Durable Marked Response of Unresectable Esophageal Squamous Cell Carcinoma After Radiotherapy Alone Followed by Combination Immunotherapy.

We report the case of a 70-year-old man with unresectable esophageal squamous cell carcinoma who achieved durable marked response with combined immune checkpoint inhibitor (ICI) therapy following radiotherapy (RT) alone. The patient presented with dysphagia and stridor due to a bulky esophageal tumor and cervical lymph node metastasis compressing the trachea. He was diagnosed with cT3N1M0 (Stage IIIB; 8th edition of the TNM classification) or cT4(101R-Trachea)N1M0 (Stage IVA; 12th edition of the Japanese classification). He underwent RT alone (total dose, 50 Gy), resulting in substantial tumor shrinkage and improvement in Eastern Cooperative Oncology Group performance status from 4 (due to ventilator dependence) to 1. Following confirmation of programmed death-ligand 1 positivity (tumor proportion score ≧ 1%), treatment with nivolumab (anti-programmed cell death-1 antibody) and ipilimumab (anti-cytotoxic T-lymphocyte antigen-4 antibody) was initiated. The therapeutic effect was remarkable, and treatment continued for 14 courses until an immune-related adverse event of secondary adrenal insufficiency interrupted therapy. Thereafter, there was no apparent recurrence on imaging for 31 months after treatment initiation. This case highlights the potential effect of RT followed by ICI combination therapy. Preclinical and clinical data suggest that prior RT may enhance systemic tumor immune responses. This therapeutic approach is currently being prospectively evaluated in the ongoing Phase II trial by the Japan Clinical Oncology Group (JCOG2311).