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Defining precision medicine in laryngeal cancer: developing an enhanced clinical cohort

定义喉癌精准医学：开发增强的临床队列

基本信息

批准号：
MR/V037528/1
负责人：
David Hamilton
金额：
$ 23.26万
依托单位：
Newcastle University
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2021
资助国家：
英国
起止时间：
2021 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=MR%2FV037528%2F1
关键词：
Defining precision medicine laryngeal cancer

项目摘要

Cancer of the voice box (laryngeal cancer) is one of the most common cancers of the head and neck. Patients are often quite severely affected; the disease and its treatment affect a patient's swallow, voice, appearance, and wellbeing. At the moment there are various treatments available including radiotherapy, chemotherapy, laser surgery or total laryngectomy (complete removal of the voice box). Any of these treatments can lead to a permanent tube in the neck for breathing (tracheostomy) or a feeding tube. Although there has been research performed on which treatments are best for patients with laryngeal cancer, we have not made any significant progress in the treatment of this disease for around 30 years. There is a huge variation in how patients respond to treatment; some patients respond very well, whereas others have a lot of severe side effects with a subsequent impact on their quality of life. It is impossible to predict which patients will do well or badly on which treatment meaning that there is huge variation around the country in the treatments offered. Ultimately, we need to be able to predict how a patient with laryngeal cancer is likely to respond to treatment. If we were able to do this, this would allow us to make progress in the treatment of this disease, inform our discussions with patients, and allow us to develop new ways of tailoring treatments to individual patients. We aim to achieve this by establishing a "enhanced cohort study" - that, is, a large group of patients with newly diagnosed laryngeal cancer, from whom data and samples will be collected, and who will be followed through treatment and beyond. We could then use the details about them and their cancer (such as their swallowing function or CT scans) and compare these to their treatment outcome. This cohort could then be used as a foundation for future research in this disease, including working out which treatment will be best for which patient - this is called personalised medicine. This project is divided into three workstreams:Workstream one: We will analyse the data from an existing cohort of patients (called the "Head and Neck 5000" cohort) which was collected several years ago. This cohort includes 1096 patients with laryngeal cancer. It contains some detail about the quality of life and survival (and no samples), but not as much detail as we plan for our enhanced cohort. Nevertheless, analysis of these data will help us to form the blueprint of our enhanced cohort and provide us some initial data. We will take advice from the researcher who led this cohort about how to go about setting up a successful cohort study.Workstream 2: We will set up our enhanced cohort in two large head neck centres (Liverpool and Newcastle). Both see a lot of patients with laryngeal cancer and are committed to making this project work successfully. The doctor leading the project has worked in both centres and will ensure this study is offered to all patients with laryngeal cancer. He has expertise in ensuring patients are offered recruitment to trials and has worked in trial recruitment for many years. We will work out the best ways to recruit patients, record high-quality and complete data, collect samples, and follow people over time to find out how they are getting on. Once the project is established in these centres, we have roll it out to some other large head and neck cancer centres in northern England with whom we have excellent links.Workstream 3: Once we have the cohort set up, we will arrange to use the tissue biopsies which we take from the patients' cancers and their diagnosis scans. We will conduct analyses of these samples to compare the molecular and genetic detail as well as the data generated from the CT scan with the response of the patient and the cancer to the treatment. In this way we will be able to begin the analysis of disease biomarkers which, in turn, may lead us to new and novel therapies

喉癌是头颈部最常见的癌症之一。患者通常受到相当严重的影响;疾病及其治疗影响患者的吞咽，声音，外观和健康。目前有各种治疗方法，包括放疗，化疗，激光手术或全喉切除术（完全切除声带）。这些治疗中的任何一种都可能导致颈部永久性的呼吸管（气管造口术）或喂食管。虽然已经有研究表明哪种治疗方法对喉癌患者最好，但我们在治疗这种疾病方面没有取得任何重大进展，大约30年。患者对治疗的反应存在巨大差异;有些患者反应非常好，而另一些患者则有很多严重的副作用，随后影响他们的生活质量。这是不可能预测哪些病人会做好或坏的治疗意味着有巨大的差异在全国各地提供的治疗。最终，我们需要能够预测喉癌患者对治疗的反应。如果我们能够做到这一点，这将使我们能够在治疗这种疾病方面取得进展，为我们与患者的讨论提供信息，并使我们能够开发针对个体患者的治疗方法。我们的目标是通过建立一个“增强的队列研究”来实现这一目标--也就是说，一个新诊断的喉癌患者的大群体，从他们那里收集数据和样本，并在治疗期间和以后对其进行随访。然后，我们可以使用他们和他们的癌症的细节（如他们的吞咽功能或CT扫描），并将这些与他们的治疗结果进行比较。然后，这个队列可以作为这种疾病未来研究的基础，包括确定哪种治疗方法最适合哪种患者-这被称为个性化医疗。该项目分为三个工作流：工作流一：我们将分析几年前收集的现有患者队列（称为“头颈部5000”队列）的数据。该队列包括1096例喉癌患者。它包含了一些关于生活质量和生存率的细节（没有样本），但没有我们为增强队列计划的那么多细节。然而，分析这些数据将有助于我们形成我们的增强队列的蓝图，并为我们提供一些初步数据。工作流程2：我们将在两个大型头颈部中心（利物浦和纽卡斯尔）建立我们的增强队列。两人都看到了很多喉癌患者，并致力于使这个项目的工作成功。领导该项目的医生曾在两个中心工作，并将确保这项研究提供给所有喉癌患者。他在确保为患者提供试验招募方面具有专业知识，并在试验招募方面工作多年。我们将制定最佳的方法招募患者，记录高质量和完整的数据，收集样本，并随着时间的推移跟踪人们，以了解他们的进展情况。一旦该项目在这些中心建立，我们已经将其推广到英格兰北方的其他大型头颈部癌症中心，我们与他们有着良好的联系。工作流程3：一旦我们建立了队列，我们将安排使用我们从患者的癌症和他们的诊断扫描中获取的组织活检。我们将对这些样本进行分析，以比较分子和遗传细节以及CT扫描产生的数据与患者和癌症对治疗的反应。通过这种方式，我们将能够开始对疾病生物标志物的分析，这反过来可能会引导我们找到新的和新颖的治疗方法