Low-dose Radiation Combined With Neoadjuvant Immunochemotherapy for Esophageal Squamous Cell Carcinoma

Inclusion Criteria:

1. Histologically confirmed thoracic esophageal squamous cell carcinoma with clinical staging of: cT1b-cT2 N1-2 M0 or cT3-cT4a N0-2 M0 (AJCC/UICC esophageal cancer staging, 8th edition)
2. Candidates eligible for an R0 curative resection
3. ECOG performance status of 0-1
4. Male or female patients aged ≥18 years and ≤75 years
5. Adequate major organ and bone marrow function (without transfusion or medication correction): Complete blood count: White blood cells ≥ 3.5×10\^9/L, Absolute Neutrophil Count (ANC) ≥1.5 ×10\^9/L, Platelets ≥100×10\^9/L, Hemoglobin ≥9g/dL
6. Radiation oncologist assessment confirms no severe pulmonary ventilatory dysfunction and no acute cardiac failure. (Pulmonary function: FEV1/FVC≥70%, FEV1≥50% of the normal value, DLCO (lung diffusion capacity) actual versus predicted value \>80%)
7. Liver function: Total bilirubin ≤1.5 times the upper limit of normal (ULN), Alanine aminotransferase (ALT) and/or Aspartate aminotransferase (AST) ≤2.5 times ULN, Serum albumin ≥3g/dL
8. Renal function: Serum creatinine ≤1.5×ULN, or creatinine clearance ≥ 60ml/min (calculated using the Cockcroft/Gault formula): Female: CrCl = (140 - age) x weight (kg) x 0.85 / 72 x serum creatinine (mg/dL) Male: CrCl = (140 - age) x weight (kg) x 1.00 / 72 x serum creatinine (mg/dL)
9. Study participants voluntarily join the study and sign a written informed consent form, and are able to comply with the protocol-specified visits and related procedures
10. Expected survival \>6 months
11. Patients agree to undergo surgical treatment as well as radiotherapy, chemotherapy, and immunotherapy
12. Women of childbearing potential must have a negative pregnancy test within 7 days prior to the initiation of treatment; all participants, regardless of gender, are willing to use appropriate contraceptive methods during the trial and for 8 weeks after the last dose of study medication
13. No esophageal perforation or active esophageal bleeding, and no tracheal or major thoracic vascular invasion
14. According to the solid tumor response evaluation criteria (RECIST version 1.1), at least one measurable lesion by imaging

Exclusion Criteria:

1. Patients who are unsuitable for the immunotherapy and chemotherapy specified in the protocol
2. Patients with a history of treatment for ESCC, including experimental drugs, chemotherapy, radiotherapy, or therapies targeting T-cell co-stimulation checkpoint pathways such as anti-PD-1, anti-PD-L1, anti-PD-L2 antibodies or drugs
3. Patients with a history of primary tumor infiltration causing fistula
4. Patients assessed as having a high risk of fistula or signs of perforation
5. Patients who have required systemic corticosteroid treatment (prednisone \> 10 mg/day or equivalent dosage) or other immunosuppressive therapies within 14 days prior to the first administration. However, use of adrenocortical replacement steroids (prednisone ≤ 10 mg/day or equivalent) and minimal systemic absorption of topical, ocular, intra-articular, nasal, and inhaled corticosteroids, as well as short-term (≤ 7 days) use of corticosteroids for non-autoimmune conditions are allowed (dexamethasone can be used for paclitaxel pre-treatment)
6. Patients with active autoimmune diseases or a history of autoimmune diseases that might recur. However, participants with well-controlled type 1 diabetes, hypothyroidism requiring only hormone replacement, well-controlled celiac disease, and non-systemic treated skin conditions like vitiligo, psoriasis, or alopecia, or conditions not likely to recur without an external trigger are eligible
7. Patients with a history of interstitial lung disease, non-infectious pneumonia, or poorly controlled pulmonary diseases including pulmonary fibrosis or acute lung diseases
8. Patients needing systemic antibacterial, antifungal, or antiviral treatment for infections such as tuberculosis. Patients who have had a severe infection including but not limited to hospitalization-required complications, bacteremia, or severe infectious pneumonia within 4 weeks before the first administration, or those who have received therapeutic oral or intravenous antibiotics within 2 weeks before the first administration
9. Patients with a history of allogeneic organ transplant (excluding corneal transplant) or allogeneic hematopoietic stem cell transplant
10. Patients known to be allergic to the study drug tiragolumab, or to the active ingredients or excipients in the combined chemotherapy drugs
11. Patients with significant and severely symptomatic rhythm, conduction, or morphological abnormalities on a resting electrocardiogram, such as complete left bundle branch block, second-degree or higher heart block, ventricular arrhythmias, atrial fibrillation; unstable angina, congestive heart failure, or chronic heart failure with an NYHA classification of ≥ 2