The Impact of Next-Generation Sequencing Workflows on Outcomes in Advanced Lung Cancer: A Retrospective Analysis at One Academic Health System.

Abstract

Broad-based molecular testing with next-generation sequencing (NGS) is now the standard of care in advanced non-small cell lung cancer (NSCLC). Two approaches to molecular testing are (1) reflexive testing at pathologic NSCLC confirmation, often using an in-house molecular panel, and (2) send-out testing to private vendors, ordered by a clinician. This study explored the outcomes with reflex versus send-out testing. A retrospective chart review was conducted of patients diagnosed with de novo stage IV NSCLC in 2019 and 2020 at three hospitals in the same system, one academic hospital (Northwestern Memorial Hospital, or NMH) utilizing reflex, in-house NGS, and two community-based hospitals (Central DuPage Hospital, or CDH, and Delnor, or D) sending out tissue samples for testing. The outcomes assessed were the time from biopsy to results, biopsy to treatment, the incidence of first-line targetable mutations and the use of first-line targeted therapies, and overall survival. In total, 191 patients met the inclusion criteria, 85 at NMH, 106 at CDH + D, and in total, 131 in 2019 and 60 in 2020. The time to results was significantly shorter with reflexive NGS when compared with send-out testing; the time to treatment was also shorter but not statistically significant. At CDH + D, the time to results was significantly shorter with a limited panel than with comprehensive testing, but the time to treatment was similar. NGS testing rates were 95% at NMH and 84.5% at CDH + D (p = 0.009), with 31.0% at NMH receiving 1L targeted therapies versus 20.8% at CDH + D (p = 0.08). In 2019, the median time from biopsy to treatment was 35 days at NMH and 38 days at CDH and Delnor; in 2020, time to treatment was 26 days and 37 days, respectively. Overall survival trended longer in 2020 relative to 2019 independent of site. Reflexive NGS testing is associated with a shorter time to actionable results and higher rates of first-line targetable mutations than send-out testing. In practices with send-out testing, limited panels had slightly faster turnaround times but no difference in time to treatment. If resources allow, reflexive NGS should be considered in healthcare systems for patients with NSCLC.