Department of Medicine III, University Hospital, LMU, Munich, Germany.
Sysmex Inostics, Hamburg, Germany.
Ann Oncol. 2018 Dec 1;29(12):2348-2355. doi: 10.1093/annonc/mdy417.
The presence of mutated KRAS (mutKRAS ctDNA) in plasma samples has been consistently shown to be a negative prognostic indicator in pancreatic cancer (PC). Only small pilot studies have evaluated the value of serial mutKRAS ctDNA-measurements in PC.
The aim of the present study was to explore the potential of repeated mutKRAS ctDNA measurements for response prediction and therapy monitoring in advanced PC patients. We used the BEAMing technology to determine levels of mutKRAS ctDNA, CA 19-9, CEA and CYFRA 21-1 in 284 plasma samples of 54 patients with advanced PC receiving gemcitabine-based chemotherapy. Absolute levels and kinetics of mutKRAS ctDNA, CA 19-9, CEA and CYFRA 21-1 were correlated to radiological response, progression-free and overall survival.
mutKRAS ctDNA was present in a majority of advanced PC patients (n = 36/54, 67%) and indicated tissue KRAS mutation status with a high sensitivity (75%) and specificity (100%). The presence of mutKRAS ctDNA, as well as higher levels of CA 19-9, CEA and CYFRA 21-1 before initiation of the first-line chemotherapy, was significantly correlated to an adverse overall survival. During therapy, changes in mutKRAS ctDNA levels were more rapid and pronounced than changes in protein-based tumor markers. A decrease in mutKRAS ctDNA levels during therapy was an early indicator of response to therapy, while there was no significant correlation between kinetics of CA 19-9, CEA or CYFRA 21-1 and response to chemotherapy during the first four weeks of treatment. Repeated mutKRAS ctDNA measurements during follow-up appeared to be superior to protein-based tumor markers in detecting progressive disease (sensitivity: 83%, specificity: 100%).
mutKRAS ctDNA kinetics appear to be a powerful and highly specific tool in early response prediction and therapy monitoring of advanced PC patients receiving chemotherapy.
血浆样本中突变 KRAS（mutKRAS ctDNA）的存在一直被证明是胰腺癌（PC）的不良预后指标。只有少数小型试点研究评估了连续 mutKRAS ctDNA 测量在 PC 中的价值。
本研究的目的是探讨重复 mutKRAS ctDNA 测量在接受吉西他滨为基础的化疗的晚期 PC 患者中的反应预测和治疗监测的潜力。我们使用 BEAMing 技术来确定 54 名接受吉西他滨为基础的化疗的晚期 PC 患者的 284 个血浆样本中的 mutKRAS ctDNA、CA 19-9、CEA 和 CYFRA 21-1 的水平。mutKRAS ctDNA、CA 19-9、CEA 和 CYFRA 21-1 的绝对水平和动力学与影像学反应、无进展生存期和总生存期相关。
mutKRAS ctDNA 存在于大多数晚期 PC 患者（n=36/54，67%）中，并具有较高的灵敏度（75%）和特异性（100%），指示组织 KRAS 突变状态。在一线化疗开始前存在 mutKRAS ctDNA 以及更高水平的 CA 19-9、CEA 和 CYFRA 21-1 与不良的总生存期显著相关。在治疗过程中，mutKRAS ctDNA 水平的变化比基于蛋白的肿瘤标志物的变化更快更明显。治疗过程中 mutKRAS ctDNA 水平的下降是对治疗反应的早期指标，而在治疗的前四周，CA 19-9、CEA 或 CYFRA 21-1 的动力学与化疗反应之间没有显著相关性。在随访期间重复 mutKRAS ctDNA 测量在检测进展性疾病方面似乎优于基于蛋白的肿瘤标志物（灵敏度：83%，特异性：100%）。
mutKRAS ctDNA 动力学似乎是一种强大的、高度特异的工具，可用于预测接受化疗的晚期 PC 患者的早期反应和治疗监测。
