Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-small-cell lung cancer: a pooled analysis of two randomised trials.
Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-small-cell lung cancer: a pooled analysis of two randomised trials.
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DOI：
10.1016/s1470-2045(15)70168-3
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发表时间：
2015-06
期刊：
影响因子：
51.1
通讯作者：
Roth, Jack A.
中科院分区：
文献类型：
--
作者：
Chang, Joe Y.;Senan, Suresh;Paul, Marinus A.;Mehran, Reza J.;Louie, Alexander V.;Balter, Peter;Groen, Harry J. M.;McRae, Stephen E.;Widder, Joachim;Feng, Lei;van den Borne, Ben E. E. M.;Munsell, Mark F.;Hurkmans, Coen;Berry, Donald A.;van Werkhoven, Erik;Kresl, John J.;Dingemans, Anne-Marie;Dawood, Omar;Haasbeek, Cornelis J. A.;Carpenter, Larry S.;De Jaeger, Katrien;Komaki, Ritsuko;Slotman, Ben J.;Smit, Egbert F.;Roth, Jack A.
可手术的I期非小细胞肺癌（NSCLC）的标准治疗是肺叶切除术并纵膈淋巴结清扫或取样。立体定向消融放疗（SABR）治疗不能手术的I期NSCLC已显示出令人鼓舞的结果，但两项独立、随机、SABR治疗可手术的I期NSCLC （STARS和ROSEL）的3期试验由于累积缓慢而提前结束。我们的目的是通过汇总这些试验的数据来评估SABR与手术的总生存率。STARS和ROSEL研究的合格患者是临床T1-2a （<4 cm）、N0M0、可手术的NSCLC患者。患者按1:1的比例随机分配到SABR或肺叶切除术合并纵隔淋巴结清扫或取样。我们对意向治疗人群进行了汇总分析，以总生存率为主要终点。两项试验均已在ClinicalTrials.gov注册（STARS: NCT00840749; ROSEL: NCT00687986）。58例患者入组并随机分配（31例SABR组，27例手术组）。SABR组中位随访时间为40.2个月（IQR 23.0-47.3），手术组中位随访时间为35.4个月（18.9-40.7）。手术组有6名患者死亡，而SABR组只有1名患者死亡。SABR组3年总生存率为95% (95% CI 85-100)，而手术组为79%(64-97)（风险比[HR] 0.14 [95% CI 0.017-1.190], log-rank p=0.037）。SABR组3年无复发生存率为86% (95% CI 74-100)，手术组为80% (65-97)（HR 0.69 [95% CI 0.21-2.29], log-rank p=0.54）。手术组1例局部淋巴结复发，2例远处转移；SABR组1例局部复发，4例局部淋巴结复发，1例远处转移。SABR组中有3例（10%）患者出现3级治疗相关不良事件（3例[10%]胸壁疼痛，2例[6%]呼吸困难或咳嗽，1例[3%]疲劳和肋骨骨折）。没有接受SABR治疗的患者发生4级事件或治疗相关死亡。在手术组中，1例（4%）患者死于手术并发症，12例（44%）患者发生3-4级治疗相关不良事件。手术组中不止一名患者发生的3级事件为呼吸困难（4例[15%]）、胸痛（4例[15%]）和肺部感染（2例[7%]）。SABR可能是治疗可手术I期非小细胞肺癌的一种选择。由于患者样本量小，随访时间短，因此有必要对可手术患者进行SABR与手术的随机对照研究。Accuray公司，荷兰卫生研究与发展组织，NCI癌症中心支持，NCI临床和转化科学奖。
The standard of care for operable, stage I, non-small-cell lung cancer (NSCLC) is lobectomy with mediastinal lymph node dissection or sampling. Stereotactic ablative radiotherapy (SABR) for inoperable stage I NSCLC has shown promising results, but two independent, randomised, phase 3 trials of SABR in patients with operable stage I NSCLC (STARS and ROSEL) closed early due to slow accrual. We aimed to assess overall survival for SABR versus surgery by pooling data from these trials. Eligible patients in the STARS and ROSEL studies were those with clinical T1–2a (<4 cm), N0M0, operable NSCLC. Patients were randomly assigned in a 1:1 ratio to SABR or lobectomy with mediastinal lymph node dissection or sampling. We did a pooled analysis in the intention-to-treat population using overall survival as the primary endpoint. Both trials are registered with ClinicalTrials.gov (STARS: NCT00840749; ROSEL: NCT00687986). 58 patients were enrolled and randomly assigned (31 to SABR and 27 to surgery). Median follow-up was 40.2 months (IQR 23.0–47.3) for the SABR group and 35.4 months (18.9–40.7) for the surgery group. Six patients in the surgery group died compared with one patient in the SABR group. Estimated overall survival at 3 years was 95% (95% CI 85–100) in the SABR group compared with 79% (64–97) in the surgery group (hazard ratio [HR] 0.14 [95% CI 0.017–1.190], log-rank p=0.037). Recurrence-free survival at 3 years was 86% (95% CI 74–100) in the SABR group and 80% (65–97) in the surgery group (HR 0.69 [95% CI 0.21–2.29], log-rank p=0.54). In the surgery group, one patient had regional nodal recurrence and two had distant metastases; in the SABR group, one patient had local recurrence, four had regional nodal recurrence, and one had distant metastases. Three (10%) patients in the SABR group had grade 3 treatment-related adverse events (three [10%] chest wall pain, two [6%] dyspnoea or cough, and one [3%] fatigue and rib fracture). No patients given SABR had grade 4 events or treatment-related death. In the surgery group, one (4%) patient died of surgical complications and 12 (44%) patients had grade 3–4 treatment-related adverse events. Grade 3 events occurring in more than one patient in the surgery group were dyspnoea (four [15%] patients), chest pain (four [15%] patients), and lung infections (two [7%]). SABR could be an option for treating operable stage I NSCLC. Because of the small patient sample size and short follow-up, additional randomised studies comparing SABR with surgery in operable patients are warranted. Accuray Inc, Netherlands Organisation for Health Research and Development, NCI Cancer Center Support, NCI Clinical and Translational Science Award.