Liver Regeneration Following Radiation Therapy in Hepatocellular Carcinoma Patients: Insights from Functional Liver Imaging

Abstract

A critical need for hepatocellular carcinoma (HCC) patients is understanding how the liver recovers following radiation therapy (RT). While liver regeneration after hepatic resection has been well-studied, liver recovery following RT is less understood. We have previously studied 99mTc-sulphur colloid (SC) single photon emission tomography (SPECT)/CT to spatially and quantitatively analyze liver function. The purpose of this study was to assess both volumetric and functional liver changes following RT. Patients with HCC had liver function assessed with SC SPECT/CT before and after definitive RT. Patients received 30-67.5 Gy in 4-15 fractions. Anatomic and functional liver metrics were assessed before and after treatment. The anatomic liver volume (ALV) was drawn on CT imaging. Liver function was measured as the functional volume encompassing 30% of maximum uptake (FLV) and mean liver-to-spleen uptake ratio (L/S). Changes in liver size and function were compared to clinical characteristics, including Child-Pugh (CP) score. Parametric t-tests were used to analyze the data. Of 23 evaluable patients (proton RT, n = 16 or photon RT, n = 7), 15 patients had CP-A5/6, 7 had CP-B7/8, and 1 had CP-C10 scores. The mean interval of SC SPECT was 67 days following RT (range, 44 to 113 days). The mean PTV was 272 cc (range 22-802 cc). Regarding baseline liver status, mean pre-treatment ALV was 1584 cc (range 810-2749 cc) with no significant difference in ALV between CP-A and B/C patients (p = 0.285). Pre-treatment mean liver function as assessed with L/S was 1.06 ± 0.43 with significantly greater function in CP-A compared to CP-B/C patients (1.27 vs 0.66, respectively, p<0.001). Mean pre-treatment FLV was 1351 ± 430.8 cc with no significant difference in FLV between CP-A and B/C patients (1422 ± 441 cc vs 1220 ± 436 cc, respectively, p = 0.31). When evaluating change following RT, the mean change in ALV was 0.9% (range, -29% to 23%) with no significant difference between CP-A and CP-B/C patients (-1.5% vs 5.4%, respectively, p = 0.19). In contrast, change in liver function following RT was larger; mean change in FLV was -20% (range, -55% to 33%) and mean change in L/S was -16% (range, -66% to 105%). While change in FLV was not significantly different between CP-A and CP-B/C patients, CP-B/C patients had significantly greater decline in mean liver function (L/S) than CP-A patients (-40 ± 18% vs -3.6 ± 36%, respectively, p = 0.018). There was no association between change in liver volume and change in L/S, p = 0.543. Functional liver imaging metrics reveal different information about the potential functional reserve of irradiated livers compared to anatomic measurements. These data imply that functional liver imaging may more accurately assess the regenerative potential of irradiated and non-irradiated volumes of liver, which may be useful in clinical scenarios where assessment of the function of future liver remnants become critical.