Involved-field Radiotherapy-TNT Combined With PD-1 Inhibitor for pMMR Locally Advanced Rectal Cancer (Neo-Field I)

Inclusion criteria

• Age ≥18 years old, male or female;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;
• Pathologic diagnosis of adenocarcinoma of the rectum, definite pMMR type;
• Clinical staging of T3-4NanyM0 or T1-2N+M0 (based on AJCC 8th edition staging criteria);
• The lower margin of the primary tumor is located below the peritoneal reflex or the lower margin of the tumor is ≤10 cm from the anal verge;
• Pre-enrollment laboratory indicators meet the following indicator ranges： 1)Blood: absolute neutrophils ≥1.5×10^9/L, platelets ≥100×10^9/L, hemoglobin ≥90g/L; 2)Liver and kidney function: ALT/AST ≤ 2.5 x ULN, total bilirubin ≤ 1.5 x ULN, creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 60mL/min (Cockcroft-Gault formula)； 3)Coagulation: INR ≤ 1.5, APTT ≤ 1.5 x ULN (for those not receiving anticoagulation)；
• Women or men of childbearing potential need to agree to use effective contraception during the study and for 6 months after the last treatment session;
• Voluntary written informed consent and commitment to complete the full treatment and follow-up program.

Exclusion criteria

• Pathologic type is other specific types such as neuroendocrine carcinoma, squamous carcinoma, etc;
• Previous radiotherapy, chemotherapy, targeted or immunotherapy for rectal cancer;
• Active autoimmune diseases (e.g., systemic lupus erythematosus, rheumatoid arthritis requiring long-term immunosuppressive therapy)；
• Presence of active infection (e.g. HIV, HBV/HCV viral load positive requiring stabilization on antiretroviral therapy)；
• Severe cardiovascular disease (e.g., myocardial infarction within 6 months, unstable angina, uncontrolled hypertension >160/100 mmHg)；
• History of other malignant tumors (except non-melanoma skin cancers, cervical cancer in situ, etc. cured for ≥5 years)；
• Uncontrolled diabetes mellitus (HbA1c > 8%), abnormal thyroid function (TSH outside normal range and requiring pharmacologic intervention)；
• Severe chronic bowel disease (e.g., Crohn's disease, active ulcerative colitis)； Patients deemed by the investigator to be unsuitable for participation in this study.