TY  - JOUR
AU  - Rühle, Alexander
AU  - Wiedenmann, Nicole
AU  - Fennell, Jamina T
AU  - Mix, Michael
AU  - Ruf, Juri
AU  - Stoian, Raluca
AU  - Thomsen, Andreas R
AU  - Vaupel, Peter
AU  - Baltas, Dimos
AU  - Grosu, Anca-L
AU  - Nicolay, Nils
TI  - 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.
JO  - European journal of nuclear medicine and molecular imaging
VL  - 49
IS  - 5
SN  - 1619-7089
CY  - Heidelberg [u.a.]
PB  - Springer-Verl.
M1  - DKFZ-2021-02499
SP  - 1650-1660
PY  - 2022
N1  - #EA:E055#LA:E055# / 2022 Apr;49(5):1650-1660
AB  - 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.
KW  - Biomarker (Other)
KW  - FMISO-PET (Other)
KW  - Head-and-neck cancer (Other)
KW  - Hypoxia (Other)
KW  - Interleukin-6 (Other)
KW  - Radiotherapy (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:34773163
DO  - DOI:10.1007/s00259-021-05602-x
UR  - https://inrepo02.dkfz.de/record/177407
ER  -