Retrospective Comparison of Operational Metrics Across Diagnostic Approaches for Molecular Testing in Lung and Colon Cancers in a Community-Based Setting.

Abstract

Identifying oncogenic driver mutations in non-small cell lung cancer (NSCLC) and colorectal cancer (CRC) is critical for targeted therapies, requiring accurate and timely molecular testing. To compare turnaround time (TAT; days from order to results), quantity not sufficient (QNS) rate, and detection rates of National Comprehensive Cancer Network-recommended alterations in NSCLC (epidermal growth factor receptor [EGFR]; MET proto-oncogene, receptor tyrosine kinase [MET] exon 14 skipping; ROS proto-oncogene 1, receptor tyrosine kinase [ROS1]; ALK receptor tyrosine kinase [ALK]; ret proto-oncogene [RET]; erb-b2 receptor tyrosine kinase 2 [ERBB2] mutations; neurotrophic receptor tyrosine kinase 1, 2, and 3 [NTRK1/2/3]; B-Raf proto-oncogene, serine/threonine kinase [BRAF]; KRAS proto-oncogene, GTPase [KRAS] [G12C]) and CRC (RET; ERBB2 amplification; NTRK1/2/3; BRAF; KRAS; NRAS proto-oncogene, GTPase [NRAS]; microsatellite instability) using 3 testing algorithms: in-house single-gene panel (SGP; 5 of 9 NSCLC, 4 of 7 CRC alterations); ThermoFisher Oncomine Focus Assay (OFA; covers all NSCLC, 6 of 7 CRC alterations); and send-out next-generation sequencing (SO-NGS; all National Comprehensive Cancer Network alterations). Three hundred fourteen tumors (181 NSCLC, 133 CRC) were tested with SGP, 377 (239 NSCLC, 138 CRC) with OFA, and 238 (185 NSCLC, 53 CRC) with SO-NGS. NSCLC TATs were 7.6 days (SGP), 11.1 days (OFA), and 11.9 days (SO-NGS). QNS rates were 10.4% (SGP), 6.3% (OFA), and 11.9% (SO-NGS). Detection rates were 19.8% (SGP), 26.8% (OFA), and 29.4% (SO-NGS). For CRC, TATs were 6.0 days (SGP), 10.1 days (OFA), and 10.2 days (SO-NGS). QNS rates were 0.8% (SGP), 0.7% (OFA), and 7.5% (SO-NGS). Detection rates were 62.9% (SGP), 58.4% (OFA), and 56.5% (SO-NGS). SGP provides the fastest TAT but lower detection and higher QNS rates in NSCLC. OFA balances TAT, QNS, and detection, whereas SO-NGS offers comprehensive detection with longer TAT and higher QNS. An optimized assay combining SGP's speed, OFA's reliability, and SO-NGS's comprehensiveness could improve outcomes.