Wang Hong, Zhang Bingfeng, Chen Dan, Xia Wenying, Zhang Jiexin, Wang Fang, Xu Jian, Zhang Yan, Zhang Meijuan, Zhang Lixia, Lu Yachun, Geng Yan, Huang Peijun, Huang Puwen, Wang Hong, Pan Shiyang
Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029 China.
National Key Clinical Department of Laboratory Medicine, Nanjing, 210029 China.
Clin Epigenetics. 2015 Nov 5;7:119. doi: 10.1186/s13148-015-0150-9. eCollection 2015.
The Response Evaluation Criteria in Solid Tumors (RECIST) guideline and Common Terminology Criteria for Adverse Events (CTCAE) criteria are used to assess chemotherapy efficiency and toxicity in patients with advanced lung cancer. However, no real-time, synchronous indicators that can evaluate chemotherapy outcomes are available. We wanted to evaluate tumor response and toxicity in advanced lung cancer chemotherapy by using a novel synchronous strategy.
We enrolled 316 patients with advanced lung cancer who were treated with cisplatin-based therapy and followed up them for 3 years. Plasma was obtained before and after every chemotherapy cycle. We quantitative assayed total plasma DNA and methylation of the APC/RASSF1A genes. Four parameters were assessed: methylation level before chemotherapy (meth0 h), methylation level 24 h after chemotherapy (meth24 h), total plasma DNA concentration before chemotherapy (DNA0 h), and total plasma DNA concentration 24 h after chemotherapy (DNA24 h). When meth24 h > meth0 h of at least one gene was used to predict tumor response, the correct prediction rate was 82.4 %. Additionally, patients for whom DNA24 h/DNA0 h ≤ 2 had mild toxicities. Therefore, meth24 h > meth0 h and DNA24 h/DNA0 h ≤ 2 were defined as criteria for better tumor response and fewer adverse events with a high correct prediction rate (84.7 %).
Quantitative analysis of total plasma DNA and plasma APC/RASSF1A methylation provide a real-time synchronous rapid monitoring indicator for therapeutic outcomes of advanced lung cancer, which could be a reference or supplementary guidelines in evaluating chemotherapy effects.
实体瘤疗效评价标准(RECIST)指南和不良事件通用术语标准(CTCAE)标准用于评估晚期肺癌患者的化疗疗效和毒性。然而,目前尚无能够评估化疗结果的实时、同步指标。我们希望通过一种新的同步策略来评估晚期肺癌化疗中的肿瘤反应和毒性。
我们纳入了316例接受含顺铂方案治疗的晚期肺癌患者,并对其进行了3年的随访。在每个化疗周期前后采集血浆。我们对血浆总DNA和APC/RASSF1A基因的甲基化进行了定量分析。评估了四个参数:化疗前甲基化水平(meth0 h)、化疗后24小时甲基化水平(meth24 h)、化疗前血浆总DNA浓度(DNA0 h)和化疗后24小时血浆总DNA浓度(DNA24 h)。当使用至少一个基因的meth24 h > meth0 h来预测肿瘤反应时,正确预测率为82.4%。此外,DNA24 h/DNA0 h≤2的患者毒性较轻。因此,meth24 h > meth0 h且DNA24 h/DNA0 h≤2被定义为肿瘤反应较好且不良事件较少的标准,正确预测率较高(84.7%)。
血浆总DNA和血浆APC/RASSF1A甲基化的定量分析为晚期肺癌的治疗结果提供了实时同步的快速监测指标,可为评估化疗效果提供参考或补充指南。