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000177407 0247_ $$2ISSN$$a1619-7070
000177407 0247_ $$2ISSN$$a1619-7089
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000177407 1001_ $$0P:(DE-He78)80e100a16534f5fc67f7436ee67a47f9$$aRühle, Alexander$$b0$$eFirst author$$udkfz
000177407 245__ $$aInterleukin-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.
000177407 260__ $$aHeidelberg [u.a.]$$bSpringer-Verl.$$c2022
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000177407 500__ $$a#EA:E055#LA:E055# / 2022 Apr;49(5):1650-1660
000177407 520__ $$aIntratumoral 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.
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000177407 650_7 $$2Other$$aBiomarker
000177407 650_7 $$2Other$$aFMISO-PET
000177407 650_7 $$2Other$$aHead-and-neck cancer
000177407 650_7 $$2Other$$aHypoxia
000177407 650_7 $$2Other$$aInterleukin-6
000177407 650_7 $$2Other$$aRadiotherapy
000177407 7001_ $$0P:(DE-HGF)0$$aWiedenmann, Nicole$$b1
000177407 7001_ $$0P:(DE-HGF)0$$aFennell, Jamina T$$b2
000177407 7001_ $$aMix, Michael$$b3
000177407 7001_ $$aRuf, Juri$$b4
000177407 7001_ $$0P:(DE-He78)75b4c256a6de824414938cf2aaeff88e$$aStoian, Raluca$$b5$$udkfz
000177407 7001_ $$0P:(DE-HGF)0$$aThomsen, Andreas R$$b6
000177407 7001_ $$0P:(DE-HGF)0$$aVaupel, Peter$$b7
000177407 7001_ $$0P:(DE-HGF)0$$aBaltas, Dimos$$b8
000177407 7001_ $$0P:(DE-HGF)0$$aGrosu, Anca-L$$b9
000177407 7001_ $$0P:(DE-He78)8d52e7ff1ccaac7dbf0232fdcb0168bd$$aNicolay, Nils$$b10$$eLast author$$udkfz
000177407 773__ $$0PERI:(DE-600)2098375-X$$a10.1007/s00259-021-05602-x$$n5$$p1650-1660$$tEuropean journal of nuclear medicine and molecular imaging$$v49$$x1619-7089$$y2022
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