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Abstract：
Large cell neuroendocrine carcinoma (LCNEC) is a rare and highly invasive lung cancer subtype with an overall poor prognosis. Due to its low incidence rate and unusual pathological features, the clinical management of LCNEC remains controversial. The present study aimed to assess the effect of immune checkpoint inhibitors (ICIs) on treatment response and survival outcomes in patients with advanced LCNEC. The clinical data from 148 patients with LCNEC treated with ICIs at The First Affiliated Hospital of Zhengzhou University (Zhengzhou, China) between January 2019 and September 2021 were retrospectively analyzed. Kaplan-Meier and multivariable Cox regression analyses were used to evaluate associations between clinicopathological variables and patient outcomes. Patients treated with ICIs demonstrated extended median overall survival (mOS) times [23.5 months; 95% confidence interval (CI), 18.524-28.476] compared with patients who did not receive ICIs (11.2 months; 95% CI, 4.530-18.930) (P<0.001). Univariate analysis revealed that histological subtype (P=0.043), lymph node metastases (P=0.032) and number of metastatic organs (P=0.009) were associated with a poor prognosis. The heterogeneity of pathological components was associated with prognosis, and the mOS time was shorter for mixed LCNEC than that for pure LCNEC (P=0.043). The median progression-free survival (mPFS) (9.78 vs. 9.37 months; P=0.82) and mOS (20.70 vs. 25.79 months; P=0.181) times showed no significant association with regard to different regimens of immuno-based combination therapy (chemotherapy combined with ICIs vs. anti-angiogenic agents combined with ICIs). Poor Eastern Cooperative Oncology Group performance status score (P=0.04), multiple organ metastases (P=0.02) and high cancer antigen 125 levels (P=0.01) were independent risk factors of a poor prognosis. The present findings offer valuable insights into potential prognostic markers and highlight the favorable impact of ICIs on OS in advanced LCNEC. Prospective clinical studies are required to validate the therapeutic value of ICIs in LCNEC.
摘要：
大细胞神经内分泌癌（LCNEC）是一种罕见且高侵袭性的肺癌亚型，总体预后较差。由于其发病率低和异常的病理特征，LCNEC的临床治疗仍存在争议.本研究旨在评估免疫检查点抑制剂（ICIs）对晚期LCNEC患者治疗反应和生存结果的影响。郑州大学第一附属医院148例接受ICIs治疗的LCNEC患者的临床资料(郑州，中国）在2019年1月至2021年9月期间进行了回顾性分析。使用Kaplan-Meier和多变量Cox回归分析来评估临床病理变量与患者预后之间的关联。用ICIs治疗的患者表现出延长的中位总生存期（mOS）时间[23.5个月；95%置信区间（CI），18.524-28.476]与未接受ICIs的患者相比（11.2个月；95％CI，4.530-18.930）（P<0.001）。单因素分析显示组织学亚型(P=0.043),淋巴结转移（P=0.032）和转移器官的数量（P=0.009）与不良预后相关。病理成分的异质性与预后相关,混合LCNEC的mOS时间短于纯LCNEC（P=0.043）。中位无进展生存期（mPFS）（9.78vs.9.37个月；P=0.82）和mOS（20.70vs.25.79个月；P=0.181）时间与基于免疫的联合治疗的不同方案没有显着关联（化疗联合ICIs与抗血管生成剂与ICIs联合使用)。东部肿瘤协作组表现状态得分差（P=0.04），多器官转移(P=0.02)和高癌抗原125水平(P=0.01)是预后不良的独立危险因素.本发现为潜在的预后标志物提供了有价值的见解，并强调了ICI对高级LCNEC中OS的有利影响。需要前瞻性临床研究来验证ICIs在LCNEC中的治疗价值。
