Clinical OMICS

MAY-JUN 2019

Healthcare magazine for research scientists, labs, pathologists, hospitals, cancer centers, physicians and biopharma companies providing news articles, expert interviews and videos about molecular diagnostics in precision medicine

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16 Clinical OMICs May/June 2019 www.clinicalomics.com SPONSORED CONTENT 16 Clinical OMICs May/June 2019 www.clinicalomics.com Precision Medicine Adopts Cancer Variant Guidelines, But the Work Isn't Over Christina Bennett The field of cancer diagnostics has benefited tremendously from the widespread use of next-generation sequencing in the clinical laboratory setting. Clinicians can order genomic testing to identify somatic variants, receive the results in a timely manner, and use the information to provide tailored treatment decisions to their cancer patients. However, as gene panels have grown larger and detection methods and sequencing have become more sensitive, the lists of variants on reports have become much longer. "Physicians want to make use of new technology, but long lists of undifferentiated variants can cause confusion," says Sheryl Krevsky Elkin, PhD, Chief Scientific Officer at N-of-One, a QIAGEN company focusing on molecular decision support. Increasing use of larger gene panels, and even whole-exome and whole-genome sequencing further complicates the task of interpretation, and the interpretation of somatic variants has direct clinical implications for the clinician to consider. For example, a somatic variant may serve as a biomarker and be used to identify a targeted therapy most likely to work in a patient whose tumor harbors that variant. For years, the industry lacked standards for reporting of molecular results, making it difficult for physicians to confidently interpret the clinical significance of a variant and use the information in their treatment decision-making. "At the beginning it was somewhat chaotic," recalled Marilyn M. Li, MD, Professor of Pediatrics and Professor of Clinical Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine. "The field lacked consistency, with some laboratories reporting all the variants and others reporting certain variants but not others." Several different organizations released their own rubric for determining or reporting levels of evidence, but it wasn't until 2017 that a set of formal guidelines to standardize molecular results reporting was published by Dr. Li and her colleagues on behalf of the Association for Molecular Pathology (AMP), American Society of Clinical Oncology (ASCO), and College of American Pathologists (CAP). "When the guidelines were released, we quickly determined that this set of guidelines was likely to be the industry standard that we had been waiting for," explains Dr. Elkin. Standardization Excites, but Adoption is Complex The guidelines were the product of a collaborative effort among AMP, ASCO, and CAP and provided recommendations for the interpretation and reporting of sequence variants in cancer. Commonly referred to as the AMP guidelines, the recommendations were based on the existing literature, empirical data, and professional judgement, and effectively created industry standards for the classification, annotation, interpretation, and reporting of cancer variants. "There has been a lot of excitement about the guidelines in the industry," says Dr. Elkin. Part of the guidelines included the establishment of four tiers of evidence that can be used in molecular results reports to show the clinician the strength of evidence behind a particular therapy associated with a variant in a particular disease or the level of prognostic or diagnostic significance of that variant in that specific type of cancer. "Standardized tiers and levels of evidence allows stratification of variants as well as therapies to help doctors to quickly identify which are the important and well-known biomarkers, and what are the therapies with the most evidence to target their patients' cancers," she explains. Although the AMP guidelines provide structure to the molecular reporting of cancer variants, adoption has been variable. "Many groups that are entering the somatic testing arena for the first time are immediately adopting the AMP guidelines, and the guidelines are helping to standardize reporting of somatic variants, making reports easier for physicians to interpret," explains Dr. Elkin. N-of-One is an interpretation company that has adopted the guidelines, helping its diagnostic lab customers to report using the new tier-based system. "But for companies that have already established a reporting system, given the realities of the work required to make changes to the reports, adoption has been comparatively modest." A major barrier to guideline adoption has been requirements to update software and reporting methodology for laboratories with an existing report. For example, if a laboratory was already performing next-generation sequencing and producing a report, the laboratory would

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