title: Superior Treatment Response and In-field Tumor Control in Epidermal Growth Factor Receptor-mutant Genotype of Stage III Nonsquamous Non-Small cell Lung Cancer Undergoing Definitive Concurrent Chemoradiotherapy.
abstract: Although previous in vitro data have suggested a more radio-sensitive nature of epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) cell lines, the clinical behavior according to the EGFR mutational status has not been well-established. In this study, we performed a comparative outcome analysis of EGFR-mutant and wild-type locally advanced NSCLC with chemoradiotherapy (CRT).
  
  
  
  A total of 102 patients with stage III nonsquamous NSCLC undergoing primary CRT were identified. Clinicopathologic characteristics, including the degree of glucose uptake, were evaluated. Failure patterns considering the radiation field and survival outcomes were compared according to the EGFR mutational status.
  
  
  
  Pre- and post-CRT maximum standardized uptake values were significantly lower in EGFR-mutant tumors (P = .010 and .018, respectively). The overall response rate was higher in the EGFR-mutant group compared with the wild-type (89% vs. 64%, respectively; P = .023). The 3-year overall survival rate was better with the genetic alteration (68.0% vs. 47.4%, P = .046), but the statistical significance did not remain in multivariate analysis (hazard ratio, 0.68; 95% confidence interval, 0.30-1.55). Considering the tumor progression inside or outside the radiation field, the EGFR-mutant group showed longer in-field time to progression (P = .002), even after adjusting for other related baseline variables (hazard ratio, 0.27; 95% confidence interval, 0.11-0.71).
  
  
  
  The differential metabolic activity, failure patterns, and prognosis suggest the distinct nature of the EGFR-mutant tumors. EGFR mutational status needs to be considered for more precise curative-intent treatment strategies of locally advanced nonsquamous NSCLC.
authors.affiliation: Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Yu Jin
authors.initials: YJ
authors.lastname: Lim
authors.affiliation: Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Chang
authors.affiliation: Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Hak-Jae
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Bhumsuk
authors.initials: B
authors.lastname: Keam
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Tae Min
authors.initials: TM
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Dong-Wan
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jin Chul
authors.initials: JC
authors.lastname: Paeng
authors.affiliation: Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea; Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul, Korea.
authors.forename: Keon Wook
authors.initials: KW
authors.lastname: Kang
authors.affiliation: Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea; Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul, Korea.
authors.forename: June-Key
authors.initials: JK
authors.lastname: Chung
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Yoon Kyung
authors.initials: YK
authors.lastname: Jeon
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Doo Hyun
authors.initials: DH
authors.lastname: Chung
authors.affiliation: Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea; Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul, Korea. Electronic address: wuhg@snu.ac.kr.
authors.forename: Hong-Gyun
authors.initials: HG
authors.lastname: Wu
mesh_terms: D054316:Biomarkers, Pharmacological / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009367:Neoplasm Staging; D018579:Patient Selection; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D054316:Biomarkers, Pharmacological; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Chemoradiation; Epidermal growth factor receptor mutation; Local neoplasm recurrence; Non-small cell lung cancer; Radiation field