Publications Repository - Helmholtz-Zentrum Dresden-Rossendorf

1 Publication
Repeat FMISO-PET imaging weakly correlates with hypoxia-associated gene expressions for locally advanced HNSCC treated by primary radiochemotherapy
Löck, S.; Linge, A.; Seidlitz, A.; Bandurska-Luque, A.; Nowak, A.; Gudziol, V.; Buchholz, F.; Aust, D. E.; Baretton, G. B.; Zöphel, K.; Steinbach, J.; Kotzerke, J.; Overgaard, J.; Zips, D.; Krause, M.; Baumann, M.; Troost, E. G. C.;
Background: Hypoxia is an important factor of tumour resistance to radiotherapy, chemotherapy and potentially immunotherapy. It can be measured e.g. by positron emission tomography (PET) imaging or hypoxia-associated gene expressions from tumour biopsies. Here we correlate [ 18 F]fluoromisonidazole (FMISO)-PET/CT imaging with hypoxia-associated gene expressions on a cohort of 50 head and neck squamous cell carcinoma (HNSCC) patients and compare their prognostic value for response to radiochemotherapy (RCTx). Methods: FMISO-PET/CT images of 50 HNSCC patients were acquired at four time-points before and during RCTx. For 42 of these patients, hypoxia-associated gene expressions were evaluated by nanoString technology based on a biopsy obtained before any treatment. The FMISO-PET parameters tumour-to-background ratio and hypoxic volume were correlated to the expressions of 58 hypoxia-associated genes using the Spearman correlation coefficient ρ. Three hypoxia-associated gene signatures were compared regarding their correlation with the FMISO-PET parameters using their median expression. In addition, the correlation with tumour volume was analysed. The impact of both hypoxia measurement methods on loco-regional tumour control (LRC) and overall survival (OS) was assessed by Cox regression. Results: The median expression of hypoxia-associated genes was weakly correlated to hypoxia measured by FMISO-PET imaging (ρ ≤ 0.43), with higher correlations to imaging after weeks 1 and 2 of treatment (p < 0.001). Moderate correlations were obtained between FMISO-PET imaging and tumour volume (ρ ≤ 0.69). Prognostic models for LRC and OS based on the FMISO-PET parameters could not be improved by including hypoxia classifiers. Conclusion: We observed low correlations between hypoxia FMISO-PET parameters and expressions of hypoxia-associated genes. Since FMISO-PET showed a superior patient stratification, it may be the preferred biomarker over hypoxia-associated genes for stratifying patients with locally advanced HNSCC treated by primary RCTx.
Keywords: FMISO-PET, Gene signature, Hypoxia, Locally advanced HNSCC, Radiochemotherapy

Publ.-Id: 29032 - Permalink