Compensatory Enlargement of the Liver after Proton Beam Therapy for Hepatocellular Carcinoma

Abstract

Charged particle therapy (CPT) has been applied as a safe and effective treatment option for hepatocellular carcinoma (HCC). Although most HCC patients have cirrhosis, favorable treatment outcome has been achieved with CPT preserving liver function. After proton beam therapy (PBT) for patients with HCC, the liver volume in the non-irradiated area is often enlarged. Here, we evaluated whether enlargement of the non-irradiated liver affects preserving hepatic function and prognosis in HCC patients treated with PBT. Among consecutive patients with HCC treated with PBT between April 2011 and July 2017, we retrospectively identified patients who fulfilled the following criteria: (i) receiving PBT to the right hepatic lobe, (ii) the left lateral segment was not irradiated, (iii) no local treatment was performed for liver within 12 months after PBT, and (iv) the albumin-bilirubin (ALBI) score was evaluable at 12 months after PBT. The left lateral segment was defined as the non-irradiated region and measured by contrast-enhanced CT just before and 3 months after PBT. ALBI scores just before and 12 months after PBT were compared to evaluate changes of hepatic function. Overall survival rate was estimated using the Kaplan-Meier method, and differences in survival between subgroups were examined using the log-rank test. The ALBI scores were compared using the Wilcoxon signed-rank test. We identified 40 patients (male/female = 32/8). The median age at the start date of PBT was 72 (range, 54-87) years. The prescribed dose was 66.0-76.0 Gy (relative biological effectiveness) delivered in 10-38 fractions. The median follow-up was 61 (range, 12-126) months. The 5-year overall survival rates were 79.0% (95% CI: 60.4-100.0%) in the larger enlargement group (n = 16, enlarged volume of non-irradiated region 3 months after PBT ≥75 cm3) and 53.7% (95% CI: 36.0-79.9%) in the smaller enlargement group (n = 24, as above, <75 cm3), respectively (p = 0.21). The median ALBI scores just before and 12 months after PBT were -3.14 (95% CI: -3.22- (-2.53)) and -2.74 (95% CI: -3.07- (-2.42)) in the larger enlargement group (p = 0.09), and -2.91 (95% CI: -3.15- (-2.40)) and -2.59 (95% CI: -2.74- (-2.12)) in the smaller enlargement group (p = 0.006), respectively. Our study suggests that larger enlargement of the non-irradiated liver after PBT is related to well-preserved liver function at 1 year and modestly associated with a favorable prognosis.