Simultaneous Boost in Neoadjuvant Radiotherapy for Rectal Cancer

Simultaneous Boost in Neoadjuvant Radiotherapy for Rectal Cancer：A Phase 2, Randomized Controlled Study

The goal of this clinical trial is to learn whether new adjuvant radiotherapy with gross tumor volume(GTV) escalated to 58.75 Gy can improve complete response (CR) rates compared with GTV dose of 50 Gy in adult patients (18-79 years) with locally advanced rectal adenocarcinoma (T3-T4/N+, M0) located ≤10 cm from the anal verge.The main questions it aims to answer are:

1. Does GTV simultaneously boost to 58.75 Gy/25f increase complete response (pCR or cCR) compared with 50 Gy/25f?
2. How do the two regimens differ in terms of progression-free survival (PFS), pelvic local control (LC), tumor regression grade (TRG), organ preservation, and treatment-related toxicity? Researchers will compare GTV 58.75 Gy/25f (experimental arm) versus GTV 50 Gy/25f (control arm) to see if dose escalation improves tumor response rate.

Participants will:

1. Receive neoadjuvant radiotherapy with one of the two PGTV dose escalated regimens (with concurrent chemotherapy: oral capecitabine or XELOX).
2. Undergo restaging with imaging and clinical assessment before surgery or observation.
3. Proceed to total mesorectal excision (TME), local excision, or "watch-and-wait" strategy depending on treatment response and patient preference.
4. Be followed regularly with clinical exams, imaging, endoscopy, and laboratory tests to assess efficacy, safety, and long-term outcomes.

Inclusion Criteria:

1. Age ≥18 and <80 years
2. Histologically confirmed rectal adenocarcinoma
3. Tumor located within 10 cm from the anal verge
4. MRI staging: T3-T4 and/or N+, M0 (AJCC 8th edition)
5. ECOG performance status 0-2
6. Adequate bone marrow function: WBC ≥3×10⁹/L, ANC ≥1.5×10⁹/L, PLT ≥100×10⁹/L, Hb ≥90 g/L
7. Adequate liver function: TBIL ≤1.5 × ULN, ALT/AST ≤2.5 × ULN
8. Adequate renal function: Cr ≤1.5 × ULN or CCr ≥60 mL/min
9. Signed informed consent

Exclusion Criteria:

1. Prior rectal cancer surgery
2. Prior induction chemotherapy, immunotherapy, or pelvic radiotherapy
3. History of other malignancies
4. History of chronic colitis, ulcerative colitis, or nonspecific proctitis
5. Pregnant or breastfeeding women
6. Active infection or fever
7. Severe uncontrolled comorbidities (e.g., unstable heart disease, renal disease, chronic hepatitis, uncontrolled diabetes, psychiatric disorders)
8. Inability to comply with study protocol