Preoperative radiotherapy plus surgery versus surgery alone for patients with primary retroperitoneal sarcoma (EORTC-62092: STRASS): a multicentre, open-label, randomised, phase 3 trial
Preoperative radiotherapy plus surgery versus surgery alone for patients with primary retroperitoneal sarcoma (EORTC-62092: STRASS): a multicentre, open-label, randomised, phase 3 trial
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DOI：
10.1016/s1470-2045(20)30446-0
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发表时间：
2020-10-01
期刊：
影响因子：
51.1
通讯作者：
Haas, Rick L.
中科院分区：
文献类型：
--
作者：
Bonvolot, Sylvie;Gronchi, Alessandro;Haas, Rick L.
背景与四肢肉瘤不同，放射治疗腹膜后肉瘤的疗效尚未确定。本研究的目的是评估术前放疗加手术与单纯手术对腹部无复发survival.Methods EORTC-62092的影响是一个开放标签，随机，3期研究在31个研究机构，医院和癌症中心在13个国家在欧洲和北美。采用交互式网络应答系统和最小化算法，将患有组织学证实的局部原发性腹膜后肉瘤、可手术且适合放疗、既往未接受过治疗且WHO体能状态和美国麻醉医师学会评分为2分或更低的成人（年龄≥ 18岁）集中随机分配（1：1），接受单纯手术或术前放疗后手术。按医院和体能状态对随机化进行分层。放射治疗为50.4戈伊（每日28次，每次1.8戈伊），采用3D适形放射治疗或调强放射治疗，手术的目的是肉眼完全切除肿瘤块，必要时进行整块器官切除。主要终点是腹部无复发生存期，由研究者评估，并在意向治疗人群中进行分析。在开始分配治疗的所有患者中分析安全性。该试验注册于ClinicalTrials.gov，NCT 01344018。结果2012年1月18日至2017年4月10日，266例患者入组，其中133例随机分配至每组。中位随访时间为43.1个月（IQR 28.8-59.2）。单纯手术组128例（96%）患者接受了手术，放疗和手术组119例（89%）患者接受了放疗和手术。放疗加手术组中位腹部无复发生存期为4.5年（95%CI 3.9至无法估计），仅手术组为5.0年（3.4至无法估计）（风险比1.01，95%CI 0.71-1.44;对数秩p=0.95）。最常见的3-4级不良事件是淋巴细胞减少症（放疗加手术组127例患者中有98例[77%] vs单纯手术组128例患者中有1例[1%]）、贫血（15例[12%] vs 10例[8%]）和低白蛋白血症（15例[12%] vs 5例[4%]）。放疗加手术组127例患者中有30例（24%）报告了严重不良事件，单纯手术组128例患者中有13例（10%）报告了严重不良事件。放疗加手术组127例患者中有1例（1%）死于治疗相关的严重不良事件（胃胸膜瘘），单纯手术组无患者死于治疗相关的严重不良事件。版权所有（C）2020爱思唯尔有限公司保留所有权利。
Background Unlike for extremity sarcomas, the efficacy of radiotherapy for retroperitoneal sarcoma is not established. The aim of this study was to evaluate the impact of preoperative radiotherapy plus surgery versus surgery alone on abdominal recurrence-free survival.Methods EORTC-62092 is an open-label, randomised, phase 3 study done in 31 research institutions, hospitals, and cancer centres in 13 countries in Europe and North America. Adults (aged >= 18 years) with histologically documented, localised, primary retroperitoneal sarcoma that was operable and suitable for radiotherapy, who had not been previously treated and had a WHO performance status and American Society of Anesthesiologists score of 2 or lower, were centrally randomly assigned (1:1), using an interactive web response system and a minimisation algorithm, to receive either surgery alone or preoperative radiotherapy followed by surgery. Randomisation was stratified by hospital and performance status. Radiotherapy was delivered as 50.4 Gy (in 28 daily fractions of 1.8 Gy) in either 3D conformal radiotherapy or intensity modulated radiotherapy, and the objective of surgery was a macroscopically complete resection of the tumour mass with en-bloc organ resection as necessary. The primary endpoint was abdominal recurrence-free survival, as assessed by the investigator, and was analysed in the intention-to-treat population. Safety was analysed in all patients who started their allocated treatment. This trial is registered with ClinicalTrials.gov, NCT01344018.Findings Between Jan 18, 2012 and April 10, 2017, 266 patients were enrolled, of whom 133 were randomly assigned to each group. The median follow-up was 43.1 months (IQR 28.8-59.2). 128 (96%) patients from the surgery alone group had surgery, and 119 (89%) patients in the radiotherapy and surgery group had both radiotherapy and surgery. Median abdominal recurrence-free survival was 4.5 years (95% CI 3.9 to not estimable) in the radiotherapy plus surgery group and 5.0 years (3.4 to not estimable) in the surgery only group (hazard ratio 1.01, 95% CI 0.71-1.44; log rank p=0.95). The most common grade 3-4 adverse events were lymphopenia (98 [77%] of 127 patients in the radiotherapy plus surgery group vs one [1%] of 128 patients in the surgery alone group), anaemia (15 [12%] vs ten [8%]), and hypoalbuminaemia (15 [12%] vs five [4%]). Serious adverse events were reported in 30 (24%) of 127 patients in the radiotherapy plus surgery group, and in 13 (10%) of 128 patients in the surgery alone group. One (1%) of 127 patients in the radiotherapy plus surgery group died due to treatment-related serious adverse events (gastropleural fistula), and no patients in the surgery alone group died due to treatment-related serious adverse events.Interpretation Preoperative radiotherapy should not be considered as standard of care treatment for retroperitoneal sarcoma. Copyright (C) 2020 Elsevier Ltd. All rights reserved.