Short Course or Long Course Radiotherapy as Total Neoadjuvant Therapy in Locally Advanced Rectal Cancer

Inclusion Criteria:

1. Histologically confirmed adenocarcinoma of the rectum
2. Locally advanced disease based on MRI including cT3-T4 and/or node positive disease (cN1 or N2)
3. Tumor located within 15 cm from the anal verge (confirmed by endoscopy or MRI)
4. ECOG performance status 0-2
5. Hemoglobin ≥ 9 g/dL
6. Absolute neutrophil count ≥ 1,500/mm³
7. Platelets ≥ 100,000/mm³
8. Total bilirubin ≤ 1.5 × ULN
9. Aspartate transaminase/Alanine transaminase ≤ 2.5 × ULN
10. Serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 60 mL/min
11. Fit for neoadjuvant therapy and curative resection
12. Willing and able to provide written, informed consent
13. Baseline MRI and biopsy (even if done outside) must be reviewed and approved by the institutional radiology and pathology review board, requiring concurrence from two independent pathologists and two independent radiologists

Exclusion Criteria:

1. Metastatic disease at presentation (distant nodes, liver, lung, peritoneum, etc.)
2. Prior pelvic radiotherapy or systemic chemotherapy for rectal cancer
3. Presence of synchronous malignancies or previous malignancy within 5 years except: Treated basal cell or squamous cell carcinoma of the skin, In situ cervical cancer, Active uncontrolled infection
4. Known HIV infection with CD4 \< 200 cells/μL, or active hepatitis B or C
5. Severe comorbid conditions precluding therapy (e.g., decompensated cardiac, hepatic, or renal disease)
6. Pregnant or breastfeeding women
7. Inability to comply with protocol requirements or follow-up schedule
8. Psychiatric illness or social situations that may limit compliance with study requirements