Adaptive Stereotactic Radiotherapy With Superparamagnetic Iron Oxide Nanoparticles (SPION) Cellular Magnetic Resonance Imaging on MR-Linac (MR-L-SPION) for Primary and Metastatic Hepatic Malignancies With Assessment of Treatment Response.
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Develop a platform to maintain liver functionality during treatment for liver cancer
研究概览
简要总结
There is a high prevalence of hepatic cirrhosis in patients with hepatocellular carcinomas (HCC), or chemotherapy-induced hepatic atrophy or hepatosteatosis in patients with liver metastases associated with high risk of radiation-induced liver disease (RILD) after stereotactic body radiotherapy (SBRT). MRI-SPION radiotherapy planning will facilitate detection and maximize avoidance of residual functionally active hepatic parenchyma from over-the-threshold irradiation thus increasing safety of liver SBRT in patients with pre-existing liver conditions. The investigators have previously demonstrated that liver SBRT with SPECT/CT functional treatment planning utilizing 99mTc sulfur colloid in transplant eligible patients associated with minimal hepatotoxicity and without hastening of advanced hepatic cirrhosis progression while patients await liver transplant. Switching from nuclear medicine to an MR-Linac-SPION based quantitative treatment-planning platform will substantially improve diagnostic accuracy in defining safe volumes of residual functional hepatic parenchyma for liver SBRT planning on MR-Linac.
详细描述
Setting/Participants:
The study will be performed at a single center - Allegheny General Hospital (AGH) in a setting of referral-based outpatients within the Allegheny Health (AHN) network.
25 patients with primary and metastatic liver tumors and hepatic cirrhosis eligible for liver SBRT will be enrolled in this study.
Study Interventions and Measures:
MRI cellular imaging of hepatic parenchyma with SPION will be performed on a 1.5T MRI (Elekta MR-Linac) on the day of radiotherapy planning. Hepatic SPION accumulation will be quantified and delineated to designate volumes for conformal avoidance on the MR-Linac during liver SBRT. This quantitative assessment will be compared to the already established methodology using CT/SPECT images developed at AGH. Treatment outcomes and toxicity due to improved conformal avoidance of functional normal liver volumes will be assessed for these patients. Dose-response of tumor and hepatic parenchyma to SBRT will be examined using MR-Linac imaging, pathologic criteria and molecular profiling of explanted livers in a subset of patients who received liver SBRT as a bridge to transplant.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 89 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients age 18-89 years
- •Women of childbearing age must have a negative urine/serum pregnancy test (per standard of care) and must use an acceptable method of contraception, including abstinence, a barrier method (diaphragm or condom), Depo-Provera, or an oral contraceptive, for the duration of the study Women beyond childbearing are not required to use contraception.
- •Child-Pugh A or B liver function;
- •Child-Pugh C liver function for transplant eligible patients only.
- •Single or multinodular tumors (up to four) are permitted.
- •Patients required to have more than 30% of functionally active uninvolved liver outside radiation target volume;
- •No prior liver radiation, including radioembolization;
- •ECOG (Eastern Cooperative Oncology Group) performance score >=2
排除标准
- •Patients over 90 year of age
- •Bilirubin x3 upper limit of normal;
- •AST (aspartate aminotransferase) or ALT (alanine transaminase) x6 upper limit of normal;
- •Hemoglobin less than 80 g/L;
- •Patients with recurrent ascites (paracentesis q ≥2 weeks);
- •Patients with history of hypersensitivity to Feraheme or any other IV iron products;
- •Patients with hemochromatosis (iron overload).
研究组 & 干预措施
Primary and metastatic liver tumors and hepatic cirrhosis
This study is a single arm prospective study that will enroll 25 patients with primary and metastatic liver tumors and hepatic cirrhosis eligible for liver SBRT who will be receiving treatment at a single center - Allegheny General Hospital.
干预措施: Ferumoxytol injection (Drug)
结局指标
主要结局
Develop a platform to maintain liver functionality during treatment for liver cancer
时间窗: Two Years
The primary goal of the study is to develop MRI-linac SPION based radiotherapy planning platform for detection and conformal avoidance of residual, functionally active hepatic parenchyma during liver SBRT for primary and metastatic hepatic malignancies in patients with hepatic cirrhosis. Treatment outcomes and toxicity due to improved conformal avoidance of functional normal liver volumes will be assessed for these patients. Progression in Child-Pugh and MELD scores, disease free survival, and overall survival (with and without liver transplant) will be evaluated via Kaplan Meier analysis. Freedom from MELD score progression will be measured against residual volumes of functionally active hepatic parenchyma defined on MRI-linac SPION via Cox proportional hazard regression models. Statistical analysis will be conducted with MedCalc version 11.3.
次要结局
- Examine the dose-response of tumor and liver tissue in patients who received liver transplant after receiving SBRT(Two Years)
- Develop applications for assessing the liver functionality of those with liver cancer(Two Years)
研究者
Alexander Kirichenko
Associate Professor Temple University School of Medicine System Director Stereotactic Body Radiotherapy and GI Cancer Programs Division of Radiation Oncology Allegheny Health Network Cancer Institute
Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)