Department of Radiology, Unit 1473, University of Texas, M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA.
Department of Biostatistics, Unit 1411, University of Texas, M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA.
Abdom Radiol (NY). 2018 Jul;43(7):1661-1669. doi: 10.1007/s00261-017-1367-1.
To assess the effects of bevacizumab and everolimus, individually and combined, on CT perfusion (CTp) parameters in liver metastases from neuroendocrine tumors (mNET) and normal liver.
This retrospective study comprised 27 evaluable patients with mNETs who had participated in a two-arm randomized clinical trial of mono-therapy with bevacizumab (Arm B) or everolimus (Arm E) for 3 weeks, followed by combination of both targeted agents. CTp was undertaken at baseline, 3 and 9 weeks, to evaluate blood flow (BF), blood volume (BV), mean transit time (MTT), permeability surface area product (PS), and hepatic arterial fraction (HAF) of mNET and normal liver, using a dual-input distributed parameter physiological model. Linear mixed models were used to estimate and compare CTp parameter values between time-points.
In tumor, mono-therapy with bevacizumab significantly reduced BV (p = 0.05); everolimus had no effects on CTp parameters. Following dual-therapy, BV and BF were significantly lower than baseline in both arms (p ≤ 0.04), and PS was significantly lower in Arm E (p < 0.0001). In normal liver, mono-therapy with either agent had no significant effects on CTp parameters: dual-therapy significantly reduced BV, MTT, and PS, and increased HAF, relative to baseline in Arm E (p ≤ 0.04); in Arm B, only PS reduced (p = 0.04).
Bevacizumab and everolimus, individually and when combined, have significant and differential effects on CTp parameters in mNETs and normal liver, which is evident soon after starting therapy. CTp may offer an early non-invasive means to investigate the effects of drugs in tumor and normal tissue.
评估贝伐珠单抗和依维莫司单独及联合应用对神经内分泌肿瘤（NET）肝转移瘤（mNET）及正常肝脏 CT 灌注（CTp）参数的影响。
本回顾性研究纳入 27 例 mNET 患者，这些患者参加了一项贝伐珠单抗（Arm B）或依维莫司（Arm E）单药治疗的 2 臂随机临床试验，治疗 3 周，然后联合应用这两种靶向药物。基线、3 周和 9 周时进行 CTp 检查，使用双输入分布参数生理模型评估 mNET 和正常肝脏的血流量（BF）、血容量（BV）、平均通过时间（MTT）、通透性表面积乘积（PS）和肝动脉分数（HAF）。采用线性混合模型估计并比较不同时间点 CTp 参数值。
在肿瘤中，贝伐珠单抗单药治疗显著降低了 BV（p=0.05）；依维莫司对 CTp 参数无影响。在双药治疗后，与基线相比，2 个臂的 BV 和 BF 均显著降低（p≤0.04），且 Arm E 的 PS 显著降低（p<0.0001）。在正常肝脏中，任一药物的单药治疗对 CTp 参数均无显著影响：与基线相比，双药治疗显著降低了 Arm E 的 BV、MTT 和 PS，增加了 HAF（p≤0.04）；在 Arm B，仅 PS 降低（p=0.04）。
贝伐珠单抗和依维莫司单独及联合应用对 mNET 及正常肝脏的 CTp 参数有显著且不同的影响，在开始治疗后很快就显现出来。CTp 可能为早期研究药物在肿瘤和正常组织中的作用提供一种非侵入性的方法。
