Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
Central Laboratory, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
Ann Surg Oncol. 2022 Sep;29(9):5666-5678. doi: 10.1245/s10434-022-11610-4. Epub 2022 May 11.
Large cell neuroendocrine carcinoma (LCNEC) is a rare high-grade neuroendocrine carcinoma of the lung. Little is known about the differences between the pure and combined LCNEC subtypes, and thus we conducted this study to provide more comprehensive insight into LCNEC.
We reviewed 221 patients with pure LCNEC (P-LCNEC) and 120 patients with combined LCNEC (C-LCNEC) who underwent pulmonary surgery in our hospital to compare their clinical features, driven genes' status (EGFR/ALK/ROS1/KRAS/BRAF), and adjuvant chemotherapy regimens. Propensity score matching (PSM) was applied to reduce selection bias.
The P-LCNEC group included a higher proportion of males and smokers than the C-LCNEC group. Furthermore, the C-LCNEC group had higher incidences of visceral pleural invasion (VPI), EGFR mutation and ALK rearrangement compared with the P-LCNEC group. Expression of neuroendocrine markers (CD56, CGA, and SYN) and recurrence patterns were not significantly different between the two groups. The P-LCNEC group had better disease-free survival (DFS) and overall survival (OS) compared with the C-LCNEC group (median DFS: 67.0 vs. 28.1 months, p = 0.021; median OS: 72.0 vs. 45.0 months, p = 0.001), which was further confirmed by the PSM method (p = 0.004 and p < 0.001, respectively). Adjuvant chemotherapy was also an independent factor for DFS and OS. Subgroup analysis found that regardless of whether it was for the entire LCNEC group or the P- and C-LCNEC subtypes, the small cell lung cancer (SCLC) regimens presented with superior survival compared with the non-small cell lung cancer (NSCLC) regimens.
P-LCNEC was associated with more favorable prognosis compared with C-LCNEC. SCLC-based adjuvant chemotherapy was more appropriate for LCNEC patients than NSCLC-based regimens, regardless of whether they were the pure or combined LCNEC subtypes. C-LCNEC patients may be the potential beneficiary of targeted therapy.
大细胞神经内分泌癌（LCNEC）是一种罕见的肺高级别神经内分泌癌。对于纯 LCNEC 与合并 LCNEC 这两种亚型之间的差异，人们知之甚少，因此我们开展了这项研究，旨在更全面地了解 LCNEC。
我们回顾性分析了 221 例在我院行肺切除术的纯 LCNEC（P-LCNEC）患者和 120 例合并 LCNEC（C-LCNEC）患者的临床特征、驱动基因状态（EGFR/ALK/ROS1/KRAS/BRAF）和辅助化疗方案。采用倾向评分匹配（PSM）以减少选择偏倚。
P-LCNEC 组中男性和吸烟者的比例高于 C-LCNEC 组。此外，与 P-LCNEC 组相比，C-LCNEC 组中存在内脏胸膜侵犯（VPI）、EGFR 突变和 ALK 重排的比例更高。两组之间神经内分泌标志物（CD56、CGA 和 SYN）的表达和复发模式无显著差异。与 C-LCNEC 组相比，P-LCNEC 组的无病生存期（DFS）和总生存期（OS）更好（中位 DFS：67.0 与 28.1 个月，p=0.021；中位 OS：72.0 与 45.0 个月，p=0.001），PSM 方法也进一步证实了这一点（p=0.004 和 p<0.001）。辅助化疗也是 DFS 和 OS 的独立因素。亚组分析发现，无论对于整个 LCNEC 组还是 P-LCNEC 和 C-LCNEC 亚型，小细胞肺癌（SCLC）方案的生存结果均优于非小细胞肺癌（NSCLC）方案。
与 C-LCNEC 相比，P-LCNEC 与更好的预后相关。对于 LCNEC 患者，无论其为纯或合并 LCNEC 亚型，SCLC 为基础的辅助化疗方案优于 NSCLC 方案。C-LCNEC 患者可能是靶向治疗的潜在获益者。
