Rectal CancerStockholm IIINCT00904813
The Stockholm III Trial on Different Preoperative Radiotherapy Regimens in Rectal Cancer
A study testing Short-course RT and Long-course RT in people with Rectal Cancer, run by Karolinska Institutet at 18 sites in Sweden.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rectal Cancer
- What is being tested?
- Short-course RT and Long-course RT
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 840 participants
- Where
- 18 sitesSweden
- Study dates
- Nov 1998to 31 Mar 2018
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Biopsy confirmed clinically resectable rectal adenocarcinoma within 15 cm from the anal verge
- Planned for bowel resection with an abdominal procedure.
- Informed consent.
Who cannot join
- 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
Trial locations and contacts
18 sites in 1 country.
18 sites in 1 country
Sweden18 sites
Danderyds Hospital
Danderyd, Stockholm County
Eskilstuna Hospital
Eskilstuna
Falun Hospital
Falun
Gävle Sjukhus
Gävle
Helsingborg Hospital
Helsingborg
Linköping University Hospital
Linköping
MAS University Hospital
Malmö
Mora Hospital
Mora, Dalarna County
Vrinnevi Hospital
Norrköping
Norrtälje Hospital
Norrtälje, Stockholm County
Södertälje Hospital
Södertälje, Stockholm County
Karolinska University Hospital
Stockholm, 17176
Ersta Hospital
Stockholm
South Hospital
Stockholm
St Görans Hospital
Stockholm
Norrlands Universitetssjukhus
Umeå
Uppsala University Hospital
Uppsala
Visby Hospital
Visby
About this study
Official title: A Prospective Randomized Trial on Different Preoperative Radiotherapy Regimens in Rectal Cancer, Stockholm III.
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.
Read the 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:
- Time to local recurrence.
Secondary outcomes:
- Recurrence-free survival
- Frequency of postoperative complications
- Frequency of tumour regression
- Conditions
- Rectal Cancer
- Being tested
- Short-course RT, Long-course RT
- Keywords
- Rectal cancer, Preoperative radiotherapy, Timing of Surgery, Prognosis
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Short-course RTRadiation
Preoperative radiotherapy (RT) given 5 times 5 Gray during five consecutive days, preferably Monday - Friday, with a four-field box technique, including the primary tumour and the primary and secondary lymph nodes in the pelvis.
Long-course RTRadiation
Preoperative radiotherapy (RT) given 2 Gy in 25 fractions during 5 weeks, total dose 50 Gy with a four-field box technique, including the primary tumour and the primary and secondary lymph nodes in the pelvis.
| Study group | Role | What they receive |
|---|---|---|
| 1. Short-course RT (5x5 Gy) + surgery within 1 week (SRT) | Active comparator | RT=Preoperative radiotherapy Gy=Gray Receives: Radiation: Short-course RT |
| 2. Short-course RT (5x5 Gy) + surgery after 4-8 weeks (SRT-delay) | Active comparator | RT=Preoperative radiotherapy Gy= Gray Receives: Radiation: Short-course RT |
| 3. Long-course RT (25x2 Gy) + surgery after 4-8 weeks (LRT-delay) | Active comparator | RT= Preoperative radiotherapy Gy= Gray Receives: Radiation: Long-course RT |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Local Recurrence.
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.
Measured: 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.
Secondary outcomes (2)
Number of Participants With Postoperative Complications in Relation to Preoperative Radiotherapy Regimen and Overall Treatment Time.
Postoperative complications was defined as any cardiovascular event, infectious, neurological or surgical complications occurring within 30 days after surgery, or during the same hospital admission, validated from medial records. Overall postoperative complication was defined as having at least one postoperative complication. Participants were grouped based on type of preoperative radiotherapy (RT) regimen (eg short- or long course) and overall treatment time (OTT), defined as time between start of RT and surgery. Participants receiving short-course RT were categorised into four different groups; Group A: OTT 7 days, Group B: OTT 8-13 days, Group C: OTT 5-7 weeks, Group D: OTT 8-13 weeks. Participants receiving long-course RT were categorised into two different groups; Group E: OTT 9-11 weeks, Groups F: OTT 12-14 weeks.
Measured: From surgery until 30 days postoperatively.
Tumour Regression Based on the Dworak Grading Scoring System
Tumour regression (TRG) was assessed using the Dworak grading scoring system, ranging from scores 0 to 4 with higher scores indicating better tumour regression. Definition of scores; 0 = no regression, 1 = dominant tumour mass with obvious fibrosis and/or vasculopathy, 2 = dominantly fibrotic changes with few tumour cells or groups (easy to find), 3 = very few (difficult to find microscopically) tumour cells in fibrotic tissue with or without mucous substance, 4 = no tumour cells, only fibrotic mass (total regression or complete response). All available microscopy slides were assessed by one pathologist, blinded to treatment.
Measured: At the time of surgery.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2009 (estimated)
- Study startNov 1998
- Primary completionFeb 2015
- Study completion31 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Rectal CancerStudies of the same condition, open and under way.
- More trials run by Karolinska InstitutetThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 840 participants (actual)
Sponsor and investigators
- Lead sponsor
- Karolinska Institutet
- Sponsor type
- University, hospital or other
- Collaborators
- Swedish Cancer Society, The Swedish Research Council
- Responsible party
- Principal investigator, Anna Martling, Karolinska Institutet
- Investigators
- Anna Martling, Professor, Principal investigator, Karolinska Institutet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00904813
- Sponsor's protocol ID
- 98/240
- Acronym
- Stockholm III
- Status last verified
- Apr 2021
- First submitted
- 19 May 2009
- Last updated
- 7 May 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Pettersson D, Lorinc E, Holm T, Iversen H, Cedermark B, Glimelius B, Martling A. Tumour regression in the randomized Stockholm III Trial of radiotherapy regimens for rectal cancer. Br J Surg. 2015 Jul;102(8):972-8; discussion 978. doi: 10.1002/bjs.9811.
PubMed 26095256Pettersson D, Cedermark B, Holm T, Radu C, Pahlman L, Glimelius B, Martling A. Interim analysis of the Stockholm III trial of preoperative radiotherapy regimens for rectal cancer. Br J Surg. 2010 Apr;97(4):580-7. doi: 10.1002/bjs.6914.
PubMed 20155787Pettersson D, Glimelius B, Iversen H, Johansson H, Holm T, Martling A. Impaired postoperative leucocyte counts after preoperative radiotherapy for rectal cancer in the Stockholm III Trial. Br J Surg. 2013 Jun;100(7):969-75. doi: 10.1002/bjs.9117. Epub 2013 Apr 2.
PubMed 23553796Erlandsson J, Holm T, Pettersson D, Berglund A, Cedermark B, Radu C, Johansson H, Machado M, Hjern F, Hallbook O, Syk I, Glimelius B, Martling A. Optimal fractionation of preoperative radiotherapy and timing to surgery for rectal cancer (Stockholm III): a multicentre, randomised, non-blinded, phase 3, non-inferiority trial. Lancet Oncol. 2017 Mar;18(3):336-346. doi: 10.1016/S1470-2045(17)30086-4. Epub 2017 Feb 10.
PubMed 28190762Erlandsson J, Lorinc E, Ahlberg M, Pettersson D, Holm T, Glimelius B, Martling A. Tumour regression after radiotherapy for rectal cancer - Results from the randomised Stockholm III trial. Radiother Oncol. 2019 Jun;135:178-186. doi: 10.1016/j.radonc.2019.03.016. Epub 2019 Apr 1.
PubMed 31015165Erlandsson J, Pettersson D, Glimelius B, Holm T, Martling A. Postoperative complications in relation to overall treatment time in patients with rectal cancer receiving neoadjuvant radiotherapy. Br J Surg. 2019 Aug;106(9):1248-1256. doi: 10.1002/bjs.11200. Epub 2019 Jun 14.
PubMed 31197822