Liverpool Lung Project

The project is led by Prof John Field, with Dr Michael Davies, Roy Castle Lung Cancer Senior Research Fellow, and Lakis Liloglou, Senior Lecturer in molecular oncology (now based at Edge Hill University).

Dr Liloglou leads molecular biomarker research and Dr Davies the clinical resources group (incorporating the Liverpool Lung Project biobank), working with international academic, clinical and industrial partners to develop new ways to diagnose and characterise lung cancers.

Background

The Liverpool Lung Project (LLP) collects data and tissue samples from individuals at risk of lung cancer in the general population, from those undergoing diagnosis in hospitals and from those receiving treatment after diagnosis. 

The data collected include personal history and lifestyle (epidemiology), clinical data (from medical notes) and follow-up data (data collected about the diseases, cancer or mortality after recruitment). 

This information is used by scientists locally, nationally and internationally to better understand lung cancer and to develop new, or improved, ways of detecting the disease, identify high risk individuals for screening programmes and determine the best treatment of the disease.

What is the problem to be addressed?

Our charity has funded one of the largest collections of data and samples from a lung cancer population cohort (approximately 13,000 individuals from the Liverpool area, including 9000 recruited while healthy, with around 200,000 different tissue samples); by determining which individuals get lung cancer we can perform scientific studies to determine the risk factors for lung cancer, as in the LLP Lung Cancer Risk Model. 

The aim of this Lung Cancer Risk prediction model is to identify individuals at high risk of developing lung cancer. An updated risk model (LLP LLP_v2) was used in the UK Lung Cancer Screening Trial (UKLS), which showed it was possible to detect lung cancer at an earlier stage by targeted low-dose CT scans for those with the greatest risk. The cancer incidence data from the 75,000 individuals who responded to the first UKLS risk questionnaire has been used to validate LLP_v2 and calibrate the LLP risk model, subsequently published as the LLP_v3 risk score.

The Liverpool Lung Project also recruits patients at the time of diagnosis and those undergoing surgery.  Samples and data from these individuals, together with controls from our population cohort, are primarily used in scientific studies to discover new biomarkers – substances that can be measured in samples of blood, sputum or tissue that tell us something useful about the disease.  This may be, for example, changes in a patient’s DNA (mutation or methylation) that, when detected in biopsy samples or blood, can indicate the person’s risks of lung cancer, can confirm the present of lung cancer or tell us what type of lung cancer a person has (which may lead to personalised treatment).

Sample and data collection must be done with the greatest of care under strict conditions of: confidentiality (data protection); informed consent (ensuring those who take part in research are aware of the reasons why it is being done, understand what is required and any risks of taking part); ethical approval (oversight by regulating authorities); transparency (reporting on activity and outcomes); governance (ensuring adherence to legal, ethical and moral guidelines) and scientific rigour (performing useful and insightful research to the highest international standards).

Collection, storage, documentation, governance, and provision of samples for research involves a core team of research nurses, technicians, administrators and scientists, funded by RCLCF.  Additionally, it relies on a network of healthcare professionals across multiple NHS trusts, the support of the University of Liverpool, and most importantly, on the trust and generosity of our tissue donors. 

Maximising the use of these samples in research of the highest quality is the ultimate aim; this is achieved through additional research funding within the RCLCRP and studies in collaboration with a range of international academic projects and commercial laboratories.

Key achievements of the project:

• We have significantly contributed to successful completion of three EU-funded research projects: the European Early Lung Cancer (EUELC) project to determine if specific genetic alterations occurring in lung cancers are detectable in the pre-cancerous normal lung; CURELUNG, examining the alterations in DNA associated with lung cancer; LCAOS, developing a novel breath detection device for lung cancer detection and characterisation.
• We have completed initial recruitment of the LLP population cohort, a major bioresource of over 9000 at risk individuals that we follow-up and that are available for further clinic appointments and questionnaires to gather further samples and data.
• Our hospital cohort, of diagnostic and surgical patients, now stands in excess of 4000 individuals, an important resource for diagnostic biomarker discovery and validation.
• LLP Biobank samples and data has supported a range of research projects funded by a variety of agencies (e.g., NIH (USA), RCLCF, NWCRF, CRUK); ongoing multi-centre international studies of lung cancer epidemiology (ILCCO) and genetic risk (TRICL/Oncoarray); pilot projects, PhD studentships and post-doctoral studies led by RCLCRP.
• Recognising the increasing importance of biotechnology companies in development of novel diagnostic methods, we have instigated pilot studies with different samples and techniques (partly through funding from by Knowledge Exchange awards from the University of Liverpool).  The analytical work in these studies is funded by the companies, but contributes to publication and opportunities for subsequent external funding or internal investment.  One study with a US company looked at using a novel technique to analyse sputum for lung cancer detection; sputum samples from cases and controls were provided and results presented at the World Conference on Lung Cancer.  Three studies used blood plasma as a source of biomarkers, but using different technologies.  One looked at mutations in circulating DNA, initially in a set of cases with known mutations in their tumour; this technology is now used clinically for lung cancer patients.  Another looked at profiles of metabolites and has produced exciting results in a pilot study, which were then validated in a larger cohort of samples. The third looked at small molecules called miRNA that help control how cells behave and that we previously showed were significantly different between cancers and normal lung.
• The LLP Risk Model was an integral part of the UKLS (UK Lung Screening) low-dose CT screening trial, which has now been completed and has made an important contribution to the case for introduction of lung cancer screening in the UK.
• The UKLS findings and the LLP Risk Model were used in an ambitious project aimed at earlier diagnosis of lung cancers run by Liverpool Clinical Commissioning Group and Liverpool Health Partners, based at Liverpool Heart and Chest Hospital – Targeted Lung Health checks.
• The LLP Risk Model is also an integral part of the ambitious NHS Targeted Healthy Lung Check, which aims to further demonstrate that low-dose CT early detection of lung cancer saves lives.
• We continue to support scholarship through research, including supporting externally funded research students who have successfully completed their PhDs