The Contribution of Cirrhosis Progression in Liver Dysfunction After Stereotactic Body Radiation Therapy

Patients with cirrhosis and hepatocellular carcinoma (HCC) often have progressive liver dysfunction after stereotactic body radiation therapy (SBRT), but the relative contribution of direct radiation toxicity versus cirrhosis progression is unknown. Our goal was to estimate the proportion of post-SBRT deterioration in the albumin-bilirubin (ALBI) score that is due to cirrhosis progression versus radiation toxicity.

We first developed mixed-effects models to predict longitudinal ALBI trajectories among 6789 patients with cirrhosis within the University of Michigan system who did not have HCC. This resulted in a model for the expected change in ALBI over time due solely to cirrhosis progression. The model was then applied to a multi-institutional data set of 260 patients with cirrhosis and HCC treated with SBRT, resulting in patient-level predictions for ALBI deterioration due to cirrhosis progression alone. This predicted post-SBRT ALBI trajectory due to cirrhosis progression was then compared with the observed trajectory for each patient, resulting in an estimate of the proportion of post-SBRT ALBI change attributable to cirrhosis progression versus radiation toxicity.

In the cirrhosis cohort used for longitudinal modeling, ALBI trajectories were nonlinear, with an average 0.25-point improvement in the first year, followed by a worsening of 0.08 points on average per year. In the HCC cohort, the median baseline ALBI was -2.19 (unitless), reflecting a median albumin of 3.50 g/dL and a total bilirubin of 1.20 mg/dL. After SBRT, the mean ALBI increased (worsened) to -1.86 at 12 months. The estimated proportion of post-SBRT ALBI worsening due to cirrhosis was 14.2% (95% CI, 9.5%-18.8%) at 6 months and 24.9% (95% CI, 15.0%-34.7%) at 12 months, with the remainder attributed to SBRT.

A significant proportion of post-SBRT liver function decline is due to the natural progression of cirrhotic liver dysfunction, and this proportion increases with time. These findings should improve estimates of SBRT treatment toxicity.