CT Volume Measurement of Lung Cancer treated with Erlotinib: Genomic Correlation

项目摘要 肺癌是美国和世界范围内癌症死亡的主要原因。最近的一个 肺癌治疗的突破是发现了表皮的体细胞激活突变 生长因子受体(EGFR)酪氨酸激酶结构域在非小细胞肺癌(NSCLC)中的表达 与EGFR抑制剂如吉非替尼和厄洛替尼的显著临床反应有关。厄洛替尼是 对有EGFR突变的患者尤其有效。然而，大多数对厄洛替尼有初步反应的患者 由于对厄洛替尼的获得性耐药，治疗最终复发。 这项建议的目的是分析晚期肿瘤大小和体积的时间变化。 在达纳-法伯癌症研究所进行的临床试验中，使用厄洛替尼治疗的非小细胞肺癌患者，并确定 肿瘤体积比肿瘤大小更早发现获得性耐药引起的复发。如果这一点得到证实， 肿瘤体积可作为监测治疗反应的主要指标，而不是 常规标记物，肿瘤大小。肿瘤体积分析早期检测厄洛替尼获得性耐药 将允许肿瘤学家改变治疗方案以延长无进展生存期。我们还瞄准了 为了确定肿瘤大小和体积的初始比例减少是否与无进展相关 患者的存活率和总体存活率。如果是这样的话，CT测量的肿瘤体积可以作为 预测预后的生物标志物。我们还将确定肿瘤大小和体积的变化是否与基因组相关 晚期非小细胞肺癌患者循环肿瘤细胞和血浆游离DNA的变化白粉菌的基因组分析 在非小细胞肺癌中循环肿瘤细胞和游离血浆DNA是一种新兴的非侵入性技术，它允许 频繁评估治疗过程中的基因组变化。 这项研究将使用厄洛替尼晚期II期前瞻性临床试验中收集的数据进行。 达纳-法伯癌症研究所的非小细胞肺癌患者。数据包括每隔一年进行的胸部CT检查 8周和EGFR突变分析。肿瘤的大小和体积将使用商业上的 可用的，食品和药物管理局(FDA)批准的体积分析软件。肿瘤大小的变化 和体积将被计算，并将与临床结果和基因组分析结果相关联。 该项目的长期目标是确定最有效地预测所获得的成像参数 通过将基因组信息整合到肿瘤体积分析中来对抗厄洛替尼，以便 优化厄洛替尼的治疗效益，为延长肺癌患者的生存期做出贡献。

Project Summary Lung cancer is a leading cause of cancer death in the United States and worldwide. One of the recent breakthroughs in lung cancer treatment was the discovery of the somatic activating mutations of the epidermal growth factor receptor (EGFR) tyrosine kinase domain in non-small cell lung cancer (NSCLC), which is associated with a dramatic clinical response to EGFR inhibitors such as gefitinib and erlotinib. Erlotinib is particularly effective in patients with EGFR mutations. However, most patients with initial responses to erlotinib treatment eventually relapse due to acquired resistance to erlotinib. The purpose of this proposal is to analyze chronological changes in tumor size and volume in advanced NSCLC patients treated with erlotinib in clinical trials at Dana-Farber Cancer Institute, and determine if the tumor volume detects relapse caused by acquired resistance earlier than the tumor size does. If this is proven, tumor volume can be used as the primary marker for monitoring response to therapy instead of the conventional marker, tumor size. Early detection of acquired resistance to erlotinib by tumor volume analysis will allow oncologists to change therapeutic regimen for prolongation of progression-free survival. We also aim to determine if the initial proportional decreases in tumor size and volume correlate with progression-free survival and overall survival of the patients. If this is the case, tumor volume measured by CT can be used as a biomarker for prognosis. We will also determine if the tumor size and volume changes correlate with genomic changes in circulating tumor cells and free plasma DNA in advanced NSCLC patients. Genomic analysis of circulating tumor cells and free plasma DNA in NSCLC is an emerging non-invasive technique which allows for frequent assessment of genomic changes during therapy. The study will be performed using data collected in phase II prospective clinical trials of erlotinib in advanced NSCLC patients at the Dana-Farber Cancer Institute. Data includes chest CT examinations performed every eight weeks and EGFR mutation analysis. Tumor size and volume will be measured using a commercially available, Food and Drug Administration (FDA) approved volume analysis software. Changes of tumor size and volume will be calculated, and will be correlated with clinical outcome and genomic analysis results. The long term goal of the project is to determine the imaging parameters that most efficiently predict acquired resistance to erlotinib by integrating the genomic information into the tumor volume analysis, in order to optimize the therapeutic benefit of erlotinib and contribute to the prolongation of survival in lung cancer patients.