group (one-sided stratified log-rank p=0·98; adjusted hazard ratio1·14 [95% CI 0·85-1·52]; p=0·39; median follow-up for six censored patients 4·1 months [IQR 2·3-6·6]).

在 FET-PET 组中，中位无进展生存期为 4.0 个月（95% 置信区间 3.7-5.2），而在 CE-T1MRI 组中为 4.9 个月（3.7-6.0）（单侧分层对数秩检验 p=0.98；调整后风险比 1.14 [95% 置信区间 0.85-1.52]；p=0.39；六名被删失患者的中位随访时间为 4.1 个月 [四分位数间距 2.3-6.6]）。

The most common grade 3-4 adverse eventwas radionecrosis (eight [8%] of 99 in the FET-PET group vs seven [7%] of 99 in the CE-T1MRI group).

最常见的 3-4 级不良事件是放射性坏死（FET-PET 组中有 99 名患者中的八名 [8%]，CE-T1MRI 组中有 99 名患者中的七名 [7%]）。

Acute and subacute serious adverse events occurred in 15 (15%) of 99 patients in each group; possibly re-irradiation-related late serious adverse events occurred in ten (10%) of 97 patients in the FET-PET group and 18 (19%) of 96 in the CE-T1MRI group.

在每组99名患者中，有15名（15%）患者发生了急性或亚急性严重不良事件；在FET-PET组的97名患者中，可能与再次放疗相关的晚期严重不良事件发生在10名（10%）患者中，在CE-T1MRI组的96名患者中，这一数字为18名（19%）

There were no treatment-related deaths.

没有治疗相关的死亡事件。

interpretation

FET-PET-based target volume delineation for re-irradiation did not lead to a significant clinical benefit compared with CE-T1MRI-based treatment in patients with recurrent glioblastoma.

基于FET-PET的靶区体积划分在复发性胶质母细胞瘤患者的再放疗中，并没有带来与基于CE-T1MRI治疗相比显著的临床益处。

Thus, CE-T1MRI remains the preferred delineation method in this setting.

因此，在这种情况下，CE-T1MRI仍然是首选的划分方法。

funding

Deutsche Krebshilfe.

德国抗癌协会。