The goal of this clinical trial is to investigate the safety and efficacy of a new treatment approach for T4-stage esophageal cancer, which involves chemoradiotherapy after induction chemotherapy. The main questions it aims to answer are:

• Does the new induction chemotherapy followed by chemoradiation reduce esophageal perforation rate?
• Does the new induction chemotherapy followed by chemoradiation increase treatment response rate and patient survival? Researchers will analyze the above data to see if the new treatment approach works to treat T4 esophageal cancer.

Participants will:

• Receive induction chemotherapy for 4 to 8 cycles, followed by chemoradiation therapy if downstage to T3
• Visit the clinic once every week for checkups and tests
• Keep a diary of their symptoms

The treatment of T4-stage esophageal cancer is challenging because of a high esophageal perforation rate (19%) after concurrent chemoradiotherapy. This research aims to investigate whether a novel sequential chemoradiotherapy approach can improve the treatment response rate and reduce the incidence of esophageal perforation in participants with T4-stage esophageal cancer. The proposed novel treatment strategy involves induction chemotherapy for 4 to 8 cycles. It is followed by concurrent chemoradiotherapy if down-stage had been achieved by induction chemotherapy. The study will be conducted in two phases, starting with a phase I study to determine safety, followed by a phase II study to evaluate overall efficacy. Expected outcomes include improved treatment response rates and reduced esophageal perforation rates in T4-stage esophageal cancer, offering a better treatment option for these patients.

Inclusion Criteria:

1. Histologically confirmed esophageal squamous cell carcinoma
2. Tumor or lymph nodes invade adjacent organs (T4 stage)
3. Aged between 18-70 years old
4. Patient health status score Eastern Cooperative Oncology Group (ECOG) performance status (PS) <2
5. Hemoglobin ≥ 10 g/L, absolute neutrophil count ≥ 2×10^3/L, platelet count ≥ 100×10^9/L, total bilirubin ≤ 1.5 mg/L, serum transaminases ≤ 105 U/L, creatinine clearance ≥ 40 mL/min.

Exclusion Criteria:

1. Previous chemotherapy history
2. Myocardial infarction within the last three months
3. History of unstable angina, interstitial pneumonia, fibrotic lung disease, or severe emphysema
4. Has other malignancies currently
5. Uncontrolled infection
6. Pregnancy or lactation
7. Perforated esophagus at the time of diagnosis

No individual participant data will be shared. Results will be published by the investigators in academic journals.