Prospective evaluation of cell-free dna fragmentation profiles for lung cancer detection

SESSION TITLE: Updates in Lung Cancer SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/10/2023 12:00 pm - 12:45 pm PURPOSE: While <20% of annual lung cancer cases are diagnosed with stage I disease, approximately 53% of screen-detected lung cancers are diagnosed in stage I. Annual LDCT screening has life-saving potential by shifting the diagnosis of lung cancer to earlier-stage disease, when there is greater potential for cure. However, <10% of eligible persons screen each year, with sharp declines in year-after-year screening adherence. Barriers to lung cancer screening nonadherence include active smoking status, lack of insurance, high costs, and uncertainty of individual-level benefit and risk. A simple, cost-effective initial blood test with high sensitivity for early-stage lung cancer detection may augment LDCT screening rates. METHODS: DELFI-L101 (NCT04825834) is a prospective, observational case-control study designed to train and test classifiers for lung cancer detection using DELFI (DNA evaluation of fragments for early interception), a technology that identifies patterns of cell-free DNA fragmentation associated with cancer. Participants were ≥50 years old with current or previous smoking histories of ≥20 pack-years and recent or planned chest CT imaging. Medical history was recorded at enrollment, and blood samples were collected for DELFI analysis. A classifier was trained using supervised machine learning to discriminate between samples from individuals with lung cancer and without cancer; its performance was evaluated by repeated 10-fold cross-validation. A split study approach, along with testing of cohorts separated by enrollment period and processing batch, is planned for independent validation of the classifier. Performance of the classifier was assessed in the overall study population and in subsets of clinical interest. RESULTS: This analysis included 242 persons with lung cancer and 652 without cancer. Median age (range) was 67 (50-91) years, 37%/63% had current/former smoking status, and 81% had ≥30 pack-year smoking history. Higher median DELFI scores (range) were more strongly associated with lung cancer than no cancer, even among groups with COPD [lung cancer 0.38 (0.09-1.00) vs no cancer 0.22 (0.04-0.80)], active smoking status [lung cancer 0.40 (0.05-1.00) vs no cancer 0.21 (0.06-0.80)], and ≥30 pack-years [lung cancer 0.38 (0.05-1.00) vs no cancer 0.22 (0.04-0.83)]. CONCLUSIONS: A classifier that analyzes cfDNA fragmentation patterns using DELFI was developed that distinguishes lung cancer from no cancer with cross-validated performance across groups categorized by COPD status, smoking status, smoking intensity. CLINICAL IMPLICATIONS: A high-performing, blood-based DELFI fragmentome test has the potential to inform individual-level benefit and risk of LDCT screening, which may improve the population-level efficiency and benefits of screening. DISCLOSURES: No relevant relationships by Kavita Arjungi No disclosure on file for Peter Bach No relevant relationships by Ashley Birch No disclosure on file for Jacob Carey No disclosure on file for Joseph Catallini Owner/Founder relationship with Delfi Diagnostics Please note: 2109-2023 Added 04/13/2023 by Nicholas Dracopoli, source=Web Response, value=Ownership interest Employee relationship with Delfi Diagnostics Please note: April 2021 - Present Added 03/28/2023 by Keith Lumbard, source=Web Response, value=Salary Research support to my institution relationship with Adela Please note: 2022 - by Peter Mazzone, value=Grant/Research Support Research support to my institution relationship with Exact Sciences Please note: 2022 - by Peter Mazzone, value=Grant/Research Support Research support to my institution relationship with MagArray Please note: 2021 by Peter Mazzone, value=Grant/Research Support Research support to my institution relationship with PrognomIQ Please note: 2021 - by Peter Mazzone, value=Grant/Research Support Research support to my institution relationship with Biodesix Please note: 2021 - by Peter Mazzone, value=Grant/Research Support Research support to my institution relationship with Nucleix Please note: 6/2021 - ongoing by Peter Mazzone, value=Grant/Research Support Research support to my institution relationship with DELFI Please note: 6/2021 - ongoing by Peter Mazzone, value=Grant/Research Research support to my institution relationship with Veracyte Please note: $5001 - $20000 by Peter Mazzone, value=Grant/Research Support Employee relationship with Delfi Diagnostics Please note: 2/22/2022 - present Added 03/29/2023 by Carter Portwood, source=Web Response, value=Salary stock holder relationship with Natera Please note: 2008 - present Added 03/30/2023 by allison ryan, source=Web Response, value=I held shares Employee relationship with Delfi Diagnostics Please note: 2/1/2021 - present Added 03/30/2023 by allison ryan, source=Web Response, value=Salary Consultant relationship with Delfi Diagnostics Please note: 4/2019-present by Robert Scharpf, value=Salary Research to Institution relationship with Incyte Please note: 2022-2023 Added 03/28/2023 by Jeffrey Thompson, value=Grant/Research Support Research to Institution relationship with Delfi Diagnostics Please note: 2021-2023 Added 03/28/2023 by Jeffrey Thompson, value=Grant/Research Consultant relationship with AstraZeneca Please note: 2021-2023 Added 03 /28 /2023 by Jeffrey Thompson, value=Consulting Research to Institution relationship with United Health Group Please note: 2021-2023 Added 03/28/2023 by Jeffrey Thompson, value=Grant/Research Support No relevant relationships by James Tsay My spouse/partner as a Researcher relationship with Lungevity Foundation Please note: 2021 - present Added 04/08/2023 by Anil Vachani, source=Web Response, value=Grant/Research Support My spouse/partner as a Researcher relationship with Precyte, Inc. Please note: 2019 - present Added 04/08/2023 by Anil Vachani, source=Web Response, value=Grant/Research Support My spouse/partner as a Researcher relationship with MagArray, Inc. Please note: 2018 - present Added 04/08/2023 by Anil Vachani, source=Web Response, value=Grant/Research Support My spouse/partner as a Researcher relationship with Optellum, Ltd Please note: 2022 - present Added 04/08/2023 by Anil Vachani, source=Web Response, value=Grant/Research Support Scientific Medical Advisor relationship with Johnson and Johnson Please note: 2020 - present by Anil Vachani, value=Consulting fee No disclosure on file for Victor Velculescu No disclosure on file for Kwok-Kin Wong Employee relationship with Delfi Diagnostics Please note: September 2021 - Pre Added 03/28/2023 by Tony Wu, source=Web Response, value=Salary Employee relationship with GRAIL Please note: 2018 - 2021 Added 03/28/2023 by Tony Wu, source=Web Response, value=Salary Employee relationship with GRAIL Please note: 2018 - 2021 Added 03/28/2023 by Tony Wu, source=Web Response, value=Salary Removed 03/28/2023 by Tony Wu, source=Web Response Employee relationship with GRAIL Please note: 2018 - 2021 Added 03/28/2023 by Tony Wu, source=Web Response, value=Salary Removed 03/28/2023 by Tony Wu, source=Web Response Employee relationship with GRAIL Please note: 2018 - 2021 Added 03/28/2023 by Tony Wu, source=Web Response, value=Salary Removed 03/28/2023 by Tony Wu, source=Web Response No relevant relationships by Yuhua Zong