Usefulness of cumulative smoking dose for identifying the EGFR mutation and patients with non-small-cell lung cancer for gefitinib treatment.
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.
Jida
Masaru
M
Departments of Cancer and Thoracic Surgery, Graduate School of Medicine, Okayama University, Kita-ku, Okayama, Japan.
Toyooka
Shinichi
S
Mitsudomi
Tetsuya
T
Takano
Toshimi
T
Matsuo
Keitaro
K
Hotta
Katsuyuki
K
Tsukuda
Kazunori
K
Kubo
Takafumi
T
Yamamoto
Hiromasa
H
Yamane
Masaomi
M
Oto
Takahiro
T
Sano
Yoshifumi
Y
Kiura
Katsuyuki
K
Yatabe
Yasushi
Y
Ohe
Yuichiro
Y
Date
Hiroshi
H
Miyoshi
Shinichiro
S
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*
D000970:Antineoplastic Agents; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib