Tumor mutational burden assessment in non-small-cell lung cancer samples: results from the TMB 2 harmonization project comparing three NGS panels

Tumor mutational burden (TMB) is a recently proposed predictive biomarker for immunotherapy in solid tumors, including non-small cell lung cancer (NSCLC). Available assays for TMB determination differ in horizontal coverage, gene content and algorithms, leading to discrepancies in results, impacting...

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Bibliographic Details
Published in:Journal for immunotherapy of cancer 2021-05, Vol.9 (5), p.e001904
Main Authors: Ramos-Paradas, Javier, Hernández-Prieto, Susana, Lora, David, Sanchez, Elena, Rosado, Aranzazu, Caniego-Casas, Tamara, Carrizo, Nuria, Enguita, Ana Belén, Muñoz-Jimenez, María Teresa, Rodriguez, Borja, Perez-Gonzalez, Urbicio, Gómez-Sánchez, David, Ferrer, Irene, Ponce Aix, Santiago, Nuñez Buiza, Ángel, Garrido, Pilar, Palacios, José, Lopez-Rios, Fernando, Garrido-Martin, Eva M, Paz-Ares, Luis
Format: Article
Language:English
Subjects:
Biomarkers, Tumor - genetics
Carcinoma, Non-Small-Cell Lung - genetics
Carcinoma, Non-Small-Cell Lung - pathology
Carcinoma, Non-Small-Cell Lung - surgery
DNA Mutational Analysis
Genetic Predisposition to Disease
High-Throughput Nucleotide Sequencing
Humans
Lung Neoplasms - genetics
Lung Neoplasms - pathology
Lung Neoplasms - surgery
Mutation
Observer Variation
Phenotype
Predictive Value of Tests
Prognosis
Reproducibility of Results
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Summary:Tumor mutational burden (TMB) is a recently proposed predictive biomarker for immunotherapy in solid tumors, including non-small cell lung cancer (NSCLC). Available assays for TMB determination differ in horizontal coverage, gene content and algorithms, leading to discrepancies in results, impacting patient selection. A harmonization study of TMB assessment with available assays in a cohort of patients with NSCLC is urgently needed. We evaluated the TMB assessment obtained with two marketed next generation sequencing panels: TruSight Oncology 500 (TSO500) and Oncomine Tumor Mutation Load (OTML) versus a reference assay (Foundation One, FO) in 96 NSCLC samples. Additionally, we studied the level of agreement among the three methods with respect to PD-L1 expression in tumors, checked the level of different immune infiltrates versus TMB, and performed an inter-laboratory reproducibility study. Finally, adjusted cut-off values were determined. Both panels showed strong agreement with FO, with concordance correlation coefficients (CCC) of 0.933 (95% CI 0.908 to 0.959) for TSO500 and 0.881 (95% CI 0.840 to 0.922) for OTML. The corresponding CCCs were 0.951 (TSO500-FO) and 0.919 (OTML-FO) in tumors with
ISSN:2051-1426
2051-1426
DOI:10.1136/jitc-2020-001904