AMP Clinical Practice Committee Working Group on Liquid Biopsy Publishes Recommendations to Standardize Industry Practices
A study conducted by the Association for Molecular Pathology Clinical Practice Committee’s Liquid Biopsy Working Group (LBxWG) highlights the need for standardized procedures in the development, validation, and reporting of circulating tumor DNA (ctDNA) assays in the context of cancer diagnosis and treatment. The study’s findings reflect the variability in how ctDNA assays are conducted and reported in the medical literature, creating hurdles for clinical adoption and potentially impacting patient care. Based on the findings, the committee has published a set of recommendations for labs that provide these testing services.
The study emphasizes the critical importance of standardization in various aspects of ctDNA assays, including pre-analytical variables, analytical considerations, and elements of laboratory assay reporting. To address these concerns, the LBxWG developed a set of 13 best practice consensus recommendations for validating, reporting, and publishing clinical ctDNA assays. These recommendations aim to assist clinical laboratories in ensuring high-quality data in ctDNA publications and encourage clinical adoption.
The Association for Molecular Pathology Clinical Practice Committee’s Liquid Biopsy Working Group (LBxWG) recommendations focus on pre-analytical, analytical, and post-analytical phases of ctDNA assays. These recommendations aim to establish guidelines for ensuring the quality and consistency of ctDNA testing across different cancer types and clinical indications. Key recommendations include adhering to relevant regulatory requirements, particularly Clinical Laboratory Improvement Amendments (CLIA) standards in the United States, while considering the diversity of cancer types and testing purposes. This includes treatment selection, resistance monitoring, and longitudinal testing.
The LBxWG emphasizes the importance of clinical laboratory reports in conveying clinically significant genomic information to healthcare providers, including pathologic diagnosis, gene variants detected, transcript details, variant annotations, variant allele frequency (VAF), and medically significant information such as prognostic and therapeutic implications. Furthermore, reports should clearly specify the genes and variants included in a panel to facilitate the understanding of results by healthcare providers. Limitations of the assay and the limit of detection should be included, and variants of unknown significance should be reviewed regularly.
In the context of new targeted therapies and evolving clinical standards, ctDNA reports should mention the presence or absence of mutations that are therapeutically relevant. The potential presence of germline variants in plasma-derived samples should be considered and, when necessary, prompt germline testing should be recommended.
The LBxWG recommends the widespread adoption of these recommendations to improve the analytical and clinical performance of ctDNA assays. The LBxWG believes achieving consistent and complete reporting of critical variables in diagnostic assay publications will help standardize ctDNA assay development, highlight variables affecting performance, and accelerate clinical implementation.