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000168136 0247_ $$2doi$$a10.1016/j.radonc.2021.03.014
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000168136 1001_ $$0P:(DE-He78)80e100a16534f5fc67f7436ee67a47f9$$aRühle, Alexander$$b0$$eFirst author
000168136 245__ $$aImmunohistochemistry-based hypoxia-immune prognostic classifier for head-and-neck cancer patients undergoing chemoradiation - Post-hoc analysis from a prospective imaging trial.
000168136 260__ $$aAmsterdam [u.a.]$$bElsevier Science$$c2021
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000168136 500__ $$a2021 Mar 19;159:75-81 / #EA:E055#LA:E055#
000168136 520__ $$aAs both tumor hypoxia and an immunosuppressing tumor microenvironment hamper the anti-tumor activity of radiotherapy in head-and-neck squamous cell carcinoma (HNSCC), we aimed to develop an immunohistochemistry-based hypoxia-immune classifier.39 patients receiving definitive chemoradiation for HNSCC within a prospective trial were included in this analysis. Baseline tumor samples were analyzed for the hypoxia marker carbonic anhydrase IX (CAIX) and tumor-infiltrating lymphocytes (TILs) and were correlated with [18F]-misonidazole ([18F]FMISO) PET measurements. The impact of the biomarkers on the locoregional control (LRC) was examined using Cox analyses and concordance index statistics.Low CAIX (HR=0.352, 95%CI 0.124-1.001, p=0.050) and high TIL levels (HR=0.308, 95%CI 0.114-0.828, p=0.020) were independent parameters for improved LRC and did not correlate with each other (Spearman's ρ=0.034, p=0.846). Harrell's C was 0.66 for CAIX and TIL levels alone and 0.71 for the combination. 2-year LRC was 73%, 62% and 11% for the prognostically good (CAIXlow/TILhigh), intermediate (CAIXlow/TILlow or CAIXhigh/TILhigh) and poor groups (CAIXhigh/TILlow), respectively (p=0.001). Focusing on T lymphocytes, the hypoxia-immune classifier could still stratify between favorable (CAIXlow/CD3+ TILhigh), intermediate (CAIXlow/CD3+ TILlow or CAIXhigh/CD3+ TILhigh) and poor subgroups (CAIXhigh/CD3+ TILlow) with a 2-year LRC of 80%, 59% and 14%, respectively (p=0.001). There was a positive correlation between baseline CAIX levels and [18F]FMISO SUV in week 2 of chemoradiation (ρ=0.324, p=0.050), indicating an association between higher baseline CAIX expression and tumor hypoxia persistence.We developed a clinically feasible hypoxia-immune prognostic classifier for HNSCC patients based on pre-treatment immunohistochemistry. However, external validation is required to determine the prognostic value and the potential usage for personalized radiation oncology.
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000168136 650_7 $$2Other$$aCarbonic anhydrase IX
000168136 650_7 $$2Other$$aFMISO PET
000168136 650_7 $$2Other$$aHead-and-neck squamous cell carcinoma
000168136 650_7 $$2Other$$aHypoxia
000168136 650_7 $$2Other$$aRadiotherapy biomarker
000168136 650_7 $$2Other$$aTumor-infiltrating lymphocytes
000168136 7001_ $$0P:(DE-HGF)0$$aGrosu, Anca-L$$b1
000168136 7001_ $$0P:(DE-HGF)0$$aWiedenmann, Nicole$$b2
000168136 7001_ $$0P:(DE-He78)75b4c256a6de824414938cf2aaeff88e$$aStoian, Raluca$$b3
000168136 7001_ $$0P:(DE-HGF)0$$aHaehl, Erik$$b4
000168136 7001_ $$0P:(DE-HGF)0$$aZamboglou, Constantinos$$b5
000168136 7001_ $$0P:(DE-HGF)0$$aBaltas, Dimos$$b6
000168136 7001_ $$0P:(DE-HGF)0$$aWerner, Martin$$b7
000168136 7001_ $$0P:(DE-HGF)0$$aKayser, Gian$$b8
000168136 7001_ $$0P:(DE-He78)8d52e7ff1ccaac7dbf0232fdcb0168bd$$aNicolay, Nils$$b9$$eLast author
000168136 773__ $$0PERI:(DE-600)1500707-8$$a10.1016/j.radonc.2021.03.014$$gp. S0167814021061405$$p75-81$$tRadiotherapy and oncology$$v159$$x0167-8140$$y2021
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