CTP联合PET-CT监测非小细胞肺癌EGFR基因突变与靶向治疗的实验研究

The epidermal growth factor receptor (EGFR) has been intensively investigated as a target of antineoplastic therapy in advanced-stage non-small cell lung cancer (NSCLC). Sequencing of the EGFR gene revealed that most tumors that respond to EGFR kinase inhibitors harbor activating mutations in the EGFR kinase domain. Activating EGFR mutations play important roles in determining responsiveness or resistance to small molecule tyrosine kinase inhibitor (TKI). Detecting EGFR mutations using tumor tissues obtained via a biopsy or surgical resection is now routinely used to diagnosed NSCLC. Because a biopsy is an invasive procedure, it is desirable to replace it with a noninvasive procedure. The complexity and limitations of invasive methods of analysis of EGFR mutations promoted the development of novel imaging biomarkers from noninvasive imaging methods, which may help in identification of NSCLC patients who may benefit from EGFR kinase inhibitors. The imaging biomarkers derived from computed tomography perfusion (CTP) and positron emission tomography (PET) have been demonstrated as ideal and effective ways to be applied in clinical settings for noninvasive assessment of molecular target therapy in advanced chemotherapy-refractory NSCLC. Therefore, based on our previous work, we postulate that the imaging biomarkers from CTP and PET have the potential to serve as predictors for determining which patients will benefit most from EGFR-TKI treatment. The aim of this study is to detect whether the imaging biomarkers from CTP and PET are selective of the EGFR mutation in tumor tissue from tumor-bearing mice and surgical NSCLC patients, and to detect whether the imaging biomarkers from CTP and PET are selective of the EGFR mutation in tumor tissue by biopsy from advanced-stage NSCLC who will be treated with EGFR-TKI or acquired resistance to them. Then, we will see to determine whether the imaging biomarkers from CTP and PET correlated with clinical outcome in patients treated with EGFR-TKI for advanced chemotherapy-refractory NSCLC.

表皮生长因子受体（EGFR）突变是酪氨酸激酶抑制剂（TKI）治疗非小细胞肺癌（NSCLC）有效的预测指标。目前监测EGFR突变的手段多为有创性，不易重复获取，不能全面评价肿瘤组织EGFR状态。CT灌注成像（CTP）联合PET-CT是目前临床无创性评价NSCLC患者分子靶向治疗的理想方式。本项目组拟在前期基础上，利用CTP联合PET-CT成像，对手术前原发NSCLC病灶影像学参数与术后肿瘤组织标本、外周血清EGFR突变的相关性以及EGFR-TKI治疗前和治疗进展或耐药时原发病灶、转移灶影像学参数与相应肿瘤组织、外周血清EGFR突变的相关性进行研究，并进一步对EGFR-TKI治疗前和治疗过程中影像学参数与疾病变化的相关性进行研究，从而实现无创性、实时监测活体NSCLC组织EGFR突变状态及EGFR-TKI疗效的目标，为NSCLC靶向治疗患者筛选、疗效评价和预后分析提供新型有效的影像手段。

表皮生长因子受体（EGFR）突变是酪氨酸激酶抑制剂（TKI）治疗非小细胞肺癌（NSCLC）有效的预测指标。目前监测EGFR突变的手段多为有创性，不易重复获取，不能全面评价肿瘤组织EGFR状态。CT灌注成像（CTP）联合PET-CT是目前临床无创性评价NSCLC患者分子靶向治疗的理想方式。本项目组拟在前期基础上，利用CTP联合PET-CT成像，对手术前原发NSCLC病灶影像学参数与术后肿瘤组织标本、外周血清EGFR突变的相关性以及EGFR-TKI治疗前和治疗进展或耐药时原发病灶、转移灶影像学参数与相应肿瘤组织、外周血清EGFR突变的相关性进行研究，并进一步对EGFR-TKI治疗前和治疗过程中影像学参数与疾病变化的相关性进行研究，从而实现无创性、实时监测活体NSCLC组织EGFR突变状态及EGFR-TKI疗效的目标，为NSCLC靶向治疗患者筛选、疗效评价和预后分析提供新型有效的影像手段。目前已经发表标注本项目支持的SCI论文2篇（其中IF>5.0的1篇），中文核心期刊4篇。