Lecture
HiLiB-MTB: Harmonized Liquid Biopsy Precision Medicine Platform for Molecular Tumor Boards
- at -
- ICM Saal 4a
- Type: Lecture
Lecture description
E Dazert-Klebsattel, Lübeck/DE, S Feierabend, Lübeck/DE, T Helbing, Lübeck/DE, A Künstner, Lübeck/DE, M Forster, Kiel/DE, J Wigger, Lübeck/DE, L Ranganathan, Freiburg/DE, SMJ Fliedner, Lübeck/DE, M Oberländer, Lübeck/DE, J Vorwerk, Lübeck/DE, Christina Schwitlick, Lübeck/DE, C Khandanpour, Oldenburg/DE, I Tinhofer-Keilholz, Berlin/DE, D Rieke, Berlin/DE, S Füssel, Dresden/DE, SS Lueong, Essen/DE, M Christopeit, Hamburg/DE, H Sültmann, Heidelberg/DE, P Horak, Heidelberg/DE, M Lablans, Heidelberg/DE, A Desuki, Mainz/DE, N Hartmann, Mainz/DE, M Janning, Mannheim/DE, C Winter, München/DE, L Illert, München/DE, M Bitzer, Tübingen/DE, K Pantel, Hamburg/DE, A Zapf, Hamburg/DE, C Schröder, Tübingen/DE, J Broche, Tübingen/DE, F Scherer, Freiburg/DE, S Ossowski, Tübingen/DE, H Busch, Lübeck/DE, N von Bubnoff, Lübeck/DE
Next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) is a promising, minimally invasive method for comprehensive genomic tumor profiling, treatment monitoring and mirrors tumor heterogeneity. However, its integration into routine clinical decisionmaking within Molecular Tumor Boards (MTBs) is still pending. The HiLiB-MTB project seeks to establish a standardized liquid biopsy (LB) platform for MTBs across Germany. Here we describe a pilot study for NGS panel analysis of ctDNA in MTB patients. A customized targeted NGS panel was developed to detect mutations of the 109 most relevant cancer genes. Raw sequencing output was analyzed by an in-house bioinformatic workflow. The NGS panel was validated using digital droplet (dd)PCR or by comparison with whole-exome sequencing (WES) data from matched tumor tissue biopsies (TB). We analyzed 87 samples, including 49 patient samples, 21 healthy blood donors (negative control) and 17 reference genome samples (positive control). We observed a strong correlation between ctDNA genotyping by NGS and ddPCR (R²=0.97) for 8 mutations measured in parallel in 28 samples of 15 cancer patients, reliably detecting also low-frequency mutations (VAF³0.25%). Clinical concordance, namely finding the same driver mutation by NGS was 82% for ddPCR and 75% for WES as previous analyses, demonstrating the potential of LBgenotyping for therapy recommendation. This pilot data set demonstrates that NGS of ctDNA allows genotyping of cancer mutations in MTB patients. The standardized HiLiB-MTB platform aims to harmonize NGS panel design and bioinformatic workflows across 13 MTBs in Germany. The NGS panel will be further optimized to detect tumor mutational burden (TMB), microsatellite instability (MSI) and homologous recombination deficiency (HRD). The HiLiB consortium plans to perform a retrospective validation study and launch a prospective multicenter trial comparing LB to TB sequencing. Key endpoints include turnaround time, recall rate of variants and treatment recommendation rates. This consortial activity aims to overcome limitations of TB genotyping in a clinical MTB setting such as limited sample availability, long processing times and incomplete representation of tumor heterogeneity.
Next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) is a promising, minimally invasive method for comprehensive genomic tumor profiling, treatment monitoring and mirrors tumor heterogeneity. However, its integration into routine clinical decisionmaking within Molecular Tumor Boards (MTBs) is still pending. The HiLiB-MTB project seeks to establish a standardized liquid biopsy (LB) platform for MTBs across Germany. Here we describe a pilot study for NGS panel analysis of ctDNA in MTB patients. A customized targeted NGS panel was developed to detect mutations of the 109 most relevant cancer genes. Raw sequencing output was analyzed by an in-house bioinformatic workflow. The NGS panel was validated using digital droplet (dd)PCR or by comparison with whole-exome sequencing (WES) data from matched tumor tissue biopsies (TB). We analyzed 87 samples, including 49 patient samples, 21 healthy blood donors (negative control) and 17 reference genome samples (positive control). We observed a strong correlation between ctDNA genotyping by NGS and ddPCR (R²=0.97) for 8 mutations measured in parallel in 28 samples of 15 cancer patients, reliably detecting also low-frequency mutations (VAF³0.25%). Clinical concordance, namely finding the same driver mutation by NGS was 82% for ddPCR and 75% for WES as previous analyses, demonstrating the potential of LBgenotyping for therapy recommendation. This pilot data set demonstrates that NGS of ctDNA allows genotyping of cancer mutations in MTB patients. The standardized HiLiB-MTB platform aims to harmonize NGS panel design and bioinformatic workflows across 13 MTBs in Germany. The NGS panel will be further optimized to detect tumor mutational burden (TMB), microsatellite instability (MSI) and homologous recombination deficiency (HRD). The HiLiB consortium plans to perform a retrospective validation study and launch a prospective multicenter trial comparing LB to TB sequencing. Key endpoints include turnaround time, recall rate of variants and treatment recommendation rates. This consortial activity aims to overcome limitations of TB genotyping in a clinical MTB setting such as limited sample availability, long processing times and incomplete representation of tumor heterogeneity.
