Nodule IMmunophenotyping Biomarker for Lung Cancer Early Diagnosis Study

1.1 Lung cancer & Indeterminate Lung Nodule Surveillance Over 46,000 cases of lung cancer are diagnosed every year in the UK, making it the 3rd most common cancer type. Lung cancer is the biggest cause of cancer mortality in the UK and worldwide due to late presentation in the majority of cases. One-year survival for lung cancer ranges from 83% at stage I to 17% in stage IV disease (CRUK data).

1.2 Incidental Lung Nodules A significant challenge posed by lung screening is the identification of incidental lung nodules. 9.3% of all patients in the NELSON study had indeterminate nodules, and only 10% of these were diagnosed with cancer.

Such nodules are very frequently picked up on CT scans performed for other reasons, and may generate anxiety and uncertainty for patients and clinicians as well as using considerable NHS CT scan capacity. Current methods of stratification are based on a combination of The British Thoracic Society guidelines and the Brock, Herder and Fleischner risk models. Depending on the size of the lesion, guidelines recommend surveillance CT scans at 3-12 monthly intervals for solid and sub-solid lesions. Previous studies have suggested that persistent sub-solid nodules have a high risk of malignancy (~63%), and using Brock guidelines, larger nodules are often referred for biopsy (Henschke, 2002). However, a proportion of patients who score highly on these models will have negative biopsies, and there is a definite need for improved stratification.

In the screening setting, identification of early lung cancers and nodules in 'Lung Health Checks' - which use 'low dose' CT (LDCT) scan screening of high-risk populations (e.g. heavy smokers) has been shown to reduce lung cancer mortality by 20-26% as observed in the National Lung Cancer Screening Trial (NLST) and NELSON studies. A number of pilot trials within the UK have led to a commitment by NHS England to roll-out a £70m national program in a number of test sites. This program will lead to an expected 10% indeterminate finding rate putting further strain on the management of indeterminate nodules. RM Partners is undertaking one of the early lung screening pilots that led to this program across two clinical commissioning groups (CCGs) in West London in 2018, inviting over 8000 patients for a lung health check. This pilot has been extended in 2019-2020 and will also be incorporated in the NHS England National program.

1.3 Imaging and blood biomarkers in lung cancer early diagnosis Recent data suggest that the application of machine-learning approaches to the NLST trial data improves radiological risk-stratification of nodules (Ardila et al., 2019). Through the retrospective RMH LIBRA study, we are currently developing radiomics and Artificial Intelligence (AI) signatures to stratify lung nodules in patients from across the London cancer alliances. There is increasing interest in multi-model approaches, and the incorporation of 'multi-omic' data may enhance diagnostic accuracy and risk stratification (Bakr et al., 2018; Lu et al., 2018).