A Prospective Randomized Trial on Different Preoperative Radiotherapy Regimens in Rectal Cancer, Stockholm III.
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Rectal Cancer
- Sponsor
- Karolinska Institutet
- Enrollment
- 840
- Locations
- 18
- Primary Endpoint
- Time to Local Recurrence.
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
Preoperative radiotherapy (RT) is recommended to many patients with localised rectal cancer, not previously treated with pelvic RT. However, the optimum fractionation, the timing of surgery and the best use of concomitant chemotherapy remains controversial. There are theoretical reasons to believe that radiotherapy given in larger fractions during a shorter period of time might result in more late side effects than giving a conventional, more protracted RT in patients with rectal cancer. In addition, the optimum timing of surgery after RT, with respect to postoperative morbidity, mortality and potential downsizing of the tumour is not known.
To address these questions, a prospective randomized multicenter trial was initiated, the Stockholm III trial, in which patients with primarily resectable rectal cancer were randomized to short-course preoperative RT (5x5 Gy) followed by surgery within one week or after 4-8 weeks or long-course preoperative RT(25x2 Gy) followed by surgery after 4-8 weeks.
Detailed Description
840 participants (men and women) with a biopsy verified adenocarcinoma of the rectum scheduled for an open abdominal procedure were enrolled at 18 Swedish Hospitals during 1998-2013. In the initial protocol patients were randomly assigned (1:1:1) between three different RT courses; 5x5 Gy with surgery within 1 week (SRT), 5x5 Gy with surgery after 4-8 weeks (SRT-delay) or 25x2 Gy during 5 weeks without concomitant chemotherapy and surgery after 4-8weeks (LRT-delay). After a protocol amendment on May 21, 1999, participating hospitals could choose to randomise patients to just the short-course radiotherapy arms (1:1) or to all three arms. Randomisation was done by telephone by the Regional Cancer Centre in Stockholm, Sweden, after assessing inclusion and exclusion criteria. Computer generated randomisation lists were constructed by use of permuted block technique (block size of six for the three- arm randomisation, block size of four for the two-arm randomisation) and stratified by participating center. Investigators and patients were not masked to treatment. Follow-up was recommended at 3-, 6- and 12 months after surgery, and yearly thereafter. Although follow-up according to national guidelines with a minimum follow-up at 1 and 3 years was allowed. Patient data was also collected from the Swedish ColoRectal Cancer Register (SCRCR) and medical records. Primary outcome: 1. Time to local recurrence. Secondary outcomes: 1. Recurrence-free survival 2. Frequency of postoperative complications 3. Frequency of tumour regression
Investigators
Anna Martling
Professor, Senior Consultant Surgeon
Karolinska Institutet
Eligibility Criteria
Inclusion Criteria
- •Biopsy confirmed clinically resectable rectal adenocarcinoma within 15 cm from the anal verge
- •Planned for bowel resection with an abdominal procedure.
- •Informed consent.
Exclusion Criteria
- •Distant metastases
- •Locally advanced unresectable tumors
- •Planned for local excision
- •Previous radiotherapy to the abdominal or pelvic region
- •Severe ischemic heart disease or symptoms of severe arteriosclerosis
Outcomes
Primary Outcomes
Time to Local Recurrence.
Time Frame: From date of randomisation until date of local recurrence or date of death from any cause, whichever came first, assessed up to end of follow-up.
Local recurrence was defined as tumour growth below the level of the sacral promontory, related to the previous rectal cancer, and diagnosed radiographically with MRI, CT, or both, or clinically (preferably with histological confirmation). A diagnosis of local recurrence was confirmed and reported by the patient-responsible physician to the Swedish ColoRectal Cancer Registry (SCRCR), a nationwide validated national registry. Local recurrence was measured both as first and any event occurring during follow-up (censoring date March 30 2015), when all patients had been followed for at least 2 years.
Secondary Outcomes
- Tumour Regression Based on the Dworak Grading Scoring System(At the time of surgery.)
- Number of Participants With Postoperative Complications in Relation to Preoperative Radiotherapy Regimen and Overall Treatment Time.(From surgery until 30 days postoperatively.)