Tumor mutational burden standardization initiatives

• Verfasst von: Stenzinger, Albrecht [VerfasserIn]
• Verfasst von: Allen, Jeffrey D. [VerfasserIn]
• Verfasst von: Maas, Jörg [VerfasserIn]
• Verfasst von: Stewart, Mark D. [VerfasserIn]
• Verfasst von: Merino, Diana M. [VerfasserIn]
• Verfasst von: Wempe, Madison M. [VerfasserIn]
• Verfasst von: Dietel, Manfred [VerfasserIn]
• Titel: Tumor mutational burden standardization initiatives
• Titelzusatz: Recommendations for consistent tumor mutational burden assessment in clinical samples to guide immunotherapy treatment decisions
• Verf.angabe: Albrecht Stenzinger, Jeffrey D. Allen, Jörg Maas, Mark D. Stewart, Diana M. Merino, Madison M. Wempe, Manfred Dietel
• E-Jahr: 2019
• Jahr: 21 January 2019
• Umfang: 11 S.
• Fussnoten: Gesehen am 16.01.2020
• Titel Quelle: Enthalten in: Genes, chromosomes & cancer
• Ort Quelle: New York, NY : Wiley-Liss, 1989
• Jahr Quelle: 2019
• Band/Heft Quelle: 58(2019), 8, Seite 578-588
• ISSN Quelle: 1098-2264
• DOI: doi:10.1002/gcc.22733
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: biomarkers
• Sach-SW: immune checkpoint inhibitors
• Sach-SW: neoantigens
• Sach-SW: next-generation sequencing
• Sach-SW: tumor mutational burden/load
• K10plus-PPN: 1687525285

Abstract

Characterization of tumors utilizing next-generation sequencing methods, including assessment of the number of somatic mutations (tumor mutational burden [TMB]), is currently at the forefront of the field of personalized medicine. Recent clinical studies have associated high TMB with improved patient response rates and survival benefit from immune checkpoint inhibitors; hence, TMB is emerging as a biomarker of response for these immunotherapy agents. However, variability in current methods for TMB estimation and reporting is evident, demonstrating a need for standardization and harmonization of TMB assessment methodology across assays and centers. Two uniquely placed organizations, Friends of Cancer Research (Friends) and the Quality Assurance Initiative Pathology (QuIP), have collaborated to coordinate efforts for international multistakeholder initiatives to address this need. Friends and QuIP, who have partnered with several academic centers, pharmaceutical organizations, and diagnostic companies, have adopted complementary, multidisciplinary approaches toward the goal of proposing evidence-based recommendations for achieving consistent TMB estimation and reporting in clinical samples across assays and centers. Many factors influence TMB assessment, including preanalytical factors, choice of assay, and methods of reporting. Preliminary analyses highlight the importance of targeted gene panel size and composition, and bioinformatic parameters for reliable TMB estimation. Herein, Friends and QuIP propose recommendations toward consistent TMB estimation and reporting methods in clinical samples across assays and centers. These recommendations should be followed to minimize variability in TMB estimation and reporting, which will ensure reliable and reproducible identification of patients who are likely to benefit from immune checkpoint inhibitors.