Safety of Stereotactic Body Radiation Therapy after Trans-Arterial Radioembolization for Hepatocellular Carcinoma

Abstract

For unresectable hepatocellular carcinoma (HCC), both trans-arterial radioembolization (TARE) and stereotactic body radiation therapy (SBRT) are increasing in usage, and there is concern that using SBRT after TARE might increase risk of toxicity given cumulative radiation exposure to the liver. We analyzed the safety of SBRT in patients who had previously undergone TARE. A retrospective chart review identified patients with HCC who received SBRT after TARE from the years 2014-2016 with at least one month of follow up. TARE was administered trans-arterially with yttrium-90, dose adjusted based on a technetium-99m macroaggregated albumin (MAA) scan before treatment. SBRT was delivered in 5 fractions from 30-50 Gy with stereotactic conebeam guidance. Patients were analyzed for Child-Turcott-Pugh score (CTP), Albumin-Bilirubin (ALBI) score, and Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 events. Differences in cohorts were compared using Chi-square and paired t-test. 24 patients met criteria with median follow up of 184 days (range 45-849). At time of SBRT, 9 patients were Barcelona Clinic Liver Cancer (BCLC) stage A, 7 were B, and 8 were C. Prior to SBRT, patients had median 2 trans-arterial chemobolizations (TACE) (range 0-7), median 0 resections (range 0-1), and median 1 TARE (range 1-3). 38.5% received Sorafenib: 20% pre-SBRT, 20% post, and 60% pre and post. 17% received Nivolumab: 75% post-SBRT and 25% pre and post. Median time from TARE to SBRT was 153 days (range 24-726). 12 (50%) received SBRT to the same site as a prior TARE. Median SBRT dose was 40 Gy. Baseline and follow up characteristics are shown in the Table. There was a significant increase in CTP score at 1 month post-SBRT (p=0.008) and 3 months (p=0.036) but not at later time points. There was a significant increase in ALBI score at 1 month (p<0.001), 3 months (p<0.001), and 6 months (p=0.0086), but not at later time points. Grade ≥ 3 CTCAE events above baseline are as follows: increased AST n=3, increased ALT n=0, increased alkaline phosphatase n=0, GI ulcer/bleed n=0, and liver failure n=4. There were 8 known deaths: 1 of unknown etiology, 5from progressive HCC, and 2 grade 5 liver toxicities likely from treatment. One grade 5 toxicity was after a TARE missed its target and treated normal liver parenchyma, and the other received TARE and SBRT within 2 weeks in a heavily pretreated liver. Exploratory analyses found significant differences in 1 month CTP scores when stratified for ≥ 120 days between TARE and SBRT (p=0.001), but not for baseline CTP score ≥ 8, ≥2 TAREs vs. 1, or SBRT to a previously treated lesion with TARE vs. a novel site. SBRT following TARE appears to show acceptable toxicity for the majority of patients. Further analysis is needed to determine parameters predictive for liver toxicity.Abstract 2364Baseline (n=24)1 mo (n = 24)3 mo (n = 18)6 mo (n =12 )9 mo (n = 9)1 yr (n =8)Median CTP score5666.576.5Median ALBI raw score-2.25-1.83-1.76-1.87-1.74-1.82Median ALBI gradeIIIIIIIIIIII Open table in a new tab