Abstract
PURPOSE: This study aimed to evaluate the clinical utility of a pan-cancer circulating tumor DNA (ctDNA) next-generation sequencing (NGS) panel for predicting treatment response and progression-free survival (PFS) in patients with advanced solid tumors. PATIENTS AND METHODS: A total of 41 patients with advanced solid tumors, including gastric cancer (n=13), non-small cell lung cancer (n=10), head and neck cancer (n=9), esophageal cancer (n=7), breast cancer (n=1), and colon cancer (n=1), were prospectively enrolled and included in the analysis. ctDNA was analyzed at three time points: pretreatment (41 patients), post-treatment evaluation (37 patients), and follow-up (18 patients). RESULTS: Among 41 patients analyzed at pretreatment, 35 (85.4%) exhibited tier 1 or 2 somatic variants in ctDNA, with TP53 being the most frequently mutated gene. At the post-treatment evaluation, ctDNA was assessed in 37 patients (3 with rapid deterioration and 1 lost to follow-up were not evaluable). Newly emerging variants after treatment were strongly associated with poor clinical outcomes. Consistent with the Kaplan-Meier analysis, Cox proportional hazards regression confirmed that post-treatment ctDNA positivity was significantly associated with inferior PFS (HR 10.5, 95% CI 1.4-80.0, P=0.024). At follow-up, 18 patients were evaluable, while the others were not due to follow-up loss, rapid deterioration, or study termination. ctDNA positivity at post-treatment evaluation was significantly associated with shorter PFS (median PFS, 5.0 months [95% CI: 2.0-12.0] vs not reached; HR, 4.87; 95% CI: 1.69-14.09; P = 0.0035). CONCLUSION: Longitudinal monitoring of ctDNA using a pan-cancer NGS panel provides meaningful prognostic information in patients with advanced cancers. Post-treatment ctDNA dynamics may better reflect disease progression than baseline ctDNA status alone, highlighting the need for further validation in larger cohorts, particularly in gastric, lung, head and neck, and esophageal cancers.