title: Circulating cell-free DNA in plasma of never smokers with advanced lung adenocarcinoma receiving gefitinib or standard chemotherapy as first-line therapy.
abstract: OBJECTIVE
  Circulating cell-free DNA (CFDNA) was investigated as potential screening or prognostic markers in a variety of cancers. This study investigated its clinical significance in a homogeneous group of lung cancer patients.
  
  
  METHODS
  We analyzed the blood samples of 134 never smokers with advanced lung adenocarcinoma, who were enrolled in a prospective randomized phase III study (First-SIGNAL) comparing gefitinib with gemcitabine plus cisplatin (GP) as first-line therapy. The amount of plasma CFDNA was measured by real-time quantitative PCR targeting the human ACTB genomic sequence. The patients were divided into three groups according to the tertiles of baseline plasma CFDNA.
  
  
  RESULTS
  Baseline plasma CFDNA did not correlate with primary tumor size (P = 0.961), whereas the number of metastatic sites correlated significantly with baseline plasma CFDNA (P = 0.015). In the GP arm, the low-CFDNA group showed a lower response rate than the middle- or high-CFDNA group (26.1%, 57.9%, and 60.9%, respectively; P = 0.035). However, in the gefitinib arm, there was no difference in response rate between the three CFDNA groups (57.1%, 47.4%, and 51.9%; respectively; P = 0.825). The high tertile CFDNA group showed a significantly shorter survival than the low tertile CFDNA group (median overall survival, 16.0 vs. 28.6 months, respectively; P = 0.030). The risk of death increased with increased baseline plasma CFDNA (HR = 1.23, 95% CI, 1.01-1.50; P = 0.045).
  
  
  CONCLUSIONS
  High plasma CFDNA is associated with aggressive tumor behavior and poor survival outcomes in these patients.
authors.affiliation: Center for Lung Cancer and Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea.
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Lee
authors.forename: Kyong-Ah
authors.initials: KA
authors.lastname: Yoon
authors.forename: Ji-Youn
authors.initials: JY
authors.lastname: Han
authors.forename: Heung Tae
authors.initials: HT
authors.lastname: Kim
authors.forename: Tak
authors.initials: T
authors.lastname: Yun
authors.forename: Geon Kook
authors.initials: GK
authors.lastname: Lee
authors.forename: Hyae Young
authors.initials: HY
authors.lastname: Kim
authors.forename: Jin Soo
authors.initials: JS
authors.lastname: Lee
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002474:Cell-Free System; D004247:DNA / Q000097:blood*; D005260:Female; D000077156:Gefitinib; D018773:Genes, erbB-1; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D011799:Quinazolines / Q000627:therapeutic use*; D012907:Smoking; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D004247:DNA; D000077156:Gefitinib