基于AIDR-3D结直肠癌全肿瘤CT灌注成像对肿瘤增殖及预后指标的影像生物学标记研究

The morbidity and mortality of colorectal cancer have been increasing in the past years. The prognosis and treatment strategies are related to the tumor stage and the histological type. However, it is found in clinical practice that even in patients with the cancer of the same stage, the prognosis may be different. The reasons may be related with the molecular biology features of the tumor. In recent years, more and more attention is paid on the tumor biomarkers of colorectal cancer, which have been used to evaluate the pathophysiological characteristics and prognosis of the tumors. Unfortunately, the biological markers can only be obtained through pathologic specimens postoperatively, which leads to the inadequate evaluation and treatment preoperatively. This research aims to determine the imaging biomarker of the colorectal cancer by exploring the relationship between perfusion parameters of AIDR-3D CT whole tumor perfusion imaging and the biomarkers indicating the proliferation and prognosis of the colorectal cancer, including Ki-67 and MSI. The results of the research will determine the imaging biological markers and the quantitative parameters related to the prognosis of the colorectal cancer, which will help to evaluate the biological characteristics of the colorectal cancer and to make the individualized treatment strategy preoperatively to improve the prognosis of the colorectal cancer.

结直肠癌发病率和死亡率逐年上升，肿瘤的分期和病理分型直接影响患者的治疗和预后。但在临床治疗过程中发现，即使处于同一分期结直肠癌患者的预后也存在极大的差异，究其原因可能与肿瘤的分子生物学特点有关。近年来，肿瘤生物学标记物的研究进展很快，很多分子生物学标记物被用于评估肿瘤的病理生理学特点和预后，但各种生物学标记物只能通过术后病理标本获得，因此，术前对肿瘤的评价和对患者的治疗并不充分。本研究对基于AIDR-3D结直肠癌全肿瘤CT灌注成像参数与肿瘤增殖及预后指标（Ki-67、MSI）的相关性进行研究，探索对应的影像生物学标记，旨在术前预估肿瘤的生物学特点，总结出可以评估个体化治疗和预后结直肠癌影像生物学标记物及其量化参数，为实现结直肠癌术前个体化分型和个体化治疗，改善患者预后奠定基础。

本研究利用宽探测器螺旋CT和高场强核磁共振设备，对结直肠癌进行精准术前分期，评估新辅助治疗疗效以及治疗后再分期，并利用IVIM-DWI，DCE-MRI，T2* mapping等功能成像技术对直肠癌KRAS基因突变情况预估进行探索性研究。研究发现：（1）全肿瘤CT灌注参数测量，即3D-volume测量较2D测量数据重复性更好，组间以及组内重复性更好；（2）全肿瘤CT灌注参数（BF,BV,TTP）在一定程度上反应肿瘤分化程度；BV参数值有助于结直肠癌KRAS突变状态的预测；（3）直肠癌IVIM相关参数与肿瘤分期及分级之间存在一定相关性，有助于肿瘤预后评估；（4）直肠癌IVIM相关参数有助于新辅助治疗判定，尤其是假性弥散系数D，有助于对新辅助治疗完全缓解患者的预测；（5）DWI相关参数（ADC,D）以及定量T2*值有助于术前肿瘤KRAS基因突变状态的预估。以上研究结果证实我们研究最初提出的假说“量化的影响学指标能够有助于反映肿瘤的侵袭性和预后”，为结直肠癌的个体化治疗奠定基础，具有重要的科学意义和实际应用价值。