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Cell-free DNA fragmentomes in the diagnostic evaluation of patients with symptoms suggestive of lung cancer.
Chest 2023 April 27
BACKGROUND: The diagnostic workup of individuals suspected of lung cancer can be complex and protracted because conventional symptoms of lung cancer have low specificity and sensitivity.
RESEARCH QUESTION: Among individuals with symptoms of lung cancer, can a blood-based approach to analyze cell-free DNA fragmentation (the "DELFI score") enhance the evaluation for the possible presence of lung cancer?
STUDY DESIGN AND METHODS: Adults were referred to Bispebjerg Hospital (Copenhagen, Denmark) for diagnostic evaluation of initial imaging anomalies, symptoms consistent with lung cancer. Numbers and types of symptoms were extracted from medical records. Cell-free DNA from plasma samples obtained at the pre-diagnostic visit was isolated, sequenced, and analyzed for genome-wide cfDNA fragmentation patterns. The relationships between clinical presentation, cancer status, and DELFI score were examined.
RESULTS: A 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 multivariable model adjusted for age, smoking history, and presenting symptoms, the addition of the DELFI score improved the prediction of lung cancer for those who presented with symptoms (area under the curve from 0.74 to 0.94).
INTERPRETATION: The DELFI score distinguishes individuals with lung cancer from those without cancer better than suspicious symptoms. These results represent proof-of-concept support that fragmentation-based biomarker approaches may facilitate diagnostic resolution for patients with concerning symptoms of lung cancer.
RESEARCH QUESTION: Among individuals with symptoms of lung cancer, can a blood-based approach to analyze cell-free DNA fragmentation (the "DELFI score") enhance the evaluation for the possible presence of lung cancer?
STUDY DESIGN AND METHODS: Adults were referred to Bispebjerg Hospital (Copenhagen, Denmark) for diagnostic evaluation of initial imaging anomalies, symptoms consistent with lung cancer. Numbers and types of symptoms were extracted from medical records. Cell-free DNA from plasma samples obtained at the pre-diagnostic visit was isolated, sequenced, and analyzed for genome-wide cfDNA fragmentation patterns. The relationships between clinical presentation, cancer status, and DELFI score were examined.
RESULTS: A 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 multivariable model adjusted for age, smoking history, and presenting symptoms, the addition of the DELFI score improved the prediction of lung cancer for those who presented with symptoms (area under the curve from 0.74 to 0.94).
INTERPRETATION: The DELFI score distinguishes individuals with lung cancer from those without cancer better than suspicious symptoms. These results represent proof-of-concept support that fragmentation-based biomarker approaches may facilitate diagnostic resolution for patients with concerning symptoms of lung cancer.
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