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- 可选辅助化疗方案包括：长春瑞滨/ 紫杉醇/ 多西他赛/ 培美曲塞（非鳞癌）/ 吉西他滨+ 顺铂 / 卡铂。
- 对于ⅡA 期患者，完全性切除后，可考虑给予辅助化疗［9］。
- 对于 EGFR 突变阳性患者，NMPA 已批准奥希替尼或埃克替尼用于术后辅助治疗［10-11］。
- IMpower010 研究结果显示，对于Ⅱ~ ⅢA 期适宜手术患者，根治性手术及含铂双药化疗后，阿替利珠单抗对比最佳支持治疗显著延长了 PD-L1 TC ≥ 1% 患者的无病生存期（未达到 vs.35.3 个月，HR=0.66，P=0.004）［12］，基于此，NMPA 已批准阿替利珠单抗用于Ⅱ~ ⅢA 期 PD-L1 TC ≥ 1% 且接受根治性手术及含铂双药化疗后的辅助治疗，本指南将“根治性手术后，阿替利珠单抗辅助治疗（限 PD-L1 TC ≥ 1%）”从Ⅱ级推荐上升至Ⅰ级推荐。
- KEYNOTE-091/PEARLS 研究［14］结果显示：对于ⅠB（T2a ≥ 4cm）- ⅢA 期适宜手术患者，根治性手术及含铂双药化疗后，帕博利珠单抗对比安慰剂显著延长了患者的无病生存期（53.6 个月 vs. 40.2 个月，HR=0.76，P=0.001 4），基于此，美国 FDA 已批准帕博利珠单抗用于ⅠB（T2a ≥ 4cm）~ ⅢA 期 NSCLC 切除和铂类化疗后的辅助治疗，本指南新增“根治性手术后，帕博利珠单抗辅助治疗”并作为Ⅱ级推荐。
- CheckMate 816 研究［13］结果显示，对于ⅠB ~ ⅢA 期适宜手术患者，纳武利尤单抗联合化疗与单独化疗相比，显著延长中位无事件生存期（31.6 个月 vs. 20.8 个月，HR=0.63， P=0.005）。基于此，NMPA 已批准纳武利尤单抗联合含铂双药化疗用于肿瘤直径≥ 4cm 或淋巴结阳性的可切除 NSCLC 新辅助治疗，本指南新增“化疗联合纳武利尤单抗新辅助治疗Ⅱ~ⅢA 期 NSCLC 患者”并作为Ⅰ级推荐。在临床实践中，建议严格按照药物适应证推荐治疗，不宜将同类药物进行简单替换。
- 卡瑞利珠、信迪利、替雷利珠单抗联合治疗（联合化疗或抗血管治疗） 等多个Ⅱ期新辅助研究在Ⅱ~ ⅢA 期 NSCLC 患者中展现出良好效果。近期，特瑞普利单抗联合含铂双药作为新辅助治疗的Ⅲ期研究 Neotorch 公布达到主要研究终点（无事件生存期）。一项研究卡瑞利珠单抗联合阿帕替尼作为ⅡA~ ⅢB 期（仅 T3N2M0） 新辅助治疗的Ⅱ期研究显示，MPR 率为 57%，pCR 率为 23%，显示治疗前景［19］。
- 不完全切除患者，行二次手术 + 含铂双药方案化疗或术后放疗 + 含铂双药方案化疗。
- 对于不适宜手术患者，可考虑采用同步放化疗，化疗方案一般参考Ⅲ期患者的方案。
⏫ Ⅱ期非小细胞肺癌的诊断和治疗管理
参考指南：
- 中国临床肿瘤学会指南工作委员会.中国临床肿瘤学会 (CSCO) 非小细胞肺癌诊疗指南2024.人民卫生出版社.北京 2024
参考文献：
［1］ SAJI H, OKADA M, TSUBOI M, et al. Segmentectomy versus lobectomy in small-sized peripheral non-small-cell lung cancer (JCOG0802/WJOG4607L): A multicentre, open-label, phase 3, randomised, controlled, non-inferiority trial. Lancet, 2022, 399 (10335): 1607-1617.
［2］ ALTORKI N, WANG X, KOZONO D, et al. Lobar or sublobar resection for peripheral stage ⅠA non-small-cell lung cancer. N Engl J Med, 2023, 388 (6): 489-498.
［3］ ONISHI H, SHIRATO H, NAGATA Y, et al. Stereotactic body radiotherapy (SBRT) for operable stage Ⅰ non-small- cell lung cancer: Can SBRT be comparable to surgery ？. Int J Radiat Oncol Biol Phys, 2011, 81 (5): 1352-1358.
［4］ GRILLS IS, MANGONA VS, WELSH R, et al. Outcomes after stereotactic lung radiotherapy or wedge resection for stage Ⅰnon-small-cell lung cancer. J Clin Oncol, 2010, 28 (6): 928-935.
［5］ CRABTREE TD, DENLINGER CE, MEYERS BF, et al. Stereotactic body radiation therapy versus surgical resection for stage Ⅰnon-small cell lung cancer. J Thorac Cardiovasc Surg, 2010, 140 (2): 377-386.
［6］ TIMMERMAN R, PAULUS R, GALVIN J, et al. Stereotactic body radiation therapy for inoperable early stage lung cancer. JAMA, 2010, 303 (11): 1070-1076.
［7］ PALMA D, VISSER O, LAGERWAARD FJ, et al. Impact of introducing stereotactic lung radiotherapy for elderly patients with stage Ⅰ non-small-cell lung cancer: A population-based time-trend analysis. J Clin Oncol, 2010, 28 (35): 5153-5159.
［8］ SHIRVANI SM, JIANG J, CHANG JY, et al. Comparative effectiveness of 5 treatment strategies for early-stage non- small cell lung cancer in the elderly. Int J Radiat Oncol Biol Phys, 2012, 84 (5): 1060-1070.
［9］ ARRIAGADA R, BERGMAN B, DUNANT, et al. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med, 2004, 350 (4): 351-360.
［10］ ZHOU C, HE J, SU C, et al. Icotinib versus chemotherapy as adjuvant treatment for stage Ⅱ- ⅢA EGFR-mutant NSCLC (EVIDENCE): A randomized, open-label, phase 3 study. J Thorac Oncol, 2021, 16 (3): S232-S232.
［11］ WU YL, TSUBOI M, HE J, et al. Osimertinib in resected EGFR-mutated non-small-cell lung cancer. N Engl J Med, 2020, 383 (18): 1711-1723.
［12］ FELIP E, ALTORKI N, ZHOU CC, et al. Adjuvant atezolizumab after adjuvant chemotherapy in resected stage ⅠB- ⅢA non-small-cell lung cancer (IMpower010): A randomised, multicentre, open-label, phase 3 trial. Lan- cet, 2021, 398 (10308): 1344-1357.
［13］ FORDE PM, SPICER J, LU S, et al. Neoadjuvant nivolumab plus chemotherapy in resectable lung cancer. N Engl J Med, 2022, 386 (21): 1973-1985.
［14］ O′BRIEN M, PAZ-ARES L, MARREAUD S, et al. Pembrolizumab versus placebo as adjuvant therapy for com- pletely resected stage ⅠB- ⅢA non-small-cell lung cancer (PEARLS/KEYNOTE-091): An interim analysis of a randomised, triple-blind, phase 3 trial. Lancet Oncol, 2022, 23 (10): 1274-1286.
［15］ AUPÉRIN A, LE PÉCHOUX C, ROLLAND E, et al. Meta-analysis of concomitant versus sequential radiochemo- therapy in locally advanced non-small-cell lung cancer. J Clin Oncol, 2010, 28 (13): 2181-2190.
［16］ O’ROURKE N, ROQUÉ I FIGULS M, FARRÉ BERNADÓ N, et al. Concurrent chemoradiotherapy in non-small cell lung cancer. Cochrane Database Syst Rev, 2010, 16 (6): CD002140.
［17］ CURRAN WJ JR, PAULUS R, LANGER CJ, et al. Sequential vs. concurrent chemoradiation for stage Ⅲnon-small cell lung cancer: Randomized phase Ⅲ trial RTOG 9410. J Natl Cancer Inst, 2011, 103 (19): 1452-1460.
［18］ ALBAIN KS, CROWLEY JJ, TURRISI AT Ⅲ, et al. Concurrent cisplatin, etoposide, and chest radiotherapy in pathologic stage ⅢB non-small-cell lung cancer: A Southwest Oncology Group Phase ⅠStudy, SWOG 9019. J Clin Oncol, 2002, 20 (16): 3454-3360.
［19］ ZHAO J, ZHAO L, GUO W, et al. Efficacy, safety, and biomarker analysis of neoadjuvant camrelizumab and apa- tinib in patients with resectable non-small-cell lung cancer: A phase 2 clinical trial. J Thorac Oncol, 2023, S1556- 0864 (23): 00161-2.
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