• Alessandro I C Leal, Dimitrios Mathios, Debbie Jakubowski, Jakob S Johansen, Anna Lau, Tony Wu, Stephen Cristiano, Jamie E Medina, Jillian Phallen, Daniel C Bruhm, Jacob Carey, Nicholas C Dracopoli, Stig E Bojesen, Robert B Scharpf, Victor E Velculescu, Anil Vachani, and Peter B Bach.
• Delfi Diagnostics, Inc., Baltimore, MD. Electronic address: leal@delfidiagnostics.com.
• Chest. 2023 Oct 1; 164 (4): 101910271019-1027.

BackgroundThe diagnostic workup of individuals suspected of having lung cancer can be complex and protracted because conventional symptoms of lung cancer have low specificity and sensitivity.Research QuestionAmong individuals with symptoms of lung cancer, can a blood-based approach to analyze cell-free DNA (cfDNA) fragmentation (the DNA evaluation of fragments for early interception [DELFI] score) enhance evaluation for the possible presence of lung cancer?Study Design And MethodsAdults were referred to Bispebjerg Hospital (Copenhagen, Denmark) for diagnostic evaluation of initial imaging anomalies and symptoms consistent with lung cancer. Numbers and types of symptoms were extracted from medical records. cfDNA from plasma samples obtained at the prediagnostic visit was isolated, sequenced, and analyzed for genome-wide cfDNA fragmentation patterns. The relationships among clinical presentation, cancer status, and DELFI score were examined.ResultsA total of 296 individuals were analyzed. Median DELFI scores were higher for those with lung cancer (n = 98) than those without cancer (n = 198; 0.94 vs 0.19; P < .001). In a multivariate model adjusted for age, smoking history, and presenting symptoms, the addition of the DELFI score improved the prediction of lung cancer for those who demonstrated symptoms (area under the receiver operating characteristic curve, 0.74-0.94).InterpretationThe DELFI score distinguishes individuals with lung cancer from those without cancer better than suspicious symptoms do. These results represent proof-of-concept support that fragmentation-based biomarker approaches may facilitate diagnostic resolution for patients with concerning symptoms of lung cancer.Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

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