Background
Patients with EGFR-mutant NSCLC with brain metastases show a different trajectory with tyrosine kinase inhibitor (TKI) treatment. Exploring concomitant genetic alterations may have underlying mechanisms and identify distinct subpopulations of patients with and .
Methods
From January 2013 to December 2020, NSCLC patients with brain metastases were screened and patients carrying EGFR mutations were included. Clinical data from patients with next-generation sequencing (NGS) data were then analyzed. The Kaplan-Meier method and Cox proportional hazards model were used for survival analysis. Based on multivariate analysis, a nomogram was constructed using R version 4.0.5.
Results
A total of 2657 NSCLC patients with brain metastases were screened, 737 of whom carried EGFR mutations, and 73 patients with NGS data all received EGFR TKI treatment. The median age was 58.1 years old, 35 were male (47.9%), and 35 were male ( 47.9%) is EGFR 19Del. Median overall survival (OS) was 23.6 months. Concomitant alterations were present in 55 patients (75.3%), with TP53 (45.2%), EGFR amplification (12.3%), and RB1 (9.6%) being the top three most common alterations. Concomitant genetic changes were significantly associated with reduced OS (23.2 months vs NR, P=0.016). In particular, TP53 mutations (HR=1.8, 95%CI:1.0-3.2) and EGFR amplification (HR=2.5, 95%CI:1.2-5.6) were associated with significantly worse OS. in patients with driver genes (HR=8.0, 95%CI:2.0-31.1) or tumor suppressor genes (HR=10.6, 95%CI:1.8-60).
had significantly worse OS compared with patients without concomitant changes. However, the OS of patients who underwent local surgery or radiation therapy was comparable. As shown in the nomogram, higher total scores were associated with EGFR 19del mutations without concomitant changes indicating a higher likelihood of longer OS.
Conclusion
This study revealed that concomitant changes are common in EGFR-mutated NSCLC patients with brain metastasis. Concomitant changes are associated with poorer clinical outcomes for patients. Based on the nomogram, we determined that a subpopulation of patients without concomitant alterations and EGFR 19Del may derive greater survival benefit from EGFR-TKI treatment.
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