Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Lancet Oncol. 2021 Oct;22(10):1448-1457. doi: 10.1016/S1470-2045(21)00401-0. Epub 2021 Sep 13.
A previous pooled analysis of the STARS and ROSEL trials showed higher survival after stereotactic ablative radiotherapy (SABR) than with surgery for operable early-stage non-small-cell lung cancer (NSCLC), but that analysis had notable limitations. This study reports long-term results of the revised STARS trial, in which the SABR group was re-accrued with a larger sample size, along with a protocol-specified propensity-matched comparison with a prospectively registered, contemporary institutional cohort of patients who underwent video-assisted thoracoscopic surgical lobectomy with mediastinal lymph node dissection (VATS L-MLND).
This single-arm prospective trial was done at the University of Texas MD Anderson Cancer Center (Houston, TX, USA) and enrolled patients aged 18 years or older with a Zubrod performance status of 0-2, newly diagnosed and histologically confirmed NSCLC with N0M0 disease (squamous cell, adenocarcinoma, large cell, or NSCLC not otherwise specified), and a tumour diameter of 3 cm or less. This trial did not include patients from the previous pooled analysis. SABR dosing was 54 Gy in three fractions (for peripheral lesions) or 50 Gy in four fractions (for central tumours; simultaneous integrated boost to gross tumour totalling 60 Gy). The primary endpoint was the 3-year overall survival. For the propensity-matching analysis, we used a surgical cohort from the MD Anderson Department of Thoracic and Cardiovascular Surgery's prospectively registered, institutional review board-approved database of all patients with clinical stage I NSCLC who underwent VATS L-MLND during the period of enrolment in this trial. Non-inferiority could be claimed if the 3-year overall survival rate after SABR was lower than that after VATS L-MLND by 12% or less and the upper bound of the 95% CI of the hazard ratio (HR) was less than 1·965. Propensity matching consisted of determining a propensity score using a multivariable logistic regression model including several covariates (age, tumour size, histology, performance status, and the interaction of age and sex); based on the propensity scores, one patient in the SABR group was randomly matched with one patient in the VATS L-MLND group using a 5:1 digit greedy match algorithm. This study is registered with ClinicalTrials.gov, NCT02357992.
Between Sept 1, 2015, and Jan 31, 2017, 80 patients were enrolled and included in efficacy and safety analyses. Median follow-up time was 5·1 years (IQR 3·9-5·8). Overall survival was 91% (95% CI 85-98) at 3 years and 87% (79-95) at 5 years. SABR was tolerated well, with no grade 4-5 toxicity and one (1%) case each of grade 3 dyspnoea, grade 2 pneumonitis, and grade 2 lung fibrosis. No serious adverse events were recorded. Overall survival in the propensity-matched VATS L-MLND cohort was 91% (95% CI 85-98) at 3 years and 84% (76-93) at 5 years. Non-inferiority was claimed since the 3-year overall survival after SABR was not lower than that observed in the VATS L-MLND group. There was no significant difference in overall survival between the two patient cohorts (hazard ratio 0·86 [95% CI 0·45-1·65], p=0·65) from a multivariable analysis.
Long-term survival after SABR is non-inferior to VATS L-MLND for operable stage IA NSCLC. SABR remains promising for such cases but multidisciplinary management is strongly recommended.
Varian Medical Systems and US National Cancer Institute (National Institutes of Health).
之前的 STARS 和 ROSEL 试验的汇总分析显示，立体定向消融放疗（SABR）后早期非小细胞肺癌（NSCLC）的生存率高于手术，但该分析存在显著局限性。本研究报告了修订后的 STARS 试验的长期结果，其中 SABR 组的样本量更大，同时根据协议进行了倾向性匹配比较，与前瞻性注册的机构队列进行了比较，该队列的患者接受了电视辅助胸腔镜肺叶切除术伴纵隔淋巴结清扫术（VATS L-MLND）。
这项单臂前瞻性试验在德克萨斯大学 MD 安德森癌症中心（休斯顿，德克萨斯州，美国）进行，纳入了年龄在 18 岁或以上、Zubrod 表现状态为 0-2、新诊断且组织学证实为 NSCLC 的患者，且无 N0M0 疾病（鳞状细胞癌、腺癌、大细胞癌或未特指的 NSCLC），肿瘤直径为 3 厘米或以下。该试验不包括之前汇总分析中的患者。SABR 剂量为 54 Gy 分 3 次（对于外周病变）或 50 Gy 分 4 次（对于中央肿瘤；同时整合的增敏照射使肿瘤总量达到 60 Gy）。主要终点是 3 年总生存率。对于倾向匹配分析，我们使用了来自 MD 安德森胸心血管外科系的前瞻性注册、机构审查委员会批准的数据库中的一个外科队列，该队列包括在该试验入组期间接受 VATS L-MLND 的所有 I 期 NSCLC 患者。如果 SABR 后 3 年总生存率比 VATS L-MLND 低 12%或更低，且危险比（HR）的 95%CI 上限小于 1.965，则可声称非劣效性。倾向匹配包括使用多变量逻辑回归模型确定倾向评分，该模型包括几个协变量（年龄、肿瘤大小、组织学、表现状态以及年龄和性别之间的相互作用）；根据倾向评分，使用 5:1 的数字贪婪匹配算法，从 SABR 组中随机匹配一名患者与 VATS L-MLND 组中的一名患者。这项研究在 ClinicalTrials.gov 上注册，NCT02357992。
2015 年 9 月 1 日至 2017 年 1 月 31 日期间，共纳入 80 例患者进行疗效和安全性分析。中位随访时间为 5.1 年（IQR 3.9-5.8）。3 年总生存率为 91%（95%CI 85-98），5 年总生存率为 87%（79-95）。SABR 耐受性良好，无 4-5 级毒性，各有 1 例（1%）患者出现 3 级呼吸困难、2 级肺炎和 2 级肺纤维化。没有严重的不良事件记录。倾向匹配的 VATS L-MLND 队列中，3 年总生存率为 91%（95%CI 85-98），5 年总生存率为 84%（76-93）。由于 SABR 后 3 年的总生存率不低于 VATS L-MLND 组观察到的水平，因此声称非劣效性。多变量分析显示，两组患者的总生存率无显著差异（风险比 0.86 [95%CI 0.45-1.65]，p=0.65）。
SABR 治疗可手术的 IA 期 NSCLC 的长期生存率不劣于 VATS L-MLND。SABR 仍然适用于此类病例，但强烈建议进行多学科管理。
瓦里安医疗系统和美国国家癌症研究所（美国国立卫生研究院）。
