Abstract
Liver metastases are associated with poor prognosis in non-small cell lung cancer patients. In this study, we explored the relationship between EGFR mutation status, incidence of liver metastases within one year of stage IV diagnosis, and overall survival in an unselected lung adenocarcinoma real-world population. Stage IV lung adenocarcinoma patients routinely tested for EGFR and ALK molecular alterations between 2014-2016 were included in this retrospective cohort analysis. Patients with ALK-rearrangements were excluded in this analysis. Clinico-demographic and pathologic data was abstracted from electronic patient records. Continuous variables were evaluated using the Mann-Whitney’s U test and categorical variables with the chi-squared test. Multivariable analyses were performed to obtain adjusted hazard ratios (aHR) for overall survival. Of 642 stage IV patients, 207 (30.4%) had EGFR-mutated tumors and 435 (64%) had wild-type (EGFR/ALK-negative) tumors. 31/207 (15%) patients with EGFR-mutated tumors and 72/435 (17%) patients with wildtype tumors developed one or more liver metastases within one year of stage IV diagnosis. Liver metastases were associated with statistically significant reduction in overall survival in the wildtype group (p<0.001; Figure 1); there was a trend of reduced overall survival in patients with EGFR-mutated tumors and liver metastases (p=0.11; Figure 2). The aHR for overall survival in the wildtype group was 1.77 (95%CI:1.31-2.41) while in the EGFR-positive group, the aHR was 1.63 (95%CI:0.96-2.77). Among the 103 patients with liver metastases, overall survival was non-significantly better in patients with EGFR mutations (aHR 0.63; 95%CI:0.28-1.40; p=0.257). In stage IV patients with tumors carrying EGFR mutations, as with patients with EGFR/ALK wildtype tumors, developing liver metastases at diagnosis or within one-year of diagnosis of stage IV disease was associated with poorer survival.
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