PDF(Pubmed)
Abstract：
We describe the analytical validation of NeXT Personal®, an ultra-sensitive, tumor-informed circulating tumor DNA (ctDNA) assay for detecting residual disease, monitoring therapy response, and detecting recurrence in patients diagnosed with solid tumor cancers. NeXT Personal uses whole genome sequencing of tumor and matched normal samples combined with advanced analytics to accurately identify up to ~1,800 somatic variants specific to the patient\'s tumor. A personalized panel is created, targeting these variants and then used to sequence cell-free DNA extracted from patient plasma samples for ultra-sensitive detection of ctDNA. The NeXT Personal analytical validation is based on panels designed from tumor and matched normal samples from two cell lines, and from 123 patients across nine cancer types. Analytical measurements demonstrated a detection threshold of 1.67 parts per million (PPM) with a limit of detection at 95% (LOD95) of 3.45 PPM. NeXT Personal showed linearity over a range of 0.8 to 300,000 PPM (Pearson correlation coefficient = 0.9998). Precision varied from a coefficient of variation of 12.8% to 3.6% over a range of 25 to 25,000 PPM. The assay targets 99.9% specificity, with this validation study measuring 100% specificity and in silico methods giving us a confidence interval of 99.92 to 100%. In summary, this study demonstrates NeXT Personal as an ultra-sensitive, highly quantitative and robust ctDNA assay that can be used to detect residual disease, monitor treatment response, and detect recurrence in patients.
摘要：
我们描述了NeXTPersonal®的分析验证，一个超敏感的，肿瘤知情循环肿瘤DNA（ctDNA）检测残留病，监测治疗反应，并检测被诊断为实体瘤癌症的患者的复发。NeXTPersonal使用对肿瘤和匹配的正常样本进行全基因组测序，并结合高级分析技术，可准确识别患者肿瘤特有的约1,800种体细胞变异。创建个性化面板，靶向这些变体，然后用于测序从患者血浆样品中提取的无细胞DNA，用于超灵敏检测ctDNA。NeXT个人分析验证基于从肿瘤和来自两个细胞系的匹配的正常样品设计的面板，来自9种癌症类型的123名患者。分析测量表明检测阈值为1.67ppm(PPM),检测极限为95%(LOD95)为3.45PPM。NeXTPersonal在0.8至300,000PPM的范围内显示出线性（皮尔逊相关系数=0.9998）。在25至25,000PPM的范围内，精度从12.8％到3.6％的变异系数变化。该测定的目标是99.9%的特异性，这项验证研究测量了100％的特异性和计算机模拟方法，使我们的置信区间为99.92％至100％。总之,这项研究表明，NeXTPersonal是一种超敏感的人，高度定量和强大的ctDNA测定，可用于检测残留疾病，监测治疗反应，并检测患者的复发。
