Outcomes for localized treatment of large cell neuroendocrine carcinoma of the lung in the United States

Abstract

Background: Treatment paradigms for large cell neuroendocrine carcinoma (LCNEC) of the lung are based largely upon small retrospective studies and smaller prospective trials. It is unclear if these tumors behave like non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC). Data are lacking with regard to the role of radiotherapy (RT). U. S. guidelines recommend that LCNEC be treated as a NSCLC.We sought to perform a cross-sectional study of LCNEC cases to understand treatment paradigms and outcomes in this disease. Methods:The Surveillance, Epidemiology and End Results database was queried for cases of stage I-III pulmonary LCNEC diagnosed 2004-2013. Treatment groups were defined as no surgery, RT alone, surgery alone, and surgery + RT. The Cox-proportional hazards regression model was used to compare overall survival and cause-specific survival (OS/CSS), stratified by AJCC 6th Staging. Factors that were significant on univariable analysis were included in multivariable analysis. Results:We identified 1,523 cases of LCNEC, with 748, 177, and 598 cases of stage I, II, and III disease, respectively. In stage I and II disease, RT was associated with improved survival for non-surgical patients, but not for those who underwent surgery. In stage I disease, the adjusted hazard ratios for OS for RT alone, surgery, and surgery + RT were 0.39, 0.21, and 0.22, respectively (P<0.001). In stage II disease, the adjusted hazard ratios for RT alone, surgery, and surgery + RT were 0.51 (P=0.15), 0.39 (P=0.004), and 0.38 (P=0.01), respectively. For patients with stage III disease, RT was associated with improved survival in surgical and non-surgical patients. The adjusted hazard ratios for RT alone, surgery, and surgery + RT were 0.49, 0.43, and 0.36, respectively (P<0.001). Conclusions:Our findings indicate that non-metastatic LCNEC may be treated as a NSCLC with respect to RT. Prospective studies are necessary to increase our understanding of optimal treatment regimens.

Surgical Principles in the Management of Lung Neuroendocrine Tumors: Open Questions and Controversial Technical Issues

“…Both the unadjusted and the multivariable analysis proved surgery to be associated with improved survival compared to chemoradiation (HR 0.68; 95%CI 0.56–0.82; p <0.001). Similar results are those found by Lo et al [ 89 ] and May et al [ 90 ] who both compared the outcomes of surgery vs SBRT in stage I patients with LCNEC, confirming surgery as the mainstay of therapy in early-stages large cells neoplasms. Different studies have also addressed the question about the proper extent of resection, by comparing lobar vs sublobar resections in stage I LCNEC.…”

“…[ 89 ] 2020 LCNEC R 39036 S SBRT 2971 238 6661 48.0 25.0 57.2 34.6 May et al . [ 90 ] 2021 LCNEC R 1523 S SBRT 666 82 748 <0.001 Sun et al . [ 102 ] 2021 LCNEC R 5068 S NS 394 60 454 <0.001 R retrospective, S surgery, ADJ adjuvant chemo/chemoradiotherapy, CRT definitive chemoradiotherapy, 5YOS five years overall survival, OS overall survival, mo months, NS non-surgery, SBRT stereotactic body radiation therapy …”

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

“…For instance, a recent study by Michael May et al indicate that radiation therapy offers significant benefit in stage I disease and possibly in stage II disease in patients who are not candidates for surgery or prefer nonoperative management. 30 This is probably because this analysis based on treatment is highly biased due to the patient selection and confounders, patients with better prognostic expectations will often receive more active antitumor treatment, and have better survival.…”

Pulmonary Neuroendocrine Neoplasms Overexpressing Epithelial-Mesenchymal Transition Mechanical Barriers Genes Lack Immune-Suppressive Response and Present an Increased Risk of Metastasis

“…Patients with PNENs have tumors sufficiently localized to be considered treatable by surgical resection, and among those whose tumors are successfully resected, approximately 90-98% of patients with typical carcinoid, and 50-60% of atypical carcinoid, survive 5 years ( 2 , 3 ) even developing local invasiveness, dissemination to regional lymph nodes, and distant metastasis ( 4 , 5 ) which occur in 3% of typical carcinoids and 21% for atypical carcinoids ( 6 – 8 ). In contrast, only 20-30% of the patients with large cell neuroendocrine carcinoma survive 5 years after surgical resection and adjuvant chemotherapy ( 9 ), and only 10% of the patients with small cell lung carcinoma survive 5 years after Cisplatin + Carboplatin + Etoposide ( 10 ).…”