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[<jats:sup>18<\/jats:sup>F]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 [<jats:sup>18<\/jats:sup>F]FMISO PET\/CT as reference.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>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 [<jats:sup>18<\/jats:sup>F]FMISO PET\/CT imaging. The association between PET-based hypoxia and IL-6 was examined using Pearson\u2019s correlation and multiple regression analyses, and the diagnostic power of IL-6 for tumor hypoxia response prediction was determined with receiver-operating characteristic analyses.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Mean IL-6 concentrations were 15.1, 19.6, and 31.0 pg\/mL at baseline, week 2 and week 5, respectively. Smoking (<jats:italic>p<\/jats:italic>=0.050) and reduced performance status (<jats:italic>p<\/jats:italic>=0.011) resulted in higher IL-6 levels, whereas tumor (<jats:italic>p<\/jats:italic>=0.427) and nodal stages (<jats:italic>p<\/jats:italic>=0.334), tumor localization (<jats:italic>p<\/jats:italic>=0.439), and HPV status (<jats:italic>p<\/jats:italic>=0.294) had no influence. IL-6 levels strongly correlated with the intratumoral hypoxic subvolume during treatment (baseline: <jats:italic>r<\/jats:italic>=0.775, <jats:italic>p<\/jats:italic>&lt;0.001; week 2: <jats:italic>r<\/jats:italic>=0.553, <jats:italic>p<\/jats:italic>=0.007; week 5: <jats:italic>r<\/jats:italic>=0.734, <jats:italic>p<\/jats:italic>&lt;0.001). IL-6 levels in week 2 were higher in patients with absent early tumor hypoxia response (<jats:italic>p<\/jats:italic>=0.016) and predicted early hypoxia response (AUC=0.822, <jats:italic>p<\/jats:italic>=0.031). Increased IL-6 levels at week 5 resulted in a trend towards reduced progression-free survival (<jats:italic>p<\/jats:italic>=0.078) and overall survival (<jats:italic>p<\/jats:italic>=0.013).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Plasma IL-6 is a promising surrogate marker for tumor hypoxia dynamics in HNSCC patients and may facilitate hypoxia-directed personalized radiotherapy concepts.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p>The prospective trial was registered in the German Clinical Trial Register (DRKS00003830). Registered 20 August 2015<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00259-021-05602-x","type":"journal-article","created":{"date-parts":[[2021,11,13]],"date-time":"2021-11-13T03:02:20Z","timestamp":1636772540000},"page":"1650-1660","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Interleukin-6 as surrogate marker for imaging-based hypoxia dynamics in patients with head-and-neck cancers undergoing definitive chemoradiation\u2014results from a prospective pilot trial"],"prefix":"10.1007","volume":"49","author":[{"given":"Alexander","family":"R\u00fchle","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Wiedenmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamina T.","family":"Fennell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Mix","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juri","family":"Ruf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raluca","family":"Stoian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas R.","family":"Thomsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Vaupel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimos","family":"Baltas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anca-L.","family":"Grosu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2550-1410","authenticated-orcid":false,"given":"Nils H.","family":"Nicolay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,11,13]]},"reference":[{"key":"5602_CR1","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.1080\/0284186X.2016.1185148","volume":"55","author":"MF Svahn","year":"2016","unstructured":"Svahn MF, Munk C, Nielsen TSS, von Buchwald C, Frederiksen K, Kjaer SK. 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