OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Germany; Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; German Cancer Consortium (DKTK), Partner Site Dresden, Germany; Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Germany; Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; German Cancer Consortium (DKTK), Partner Site Dresden, Germany; Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
Radiother Oncol. 2019 Jun;135:43-50. doi: 10.1016/j.radonc.2019.02.020. Epub 2019 Mar 9.
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 [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).
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.
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.
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.
缺氧是肿瘤对放疗、化疗和潜在免疫治疗产生抵抗的一个重要因素。它可以通过正电子发射断层扫描（PET）成像或肿瘤活检的缺氧相关基因表达来测量。在这里，我们对 50 例头颈部鳞状细胞癌（HNSCC）患者的[F]氟米索硝唑（FMISO）-PET/CT 成像与缺氧相关基因表达进行了相关性分析，并比较了它们对放化疗（RCTx）反应的预后价值。
对 50 例 HNSCC 患者在 RCTx 前和期间进行了 4 次 FMISO-PET/CT 扫描。对于其中 42 例患者，采用纳米串技术基于治疗前获得的活检评估缺氧相关基因的表达。采用 Spearman 相关系数ρ 对 FMISO-PET 参数肿瘤与背景比和缺氧体积与 58 个缺氧相关基因的表达进行相关性分析。比较了 3 个与 FMISO-PET 参数相关的缺氧相关基因特征，使用它们的中位数表达进行比较。此外，还分析了与肿瘤体积的相关性。采用 Cox 回归分析两种缺氧测量方法对局部区域肿瘤控制（LRC）和总生存（OS）的影响。
缺氧相关基因的中位表达与 FMISO-PET 成像测量的缺氧呈弱相关（ρ≤0.43），与治疗第 1 和 2 周后的成像呈较高相关性（p<0.001）。FMISO-PET 成像与肿瘤体积之间存在中度相关性（ρ≤0.69）。基于 FMISO-PET 参数的 LRC 和 OS 预后模型不能通过纳入缺氧分类器来改善。
我们观察到缺氧 FMISO-PET 参数与缺氧相关基因的表达之间存在低相关性。由于 FMISO-PET 显示出更好的患者分层能力，因此它可能是局部晚期 HNSCC 患者接受原发 RCTx 治疗的首选生物标志物，优于缺氧相关基因。
