Hilary Robbins

PhD MHS MSPH

International Agency for Research on Cancer

Scientist

PLCO (Learn more about this study)

2021-1022

Feb 3, 2022

The Lung EArly Proteins (LEAP) Project

Lung cancer is the most common cause of cancer death worldwide. Several randomized trials have now demonstrated that screening by low-dose CT can reduce lung cancer mortality among current and former smokers. However, current eligibility criteria exclude about half of future lung cancer cases from screening programs, and there are important harms due to identification of benign nodules. The balance of benefits and harms could be improved by leveraging novel tools to optimize decision making. Our objective is to translate a custom panel of protein biomarkers – the Lung EArly Proteins (LEAP) panel – to optimize (1) the decision to initiate screening and (2) the decision to biopsy a nodule.

Current work by our group, within the framework of an NCI-funded U19 project, is finalizing the design of the LEAP panel for early lung cancer detection. Our full discovery phase analyzed 1,158 annotated proteins in pre-diagnostic plasma samples collected up to 3 years before diagnosis among 504 lung cancer cases and matched controls. A targeted discovery step measured 481 of these proteins among 954 additional samples. Separately, we measured 1,081 proteins among 338 individuals who had malignant or benign nodules detected during lung cancer screening. Following excellent replication of proteins identified in the full discovery, we have selected 21 proteins to include on the LEAP panel, whose technical design is planned for completion in December 2021.

Our overarching objective is to carry out two targeted, late-stage translational studies to evaluate the potential to implement the panel in two scenarios. The specific role of PLCO in this project will be to determine whether within-person changes in proteins over time can better predict lung cancer than a single measurement. The development cohort will analyze pre-diagnostic blood samples from lung cancer cases and randomly sampled controls from the Prostate, Lung, and Ovarian Cancer Screening Trial (PLCO), with up to 5 measurements per participant. The validation cohort will analyze pre-diagnostic blood samples from cases and randomly sampled controls from the Carotene and Retinol Efficacy Trial (CARET) cohort, also with up to 5 measurements per participant. The performance of a repeat-measures model will be compared with a model that includes only a single timepoint.

Aim 1: Determine whether within-person changes in protein markers over time can better predict development of lung cancer than a single measurement.

The development cohort will analyze pre-diagnostic blood samples from lung cancer cases and randomly sampled controls from the Prostate, Lung, and Ovarian Cancer Screening Trial (PLCO), with up to 5 measurements per participant. The validation cohort will analyze pre-diagnostic blood samples from cases and randomly sampled controls from the Carotene and Retinol Efficacy Trial (CARET) cohort, also with up to 5 measurements per participant. The performance of a repeat-measures model will be compared with a model that includes only a single timepoint.