FDG PET联合灌注CT成像指导食管癌放射治疗剂量个体化的研究

In-field recurrence after definitive chemo-radiotherapy remained the predominant patterns of failure for esophageal cancer patients of local advnaced stage. But the radiation dose escalation has not translated into improved local control and enhanced survival in the cinical practice. Considering the individual differences in radiosensitivity, some subgroup patients could benifit from local dose boost. Currently effective measures in selecting these subgroup remains absent. Our previous study suggests both of computer tomography perfusion imaging and FDG – PET imaging could provide predictive information for the treatment of advanced esophageal cancer by reflecting status of microcirculation and glycometabolism in tumor tissue repectively. Therefore we proposed that the combination of these two measures, which provide comprehensive information from both tumor cells and the microenviroment, hence increase the accuracy of treantment response prediction. In the present satdy, the patients with esophageal carcinoma would be divided into 4 subgroup with different perfusion-glycometabolism phenotype (high perfusion-high glycometabolism, high perfusion-low glycometabolism, low perfusion-high glycometabolism, low perfusion-low glycometabolism). And the following questions will be analyzed: ① the predictive value of perfusion-glycometabolism phenotype in threatment response of esophageal cancer; ②the characteristic and changes of relevant biomolecules during radiochemotherapy would be documented in order to select biomakers which are valuable in prediction of response.③The underlying mechanism would also be investigated through an established patient-derived xenotransplantion modesl for esophageal cancer in nude mice and the optimal radiation dose to different phenotype would be developed. Prediction model on the basis of anatomic and functional imaging will be finally built to guide individualized radiation dose．

进展期食管癌根治性放化疗后失败模式以照射野内复发为主，但基于群体化的放疗局部增量研究未见临床获益，由于食管癌的放疗敏感性差异，部分亚组人群可能通过有限的剂量提升而改善局部控制和生存。我们的前期研究提示CT灌注成像可在一定程度上预测食管癌放化疗的近期疗效，而FDG PET显像也能提供疗效预测信息。二者分别反映肿瘤微循环和糖代谢，我们推测联合应用将能够综合分析组织微环境和肿瘤细胞本身因素，可提高预测的准确性。我们将食管癌分为4类灌注代谢表型（高灌注-高代谢；高灌注-低代谢；低灌注-高代谢；低灌注-低代谢）：① 确定灌注代谢表型在预测食管癌放化疗近期疗效中的价值；② 筛选食管癌组织中与灌注代谢表型相关的有疗效预测价值的标志物；③ 通过动物实验探索放射敏感性与灌注代谢表型的内在联系并确定不同表型所需的个体化剂量。旨在通过解剖功能影像构建疗效预测模型，指导食管癌放疗剂量个体化。

研究背景：进展期食管癌根治性放化疗后失败模式以照射野内复发为主，但基于群体化的放疗局部增量研究未见临床获益，由于食管癌的放疗敏感性差异，部分亚组人群可能通过有限的剂量提升而改善局部控制和生存。.研究内容：我们的前期研究提示CT灌注成像和FDG PET显像分别反映肿瘤微循环和糖代谢，可预测食管癌患者的放射敏感性。我们将二者结合起来根据食管癌灌注-代谢表型的不同来预测疗效。CT灌注参数预测疗效的扩大样本研究，结果显示BF 是最具有预测效能的参数指标。FDG PET 参数指导下治疗前转移淋巴结的代谢，预测不同的缓解率，可用来指导个体化淋巴结照射剂量。CT灌注与FDG PET 二者结合，根据不同的灌注代谢比值进一步探讨其代表的食管癌原发灶生物学行为。最后进行了功能影像联合外周血淋巴细胞参数进一步预测疗效的研究。.重要结果和关键数据: 我们的研究显示对于进展期食管癌原发灶，缓解者和非缓解者的治疗前CT 灌注参数有明显的差异，缓解者的 BF，BV 都显著高于非缓解者。我们的研究进一步挖掘临床常用的FDG PET的参数，发现PET源性肿瘤-肝标准摄取比(SUVTLR)在预测局部晚期食管癌放化疗后肿瘤反应和生存方面优于肿瘤SUVmax。对于转移的淋巴结， 根据不同的FDG 代谢水平和大小来给与个体化的剂量，可能提高淋巴结的缓解率，改善局部控制。对于原发灶需要大样本的数据来进一步确定。最后进一步我们把食管癌原发灶的灌注和代谢显像二者结合起来，发现高代谢低灌注的肿瘤对放射治疗最抗拒。我们基于肿瘤组织的代谢 与 机体免疫状态结合起来一起预测生存，将SUVmean和NLR联合起来构建了局部进展期食管鳞癌患者同步放化疗后治疗反应的预测模型。这些研究提示结合肿瘤代谢和负荷，再结合机体的免疫状态，这样才能够更好的预测疗效和生存。. 科学意义: 总之，本研究提出治疗前、无创性、在体预测放化疗敏感性的方法和思路。通过功能影像为主的研究，我们筛选出对放射治疗敏感且生存获益的患者，对于个体化指导治疗选择提供帮助。