Development and internal validation of prognostic models for event-free survival in newly diagnosed Ewing sarcoma patients based on routinely collected clinical characteristics from the European randomised controlled trial, EE2012
Introduction Ewing sarcoma is a rare paediatric cancer. Currently, there is no way of accurately predicting these patients’ survival at diagnosis. Disease type (ie, localised disease, lung/pleuropulmonary metastases and other metastases) is used to guide treatment decisions, with metastatic patients...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMJ Publishing Group
2024-12-01
|
| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/14/12/e082941.full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841537078598303744 |
|---|---|
| author | Richard Riley BERNADETTE BRENNAN Kym Snell Piers Gaunt Laura Kirton |
| author_facet | Richard Riley BERNADETTE BRENNAN Kym Snell Piers Gaunt Laura Kirton |
| author_sort | Richard Riley |
| collection | DOAJ |
| description | Introduction Ewing sarcoma is a rare paediatric cancer. Currently, there is no way of accurately predicting these patients’ survival at diagnosis. Disease type (ie, localised disease, lung/pleuropulmonary metastases and other metastases) is used to guide treatment decisions, with metastatic patients generally having worse outcomes than localised disease patients. However, not all patients fit this trend. An accurate prognostic model could be used to guide treatment decisions in clinical practice to avoid patients being incorrectly under or overtreated.Methods and analysis This study aims to develop and internally validate prognostic models in newly diagnosed Ewing sarcoma patients, using the EE2012 clinical trial data set. The models will incorporate prognostic factors, identified from a literature review, to predict patients’ probability of event-free survival at clinically important time points. Three models will be developed, for comparison of their performance and stability, using different methods of model selection and penalisation for overfitting (full model or backwards selection applying uniform shrinkage; and lasso variable selection). The models will be internally validated using bootstrapping to give optimism-adjusted performance statistics (calibration and discrimination) and model stability results. Patient and clinical user groups will be asked to determine risk thresholds to guide treatment decisions in clinical practice based on the model. Decision curve analyses will examine clinical utility at these thresholds.Ethics and dissemination This study is a secondary analysis of EE2012 clinical trial data. The EE2012 trial received ethical approval from the competent authorities (UK ethics reference approval number 12/NW/0827). This study is covered by the trial ethics in place. The results from this study will be published in peer-reviewed journals to act as a benchmark for future studies.Trial registration number EudraCT number 2012-002107-17. ISRCTN number 92192408. |
| format | Article |
| id | doaj-art-f5dd7c02c9484e87bc881643c50f7b63 |
| institution | Kabale University |
| issn | 2044-6055 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj-art-f5dd7c02c9484e87bc881643c50f7b632025-01-14T09:40:13ZengBMJ Publishing GroupBMJ Open2044-60552024-12-01141210.1136/bmjopen-2023-082941Development and internal validation of prognostic models for event-free survival in newly diagnosed Ewing sarcoma patients based on routinely collected clinical characteristics from the European randomised controlled trial, EE2012Richard Riley0BERNADETTE BRENNAN1Kym Snell2Piers Gaunt3Laura Kirton42 Department of Applied Health Sciences, School of Health Sciences, College of Medicine and Health, University of Birmingham, Birmingham, UK4 Royal Manchester Children`s Hospital, Manchester, UK2 Department of Applied Health Sciences, School of Health Sciences, College of Medicine and Health, University of Birmingham, Birmingham, UK1 Cancer Research UK Clinical Trials Unit, School of Medical Sciences, College of Medicine and Health, University of Birmingham, Birmingham, UK1 Cancer Research UK Clinical Trials Unit, School of Medical Sciences, College of Medicine and Health, University of Birmingham, Birmingham, UKIntroduction Ewing sarcoma is a rare paediatric cancer. Currently, there is no way of accurately predicting these patients’ survival at diagnosis. Disease type (ie, localised disease, lung/pleuropulmonary metastases and other metastases) is used to guide treatment decisions, with metastatic patients generally having worse outcomes than localised disease patients. However, not all patients fit this trend. An accurate prognostic model could be used to guide treatment decisions in clinical practice to avoid patients being incorrectly under or overtreated.Methods and analysis This study aims to develop and internally validate prognostic models in newly diagnosed Ewing sarcoma patients, using the EE2012 clinical trial data set. The models will incorporate prognostic factors, identified from a literature review, to predict patients’ probability of event-free survival at clinically important time points. Three models will be developed, for comparison of their performance and stability, using different methods of model selection and penalisation for overfitting (full model or backwards selection applying uniform shrinkage; and lasso variable selection). The models will be internally validated using bootstrapping to give optimism-adjusted performance statistics (calibration and discrimination) and model stability results. Patient and clinical user groups will be asked to determine risk thresholds to guide treatment decisions in clinical practice based on the model. Decision curve analyses will examine clinical utility at these thresholds.Ethics and dissemination This study is a secondary analysis of EE2012 clinical trial data. The EE2012 trial received ethical approval from the competent authorities (UK ethics reference approval number 12/NW/0827). This study is covered by the trial ethics in place. The results from this study will be published in peer-reviewed journals to act as a benchmark for future studies.Trial registration number EudraCT number 2012-002107-17. ISRCTN number 92192408.https://bmjopen.bmj.com/content/14/12/e082941.full |
| spellingShingle | Richard Riley BERNADETTE BRENNAN Kym Snell Piers Gaunt Laura Kirton Development and internal validation of prognostic models for event-free survival in newly diagnosed Ewing sarcoma patients based on routinely collected clinical characteristics from the European randomised controlled trial, EE2012 BMJ Open |
| title | Development and internal validation of prognostic models for event-free survival in newly diagnosed Ewing sarcoma patients based on routinely collected clinical characteristics from the European randomised controlled trial, EE2012 |
| title_full | Development and internal validation of prognostic models for event-free survival in newly diagnosed Ewing sarcoma patients based on routinely collected clinical characteristics from the European randomised controlled trial, EE2012 |
| title_fullStr | Development and internal validation of prognostic models for event-free survival in newly diagnosed Ewing sarcoma patients based on routinely collected clinical characteristics from the European randomised controlled trial, EE2012 |
| title_full_unstemmed | Development and internal validation of prognostic models for event-free survival in newly diagnosed Ewing sarcoma patients based on routinely collected clinical characteristics from the European randomised controlled trial, EE2012 |
| title_short | Development and internal validation of prognostic models for event-free survival in newly diagnosed Ewing sarcoma patients based on routinely collected clinical characteristics from the European randomised controlled trial, EE2012 |
| title_sort | development and internal validation of prognostic models for event free survival in newly diagnosed ewing sarcoma patients based on routinely collected clinical characteristics from the european randomised controlled trial ee2012 |
| url | https://bmjopen.bmj.com/content/14/12/e082941.full |
| work_keys_str_mv | AT richardriley developmentandinternalvalidationofprognosticmodelsforeventfreesurvivalinnewlydiagnosedewingsarcomapatientsbasedonroutinelycollectedclinicalcharacteristicsfromtheeuropeanrandomisedcontrolledtrialee2012 AT bernadettebrennan developmentandinternalvalidationofprognosticmodelsforeventfreesurvivalinnewlydiagnosedewingsarcomapatientsbasedonroutinelycollectedclinicalcharacteristicsfromtheeuropeanrandomisedcontrolledtrialee2012 AT kymsnell developmentandinternalvalidationofprognosticmodelsforeventfreesurvivalinnewlydiagnosedewingsarcomapatientsbasedonroutinelycollectedclinicalcharacteristicsfromtheeuropeanrandomisedcontrolledtrialee2012 AT piersgaunt developmentandinternalvalidationofprognosticmodelsforeventfreesurvivalinnewlydiagnosedewingsarcomapatientsbasedonroutinelycollectedclinicalcharacteristicsfromtheeuropeanrandomisedcontrolledtrialee2012 AT laurakirton developmentandinternalvalidationofprognosticmodelsforeventfreesurvivalinnewlydiagnosedewingsarcomapatientsbasedonroutinelycollectedclinicalcharacteristicsfromtheeuropeanrandomisedcontrolledtrialee2012 |