Abstract
Purpose: Biomarker data are critical to the delivery of precision cancer care. The average turnaround of next-generation sequencing (NGS) reports is over 2 weeks, and in-house availability is typically limited to academic centers. Lengthy turnaround times for biomarkers can adversely affect outcomes. Traditional workflows involve moving specimens through multiple facilities. This study evaluates the feasibility of rapid comprehensive NGS using the Genexus integrated sequencer and a novel streamlined workflow in a community setting. Methods: A retrospective chart review was performed to assess the early experience and performance characteristics of a novel approach to biomarker testing at a large community center. This approach to NGS included an automated workflow utilizing the Genexus integrated sequencer, validated for clinical use. NGS testing was further integrated within a routine immunohistochemistry (IHC) service, utilizing histotechnologists to perform technical aspects of NGS, with results reported directly by anatomic pathologists. Results: Between October 2020 and October 2021, 578 solid tumor samples underwent genomic profiling. Median turnaround time for biomarker results was 3 business days (IQR: 2–5). Four hundred eighty-one (83%) of the cases were resulted in fewer than 5 business days, and 66 (11%) of the cases were resulted simultaneously with diagnosis. Tumor types included lung cancer (310), melanoma (97), and colorectal carcinoma (68), among others. NGS testing detected key driver alterations at expected prevalence rates: lung EGFR (16%), ALK (3%), RET (1%), melanoma BRAF (43%), colorectal RAS/RAF (67%), among others. Conclusion: This is the first study demonstrating clinical implementation of rapid NGS. This supports the feasibility of automated comprehensive NGS performed and interpreted in parallel with diagnostic histopathology and immunohistochemistry. This novel approach to biomarker testing offers considerable advantages to clinical cancer care.
Highlights
Formalin-fixed paraffin-embedded (FFPE) samples were deparaffinized in min at 50 °C, washed in 100% ethanol (2 × 5 min), air-dried for 20–45 m digestion was performed with proteinase K (55 °C and 90°C for 1 h each)
Sixty-six cases (11%) were identified with molecular biomarker results issued simultaneously with a diagnosis
Compared to in silico single-gene testing methods, next-generation sequencing (NGS) results provided incremental utility in 12 (18%) cases, with incremental utility defined as a result that would change systemic therapy prescription. These included driver events in ERBB2/3, as well as atypical forms of KRAS activation, namely G12F or amplification of wild-type KRAS, which are not typically tested using single-gene methodologies. This is the first report, to our knowledge, of clinical NGS performed with a median turnaround time of 3 business days
Summary
Modern-day cancer treatment is heavily predicated on biomarker testing. Biomarker results influence all spheres of cancer treatment, but mainly systemic therapies. Biomarkerbased prescription of anti-cancer therapy is the cornerstone of precision oncology treatment and represents the highest standard of care. Significant barriers exist in many medical practices, precluding the timely delivery of appropriate biomarker tests and matched systemic therapy. Two major barriers include the breadth and speed of testing
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