the Efficacy of MR-guided Online Adaptive Radiotherapy for Locally Advanced Rectal Cancer

Inclusion criteria

• Age 18-75 years, regardless of gender;
• Staged as II/III (cT3-T4N0 or cT2-4N+, no distant metastasis) by MRI or endoscopic ultrasound (according to the AJCC Cancer Staging Manual, 8th Edition);
• Fibrocolonoscopy or digital rectal examination confirms the lower border of the lesion is ≤10 cm from the anal verge;
• Pathologically confirmed or reviewed diagnosis of rectal adenocarcinoma;
• ECOG performance status of 0-1;
• Laboratory test results meeting the following criteria: Hemoglobin ≥ 90 g/L, white blood cells ≥ 3.5×10⁹/L; Neutrophils ≥ 1.5×10⁹/L, platelets ≥ 100×10⁹/L; Creatinine ≤ 1.0× upper normal limit (UNL), blood urea nitrogen (BUN) ≤ 1.0× UNL; Alanine aminotransferase (ALT) ≤ 1.5× UNL; Aspartate aminotransferase (AST) ≤ 1.5× UNL; Alkaline phosphatase (ALP) ≤ 1.5× UNL; Total bilirubin (TBIL) ≤ 1.5× UNL; Urine protein (-); normal bleeding and clotting time.
• No history of allergy to 5-Fu drugs or platinum-based drugs;
• Primary rectal cancer patients must not have undergone surgery (except palliative colostomy), chemotherapy, or other antitumor treatments from diagnosis to enrollment;
• No prior radiation therapy to the intended treatment site;
• Signed informed consent form.

Exclusion criteria

• Presence of MRI-incompatible metal implants or claustrophobia;
• Previous treatment with anti-PD-1/L1, anti-CTLA-4 immunotherapy, or other experimental immunotherapeutic drugs;
• History of severe autoimmune diseases, including active inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis), rheumatoid arthritis, scleroderma, systemic lupus erythematosus, autoimmune vasculitis (e.g., Wegener's granulomatosis), etc.;
• Symptomatic interstitial lung disease or active infectious/non-infectious pneumonia;
• Risk factors for intestinal perforation, such as active diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction, abdominal malignancies, or other known predisposing conditions;
• History of other malignancies, except for curable non-melanoma skin cancer or cervical carcinoma in situ;
• Active infections, heart failure, myocardial infarction within the past 6 months, unstable angina, or unstable arrhythmia;
• Physical examination or clinical findings that, in the investigator's judgment, may interfere with results or increase the patient's risk of treatment complications, or other uncontrolled medical conditions;
• Women who are pregnant or breastfeeding;
• Congenital or acquired immunodeficiency disorders, including human immunodeficiency virus (HIV) infection, or history of organ transplantation or allogeneic stem cell transplantation.
• Active hepatitis B virus (HBV) infection (HBV-DNA ≥2000 U/mL), hepatitis C virus (HCV) infection, or active tuberculosis infection;
• Prior administration of a cancer vaccine or receipt of any other vaccine within 4 weeks before treatment initiation.

(Note: Inactivated vaccines, such as seasonal flu shots, are permitted, whereas live attenuated vaccines, such as intranasal formulations, are prohibited.)

• Concurrent use of other immunomodulators, chemotherapy, investigational drugs, or long-term corticosteroid therapy will exclude the patient from enrollment.
• Patients with psychiatric disorders, substance abuse, or social issues that may compromise compliance, as assessed by the investigator, will be excluded.
• Patients with a known allergy or contraindication to the study treatment.