TITLE:
Advances in Immune Checkpoint Inhibitors Combined with Definitive Concurrent Chemoradiotherapy for Unresectable Locally Advanced Esophageal Squamous Cell Carcinoma
AUTHORS:
Lun Zhang, Di Zhang, Zhiliang Jin
KEYWORDS:
Esophageal Squamous Cell Carcinoma, Unresectable Disease, Definitive Concurrent Chemoradiotherapy, Immune Checkpoint Inhibitor, Combination Therapy
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.17 No.10,
October
14,
2026
ABSTRACT: Definitive concurrent chemoradiotherapy (dCRT) remains the treatment backbone for anatomically unresectable locally advanced esophageal squamous cell carcinoma (ESCC), but recurrence after treatment remains relatively common. This review discusses the use of immune checkpoint inhibitors concurrently, as induction therapy, and as consolidation or maintenance therapy after dCRT. Anatomical unresectability is distinguished from medical inoperability, refusal of surgery, and organ-preservation pathways. Early studies support the feasibility of combination treatment, but differences in study populations, treatment exposure, and endpoint time origins limit comparisons across studies. EC-CRT-002 has not established a universal benefit from prolonged immunotherapy, and its historical-control comparisons should be distinguished from the randomized groups receiving different treatment durations. Studies also differ in the reporting of severe toxicity, treatment discontinuation, fistula, and treatment-related death and in the populations analyzed. Dynamic circulating tumor DNA is associated with response and survival, but no evidence has established a treatment-by-biomarker interaction for the additional benefit of immunotherapy. Confirmatory randomized studies in clearly defined target populations are still needed.