Immunochemotherapy plus radiotherapy versus immunochemotherapy alone as first-line treatment for treatment-naïve, advanced esophageal squamous cell carcinoma (AEC-ICR-1st): A multi-center cohort study

Immunochemotherapy is Currently the standard first-line treatment for advanced esophageal squamous cell carcinoma (ESCC). However, its prognosis remains unsatisfactory. We aimed to evaluate the efficacy and safety of immunochemotherapy plus radiotherapy (ICR) compared with immunochemotherapy (IC) alone as a first-line treatment for advanced ESCC. This multicenter cohort study was conducted across five cancer centers (NCT06190652). We evaluated the outcomes in patients with advanced ESCC who received first-line therapy of IC, with or without radiotherapy (RT), between 2018 and 2023. Propensity score matching (PSM) was performed to control for potential confounders. Sensitivity analysis was conducted to evaluate the robustness of the results. Overall, 23,641 patients were screened, and 702 patients were finally eligible. 270 patients included in ICR cohort, and 432 patients in IC alone cohort. Both before and after PSM, the ICR cohort had a longer median OS compared to IC alone cohort (20.4 versus 16.8 months, P =0.001; 21.3 versus 17.5 months, P =0.008; respectively); multivariate analysis further supported that RT was associated with a better OS (HR: 0.695, 95%CI: 0.558-0.867, P =0.001; HR: 0.729, 95%CI: 0.561-0.947, P =0.018; respectively). Exploratory analysis revealed that the survival benefits were most pronounced in the subgroup that received IC concurrently combined with definitive dose RT to the primary tumor, with a median OS of 23.6 months (HR: 0.515, 95%CI: 0.308-0.862, P =0.011) and PFS of 14.4 months (HR: 0.567, 95%CI: 0.370-0.870, P =0.009). The grade ≥ 3 treatment-related adverse events (TRAEs) were esophagitis (4.10% versus 0.41%; P =0.006), anemia (6.97% versus 1.64%; P =0.004), leukopenia (12.70% versus 6.56%; P =0.021) and lymphopenia (38.52% versus 4.92%, P < 0.001) in the ICR and IC cohorts. The addition of RT to IC as a first-line treatment for advanced ESCC could bring benefits, and was well-tolerated. •Adding RT in first-line IC treatment improved OS in patients with advanced ESCC.•Subgroup analysis revealed survival benefit from IC plus RT to primary tumor.•IC plus RT was generally well-tolerated.