Neoadjuvant chemoradiotherapy plus surgery versus active surveillance for oesophageal cancer: a stepped-wedge cluster randomised trial
Abstract Background Neoadjuvant chemoradiotherapy (nCRT) plus surgery is a standard treatment for locally advanced oesophageal cancer. With this treatment, 29% of patients have a pathologically complete response in the resection specimen. This provides the rationale for investigating an active surve...
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2018-02-01
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Online Access: | http://link.springer.com/article/10.1186/s12885-018-4034-1 |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Bo Jan Noordman Bas P. L. Wijnhoven Sjoerd M. Lagarde Jurjen J. Boonstra Peter Paul L. O. Coene Jan Willem T. Dekker Michael 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 Manon C. W. Spaander Roelf Valkema Edwin S. van der Zaag Ewout W. Steyerberg J. Jan B. van Lanschot on behalf of the SANO-study group |
spellingShingle |
Bo Jan Noordman Bas P. L. Wijnhoven Sjoerd M. Lagarde Jurjen J. Boonstra Peter Paul L. O. Coene Jan Willem T. Dekker Michael 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 Manon C. W. Spaander Roelf Valkema Edwin S. van der Zaag Ewout W. Steyerberg J. Jan B. van Lanschot on behalf of the SANO-study group Neoadjuvant chemoradiotherapy plus surgery versus active surveillance for oesophageal cancer: a stepped-wedge cluster randomised trial BMC Cancer Oesophageal cancer Neoadjuvant chemoradiotherapy Active surveillance Standard oesophagectomy |
author_facet |
Bo Jan Noordman Bas P. L. Wijnhoven Sjoerd M. Lagarde Jurjen J. Boonstra Peter Paul L. O. Coene Jan Willem T. Dekker Michael 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 Manon C. W. Spaander Roelf Valkema Edwin S. van der Zaag Ewout W. Steyerberg J. Jan B. van Lanschot on behalf of the SANO-study group |
author_sort |
Bo Jan Noordman |
title |
Neoadjuvant chemoradiotherapy plus surgery versus active surveillance for oesophageal cancer: a stepped-wedge cluster randomised trial |
title_short |
Neoadjuvant chemoradiotherapy plus surgery versus active surveillance for oesophageal cancer: a stepped-wedge cluster randomised trial |
title_full |
Neoadjuvant chemoradiotherapy plus surgery versus active surveillance for oesophageal cancer: a stepped-wedge cluster randomised trial |
title_fullStr |
Neoadjuvant chemoradiotherapy plus surgery versus active surveillance for oesophageal cancer: a stepped-wedge cluster randomised trial |
title_full_unstemmed |
Neoadjuvant chemoradiotherapy plus surgery versus active surveillance for oesophageal cancer: a stepped-wedge cluster randomised trial |
title_sort |
neoadjuvant chemoradiotherapy plus surgery versus active surveillance for oesophageal cancer: a stepped-wedge cluster randomised trial |
publisher |
BMC |
series |
BMC Cancer |
issn |
1471-2407 |
publishDate |
2018-02-01 |
description |
Abstract Background Neoadjuvant chemoradiotherapy (nCRT) plus surgery is a standard treatment for locally advanced oesophageal cancer. With this treatment, 29% of patients have a pathologically complete response in the resection specimen. This provides the rationale for investigating an active surveillance approach. The aim of this study is to assess the (cost-)effectiveness of active surveillance vs. standard oesophagectomy after nCRT for oesophageal cancer. Methods This is a phase-III multi-centre, stepped-wedge cluster randomised controlled trial. A total of 300 patients with clinically complete response (cCR, i.e. no local or disseminated disease proven by histology) after nCRT will be randomised to show non-inferiority of active surveillance to standard oesophagectomy (non-inferiority margin 15%, intra-correlation coefficient 0.02, power 80%, 2-sided α 0.05, 12% drop-out). Patients will undergo a first clinical response evaluation (CRE-I) 4–6 weeks after nCRT, consisting of endoscopy with bite-on-bite biopsies of the primary tumour site and other suspected lesions. Clinically complete responders will undergo a second CRE (CRE-II), 6–8 weeks after CRE-I. CRE-II will include 18F–FDG-PET-CT, followed by endoscopy with bite-on-bite biopsies and ultra-endosonography plus fine needle aspiration of suspected lymph nodes and/or PET- positive lesions. Patients with cCR at CRE-II will be assigned to oesophagectomy (first phase) or active surveillance (second phase of the study). The duration of the first phase is determined randomly over the 12 centres, i.e., stepped-wedge cluster design. Patients in the active surveillance arm will undergo diagnostic evaluations similar to CRE-II at 6/9/12/16/20/24/30/36/48 and 60 months after nCRT. In this arm, oesophagectomy will be offered only to patients in whom locoregional regrowth is highly suspected or proven, without distant dissemination. The main study parameter is overall survival; secondary endpoints include percentage of patients who do not undergo surgery, quality of life, clinical irresectability (cT4b) rate, radical resection rate, postoperative complications, progression-free survival, distant dissemination rate, and cost-effectiveness. We hypothesise that active surveillance leads to non-inferior survival, improved quality of life and a reduction in costs, compared to standard oesophagectomy. Discussion If active surveillance and surgery as needed after nCRT leads to non-inferior survival compared to standard oesophagectomy, this organ-sparing approach can be implemented as a standard of care. |
topic |
Oesophageal cancer Neoadjuvant chemoradiotherapy Active surveillance Standard oesophagectomy |
url |
http://link.springer.com/article/10.1186/s12885-018-4034-1 |
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doaj-0805a4431d264f0ebffc6b2b562c71382020-11-24T21:21:42ZengBMCBMC Cancer1471-24072018-02-0118111210.1186/s12885-018-4034-1Neoadjuvant chemoradiotherapy plus surgery versus active surveillance for oesophageal cancer: a stepped-wedge cluster randomised trialBo Jan Noordman0Bas P. L. Wijnhoven1Sjoerd M. Lagarde2Jurjen J. Boonstra3Peter Paul L. O. Coene4Jan Willem T. Dekker5Michael Doukas6Ate van der Gaast7Joos Heisterkamp8Ewout A. Kouwenhoven9Grard A. P. Nieuwenhuijzen10Jean-Pierre E. N. Pierie11Camiel Rosman12Johanna W. van Sandick13Maurice J. C. van der Sangen14Meindert N. Sosef15Manon C. W. Spaander16Roelf Valkema17Edwin S. van der Zaag18Ewout W. Steyerberg19J. Jan B. van Lanschot20on behalf of the SANO-study groupDepartment of Surgery, Erasmus MC – University Medical CentreDepartment of Surgery, Erasmus MC – University Medical CentreDepartment of Surgery, Erasmus MC – University Medical CentreDepartment of Gastroenterology, 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 – 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 Gastroenterology, Erasmus MC – University Medical CentreDepartment of Radiology and Nuclear Medicine, Erasmus MC – University Medical CentreDepartment of Surgery, Gelre HospitalDepartment of Medical Statistics and Bioinformatics, Leiden University Medical Centre, formerly department of Public Health, Erasmus MC – University Medical Centre RotterdamDepartment of Surgery, Erasmus MC – University Medical CentreAbstract Background Neoadjuvant chemoradiotherapy (nCRT) plus surgery is a standard treatment for locally advanced oesophageal cancer. With this treatment, 29% of patients have a pathologically complete response in the resection specimen. This provides the rationale for investigating an active surveillance approach. The aim of this study is to assess the (cost-)effectiveness of active surveillance vs. standard oesophagectomy after nCRT for oesophageal cancer. Methods This is a phase-III multi-centre, stepped-wedge cluster randomised controlled trial. A total of 300 patients with clinically complete response (cCR, i.e. no local or disseminated disease proven by histology) after nCRT will be randomised to show non-inferiority of active surveillance to standard oesophagectomy (non-inferiority margin 15%, intra-correlation coefficient 0.02, power 80%, 2-sided α 0.05, 12% drop-out). Patients will undergo a first clinical response evaluation (CRE-I) 4–6 weeks after nCRT, consisting of endoscopy with bite-on-bite biopsies of the primary tumour site and other suspected lesions. Clinically complete responders will undergo a second CRE (CRE-II), 6–8 weeks after CRE-I. CRE-II will include 18F–FDG-PET-CT, followed by endoscopy with bite-on-bite biopsies and ultra-endosonography plus fine needle aspiration of suspected lymph nodes and/or PET- positive lesions. Patients with cCR at CRE-II will be assigned to oesophagectomy (first phase) or active surveillance (second phase of the study). The duration of the first phase is determined randomly over the 12 centres, i.e., stepped-wedge cluster design. Patients in the active surveillance arm will undergo diagnostic evaluations similar to CRE-II at 6/9/12/16/20/24/30/36/48 and 60 months after nCRT. In this arm, oesophagectomy will be offered only to patients in whom locoregional regrowth is highly suspected or proven, without distant dissemination. The main study parameter is overall survival; secondary endpoints include percentage of patients who do not undergo surgery, quality of life, clinical irresectability (cT4b) rate, radical resection rate, postoperative complications, progression-free survival, distant dissemination rate, and cost-effectiveness. We hypothesise that active surveillance leads to non-inferior survival, improved quality of life and a reduction in costs, compared to standard oesophagectomy. Discussion If active surveillance and surgery as needed after nCRT leads to non-inferior survival compared to standard oesophagectomy, this organ-sparing approach can be implemented as a standard of care.http://link.springer.com/article/10.1186/s12885-018-4034-1Oesophageal cancerNeoadjuvant chemoradiotherapyActive surveillanceStandard oesophagectomy |