Radiotherapy versus observation following surgical resection of WHO grade 2 atypical meningioma (ROAM/EORTC-1308): an international, multicentre, open-label, phase 3, randomised controlled trial.

The role of adjuvant radiotherapy remains uncertain.

辅助放疗的作用仍然不确定。

We aimed to assess whether adjuvant radiotherapy reduces recurrence compared with observation in patients with a newly diagnosed atypical meningioma who have undergone complete surgical resection.

我们旨在评估辅助放疗是否能减少复发，与观察组相比，针对那些已经接受完全手术切除的新诊断的非典型脑膜瘤患者。

Methods

ROAM/EORTC-1308 was an international, multicentre, open-label, phase 3, randomised controlled trial, conducted at 58 hospitals and academic centres in 11 countries.

ROAM/EORTC-1308是一项国际性、多中心、开放标签、第三阶段、随机对照试验，在11个国家的58家医院和学术中心进行。

Eligible sites had appropriate multidisciplinary expertise, neurosurgery, and radiotherapy facilities.

符合资格的地点具有适当的多学科专业知识、神经外科和放疗设施。

Patients aged 16 years or older who had undergone a surgeon-assessed complete surgical resection of newly diagnosed atypical meningioma were randomly assigned (1:1) to adjuvant radiotherapy or observation.

年龄在16岁或以上的患者，如果已经接受了外科医生评估的完全手术切除的新诊断的非典型脑膜瘤，将被随机分配（1:1）到辅助放疗组或观察组。

Randomisation was done using a web-based interface using random variable blocks of sizes two and four, stratified by location (UK or non-UK).

随机分配是通过使用一个基于网络的界面进行的，使用大小为二和四的随机变量块进行分层，按地理位置（英国或非英国）进行分层。

Participants assigned to the radiotherapy group received fractionated external-beam intensity-modulated radiotherapy at a total dose of 60 Gy in 30 fractions over 6 weeks.

被分配到放疗组的参与者接受了分次外部束强度调制放疗，总剂量为60 Gy，分30次，持续6周。

Participants were followed up for a minimum of 4 years.

参与者被跟踪随访至少4年。

The primary outcome was disease-free survival, defined as time from surgery to MRI-confirmed recurrence or death due to any cause, analysed in all randomly assigned participants in their assigned treatment group.

主要结果是无病生存率，定义为从手术到MRI确认的复发或因任何原因导致的死亡的时间，在所有随机分配的参与者中进行分析，这些参与者在他们被分配的治疗组中。

Harms analysis was done in the as-treated population.

在按治疗方案治疗的人群中进行了伤害分析。

The trial was registered with ISRCTN, ISRCTN71502099, and has completed.

该试验已在ISRCTN注册，注册号为ISRCTN71502099，并已完成。

Results

Between April 28, 2016, and May 21, 2021, 990 patients were assessed for eligibility, 157 of whom were randomly assigned to radiotherapy (n=78) or observation (n=79).

在2016年4月28日至2021年5月21日期间，共有990名患者被评估为符合入组条件，其中157名被随机分配接受放射治疗（n=78）或观察（n=79）。

Median age was 57·40 years (IQR 49·09-66·93); 84 (54%) participants were female and 73 (46%) were male.

中位年龄为57·40岁（四分位数间距49·09-66·93）；84（54%）参与者为女性，73（46%）为男性。

At a median follow-up of 64 months (IQR 50-75), meningioma recurrence occurred in 11 (14%) of 78 participants in the radiotherapy group and 24 (30%) of 79 in the observation group. 5-year disease-free survival was 79·9% (95% CI 67·6-87·9) in the radiotherapy group and 64·3% (51·9-74·2) in the observation group (absolute difference 15·6% percentage points [95% CI 0·6-30·5]).

在中位随访64个月（四分位数间距50-75）时，放射治疗组中有11（14%）名参与者出现脑膜瘤复发，观察组中有24（30%）名参与者出现脑膜瘤复发。放射治疗组的5年无病生存率为79·9%（95% CI 67·6-87·9），观察组的5年无病生存率为64·3%（51·9-74·2）（绝对差异15·6个百分点[95% CI 0·6-30·5]）。

Disease-free survival was improved in the radiotherapy group compared with the observation group (hazard ratio0·51 [95% CI 0·27-0·97]; p=0·0396).

与观察组相比，放射治疗组的无病生存率有所提高（风险比0·51 [95% CI 0·27-0·97]；p=0·0396）。

Grade 2 or 3 radiation-related serious adverse events occurred in five (8%) of 66 participants in the radiotherapy group, with no treatment-related deaths.

在放射治疗组的66名参与者中，有五名（8%）发生了2级或3级与放射相关的严重不良事件，没有治疗相关的死亡。

interpretation

Our findings suggest that adjuvant radiotherapy should be considered in patients with atypical meningioma after complete surgical resection of atypical meningioma when the prevention of recurrence is valued higher than the potential delayed adverse effects of radiotherapy.

我们的发现表明，在完全切除非典型脑膜瘤后，当预防复发的价值高于放射治疗可能带来的延迟不良反应时，应考虑对非典型脑膜瘤患者进行辅助放射治疗。

This practice will benefit patients by reducing meningioma recurrence.

这种做法将通过减少脑膜瘤的复发来造福患者。

Decisions should be based on individual discussion with the patient.

决策应基于与患者的个别讨论。

funding

National Institute for Health and Care Research Health Technology Assessment programme, the European Organisation for Research and Treatment of Cancer Brain Tumour Group and Radiation Oncology Group, and the Heath Research and Medical Research Council of Australia.

国家卫生和护理研究健康技术评估计划、欧洲癌症研究和治疗组织脑肿瘤组和放射肿瘤学组以及澳大利亚卫生研究和医学研究委员会。