Changes in Liver Function after Functional Liver Image-Guided Hepatic Therapy (FLIGHT) as Assessed by Hepabobiliary Iminodiacetic Acid Scans

Abstract

Purpose/Objective(s): This prospective clinical trial incorporated hepatobiliary iminodiacetic acid (HIDA) scans that provide global and regional assessments of liver function into functional liver image-guided hepatic therapy (FLIGHT) stereotactic body radiation therapy (SBRT) planning. FLIGHT preferentially spares areas of higher functioning liver. The primary endpoint of a functional dosimetric improvement with FLIGHT vs standard planning was met. This is a preliminary analysis of a secondary endpoint evaluating changes in liver function assessed by HIDA scans. Materials/Methods: Eligible pts were ≥18 yo with 1o or 2o liver malignancy and Child-Pugh £B7. Liver function was assessed by HIDA and blood chemistry at baseline, mid-SBRT (after 2 of 3 or after 3 of 5 fractions), 3, 6, and 12 months post-SBRT. We evaluated whether the functional residual capacity (FRC15HIDA), defined through functional dose-volume histogram (fDVH) analysis as the amount of function <15 Gy, can conservatively predict post-treatment global HIDA. We predicted that the post-treatment global HIDA would be larger than the FRC15HIDA. Wilcoxon rank sum tests were used to compare global HIDA at baseline vs other time points, and also to compare baseline liver-volume normalized HIDA values. We performed voxel based analysis of the HIDA scan post-treatment vs baseline to evaluate regional changes in liver function contributed by areas receiving less than 5, 10, 15, 30 Gy. Results: Fifteen patients were enrolled, with 10 evaluable at 3 months and 7 evaluable at 6 months (follow up ongoing). The median baseline global HIDA was 3.3%/min/m2 (range 1.63-8.16). The median change in global HIDA from baseline to mid-SBRT, 3, and 6 months post-SBRT was 0.00, -0.52, and 0.05%/min/m2, respectively. The difference from baseline to 3 months post-treatment was significant (p=0.0137), but this lost significance at 6 months (p=0.8125). At 3 months 1/10 (10%) and at 6-months 5/7 (71%) had global HIDA greater than pre-treatment. At 3 months, 5 pts’ global HIDA was greater than FRC15HIDA as expected, but 5 pts had post-SBRT global HIDA lower than FRC15HIDA. Those with lower than expected post-SBRT global HIDA had a larger liver volume normalized baseline global HIDA but this difference was not significant (2.03 vs 1.77%/min/m2/L, p=0.9168). Those pts whose liver function declined more than expected had larger declines in liver function contributed by each voxel at the dose levels analyzed. Conclusion: In most pts analyzed post-FLIGHT, there were transient declines in liver function assessed by HIDA at 3-months with recovery by 6-months. In those in whom the FRC15HIDA was not a conservative estimate of post-SBRT liver function, there were regional changes in liver function seen at lower than expected doses suggesting increased radiosensitivity. This study is limited due to small sample size, and more research is needed to develop models which may be able to predict post-treatment liver function