背景:确定符合基于目标的临床试验的特定合格标准的患者的一种方法是使用患者和肿瘤登记处对患者群体进行预筛选。
目的:在这里,我们证明了全面癌症治疗(TCC)方案,一个正在进行的,观察性研究,可能为快速鉴定符合CD30靶向治疗条件的CD30阳性肿瘤患者提供解决方案,例如本妥昔单抗vedotin。
方法:回顾性筛选TCC患者基因表达谱分析数据库中使用HuRSTA-2a520709Affymetrix阵列(GPL15048)测定的CD30基因表达。用库肿瘤组织样品通过半定量免疫组织化学测定CD30蛋白表达。使用R统计软件(RFoundation)对Z和H评分进行统计比较,和预测值,准确度,灵敏度,并估计CD30基因表达与蛋白质表达的特异性。
结果:截至2015年3月,120,887名患者同意机构审查委员会批准的TCC方案。共收集新鲜冰冻肿瘤标本39157份,超过14,000个样本有基因表达数据。CD30RNA在许多实体瘤中表达;在淋巴结原发肿瘤中观察到最高的中位数CD30RNA表达,软组织(许多肉瘤),肺,皮肤,和食管(中位Z评分分别为1.011、0.399、0.202、0.152和1.011)。高水平的CD30基因表达显着丰富了乳腺中CD30阳性蛋白的表达,肺,皮肤,和卵巢癌;准确率从72%到79%,灵敏度从75%到100%,特异性从70%到76%,阳性预测值从20%到40%,阴性预测值从95%到100%。
结论:TCC基因表达谱分析数据库指导组织选择,在许多实体瘤类型中富集CD30蛋白表达。这种方法可以提高将患者纳入基于生物标志物的临床试验的筛选效率。
BACKGROUND: One approach to identify patients who meet specific eligibility criteria for target-based clinical trials is to use patient and tumor registries to prescreen patient populations.
OBJECTIVE: Here we demonstrate that the Total Cancer Care (TCC) Protocol, an ongoing, observational
study, may provide a solution for rapidly identifying patients with CD30-positive tumors eligible for CD30-targeted therapies such as brentuximab vedotin.
METHODS: The TCC patient gene expression profiling database was retrospectively screened for CD30 gene expression determined using HuRSTA-2a520709 Affymetrix arrays (GPL15048). Banked tumor tissue samples were used to determine CD30 protein expression by semiquantitative immunohistochemistry. Statistical comparisons of Z- and H-scores were performed using R statistical software (The R Foundation), and the predictive value, accuracy, sensitivity, and specificity of CD30 gene expression versus protein expression was estimated.
RESULTS: As of March 2015, 120,887 patients have consented to the institutional review board-approved TCC Protocol. A total of 39,157 fresh frozen tumor specimens have been collected, from which over 14,000 samples have gene expression data available. CD30 RNA was expressed in a number of solid tumors; the highest median CD30 RNA expression was observed in primary tumors from lymph node, soft tissue (many sarcomas), lung, skin, and esophagus (median Z-scores 1.011, 0.399, 0.202, 0.152, and 1.011, respectively). High level CD30 gene expression significantly enriches for CD30-positive protein expression in breast, lung, skin, and ovarian cancer; accuracy ranged from 72% to 79%, sensitivity from 75% to 100%, specificity from 70% to 76%, positive predictive value from 20% to 40%, and negative predictive value from 95% to 100%.
CONCLUSIONS: The TCC gene expression profiling database guided tissue selection that enriched for CD30 protein expression in a number of solid tumor types. Such an approach may improve screening efficiency for enrolling patients into biomarker-based clinical trials.