Background

Patients with advanced oesophageal cancer have a median survival of 3–6 months, and most require intervention for dysphagia. Self-expanding metal stent (SEMS) insertion is the most typical form of palliation in these patients, but dysphagia deterioration and re-intervention are common. This study examined the efficacy of adjuvant external beam radiotherapy (EBRT) compared with usual care alone in preventing dysphagia deterioration and reducing service use after SEMS insertion.

Methods

This was a multicentre, open-label, phase 3 randomised controlled trial based at cancer centres and acute care hospitals in England, Scotland, and Wales. Patients (aged ≥16 years) with incurable oesophageal carcinoma receiving stent insertion for primary management of dysphagia were randomly assigned (1:1) to receive usual care alone or EBRT (20 Gy in five fractions or 30 Gy in ten fractions) plus usual care after stent insertion. Usual care was implemented according to need as identified by the local multidisciplinary team (MDT). Randomisation was via the method of minimisation stratified by treating centre, stage at diagnosis (I–III vs IV), histology (squamous or non-squamous), and MDT intent to give chemotherapy (yes vs no). The primary outcome was difference in proportions of participants with dysphagia deterioration (>11 point decrease on patient-reported European Organisation for Research and Treatment of Cancer quality of life questionnaire-oesophagogastric module [QLQ-OG25], or a dysphagia-related event consistent with such a deterioration) or death by 12 weeks in a modified intention-to-treat (ITT) population, which excluded patients who did not have a stent inserted and those without a baseline QLQ-OG25 assessment. Secondary outcomes included survival, quality of life (QoL), morbidities (including time to first bleeding event or hospital admission for bleeding event and first dysphagia-related stent complications or re-intervention), and cost-effectiveness. Safety analysis was undertaken in the modified ITT population. The study is registered with the International Standard Randomised Controlled Trial registry, ISRCTN12376468, and ClinicalTrials.gov, NCT01915693, and is completed.

Findings

220 patients were randomly assigned between Dec 16, 2013, and Aug 24, 2018, from 23 UK centres. The modified ITT population (n=199) comprised 102 patients in the usual care group and 97 patients in the EBRT group. Radiotherapy did not reduce dysphagia deterioration, which was reported in 36 (49%) of 74 patients receiving usual care versus 34 (45%) of 75 receiving EBRT (adjusted odds ratio 0·82 [95% CI 0·40–1·68], p=0·59) in those with complete data for the primary endpoint. No significant difference was observed in overall survival: median overall survival was 19·7 weeks (95% CI 14·4–27·7) with usual care and 18·9 weeks (14·7–25·6) with EBRT (adjusted hazard ratio 1·06 [95% CI 0·78–1·45], p=0·70; n=199). Median time to first bleeding event or hospital admission for a bleeding event was 49·0 weeks (95% CI 33·3–not reached) with usual care versus 65·9 weeks (52·7–not reached) with EBRT (adjusted subhazard ratio 0·52 [95% CI 0·28–0·97], p=0·038; n=199). No time versus treatment interaction was observed for prespecified QoL outcomes. We found no evidence of differences between trial group in time to first stent complication or re-intervention event. The most common (grade 3–4) adverse event was fatigue, reported in 19 (19%) of 102 patients receiving usual care alone and 22 (23%) of 97 receiving EBRT. On cost-utility analysis, EBRT was more expensive and less efficacious than usual care.

Interpretation

Patients with advanced oesophageal cancer having SEMS insertion for the primary management of their dysphagia did not gain additional benefit from concurrent palliative radiotherapy and it should not be routinely offered. For a minority of patients clinically considered to be at high risk of tumour bleeding, concurrent palliative radiotherapy might reduce bleeding risk and the need for associated interventions.

Funding

National Institute for Health Research Health Technology Assessment Programme.

中文翻译：

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食管癌支架置入术后姑息性放疗 (ROCS)：一项多中心、开放标签、3 期随机对照试验

 背景

晚期食管癌患者的中位生存期为 3-6 个月，大多数患者需要针对吞咽困难进行干预。自膨式金属支架（SEMS）置入是这些患者最典型的姑息治疗形式，但吞咽困难恶化和重新干预也很常见。本研究检验了辅助外照射放疗 (EBRT) 与单独常规护理相比在预防吞咽困难恶化和减少 SEMS 插入后服务使用方面的功效。

 方法

这是一项在英格兰、苏格兰和威尔士的癌症中心和急症护理医院进行的多中心、开放标签、3 期随机对照试验。接受支架置入治疗吞咽困难初级治疗的无法治愈的食管癌患者（年龄≥16岁）被随机分配（1:1）接受单独常规治疗或 EBRT（5 次 20 Gy 或 10 次 30 Gy）加常规治疗支架置入后。根据当地多学科团队 (MDT) 确定的需要实施常规护理。随机化采用最小化分层方法，根据治疗中心、诊断分期（I-III与IV）、组织学（鳞状或非鳞状）以及 MDT 是否打算进行化疗（是与否）。主要结果是吞咽困难恶化的参与者比例存在差异（患者报告的欧洲癌症研究和治疗组织生活质量问卷-食管胃模块 [QLQ-OG25] 下降>11分，或与吞咽困难相关事件一致）在改良意向治疗 (ITT) 人群中，该人群排除了未插入支架的患者和未进行基线 QLQ-OG25 评估的患者，但在 12 周内出现了这种恶化）或死亡。次要结局包括生存率、生活质量（QoL）、发病率（包括首次出血事件或因出血事件入院的时间以及首次吞咽困难相关支架并发症或再次干预）和成本效益。在改良的 ITT 人群中进行了安全性分析。该研究已在国际标准随机对照试验登记处（ISRCTN12376468）和 ClinicalTrials.gov（NCT01915693）注册并已完成。

 发现

2013年12月16日至2018年8月24日期间，来自23个英国中心的220名患者被随机分配。修改后的 ITT 人群 (n=199) 包括常规护理组的 102 名患者和 EBRT 组的 97 名患者。放疗并没有减少吞咽困难恶化，据报道，接受常规护理的 74 名患者中有 36 名 (49%) 出现这种情况，而接受 EBRT 的 75 名患者中有 34 名 (45%) 出现这种情况（调整后的比值比 0·82 [95% CI 0·40–1·68] ]，p=0·59) 具有主要终点完整数据的患者。总生存期未观察到显着差异：常规护理下的中位总生存期为 19·7 周 (95% CI 14·4–27·7)，而 EBRT 组的中位总生存期为 18·9 周 (14·7–25·6)（调整后的危险比 1·06 [95% CI 0·78–1·45]，p=0·70；n=199）。常规护理下首次出血事件或因出血事件入院的中位时间为 49·0 周（95% CI 33·3 – 未达到），而 EBRT（调整后的子危险）为 65·9 周（52·7 – 未达到）比率 0·52 [95% CI 0·28–0·97]，p=0·038；n=199）。对于预先指定的生活质量结果，没有观察到时间与治疗的相互作用。我们没有发现试验组之间在首次支架并发症或再次干预事件发生时间上存在差异的证据。最常见（3-4 级）的不良事件是疲劳，在 102 名仅接受常规护理的患者中，有 19 名（19%）报告了疲劳，在 97 名接受 EBRT 的患者中，有 22 名（23%）报告了疲劳。根据成本效用分析，EBRT 比常规治疗更昂贵，但效果较差。

 解释

接受 SEMS 插入治疗吞咽困难的晚期食管癌患者并没有从同步姑息性放疗中获得额外益处，因此不应常规进行。对于临床上被认为具有高肿瘤出血风险的少数患者，同步姑息性放疗可能会降低出血风险和相关干预措施的需要。

 资金

国家卫生研究院卫生技术评估计划。