Mathematical Institute, University of Oxford, Oxford, UK.
Roche Pharma Research and Early Development, Roche Innovation Center, Basel, Switzerland.
Bull Math Biol. 2024 Jan 18;86(2):19. doi: 10.1007/s11538-023-01246-0.
Longitudinal tumour volume data from head-and-neck cancer patients show that tumours of comparable pre-treatment size and stage may respond very differently to the same radiotherapy fractionation protocol. Mathematical models are often proposed to predict treatment outcome in this context, and have the potential to guide clinical decision-making and inform personalised fractionation protocols. Hindering effective use of models in this context is the sparsity of clinical measurements juxtaposed with the model complexity required to produce the full range of possible patient responses. In this work, we present a compartment model of tumour volume and tumour composition, which, despite relative simplicity, is capable of producing a wide range of patient responses. We then develop novel statistical methodology and leverage a cohort of existing clinical data to produce a predictive model of both tumour volume progression and the associated level of uncertainty that evolves throughout a patient's course of treatment. To capture inter-patient variability, all model parameters are patient specific, with a bootstrap particle filter-like Bayesian approach developed to model a set of training data as prior knowledge. We validate our approach against a subset of unseen data, and demonstrate both the predictive ability of our trained model and its limitations.
从头颈部癌症患者的纵向肿瘤体积数据中可以看出,具有相似治疗前大小和阶段的肿瘤可能对相同的放射治疗分割方案有非常不同的反应。在这种情况下,通常会提出数学模型来预测治疗结果,并有可能指导临床决策和提供个性化的分割方案。在这种情况下,模型的有效使用受到阻碍,因为临床测量的稀疏性与产生所有可能的患者反应所需的模型复杂性形成鲜明对比。在这项工作中,我们提出了一个肿瘤体积和肿瘤组成的隔室模型,尽管相对简单,但能够产生广泛的患者反应。然后,我们开发了新的统计方法,并利用现有的临床数据队列,生成了一个既能预测肿瘤体积进展,又能预测治疗过程中不确定性变化的预测模型。为了捕捉个体间的变异性,所有模型参数都是针对每个患者的,我们采用了类似于自举粒子滤波器的贝叶斯方法来模拟一组训练数据作为先验知识。我们针对未观察到的数据子集对我们的方法进行了验证,并展示了我们训练模型的预测能力及其局限性。