PET/MRI and genetic intrapatient heterogeneity in head and neck cancers

• Published in: Strahlentherapie und Onkologie 2020-06, Vol.196 (6), p.542-551
• Main Authors: Clasen, Kerstin, Leibfarth, Sara, Hilke, Franz J., Admard, Jakob, Winter, René M., Welz, Stefan, Gatidis, Sergios, Nann, Dominik, Ossowski, Stephan, Breuer, Thomas, la Fougère, Christian, Nikolaou, Konstantin, Riess, Olaf, Zips, Daniel, Schroeder, Christopher, Thorwarth, Daniela
• Format: Article
• Language: English
• Subjects: Aged; Cancer; Carcinoma, Squamous Cell - diagnostic imaging; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - secondary; Carcinoma, Squamous Cell - ultrastructure; Fluorine Radioisotopes; Fluorodeoxyglucose F18; Gene sequencing; Genes, Neoplasm; Genes, p53; Genetic Heterogeneity; Head & neck cancer; Heterogeneity; Humans; Lymphatic system; Magnetic Resonance Imaging; Male; Medical imaging; Medicine; Medicine & Public Health; Middle Aged; Multimodal Imaging; Mutation; Neoplasms, Multiple Primary - diagnostic imaging; Neoplasms, Multiple Primary - genetics; Neoplasms, Multiple Primary - ultrastructure; Nodes; Oncology; Original Article; Oropharyngeal Neoplasms - diagnostic imaging; Oropharyngeal Neoplasms - genetics; Oropharyngeal Neoplasms - ultrastructure; Pilot Projects; Positron emission; Positron-Emission Tomography; Prospective Studies; Radiopharmaceuticals; Radiotherapy; Receptor, Notch1 - genetics; Sampling; Throat cancer; Tomography; Tumors
• ISSN: 0179-7158; 1439-099X
• DOI: 10.1007/s00066-020-01606-y

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.