title: Impact of the oncogenic status on the mode of recurrence in resected non-small cell lung cancer.
abstract: OBJECTIVE
  Surgical resection is employed in patients with resectable non-small cell lung cancer. Despite complete resection, recurrence is sometimes observed. Oncogenic mutations promote initiation and progression of lung cancer, and mutation status predicts treatment outcome of advanced non-small cell lung cancer; however, their impact on the recurrence patterns remains poorly understood.
  
  
  METHODS
  We retrospectively studied 401 patients showing recurrence after complete resection of non-small cell lung cancer. Clinicopathological factors were reviewed for time to recurrence, and recurrence patterns were compared according to oncogenic status and examined according to EGFR mutational subtype.
  
  
  RESULTS
  Among 401 patients, 185 with EGFR mutation, 46 with KRAS mutation, 15 with ALK rearrangement and 155 with triple-negative mutation were identified. Multivariate analysis following univariate analyses showed that younger age, well-moderately-differentiated histology, earlier pathologic stage and presence of EGFR or ALK mutation were favorable prognostic factors for time to recurrence. Locoregional recurrence was observed in 53.3% of ALK-positive patients, being significantly common in these patients than in EGFR- and KRAS-positive patients. EGFR-positive patients mostly experienced pleural recurrence, the incidence of which was significantly higher in triple-negative mutation patients. Adrenal recurrence was observed in 7.2% of triple-negative mutation patients, but it was rarely identified in EGFR-positive patients. Among EGFR-positive patients, the incidence of brain metastases was significantly higher in L858R cohort than in Del Ex19 cohort.
  
  
  CONCLUSIONS
  In resected non-small cell lung cancer, younger age, well-moderately-differentiated histology, earlier pathologic stage and presence of EGFR or ALK mutation were favorable factors for TTR, and distinct recurrence patterns were revealed according to oncogenic mutation status and mutational EGFR subtype. Our results may provide suggestions for developing a strategy for follow-up and adjuvant therapies after resection.
authors.affiliation: Division of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mizuno
authors.affiliation: Division of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Yatabe
authors.affiliation: Division of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kuroda
authors.affiliation: Division of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Sakakura
authors.affiliation: Division of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya ysakao@aichi-cc.jp.
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Sakao
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000077548:Anaplastic Lymphoma Kinase; D063646:Carcinogenesis; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology* / Q000601:surgery; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D016016:Proportional Hazards Models; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D012189:Retrospective Studies; D016896:Treatment Outcome; D018631:ras Proteins / Q000235:genetics
chemical_list: C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D018631:ras Proteins
keywords: ALK; EGFR; KRAS; oncogenic status; recurrence