Independent prospective validation of a predictive test for risk of radiation induced fibrosis based on the gene expression pattern in fibroblasts irradiated in vitro
Independent prospective validation of a predictive test for risk of radiation induced fibrosis based on the gene expression pattern in fibroblasts irradiated in vitro
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DOI：
10.1016/j.radonc.2013.08.029
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发表时间：
2013-09-01
影响因子：
5.7
通讯作者：
Alsner, Jan
中科院分区：
文献类型：
--
作者：
Andreassen, Christian Nicolaj;Overgaard, Jens;Alsner, Jan
目的：在先前发表的一项研究中，我们根据体外照射的培养成纤维细胞的基因表达模式，建立了一项关于辐射诱导纤维化风险的预测测试。本研究旨在寻求对接受根治性放射治疗的头颈癌患者队列中的预测性检验的独立前瞻性验证。材料和方法：研究队列包括在2000至2004年间连续接受根治性放射治疗的160名头颈癌患者。所有患者均按DAHANCA方案治疗。作为常规随访的一部分，对患者进行皮下纤维化评分。成纤维细胞培养从皮肤活检建立。体外照射成纤维细胞，照射剂量为3次3.5Gy3次。用实时定量聚合酶链式反应检测细胞照射前后9个基因的表达。结果：根据辐射诱导基因的表达情况，将材料分为136例具有“敏感表达谱”的患者和24例具有“抗性表达谱”的患者。在具有“敏感特征”的患者子集中，9年时严重纤维化的累积风险为34%(Kaplan-Meier)，而具有“耐受特征”的患者没有发生严重纤维化(p=0.035)。结论：我们的研究为先前建立的辐射诱导纤维化的预测试验提供了一个独立的前瞻性验证。与我们最初的发现一致，分类器能够识别一小部分患者，这些患者似乎相当抵抗辐射，因此可能被考虑增加剂量。(C)2013爱思唯尔爱尔兰有限公司。保留所有权利。放射治疗与肿瘤学108(2013)469-472
Purpose: In a previously published study, we established a predictive test for the risk of radiation-induced fibrosis based on the gene expression pattern in cultured fibroblast irradiated in vitro. The present study was conducted to seek an independent prospective validation of the predictive test in a cohort of patients given curative radiotherapy for head and neck cancer.Materials and methods: The study cohort comprised 160 consecutive head and neck cancer patients given curative radiotherapy between 2000 and 2004. The patients were treated according to the DAHANCA protocols. The patients were scored for subcutaneous fibrosis as part of routine follow up. Fibroblast culture was established from skin biopsies. The fibroblasts were irradiated in vitro using a fractionation scheme of 3 times 3.5 Gy. The expression of 9 genes was assessed before and after irradiation of the cells using real time PCR.Results: Based on the radiation-induced expression of the assessed genes, the material was divided into 136 patients having the 'sensitive expression profile' and 24 patients having the 'resistant expression profile'. Within the subset of patients with the 'sensitive profile', the cumulative risk of severe fibrosis was 34% at 9 years (Kaplan-Meier) whereas no patients with the 'resistant profile' developed severe fibrosis (p = 0.035).Conclusion: Our study provided an independent prospective validation of the previously established predictive test for radiation induced fibrosis. In agreement with our initial findings, the classifier was able to identify a smaller subset of patients that seems to be rather radioresistant and could therefore potentially be considered for dose escalation. (C) 2013 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 108 (2013) 469-472