MEDIASTinal staging of non-small cell lung cancer by endobronchial and endoscopic ultrasonography with or without additional surgical mediastinoscopy (MEDIASTrial): a statistical analysis plan
Abstract Background Invasive mediastinal nodal staging is recommended by guidelines in selected patients with resectable non-small cell lung cancer (NSCLC). Endosonography is recommended as initial staging technique, followed by confirmatory mediastinoscopy in case of negative N2 or N3 cytology afte...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2021-02-01
|
| Series: | Trials |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13063-021-05127-6 |
| _version_ | 1829521398546038784 |
|---|---|
| author | Jelle E. Bousema Jouke T. Annema Erik H. F. M. van der Heijden Ad F. T. M. Verhagen Marcel G. W. Dijkgraaf Frank J. C. van den Broek on behalf of the MEDIASTrial study group |
| author_facet | Jelle E. Bousema Jouke T. Annema Erik H. F. M. van der Heijden Ad F. T. M. Verhagen Marcel G. W. Dijkgraaf Frank J. C. van den Broek on behalf of the MEDIASTrial study group |
| author_sort | Jelle E. Bousema |
| collection | DOAJ |
| description | Abstract Background Invasive mediastinal nodal staging is recommended by guidelines in selected patients with resectable non-small cell lung cancer (NSCLC). Endosonography is recommended as initial staging technique, followed by confirmatory mediastinoscopy in case of negative N2 or N3 cytology after endosonography. Confirmatory mediastinoscopy however is under debate owing its limited additional diagnostic value, its associated morbidity and its delay in the start of lung cancer treatment. The MEDIASTrial examines whether confirmatory mediastinoscopy can be safely omitted after negative endosonography in mediastinal nodal staging of NSCLC. The present work is the proposed statistical analysis plan of the clinical consequences of omitting mediastinoscopy, which is submitted before closure of the MEDIASTrial and before knowledge of any results was done to enhance transparency of scientific behaviour. Methods The primary outcome measure of this non-inferiority trial will be unforeseen N2 disease resulting from lobe-specific mediastinal lymph node dissection. For non-inferiority, the upper limit of the 95% confidence interval of the unforeseen N2 rate in the group without mediastinoscopy should not exceed 14.3% in order to probably have no negative impact on survival. Since this is a non-inferiority trial, both an intention to treat (ITT) and a per protocol (PP) analyses will be done. The ITT and the PP analyses should both indicate non-inferiority before the diagnostic strategy omitting mediastinoscopy will be interpreted as non-inferior to the strategy with mediastinoscopy. Secondary outcome measures include 30-day major morbidity and mortality, the total number of days of hospital care, overall and disease free 2-year survival, generic and disease-specific health related quality of life and cost-effectiveness and cost-utility of staging strategies with and without mediastinoscopy. Discussion The MEDIASTrial will determine if confirmatory mediastinoscopy can be omitted after tumour negative systematic endosonography in invasive mediastinal staging of patients with resectable NSCLC. Trial registration Netherlands Trial Register NL6344/NTR6528 . Registered on 2017 July 06 |
| first_indexed | 2024-12-16T15:15:06Z |
| format | Article |
| id | doaj.art-6a93a431447143b6a413daabb3ff99ff |
| institution | Directory Open Access Journal |
| issn | 1745-6215 |
| language | English |
| last_indexed | 2024-12-16T15:15:06Z |
| publishDate | 2021-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Trials |
| spelling | doaj.art-6a93a431447143b6a413daabb3ff99ff2022-12-21T22:26:50ZengBMCTrials1745-62152021-02-0122111310.1186/s13063-021-05127-6MEDIASTinal staging of non-small cell lung cancer by endobronchial and endoscopic ultrasonography with or without additional surgical mediastinoscopy (MEDIASTrial): a statistical analysis planJelle E. Bousema0Jouke T. Annema1Erik H. F. M. van der Heijden2Ad F. T. M. Verhagen3Marcel G. W. Dijkgraaf4Frank J. C. van den Broek5on behalf of the MEDIASTrial study group6Department of Surgery, Máxima MC, VeldhovenDepartment of Respiratory Medicine, Amsterdam University Medical Centre, University of AmsterdamDepartment of Pulmonary Medicine, Radboud University Medical CentreDepartment of Cardiothoracic Surgery, Radboud University Medical CentreDepartment of Epidemiology and Data Science, Amsterdam University Medical Centre, University of AmsterdamDepartment of Surgery, Máxima MC, VeldhovenDepartment of Surgery, Máxima MC, VeldhovenAbstract Background Invasive mediastinal nodal staging is recommended by guidelines in selected patients with resectable non-small cell lung cancer (NSCLC). Endosonography is recommended as initial staging technique, followed by confirmatory mediastinoscopy in case of negative N2 or N3 cytology after endosonography. Confirmatory mediastinoscopy however is under debate owing its limited additional diagnostic value, its associated morbidity and its delay in the start of lung cancer treatment. The MEDIASTrial examines whether confirmatory mediastinoscopy can be safely omitted after negative endosonography in mediastinal nodal staging of NSCLC. The present work is the proposed statistical analysis plan of the clinical consequences of omitting mediastinoscopy, which is submitted before closure of the MEDIASTrial and before knowledge of any results was done to enhance transparency of scientific behaviour. Methods The primary outcome measure of this non-inferiority trial will be unforeseen N2 disease resulting from lobe-specific mediastinal lymph node dissection. For non-inferiority, the upper limit of the 95% confidence interval of the unforeseen N2 rate in the group without mediastinoscopy should not exceed 14.3% in order to probably have no negative impact on survival. Since this is a non-inferiority trial, both an intention to treat (ITT) and a per protocol (PP) analyses will be done. The ITT and the PP analyses should both indicate non-inferiority before the diagnostic strategy omitting mediastinoscopy will be interpreted as non-inferior to the strategy with mediastinoscopy. Secondary outcome measures include 30-day major morbidity and mortality, the total number of days of hospital care, overall and disease free 2-year survival, generic and disease-specific health related quality of life and cost-effectiveness and cost-utility of staging strategies with and without mediastinoscopy. Discussion The MEDIASTrial will determine if confirmatory mediastinoscopy can be omitted after tumour negative systematic endosonography in invasive mediastinal staging of patients with resectable NSCLC. Trial registration Netherlands Trial Register NL6344/NTR6528 . Registered on 2017 July 06https://doi.org/10.1186/s13063-021-05127-6Non-small cell lung carcinomaMediastinal nodal stagingEndosonographyMediastinoscopyThoracic surgeryStatistical analysis plan |
| spellingShingle | Jelle E. Bousema Jouke T. Annema Erik H. F. M. van der Heijden Ad F. T. M. Verhagen Marcel G. W. Dijkgraaf Frank J. C. van den Broek on behalf of the MEDIASTrial study group MEDIASTinal staging of non-small cell lung cancer by endobronchial and endoscopic ultrasonography with or without additional surgical mediastinoscopy (MEDIASTrial): a statistical analysis plan Trials Non-small cell lung carcinoma Mediastinal nodal staging Endosonography Mediastinoscopy Thoracic surgery Statistical analysis plan |
| title | MEDIASTinal staging of non-small cell lung cancer by endobronchial and endoscopic ultrasonography with or without additional surgical mediastinoscopy (MEDIASTrial): a statistical analysis plan |
| title_full | MEDIASTinal staging of non-small cell lung cancer by endobronchial and endoscopic ultrasonography with or without additional surgical mediastinoscopy (MEDIASTrial): a statistical analysis plan |
| title_fullStr | MEDIASTinal staging of non-small cell lung cancer by endobronchial and endoscopic ultrasonography with or without additional surgical mediastinoscopy (MEDIASTrial): a statistical analysis plan |
| title_full_unstemmed | MEDIASTinal staging of non-small cell lung cancer by endobronchial and endoscopic ultrasonography with or without additional surgical mediastinoscopy (MEDIASTrial): a statistical analysis plan |
| title_short | MEDIASTinal staging of non-small cell lung cancer by endobronchial and endoscopic ultrasonography with or without additional surgical mediastinoscopy (MEDIASTrial): a statistical analysis plan |
| title_sort | mediastinal staging of non small cell lung cancer by endobronchial and endoscopic ultrasonography with or without additional surgical mediastinoscopy mediastrial a statistical analysis plan |
| topic | Non-small cell lung carcinoma Mediastinal nodal staging Endosonography Mediastinoscopy Thoracic surgery Statistical analysis plan |
| url | https://doi.org/10.1186/s13063-021-05127-6 |
| work_keys_str_mv | AT jelleebousema mediastinalstagingofnonsmallcelllungcancerbyendobronchialandendoscopicultrasonographywithorwithoutadditionalsurgicalmediastinoscopymediastrialastatisticalanalysisplan AT jouketannema mediastinalstagingofnonsmallcelllungcancerbyendobronchialandendoscopicultrasonographywithorwithoutadditionalsurgicalmediastinoscopymediastrialastatisticalanalysisplan AT erikhfmvanderheijden mediastinalstagingofnonsmallcelllungcancerbyendobronchialandendoscopicultrasonographywithorwithoutadditionalsurgicalmediastinoscopymediastrialastatisticalanalysisplan AT adftmverhagen mediastinalstagingofnonsmallcelllungcancerbyendobronchialandendoscopicultrasonographywithorwithoutadditionalsurgicalmediastinoscopymediastrialastatisticalanalysisplan AT marcelgwdijkgraaf mediastinalstagingofnonsmallcelllungcancerbyendobronchialandendoscopicultrasonographywithorwithoutadditionalsurgicalmediastinoscopymediastrialastatisticalanalysisplan AT frankjcvandenbroek mediastinalstagingofnonsmallcelllungcancerbyendobronchialandendoscopicultrasonographywithorwithoutadditionalsurgicalmediastinoscopymediastrialastatisticalanalysisplan AT onbehalfofthemediastrialstudygroup mediastinalstagingofnonsmallcelllungcancerbyendobronchialandendoscopicultrasonographywithorwithoutadditionalsurgicalmediastinoscopymediastrialastatisticalanalysisplan |