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

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

Laryngeal cancer is diagnosed in 2400 new patients each year in the UK and disproportionately affects those who are socioeconomically disadvantaged. Half of patients present with advanced disease and have poor survival. Treatment can render a patient permanently nil by mouth or in need of a permanent tracheostomy. Progress has stalled over the past 30 years with survival has remaining at best static, and at worst it has declined. Currently, we have no method of prognosticating how a specific tumour or patient will respond to treatment

We require an understanding of how an individual patient with laryngeal cancer responds to treatment. This project aims to inaugurate an enhanced clinical cohort of patients with laryngeal cancer, to define precision medicine in this disease:

Workstream 1: The head and neck 5000 cohort recruited 1065 patients with laryngeal cancer; these patients have three year oncological and quality of life follow up data. Initial analysis of these data will allow some information on outcome and inform development of the enhanced cohort.

Workstream 2: We will pilot processes to establish this cohort in two cancer centres and maximise recruitment and retention of patients and data collection. Analyses will assess data quality and provide a demonstration of the value of the cohort. We have opportunity to roll out the cohort to The Northern Head and Neck Cancer Alliance: this is a group of seven head and neck cancer centres, committed to improving outcomes.

Workstream 3: We will explore inclusion of radiomics and tissue biomarkers within the patient cohort. This workstream will establish governance and processes for collection of biological samples and radiological data to the cohort. "Proof of principle" pilot studies will be undertaken.

Following the fellowship, the ambition is to roll the cohort out nationally. In time, the cohort will have the potential to revolutionise progress in laryngeal cancer