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

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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.

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Acknowledgements

We acknowledge the support of Prof. B. Sipos, Institute of Pathology and Neuropathology; Department of General and Molecular Pathology and Pathological Anatomy, Tübingen, Germany and Prof. I. Tinhofer, Department of Radiation Oncology and Radiotherapy, Charité Berlin, Germany. Furthermore, we would like to thank C. Goltermann for the language editing.

Funding

This project was funded by the Center for Personalised Medicine (ZPM) Tübingen/Germany (grant number 025/2015BO1). Kerstin Clasen was supported by the Fortüne/PATE Program of the Medical Faculty, Eberhard Karls University Tübingen (grant number: 2447-0-0). O. Riess and S. Ossowski receive funding by the German Research Foundation (DFG) as an NGS Competence Center (INST 37/1049-1). Parts of the research leading to these results have received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013), ERC Grant Agreement no. 335367. None of our funding sources was involved in the study design, data analysis or data interpretation.

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Authors and Affiliations

  1. Department of Radiation Oncology, Medical Faculty and University Hospital, Eberhard Karls University, Hoppe-Seyler-Straße 3, 72076, Tübingen, Germany

    Kerstin Clasen M.D., Stefan Welz & Daniel Zips

  2. Section for Biomedical Physics, Department of Radiation Oncology, Medical Faculty and University Hospital, Eberhard Karls University, Hoppe-Seyler-Straße 3, 72076, Tübingen, Germany

    Sara Leibfarth, René M. Winter & Daniela Thorwarth

  3. Institute of Medical Genetics and Applied Genomics, Medical Faculty and University Hospital, Eberhard Karls University, Calwerstraße 7, 72076, Tübingen, Germany

    Franz J. Hilke, Jakob Admard, Stephan Ossowski, Olaf Riess & Christopher Schroeder

  4. German Cancer Research Center (DKFZ) partner site Tübingen, German Cancer Consortium (DKTK), Hoppe-Seyler-Straße 3, 72076, Tübingen, Germany

    Stefan Welz, Sergios Gatidis, Christian la Fougère, Konstantin Nikolaou, Daniel Zips & Daniela Thorwarth

  5. Department of Diagnostic and Interventional Radiology, Medical Faculty and University Hospital, Eberhard Karls University, Hoppe-Seyler-Straße 3, 72076, Tübingen, Germany

    Sergios Gatidis & Konstantin Nikolaou

  6. Institute of Pathology and Neuropathology, Medical Faculty and University Hospital, Eberhard Karls University, Liebermeisterstraße 8, 72076, Tübingen, Germany

    Dominik Nann

  7. Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, C/Dr. Aiguader 88, 08003, Barcelona, Spain

    Stephan Ossowski

  8. Department of Otolaryngology, Head and Neck Surgery, Medical Faculty and University Hospital, Eberhard Karls University, Elfriede-Aulhorn-Straße 5, 72076, Tübingen, Germany

    Thomas Breuer

  9. 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

    Christian la Fougère

  10. NGS Competence Center Tübingen (NCCT), Eberhard Karls University, Calwerstraße 7, 72076, Tübingen, Germany

    Stephan Ossowski & Olaf Riess

Authors
  1. Kerstin Clasen M.D.
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  2. Sara Leibfarth
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Correspondence to Kerstin Clasen M.D..

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Conflict of interest

C. la Fougère has research collaborations with Siemens Healthineers. D. Zips and D. Thorwarth have research collaborations with Elekta, Philips and Siemens. K. Clasen, S. Leibfarth, F.J. Hilke, J. Admard, R.M. Winter, S. Welz, S. Gatidis, D. Nann, S. Ossowski, T. Breuer, K. Nikolaou, O. Riess and C. Schroeder declare that they have no competing interests.

Ethical standards

The study was approved by the local ethics committee (reference number 025/2015) and all patients declared their written informed consent. The study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments.

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Clasen, K., Leibfarth, S., Hilke, F.J. et al. PET/MRI and genetic intrapatient heterogeneity in head and neck cancers. Strahlenther Onkol 196, 542–551 (2020). https://doi.org/10.1007/s00066-020-01606-y

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