预测晚期癌症患者治疗反应的新型生物标志物的发现需要获得高质量的肿瘤样品。随着癌症的发展,理想的是在每次治疗开始之前获得组织。最好,样品是新鲜冷冻的,可以通过下一代DNA/RNA测序(NGS)进行分析,也可以使其他新兴的系统技术,例如蛋白质组学和代谢组学成为可能。这里,我们描述了在荷兰(个性化癌症治疗中心)的大型合作中收集的第一批469例图像引导活检,并显示了这些标本在NGS分析中的实用性。
在晚期癌症患者中进行图像引导的肿瘤活检。样品是新鲜冷冻的,估计了重要的肿瘤细胞数量,在肿瘤丰富区域的宏观解剖后分离DNA。通过在活检程序后14天内报告严重不良事件来评估图像引导活检程序的安全性。
活检程序通常耐受良好。主要并发症发生率为2.1%,最常见的是疼痛。在7.3%的经皮肺活检中,发生需要引流的气胸。大多数样本(81%)含有至少30%的重要肿瘤百分比,其中至少500ngDNA可以分离出91%。鉴于我们预设的标准,74%的样品具有足够的生物标志物发现质量。该队列中的NGS结果与其他组的结果一致。
用于发现生物标志物以实现个性化癌症治疗的图像引导活检程序是安全可行的,并产生了非常有价值的生物样本库。肿瘤学家2017;22:33-40实践意义:这项研究表明,执行图像引导活检程序以获得新鲜的冷冻肿瘤样本是安全的,并且在荷兰多中心合作中使用这些活检用于生物标志物发现目的是可行的。从大多数样本中,可以产生足够的DNA来进行下一代测序。这些结果表明,该方法为财团前瞻性地收集新鲜的冷冻肿瘤组织铺平了道路。
The discovery of novel biomarkers that predict treatment response in advanced cancer patients requires acquisition of high-quality tumor samples. As cancer evolves over time, tissue is ideally obtained before the start of each treatment. Preferably, samples are freshly frozen to allow analysis by next-generation DNA/RNA sequencing (NGS) but also for making other emerging systematic techniques such as proteomics and metabolomics possible. Here, we describe the first 469 image-guided biopsies collected in a large collaboration in The Netherlands (Center for Personalized Cancer Treatment) and show the utility of these specimens for NGS analysis.
Image-guided tumor biopsies were performed in advanced cancer patients. Samples were fresh frozen, vital tumor cellularity was estimated, and DNA was isolated after macrodissection of tumor-rich areas. Safety of the image-guided biopsy procedures was assessed by reporting of serious adverse events within 14 days after the biopsy procedure.
Biopsy procedures were generally well tolerated. Major complications occurred in 2.1%, most frequently consisting of pain. In 7.3% of the percutaneous lung biopsies, pneumothorax requiring drainage occurred. The majority of samples (81%) contained a vital tumor percentage of at least 30%, from which at least 500 ng DNA could be isolated in 91%. Given our preset criteria, 74% of samples were of sufficient quality for biomarker discovery. The NGS results in this cohort were in line with those in other groups.
Image-guided biopsy procedures for biomarker discovery to enable personalized cancer treatment are safe and feasible and yield a highly valuable biobank. The Oncologist 2017;22:33-40Implications for Practice: This study shows that it is safe to perform image-guided biopsy procedures to obtain fresh frozen tumor samples and that it is feasible to use these biopsies for biomarker discovery purposes in a Dutch multicenter collaboration. From the majority of the samples, sufficient DNA could be yielded to perform next-generation sequencing. These results indicate that the way is paved for consortia to prospectively collect fresh frozen tumor tissue.