title: Large Cell Neuroendocrine Carcinoma of the Lung: Clinico-Pathologic Features, Treatment, and Outcomes.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Upper Aerodigestive Division, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD. Electronic address: jnaidoo1@jhmi.edu.
authors.forename: Jarushka
authors.initials: J
authors.lastname: Naidoo
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Maria L
authors.initials: ML
authors.lastname: Santos-Zabala
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Tunc
authors.initials: T
authors.lastname: Iyriboz
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Kaitlin M
authors.initials: KM
authors.lastname: Woo
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Camelia S
authors.initials: CS
authors.lastname: Sima
authors.affiliation: Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Medicine, Weill Cornell Medical College, New York, NY.
authors.forename: John J
authors.initials: JJ
authors.lastname: Fiore
authors.affiliation: Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Medicine, Weill Cornell Medical College, New York, NY.
authors.forename: Mark G
authors.initials: MG
authors.lastname: Kris
authors.affiliation: Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Medicine, Weill Cornell Medical College, New York, NY.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Riely
authors.affiliation: Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Medicine, Weill Cornell Medical College, New York, NY.
authors.forename: Piro
authors.initials: P
authors.lastname: Lito
authors.affiliation: Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Medicine, Weill Cornell Medical College, New York, NY.
authors.forename: Afsheen
authors.initials: A
authors.lastname: Iqbal
authors.affiliation: Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Medicine, Weill Cornell Medical College, New York, NY.
authors.forename: Stephen
authors.initials: S
authors.lastname: Veach
authors.affiliation: Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Medicine, Weill Cornell Medical College, New York, NY.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Smith-Marrone
authors.affiliation: Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA.
authors.forename: Inderpal S
authors.initials: IS
authors.lastname: Sarkaria
authors.affiliation: Department of Immuno-Oncology, Bristol Myers-Squibb, New York, NY.
authors.forename: Lee M
authors.initials: LM
authors.lastname: Krug
authors.affiliation: Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Medicine, Weill Cornell Medical College, New York, NY.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Rudin
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: William D
authors.initials: WD
authors.lastname: Travis
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Natasha
authors.initials: N
authors.lastname: Rekhtman
authors.affiliation: Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Medicine, Weill Cornell Medical College, New York, NY.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Pietanza
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000453:epidemiology / Q000556:secondary; D018287:Carcinoma, Large Cell / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D018278:Carcinoma, Neuroendocrine / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D011379:Prognosis; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D012189:Retrospective Studies; D012907:Smoking / Q000453:epidemiology; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: C117307:KRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)
keywords: Brain metastases; KRAS mutation; Platinum-etoposide chemotherapy; Small cell lung carcinoma; Stage IV