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.

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.

Main outcome of the study:

Development and evaluation of a novel MRI-Linac based functional treatment planning platform with DICOM-compatible applications for visualization and subsequent conformal avoidance of residual, functionally active hepatic parenchyma in patients undergoing liver SBRT to primary and metastatic malignancies with the assessment of tumor and hepatic parenchyma response using MR imaging correlated with both pathologic and genomic criteria in a subset of patients receiving SBRT as a bridge to liver transplant.

Inclusion Criteria:

1. Patients age 18-89 years
2. 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.
3. Child-Pugh A or B liver function;
4. Child-Pugh C liver function for transplant eligible patients only.
5. Single or multinodular tumors (up to four) are permitted.
6. Patients required to have more than 30% of functionally active uninvolved liver outside radiation target volume;
7. No prior liver radiation, including radioembolization;
8. ECOG (Eastern Cooperative Oncology Group) performance score >=2

Exclusion Criteria:

1. Patients over 90 year of age
2. Bilirubin x3 upper limit of normal;
3. AST (aspartate aminotransferase) or ALT (alanine transaminase) x6 upper limit of normal;
4. Hemoglobin less than 80 g/L;
5. Patients with recurrent ascites (paracentesis q ≥2 weeks);
6. Patients with history of hypersensitivity to Feraheme or any other IV iron products;
7. Patients with hemochromatosis (iron overload).

Patients with primary and metastatic liver tumors and hepatic cirrhosis eligible for liver SBRT will be enrolled in this study who will be receiving treatment at Allegheny General Hospital, Pittsburgh, PA.

Only de-identified data will be shared with collaborators of the trial.