Yittrium-90 radiation lobectomy: Dose optimization and prediction of FLR hypertrophy to enable resection of HCC

Yittrium-90 放射肺叶切除术：FLR 肥大的剂量优化和预测，以实现 HCC 切除

基本信息

批准号：
10241994
负责人：
Jeremy Douglas Collins
金额：
$ 58.21万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-01 至 2026-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10241994
关键词：
4D MRI 90Y Address Angiography Atrophic Automobile Driving Biodistribution Biological Markers Blood Blood flow Catheters Cirrhosis Clinical Complex Data Diagnosis Dose Excision Fibrosis Future Glass Hepatic Hepatic Tissue Hepatology Hypertrophy Image Enhancement Individual Adjustment Infusion procedures Intervention Lead Lesion Life Literature Liver Liver Failure Liver Fibrosis Liver diseases Liver parenchyma Lobar Lobectomy Magnetic Resonance Imaging Measurement Methods Microspheres Multi-Institutional Clinical Trial Multi-site clinical study Nature Neoplasm Metastasis Oncology Operative Surgical Procedures Organ Outcome PET/CT scan Patients Perfusion Play Portal Hypertension Portal vein structure Prediction of Response to Therapy Primary carcinoma of the liver cells Procedures Prospective Studies Radiation Radiation Dose Unit Radiation Fibrosis Radiation Injuries Radioembolization Recurrence Role Savings Techniques Therapeutic Embolization Time Transplantation Surgery Tumor Tissue Unresectable contrast enhanced curative treatments disorder control dosimetry early detection biomarkers efficacy evaluation elastography hemodynamics imaging biomarker improved in vivo individual patient innovation liver function liver stiffness liver transplantation multidisciplinary novel patient population recruit response risk minimization symposium treatment strategy tumor

项目摘要

Project Summary / Abstract: Liver transplantation is curative in patients with unresectable hepatocellular carcinoma (HCC). However, the clinical need for organs greatly exceeds their availability. In addition, few patients diagnosed with HCC are candidates for primary surgical resection, due to an insufficient future liver remnant (FLR) in the presence of underlying liver disease. Portal vein embolization (PVE), a technique known to induce FLR hypertrophy by redirecting portal flow, is relatively contraindicated in cirrhosis due to concerns to induce liver failure and worsen pre-existent portal hypertension following the procedure. We have recently demonstrated the potential efficacy of a new paradigm to achieve locoregional HCC control while inducing FLR hypertrophy with lobar infusion of 90Y impregnated glass beads (90Y radiation lobectomy [90Y-RL]). Although preliminary data demonstrates the utility of this approach, the optimal dose strategy to induce FLR hypertrophy while minimizing the risk of worsening liver function and portal hypertension is unknown. Our proposed study investigates the underlying mechanisms of embolized liver atrophy and FLR hypertrophy following 90Y-RL through improved dosimetry and advanced quantitative MR imaging. Patients with unresectable HCC will be recruited at the time of referral for 90Y-RL following review in our multidisciplinary HCC treatment conference. In Aim #1 we will investigate the influence of proscribed radiation dose and glass bead embolic load on FLR hypertrophy calculating actual parenchymal doses with the use of non-FDG PET/CT to visualize glass bead distribution following 90Y-RL. The optimal dose/embolic load paradigm will be applied in a prospective study of 64 subjects with unresectable HCC referred for 90Y-RL in Aim #2. These subjects will undergo quantitative MR imaging, assessing changes in liver stiffness with MR elastography, liver hemodynamics with non-contrast 4D flow MRI, and parenchymal perfusion with accelerated time-resolved MR angiography before and at 1- and 3-months after 90Y-RL. Quantitative MRI derived biomarkers will be correlated with FLR hypertrophy and trophic factors to delineate changes predictive of adequate FLR following 90Y-RL. Finally, we will assess differences in recurrence-free survival 90Y-RL patients who underwent surgical resection and those whose FLR deemed them candidates for surgical resection at presentation. This project will deepen our understanding of the mechanisms leading to the liver atrophy- hypertrophy complex following 90Y-RL endeavoring to make the procedure safer and more effective. The results of this study will support a multicenter clinical trial evaluating the survival of patients with unresectable HCC treated with 90Y-RL.

项目摘要/摘要：肝移植对于无法切除的肝细胞癌（HCC）患者有疗效。然而，临床对器官的需求远远超过其可用性。另外，很少有患者由于未来前景不足，诊断为 HCC 是初次手术切除的候选者存在潜在肝病时的肝残余（FLR）。门静脉栓塞术（PVE），一种已知通过重定向门脉血流诱导 FLR 肥大的技术相对来说是相对有效的。肝硬化患者禁用，因为担心会诱发肝功能衰竭并恶化已存在的门静脉手术后高血压。我们最近展示了一种潜在的功效实现局部 HCC 控制同时诱导 FLR 肥大的新范例输注 90Y 浸渍玻璃珠（90Y 放射性肺叶切除术 [90Y-RL]）。虽然初步数据证明了这种方法的实用性，即诱导的最佳剂量策略 FLR 肥大同时最大限度地降低肝功能恶化和门静脉高压的风险未知。我们提出的研究调查了肝栓塞的潜在机制通过改进剂量测定和先进技术，90Y-RL 后出现萎缩和 FLR 肥大定量 MR 成像。无法切除的 HCC 患者将在转诊时被招募在我们的多学科 HCC 治疗会议上进行审查后，针对 90Y-RL。在目标#1中，我们将研究禁止辐射剂量和玻璃珠栓塞负荷对 FLR 的影响使用非 FDG PET/CT 可视化计算实际实质剂量的肥大玻璃珠分布遵循90Y-RL。将应用最佳剂量/栓塞负荷范例在一项前瞻性研究中，对 64 名患有不可切除 HCC 的受试者进行了目标 2 中的 90Y-RL 治疗。这些受试者将接受定量 MR 成像，评估肝脏硬度的变化 MR 弹性成像、非对比 4D 流 MRI 的肝脏血流动力学和实质在术前以及术后 1 个月和 3 个月时进行加速时间分辨 MR 血管造影灌注 90Y-RL。定量 MRI 衍生的生物标志物将与 FLR 肥大相关营养因子描述 90Y-RL 后预测足够 FLR 的变化。最后，我们将评估接受手术切除的 90Y-RL 患者无复发生存率的差异以及 FLR 在就诊时认为他们适合手术切除的患者。这该项目将加深我们对导致肝萎缩的机制的理解- 90Y-RL 后的肥大复合体努力使手术更安全、更高效有效的。这项研究的结果将支持评估生存率的多中心临床试验接受 90Y-RL 治疗的不可切除 HCC 患者的比例。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Coagulopathy and hemostasis management in patients undergoing liver transplantation: Defining a dynamic spectrum across phases of care.

DOI：
10.1002/lt.26451
发表时间：
2022-10
期刊：
LIVER TRANSPLANTATION
影响因子：
4.6
作者：
Pillai, Anjana A.;Kriss, Michael;Al-Adra, David P.;Chadha, Ryan M.;Cushing, Melissa M.;Farsad, Khashayar;Fortune, Brett E.;Hess, Aaron S.;Lewandowski, Robert;Nadim, Mitra K.;Nydam, Trevor;Sharma, Pratima;Karvellas, Constantine J.;Intagliata, Nicolas
通讯作者：
Intagliata, Nicolas

4D Flow cardiovascular magnetic resonance consensus statement: 2023 update.