免疫检查点抑制剂联合化疗后手术治疗Ⅲ期不可切除非小细胞肺癌的效果

Effect of surgical resection after preoperative immunotherapy combined chemotherapy on unresectable stage Ⅲ non-small cell lung cancer

目的评估免疫检查点抑制剂联合化疗在Ⅲ期不可切除的非小细胞肺癌术前应用的安全性和手术效果。方法回顾2019年11月至2021年11月通过术前免疫联合化疗"转化"后进行手术切除的23例患者。所有患者均经活检明确非小细胞肺癌的病理诊断。经多学科会诊(MDT)讨论和术前影像学评估符合《Ⅲ期非小细胞肺癌多学科诊疗专家共识2019版》中所描述的Ⅲ期不可切除的情况。经过术前2~4个周期的抗PD-1单抗联合化疗治疗后, 由外科团队评估手术切除机会并进行手术切除。统计手术切除率、R0切除率、主要病理缓解率(MPR)、病理完全缓解率(pCR)、3~5级不良反应发生率等重要指标和其他各项围手术期数据。结果全组患者初始影像学评估cⅢA期10例, cⅢB期13例。出现多站N2转移15例、巨块融合N2转移9例、侵犯大血管(T4)6例、对侧纵隔淋巴结转移(N3)1例。术前新辅助治疗后, 影像学评估部分缓解17例, 疾病稳定3例, 疾病进展3例。全组手术切除率达91.3%(21/23, 上腔静脉人工血管置换+肺叶切除1例;肺叶袖式切除2例;全肺切除5例;肺叶/复合肺叶切除12例;楔形切除1例;探查后无法行手术切除2例)。21例手术的R0切除率95.2%(20/21);术后病理评估MPR为13例, 其中8例达到pCR。围手术期无死亡病例, 中位手术时间260(190~460)min, 中位出血量100(50~750)ml, 中位术后胸腔引流管留置时间5(3~9)天, 中位术后住院天数7(5~11)天。免疫治疗相关3级不良反应2例, 1例为免疫相关间质性肺炎, 1例为累及眼、口腔、生殖器黏膜的免疫相关性损伤。手术并发症2例, 1例为持续性肺漏气, 经46天保守治疗后自行停止漏气;另1例为胸腔积液, 经穿刺引流后缓解。结论对于Ⅲ期不可切除非小细胞肺癌, 免疫联合化疗是一种有效的术前降期手段, 可将91.3%的"不可切除"转化为"可切除", 同时实现较大程度的病理缓解。其副反应总体可控, 安全性较好。

Objective Immune checkpoint inhibitors have a high remission rate in the preoperative application of resectable and potentially resectable non-small cell lung cancer when combined with chemotherapy.For the unresectable stageⅢnon-small cell lung cancer,whether the transformation can be achieved through this regimen to provide opportunities for surgical resection is controversial.In this study,we evaluated the pattern of transformation therapy by reviewing the efficacy and safety of preoperative therapy and surgery of this group.Methods A review of 23 patients undergoing surgical resection after transformation therapy by preoperative immunotherapy combined chemotherapy between November 2019 and November 2021 was performed.All patients must clarify the pathological diagnosis of non-small cell lung cancer by biopsy.After the multi-disciplinary treatment team and preoperative imaging assessment,the diagnosis should be consistent with unresectable stage III as described in the Expert Consensus on Multidisciplinary Management of StageⅢNon-Small Cell Lung Cancer,2019 Edition.After 2 to 4 cycles of preoperative anti-PD-1 monoclonal antibody combined with chemotherapy,the surgical team assessed the chance of resection and performed surgery.Important indicators such as surgical resection rate,R0 resection rate,MPR,pCR,incidence of grade 3-5 adverse reactions and various other perioperative data were counted.Results In the whole group,initial imaging evaluation was 10 of stage cⅢA and 13 of stage cⅢB.15 cases had multiple stations N2 lymph nodes metastasis,9 had enlarged fused N2 lymph nodes metastasis,6 had large vessel invasion(T4),and 1 had contralateral mediastinal lymph node metastasis(N3).After preoperative neoadjuvant therapy,17 cases achieved PR,3 achieved SD and 3 achieved PD.The surgical resection rate of the whole group was 91.3%(21/23,1 lobectomy combined with superior vena cava reconstruction,2 sleeve lobectomy,5 pneumonectomy,12 lobectomy/combined lobectomy,1 wedge resection and 2 unresectable cases),R0 resection rate was 95.2%(20/21).MPR was achieved in 13 cases,8 of them reached pCR.There were no perioperative deaths,median surgical time was 260(190-460)min,median bleeding volume was 100(50-750)ml,median drainage time was 5(3-9)days,and median hospitalization was 7(5-11)days.Two cases got immunotherapy-related grade 3 adverse reactions,one was interstitial pneumonia and the other was immune-related injury involving the eye,oral and genital mucosa.Two cases got surgical complications and one was persistent lung leakage,which stopped after 46 days of conservative treatment;The other was pleural effusion,which was relieved after drainage.Conclusion For the unresectable stageⅢNSCLC,immunotherapy combined chemotherapy is an effective preoperative downstage method.It can convert 91.3%cases to resectable ones while achieving a good degree of pathological remission.Its side reactions are generally controllable and safety.