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首页> 外文期刊>Radiotherapy and oncology: Journal of the European Society for Therapeutic Radiology and Oncology >Gene expression classifier predicts for hypoxic modification of radiotherapy with nimorazole in squamous cell carcinomas of the head and neck
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Gene expression classifier predicts for hypoxic modification of radiotherapy with nimorazole in squamous cell carcinomas of the head and neck

机译：基因表达分类器预测尼莫拉唑对头颈部鳞状细胞癌放疗的低氧修饰

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Purpose: To validate the predictive impact of a hypoxia gene expression classifier in identifying patients with head and neck squamous cell carcinoma (HNSCC) having benefit from hypoxic modification of radiotherapy. Patients and methods: Gene expressions were quantified from formalin-fixed, paraffin-embedded tumour biopsies of 323 HNSCC patients randomized for placebo or nimorazole in conjunction with radiotherapy in the DAHANCA 5 study. Tumours were classified as either "more" or "less" hypoxic with a classifier constituting of 15 hypoxia responsive genes. The predictive impact was evaluated by analysing the response to nimorazole vs. placebo in terms of loco-regional tumour control (LRC) and disease-specific survival (DSS) in the two classified groups. Results: Hundred and fourteen patients (35%) were classified as having "more" hypoxic tumours. These patients had a significant benefit of hypoxic modification with nimorazole compared with placebo in terms of LRC (5-year actuarial values 49% vs. 18%; p = 0.001) and DSS (48% vs. 30%; p = 0.04). "Less" hypoxic tumours had no significant effect of hypoxic modification (LRC: 50% vs. 44%; p = 0.39, DSS: 57% vs. 51%; p = 0.49) and generally an outcome, which was similar to "more" hypoxic tumours treated with nimorazole. In contrast to HPV-negative tumours, HPV-positive tumours had a substantially better outcome in response to radiotherapy, which was irrespective of hypoxic modification. Conclusions: A predictive 15-gene hypoxia classifier could identify patients associated with improved outcome after combining radiotherapy with hypoxic modification and underlines the relevance of such therapy. The impact of the classifier was limited to HPV-negative tumours.
机译：目的：验证缺氧基因表达分类器在鉴定受益于低氧放疗的头颈部鳞状细胞癌（HNSCC）患者中的预测作用。患者和方法：在DAHANCA 5研究中，从323名HNSCC患者的福尔马林固定，石蜡包埋的肿瘤活检样本中量化了基因表达，这些患者随机接受安慰剂或尼莫拉唑联合放疗。用由15个缺氧反应性基因组成的分类器将肿瘤分类为“较多”或“较少”低氧。通过分析两个分类组的局部区域肿瘤控制（LRC）和疾病特异性生存率（DSS），通过分析对尼莫拉唑和安慰剂的反应来评估预测性影响。结果：一百零四例患者（35％）被分类为具有“更多”的缺氧肿瘤。与LRC（5年精算值49％比18％; p = 0.001）和DSS（48％vs. 30％; p = 0.04）相比，这些患者与安慰剂相比，使用尼莫拉唑进行低氧修饰具有显着的益处。 “较少”的低氧肿瘤对低氧修饰无明显影响（LRC：50％vs. 44％; p = 0.39，DSS：57％vs. 51％; p = 0.49），并且通常具有结局，类似于“更多用尼莫拉唑治疗缺氧性肿瘤。与HPV阴性肿瘤相反，HPV阳性肿瘤对放疗的反应明显好转，而与低氧修饰无关。结论：预测性15基因缺氧分类器可以确定放疗联合低氧修饰后预后改善的患者，并强调这种治疗的相关性。分类器的影响仅限于HPV阴性肿瘤。

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