Exploratory analysis of prognostic factors and hematologic dynamics in unresectable ESCC treated with concurrent versus interval immune checkpoint inhibitors combined with (chemo)radiotherapy: a multicenter real-world study

Background The optimal integration of radiotherapy (RT) and immune checkpoint inhibitors (ICI) for esophageal squamous cell carcinoma (ESCC) remains undefined. This study aimed to evaluate treatment patterns, hematologic dynamics, and prognostic factors in patients receiving combined RT and ICI. Methods We conducted a multicenter retrospective analysis of 426 patients with unresectable ESCC treated with RT and ICI, with and without chemotherapy. Survival outcomes were compared between concurrent and Interval (chemo)radiotherapy ((C)RT) and ICI strategies. Hematologic parameters, including lymphocyte counts and the systemic inflammation score (SIS), were dynamically assessed at baseline, during RT, and post-RT. Prognostic factors for overall survival (OS) and progression-free survival (PFS) were analyzed using univariate and multivariate Cox regression models. Results Concurrent and Interval (C)RT-ICI strategies demonstrated comparable OS and PFS. Concurrent (C)RT-ICI was associated with a more pronounced decline in lymphocyte counts and a slightly higher incidence of adverse events, though generally manageable. Patients with isolated lymph node metastases achieved survival similar to those without metastasis and significantly better than those with organ metastases. During concurrent(C)RT-ICI, lymphocyte counts showed the most significant decline but gradually recovered 1–2 months after radiotherapy. Notably, SIS measured 1–2 months after RT emerged as a superior independent prognostic indicator for OS. Conclusions In real-world practice, concurrent (C)RT-ICI is a safe and feasible treatment option for ESCC, though associated with greater lymphocyte suppression. During ICI treatment, SIS assessed after RT may serve as a simple and reliable prognostic biomarker. Patients with isolated nodal metastases appear to derive substantial benefit from (C)RT-ICI, warranting further validation in prospective randomized trials.