Updated protocol of the SANO trial: a stepped-wedge cluster randomised trial comparing surgery with active surveillance after neoadjuvant chemoradiotherapy for oesophageal cancer
Abstract Background The Surgery As Needed for Oesophageal cancer (SANO) trial compares active surveillance with standard oesophagectomy for patients with a clinically complete response (cCR) to neoadjuvant chemoradiotherapy. The last patient with a clinically complete response is expected to be incl...
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2021-05-01
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Online Access: | https://doi.org/10.1186/s13063-021-05274-w |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ben M. Eyck Berend J. van der Wilk Bo Jan Noordman Bas P. L. Wijnhoven Sjoerd M. Lagarde Henk H. Hartgrink Peter Paul L. O. Coene Jan Willem T. Dekker Michail Doukas Ate van der Gaast Joos Heisterkamp Ewout A. Kouwenhoven Grard A. P. Nieuwenhuijzen Jean-Pierre E. N. Pierie Camiel Rosman Johanna W. van Sandick Maurice J. C. van der Sangen Meindert N. Sosef Edwin S. van der Zaag Manon C. W. Spaander Roelf Valkema Hester F. Lingsma Ewout W. Steyerberg J. Jan B. van Lanschot on behalf of the SANO-study group |
spellingShingle |
Ben M. Eyck Berend J. van der Wilk Bo Jan Noordman Bas P. L. Wijnhoven Sjoerd M. Lagarde Henk H. Hartgrink Peter Paul L. O. Coene Jan Willem T. Dekker Michail Doukas Ate van der Gaast Joos Heisterkamp Ewout A. Kouwenhoven Grard A. P. Nieuwenhuijzen Jean-Pierre E. N. Pierie Camiel Rosman Johanna W. van Sandick Maurice J. C. van der Sangen Meindert N. Sosef Edwin S. van der Zaag Manon C. W. Spaander Roelf Valkema Hester F. Lingsma Ewout W. Steyerberg J. Jan B. van Lanschot on behalf of the SANO-study group Updated protocol of the SANO trial: a stepped-wedge cluster randomised trial comparing surgery with active surveillance after neoadjuvant chemoradiotherapy for oesophageal cancer Trials Oesophageal cancer Neoadjuvant chemoradiotherapy Active surveillance Standard oesophagectomy |
author_facet |
Ben M. Eyck Berend J. van der Wilk Bo Jan Noordman Bas P. L. Wijnhoven Sjoerd M. Lagarde Henk H. Hartgrink Peter Paul L. O. Coene Jan Willem T. Dekker Michail Doukas Ate van der Gaast Joos Heisterkamp Ewout A. Kouwenhoven Grard A. P. Nieuwenhuijzen Jean-Pierre E. N. Pierie Camiel Rosman Johanna W. van Sandick Maurice J. C. van der Sangen Meindert N. Sosef Edwin S. van der Zaag Manon C. W. Spaander Roelf Valkema Hester F. Lingsma Ewout W. Steyerberg J. Jan B. van Lanschot on behalf of the SANO-study group |
author_sort |
Ben M. Eyck |
title |
Updated protocol of the SANO trial: a stepped-wedge cluster randomised trial comparing surgery with active surveillance after neoadjuvant chemoradiotherapy for oesophageal cancer |
title_short |
Updated protocol of the SANO trial: a stepped-wedge cluster randomised trial comparing surgery with active surveillance after neoadjuvant chemoradiotherapy for oesophageal cancer |
title_full |
Updated protocol of the SANO trial: a stepped-wedge cluster randomised trial comparing surgery with active surveillance after neoadjuvant chemoradiotherapy for oesophageal cancer |
title_fullStr |
Updated protocol of the SANO trial: a stepped-wedge cluster randomised trial comparing surgery with active surveillance after neoadjuvant chemoradiotherapy for oesophageal cancer |
title_full_unstemmed |
Updated protocol of the SANO trial: a stepped-wedge cluster randomised trial comparing surgery with active surveillance after neoadjuvant chemoradiotherapy for oesophageal cancer |
title_sort |
updated protocol of the sano trial: a stepped-wedge cluster randomised trial comparing surgery with active surveillance after neoadjuvant chemoradiotherapy for oesophageal cancer |
publisher |
BMC |
series |
Trials |
issn |
1745-6215 |
publishDate |
2021-05-01 |
description |
Abstract Background The Surgery As Needed for Oesophageal cancer (SANO) trial compares active surveillance with standard oesophagectomy for patients with a clinically complete response (cCR) to neoadjuvant chemoradiotherapy. The last patient with a clinically complete response is expected to be included in May 2021. The purpose of this update is to present all amendments to the SANO trial protocol as approved by the Institutional Research Board (IRB) before accrual is completed. Design The SANO trial protocol has been published ( https://doi.org/10.1186/s12885-018-4034-1 ). In this ongoing, phase-III, non-inferiority, stepped-wedge, cluster randomised controlled trial, patients with cCR (i.e. after neoadjuvant chemoradiotherapy no evidence of residual disease in two consecutive clinical response evaluations [CREs]) undergo either active surveillance or standard oesophagectomy. In the active surveillance arm, CREs are repeated every 3 months in the first year, every 4 months in the second year, every 6 months in the third year, and yearly in the fourth and fifth year. In this arm, oesophagectomy is offered only to patients in whom locoregional regrowth is highly suspected or proven, without distant metastases. The primary endpoint is overall survival. Update Amendments to the study design involve the first cluster in the stepped-wedge design being partially randomised as well and continued accrual of patients at baseline until the predetermined number of patients with cCR is reached. Eligibility criteria have been amended, stating that patients who underwent endoscopic treatment prior to neoadjuvant chemoradiotherapy cannot be included and that patients who have highly suspected residual tumour without histological proof can be included. Amendments to the study procedures include that patients proceed to the second CRE if at the first CRE the outcome of the pathological assessment is uncertain and that patients with a non-passable stenosis at endoscopy are not considered cCR. The sample size was recalculated following new insights on response rates (34% instead of 50%) and survival (expected 2-year overall survival of 75% calculated from the moment of reaching cCR instead of 3-year overall survival of 67% calculated from diagnosis). This reduced the number of required patients with cCR from 264 to 224, but increased the required inclusions from 480 to approximately 740 patients at baseline. Conclusion Substantial amendments were made prior to closure of enrolment of the SANO trial. These amendments do not affect the outcomes of the trial compared to the original protocol. The first results are expected late 2023. If active surveillance plus surgery as needed after neoadjuvant chemoradiotherapy for oesophageal cancer leads to non-inferior overall survival compared to standard oesophagectomy, active surveillance can be implemented as a standard of care. |
topic |
Oesophageal cancer Neoadjuvant chemoradiotherapy Active surveillance Standard oesophagectomy |
url |
https://doi.org/10.1186/s13063-021-05274-w |
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doaj-03db1ac699e94e918426800e18e2f6682021-05-23T11:31:10ZengBMCTrials1745-62152021-05-012211610.1186/s13063-021-05274-wUpdated protocol of the SANO trial: a stepped-wedge cluster randomised trial comparing surgery with active surveillance after neoadjuvant chemoradiotherapy for oesophageal cancerBen M. Eyck0Berend J. van der Wilk1Bo Jan Noordman2Bas P. L. Wijnhoven3Sjoerd M. Lagarde4Henk H. Hartgrink5Peter Paul L. O. Coene6Jan Willem T. Dekker7Michail Doukas8Ate van der Gaast9Joos Heisterkamp10Ewout A. Kouwenhoven11Grard A. P. Nieuwenhuijzen12Jean-Pierre E. N. Pierie13Camiel Rosman14Johanna W. van Sandick15Maurice J. C. van der Sangen16Meindert N. Sosef17Edwin S. van der Zaag18Manon C. W. Spaander19Roelf Valkema20Hester F. Lingsma21Ewout W. Steyerberg22J. Jan B. van Lanschot23on behalf of the SANO-study groupDepartment of Surgery, Erasmus MC Cancer Institute, Erasmus University Medical CentreDepartment of Surgery, Erasmus MC Cancer Institute, Erasmus University Medical CentreDepartment of Surgery, Erasmus MC Cancer Institute, Erasmus University Medical CentreDepartment of Surgery, Erasmus MC Cancer Institute, Erasmus University Medical CentreDepartment of Surgery, Erasmus MC Cancer Institute, Erasmus University Medical CentreDepartment of Surgery, Leiden University Medical CentreDepartment of Surgery, Maasstad HospitalDepartment of Surgery, Reinier de Graaf GroupDepartment of Pathology, Erasmus MC – University Medical CentreDepartment of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical CentreDepartment of Surgery, Elisabeth Tweesteden HospitalDepartment of Surgery, Zorggroep TwenteDepartment of Surgery, Catharina HospitalDepartment of Surgery, Medical Centre LeeuwardenDepartment of Surgery, Radboud University Medical CentreDepartment of Surgery, The Netherlands Cancer Institute - Antoni van Leeuwenhoek HospitalDepartment of Radiation Oncology, Catharina HospitalDepartment of Surgery, Zuyderland Medical CentreDepartment of Surgery, Gelre HospitalDepartment of Gastroenterology, Erasmus MC – University Medical CentreDepartment of Radiology and Nuclear Medicine, Erasmus MC – University Medical CentreDepartment of Public Health, Erasmus MC – University Medical Centre RotterdamDepartment of Public Health, Erasmus MC – University Medical Centre RotterdamDepartment of Surgery, Erasmus MC Cancer Institute, Erasmus University Medical CentreAbstract Background The Surgery As Needed for Oesophageal cancer (SANO) trial compares active surveillance with standard oesophagectomy for patients with a clinically complete response (cCR) to neoadjuvant chemoradiotherapy. The last patient with a clinically complete response is expected to be included in May 2021. The purpose of this update is to present all amendments to the SANO trial protocol as approved by the Institutional Research Board (IRB) before accrual is completed. Design The SANO trial protocol has been published ( https://doi.org/10.1186/s12885-018-4034-1 ). In this ongoing, phase-III, non-inferiority, stepped-wedge, cluster randomised controlled trial, patients with cCR (i.e. after neoadjuvant chemoradiotherapy no evidence of residual disease in two consecutive clinical response evaluations [CREs]) undergo either active surveillance or standard oesophagectomy. In the active surveillance arm, CREs are repeated every 3 months in the first year, every 4 months in the second year, every 6 months in the third year, and yearly in the fourth and fifth year. In this arm, oesophagectomy is offered only to patients in whom locoregional regrowth is highly suspected or proven, without distant metastases. The primary endpoint is overall survival. Update Amendments to the study design involve the first cluster in the stepped-wedge design being partially randomised as well and continued accrual of patients at baseline until the predetermined number of patients with cCR is reached. Eligibility criteria have been amended, stating that patients who underwent endoscopic treatment prior to neoadjuvant chemoradiotherapy cannot be included and that patients who have highly suspected residual tumour without histological proof can be included. Amendments to the study procedures include that patients proceed to the second CRE if at the first CRE the outcome of the pathological assessment is uncertain and that patients with a non-passable stenosis at endoscopy are not considered cCR. The sample size was recalculated following new insights on response rates (34% instead of 50%) and survival (expected 2-year overall survival of 75% calculated from the moment of reaching cCR instead of 3-year overall survival of 67% calculated from diagnosis). This reduced the number of required patients with cCR from 264 to 224, but increased the required inclusions from 480 to approximately 740 patients at baseline. Conclusion Substantial amendments were made prior to closure of enrolment of the SANO trial. These amendments do not affect the outcomes of the trial compared to the original protocol. The first results are expected late 2023. If active surveillance plus surgery as needed after neoadjuvant chemoradiotherapy for oesophageal cancer leads to non-inferior overall survival compared to standard oesophagectomy, active surveillance can be implemented as a standard of care.https://doi.org/10.1186/s13063-021-05274-wOesophageal cancerNeoadjuvant chemoradiotherapyActive surveillanceStandard oesophagectomy |