Prognosis of EGFR-mutant advanced lung adenocarcinoma patients with different intrathoracic metastatic patterns

Abstract

Introduction: Lung cancer diagnosed solely with the presence of intrathoracic metastases is classified as M1a. However, intrathoracic metastases can be further divided into different patterns. The objective of our study was to analyze the differences in survival between the different metastatic patterns of intrathoracic metastases in lung adenocarcinoma patients who have epidermal growth factor receptor (EGFR) mutations. Materials and Methods: Patients who were diagnosed only with intrathoracic metastasis between March 2011 and October 2016 and had EGFR-mutations were selected for this study. Prognosis was determined based on metastatic patterns by univariate and multivariate analysis. Results: A total of 137 patients (60 patients who only had pleural metastasis [Group A], 44 patients who only had contralateral lung metastasis [Group B] and 33 patients who had both pleural and contralateral lung metastasis with or without pericardial effusion [Group C]) were selected for this in the study. The median OS (overall survival) time was 38.1 (95%confidence interval [CI]: 27.8-48.4), 35.7(95%CI: 23.4-48.0), and 29.7(95%CI: 22.8-36.6) months for Group A, Group B, and Group C, respectively (p=0.037). Multivariate analysis demonstrated that Group A and Group B had higher OS compared to Group C (hazard ratio [HR]=0.524, 95%CI: 0.307-0.894, p=0.018; HR=0.473, 95%CI: 0.241-0.931, p=0.030, respectively) among lung adenocarcinoma patients with EGFR mutations. With regard to patients with pleural or contralateral metastasis only, OS benefit (p=0.579) was not significant between the two groups. Subgroup analysis demonstrated that OS benefit in Group A was significant in patients with N0-1 disease and 21L858R mutations but not in EGFR exon 19 deletions, N2-3 stage or T3-4 stage patients. Conclusion: The prognosis of EGFR-mutant lung adenocarcinoma patients diagnosed only with intrathoracic metastasis was different, indicating that M1a staging should be refined.

Keywords: adenocarcinoma; intrathoracic metastases; overall survival..

Figure 1

OS for Group A, Group B and Group C patients. Abbreviations: OS, overall survival.

Figure 2

OS survival curve for patients with and without pleural effusion. Abbreviations: OS, overall survival

Figure 3

Forest Plot of Cox Proportional Hazard Multivariable Modeling on Overall Survival for lung adenocarcinoma patients with EGFR mutation who received EGFR-TKI. The covariates that are adjusted in the multivariate Cox model included metastasis site, age, sex, smoking status, EGFR mutation status, LCT history, primary lung cancer treatment, T stage, N stage, different lines of EGFR TKIs, brain metastasis and treatment with Osimertinib. Abbreviations: EGFR, epidermal growth factor receptor; TKI, tyrosine kinase inhibitor; LCT, local consolidative therapy; HR, hazard ratios.

Figure 4

PFS for first-line EGFR-TKIs for Group A, Group B, and Group C patients. Abbreviations: PFS, progression-free survival.

Figure 5

OS for Group A, Group B and Group C among the subgroups of T1-2 (A), T3-4 (B), N0-1 (C) and N2-3 (D) patients. Abbreviations: OS, overall survival.