SPOT/Dx Pilot Reanalysis and College of American Pathologists Proficiency Testing for KRAS and NRAS Demonstrate...

Area of Science:

• Molecular Oncology
• Genomic Diagnostics
• Quality Assurance

Background:

• The Sustainable Predictive Oncology Therapeutics and Diagnostics (SPOT/Dx) pilot study assessed next-generation sequencing (NGS) laboratory-developed tests.
• Reported limitations included discrepancies with FDA-approved companion diagnostics and differing methodologies from proficiency testing (PT) programs.

Purpose of the Study:

• To reanalyze SPOT/Dx pilot data using established proficiency testing (PT) program methods.
• To compare the reanalyzed SPOT/Dx data with existing CAP NGS PT program data.

Main Methods:

• The College of American Pathologists (CAP) Molecular Oncology Committee reanalyzed SPOT/Dx pilot data.
• Methods were adjusted for confounding conditions and compared against CAP NGS PT program performance from 2019-2022.

Main Results:

• Detection rates for KRAS/NRAS single-nucleotide variants (SNVs) were 96.8% in the pilot and 97.2% in CAP PT programs.
• Detection rates for KRAS/NRAS multi-nucleotide variants (MNVs) were 81.1% in the pilot and 91.8% in CAP PT programs.
• In 2022, CAP PT programs showed a 97.3% detection rate for 5 KRAS/NRAS MNVs.

Conclusions:

• CAP PT program data confirm consistent high detection rates for KRAS/NRAS variants.
• Reanalyzed SPOT/Dx data, adjusted for confounders, show proficient SNV detection but less success with rare MNVs.
• SPOT/Dx pilot results are not generalizable to all molecular oncology testing and should not influence product marketing or policy changes.