Circulating Tumor Cells Analyses and Molecular Profiling for Patients Receiving Radiation Therapy

循环肿瘤细胞分析和分子特征分析用于接受 放射治疗 摘要 我们建议开发一种具有独特功能和功效的循环肿瘤细胞（CTC）检测方法 上级目前可用的CTC测定。CTC测定最近引起了强烈的关注 因为它有可能以最小的风险连续地研究实体瘤的生物学。的 获得的结果信息，包括预测对靶向 治疗，可以告知接受放射治疗（RT）的患者的临床管理，因此 “个性化治疗”的方式以前无法实现。我们建议研究非小细胞 肺癌（NSCLC）和黑色素瘤，这两种具有战略重要性的实体肿瘤， 有快速增加病人的协议。这些疾病部位代表RT的高度优先级 在我们的临床试验研究中， 和非上皮肿瘤。我们已经获得了初步数据， 成功地检测了患者的CTC，目前FDA批准的CTC检测方法是 无效。关于反恐委员会分析的关键问题仍然存在， 如何最好地将这些分析纳入标准放射肿瘤学实践。这些 问题包括：（1）在接受放射治疗的一系列实体瘤中能否检测到CTC 治疗（RT）或其他形式的治疗？(2)CTC计数是否能提前通知疾病 复发还是进展？(3)所鉴定的CTC的遗传背景是否可以 它是否会随着时间的推移和治疗后发生变化？我们将使用CTC检测 这种方法依赖于几乎所有肿瘤中端粒酶活性的升高，端粒酶活性是癌症的标志， 其不受肿瘤标志物表面表达缺乏所带来的限制的影响。在 具体目标1：我们将跟踪具有一系列局限性肿瘤表现的患者的CTC计数。 接受RT的NSCLC，以测试CTC分析是否可以提供肿瘤的提前通知 复发目的2将测试CTC分析在接受化疗的黑素瘤患者中是否有效。 治疗，包括放射治疗和免疫治疗。对于目标3，我们将测试基因是否 治疗后CTC的变化特征，包括预测对 生物靶向制剂。我们成功地实现这些科学目标， 阐明了CTC检测对广泛接受RT的患者的潜在有用性， 其他抗癌治疗。

Circulating Tumor Cells Analyses and Molecular Profiling for Patients Receiving Radiation Therapy ABSTRACT We propose to develop a circulating tumor cell (CTC) assay with unique features and efficacy superior to currently available CTC assays. CTC assays have attracted intense recent attention because of the potential to serially interrogate the biology of solid tumors with minimal risk. The resulting information obtained, including genetic information predicting response to targeted therapy, may inform the clinical management of patients receiving radiation therapy (RT), thus “personalizing treatment” in ways previously unachievable. We propose to study non-small cell lung cancer (NSCLC) and melanoma, two solid tumors of strategic importance and for which we have protocols rapidly accruing patients. These disease sites represent high priority for RT treatment in our investigational clinical trials and represent examples of respectively, epithelial and non-epithelial tumors. We have achieved preliminary data that suggests our approach successfully detects CTCs in patients for whom the current FDA-approved CTC assay is ineffective. Key questions regarding CTC analyses remain, the answers to which would inform how best to incorporate these assays into standard radiation oncology practice. These questions include: (1) Can CTCs be detected in a range of solid tumors undergoing radiation therapy (RT) or other forms of treatment? (2) Do CTC counts give lead-time notice of disease recurrence or progression? (3) Can the genetic background of the identified CTCs be elucidated and does it change over time and after treatment? We will employ a CTC detection method that relies on the elevated telomerase activity in almost all tumors, a hallmark of cancer, which is impervious to limitations posed by the lack of surface expression of tumor markers. In Specific Aim 1 we will track CTC counts in patients with a range of presentations of localized NSCLC undergoing RT to test whether CTC analysis can give lead time notice of tumor recurrence. Aim 2 will test whether CTC analysis is effective in melanoma patients undergoing treatment, including radiation and immunotherapy. For Aim 3, we will test whether the genetic profile of CTCs changes after treatment, including DNA mutations that predict for response to biologically targeted agents. Our successful accomplishment of these scientific aims will illuminate the potential usefulness of CTC assays for a wide range of patients receiving RT and other anticancer treatment.