Department of Oncology, Western University, London Health Sciences Centre, London, Ontario, Canada.
Department of Radiation Oncology, University of Toronto, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
JAMA Oncol. 2022 Apr 1;8(4):1-7. doi: 10.1001/jamaoncol.2021.7664.
Palliative thoracic radiotherapy (RT) can alleviate local symptoms associated with advanced non-small cell lung cancer (NSCLC), but esophagitis is a common treatment-related adverse event. Whether esophageal-sparing intensity-modulated RT (ES-IMRT) achieves a clinically relevant reduction in esophageal symptoms remains unclear.
To examine whether ES-IMRT achieves a clinically relevant reduction in esophageal symptoms compared with standard RT.
DESIGN, SETTING, AND PARTICIPANTS: Palliative Radiation for Advanced Central Lung Tumors With Intentional Avoidance of the Esophagus (PROACTIVE) is a multicenter phase 3 randomized clinical trial that enrolled patients between June 24, 2016, and March 6, 2019. Data analysis was conducted from January 23, 2020, to October 22, 2021. Patients had up to 1 year of follow-up. Ninety patients at 6 tertiary academic cancer centers who had stage III/IV NSCLC and were eligible for palliative thoracic RT (20 Gy in 5 fractions or 30 Gy in 10 fractions) were included.
Patients were randomized (1:1) to standard RT (control arm) or ES-IMRT. Target coverage was compromised to ensure the maximum esophagus dose was no more than 80% of the RT prescription dose.
The primary outcome was esophageal quality of life (QOL) 2 weeks post-RT, measured by the esophageal cancer subscale (ECS) of the Functional Assessment of Cancer Therapy: Esophagus questionnaire. Higher esophageal cancer subscale scores correspond with improved QOL, with a 2- to 3-point change considered clinically meaningful. Secondary outcomes included overall survival, toxic events, and other QOL metrics. Intention-to-treat analysis was used.
Between June 24, 2016, and March 6, 2019, 90 patients were randomized to standard RT or ES-IMRT (median age at randomization, 72.0 years [IQR, 65.6-80.3]; 50 [56%] were female). Thirty-six patients (40%) received 20 Gy and 54 (60%) received 30 Gy. For the primary end point, the mean (SD) 2-week ECS score was 50.5 (10.2) in the control arm (95% CI, 47.2-53.8) and 54.3 (7.6) in the ES-IMRT arm (95% CI, 51.9-56.7) (P = .06). Symptomatic RT-associated esophagitis occurred in 24% (n = 11) of patients in the control arm vs 2% (n = 1) in the ES-IMRT arm (P = .002). In a post hoc subgroup analysis based on the stratification factor, reduction in esophagitis was most evident in patients receiving 30 Gy (30% [n = 8] vs 0%; P = .004). Overall survival was similar with standard RT (median, 8.6; 95% CI, 5.7-15.6 months) and ES-IMRT (median, 8.7; 95% CI, 5.1-10.2 months) (P = .62).
In this phase 3 randomized clinical trial, ES-IMRT did not significantly improve esophageal QOL but significantly reduced the incidence of symptomatic esophagitis. Because post hoc analysis found that reduced esophagitis was most evident in patients receiving 30 Gy of RT, these findings suggest that ES-IMRT may be most beneficial when the prescription dose is higher (30 Gy).
ClinicalTrials.gov Identifier: NCT02752126.
姑息性胸部放射治疗（RT）可以缓解晚期非小细胞肺癌（NSCLC）相关的局部症状，但食管炎是一种常见的治疗相关不良反应。食管保护调强放射治疗（ES-IMRT）是否能在临床上显著减轻食管症状尚不清楚。
研究 ES-IMRT 是否能在临床上显著减轻食管症状，与标准 RT 相比。
设计、地点和参与者：旨在有意避免食管的晚期中央肺部肿瘤的姑息性放射治疗（PROACTIVE）是一项多中心的 3 期随机临床试验，纳入了 2016 年 6 月 24 日至 2019 年 3 月 6 日之间的患者。数据分析于 2020 年 1 月 23 日至 2021 年 10 月 22 日进行。患者随访时间长达 1 年。共有 6 家三级学术癌症中心的 90 名 III/IV 期 NSCLC 患者有资格接受姑息性胸部 RT（20 Gy 分 5 次或 30 Gy 分 10 次），他们被纳入研究。
患者随机（1:1）分为标准 RT（对照组）或 ES-IMRT。为了确保最大食管剂量不超过 RT 处方剂量的 80%，目标覆盖范围受到限制。
主要结局是 RT 后 2 周的食管生活质量（QOL），通过食管癌子量表（ECS）的癌症治疗功能评估问卷来衡量。更高的食管癌子量表分数对应着更好的 QOL，2-3 分的变化被认为具有临床意义。次要结局包括总生存、毒性事件和其他 QOL 指标。采用意向治疗分析。
在 2016 年 6 月 24 日至 2019 年 3 月 6 日之间，共有 90 名患者被随机分配到标准 RT 或 ES-IMRT（随机分组时的中位年龄为 72.0 岁[IQR，65.6-80.3]；50[56%]名女性）。36 名患者（40%）接受 20 Gy，54 名患者（60%）接受 30 Gy。主要终点是，对照组的 2 周 ECS 评分平均（SD）为 50.5（10.2）（95%CI，47.2-53.8），ES-IMRT 组为 54.3（7.6）（95%CI，51.9-56.7）（P=0.06）。对照组有 24%（n=11）的患者发生症状性 RT 相关食管炎，而 ES-IMRT 组为 2%（n=1）（P=0.002）。基于分层因素的事后亚组分析表明，在接受 30 Gy 的患者中，食管炎的减少最为明显（30%[n=8] vs 0%；P=0.004）。标准 RT（中位，8.6 个月；95%CI，5.7-15.6 个月）和 ES-IMRT（中位，8.7 个月；95%CI，5.1-10.2 个月）的总生存率相似（P=0.62）。
在这项 3 期随机临床试验中，ES-IMRT 并没有显著改善食管 QOL，但显著降低了症状性食管炎的发生率。由于事后分析发现，在接受 30 Gy RT 的患者中，食管炎的减少最为明显，这些发现表明，当处方剂量较高（30 Gy）时，ES-IMRT 可能最有益。
ClinicalTrials.gov 标识符：NCT02752126。
