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

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

Sebastian Zschaeck  1   2   3   4   5 , Julian Weingärtner  1   2 , Elia Lombardo  6 , Sebastian Marschner  6   7 , Marina Hajiyianni  1 , Marcus Beck  1 , Daniel Zips  1   8   9 , Yimin Li  10 , Qin Lin  10 , Holger Amthauer  11 , Esther G C Troost  3   4   5   12   13   14   15 , Jörg van den Hoff  16 , Volker Budach  1 , Jörg Kotzerke  4   5   17 , Konstantinos Ferentinos  18 , Efstratios Karagiannis  18 , David Kaul  1 , Vincent Gregoire  19 , Adrien Holzgreve  20 , Nathalie L Albert  20 , Pavel Nikulin  16 , Michael Bachmann  16 , Klaus Kopka  16 , Mechthild Krause  3   4   5   12   13   14   15 , Michael Baumann  3   4   5   12   21 , Joanna Kazmierska  22   23 , Paulina Cegla  24 , Witold Cholewinski  22   24 , Iosif Strouthos  18 , Klaus Zöphel  4   5   17   25 , Ewa Majchrzak  26 , Guillaume Landry  6 , Claus Belka  6   7 , Carmen Stromberger  1 , Frank Hofheinz  16
Affiliations

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

Sebastian Zschaeck et al. Front Oncol. .

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 SUVmax, SUVmean, 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) SUVmax was well suited to identify patients with excellent LRC for organ preservation. Patients with SUVmax 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).

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Conflict of interest statement

In the past 5 years, MBau received funding for his research projects and for educational grants to the University of Dresden by Bayer AG (2016–2018), Merck KGaA (2014-open) and Medipan GmbH (2014–2018). He is on the supervisory board of HI-STEM gGmbH (Heidelberg) for the German Cancer Research Center (DKFZ, Heidelberg) and also member of the supervisory body of the Charité University Hospital, Berlin. As former chair of OncoRay (Dresden) and present CEO and Scientific Chair of the German Cancer Research Center (DKFZ, Heidelberg), he has been or is responsible for collaborations with a multitude of companies and institutions, worldwide. In this capacity, he has discussed potential projects and signed contracts for research funding and/or collaborations with industry and academia for his institute(s) and staff, including but not limited to pharmaceutical companies such as Bayer, Boehringer Ingelheim, Bosch, Roche and other companies such as Siemens, IBA, Varian, Elekta, Bruker, etc. In this role, he was/is also responsible for the commercial technology transfer activities of his institute(s), including the creation of start-ups and licensing. This includes the DKFZ-PSMA617 related patent portfolio [WO2015055318 (A1), ANTIGEN (PSMA)] and similar IP portfolios. MBau confirms that, to the best of his knowledge, none of the above funding sources were involved in the preparation of this paper. In the past 5 years, MK received funding for her research projects by IBA (2016), Merck KGaA (2014-2018 for preclinical study; 2018-2020 for clinical study), Medipan GmbH (2014–2018). She is involved in an ongoing publicly funded (German Federal Ministry of Education and Research) project with the companies Medipan, Attomol GmbH, GA Generic Assays GmbH, Gesellschaft für medizinische und wissenschaftliche genetische Analysen, Lipotype GmbH and PolyAn GmbH (2019–2021). For the present manuscript, MK confirms that none of the above funding sources were involved in the preparation of this paper. HA declares research grants, travel grants, and lecture fees from Sirtex Medical Europe; HA confirms that none of the above funding sources were involved in the preparation of this paper. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer FH declared a past co-authorship with one of the authors ET to the handling Editor.

Figures

Figure 1
Figure 1
Overall survival of all patients when stratified by PET parameters.
Figure 2
Figure 2
Loco-regional control of all patients when stratified by PET parameters.
Figure 3
Figure 3
Forest plots showing the prognostic value of the FDG-PET parameter metabolic tumor volume (MTV) in subgroups of patients regarding the clinical endpoints EFS, OS, LRC and FFDM.
Figure 4
Figure 4
Forest plots showing the prognostic value of the FDG-PET parameter maximum standardized uptake value (SUVmax) in subgroups of patients regarding the clinical endpoints EFS, OS, LRC and FFDM.
Figure 5
Figure 5
Loco-regional control of HPV-positive oropharyngeal carcinomas when stratified by PET parameters.
See this image and copyright information in PMC

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