Characterization and Predication of Signal Changes in Normal Liver Parenchyma on Gadoxetic Acid Enhanced Magnetic Resonance Imaging After Liver Directed Radiation Therapy

Abstract

Focal liver reactions (FLR) in areas of prior radiation therapy (RT) on MRI are a phenomenon that has been reported in small series. However, little is known about the temporality and dosimetry of FLR and how they evolve over time. Understanding dosimetry, temporality, and clinical predictors for FLR formation might help us understand the biology of radiation induced liver changes and prevent toxicity.We identified 122 patients who received RT to the liver. The 1-6 month and 6-12 month post-RT MRI scans (hepatobiliary phase with gadoxetic acid) were fused to treatment planning CT scans in areas of prior RT. FLR were delineated by two independent raters. A dose-volume-histogram was used to identify the threshold isodose line (IDL) for each FLR. IDL were converted to a bioequivalent dose (BED) using α/β = 9 for liver parenchyma. MRI scans with no FLR were evaluated by a radiologist to assess for adequate contrast excretion.146 MRI scans for 100 patients were available for analysis. The median age was 65 years. Hepatocellular carcinoma accounted for 79% of cases. Baseline ALBI scores of 1,2 and 3 were observed in 26%, 57% and 17% of patients, respectively. 66% of patients had cirrhosis, with hepatitis C being most common cause (37%). The median dose delivered was 45 gray in 5 fractions. FLR were identified for 73% and 67% of patients at 1-6 months and 6-12 months. Of 26 patients with no FLR at 1-6 months, 54% exhibited poor contrast excretion. The median volume of FLR was 99 cc at 1-6 months, contracting to 43 cc at 6-12 months (P < 0.001). The median (IDL) for FLR was 3541 cGy at 1-6 months, increasing to 4519 cGy (P < 0.001). The median BED was 6355 cGy at 1-6 months, increasing to 8871 cGy (P < 0.001). There was excellent agreement between raters for the presence of FLR at 1-6 (κ = 0.82) and 6-12 months (κ = 0.83) and for FLR volumes (ICC of 0.94 at 1-6 and 0.88 at 6-12-months). 45 patients were evaluated at both time points. Of the 33 patients with an FLR at 1-6 months, 15% experienced resolution at 6-12 months. None of the 12 patients without an FLR on 1-6 months MRI demonstrated one at 6-12 months. On multivariate analysis, cirrhosis (PR: 1.35; P = 0.05) was associated with a higher likelihood of FLR. ALBI score 2 (PR: 0.77; P = 0.04), ALBI score 3 (PR 0.61; P = 0.01), and receipt of systemic therapy within 1 month of RT (PR: 0.74; P = 0.03) were associated a lower likelihood. Prior RT or treatment with Y-90 did not predict for FLR.We report the median volume, IDL and BED associated with FLR at two time points and demonstrate resolution or improvement in a significant proportion of patients over time. Absence of FLR was associated with poor liver function and contrast excretion. Excellent inter-rater agreement indicates that our results are reproducible. Additional analysis is needed to determine the clinical significance of these findings.