2024 World Conference on Lung Cancer (WCLC) - Posters-P3.06D.03 Prognostic and Predictive ctDNA Signature for Patients on Targeted Therapy for Metastatic NSCLC: A Pathway-based Approach

P3.06D.03 Prognostic and Predictive ctDNA Signature for Patients on Targeted Therapy for Metastatic NSCLC: A Pathway-based Approach

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Pdf Summary

The study aimed to develop a prognostic and predictive circulating tumor DNA (ctDNA) risk score (CRS) for patients with metastatic non-small cell lung cancer (mNSCLC) undergoing targeted therapy. It was observed that patients with the same actionable genomic alterations (GAs) responded differently to treatment. Researchers hypothesized that co-occurring GAs linked to signaling pathways, p53 interactions, and immune activation contributed to these varied responses.<br /><br />Using a multi-institutional cohort study of ctDNA-sequenced mNSCLC patients, researchers identified specific GAs, including mutations, structural variations, and copy number alterations. A CRS was calculated for each patient's ctDNA profile, assessing potential molecular pathway disturbances that could lead to therapy resistance. Points were assigned based on the involvement of the identified genes in particular signaling pathways: cell surface receptor signaling, nucleotide binding, and immune system response.<br /><br />The study included 1,127 patients enrolled between 2016 and 2020, with 418 receiving targeted therapy. Results indicated that a higher CRS was associated with decreased overall survival (OS), with notable differences between CRS increments, particularly from 0 to 1 and 2 to 3. The survival impact remained significant even after adjusting for demographic and clinical variables. For patients without actionable GAs, CRS was not predictive of OS.<br /><br />The findings underscore the importance of the genomic landscape surrounding actionable GAs in predicting treatment outcomes. The developed CRS, based on ctDNA and biological pathways, offers a prognostic and predictive tool for mNSCLC treatment, though further validation is recommended to confirm its utility. The study suggests that understanding the genomic context can enhance personalized approaches to cancer therapy, addressing the variable responses to targeted treatments.

Asset Subtitle

David Qian

Meta Tag

Speaker David Qian

Topic Pathology & Biomarkers

Keywords

circulating tumor DNA

ctDNA

metastatic non-small cell lung cancer

mNSCLC

genomic alterations

CRS

targeted therapy

signaling pathways

prognostic tool

personalized cancer therapy