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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Adenocarcinoma of the Rectum
• Intervention / Treatment: Radiation: SCRT : 25 Gy in 5 fractions over 1 week to the pelvis using IGRT technique; Radiation: LCRT + Consolidation Chemotherapy

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.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Shivendra Singh, MCh; Phone Number: 919818975024; Email: drshivendraonco@gmail.com

Study Locations

• India
  • New Delhi, India, 110085
    • Rajiv Gandhi Cancer Institute And Research Centre
    • Contact: Shaifali Goel, DrNB SG; Phone Number: 918368382060; Email: doctor.shaifali@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: SCRT + Consolidation Chemotherapy; Radiotherapy: 25 Gy in 5 fractions over 1 week to the pelvis using IGRT technique.; Interval before Chemotherapy: 1-2 weeks after completion of radiotherapy.; Chemotherapy: Modified FOLFOX6 every 2 weeks (total of 12 cycles).	Radiation: SCRT : 25 Gy in 5 fractions over 1 week to the pelvis using IGRT technique; Arm A - SCRT + Consolidation Chemotherapy; Radiotherapy: 25 Gy in 5 fractions over 1 week to the pelvis using IGRT technique.; Interval before Chemotherapy: 1-2 weeks after completion of radiotherapy.; 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
Active Comparator: LCRT + Consolidation Chemotherapy; Radiotherapy: Primary tumor and involved nodes: 50 Gy in 25 fractions.; Elective nodal basin: 45 Gy in 25 fractions. Delivered concurrently with oral Capecitabine (825 mg/m² twice daily on radiotherapy days).	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological complete response (pCR) rate measured in proportion of participants (%)	Proportion of participants achieving pathological complete response, defined as ypT0N0 on histopathological examination of resected tumor specimens after surgery. Assessment will be performed by institutional pathologists according to standardized reporting guidelines. The pCR rate is central to evaluating early tumor response to total neoadjuvant therapy. Unit of Measure: Proportion of participants (%)	3 and 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local Recurrence Rate measured in percentage of participants (%)	Proportion of participants experiencing loco-regional relapse, defined as reappearance of tumor at the primary site or regional lymph nodes, as confirmed by clinical evaluation and imaging (pelvic MRI or CT scan) at specified intervals post-treatment. Unit of Measure: Percentage of participants (%)	3 and 5 years
Overall Survival (OS) in months	Overall survival is defined as the time from randomization to death from any cause. Participants who are alive at the time of analysis or are lost to follow-up will be censored at the last date known to be alive. Outcome will be summarized using median survival and survival rates at specified time points. Unit of Measure: Time in months	Evaluated at 3 years and 5 years
Acute Toxicities graded using CTCAE version 5.0	All adverse events occurring during RT and chemotherapy up to 3 months post-surgery	3 months post surgery
Late Toxicities documented using clinician assessment and patient reported outcomes EORTC QLQ-C30 and QLQ-CR29	Number and proportion of participants experiencing treatment-related adverse effects arising between 6 months and 2 years post-treatment, including bowel dysfunction (e.g., frequency, urgency), bladder dysfunction (e.g., incontinence, retention), and sexual dysfunction. Assessment will be performed through standardized clinician evaluation and patient-reported outcome measures using validated questionnaires. Unit of Measure: Percentage of participants (%)	6 months to 2 years post-treatment
Treatment completion Rate measured in percentage of participants (%)	Proportion of participants who complete the planned treatment regimen, including radiotherapy (RT), chemotherapy cycles, and surgery. Reasons for any deviations from the planned treatment, such as toxicity, patient refusal, or disease progression, will be documented and analyzed. Unit of Measure: Percentage of participants (%)	1 year
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0	Assessed by the proportion of participants adhering to the treatment protocol as planned, rates of treatment delays or dose reductions due to adverse events, and multidisciplinary team (MDT) decision-making trends regarding treatment modifications. These measures collectively evaluate the practical implementation and patient tolerance of the therapeutic regimen. Unit of Measure: Percentage of participants (%) and descriptive trends	1 year

Collaborators and Investigators

• Sponsor: Rajiv Gandhi Cancer Institute & Research Center, India
• Investigators: Study Director: Jaskaran Sethi, MD, Rajiv Gandhi Cancer Hospital and Research Centre, New Delhi

Publications and helpful links

General 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) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial. Lancet Oncol. 2021 Jan;22(1):29-42. doi: 10.1016/S1470-2045(20)30555-6. Epub 2020 Dec 7.

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): March 31, 2029

Study Registration Dates

• First Submitted: November 14, 2025
• First Submitted That Met QC Criteria: November 20, 2025
• First Posted (Actual): December 2, 2025

Study Record Updates

• Last Update Posted (Actual): December 2, 2025
• Last Update Submitted That Met QC Criteria: November 20, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: OUTCOMES; SURVIVAL; RECTAL CANCER; SHORT COURSE RADIOTHERAPY; LONG COURSE RADIOTHERAPY
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Rectal Diseases; Rectal Neoplasms; Therapeutics; Drug Therapy; Consolidation Chemotherapy
• Other Study ID Numbers: RGCIRC/IRB-BHR/52/2025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified data sets will include participant demographics, baseline measures, intervention details, clinical outcomes, and adverse events recorded during the study.
• IPD Sharing Time Frame: IPD and supporting information will be available beginning six months after publication of the primary results or completion of the study, whichever is later. Data will remain accessible for five years from the start date of availability.
• IPD Sharing Access Criteria: Qualified researchers who submit a methodologically sound research proposal will be able to access de-identified individual participant data underlying the main results, as well as supporting documents such as the study protocol and statistical analysis plan. Access will be granted through a secure data sharing portal, subject to data use agreements that ensure participant confidentiality and limit use to the specified research purpose
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No