术后放疗对完全切除术后辅助化疗的 pIIIA-N2 期非小细胞肺癌患者的影响：III 期 PORT-C 随机临床试验。
Effect of Postoperative Radiotherapy for Patients With pIIIA-N2 Non-Small Cell Lung Cancer After Complete Resection and Adjuvant Chemotherapy: The Phase 3 PORT-C Randomized Clinical Trial.
机构信息
Department of VIP Medical Services & Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Division of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
出版信息
JAMA Oncol. 2021 Aug 1;7(8):1178-1185. doi: 10.1001/jamaoncol.2021.1910.
IMPORTANCE
The role of postoperative radiotherapy (PORT) has not been well defined in resected pIIIA-N2 non-small cell lung cancer (NSCLC).
OBJECTIVE
To evaluate the effect of PORT using modern techniques on survival and safety in patients with pIIIA-N2 NSCLC after complete resection and adjuvant chemotherapy.
DESIGN, SETTING, AND PARTICIPANTS: The PORT-C randomized clinical trial was conducted in 394 patients with pIIIA-N2 NSCLC treated with complete resection and 4 cycles of platinum-based chemotherapy between January 2009 and December 2017. Data were analyzed between March 2019 and December 2020.
INTERVENTIONS
Patients were randomized equally into the PORT arm (n = 202) or the observation arm (n = 192). The total dose of PORT was 50 Gy.
MAIN OUTCOMES AND MEASURES
The primary end point was disease-free survival (DFS). Secondary end points included overall survival (OS), locoregional recurrence-free survival (LRFS), distant metastasis-free survival, and toxic effects.
RESULTS
In total, 394 patients were enrolled and 364 were eligible, with a median (range) age of 55 (25-70) years. There were 202 (55.5%) male and 162 (44.5%) female patients. The median follow-up was 46.0 (95% CI, 41.9-51.4) months, and 230 DFS events were reported. There were 184 patients in the PORT arm and 180 patients in the observation arm. The 3-year DFS rates were 40.5% with PORT vs 32.7% with observation (median, 22.1 vs 18.6 months), and the difference in DFS was not statistically significant without adjustment (hazard ratio [HR], 0.84; 95% CI, 0.65-1.09; P = .20), though it was significant with preplanned yet exploratory analysis (stratified analysis by the number of detected lymph nodes and positive lymph nodes, HR, 0.75; log-rank P = .04). The 3-year OS rates were 78.3% vs 82.8% (HR, 1.02; P = .93), and LRFS was 66.5% vs 59.7% (HR, 0.71; 95% CI, 0.51-0.97; P = .03), respectively. For 310 per-protocol patients (140 with PORT and 170 with observation), PORT significantly improved DFS (42.8% vs 30.6%; HR, 0.75; 95% CI, 0.57-1.00; P = .05) but not OS (HR, 0.83; 95% CI, 0.53-1.30; P = .41). The 3-year local recurrence only rates were 9.5% and 18.3% in the 2 arms, respectively (Fine-Gray HR, 0.55; Gray test P = .04). No radiotherapy-related grade 4 or 5 adverse event was observed.
CONCLUSIONS AND RELEVANCE
In this phase 3 randomized clinical trial of patients with pIIIA-N2 NSCLC after complete resection and adjuvant chemotherapy, PORT did not improve DFS. Further studies exploring patients who might best benefit from PORT are needed.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT00880971.
重要性：在完全切除和辅助化疗后，pIIIA-N2 非小细胞肺癌（NSCLC）患者的术后放疗（PORT）作用尚未明确。
目的：评估使用现代技术进行 PORT 对完全切除和 4 个周期铂类化疗后的 pIIIA-N2 NSCLC 患者的生存和安全性的影响。
设计、地点和参与者：PORT-C 是一项随机临床试验，共纳入 394 例完全切除和 4 个周期铂类化疗的 pIIIA-N2 NSCLC 患者，研究时间为 2009 年 1 月至 2017 年 12 月，数据于 2019 年 3 月至 2020 年 12 月进行分析。
干预措施：患者被随机分为 PORT 组（n=202）和观察组（n=192）。PORT 的总剂量为 50 Gy。
主要结局和测量指标：主要终点为无病生存期（DFS）。次要终点包括总生存期（OS）、局部区域无复发生存期（LRFS）、远处无转移生存期和毒性作用。
结果：共纳入 394 例患者，364 例符合条件，中位（范围）年龄为 55（25-70）岁，其中男性 202 例（55.5%），女性 162 例（44.5%）。中位随访时间为 46.0（95%CI，41.9-51.4）个月，报告了 230 例 DFS 事件。PORT 组 184 例，观察组 180 例。PORT 组 3 年 DFS 率为 40.5%，观察组为 32.7%（中位时间，22.1 vs 18.6 个月），未调整时 DFS 差异无统计学意义（风险比[HR]，0.84；95%CI，0.65-1.09；P=0.20），但在预先计划的探索性分析中具有统计学意义（按检测到的淋巴结和阳性淋巴结的数量分层分析，HR，0.75；对数秩 P=0.04）。3 年 OS 率分别为 78.3%和 82.8%（HR，1.02；P=0.93），LRFS 分别为 66.5%和 59.7%（HR，0.71；95%CI，0.51-0.97；P=0.03）。对于 310 例符合方案的患者（PORT 组 140 例，观察组 170 例），PORT 显著改善了 DFS（42.8% vs 30.6%；HR，0.75；95%CI，0.57-1.00；P=0.05），但未改善 OS（HR，0.83；95%CI，0.53-1.30；P=0.41）。2 组局部复发率分别为 9.5%和 18.3%（Fine-Gray HR，0.55；Gray 检验 P=0.04）。未观察到与放疗相关的 4 级或 5 级不良事件。
结论和相关性：在这项完全切除和辅助化疗后的 pIIIA-N2 NSCLC 患者的 III 期随机临床试验中，PORT 并未改善 DFS。需要进一步研究探索哪些患者可能从 PORT 中获益最大。
试验注册：ClinicalTrials.gov 标识符：NCT00880971。
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