Large Cell Neuroendocrine Carcinoma of the Lung: Clinico-Pathologic Features, Treatment, and Outcomes

Clin Lung Cancer. 2016 Sep;17(5):e121-e129. doi: 10.1016/j.cllc.2016.01.003. Epub 2016 Jan 21.


Background: Large cell neuroendocrine carcinoma (LCNEC) accounts for approximately 3% of lung cancers. Pathologic classification and optimal therapies are debated. We report the clinicopathologic features, treatment and survival of a series of patients with stage IV LCNEC.

Materials and methods: Cases of pathologically-confirmed stage IV LCNEC evaluated at Memorial Sloan Kettering Cancer Center from 2006 to 2013 were identified. We collected demographic, treatment, and survival data. Available radiology was evaluated by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria.

Results: Forty-nine patients with stage IV LCNEC were identified. The median age was 64 years, 63% of patients were male, and 88% were smokers. Twenty-three patients (n = 23/49; 47%) had brain metastases, 17 at diagnosis and 6 during the disease course. Seventeen LCNEC patients (35%) had molecular testing, of which 24% had KRAS mutations (n = 4/17). Treatment data for first-line metastatic disease was available on 37 patients: 70% (n = 26) received platinum/etoposide and 30% (n = 11) received other regimens. RECIST was completed on 23 patients with available imaging; objective response rate was 37% (95% confidence interval, 16%-62%) with platinum/etoposide, while those treated with other first-line regimens did not achieve a response. Median overall survival was 10.2 months (95% confidence interval, 8.6-16.4 months) for the entire cohort.

Conclusion: Patients with stage IV LCNEC have a high incidence of brain metastases. KRAS mutations are common. Patients with stage IV LCNEC do not respond as well to platinum/etoposide compared with historic data for extensive stage small-cell lung cancer; however, the prognosis is similar. Prospective studies are needed to define optimum therapy for stage IV LCNEC.

Keywords: Brain metastases; KRAS mutation; Platinum-etoposide chemotherapy; Small cell lung carcinoma; Stage IV.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Brain Neoplasms / epidemiology
  • Brain Neoplasms / secondary
  • Carcinoma, Large Cell / drug therapy
  • Carcinoma, Large Cell / genetics
  • Carcinoma, Large Cell / pathology*
  • Carcinoma, Neuroendocrine / drug therapy
  • Carcinoma, Neuroendocrine / genetics
  • Carcinoma, Neuroendocrine / pathology*
  • Female
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm Staging
  • Prognosis
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Retrospective Studies
  • Smoking / epidemiology
  • Survival Rate
  • Treatment Outcome


  • KRAS protein, human
  • Proto-Oncogene Proteins p21(ras)