title: Epidermal growth factor receptor mutation is associated with longer local control after definitive chemoradiotherapy in patients with stage III nonsquamous non-small-cell lung cancer.
abstract: OBJECTIVE
  To determine the frequency and clinical significance of epidermal growth factor receptor (EGFR) mutations in patients with potentially curable stage III non-small-cell lung cancer (NSCLC) who are eligible for definitive chemoradiotherapy (CRT).
  
  
  METHODS
  Between January 2001 and December 2010, we analyzed the EGFR mutational status in consecutive NSCLC patients who were treated by CRT. The response rate, relapse-free survival, 2-year relapse-free rate, initial relapse sites, and overall survival of the patients were investigated.
  
  
  RESULTS
  A total of 528 patients received CRT at our hospital during the study period. Of these, 274 were diagnosed as having nonsquamous NSCLC. Sufficient specimens for mutational analyses could be obtained from 198 of these patients. The proportion of patients with EGFR activating mutations was 17%. In addition to the well-known characteristics of patients carrying EGFR mutations (female, adenocarcinoma, and never/light smoker), the proportion of cases with smaller primary lesions (T1/2) was found to be higher in patients with EGFR mutations than in those with wild-type EGFR. Patients with EGFR mutations showed similar response rate, relapse-free survival, and 2-year relapse-free rates as compared to patients with wild-type EGFR. Local relapses as the site of initial relapse occurred significantly less frequently in patients with EGFR mutation (4% vs 21%; P=.045). Patients with EGFR mutations showed longer local control (adjusted hazard ratio 0.49; P=.043). After disease progression, a majority of the patients with EGFR mutations received EGFR tyrosine kinase inhibitors (62%), and these patients showed longer postprogression survival than those with wild-type EGFR.
  
  
  CONCLUSIONS
  Our study is the first to show radiosensitive biology of EGFR-mutated tumors in definitive CRT with curative intent. This finding could serve as a credible baseline estimate of EGFR-mutated population in stage III nonsquamous NSCLC.
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Shigehiro
authors.initials: S
authors.lastname: Yagishita
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan. Electronic address: hhorinou@ncc.go.jp.
authors.forename: Hidehito
authors.initials: H
authors.lastname: Horinouchi
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Katsui Taniyama
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Nakamichi
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Kitazono
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Mizugaki
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Kanda
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Fujiwara
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nokihara
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Noboru
authors.initials: N
authors.lastname: Yamamoto
authors.affiliation: Department of Radiation Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Minako
authors.initials: M
authors.lastname: Sumi
authors.affiliation: Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Kouya
authors.initials: K
authors.lastname: Shiraishi
authors.affiliation: Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kohno
authors.affiliation: Department of Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Koh
authors.initials: K
authors.lastname: Furuta
authors.affiliation: Department of Pathology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Tsuta
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Tomohide
authors.initials: T
authors.lastname: Tamura
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016190:Carboplatin; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D059248:Chemoradiotherapy; D002945:Cisplatin / Q000008:administration & dosage; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011836:Radiation Tolerance / Q000235:genetics*; D011879:Radiotherapy Dosage; D012737:Sex Factors; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine
chemical_list: D047428:Protein Kinase Inhibitors; D014747:Vinblastine; D016190:Carboplatin; D066246:ErbB Receptors; D017239:Paclitaxel; D002945:Cisplatin; D000077235:Vinorelbine