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 Grégoire, Adrien Holzgreve, Nathalie L. Albert, Pavel Nikulin, Michael Bachmann, Klaus Kopka, Mechthild Krause, Michaël Baumann, Joanna Kaźmierska, Paulina Cegła, Witold Cholewiński, Iosif Strouthos, Klaus Zöphel, Ewa Majchrzak, Guillaume Landry, Claus Belka, Carmen Stromberger, Frank Hofheinz
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.