title: EGFR Mutation Impact on Definitive Concurrent Chemoradiation Therapy for Inoperable Stage III Adenocarcinoma.
abstract: BACKGROUND
  Concurrent chemoradiation therapy (CRT) is the current standard of care for patients with locally advanced lung adenocarcinoma; however, little has been reported about the impact of epidermal growth factor receptor (EGFR) mutation on CRT efficacy.
  
  
  METHODS
  From 2006 to 2013, we retrospectively screened 104 unresectable stage III adenocarcinoma patients who were examined for EGFR mutation status and received definitive concurrent CRT consisting of platinum doublet chemotherapy in first-line setting and compared the clinical outcomes and recurrence patterns according to mutation status.
  
  
  RESULTS
  Among 104 patients, EGFR mutation was detected in 29 (28%). The overall response rate did not differ between EGFR-mutant and wild-type patients (72.4% versus 72.0%, p = 0.607). The median progression-free survival in concurrent CRT was significantly shorter in EGFR-mutant patients than in wild-type patients (9.8 [95% confidence interval, CI: 7.6-19.0] versus 16.5 [95% CI: 11.8-19.9] months, p = 0.041). The 2-year recurrence-free survival rate was 7.7% and 28.1% in EGFR-mutant and wild-type patients, respectively (p = 0.028). Distant metastases were more frequently identified as the first recurrence site in EGFR-mutant patients than in wild-type patients (76% versus 40%, p = 0.001). The brain was the most often affected site in EGFR-mutant patients (35%). However, locoregional recurrence was less common in EGFR-mutant patients than in the wild-type population (14% versus 35%, p = 0.027). Overall survival was similar between EGFR-mutant and wild-type patients (51.1 [95% CI: 28.2-70.2] versus 42.9 [95% CI: 35.3 to not available] months, p = 0.637). Among the EGFR wild-type population who were examined for Kras mutation, Kras-mutant patients had significantly worse overall survival than Kras wild-type patients (21.6 versus 49.8 months, p = 0.024).
  
  
  CONCLUSIONS
  Concurrent CRT resulted in shorter progression-free survival in EGFR-mutant stage III adenocarcinoma patients than in wild-type patients, mainly because of distant metastasis relapse, regardless of better local control. Because of these distinct biological features, a different strategy, including EGFR-tyrosine kinase inhibitors for EGFR-mutant locally advanced adenocarcinoma patients receiving definitive CRT may be needed.
authors.affiliation: Department of Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya, Japan; Division of Molecular Oncology, Aichi Cancer Center Research Institute, Nagoya, Japan. Electronic address: kosuke624t@gmail.com.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Department of Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Hida
authors.affiliation: Department of Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Oya
authors.affiliation: Department of Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
authors.forename: Tomoyo
authors.initials: T
authors.lastname: Oguri
authors.affiliation: Department of Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Yoshida
authors.affiliation: Department of Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Shimizu
authors.affiliation: Department of Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Horio
authors.affiliation: Division of Integrated Oncology, Institute of Biomedical Research and Innovation, Kobe-City, Hyogo, Japan.
authors.forename: Akito
authors.initials: A
authors.lastname: Hata
authors.affiliation: Division of Integrated Oncology, Institute of Biomedical Research and Innovation, Kobe-City, Hyogo, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Kaji
authors.affiliation: Division of Integrated Oncology, Institute of Biomedical Research and Innovation, Kobe-City, Hyogo, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Fujita
authors.affiliation: Division of Molecular Oncology, Aichi Cancer Center Research Institute, Nagoya, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Sekido
authors.affiliation: Department of Radiation Oncology, Aichi Cancer Center Hospital, Nagoya, Japan; Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kodaira
authors.affiliation: Department of Radiation Oncology, Kobe City Medical Center General Hospital, Kobe-city, Hyogo, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Kokubo
authors.affiliation: Division of Integrated Oncology, Institute of Biomedical Research and Innovation, Kobe-City, Hyogo, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Katakami
authors.affiliation: Division of Integrated Oncology, Institute of Biomedical Research and Innovation, Kobe-City, Hyogo, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Yatabe
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D059248:Chemoradiotherapy; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D012189:Retrospective Studies
chemical_list: C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Chemoradiation therapy; EGFR mutation; Locally advanced NSCLC; Lung adenocarcinoma