Jamie Chaft

Overall survival with circulating tumor DNA-guided therapy in advanced non-small-cell lung cancer.

Publisher: Springer Science and Business Media LLC

Date: 11-2022

DOI: 10.1038/S41591-022-02047-Z

Abstract: Circulating tumor DNA (ctDNA) sequencing guides therapy decisions but has been studied mostly in small cohorts without sufficient follow-up to determine its influence on overall survival. We prospectively followed an international cohort of 1,127 patients with non-small-cell lung cancer and ctDNA-guided therapy. ctDNA detection was associated with shorter survival (hazard ratio (HR), 2.05 95% confidence interval (CI), 1.74-2.42 P < 0.001) independently of clinicopathologic features and metabolic tumor volume. Among the 722 (64%) patients with detectable ctDNA, 255 (23%) matched to targeted therapy by ctDNA sequencing had longer survival than those not treated with targeted therapy (HR, 0.63 95% CI, 0.52-0.76 P < 0.001). Genomic alterations in ctDNA not detected by time-matched tissue sequencing were found in 25% of the patients. These ctDNA-only alterations disproportionately featured subclonal drivers of resistance, including RICTOR and PIK3CA alterations, and were associated with short survival. Minimally invasive ctDNA profiling can identify heterogeneous drivers not captured in tissue sequencing and expand community access to life-prolonging therapy.

HER2 insertion YVMA mutant lung cancer: Long natural history and response to afatinib

Publisher: Elsevier BV

Date: 12-2015

DOI: 10.1016/J.LUNGCAN.2015.10.025

Memorial Sloan Kettering Cancer Center

Location: United States of America

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New York University School Of Medicine

Location: United States of America

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Princeton University

Location: United States of America

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