%0 Journal Article
%A Rühle, Alexander
%A Wiedenmann, Nicole
%A Fennell, Jamina T
%A Mix, Michael
%A Ruf, Juri
%A Stoian, Raluca
%A Thomsen, Andreas R
%A Vaupel, Peter
%A Baltas, Dimos
%A Grosu, Anca-L
%A Nicolay, Nils
%T Interleukin-6 as surrogate marker for imaging-based hypoxia dynamics in patients with head-and-neck cancers undergoing definitive chemoradiation-results from a prospective pilot trial.
%J European journal of nuclear medicine and molecular imaging
%V 49
%N 5
%@ 1619-7089
%C Heidelberg [u.a.]
%I Springer-Verl.
%M DKFZ-2021-02499
%P 1650-1660
%D 2022
%Z #EA:E055#LA:E055# / 2022 Apr;49(5):1650-1660
%X Intratumoral hypoxia increases resistance of head-and-neck squamous cell carcinoma (HNSCC) to radiotherapy. [18F]FMISO PET imaging enables noninvasive hypoxia monitoring, though requiring complex logistical efforts. We investigated the role of plasma interleukin-6 (IL-6) as potential surrogate parameter for intratumoral hypoxia in HNSCC using [18F]FMISO PET/CT as reference.Within a prospective trial, serial blood samples of 27 HNSCC patients undergoing definitive chemoradiation were collected to analyze plasma IL-6 levels. Intratumoral hypoxia was assessed in treatment weeks 0, 2, and 5 using [18F]FMISO PET/CT imaging. The association between PET-based hypoxia and IL-6 was examined using Pearson's correlation and multiple regression analyses, and the diagnostic power of IL-6 for tumor hypoxia response prediction was determined with receiver-operating characteristic analyses.Mean IL-6 concentrations were 15.1, 19.6, and 31.0 pg/mL at baseline, week 2 and week 5, respectively. Smoking (p=0.050) and reduced performance status (p=0.011) resulted in higher IL-6 levels, whereas tumor (p=0.427) and nodal stages (p=0.334), tumor localization (p=0.439), and HPV status (p=0.294) had no influence. IL-6 levels strongly correlated with the intratumoral hypoxic subvolume during treatment (baseline: r=0.775, p<0.001; week 2: r=0.553, p=0.007; week 5: r=0.734, p<0.001). IL-6 levels in week 2 were higher in patients with absent early tumor hypoxia response (p=0.016) and predicted early hypoxia response (AUC=0.822, p=0.031). Increased IL-6 levels at week 5 resulted in a trend towards reduced progression-free survival (p=0.078) and overall survival (p=0.013).Plasma IL-6 is a promising surrogate marker for tumor hypoxia dynamics in HNSCC patients and may facilitate hypoxia-directed personalized radiotherapy concepts.The prospective trial was registered in the German Clinical Trial Register (DRKS00003830). Registered 20 August 2015.
%K Biomarker (Other)
%K FMISO-PET (Other)
%K Head-and-neck cancer (Other)
%K Hypoxia (Other)
%K Interleukin-6 (Other)
%K Radiotherapy (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:34773163
%R 10.1007/s00259-021-05602-x
%U https://inrepo02.dkfz.de/record/177407