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BMC Cancer. 2018 Jul 28;18(1):768. doi: 10.1186/s12885-018-4691-0.

Cumulative smoking dose affects the clinical outcomes of EGFR-mutated lung adenocarcinoma patients treated with EGFR-TKIs: a retrospective study.

Kim IA1,2, Lee JS1, Kim HJ1,2, Kim WS1,3, Lee KY4,5.

Author information

1
Lung Cancer Center, Konkuk University Medical Center, 120-1 Hwayang-dong, Gwangjin-Gu, Seoul, 05030, Republic of Korea.
2
Department of Pulmonary Medicine, Konkuk University School of Medicine, 120-1 Hwayang-dong, Gwangjin-Gu, Seoul, 05030, Republic of Korea.
3
Department of Pathology, Konkuk University School of Medicine, Seoul, Republic of Korea.
4
Lung Cancer Center, Konkuk University Medical Center, 120-1 Hwayang-dong, Gwangjin-Gu, Seoul, 05030, Republic of Korea. kyleemd@kuh.ac.kr.
5
Department of Pulmonary Medicine, Konkuk University School of Medicine, 120-1 Hwayang-dong, Gwangjin-Gu, Seoul, 05030, Republic of Korea. kyleemd@kuh.ac.kr.

Abstract

BACKGROUND:

Although lung adenocarcinoma with activating epidermal growth factor receptor (EGFR) mutations is common in never smokers, one-third of the patients are ever-smokers. We aimed to investigate the effect of cumulative smoking dose(CSD) on clinical outcomes, including progression-free survival (PFS) and overall survival (OS), in patients with EGFR-mutated lung adenocarcinoma receiving EGFR-tyrosine kinase inhibitors (TKIs).

METHODS:

We retrospectively analyzed 142 patients with EGFR-mutation positive advanced or recurrent lung adenocarcinoma who were administered gefitinib, erlotinib, afatinib, and osimertinib. These patients were classified based on their CSD as never smokers, light smokers (≤10 pack-years [PYs]), moderate smokers (11-30 PYs), and heavy smokers (> 30 PYs). PFS and OS were analyzed according to smoking subgroups via Kaplan-Meier curves.

RESULTS:

Among the 142 patients, 91 (64.1%), 12 (8.5%), 22 (15.5%), and 17 (12%) were never, light, moderate, and heavy smokers, respectively. CSD was inversely associated with median PFS in a statistically significant dose-dependent manner (11.8 months (mo), 11.0 mo, 7.4 mo, and 3.9 mo; p < 0.001). Statistically significant negative association was observed between CSD and median OS (33.6 mo, 26.3 mo, 20 mo, and 8.9 mo; p < 0.001). In the multivariate analysis adjusted for age, sex, performance status, stage, and timing of EGFR-TKIs, CSD was an independent predictive factor for disease progression (hazard ratio [HR], 4.00; 95% confidence interval [CI], 1.95-8.23; p = 0.012) and OS (HR, 3.9; 95% CI, 1.84-8.28; p < 0.001).

CONCLUSION:

CSD is an important predictive and prognostic factor in patients with EGFR-mutated lung adenocarcinoma, and associated smoking-related gene signatures might affect the outcomes.

KEYWORDS:

Cumulative smoking dose; EGFR mutations; EGFR-TKIs; Lung adenocarcinoma; Prognosis

PMID:
30055587
PMCID:
PMC6064083
DOI:
10.1186/s12885-018-4691-0
[Indexed for MEDLINE]
Free PMC Article

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