TY  - JOUR
AU  - Rühle, Alexander
AU  - Grosu, Anca-L
AU  - Wiedenmann, Nicole
AU  - Mix, Michael
AU  - Stoian, Raluca
AU  - Niedermann, Gabriele
AU  - Baltas, Dimos
AU  - Werner, Martin
AU  - Weber, Wolfgang A
AU  - Kayser, Gian
AU  - Nicolay, Nils H
TI  - Hypoxia dynamics on FMISO-PET in combination with PD-1/PD-L1 expression has an impact on the clinical outcome of patients with Head-and-neck Squamous Cell Carcinoma undergoing Chemoradiation.
JO  - Theranostics
VL  - 10
IS  - 20
SN  - 1838-7640
CY  - Wyoming, NSW
PB  - Ivyspring
M1  - DKFZ-2020-01681
SP  - 9395 - 9406
PY  - 2020
N1  - 2020 Jul 23;10(20):9395-9406
AB  - Tumor-associated hypoxia influences the radiation response of head-and-neck cancer (HNSCC) patients, and a lack of early hypoxia resolution during treatment considerably deteriorates outcomes. As the detrimental effects of hypoxia are partly related to the induction of an immunosuppressive microenvironment, we investigated the interaction between tumor hypoxia dynamics and the PD-1/PD-L1 axis in HNSCC patients undergoing chemoradiation and its relevance for patient outcomes in a prospective trial. Methods: 49 patients treated with definitive chemoradiation for locally advanced HNSCC were enrolled in this trial and received longitudinal hypoxia PET imaging using fluorine-18 misonidazole ([18F]FMISO) at weeks 0, 2 and 5 during treatment. Pre-therapeutic tumor biopsies were immunohistochemically analyzed regarding the PD-1/PD-L1 expression both on immune cells and on tumor cells, and potential correlations between the PD-1/PD-L1 axis and tumor hypoxia dynamics during chemoradiation were assessed using Spearman's rank correlations. Hypoxia dynamics during treatment were quantified by subtracting the standardized uptake value (SUV) index at baseline from the SUV values at weeks 2 or 5, whereby SUV index was defined as ratio of maximum tumor [18F]FMISO SUV to mean SUV in the contralateral sternocleidomastoid muscle (i.e. tumor-to-muscle ratio). The impact of the PD-1/PD-L1 expression alone and in combination with persistent tumor hypoxia on locoregional control (LRC), progression-free survival (PFS) and overall survival (OS) was examined using log-rank tests and Cox proportional hazards models. Results: Neither PD-L1 nor PD-1 expression levels on tumor-infiltrating immune cells influenced LRC (HR = 0.734; p = 0.480 for PD-L1, HR = 0.991; p = 0.989 for PD-1), PFS (HR = 0.813; p = 0.597 for PD-L1, HR = 0.796; p = 0.713 for PD-1) or OS (HR = 0.698; p = 0.405 for PD-L1, HR = 0.315; p = 0.265 for PD-1). However, patients with no hypoxia resolution between weeks 0 and 2 and PD-L1 expression on tumor cells, quantified by a tumor proportional score (TPS) of at least 1
LB  - PUB:(DE-HGF)16
C6  - pmid:32802199
C2  - pmc:PMC7415814
DO  - DOI:10.7150/thno.48392
UR  - https://inrepo02.dkfz.de/record/157525
ER  -