P1.104. Potential Survival Benefit of Longitudinal ctDNA-Guided Treatment Adaptation in Advanced Esophageal Cancer

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Abstract Topic Esophageal Cancer: Management of Metastatic Cancer Background We have developed a tumor-specific circulating tumor DNA (ctDNA) monitoring test using digital PCR, termed the OTS (off-the-shelf)-assay. While recent attention has focused on minimal residual disease detection for early relapse diagnosis and to guide adjuvant therapy decisions, we have emphasized the importance of timely treatment management based on serial ctDNA dynamics. Methods In our previous study of 42 patients with esophageal cancer (EC), the ratio of post- to pre-treatment ctDNA levels after the initial chemotherapy cycle (post/pre-ctDNA) demonstrated strong prognostic value. Patients with post/pre-ctDNA <10% showed better overall survival (OS) than those with ≥10% (HR 0.40; P = 0.031). Furthermore, patients who achieved ctDNA clearance within 90 days of treatment initiation showed markedly improved prognosis compared with those who remained ctDNA-positive (HR 0.10; P < 0.001). Based on these findings, we are conducting a randomized controlled trial (CHANGE study) to evaluate whether ctDNA-guided clinical management can improve outcomes in advanced EC. Results This trial enrolls 85 patients with Stage III/IV EC who received first-line chemotherapy. After assessment of ctDNA dynamics during the first chemotherapy cycle, patients with post/pre-ctDNA ≥10% are randomized to either the conventional arm (Group A, n=15), in which treatment decisions are made by standard clinical assessments, or the ctDNA-guided arm (Group B, n=18), in which treatment strategies are repeatedly adjusted based on serial ctDNA dynamics. The primary endpoint is 2-year OS. In an interim analysis (median follow-up 373 [36-1276] days), Group B showed improved 2-year OS compared with Group A (65.2% vs 26.0%; HR 0.28, 95% CI 0.11–0.75, P = 0.01). Conclusion These preliminary results may suggest that longitudinal personalized ctDNA monitoring with timely treatment adaptation contributes to improved survival outcomes in patients with advanced EC.