title: Usefulness of cumulative smoking dose for identifying the EGFR mutation and patients with non-small-cell lung cancer for gefitinib treatment.
abstract: We examined the diagnostic accuracy of the cumulative smoking dose for identifying the epidermal growth factor receptor (EGFR) exon 19 deletion and L858R mutation among Japanese patients with non-small-cell lung cancer (NSCLC). EGFR mutations in exon 19 and exon 21 were determined in 1001 NSCLC patients. A receiver-operating characteristic (ROC) curve methodology was applied to estimate the diagnostic accuracy. EGFR mutations were detected in 314 patients (31.4%). A cumulative smoking dose of less than 13 pack-years (PY) was the optimal cut-off point for predicting a positive EGFR mutation status, producing a balance between the sensitivity (73.5%) and the specificity (77%). The area under the ROC curve was 0.77, indicating that the smoking dose had a moderate diagnostic accuracy. The median survival time or the median progression-free survival time of patients who had smoked less than 13 pack-years (PY) were 18.6 and 6.3 months, respectively, while those of patients with equal to or more than 13 PY were 9.6 and 2.4 months, respectively. The overall survival (OS) and progression-free survival (PFS) rates were significantly different between the two groups (OS: hazard ratio [HR] = 0.64, 95% confidence interval [CI] = 0.51-0.80, P = 0.0001) (PFS: HR = 0.58, 95% CI = 0.47-0.71, P < 0.0001). Our study indicated that the smoking dose predicted EGFR mutations with a moderate diagnostic accuracy. Thus, patients who have smoked less than 13 PY might be candidates for gefitinib treatment when EGFR mutation status cannot be determined.
authors: Departments of Cancer and Thoracic Surgery, Graduate School of Medicine, Okayama University, Kita-ku, Okayama, Japan.
authors: Masaru
authors: M
authors: Jida
authors: Shinichi
authors: S
authors: Toyooka
authors: Tetsuya
authors: T
authors: Mitsudomi
authors: Toshimi
authors: T
authors: Takano
authors: Keitaro
authors: K
authors: Matsuo
authors: Katsuyuki
authors: K
authors: Hotta
authors: Kazunori
authors: K
authors: Tsukuda
authors: Takafumi
authors: T
authors: Kubo
authors: Hiromasa
authors: H
authors: Yamamoto
authors: Masaomi
authors: M
authors: Yamane
authors: Takahiro
authors: T
authors: Oto
authors: Yoshifumi
authors: Y
authors: Sano
authors: Katsuyuki
authors: K
authors: Kiura
authors: Yasushi
authors: Y
authors: Yatabe
authors: Yuichiro
authors: Y
authors: Ohe
authors: Hiroshi
authors: H
authors: Date
authors: Shinichiro
authors: S
authors: Miyoshi
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019540:Area Under Curve; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D000077156:Gefitinib; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008297:Male; D009154:Mutation; D011799:Quinazolines / Q000627:therapeutic use*; D012372:ROC Curve; D012680:Sensitivity and Specificity; D012907:Smoking / Q000009:adverse effects / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib