Concurrent immunoradiotherapy with Toripalimab versus concurrent chemoradiotherapy with S-1 in older patients with esophageal squamous cell carcinoma: a retrospective cohort study

• CIRT vs CCRT in older ESCC: similar response, shorter survival, improved tolerability. • Distant recurrences prevailed post-CIRT, while CCRT failures were mainly locoregional. • Early-treatment lymphopenia linked to poorer OS, particularly in CIRT group. Evidence for concurrent immunoradiotherapy (CIRT) in older patients with esophageal squamous cell carcinoma (ESCC) is limited, whereas S-1–based concurrent chemoradiotherapy (CCRT) has shown benefits. We retrospectively included 47 older patients with ESCC treated with CIRT (n = 22) or CCRT (n = 25). Progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (AEs) were analyzed. Absolute lymphocyte count (ALC), pan-immune-inflammation value (PIV), platelet lymphocyte ratio (PLR), lymphocyte monocyte ratio (LMR), neutrophil lymphocyte ratio (NLR), and systemic inflammation response index (SIRI) were collected at four timepoints (pre-, during1-, during2-, post-) and explored using univariate and multivariate Cox models. Objective response rate and disease control rate were 77.3% and 90.9% with CIRT, and 100% with CCRT. Median PFS (9.67 vs 20.63 months; P = 0.042) and OS (13.67 vs 23.73 months; P = 0.045) were shorter with CIRT. Grade ≥ 3 AEs occurred in 72.7% (CIRT) and 96.0% (CCRT). Distant recurrence predominated with CIRT (66.7% of recurrences), while regional/local relapse was more common with CCRT (50.0%). ALC and LMR declined during therapy and partially recovered after treatment; PIV, PLR, NLR, and SIRI showed inverse dynamics. Treatment group, during1-ALC, and pre-SIRI were independent prognostic factors for OS. Patients receiving CIRT with low during1-ALC, high pre-SIRI/PIV, or high during1-PLR/NLR had the worst OS. CIRT was tolerable in older patients with ESCC but associated with inferior outcomes, though confounding cannot be excluded. Our analysis indicated a potential correlation between lymphocyte/monocyte dynamics and response, suggesting lymphopenia mitigation could improve efficacy.