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

项目摘要 肺癌是美国和全世界癌症死亡的主要原因。最近的一 肺癌治疗的突破是发现了表皮细胞的体细胞激活突变， 生长因子受体（EGFR）酪氨酸激酶结构域在非小细胞肺癌（NSCLC）中的作用， 与EGFR抑制剂如吉非替尼和厄洛替尼的显著临床反应相关。厄洛替尼 对EGFR突变患者尤其有效。然而，大多数对厄洛替尼有初步反应的患者， 治疗最终复发，由于获得性耐药性埃罗替尼。 该建议的目的是分析晚期肿瘤大小和体积的时间变化， 在Dana-Farber癌症研究所的临床试验中使用厄洛替尼治疗的NSCLC患者，并确定 肿瘤体积比肿瘤大小更早地检测到由获得性耐药引起的复发。如果这被证实， 肿瘤体积可用作监测对治疗的反应的主要标志物， 常规标记肿瘤大小肿瘤体积分析法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。我们还旨在 以确定肿瘤大小和体积的初始比例减小是否与无进展相关， 患者的生存率和总生存率。如果是这种情况，则可以将CT测量的肿瘤体积用作 用于预后的生物标志物。我们还将确定肿瘤大小和体积变化是否与基因组相关， 晚期NSCLC患者循环肿瘤细胞和血浆游离DNA的变化。的基因组分析 NSCLC中的循环肿瘤细胞和游离血浆DNA是一种新兴的非侵入性技术， 在治疗期间频繁评估基因组变化。 该研究将使用厄洛替尼II期前瞻性临床试验中收集的数据进行。 Dana-Farber癌症研究所的NSCLC患者。数据包括每两年进行的胸部CT检查， 8周和EGFR突变分析。肿瘤大小和体积将使用市售的 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 并且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采集的成像参数 通过将基因组信息整合到肿瘤体积分析中， 优化厄洛替尼的治疗益处并有助于延长肺癌患者的生存期。

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.