title: Neoadjuvant and adjuvant chemotherapy in resected pulmonary large cell neuroendocrine carcinomas: a single institution experience.
abstract: BACKGROUND
  Pulmonary large cell neuroendocrine carcinomas (LCNEC) are aggressive neoplasms with poor prognosis. The role of neoadjuvant and adjuvant therapies in these tumors remains uncertain.
  
  
  METHODS
  We performed a retrospective review of a prospective database. Kaplan-Meier estimates of overall survival (OS) were determined and compared across prognostic factors using log-rank analysis and the Cox proportional hazards model.
  
  
  RESULTS
  One hundred patients with resected LCNEC were identified from 1992 to 2008. Of these, 54% were male and 98% current or former smokers (mean 60.3 pack-years). Twenty-two patients received neoadjuvant platinum chemotherapy with a response rate of 68% (15 of 22). Eighty percent (80 of 100) underwent lobectomy and 11% (11 of 100) pneumonectomy with a 90% (90 of 100) complete resection (R0) rate. Seventy-one percent (71 of 100) were stage I-II, and 20 of 71 received platinum adjuvant chemotherapy. Mean OS was 40 months. Univariate factors associated with decreased OS included male gender (p = 0.007), increasing tumor (T) stage (p = 0.004), and stage III-IV disease (p = 0.04). Stage IB patients fared significantly worse than IA (p = 0.006). Multivariate analyses identified male gender (hazard ratio [HR] 2.3, p = 0.007), comorbid pulmonary disease (HR 2.3, p = 0.012), and pathologic stage (HR = 2.2, p = 0.011) as associated with risk of death. Univariate analysis in stage IB-IIIA completely resected (R0) patients receiving combination platinum-based induction and (or) adjuvant chemotherapy showed a trend toward improved OS (median survival 7.4 vs 2 years, p = 0.052).
  
  
  CONCLUSIONS
  The LCNEC has a high response rate to platinum-based neoadjuvant chemotherapy. Resected advanced-stage patients receiving combination neoadjuvant and (or) adjuvant chemotherapy may have a survival advantage. These therapies should be considered in resectable patients with LCNEC.
authors.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. sarkarii@mskcc.org
authors.forename: Inderpal S
authors.initials: IS
authors.lastname: Sarkaria
authors.forename: Akira
authors.initials: A
authors.lastname: Iyoda
authors.forename: Mee Soo
authors.initials: MS
authors.lastname: Roh
authors.forename: Gabriel
authors.initials: G
authors.lastname: Sica
authors.forename: Deborah
authors.initials: D
authors.lastname: Kuk
authors.forename: Camelia S
authors.initials: CS
authors.lastname: Sima
authors.forename: Maria C
authors.initials: MC
authors.lastname: Pietanza
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Park
authors.forename: William D
authors.initials: WD
authors.lastname: Travis
authors.forename: Valerie W
authors.initials: VW
authors.lastname: Rusch
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018287:Carcinoma, Large Cell / Q000175:diagnosis / Q000188:drug therapy* / Q000601:surgery; D017024:Chemotherapy, Adjuvant / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods; D009364:Neoplasm Recurrence, Local / Q000401:mortality; D018358:Neuroendocrine Tumors / Q000175:diagnosis / Q000188:drug therapy* / Q000601:surgery; D009518:New York / Q000453:epidemiology; D011013:Pneumonectomy; D012189:Retrospective Studies; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents