Rachel Galot1, Cédric van Marcke2, Raphaël Helaers3, Antonella Mendola4, Rose-Marie Goebbels4, Xavier Caignet4, Jérôme Ambroise5, Kyril Wittouck4, Miikka Vikkula3, Nisha Limaye6, Jean-Pascal H Machiels7. 1. Department of Medical Oncology, Institut Roi Albert II - Cliniques universitaires Saint-Luc, Brussels, Belgium; Institute for Clinical and Experimental Research (MIRO), Université catholique de Louvain, Brussels, Belgium. 2. Department of Medical Oncology, Institut Roi Albert II - Cliniques universitaires Saint-Luc, Brussels, Belgium; Institute for Clinical and Experimental Research (MIRO), Université catholique de Louvain, Brussels, Belgium; Laboratory of Human Molecular Genetics, de Duve Institute, Université catholique de Louvain, Brussels, Belgium. 3. Laboratory of Human Molecular Genetics, de Duve Institute, Université catholique de Louvain, Brussels, Belgium. 4. Institute for Clinical and Experimental Research (MIRO), Université catholique de Louvain, Brussels, Belgium. 5. Institute for Clinical and Experimental Research (CTMA), Université catholique de Louvain, Brussels, Belgium. 6. Genetics of Autoimmune Diseases and Cancer, de Duve Institute, Université catholique de Louvain, Brussels, Belgium. 7. Department of Medical Oncology, Institut Roi Albert II - Cliniques universitaires Saint-Luc, Brussels, Belgium; Institute for Clinical and Experimental Research (MIRO), Université catholique de Louvain, Brussels, Belgium. Electronic address: jean-pascal.machiels@uclouvain.be.
Abstract
OBJECTIVES: The molecular landscape of head and neck squamous cell carcinoma (HNSCC) harbors potentially actionable genomic alterations. We aimed to study the utility of liquid biopsy to (i) characterize the mutational landscape of recurrent/metastatic HNSCC using a comprehensive gene panel and (ii) estimate the concordance between DNA mutations identified from circulating tumor DNA (ctDNA) and matched tumor tissues. MATERIALS AND METHODS: Targeted next-generation sequencing (NGS) was performed on cell-free DNA (cfDNA) of 39 patients with locoregional recurrent (n = 19) and/or metastatic (n = 20) HNSCC. Tumor biopsy (n = 18) was sequenced using the same technique. RESULTS: ctDNA was detected in 51% of patients (20/39) with a higher probability of detection in metastatic than locoregional recurrent disease (70% versus 30%, p = 0.025). 81% and 58% of the tissue tumor variants were not detected in plasma when considering all patients and only metastatic patients with detectable ctDNA, respectively. In a multivariate analysis, the likelihood of detecting the tissue tumor variant in plasma was related to metastatic status (p = 0.012), tumor variant allele frequency (p < 0.001) and ctDNA quantity (p < 0.001). 26% of the variants were detected only in liquid and not in the solid biopsy. Three patients without an available tumor sample had plasma containing three different potentially actionable PIK3CA mutations. CONCLUSION: CtDNA detection and characterization using targeted NGS is feasible in metastatic HNSCC. Liquid biopsies do not reflect the complete mutation profile of the tumor but have the potential to identify actionable mutations when tumor biopsies are not available as well as variants not found in matched tumor tissue.
OBJECTIVES: The molecular landscape of head and neck squamous cell carcinoma (HNSCC) harbors potentially actionable genomic alterations. We aimed to study the utility of liquid biopsy to (i) characterize the mutational landscape of recurrent/metastatic HNSCC using a comprehensive gene panel and (ii) estimate the concordance between DNA mutations identified from circulating tumor DNA (ctDNA) and matched tumor tissues. MATERIALS AND METHODS: Targeted next-generation sequencing (NGS) was performed on cell-free DNA (cfDNA) of 39 patients with locoregional recurrent (n = 19) and/or metastatic (n = 20) HNSCC. Tumor biopsy (n = 18) was sequenced using the same technique. RESULTS: ctDNA was detected in 51% of patients (20/39) with a higher probability of detection in metastatic than locoregional recurrent disease (70% versus 30%, p = 0.025). 81% and 58% of the tissue tumor variants were not detected in plasma when considering all patients and only metastatic patients with detectable ctDNA, respectively. In a multivariate analysis, the likelihood of detecting the tissue tumor variant in plasma was related to metastatic status (p = 0.012), tumor variant allele frequency (p < 0.001) and ctDNA quantity (p < 0.001). 26% of the variants were detected only in liquid and not in the solid biopsy. Three patients without an available tumor sample had plasma containing three different potentially actionable PIK3CA mutations. CONCLUSION: CtDNA detection and characterization using targeted NGS is feasible in metastatic HNSCC. Liquid biopsies do not reflect the complete mutation profile of the tumor but have the potential to identify actionable mutations when tumor biopsies are not available as well as variants not found in matched tumor tissue.
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