18F-Fluorodeoxyglucose Positron Emission Tomography of Head and Neck Cancer: Location and HPV Specific Parameters for Potential Treatment Individualization

Sebastian Zschaeck; Julian Weingärtner; Elia Lombardo; Sebastian Marschner; Marina Hajiyianni; Marcus Beck; Daniel Zips; Yimin Li; Qin Lin; Holger Amthauer; Esther G C Troost; Jörg van den Hoff; Volker Budach; Jörg Kotzerke; Konstantinos Ferentinos; Efstratios Karagiannis; David Kaul; Vincent Gregoire; Adrien Holzgreve; Nathalie L Albert; Pavel Nikulin; Michael Bachmann; Klaus Kopka; Mechthild Krause; Michael Baumann; Joanna Kazmierska; Paulina Cegla; Witold Cholewinski; Iosif Strouthos; Klaus Zöphel; Ewa Majchrzak; Guillaume Landry; Claus Belka; Carmen Stromberger; Frank Hofheinz

doi:10.3389/fonc.2022.870319

18F-Fluorodeoxyglucose Positron Emission Tomography of Head and Neck Cancer: Location and HPV Specific Parameters for Potential Treatment Individualization

Front Oncol. 2022 Jun 8:12:870319. doi: 10.3389/fonc.2022.870319. eCollection 2022.

Authors

Sebastian Zschaeck^{1

2

3

4

5}, Julian Weingärtner^{1

2}, Elia Lombardo⁶, Sebastian Marschner^{6

7}, Marina Hajiyianni¹, Marcus Beck¹, Daniel Zips^{1

8

9}, Yimin Li¹⁰, Qin Lin¹⁰, Holger Amthauer¹¹, Esther G C Troost^{3

4

5

12

13

14

15}, Jörg van den Hoff¹⁶, Volker Budach¹, Jörg Kotzerke^{4

5

17}, Konstantinos Ferentinos¹⁸, Efstratios Karagiannis¹⁸, David Kaul¹, Vincent Gregoire¹⁹, Adrien Holzgreve²⁰, Nathalie L Albert²⁰, Pavel Nikulin¹⁶, Michael Bachmann¹⁶, Klaus Kopka¹⁶, Mechthild Krause^{3

4

5

12

13

14

15}, Michael Baumann^{3

4

5

12

21}, Joanna Kazmierska^{22

23}, Paulina Cegla²⁴, Witold Cholewinski^{22

24}, Iosif Strouthos¹⁸, Klaus Zöphel^{4

5

17

25}, Ewa Majchrzak²⁶, Guillaume Landry⁶, Claus Belka^{6

7}, Carmen Stromberger¹, Frank Hofheinz¹⁶

Affiliations

¹ Department of Radiation Oncology, Berlin Institute of Health, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
² Berlin Institute of Health (BIH), Berlin, Germany.
³ Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
⁴ German Cancer Consortium (DKTK), Partner Site Dresden, and German Cancer Research Center (DKFZ) Heidelberg, Germany, Germany.
⁵ OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden - Rossendorf, Dresden, Germany.
⁶ Department of Radiation Oncology, University Hospital, Ludwig-Maximilians-University (LMU) Munich, Munich, Germany.
⁷ German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany.
⁸ German Cancer Consortium (DKTK), Partner Site Tübingen, and German Cancer Research Center (DKFZ) Heidelberg, Germany, Germany.
⁹ Department of Radiation Oncology, University Hospital and Medical Faculty, Eberhard Karls University Tübingen, Tübingen, Germany.
¹⁰ Department of Radiation Oncology, Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, Xiamen, China.
¹¹ Department of Nuclear Medicine, Berlin Institute of Health, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
¹² Institute of Radiooncology - OncoRay, Helmholtz-Zentrum Dresden - Rossendorf, Dresden, Germany.
¹³ National Center for Tumor Diseases (NCT), Partner Site Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany.
¹⁴ Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
¹⁵ Helmholtz Association/Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Germany.
¹⁶ Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany.
¹⁷ Department of Nuclear Medicine, Faculty of Medicine and University Hospital Carl Gustav Carus, Dresden, Germany.
¹⁸ Department of Radiation Oncology, German Oncology Center, European University Cyprus, Limassol, Cyprus.
¹⁹ Radiation Oncology Department, Leon Bérard Cancer Center, Lyon, France.
²⁰ Department of Nuclear Medicine, University Hospital, Ludwig-Maximilians-University (LMU) Munich, Germany.
²¹ German Cancer Research Center (DKFZ), Heidelberg, Germany.
²² Electroradiology Department, University of Medical Sciences, Poznan, Poland.
²³ Radiotherapy Department II, Greater Poland Cancer Centre, Poznan, Poland.
²⁴ Department of Nuclear Medicine, Greater Poland Cancer Centre, Poznan, Poland.
²⁵ Department of Nuclear Medicine, Klinikum Chemnitz gGmbH, Chemnitz, Germany.
²⁶ Department of Head and Neck Surgery, Poznan University of Medical Sciences, Greater Poland Cancer Centre, Poznan, Poland.

Abstract

Purpose: 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is utilized for staging and treatment planning of head and neck squamous cell carcinomas (HNSCC). Some older publications on the prognostic relevance showed inconclusive results, most probably due to small study sizes. This study evaluates the prognostic and potentially predictive value of FDG-PET in a large multi-center analysis.

Methods: Original analysis of individual FDG-PET and patient data from 16 international centers (8 institutional datasets, 8 public repositories) with 1104 patients. All patients received curative intent radiotherapy/chemoradiation (CRT) and pre-treatment FDG-PET imaging. Primary tumors were semi-automatically delineated for calculation of SUV_max, SUV_mean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Cox regression analyses were performed for event-free survival (EFS), overall survival (OS), loco-regional control (LRC) and freedom from distant metastases (FFDM).

Results: FDG-PET parameters were associated with patient outcome in the whole cohort regarding clinical endpoints (EFS, OS, LRC, FFDM), in uni- and multivariate Cox regression analyses. Several previously published cut-off values were successfully validated. Subgroup analyses identified tumor- and human papillomavirus (HPV) specific parameters. In HPV positive oropharynx cancer (OPC) SUV_max was well suited to identify patients with excellent LRC for organ preservation. Patients with SUV_max of 14 or less were unlikely to develop loco-regional recurrence after definitive CRT. In contrast FDG PET parameters deliver only limited prognostic information in laryngeal cancer.

Conclusion: FDG-PET parameters bear considerable prognostic value in HNSCC and potential predictive value in subgroups of patients, especially regarding treatment de-intensification and organ-preservation. The potential predictive value needs further validation in appropriate control groups. Further research on advanced imaging approaches including radiomics or artificial intelligence methods should implement the identified cut-off values as benchmark routine imaging parameters.

Keywords: fluorodeoxyglucose positron emission tomography (FDG PET); head and neck squamous cell carcinoma (HNSCC); metabolic tumor volume (MTV); radiotherapy; standardized uptake value (SUV).

Copyright © 2022 Zschaeck, Weingärtner, Lombardo, Marschner, Hajiyianni, Beck, Zips, Li, Lin, Amthauer, Troost, van den Hoff, Budach, Kotzerke, Ferentinos, Karagiannis, Kaul, Gregoire, Holzgreve, Albert, Nikulin, Bachmann, Kopka, Krause, Baumann, Kazmierska, Cegla, Cholewinski, Strouthos, Zöphel, Majchrzak, Landry, Belka, Stromberger and Hofheinz.