Big data for small patients - Building "child-size" individual predictive models for life after childhood cancer

许多患有癌症的儿童将放射治疗作为他们护理的一部分。至于所有的癌症治疗，都存在持续副作用的风险，如学习困难和生长减慢。需要研究来减少这种副作用，这对儿童尤其重要，因为他们的预期寿命很长。放射治疗计划对肿瘤给予最大剂量，对附近健康器官给予最小剂量。然而，即使使用最先进的辐射方式(例如，使用曼彻斯特新的质子束治疗机)，也永远不可能避免所有健康的器官。这项研究将发现健康器官的哪些部分特别受到辐射的损害(“重要区域”)。这一知识在计划放射治疗时将非常有用，因为通常可以省去靠近肿瘤的器官的重要区域，而不是整个器官。因此，发现这些重要的区域将是朝着减少许多癌症儿童的副作用迈出的一步。田纳西州孟菲斯的圣裘德儿童研究医院是世界上拥有最多和最好记录的儿童健康数据的癌症中心。在圣裘德接受放射治疗的儿童有非常详细和完整的随访，他们的副作用使用最新的方法进行测量。在这个项目中，我们将：(1)建立一个联合数据分析结构，以表明我们的新方法可以用于圣裘德的数据；通过这个结构，我们将发现，例如，大脑中辐射导致学习问题最多的区域。(2)测量不同年龄、不同大小儿童之间器官大小和形态的变化。为此，我们将使用圣犹大患者以及美国500名健康儿童的图像，这些儿童年龄从6个月到16岁，每两年扫描一次(我们有权使用这些数据进行研究)。这些信息将帮助我们使我们的方法更加精确，并能够找到更小的“重要区域”。我们还将使用这些图像来建立儿童感兴趣器官(例如语言中心、荷尔蒙腺体)的生长模型，这将对研究其他儿童疾病的研究人员有用。(3)开发新的更好的方法来衡量副作用，使用所有关于儿童成年后健康状况的后续信息。这将意味着，例如，我们可以使用图像显示每个儿童即使在治疗多年后服用的健康状况。这将是此类项目中第一个专注于了解癌症儿童副作用的项目。在未来，这个项目的结果将帮助医生进行更智能的放射治疗，副作用更少。生长器官的模型也将对其他儿童疾病的研究有用。

Many children with cancer have radiation treatment as part of their care. As for all cancer treatments, there is a risk of lasting side-effects such as learning problems and reduced growth. Research is needed to reduce such side-effects, which is particularly important for children because of their long life expectancy. Radiation treatment is planned to give maximal dose to the tumour and minimal doses to nearby healthy organs. However, even with the most advanced ways of giving radiation (e.g. using the new Proton Beam Therapy machine in Manchester) it will never be possible to avoid all healthy organs. This fellowship will find which parts of healthy organs are particularly damaged by radiation ('the important regions'). This knowledge would be incredibly useful when planning radiation treatments, because it is often possible to spare the important regions of an organ close to the tumour but not the whole organ. Hence, finding these important regions would be a step toward allowing reduced side-effects in many children with cancer. The cancer centre with the most and the best documented children's health data in the world is St Jude Children's Research Hospital in Memphis, Tennessee. Children treated with radiation at St Jude have a very detailed and complete follow-up, and their side effects are measured using the most up-to-date methods. In this project, we will:(1) Set up a joint data analysis structure to show that our new method can be used on St Jude's data; with this, we will discover, for example, regions of the brain where radiation causes the most learning problems. (2) Measure the changes in organ size and shape between children of different ages and sizes. For this we will use images from St Jude patients as well as from 500 healthy children in the United States, aged from 6 months to 16 years that were scanned every 2 years (we have permission to use these data for research). This information will help us make our method even more precise and able to find smaller "important regions". We will also use those images to build models of growth of the organs of interest (e.g. language center, hormone glands) in children, which will be useful for researchers studying other childhood diseases.(3) Develop new and better ways to measure side-effects, using all the follow-up information obtained about a child's health as they grow into adulthood. This will mean, for example, that we can use images showing the health of each child even though taken many years after treatment.This will be the first project of this kind focused on understanding side effects in children with cancer. In the future, the results from this project will help doctors give 'smarter' radiation treatments, with fewer side-effects. The models of growing organs will also be useful for research in other childhood diseases.