Dynamic Multi-omics Integration Model to Predict Neoadjuvant Therapy Response in Locally Advanced Rectal Cancer

Inclusion Criteria:

1. Histologically confirmed rectal adenocarcinoma;
2. Clinical stage T3-4NxM0, with or without positive Mesorectum Fascia(MRF), and with or without positive Extra-Mural Venous Invasion(EMVI);
3. Preoperative staging method: All patients undergo preoperative staging with enhanced CT. Criteria for mesorectal lymph node metastasis: Short axis ≥ 10mm lymph nodes or lymph node morphology and CT characteristics consistent with typical lymph node metastasis. Preoperative chest, abdominal CT, and pelvic MRI exclude distant metastases;
4. Absence of signs of intestinal obstruction; or relief of obstruction after proximal colon diversion surgery;
5. No history of previous colorectal surgery;
6. No history of previous chemotherapy or radiotherapy;
7. No history of previous biological therapy (such as monoclonal antibodies), immunotherapy \[such as anti-programmed cell death protein 1(PD-1) antibodies, anti-PD-L1 antibodies, anti-PD-L2 antibodies, or anti-Cytotoxic T Lymphocyte-Associated Antigen-4(CTLA-4)\], or other investigational drug therapy;
8. No history of previous hormonal therapy: no restrictions;
9. Signed informed consent form.

Exclusion Criteria:

1. Patients requiring antiarrhythmic therapy (excluding β-blockers or digoxin), symptomatic coronary artery disease, recent myocardial infarction within the past 6 months, or congestive heart failure exceeding New York Heart Association(NYHA) class II;
2. Poorly controlled severe hypertension;
3. History of HIV infection or active chronic hepatitis B or C (high viral DNA load);
4. Active pulmonary tuberculosis (TB) or receiving anti-TB treatment, or having received anti-TB treatment within the past year;
5. Other active clinically severe infections ;
6. Evidence of distant metastases outside the pelvis preoperatively;
7. Cachexia, organ decompensation;
8. History of pelvic or abdominal radiotherapy;
9. Multifocal colorectal cancer;
10. Patients requiring management for epileptic seizures (e.g., with steroids or antiepileptic therapy);
11. History of other malignant tumors within the past 5 years, excluding cured carcinoma in situ of the cervix or basal cell carcinoma of the skin;
12. Substance abuse or medical, psychological, or social conditions that may interfere with patient participation in the study or assessment of study results;
13. Presence of any active autoimmune disease or history of autoimmune disease (including but not limited to: interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, nephritis, hyperthyroidism, hypothyroidism; patients with vitiligo or childhood asthma that has completely resolved and does not require any intervention in adulthood may be included; patients with asthma requiring bronchodilators for medical intervention cannot be included);
14. Vaccination with any anti-infective vaccine (e.g., influenza vaccine, varicella vaccine, etc.) within 4 weeks before enrollment;
15. Complications requiring long-term use of immunosuppressive drugs or systemic or local administration of corticosteroids with immunosuppressive effects (dose \> 10mg/day of prednisone or equivalent corticosteroids);
16. Known or suspected allergy to the investigational drug or any medication administered related to this trial;
17. Any unstable condition or situation that may jeopardize patient safety and compliance;
18. Pregnancy or lactation in women of childbearing potential who have not taken adequate contraceptive measures;
19. Refusal to sign the informed consent form.