Usefulness of cumulative smoking dose for identifying the EGFR mutation and patients with non-small-cell lung cancer for gefitinib treatment

Masaru Jida, Shinichi Toyooka, Tetsuya Mitsudomi, Toshimi Takano, Keitaro Matsuo, Katsuyuki Hotta, Kazunori Tsukuda, Takafumi Kubo, Hiromasa Yamamoto, Masaomi Yamane, Takahiro Oto, Yoshifumi Sano, Katsuyuki Kiura, Yasushi Yatabe, Yuichiro Ohe, Hiroshi Date, Shinichiro Miyoshi

Research output: Contribution to journalArticle

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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. (Cancer Sci 2009; 100: 1931-1934).

Original languageEnglish
Pages (from-to)1931-1934
Number of pages4
JournalCancer Science
Volume100
Issue number10
DOIs
Publication statusPublished - Oct 2009

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Epidermal Growth Factor Receptor
Non-Small Cell Lung Carcinoma
Smoking
Mutation
Disease-Free Survival
Exons
ROC Curve
Survival
Therapeutics
Confidence Intervals
Sequence Deletion
gefitinib
Survival Rate
Sensitivity and Specificity
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Usefulness of cumulative smoking dose for identifying the EGFR mutation and patients with non-small-cell lung cancer for gefitinib treatment. / Jida, Masaru; Toyooka, Shinichi; Mitsudomi, Tetsuya; Takano, Toshimi; Matsuo, Keitaro; Hotta, Katsuyuki; Tsukuda, Kazunori; Kubo, Takafumi; Yamamoto, Hiromasa; Yamane, Masaomi; Oto, Takahiro; Sano, Yoshifumi; Kiura, Katsuyuki; Yatabe, Yasushi; Ohe, Yuichiro; Date, Hiroshi; Miyoshi, Shinichiro.

In: Cancer Science, Vol. 100, No. 10, 10.2009, p. 1931-1934.

Research output: Contribution to journalArticle

Jida, Masaru ; Toyooka, Shinichi ; Mitsudomi, Tetsuya ; Takano, Toshimi ; Matsuo, Keitaro ; Hotta, Katsuyuki ; Tsukuda, Kazunori ; Kubo, Takafumi ; Yamamoto, Hiromasa ; Yamane, Masaomi ; Oto, Takahiro ; Sano, Yoshifumi ; Kiura, Katsuyuki ; Yatabe, Yasushi ; Ohe, Yuichiro ; Date, Hiroshi ; Miyoshi, Shinichiro. / Usefulness of cumulative smoking dose for identifying the EGFR mutation and patients with non-small-cell lung cancer for gefitinib treatment. In: Cancer Science. 2009 ; Vol. 100, No. 10. pp. 1931-1934.
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AU - Takano, Toshimi

AU - Matsuo, Keitaro

AU - Hotta, Katsuyuki

AU - Tsukuda, Kazunori

AU - Kubo, Takafumi

AU - Yamamoto, Hiromasa

AU - Yamane, Masaomi

AU - Oto, Takahiro

AU - Sano, Yoshifumi

AU - Kiura, Katsuyuki

AU - Yatabe, Yasushi

AU - Ohe, Yuichiro

AU - Date, Hiroshi

AU - Miyoshi, Shinichiro

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N2 - 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. (Cancer Sci 2009; 100: 1931-1934).

AB - 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. (Cancer Sci 2009; 100: 1931-1934).

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