Microbubble Cavitation for Improving Hepatocellular Carcinoma Radioembolization

放射栓塞术的使用已被证明在治疗和降期方面是成功的 肝细胞癌和肝转移以及与传统化疗栓塞术相比的优势 已经被报道过。这项技术的局部贝塔辐射已被证明具有治疗效果。 在肿瘤内。剂量从110-150Gy值不等，但对恶性组织的辐射取决于 与钇源之间的距离。放射治疗只有在剂量超过50GY的情况下才有效。 因此，根据疗效标准，放射栓塞术后的治疗反应在25%-60%之间。 实体瘤(MRECIST)。我们建议使用超声触发的微泡破坏(UTMD)来改善 肝癌的放射栓塞术。这项技术使用商业超声造影剂，其超声 触发的空化会导致各种有据可查的生物效应。局部微气泡空化已经被 显示可通过诱导血管内皮细胞凋亡而使恶性组织对放射治疗敏感。因此， 肝细胞癌放射栓塞术后局部UTMD可能通过选择性地改善肿瘤反应 使恶性组织对放射治疗敏感。此外，破坏性脉冲后的造影剂再灌注率 可以量化并用来估计血液灌注量和血管分数。分数中的变化 血管和血流灌注可能是治疗反应的潜在早期指标，从而使 无反应患者的再治疗。 我们提出了一项临床试验，使用局部微泡空化，然后进行造影剂冲洗成像 返回肿瘤(称为再灌注)，以改善患者预后并更早地预测治疗反应 比目前的临床标准要高。计划接受肝癌放射栓塞术的患者将被随机分配到 接受单纯放射栓塞术或放射栓塞术联合超声造影检查2-4小时 放射栓塞术后7天和14天。闪电破坏-补给技术将被用来诱导 肿瘤血管内多个平面的微泡空化。肿瘤反应、安全性、放射性 然后对珠子分布、肝功能和甲胎蛋白进行评估和组间比较。 作为次要目标，实验组会根据对比度来量化肿瘤的灌注量。 每次破坏性超声脉冲后试剂再灌流。然后对患者进行分层，根据 MRECIST根据他们的临床随访MRI/CT研究，在治疗后3-4个月确定标准。 比较不同组间微泡衍生肿瘤的再通率，以确定治疗反应 可预测为治疗后7-14天。一旦得到验证，这项技术有望改善患者的预后 通过选择性地使恶性组织对放射治疗敏感，并通过 及早发现治疗无效的患者。

The use of radioembolization has been shown to be successful for the treatment and downstaging of hepatocellular carcinoma (HCC) as well as liver metastases, and advantages over traditional chemoembolizaion have been reported. The local beta emissions from this technique have been shown to provide therapeutic effect within the tumor. Dosages range from 110-150 Gy, but radiation delivered to malignant tissue is dependent on distance from the yttrium source. Radiotherapy is only effective in treating HCC in doses above 50 Gy. Consequently, treatment response after radioembolization is between 25-60% when based on response criteria in solid tumors (mRECIST). We propose to use ultrasound-triggered microbubble destruction (UTMD) to improve radioembolization of HCC. This technique uses commercial ultrasound contrast agents, whose ultrasound triggered cavitation results in a variety of well documented bioeffects. Localized microbubble cavitation has been shown to sensitize malignant tissue to radiotherapy by inducing vascular endothelial-cell apoptosis. Thus, localized UTMD after radioembolization of HCC may potentially improve tumor response by selectively sensitizing malignant tissue to radiotherapy. In addition, the rate of contrast reperfusion after a destructive pulse can be quantified and used to estimate blood perfusion and fractional vascularity. Changes in fractional vascularity and perfusion may be a potential earlier indicator of treatment response, thereby enabling earlier retreatment in non-responding patients. We propose a clinical trial using localized microbubble cavitation followed by imaging of contrast washing back into the tumor (termed reperfusion) to improve patient outcomes and predict treatment response earlier than the current clinical standards. Patients scheduled for radioembolization of HCC will be randomized to receive radioembolization alone or radioembolization in combination with a contrast ultrasound exam 2-4 hours and 7 and 14 days post radioembolization. A flash destruction-replenishment technique will be used to induce microbubble cavitation at multiple planes within the tumor vasculature. Tumoral response, safety, radioactive bead distribution, liver function, and alpha fetal protein, will then be evaluated and compared between groups. As a secondary aim, tumor perfusion will be quantified in the experimental group based on the rate of contrast agent reperfusion following each destructive ultrasound pulse. Patients will then be stratified according to mRECIST criteria 3-4 months post treatment based on their clinically scheduled follow-up MRI/CT study. Microbubble-derived tumor reperfusion rate will be compared between groups to determine if treatment response can be predicted 7-14 days post therapy. Once validated, this technique is expected to improve patient outcomes by selectively sensitizing malignant tissue to radiotherapy, and by enabling alternative forms of treatment through earlier identification of patients not responding to therapy.