Kerstin Clasen1, Sara Leibfarth2, Franz J Hilke3, Jakob Admard3, René M Winter2, Stefan Welz4,5, Sergios Gatidis5,6, Dominik Nann7, Stephan Ossowski3,8,9, Thomas Breuer10, Christian la Fougère5,11, Konstantin Nikolaou5,6, Olaf Riess3,9, Daniel Zips4,5, Christopher Schroeder3, Daniela Thorwarth2,5. 1. Department of Radiation Oncology, Medical Faculty and University Hospital, Eberhard Karls University, Hoppe-Seyler-Straße 3, 72076, Tübingen, Germany. Kerstin.Clasen@med.uni-tuebingen.de. 2. Section for Biomedical Physics, Department of Radiation Oncology, Medical Faculty and University Hospital, Eberhard Karls University, Hoppe-Seyler-Straße 3, 72076, Tübingen, Germany. 3. Institute of Medical Genetics and Applied Genomics, Medical Faculty and University Hospital, Eberhard Karls University, Calwerstraße 7, 72076, Tübingen, Germany. 4. Department of Radiation Oncology, Medical Faculty and University Hospital, Eberhard Karls University, Hoppe-Seyler-Straße 3, 72076, Tübingen, Germany. 5. German Cancer Research Center (DKFZ) partner site Tübingen, German Cancer Consortium (DKTK), Hoppe-Seyler-Straße 3, 72076, Tübingen, Germany. 6. Department of Diagnostic and Interventional Radiology, Medical Faculty and University Hospital, Eberhard Karls University, Hoppe-Seyler-Straße 3, 72076, Tübingen, Germany. 7. Institute of Pathology and Neuropathology, Medical Faculty and University Hospital, Eberhard Karls University, Liebermeisterstraße 8, 72076, Tübingen, Germany. 8. Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, C/Dr. Aiguader 88, 08003, Barcelona, Spain. 9. NGS Competence Center Tübingen (NCCT), Eberhard Karls University, Calwerstraße 7, 72076, Tübingen, Germany. 10. Department of Otolaryngology, Head and Neck Surgery, Medical Faculty and University Hospital, Eberhard Karls University, Elfriede-Aulhorn-Straße 5, 72076, Tübingen, Germany. 11. Division of Nuclear Medicine and Clinical Molecular Imaging, Department of Radiology, Medical Faculty and University Hospital, Eberhard Karls University, Otfried-Müller-Straße 14, 72076, Tübingen, Germany.
Abstract
PURPOSE: The relation between functional imaging and intrapatient genetic heterogeneity remains poorly understood. The aim of our study was to investigate spatial sampling and functional imaging by FDG-PET/MRI to describe intrapatient tumour heterogeneity. METHODS: Six patients with oropharyngeal cancer were included in this pilot study. Two tumour samples per patient were taken and sequenced by next-generation sequencing covering 327 genes relevant in head and neck cancer. Corresponding regions were delineated on pretherapeutic FDG-PET/MRI images to extract apparent diffusion coefficients and standardized uptake values. RESULTS: Samples were collected within the primary tumour (n = 3), within the primary tumour and the involved lymph node (n = 2) as well as within two independent primary tumours (n = 1). Genetic heterogeneity of the primary tumours was limited and most driver gene mutations were found ubiquitously. Slightly increasing heterogeneity was found between primary tumours and lymph node metastases. One private predicted driver mutation within a primary tumour and one in a lymph node were found. However, the two independent primary tumours did not show any shared mutations in spite of a clinically suspected field cancerosis. No conclusive correlation between genetic heterogeneity and heterogeneity of PET/MRI-derived parameters was observed. CONCLUSION: Our limited data suggest that single sampling might be sufficient in some patients with oropharyngeal cancer. However, few driver mutations might be missed and, if feasible, spatial sampling should be considered. In two independent primary tumours, both lesions should be sequenced. Our data with a limited number of patients do not support the concept that multiparametric PET/MRI features are useful to guide biopsies for genetic tumour characterization.
PURPOSE: The relation between functional imaging and intrapatient genetic heterogeneity remains poorly understood. The aim of our study was to investigate spatial sampling and functional imaging by FDG-PET/MRI to describe intrapatient tumour heterogeneity. METHODS: Six patients with oropharyngeal cancer were included in this pilot study. Two tumour samples per patient were taken and sequenced by next-generation sequencing covering 327 genes relevant in head and neck cancer. Corresponding regions were delineated on pretherapeutic FDG-PET/MRI images to extract apparent diffusion coefficients and standardized uptake values. RESULTS: Samples were collected within the primary tumour (n = 3), within the primary tumour and the involved lymph node (n = 2) as well as within two independent primary tumours (n = 1). Genetic heterogeneity of the primary tumours was limited and most driver gene mutations were found ubiquitously. Slightly increasing heterogeneity was found between primary tumours and lymph node metastases. One private predicted driver mutation within a primary tumour and one in a lymph node were found. However, the two independent primary tumours did not show any shared mutations in spite of a clinically suspected field cancerosis. No conclusive correlation between genetic heterogeneity and heterogeneity of PET/MRI-derived parameters was observed. CONCLUSION: Our limited data suggest that single sampling might be sufficient in some patients with oropharyngeal cancer. However, few driver mutations might be missed and, if feasible, spatial sampling should be considered. In two independent primary tumours, both lesions should be sequenced. Our data with a limited number of patients do not support the concept that multiparametric PET/MRI features are useful to guide biopsies for genetic tumour characterization.
Authors: Konstantin Hellwig; Stephan Ellmann; Markus Eckstein; Marco Wiesmueller; Sandra Rutzner; Sabine Semrau; Benjamin Frey; Udo S Gaipl; Antoniu Oreste Gostian; Arndt Hartmann; Heinrich Iro; Rainer Fietkau; Michael Uder; Markus Hecht; Tobias Bäuerle Journal: Front Oncol Date: 2021-10-21 Impact factor: 6.244