Abstract CT068: CASCADE-LUNG: validation of a blood-based assay that evaluates cell-free DNA fragmentation patterns to detect lung cancer
Authors: Barta Julie A. , Freedland Stephen , Mazzone Peter J. , Isaacson Amy E. , Hewitt Alisa M. , Jakubowski Debbie , Bach Peter B. , Velculescu Victor E. 
Published: April 2023

Abstract
Rationale: Despite longstanding national recommendations for lung cancer screening by low-dose computed tomography (LDCT), annual participation rates are below 15%. Cost, access, and uncertainty over individual-level benefits and harms of screening preclude greater uptake. The development of a low-cost initial blood test that detects lung cancer with high sensitivity could boost LDCT screening rates and improve screening efficiency, by identifying within the screening-eligible population those at relatively higher risk of lung cancer. DELFI (DNA evaluation of fragments for early interception) is a technology that uses low-coverage, whole-genome sequencing and machine learning to detect cancer signals in the blood. In an early study, DELFI demonstrated high sensitivity to detect stage I/II lung cancers [PMID 34417454]. CASCADE-LUNG (NCT05306288) is an ongoing study to clinically validate a DELFI-based test to detect lung cancers that would be found by chest LDCT. Study Design and
Methods: CASCADE-LUNG is an event-driven, multisite, prospective, cross-sectional, observational, blood specimen collection study. Eligible individuals are ≥50 years old with ≥20 pack-years history of smoking who are scheduled for a first-time or annual lung cancer screening by chest CT scan within ~30 days after enrollment. Individuals are excluded for any history of hematologic malignancy or organ transplantation, prior cancer diagnosis or prior cancer treatment within 2 years before enrollment, and blood transfusion within 120 days before enrollment. Blood samples are collected within 30 days after enrollment for DELFI analysis. Medical record reviews are conducted at 4 months and 12 months post-enrollment, during which medical history (including social and family history and cancer screening history), demographics, imaging reports, diagnostic reports, surgery reports, pathology reports, and other diagnostic information are collected. Objectives are to evaluate the sensitivity and specificity of a DELFI-based test to detect lung cancer (primary), including within clinically relevant subgroups such as stage, nodule size, age, and race/ethnicity (secondary). Clinical endpoints include the presence or absence of histopathologically confirmed lung cancer diagnosed between the time of the enrollment chest CT scan and the 4-month follow-up visit (primary) and the 12-month follow-up visit (secondary), and adverse events associated with blood specimen collection (secondary). About 15,000 participants are expected to enroll to reach ~70 lung cancers that are suitable for analysis. Enrollment began in April 2022 and is expected to close in 2023.
Citation Format: Julie A. Barta, Stephen Freedland, Peter J. Mazzone, Amy E. Isaacson, Alisa M. Hewitt, Debbie Jakubowski, Peter B. Bach, Victor E. Velculescu. CASCADE-LUNG: validation of a blood-based assay that evaluates cell-free DNA fragmentation patterns to detect lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT068.