ScholarWorks@성균관대학교

초록

Background: Metastatic gastric cancer (GC) is biologically heterogeneous; however, current staging classifies all metastatic cases as stage IV without reflecting this variability. Circulating tumor DNA (ctDNA)-derived biomarkers, including maximum somatic allele frequency (MSAF), may serve as surrogates for tumor burden and underlying tumor biology.Objectives: This study aimed to evaluate the prognostic significance of baseline MSAF in patients with metastatic GC receiving first-line palliative chemo or chemoimmunotherapy.Design: This was a retrospective, single-center cohort study of consecutively tested patients.Methods: We analyzed 108 patients with pathologically confirmed metastatic gastric adenocarcinoma who underwent baseline ctDNA next-generation sequencing prior to first-line systemic therapy between December 2022 and April 2024. MSAF was defined as the highest variant allele frequency detected in ctDNA and evaluated as both a continuous and categorical variable. Patients were stratified into MSAF-high and MSAF-low groups using the cohort mean (12.31%) as the cutoff. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier estimation and Cox proportional hazards regression analyses.Results: The MSAF-high group (n = 41) demonstrated significantly inferior OS compared with the MSAF-low group (n = 67; median OS, 10.0 vs 17.6 months; log-rank p = 0.006). PFS showed a nonsignificant trend favoring the MSAF-low group (median PFS, 4.5 vs 8.0 months; p = 0.1). In multivariate analysis (complete-case analysis, n = 70), high MSAF remained independently associated with worse OS (hazard ratio, 2.14; 95% confidence interval: 1.04-4.41; p = 0.039), along with older age and multiple metastatic sites. Tumors in the MSAF-high group more frequently exhibited molecular features such as deficient mismatch repair and high tumor mutational burden.Conclusion: Baseline MSAF is an independent prognostic biomarker in metastatic GC and may reflect underlying biological aggressiveness. Incorporating MSAF into risk stratification frameworks could enhance prognostic classification and inform personalized treatment strategies.

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