Supplementary Methods from Clinical Validation of a Cell-Free DNA Fragmentome Assay for Augmentation of Lung Cancer Early Detection

Mazzone, Peter J.; Bach, Peter B.; Carey, Jacob; Schonewolf, Caitlin A.; Bognar, Katalin; Ahluwalia, Manmeet S.; Cruz-Correa, Marcia; Gierada, David; Kotagiri, Sonali; Lloyd, Kathryn; Maldonado, Fabien; Ortendahl, Jesse D.; Sequist, Lecia V.; Silvestri, Gerard A.; Tanner, Nichole; Thompson, Jeffrey C.; Vachani, Anil; Wong, Kwok-Kin; Zaidi, Ali H.; Catallini, Joseph; Gershman, Ariel; Lumbard, Keith; Millberg, Laurel K.; Nawrocki, Jeff; Portwood, Carter; Rangnekar, Aakanksha; Sheridan, Carolina Campos; Trivedi, Niti; Wu, Tony; Zong, Yuhua; Cotton, Lindsey; Ryan, Allison; Cisar, Christopher; Leal, Alessandro; Dracopoli, Nicholas; Scharpf, Robert B.; Velculescu, Victor E.; Pike, Luke R. G.

doi:10.1158/2159-8290.27434356

Supplementary Methods from Clinical Validation of a Cell-Free DNA Fragmentome Assay for Augmentation of Lung Cancer Early Detection

https://doi.org/10.1158/2159-8290.27434356

journal contribution

posted on 2024-11-01, 07:22 authored by Peter J. Mazzone, Peter B. Bach, Jacob Carey, Caitlin A. Schonewolf, Katalin Bognar, Manmeet S. Ahluwalia, Marcia Cruz-Correa, David Gierada, Sonali Kotagiri, Kathryn Lloyd, Fabien Maldonado, Jesse D. Ortendahl, Lecia V. Sequist, Gerard A. Silvestri, Nichole Tanner, Jeffrey C. Thompson, Anil Vachani, Kwok-Kin Wong, Ali H. Zaidi, Joseph Catallini, Ariel Gershman, Keith Lumbard, Laurel K. Millberg, Jeff Nawrocki, Carter Portwood, Aakanksha Rangnekar, Carolina Campos Sheridan, Niti Trivedi, Tony Wu, Yuhua Zong, Lindsey Cotton, Allison Ryan, Christopher Cisar, Alessandro Leal, Nicholas Dracopoli, Robert B. Scharpf, Victor E. Velculescu, Luke R. G. Pike

<p>Additional detailed methods</p>

Funding

Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (AMRF)

Stand Up To Cancer (SU2C)

Gray Foundation

Honorable Tina Brozman Foundation (Tina’s Wish)

Commonwealth Foundation (CF)

Cole Foundation (CF)

History

Related Materials

1.
DOI - Is supplement to Clinical Validation of a Cell-Free DNA Fragmentome Assay for Augmentation of Lung Cancer Early Detection

ARTICLE ABSTRACT

Lung cancer screening via annual low-dose computed tomography has poor adoption. We conducted a prospective case–control study among 958 individuals eligible for lung cancer screening to develop a blood-based lung cancer detection test that when positive is followed by a low-dose computed tomography. Changes in genome-wide cell-free DNA fragmentation profiles (fragmentomes) in peripheral blood reflected genomic and chromatin characteristics of lung cancer. We applied machine learning to fragmentome features to identify individuals who were more or less likely to have lung cancer. We trained the classifier using 576 cases and controls from study samples and validated it in a held-out group of 382 cases and controls. The validation demonstrated high sensitivity for lung cancer and consistency across demographic groups and comorbid conditions. Applying test performance to the screening eligible population in a 5-year model with modest utilization assumptions suggested the potential to prevent thousands of lung cancer deaths.Significance: Lung cancer screening has poor adoption. Our study describes the development and validation of a novel blood-based lung cancer screening test utilizing a highly affordable, low-coverage genome-wide sequencing platform to analyze cell-free DNA fragmentation patterns. The test could improve lung cancer screening rates leading to substantial public health benefits.See related commentary by Haber and Skates, p. 2025