%0 Journal Article
%A Nicolay, Nils
%A Rühle, A.
%A Mix, M.
%A Wiedenmann, N.
%A Stoian, R. G.
%A Niedermann, G.
%A Baltas, D.
%A Werner, M.
%A Ruf, Benjamin
%A Kayser, G.
%A Grosu, A.
%T Development of a Hypoxia-Immune Prognostic Classifier for Head-and-Neck Cancer Patients Undergoing Radiotherapy - Results From a Prospective Imaging Trial.
%J International journal of radiation oncology, biology, physics
%V 111
%N 3S
%@ 0360-3016
%C Amsterdam [u.a.]
%I Elsevier Science
%M DKFZ-2021-02367
%P S63 - S64
%D 2021
%Z #EA:E050#
%X Tumor-infiltrating lymphocytes (TILs) correlate with an improved outcome of head-and-neck squamous cell cancer (HNSCC) patients undergoing radiotherapy and are influenced by the tumor microenvironment and tumor-associated hypoxia. The present analysis is based on a prospective imaging trial and analyzes the value of TILs and tumor-associated hypoxia to stratify HNSCC patients according to their response to radiotherapy.A total of 49 patients with locoregionally advanced HNSCCs were prospectively enrolled in this trial and underwent longitudinal hypoxia PET imaging using fluoro-18 misonidazole ([18F]FMISO) in weeks 0, 2 and 5 during chemoradiation. Tumor hypoxia was assumed for a tumor-to-background SUV (contralateral sternocleidomastoid muscle) exceeding 1.4, and an early hypoxia response was defined as a decrease in the normalized maximum intratumoral SUV (FMISO-SUVindex) between weeks 0 and 2. Pre-treatment tumor biopsies were analyzed for TILs and the hypoxia tissue marker carbonic anhydrase IX (CAIX). Trial patients were stratified into 4 subgroups based on their TIL numbers (> 100 vs. < 100 TILs/HPF) and expression of CAIX (above vs. below median H-score), and locoregional control (LRC) and progression-free survival (PFS) rates for all subgroups were assessed using Cox and subsequent concordance analyses (Harrell's C).High TIL levels correlated with improved LRC (HR = 0.279, P = 0.011) and PFS (HR = 0.276, P = 0.006). Similarly, a decrease in the FMISO-SUVindex within the first 2 weeks of treatment corresponded with better LRC (HR = 0.321, P = 0.015) and PFS (HR = 0.402, P = 0.043). Harrell's C was 0.68, when TILs and early hypoxia PET response were combined. The hypoxia PET-based hypoxia-immune classifier separated 3 distinct prognostic patient subgroups, a favorable (TILhigh/ early PET response), and intermediate (TILhigh/no early PET response or TILlow/early PET response) and a poor (TILlow/no early PET response) prognostic group with 2-year LRC of 71
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:34700599
%R 10.1016/j.ijrobp.2021.07.160
%U https://inrepo02.dkfz.de/record/177233