Harmonized Multisite MRI-Based Quantification of Human Liver Fat and Stiffness: A Pilot Study.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a leading cause of end-stage liver disease. NAFLD diagnosis and follow-up relies on a combination of clinical data, liver imaging, and/or liver biopsy. However, intersite imaging differences impede diagnostic consistency and reduce the repeatability of the multisite clinical trials necessary to develop effective treatments. PURPOSE/HYPOTHESIS: The goal of this pilot study was to harmonize commercially available 3 T magnetic resonance imaging (MRI) measurements of liver fat and stiffness in human participants across academic sites and MRI vendors. STUDY TYPE: Cohort. SUBJECTS: Four community-dwelling adults with obesity. FIELD STRENGTH/SEQUENCE: 1.5 and 3 T, multiecho 3D imaging, PRESS, and GRE. ASSESSMENT: Harmonized proton density fat fraction (PDFF) and magnetic resonance spectroscopy (MRS) protocols were used to quantify the FF of synthetic phantoms and human participants with obesity using standard acquisition parameters at four sites that had four different 3 T MRI instruments. In addition, a harmonized magnetic resonance elastography (MRE) protocol was used to quantify liver stiffness among participants at two different sites at 1.5 and 3 T field strengths. Data were sent to a single data coordinating site for postprocessing. STATISTICAL TESTS: Linear regression in MATLAB, ICC analyses using SAS 9.4, one-sided 95% confidence intervals for the ICC. RESULTS: PDFF and MRS FF measurements were highly repeatable among sites in both humans and phantoms. MRE measurements of liver stiffness in three individuals at two sites using one 1.5 T and one 3 T instrument showed repeatability that was high although lower than that of MRS and PDFF. CONCLUSIONS: We demonstrated harmonization of PDFF, MRS, and MRE-based quantification of liver fat and stiffness through synthetic phantoms, traveling participants, and standardization of postprocessing analysis. Multisite MRI harmonization could contribute to multisite clinical trials assessing the efficacy of interventions and therapy for NAFLD. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer.

On February 22, 2013, the FDA licensed ado-trastuzumab emtansine (Kadcyla; Genentech, Inc.) for use as a single agent for the treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) who previously received trastuzumab and a taxane, separately or in combination. The clinical basis for licensure was a phase III trial in 991 patients with HER2-positive MBC that randomly allocated patients to receive ado-trastuzumab emtansine (n=495) or lapatinib in combination with capecitabine (n=496). The coprimary endpoints were progression-free survival (PFS) based on tumor assessments by an independent review committee and overall survival (OS). Statistically significant improvements in PFS and OS were observed in patients receiving ado-trastuzumab emtansine compared with patients receiving lapatinib plus capecitabine [difference in PFS medians of 3.2 months, HR, 0.65 (95% confidence interval, CI, 0.55-0.77), P<0.0001 and difference in OS medians of 5.8 months, HR, 0.68 (95% CI, 0.55-0.85), P=0.0006]. The most common adverse reactions in patients receiving ado-trastuzumab emtansine were fatigue, nausea, musculoskeletal pain, thrombocytopenia, headache, increased aminotransferase levels, and constipation. Other significant adverse reactions included hepatobiliary disorders and left ventricular dysfunction. Given the PFS and OS results, the benefit-risk profile was considered favorable.