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. 2018 Feb 15;13(2):e0192161.
doi: 10.1371/journal.pone.0192161. eCollection 2018.

The impact of EGFR mutations on the incidence and survival of stages I to III NSCLC patients with subsequent brain metastasis

Wei-Yuan Chang  1   2 , Yi-Lin Wu  3 , Po-Lan Su  1 , Szu-Chun Yang  1 , Chien-Chung Lin  1   2 , Wu-Chou Su  1   2
Affiliations

The impact of EGFR mutations on the incidence and survival of stages I to III NSCLC patients with subsequent brain metastasis

Wei-Yuan Chang et al. PLoS One. .

Abstract

Previous studies have demonstrated the association between EGFR mutations and distant metastasis. However, the association for subsequent brain metastasis (BM) in stages I-III non-small cell lung cancer (NSCLC) patients remains inconclusive. We conducted a retrospective analysis to clarify the impact of EGFR mutations on the incidence of BM and associated survival in patients with stage I-III NSCLC. A total of 491 patients screened for EGFR mutations were retrospectively enrolled. Brain MRI or CT was used to detect the BM. Cumulative incidence of subsequent BM and overall survival (OS) after diagnosis of BM were estimated by the Kaplan-Meier method and compared using log-rank test. We performed Cox proportional hazard regression for predictors of subsequent BM and determinants of OS after BM. The cumulative incidence of BM seemed higher in patients harboring EGFR mutations than those without EGFR mutations although it did not reach statistical significance (hazard ratio [HR] = 1.75, 95% confidence interval [CI] = 0.73~1.81). After adjusting possible confounders, including age, smoking, stage, and tumor size, EGFR mutation became one of the predictors for subsequent BM (HR = 1.89, 95% CI = 1.12~3.17, p = 0.017). Though there was no statistical difference in survival after BM between patients with EGFR mutations and wild-type EGFR (median survival: 17.8 vs. 12.2 months, HR = 0.79, 95% CI = 0.45-1.40), patients with EGFR 19 deletion (Del) tended to have a longer survival after BM than the non-EGFR 19 Del group (median survival: 29.4 vs. 14.3 months, HR 0.58, 95% CI = 0.32-1.09, p = 0.089). In conclusion, our data suggested EGFR mutation to be one of the predictors for subsequent BM in stage I-III patients. Given the small sample size, more studies are warranted to corroborate our results.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Cumulative incidence of brain metastasis (BM) in EGFR mutant versus wild-type patients.
Fig 2
Fig 2. Kaplan-Meier curve for overall survival in patients with mutant EGFR mutation versus those with wild type EGFR after the diagnosis of brain metastasis.
Fig 3
Fig 3. Kaplan-Meier estimations for overall survival in patients with different EGFR mutation status after the diagnosis of brain metastasis.
(A) Exon 19 deletions versus other mutations and wild-type. (B) Exon 19 versus other mutations and exon 19 deletions versus wild type EGFR.
See this image and copyright information in PMC

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