Advanced Anatomic and Functional Response Assessment in Lung Cancer

描述(由申请人提供)：评估患者对化疗的反应的标准方法是使用计算机断层扫描(CT)使用一维(RECIST)或二维(WHO)标准测量肿瘤大小。同样的标准也被用来衡量肺癌患者研究治疗的有效性。尽管出现了新的治疗方法和成像技术的进步，但这种方法在过去30年里几乎没有改变。我们和其他人发现，仅在一维或二维上确定肿瘤大小的变化并不能充分反映新疗法对原发肿瘤和转移瘤的影响。在接受表皮生长因子受体酪氨酸激酶抑制剂(如吉非替尼或厄洛替尼)或血管生成抑制剂(如贝伐单抗)治疗的肿瘤中，放射学变化的程度或速度不一定与那些接受标准细胞毒治疗的患者相同。使用这些较新的药物，肿瘤的反应是经历囊性变化、中央坏死和密度变化，这些变化可能是最大病变直径的常规测量无法捕捉到的。只有在PET、FDG或FIT成像上才能捕捉到的功能变化也会发生。这项研究的目的是通过使用先进的成像技术将肿瘤反应与生物标记物以及无病进展和存活期相关联，来调查在接受不同类型的肺癌系统治疗(标准细胞毒性、EGFR-TKI和抗血管生成标准)的患者组中，使用成像来评估早期反应和进展的情况。具体地说，1.评估接受细胞毒性、EGFR-TKI和抗血管生成治疗的患者在CT上使用RECIST、二维、体积测量的分类反应以及FDG-PET的代谢变化和Flt-PET的增殖，并将这些反应测量得出的最佳总体反应和无进展生存率与总体生存率相关联。2.将血浆总DNA结果与基于图像的反应(最佳总反应和无进展生存率)和总生存率进行比较。3.确定使用连续量表最佳总体反应是否比目前使用的分类反应评估更好地预测。

DESCRIPTION (provided by applicant): The standard way to assess a patient's response to chemotherapy is to use computed tomography (CT) to measure tumor size using uni-dimensional (RECIST) or bi-dimensional (WHO) criteria. The same standards are used to gauge the effectiveness of investigational therapies in patients with lung cancer. This methodology has changed little in the past 30 years despite the emergence of new therapies and advances in imaging technology. We and others have found that only determining the changes in the size of tumors in one or two dimensions does not adequately capture the effects of novel therapies on primary tumors and metastases. Radiographic changes in tumors treated with epidermal growth factor receptor tyrosine kinase inhibitors such as gefitinib or erlotinib or inhibitors of angiogenesis such as bevacizumab do not necessarily occur at the same magnitude or speed as observed in those individuals treated with standard cytotoxic therapies. With these newer agents, tumors respond by undergoing cystic change, central necrosis and density changes that may not be captured by conventional measurements of the largest lesion diameter. Functional changes that can only be captured on PET FDG or FIT imaging also occur. The goals of this study are to investigate the use of imaging to assess early response and progression in groups of patients receiving different types of systemic therapy (standard cytotoxic, EGFR-TKI and antiangiogenic standard) for lung cancer by correlating tumor response using advanced imaging techniques with biomarkers as well as with disease-free progression and survival. Specifically, 1.To evaluate categorical response assessment using RECIST, bi-dimensional, volumetric measures on CT and changes in metabolism on FDG-PET and proliferation on FLT-PET in patients on cytotoxic, EGFR-TKI and antiangiogenic therapy and to correlate the Best Overall Response and Progression Free Survival derived from these measurements of response with overall survival. 2. To compare total plasma DNA results with image based response (best overall response and progression free survival) and overall survival. 3. To determine if the use of a continuous scale best overall response better predicts than the categorical response assessment currently used.