Harmonization of tumor mutation burden testing with comprehensive genomic profiling assays: an IQN Path initiative

• DOI: 10.1136/jitc-2023-007800
• Publication Date: 2024-02-03T05:45:23Z
• Authors: Riziero Esposito ...; Raffaella Pasquale; Alessandra Sacco; Vittorio Simeon; Monica Rosaria Ma...; Daniela Frezzetti; Paolo Chiodini; Nicola Normanno
• Keywords: Harmonization; Profiling (computer programming)

Although conflicting results emerged from different studies, the tumor mutational burden (TMB) appears as one of most reliable biomarkers sensitivity to immune checkpoint inhibitors. Several laboratories are reporting TMB values when performing comprehensive genomic profiling (CGP) without providing a clinical interpretation, due lack validated cut-off values. The International Quality Network for Pathology launched an initiative harmonize testing with CGP assay and favor implementation this biomarker. evaluation was performed three commercially available panels, TruSight Oncology 500 (TSO500), Oncomine Comprehensive Plus Assay (OCA) QIAseq Multimodal Panel (QIA), versus reference FoundationOne CDx (F1CDx). Archived samples derived 60 patients non-small cell lung cancer were used assessment. Adjusted each panel calculated. Testing successful 91.7%, 100%, 96.7% 100% cases using F1CDx, TSO500, OCA QIA, respectively. matrix comparison analysis, between F1CDx assays, showed linear correlation all higher TSO500 (rho=0.88) than in other two comparisons (rho=0.77 QIA; 0.72 OCA). best area under curve (AUC, value 0.96), statistically significant difference compared AUC (0.83, p value=0.01) QIA (0.88, value=0.028). Youden Index calculation allowed us extrapolate cut-offs panels corresponding 10 mutations/megabase (muts/Mb) F1CDx: 10.19, 10.4 12.37 muts/Mb Using these values, we calculated relative accuracy measures panels. 86% specificity 96% sensitivity, while had lower yet similar (73% 88%, respectively). This study estimated good performance on support better TSO500. can drive interpretation research practice.