Kirton Laura, Riley Richard, Gaunt Piers, Brennan Bernadette, Snell Kym
Cancer Research UK Clinical Trials Unit, School of Medical Sciences, College of Medicine and Health, University of Birmingham, Birmingham, UK
Department of Applied Health Sciences, School of Health Sciences, College of Medicine and Health, University of Birmingham, Birmingham, UK.
BMJ Open. 2024 Dec 20;14(12):e082941. doi: 10.1136/bmjopen-2023-082941.
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.
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.
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.
EudraCT number 2012-002107-17. ISRCTN number 92192408.
尤因肉瘤是一种罕见的儿科癌症。目前，尚无方法能在诊断时准确预测这些患者的生存率。疾病类型（即局限性疾病、肺/胸膜肺转移和其他转移）用于指导治疗决策，转移性患者的预后通常比局限性疾病患者更差。然而，并非所有患者都符合这一趋势。一个准确的预后模型可用于指导临床实践中的治疗决策，以避免患者接受不当的过度或治疗不足。
本研究旨在利用EE2012临床试验数据集，开发并内部验证新诊断的尤因肉瘤患者的预后模型。这些模型将纳入从文献综述中确定的预后因素，以预测患者在临床重要时间点无事件生存的概率。将开发三个模型，使用不同的模型选择方法和对过拟合的惩罚（完整模型或应用均匀收缩的向后选择；以及套索变量选择）来比较它们的性能和稳定性。将使用自举法对模型进行内部验证，以给出经乐观度调整的性能统计数据（校准和区分度）以及模型稳定性结果。将要求患者和临床用户群体确定风险阈值，以便在临床实践中基于该模型指导治疗决策。决策曲线分析将检验这些阈值下的临床实用性。
本研究是对EE2012临床试验数据的二次分析。EE2012试验获得了主管部门的伦理批准（英国伦理参考批准号12/NW/0827）。本研究受现有试验伦理的涵盖。本研究结果将发表在同行评审期刊上，作为未来研究的基准。
EudraCT编号2012 - 002107 - 17。ISRCTN编号92192408。
