Division of Thoracic Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada; Section of Thoracic Surgery, Department of Surgery, University of Michigan, Ann Arbor, Mich.
Division of Thoracic Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
J Thorac Cardiovasc Surg. 2020 May;159(5):2043-2054.e9. doi: 10.1016/j.jtcvs.2019.09.077. Epub 2019 Sep 30.
Large cell neuroendocrine carcinoma is a rare, high-grade neuroendocrine tumor. The mainstay of treatment for early, node-negative disease is surgical resection, and optimal adjuvant treatment strategies are not well defined.
Patients with early, node-negative large cell neuroendocrine carcinoma were identified in the National Cancer Database from 2004 to 2014. Patient, tumor, treatment, and hospital characteristics were examined. Survival differences in patients receiving adjuvant chemotherapy (AC) were evaluated using Kaplan-Meier curves, and adjusted multivariate Cox models were constructed. A conditional landmark analysis was used to address immortal time bias. T-stage-specific propensity score matching was used to address covariate imbalances between groups.
One thousand seven hundred seventy patients were identified, of whom 463 (26.2%) received AC. Patients receiving AC were younger, less comorbid, and more likely to have T2 tumors. AC was associated with significantly longer survival, which persisted after adjustment in Cox models, for patients overall (5-year overall survival, 59.2% vs 45.3%; hazard ratio, 0.69; 95% confidence interval, 0.58-0.82; P < .0001), T2 tumors (overall survival, 59.8% vs 42.1%; hazard ratio, 0.63; 95% confidence interval, 0.50-0.81; P < .0001), and tumors 2 to 3 cm (overall survival, 60.0% vs 42.6%; hazard ratio, 0.64; 95% confidence interval, 0.46-0.8; P = .002), but not tumors smaller than 2 cm. Adjuvant chest radiotherapy was not associated with longer survival. Sublobar resection was associated with worse overall survival compared with lobectomy (hazard ratio, 1.40; 95% confidence interval, 1.20-1.64; P < .0001). Propensity score matching confirmed these findings, but the association with survival for tumors 2 to 3 cm in size was not significant.
In this national study of early-stage large cell neuroendocrine carcinoma, AC was associated with significantly longer survival for tumors larger than 3 cm, and possibly for tumors 2 to 3 cm. Adjuvant radiation was not associated with prolonged survival.
大细胞神经内分泌癌是一种罕见的高级别神经内分泌肿瘤。早期、无淋巴结转移疾病的主要治疗方法是手术切除，而最佳辅助治疗策略尚未明确。
本研究从 2004 年至 2014 年在国家癌症数据库中确定了早期、无淋巴结转移的大细胞神经内分泌癌患者。检查了患者、肿瘤、治疗和医院特征。使用 Kaplan-Meier 曲线评估接受辅助化疗（AC）患者的生存差异，并构建调整后的多变量 Cox 模型。条件性 landmark 分析用于解决不朽时间偏倚。T 期特异性倾向评分匹配用于解决组间混杂因素的不平衡。
共确定了 1770 例患者，其中 463 例（26.2%）接受了 AC。接受 AC 的患者更年轻、合并症更少，且更可能患有 T2 肿瘤。在 Cox 模型中调整后，AC 与总体生存时间显著延长相关，在所有患者中（5 年总生存率，59.2%比 45.3%；危险比，0.69；95%置信区间，0.58-0.82；P<.0001）、T2 肿瘤（总生存率，59.8%比 42.1%；危险比，0.63；95%置信区间，0.50-0.81；P<.0001）和 2-3cm 大小的肿瘤（总生存率，60.0%比 42.6%；危险比，0.64；95%置信区间，0.46-0.8；P=0.002）中均如此，但在肿瘤小于 2cm 时则不然。辅助胸部放疗与生存时间延长无关。亚肺叶切除术与肺叶切除术相比，总体生存率较差（危险比，1.40；95%置信区间，1.20-1.64；P<.0001）。倾向评分匹配证实了这些发现，但对于 2-3cm 大小的肿瘤，与生存的关联并不显著。
在这项针对早期大细胞神经内分泌癌的全国性研究中，AC 与肿瘤大于 3cm 且可能与肿瘤 2-3cm 相关的生存时间显著延长相关。辅助放疗与延长生存无关。
