Chemoradiotherapy has been a standard modality for inoperable locally advance esophageal carcinoma. The goal of this randomized control study is to compare the feasibility, and survival benefits of whole-course immunonutrition combined with chemoradiotherapy±ICIs for local advanced patients with inoperable esophageal squamous cell carcinoma. The main questions it aims to answer are: • If the feasibility and safety of whole-course immunonutrition combined with chemoradiotherapy±ICIs is better. • If the survival benefits (1, 2 and 3-years progression free survival) of whole-course immunonutrition combined with chemoradiotherapy±ICIs is longer. The Experimental group will receive a combination immunonutrition of omega-3 fatty acids, and glutamine, whereas the control group will receive standard formula.

Inclusion Criteria:

• 18-85 years old;
• Eastern Cooperative Oncology Group (ECOG) 0-2;
• Esophageal squamous cell carcinoma;
• cT2-4aN0-3M0 (AJCC 8th) confirmed by radiological examination;
• initial unresectable at initial diagnosis confirmed by thoracic surgeons;
• Treatment naive;
• No contraindications for adjuvant chemoradiotherapy;
• Signature of inform consent.

Exclusion Criteria:

• younger than 18 years old or older than 85 years old;
• ECOG>2;
• Esophageal adenocarcinoma, small-cell cancer and other pathological types;
• cT1anyNM0, cT4banyNM0, c anyTanyNM0 confirmed by radiological examination;
• Resectable at initial diagnosis confirmed by thoracic surgeons;
• Previous treatment of chemotherapy, radiotherapy, and other treatment;
• Contraindications for chemoradiotherapy;
• No signature of inform consent.

• 18-85 years old;
• Eastern Cooperative Oncology Group (ECOG) 0-2;
• Esophageal squamous cell carcinoma;
• cT2-4aN0-3M0 (AJCC 8th) confirmed by radiological examination;
• initial unresectable at initial diagnosis confirmed by thoracic surgeons;
• Treatment naive;
• No contraindications for adjuvant chemoradiotherapy;
• Signature of inform consent.