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Clinical Utility of Molecular Tumor Board Review for Identification of Possible Germline Pathogenic Variants on Tumor Next-Generation Sequencing Reports
Journal article   Open access   Peer reviewed

Clinical Utility of Molecular Tumor Board Review for Identification of Possible Germline Pathogenic Variants on Tumor Next-Generation Sequencing Reports

Taylor A. Rives, James Collard, Ning Li, Donglin Yan, Charles S. Dietrich, Rachel W. Miller, Frederick R. Ueland, Justine Pickarski and Jill M. Kolesar
JCO precision oncology, Vol.8(8), e2400301
09/01/2024
DOI: 10.1200/PO.24.00301
PMCID: PMC11404756
PMID: 39259913
url
https://doi.org/10.1200/PO.24.00301View
Published (Version of record) Open Access

Abstract

PURPOSE Tumor next-generation sequencing (NGS) testing identifies possible germline pathogenic variants (PGPVs), creating a dilemma for appropriate recognition, triage, and management. The objective of this study was to determine the clinical utility of an institutional molecular tumor board (MTB) in assessing tumor NGS reports for PGPVs. METHODS Our institutional MTB reviews all NGS reports to provide treatment and further testing recommendations, including genetic counseling referral and consideration of genetic testing (GC/GT). We studied the patients reviewed by the MTB who were recommended for GC/GT to determine the frequency of referral to a GC, germline test completion, rate of pathogenic germline variants (PGVs), factors related to PGVs, and germline conversion rate (GCR). RESULTS Of the 2,355 patients reviewed by the MTB during the study period, 609 (25.9%) had a recommendation for GC/GT. Of the 609 with a GC/GT recommendation, only 181 (29.7%) were referred for GC/GT by their treating physicians, and only 107 (17.6%) completed GT. Of the 107 patients completing GT, 29 (26%) had a confirmed PGV. The only factors significantly associated with PGVs were testing due to a PGPV and higher mean variant allele fraction on the tumor NGS. Only 40 patients with a GC/GT recommendation (14.3%) due to a PGPV completed GT; however, the GCR was 42.5% (n = 17/40). CONCLUSION The MTB review of PGPV is clinically valuable, identifying PGPV in 12% of patients undergoing tumor NGS and a GCR of 42.5%. Rates of GC/GT completion were relatively low due to under-referral by treating physicians. Given the high GCR, the authors encourage institutional algorithms to help increase GC/GT rates for patients found to have PGPV following tumor NGS testing.

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