Liver Function Preservation and Outcome after SBRT with Functional Treatment Planning in Patients with HCC and Advanced Hepatic Cirrhosis: From Nuclear Medicine to MRI-Based Functional Treatment Planning Platform

Abstract

<h3>Purpose/Objective(s)</h3> To evaluate treatment outcomes of ablative SBRT with SPECT/CT and MRI-guided functional treatment planning for localized HCC in patients with Child-Pugh B (CP-B) cirrhosis. <h3>Materials/Methods</h3> Liver SPECT with ^99mTc-sulfur colloid was co-registered to 3D-CT for identification and avoidance of functional hepatic parenchyma during SBRT in patients with advanced cirrhosis. Likewise, MRI scanner of the Unity® MR-Linac with super-paramagnetic iron oxide nanoparticle (SPION) agent Feraheme® as an alternative contrast was used for treatment planning with visualization of tumor and functional liver parenchyma during SBRT. Functional liver volumes (FLV) obtained from CT-SPECT or SPION-MRI were compared to anatomical liver volumes, as were dosimetric parameters when radiation dose constraints were adapted exclusively to FLV. Hepatic function, toxicity, and radiographic response were documented every 3-4 months following SBRT. <h3>Results</h3> With a median follow-up of 25 months, 44 patients (59 lesions treated) with CP-B cirrhosis received ablative SBRT to a median dose of 48 Gy (3–5 fractions). An automated contouring algorithm was generated for delineation and guided avoidance of best functional hepatic parenchyma on SPION-MRI. Prolonged SPION-contrast retention within hepatic parenchyma allowed per fraction treatment plan adaptation with SPION-enhanced MR imaging of tumor throughout the treatment course. FLV loss (509 cc or 41.3%, p<0.001) was observed in all patients, while the functional and anatomical liver volumes matched well in a control group of non-cirrhotic/non-HCC patients. Mean dose to residual FLV was maintained well below the liver threshold tolerance to radiation in all patients. Thirty-six transplant eligible patients received SBRT as a bridging treatment and 26 patients (60% of the cohort) were listed for liver transplant after completion of SBRT. Twenty-two patients successfully completed orthotopic liver transplant (OLT) with a median time to transplant of 6.1 months. Eight of 10 patients with intrahepatic progression received additional SBRT during follow-up and four of them completed transplant. With 95% in-field local control rate, overall, 2-year survival was 63% (90% after the OLT) with no incidence of RILD or CP class migration observed at 6+ months post SBRT. <h3>Conclusion</h3> SBRT with functional treatment planning on SPEC/CT allows identification and guided avoidance of residual functionally active hepatic parenchyma in patients with advanced hepatic cirrhosis. SPION-enhanced MRI provides consistent visibility of liver tumors and functional hepatic parenchyma on the day of treatment planning and throughout the online MR-guided SBRT. We report high local control and low toxicity leading to satisfactory pre- and post-liver transplant outcomes. Prospective clinical trial investigating MRI-SPION adaptive planning on the 1.5T Elekta Unity® MR-Linac is ongoing in our institution.