Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY.
Division of Thoracic Surgery, Department of Surgery, The Johns Hopkins Medical Institutions, Baltimore, Md.
J Thorac Cardiovasc Surg. 2019 Jul;158(1):269-276. doi: 10.1016/j.jtcvs.2018.11.124. Epub 2018 Dec 13.
We conducted a phase I trial of neoadjuvant nivolumab, a monoclonal antibody to the programmed cell death protein 1 checkpoint receptor, in patients with resectable non-small cell lung cancer. We analyzed perioperative outcomes to assess the safety of this strategy.
Patients with untreated stage I-IIIA non-small cell lung cancer underwent neoadjuvant therapy with 2 cycles of nivolumab (3 mg/kg), 4 and 2 weeks before resection. Patients underwent invasive mediastinal staging as indicated and post-treatment computed tomography. Primary study end points were safety and feasibility of neoadjuvant nivolumab followed by pulmonary resection. Data on additional surgical details were collected through chart review.
Of 22 patients enrolled, 20 underwent resection. One was unresectable; another had small cell histologic subtype. There were no delays to surgical resection. Median time from first treatment to surgery was 33 (range, 17-43) days. There were 15 lobectomies, 2 pneumonectomies, 1 bilobectomy, 1 sleeve lobectomy, and 1 wedge resection. Of 13 procedures attempted via a video-assisted thoracoscopic surgery or robotic approach, 7 (54%) required thoracotomy. Median operative time was 228 (range, 132-312) minutes; estimated blood loss was 100 (range, 25-1000) mL; length of hospital stay was 4 (range, 2-17) days. There was no operative mortality. Morbidity occurred in 10 of 20 patients (50%). The most common postoperative complication was atrial arrhythmia (6/20; 30%). Major pathologic response was identified in 9 of 20 patients (45%).
Neoadjuvant therapy with nivolumab was not associated with unexpected perioperative morbidity or mortality. More than half of the video-assisted thoracoscopic surgery/robotic cases were converted to thoracotomy, often because of hilar inflammation and fibrosis.
我们对可切除的非小细胞肺癌患者进行了新辅助纳武单抗(一种程序性死亡蛋白 1 检查点受体的单克隆抗体)的 I 期试验。我们分析了围手术期结果,以评估该策略的安全性。
未经治疗的 I 期-IIIA 期非小细胞肺癌患者接受 2 个周期的纳武单抗(3mg/kg)新辅助治疗,在切除前 4 周和 2 周。根据需要对患者进行侵袭性纵隔分期和治疗后计算机断层扫描。主要研究终点是新辅助纳武单抗后进行肺切除术的安全性和可行性。通过图表审查收集了有关其他手术细节的数据。
22 名患者中,20 名患者接受了手术。1 名患者不可切除;另 1 名患者为小细胞组织学亚型。手术没有延误。从首次治疗到手术的中位时间为 33 天(范围,17-43 天)。15 例为肺叶切除术,2 例为全肺切除术,1 例为双肺叶切除术,1 例为袖状肺叶切除术,1 例为楔形切除术。在 13 例尝试经电视辅助胸腔镜手术或机器人辅助手术的手术中,7 例(54%)需要开胸。中位手术时间为 228 分钟(范围,132-312 分钟);估计失血量为 100 毫升(范围,25-1000 毫升);住院时间为 4 天(范围,2-17 天)。无手术死亡。20 例患者中有 10 例(50%)发生并发症。最常见的术后并发症是房性心律失常(6/20;30%)。20 例患者中有 9 例(45%)发现主要病理反应。
纳武单抗新辅助治疗与围手术期无意外发病率或死亡率相关。超过一半的电视辅助胸腔镜手术/机器人手术被转为开胸手术,通常是因为肺门炎症和纤维化。