# Clinical Utility of Biomarkers Driven Management of Indeterminate Pulmonary Nodules

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2024 · $766,782

## Abstract

PROJECT SUMMARY
The goal of this application is to test the clinical utility of a biomarker-informed approach to the evaluation and
management of indeterminate pulmonary nodules (IPNs). The study is designed to address this major and
growing unmet need given the adoption of lung cancer screening in the US and abroad and the common
occurrence of incidentally identified IPNs. We have developed and validated in external cohorts a high sensitivity
hs-CYFRA 21-1 biomarker assay and quantitative imaging features that together improve the current non-
invasive assessment of IPNs. In this proposal we hypothesize that a prediction model that integrates clinical
variables, hs-CYFRA 21-1 serum concentration, and quantitative imaging signature will show clinical utility by
reducing costly and invasive procedures while shortening time to diagnosis. To test this hypothesis, we propose
the following specific aims: First, we will test the clinical utility of a biomarker-informed strategy in a first of its
kind randomized clinical trial of IPN management. We will enroll 440 individuals with intermediate risk IPNs (10-
70% risk for cancer) at four institutions with the goal of reducing the number of invasive procedures and time to
diagnosis. In the control arm, participants will follow the standard of care and in the intervention arm the
biomarker results, expressed as a post-test probability for lung cancer, will be given to providers and participants
to inform nodule management. Second, to further our work in identifying new candidate biomarkers for better
risk stratification, we will apply a workflow for evaluation of candidates and validate the best candidates for entry
into a similar future trial to that proposed in Aim 1. In a set of prospectively collected specimens, evaluated
retrospectively in a blinded fashion (ProBE design), we will test the improvement in diagnostic accuracy of
candidate biomarkers in patients with IPNs of intermediate risk for lung cancer based on the Mayo risk model. A
blood biomarker signature from Abbott laboratories will be tested alone and in combination with a validated
radiomics score to determine if together they reclassify at least 20% of those at intermediate risk (10-70%) based
on the Mayo risk model alone into either a lower risk (<10%) or higher risk (>70%) group. We will determine the
optimal and most cost-effective Mayo model + biomarker combination or sequence needed to achieve the critical
decision thresholds in the management of IPNs. At the end of this project, we will have: a) demonstrated for the
first time the clinical utility of a biomarker informed approach to IPN management and acquired additional
outcomes data for a larger follow-on randomized multicenter trial, b) validated the incremental diagnostic
accuracy of new candidate biomarkers for the management of IPNs, and c) opened a new avenue for rapid
testing of the most effective combination(s) of candidates.

## Key facts

- **NIH application ID:** 10834755
- **Project number:** 5R01CA252964-04
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Anna E Baron
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $766,782
- **Award type:** 5
- **Project period:** 2021-05-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10834755

## Citation

> US National Institutes of Health, RePORTER application 10834755, Clinical Utility of Biomarkers Driven Management of Indeterminate Pulmonary Nodules (5R01CA252964-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10834755. Licensed CC0.

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