Adenocarcinoma of the Rectum
Conditions
Keywords
SHORT COURSE RADIOTHERAPY, LONG COURSE RADIOTHERAPY, RECTAL CANCER, OUTCOMES, SURVIVAL
Brief summary
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
RADIATIONSCRT : 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
RADIATIONLCRT + 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
Sponsors
Rajiv Gandhi Cancer Institute & Research Center, India
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathological complete response (pCR) rate measured in proportion of participants (%) | 3 and 5 years | 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 (%) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) in months | Evaluated at 3 years and 5 years | 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 |
| Acute Toxicities graded using CTCAE version 5.0 | 3 months post surgery | All adverse events occurring during RT and chemotherapy up to 3 months post-surgery |
| Local Recurrence Rate measured in percentage of participants (%) | 3 and 5 years | 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 (%) |
| Treatment completion Rate measured in percentage of participants (%) | 1 year | 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 (%) |
| Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 | 1 year | 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 |
| Late Toxicities documented using clinician assessment and patient reported outcomes EORTC QLQ-C30 and QLQ-CR29 | 6 months to 2 years post-treatment | 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 (%) |
Countries
India
Contacts
Primary ContactShivendra Singh, MCh
Outcome results
None listed