What question did this study set out to answer?

This research aims to evaluate the survival outcomes and progression patterns of ESCC patients receiving CRT combined with ICIs.

June 1, 2026Frontiers in Immunology0 citationsOpen Access

Definitive chemoradiotherapy plus immune checkpoint inhibitors for locally advanced unresectable esophageal squamous cell carcinoma: survival and progression patterns in a propensity‐matched cohort

ZLZhongmei Lin YSYongshi Shen QLQ Z Li

Key Points

This research aims to evaluate the survival outcomes and progression patterns of ESCC patients receiving CRT combined with ICIs.
Retrospective review of 67 ESCC patients treated with CRT+ICIs compared to 415 historical controls treated with CRT alone
1:3 propensity score matching applied to correct for baseline imbalances
Survival and progression patterns analyzed using Kaplan-Meier method and Cox proportional hazards analyses.
CRT+ICIs group had a median overall survival of 31.1 months compared to 18.6 months for CRT alone (p=0.013)
Tendency toward elongated progression-free survival of 18.6 months in CRT+ICIs versus 12.1 months in CRT alone (p=0.176)
Multivariable analysis identified M stage, LAR, and PNI as independent prognostic factors for overall survival.

Abstract

Background Locally advanced unresectable esophageal squamous cell carcinoma (ESCC) remains a therapeutic challenge, with limited survival outcomes following definitive chemoradiotherapy (CRT). Recent evidence suggests that combining immune checkpoint inhibitors (ICIs) with CRT may enhance therapeutic response. Nevertheless, its efficacy, progression behavior, and prognostic indicators require further elucidation. Methods A retrospective review was performed on ESCC patients treated at Fujian Cancer Hospital from August 2019 to August 2024. 67 patients receiving definitive CRT combined with ICIs (CRT+ICIs) were compared with 415 historical controls treated with CRT alone. To correct for baseline imbalances, 1:3 propensity score matching (PSM) was applied. The Kaplan-Meier method was employed to assess survival outcomes, while progression patterns were evaluated via Fine-Gray competing risks model. Cox proportional hazards analyses were used to determine prognostic factors for overall survival (OS). Results After PSM, 62 individuals were retained in the CRT+ICIs group and the matched CRT group included 149. The CRT+ICIs exhibited a significantly prolonged median OS (31.1 vs. 18.6 months, p = 0.013) and showed a tendency toward longer PFS (18.6 vs. 12.1 months, p = 0.176). Fine-Gray analysis indicated a nonsignificant 34% reduction in distant progression for CRT+ICIs group (p = 0.160), while local-regional progression risk was declined over time. In the CRT+ICIs group, multivariable analysis identified M stage, lactate dehydrogenase-to-albumin ratio (LAR) and prognostic nutritional index (PNI) as independent prognostic factors for OS. Among these patients, 38.7% experienced grade 3 or higher adverse events with manageable immune-related toxicity. Conclusions CRT combined with immunotherapy significantly prolongs OS and may delay early distant progression in locally advanced unresectable ESCC, with manageable toxicity. These findings warrant prospective validation and support biomarker-driven patient selection.

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