2024 World Conference on Lung Cancer (WCLC) - Posters-P3.06D.01 Quantitative and Dynamic ctDNA as a Biomarker of Response and Survival in Treatment-Naive Patients with Advanced Lung Squamous Cancer

P3.06D.01 Quantitative and Dynamic ctDNA as a Biomarker of Response and Survival in Treatment-Naive Patients with Advanced Lung Squamous Cancer

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The study investigates the efficacy of MinerVa-Delta, a novel plasma-informed model, in quantifying dynamic changes in circulating tumor DNA (ctDNA) to serve as a biomarker for evaluating treatment response in lung squamous cell carcinoma (LUSC) patients undergoing immunochemotherapy or chemotherapy. Traditional methods of assessing treatment response, such as imaging, have limitations. MinerVa-Delta offers a molecular response evaluation (MRE) by considering variant allele frequency (VAF) changes and their uncertainties, providing a more nuanced understanding of treatment outcomes. <br /><br />MinerVa-Delta works by filtering out clonal hematopoietic variants and non-druggable variants with low VAF in post-treatment plasma. The weighted VAF differences for each variant are assessed before aggregating as a sum at the sample level to generate a metric reflecting ctDNA changes. This model was applied to cohorts of LUSC patients both receiving PD-1 blockade plus chemotherapy or chemotherapy alone.<br /><br />The research shows that MinerVa-Delta can classify patients into molecular responders and non-responders, with significant implications for progression-free survival (PFS) and overall survival (OS). Kaplan-Meier curves demonstrate the prognostic differences between molecular response groups defined by the MinerVa-Delta metric, especially noting better outcomes for responders compared to non-responders.<br /><br />Results suggest MinerVa-Delta enhances treatment response monitoring as it identifies stable disease (SD) patients who benefit from initial treatment. It's seen as complementary to the RECIST system by adding molecular insights. The study emphasizes that the tool could potentially influence treatment adjustments, tailoring therapies based on individualized ctDNA kinetics.<br /><br />Future research is proposed to expand the use of MinerVa-Delta in various cancers and further validate it in different clinical settings. The model shows promise for integration into early-phase clinical trials to better assess drug efficacy and improve patient management strategies.

Asset Subtitle

Fei Zhou

Meta Tag

Speaker Fei Zhou

Topic Pathology & Biomarkers

Keywords

MinerVa-Delta

circulating tumor DNA

lung squamous cell carcinoma

immunochemotherapy

treatment response

variant allele frequency

molecular responders

Kaplan-Meier curves

RECIST system

personalized medicine