Weiss Glen J, Hoff Brandi R, Whitehead Robert P, Sangal Ashish, Gingrich Susan A, Penny Robert J, Mallery David W, Morris Scott M, Thompson Eric J, Loesch David M, Khemka Vivek
Cancer Treatment Centers of America, Western Regional Medical Center, Goodyear, AZ, USA.
Paradigm Diagnostics, Phoenix, AZ, USA.
Onco Targets Ther. 2015 Apr 24;8:959-67. doi: 10.2147/OTT.S81995. eCollection 2015.
It is widely acknowledged that there is value in examining cancers for genomic aberrations via next-generation sequencing (NGS). How commercially available NGS platforms compare with each other, and the clinical utility of the reported actionable results, are not well known. During the course of the current study, the Foundation One (F1) test generated data on a combination of somatic mutations, insertion and deletion polymorphisms, chromosomal abnormalities, and deoxyribonucleic acid (DNA) copy number changes at ~250× coverage, while the Paradigm Cancer Diagnostic (PCDx) test generated the same type of data at >5,000× coverage, plus provided messenger RNA (mRNA) expression levels. We sought to compare and evaluate paired formalin-fixed paraffin-embedded tumor tissue using these two platforms.
Samples from patients with advanced solid tumors were submitted to both the F1 and PCDx vendors for NGS analysis. Turnaround time (TAT) was calculated. Biomarkers were considered clinically actionable if they had a published association with treatment response in humans and were assigned to the following categories: commercially available drug (CA), clinical trial drug (CT), or neither option (hereafter referred to as "None").
The demographics of the 21 unique patient tumor samples included ten men and eleven women, with a median age of 56 years. Due to insufficient archival tissue from the same collection period, in one case, we used samples from different collections. PCDx reported first results faster than F1 in 20 cases. When received at both vendors on the same day, PCDx reported first results for 14 of 15 cases, with a median TAT of 9 days earlier than F1 (P<0.0001). Categorization of CA compared to CT and none significantly favored PCDx (P=0.012).
In the current analysis, commercially available NGS platforms provided clinically relevant actionable targets (CA or CT) in 47%-67% of diverse cancer types. In the samples analyzed, PCDx significantly outperformed F1 in TAT, and had statistically significant higher clinically relevant actionable targets categorized as CA.
人们普遍认识到，通过下一代测序（NGS）检测癌症的基因组畸变具有重要价值。目前尚不清楚市售的NGS平台之间如何相互比较，以及所报告的可操作结果的临床效用如何。在本研究过程中，Foundation One（F1）检测在约250倍覆盖度下生成了关于体细胞突变、插入和缺失多态性、染色体异常以及脱氧核糖核酸（DNA）拷贝数变化的数据，而Paradigm Cancer Diagnostic（PCDx）检测在>5000倍覆盖度下生成了相同类型的数据，并提供了信使核糖核酸（mRNA）表达水平。我们试图使用这两个平台对配对的福尔马林固定石蜡包埋肿瘤组织进行比较和评估。
将晚期实体瘤患者的样本提交给F1和PCDx两家供应商进行NGS分析。计算周转时间（TAT）。如果生物标志物与人类治疗反应有已发表的关联，则被认为具有临床可操作性，并分为以下几类：市售药物（CA）、临床试验药物（CT）或两者都不是（以下简称“无”）。
21个独特患者肿瘤样本的人口统计学数据包括10名男性和11名女性，中位年龄为56岁。由于同一采集期的存档组织不足，在1例中，我们使用了不同采集的样本。PCDx在20例中比F1更快报告首个结果。当两家供应商在同一天收到样本时，PCDx在15例中的14例中报告了首个结果，中位TAT比F1早9天（P<0.0001）。与CT和无相比，CA的分类显著有利于PCDx（P=0.012）。
在当前分析中，市售的NGS平台在47%-67%的不同癌症类型中提供了临床相关的可操作靶点（CA或CT）。在所分析的样本中，PCDx在TAT方面显著优于F1，并且在分类为CA的临床相关可操作靶点方面具有统计学上显著更高的比例。
