Copy number variations mediate major pathological response to induction chemo-immunotherapy in unresectable stage IIIA-IIIB lung cancer
Copy number variations mediate major pathological response to induction chemo-immunotherapy in unresectable stage IIIA-IIIB lung cancer
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DOI：
10.1016/j.lungcan.2023.02.017
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发表时间：
2023-02-27
期刊：
影响因子：
5.3
通讯作者：
Zhang，Yongchang
中科院分区：
文献类型：
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作者：
Zeng，Liang;Zhou，Yuling;Zhang，Yongchang
非小细胞肺癌(NSCLC)是最常见的肺癌类型。尽管如此，支持对某些阶段进行最佳管理的证据仍然是一个争论的话题。在这项回顾性研究中，我们考察了新辅助诱导免疫化疗在中国不能切除的III期非小细胞肺癌患者中的有效性和安全性，并探索了新辅助免疫化疗的生物标志物。方法选择2019年1月17日至2022年1月17日在中国三家医院接受新辅助化疗的不能切除的非小细胞肺癌患者。收集围手术期结果和存活期数据。在可获得的基线肿瘤标本和手术标本中进行了回顾性生物标记物的探索。结果94名患者入选并接受了化疗免疫治疗作为新的辅助治疗。鳞癌80例，IIIB期26例。手术中转率74.4%，R0切除率98.4%。手术患者的主要病理应答率为65.6%，病理完全应答率为42.2%。73%的N2病患者的临床分期降至N0。43例(45.7%)患者发生治疗相关不良事件(TRAE)，以贫血最常见。≥~3级TRAE发生率为3.2%(3/94)。结论免疫化疗联合治疗不能切除的III期非小细胞肺癌不仅有效，而且具有良好的安全性。我们首次提供了CNV状态可能是MPR的预测生物标志物的证据。
IntroductionNon-small cell lung cancer (NSCLC) is the most common type of lung cancer. Despite this, evidence supporting optimal management of certain stages remains a topic of debate. In this retrospective study we examine the efficacy and safety, as well as exploring the biomarkers of neoadjuvant induction immuno-chemotherapy, in Chinese patients with unresectable stage III NSCLC.MethodsPatients with unresectable stage III NSCLC who were identified as driver mutation-negative and who received neoadjuvant chemo-immunotherapy were enrolled from three Chinese hospitals between Jan. 17, 2019, and Jan.17, 2022. Perioperative outcomes and survival data were collected. Retrospective biomarker exploration was performed in available baseline tumor samples and surgical specimens.Results94 patients were enrolled and received chemo-immunotherapy as neoadjuvant treatment. 80 patients had squamous cell carcinoma, and 26 had stage IIIB disease. Surgery conversion rate was 74.4%, R0 resection rate was 98.4%. Of 64 patients who underwent surgery, major pathological response (MPR) rate was 65.6% and pathologic complete response (pCR) rate was 42.2%. 73% of patients with N2 disease demonstrated down-staging to N0. Treatment-related adverse events (TRAEs) occurred in 43 patients (45.7%) with anemia was the most common. The Grade ≥ 3 TRAEs rate was 3.2% (3/94). A significant association between copy number variation (CNV) ploidy was also found.ConclusionThe combination treatment of immuno-chemotherapy for unresectable stage III NSCLC is not only effective but also has a favourable safety profile. For the first time we provide evidence that CNV status may be a predictive biomarker of MPR.