Clinical Features and Outcomes Analysis of Surgical Resected Pulmonary Large-Cell Neuroendocrine Carcinoma With Adjuvant Chemotherapy

Abstract

ObjectiveLarge-cell neuroendocrine carcinoma (LCNEC) is a rare subtype of pulmonary cancer with poor survival. Optimal adjuvant chemotherapy for resected LCNEC is controversial till now; clinical features together with the prognostic factors in LCNEC should be clarified better.MethodsClinicopathological characteristics, driven genes’ status (EGFR, ALK, and ROS1), adjuvant chemotherapy strategy for 94 surgical resected LCNECs were extracted from digital database, tumor relapse or progression, and survival were analyzed with clinical profiles.ResultsDriven gene mutants were scarce in LCNEC, 8.3% (4/48) samples harbored EGFR mutations, 5.8% (3/52) with ALK positive, and none of ROS1 positive. A total of 44 patients suffered tumor relapse or progression during follow-up. Tumor/lymph node (N) stage, serum carcinoembryonic antigen (CEA) level before surgery, different adjuvant chemotherapies were associated with tumor relapse (P < 0.05); poorer disease-free survival (DFS) appeared in N2/stage III, serum CEA positive and pemetrexed based chemotherapy (P < 0.05); for overall survival (OS) analysis, the T/tumor stage, serum positive CEA/neuron-specific enolase (NSE) at baseline were associated with worse OS (P < 0.05). Moreover, in the multivariate analysis, N stage still acted as prognostic for DFS (P = 0.019); OS differed significantly in different T stages, chemotherapy selection and serum CEA levels after adjustment (P < 0.05).ConclusionClassical driven gene mutations were rare in LCNEC. Tumor N stage appeared as prognostic for DFS, while serum positive CEA, different adjuvant chemotherapy strategies, and T stage were independent prognostic factors for OS. Etoposide–platinum regime seemed to be a better choice which should be confirmed by further prospective investigations.

A Clinical Nomogram for Predicting Cancer-Specific Survival in Pulmonary Large-Cell Neuroendocrine Carcinoma Patients: A Population-Based Study

“…24 Our study confirms the predictive value of surgery and chemotherapy for prognosis in patients with LCNEC. Surgical management is recommended in early-stage patients, postoperative adjuvant chemotherapy can improve overall survival, 25 however, comparative data between the different type of surgical procedures remain scant. Chemotherapy is the main treatment for advanced patients, including NSCLC chemotherapy regimens (platinum-based combined gemcitabine, docetaxel, paclitaxel, vinorelbine or pemetrexed) and small cell lung carcinoma (SCLC) chemotherapy regimens (etoposide-based chemotherapy).…”

Pulmonary Combined Large Cell Neuroendocrine Carcinoma

“…In addition, LCNEC combined with SCLC part was classified as a type of combined SCLC [ 14 ]. More than 10% of LCNEC patients were diagnosed with CLCNEC before the first treatment [ 15 , 16 ].…”

Management of Large Cell Neuroendocrine Carcinoma

“…In this study EGFR mutants were detected from peripheral blood with an amplification refractory mutation system (ARMS) and anaplastic lymphoma kinase (ALK) rearrangement was detected by immunohistochemistry. They found driver mutations including epidermal growth factor receptor (EGFR) (8.3%), anaplastic lymphoma kinase (ALK) (5.8%) (58). Given the limited number of cases the percentage of patients with ALK-mutated LCNEC that respond to tyrosine kinase inhibitor (TKI) treatment is not known.…”