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

喉癌是头颈部最常见的癌症之一。患者往往受到严重影响；这种疾病及其治疗会影响患者的吞咽、声音、外表和健康。目前有多种治疗方法，包括放疗、化疗、激光手术或全喉切除术（完全切除喉部）。这些治疗方法中的任何一种都可能导致在颈部插入永久性的呼吸管（气管造口术）或喂食管。虽然已经有关于哪种治疗方法对喉癌患者最好的研究，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。患者对治疗的反应差异很大；一些病人的反应很好，而另一些病人则有很多严重的副作用，随后影响了他们的生活质量。不可能预测哪些患者在哪种治疗方法上效果好或不好，这意味着全国各地提供的治疗方法存在巨大差异。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别患者的量身定制治疗的新方法。我们的目标是通过建立一项“增强队列研究”来实现这一目标——也就是说，一大批新诊断的喉癌患者，将从他们身上收集数据和样本，并将对他们进行治疗和后续随访。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。这个队列可以作为未来研究这种疾病的基础，包括找出哪种治疗方法对哪个病人最好——这被称为个性化医疗。该项目分为三个工作流程：工作流程一：我们将分析几年前收集的现有患者队列（称为“头颈5000”队列）的数据。该队列包括1096例喉癌患者。它包含一些关于生活质量和生存的细节（没有样本），但没有我们计划的增强队列那么多细节。然而，对这些数据的分析将有助于我们形成我们增强队列的蓝图，并为我们提供一些初始数据。我们将听取领导这个队列的研究人员关于如何建立一个成功的队列研究的建议。工作流程2：我们将在两个大型头颈中心（利物浦和纽卡斯尔）建立我们的强化队列。他们都看到了很多喉癌患者，并致力于使这个项目成功。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。他在确保患者被招募参加试验方面具有专长，并在试验招募方面工作多年。我们将找出招募患者的最佳方式，记录高质量和完整的数据，收集样本，并长期跟踪患者，了解他们的进展情况。一旦这个项目在这些中心建立起来，我们就会把它推广到英格兰北部其他一些与我们有良好联系的大型头颈癌症中心。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提取的组织活检。我们将对这些样本进行分析，将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进行比较。通过这种方式，我们将能够开始分析疾病生物标志物，进而可能引导我们找到新的治疗方法

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