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

Official title

Short Course or Long Course Radiotherapy as Total Neoadjuvant Therapy in Locally Advanced Rectal Cancer : A Prospective, Open Label, Single Institution, Randomized, Parallel Arm Comparative Study

Overview

This study compares two standard radiotherapy approaches (short-course vs. long-course) given before surgery in patients with locally advanced rectal cancer. The goal is to see which treatment is more effective and better tolerated.

Detailed description

The SHOOL study is a single-institution, open-label, randomized prospective study designed to evaluate and compare two internationally accepted total neoadjuvant therapy (TNT) strategies in patients with locally advanced rectal cancer (LARC). These strategies differ primarily in their radiotherapy schedule and include:

Arm A: Short-course radiotherapy (SCRT; 25 Gy in 5 fractions over 1 week), followed by consolidation chemotherapy and surgery

Arm B: Long-course chemoradiotherapy (LCRT; 50.4 Gy in 28 fractions with concurrent Capecitabine over 5-5.5 weeks), followed by consolidation chemotherapy and surgery The study acronym "SHOOL" reflects the clinical dilemma of whether SHOrt-course Or Long-course radiotherapy offers better or more practical outcomes when delivered within a TNT framework.

This prospective study aims to explore how these two strategies compare in terms of tumour response (as measured by pathological complete response, pCR), toxicity, treatment compliance, feasibility, quality of life, and local recurrence rates at 3 and 5 years. Given that both arms represent evolving standards of care, this study is designed to generate real-world data that can guide institutional decision-making and inform future definitive trials.

Interventions

• Radiation SCRT : 25 Gy in 5 fractions over 1 week to the pelvis using IGRT technique
  Arm A - SCRT + Consolidation Chemotherapy 1. Radiotherapy: 25 Gy in 5 fractions over 1 week to the pelvis using IGRT technique. 2. Interval before Chemotherapy: 1-2 weeks after completion of radiotherapy. 3. Chemotherapy: Modified FOLFOX6 every 2 weeks (total of 12 cycles). If the patient is fit, the option of intensifying the chemo to mFOLFIRINOX will be discussed with the patient
• Radiation LCRT + Consolidation Chemotherapy
  Arm B - LCRT + Consolidation Chemotherapy 1) Radiotherapy: o Primary tumor and involved nodes: 50 Gy in 25 fractions. o Elective nodal basin: 45 Gy in 25 fractions. Delivered concurrently with oral Capecitabine (825 mg/m² twice daily on radiotherapy days). o Technique: IGRT 2) Interval before Chemotherapy: 1-2 weeks after completion of chemoradiotherapy. 3) Chemotherapy: Modified FOLFOX6

Primary outcome measures

• Pathological complete response (pCR) rate measured in proportion of participants (%) [Time frame: 3 and 5 years]

Secondary outcome measures (6)

• Local Recurrence Rate measured in percentage of participants (%) [Time frame: 3 and 5 years]
• Overall Survival (OS) in months [Time frame: Evaluated at 3 years and 5 years]
• Acute Toxicities graded using CTCAE version 5.0 [Time frame: 3 months post surgery]
• Late Toxicities documented using clinician assessment and patient reported outcomes EORTC QLQ-C30 and QLQ-CR29 [Time frame: 6 months to 2 years post-treatment]
• Treatment completion Rate measured in percentage of participants (%) [Time frame: 1 year]
• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [Time frame: 1 year]

Eligibility criteria

Inclusion criteria

• Histologically confirmed adenocarcinoma of the rectum
• Locally advanced disease based on MRI including cT3-T4 and/or node positive disease (cN1 or N2)
• Tumor located within 15 cm from the anal verge (confirmed by endoscopy or MRI)
• ECOG performance status 0-2
• Hemoglobin ≥ 9 g/dL
• Absolute neutrophil count ≥ 1,500/mm³
• Platelets ≥ 100,000/mm³
• Total bilirubin ≤ 1.5 × ULN
• Aspartate transaminase/Alanine transaminase ≤ 2.5 × ULN
• Serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 60 mL/min
• Fit for neoadjuvant therapy and curative resection
• Willing and able to provide written, informed consent
• 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

• Metastatic disease at presentation (distant nodes, liver, lung, peritoneum, etc.)
• Prior pelvic radiotherapy or systemic chemotherapy for rectal cancer
• 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
• Known HIV infection with CD4 < 200 cells/μL, or active hepatitis B or C
• Severe comorbid conditions precluding therapy (e.g., decompensated cardiac, hepatic, or renal disease)
• Pregnant or breastfeeding women
• Inability to comply with protocol requirements or follow-up schedule
• Psychiatric illness or social situations that may limit compliance with study requirements

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

India · 1 center

• Rajiv Gandhi Cancer Institute and Research Centre — New Delhi

Publications

• Bahadoer RR, Dijkstra EA, van Etten B, Marijnen CAM, Putter H, Kranenbarg EM, Roodvoets AGH, Nagtegaal ID, Beets-Tan RGH, Blomqvist LK, Fokstuen T, Ten Tije AJ, Capdevila J, Hendriks MP, Edhemovic I, Cervantes A, Nilsson PJ, Glimelius B, van de Velde CJH, Hospers GAP; RAPIDO collaborative investigators. Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versu PMID 33301740

Identifiers

NCT: NCT07258797 · RGCIRC/IRB-BHR/52/2025

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗