P1.058. Angiotensin System Inhibitors and Outcomes After Neoadjuvant Therapy for Locally Advanced ESCC

Topic Esophageal Cancer: Adjuvant and Neo-Adjuvant Therapies Background Renin angiotensin system signaling has been implicated in tumor growth, angiogenesis, immune modulation, and responses to cytotoxic and radiation-based therapies, yet clinical effects appear heterogeneous across tumor histologies and treatment contexts.Angiotensin system inhibitors (ASIs) are widely used for cardiovascular indications and represent a plausible, readily implementable adjunct if associated with improved oncologic outcomes. We evaluated the prognostic impact of peritreatment ASI use in patients with locally advanced esophageal squamous cell carcinoma (ESCC) treated with neoadjuvant therapy followed by curative esophagectomy. Methods We retrospectively reviewed a multicenter database of consecutive patients with locally advanced ESCC who received neoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy (nCRT) followed by radical esophagectomy. ASI exposure was prospectively documented. Overall survival (OS) and disease-free survival (DFS) estimated with Kaplan-Meier methods and compared using multivariable Cox regression. Prespecified subgroup analyses were performed by neoadjuvant regimen. A causal mediation analysis decomposed the association between ASI and OS into direct and indirect effects. Results Among 580 patients, 40 (6.9%) used ASIs, 275 (47.4%) received nCT and 305 (52.6%) received nCRT. Neoadjuvant regimen was not associated with OS (p=0.745) or DFS (p=0.358). Overall, ASI use was not significantly associated with OS (p=0.199) or DFS (p=0.642). In the nCT subgroup, ASI use was associated with improved DFS (HR=0.364; p=0.047) and borderline improved OS (HR=0.264; p=0.063), whereas no benefit was observed in the nCRT cohort (p=0.899 for OS; p= 0.109 for DFS). Mediation analysis showed significant indirect effects via DFS in the overall cohort (HR=0.629; p=0.004) and nCT subgroup (HR=0.264; p<0.001), with non-significant direct effects. Conclusion ASI use may be associated with improved outcomes in ESCC patients treated with neoadjuvant chemotherapy, with benefits appearing to operate primarily through reduced recurrence rather than a direct survival effect. No advantage was observed among patients receiving chemoradiotherapy. Given the small exposed proportion and retrospective design, these findings warrant prospective validation and mechanistic studies to clarify treatment-interaction effects and to identify patient subgroups most likely to benefit.