(511) Comparing the yield of meaningful findings in targeted versus genome-wide cell free DNA screening

Over 2 million cell free DNA (cfDNA) screens have been performed since the technology was introduced to clinical practice in 2011. Currently, three unique cfDNA screening modalities are available and range from targeted screens to genome wide. The objective of this study was to determine if genome wide cfDNA screening reveals clinically meaningful results at a higher rate than targeted cfDNA screening.

Study Design: We conducted a retrospective cohort study that included all subjects who underwent cfDNA screening at a single academic center between 5/1/2016 and 4/1/2023. A retrospective chart review was performed to identify all screens that yielded abnormal results. Outcomes were compared between three cfDNA screening modalities: 5-cfDNA screens that detect abnormalities in chromosome 13, 18, 21 X and Y, 5-cfDNA plus selected microdeletions, and genome wide cfDNA screens.

Results: 9,062 patients underwent cfDNA screening at a single institution. 1,502 were 5-cfDNA screens, 4,257 5-cfDNA and microdeletion screens and 3,303 were genome wide screens. 146 (1.6%) screens were abnormal. Of the 146 abnormal results, 118 (80.8%) would have been detected by the 5-cfDNA screen. An additional yield of 19.2% was noted when screening beyond the five most common aneuploidies. The 5-cfDNA and common microdeletion screens had an incremental yield of 8.2% (12/146) and 387 patients need to be screened for one clinically meaningful finding. There is a further 11.0% (16/146) additional yield when genome-wide cfDNA screening was performed. Compared to 5-cfDNA screen, 254 patients needed to be screened with whole genome cfDNA to find had an additional yield of 11.0% (16/146). Most abnormal results in this category ended in first trimester loss, one ended in termination and two had live births. (Table 1)

Conclusion: There is an addition 21.9% yield in screening beyond the common five chromosomes. More than half of that additional yield comes from genome-wide cfDNA screens. The number needed to screen may be considered when selecting a cfDNA screen.