Central hepatobiliary toxicity in patients treated with stereotactic body radiotherapy (SBRT) for liver malignancies.
Authors: Thawani Nitika , Tan Nicholas , Pinnaduwage Dilini , Srivastava Shiv , Sherlock Mariah , Patel Shyamal , Diaz Aidnag , Sorensen Stephen , Patel Mital Shirish 
Published: January 2022

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Background: SBRT is being increasingly utilized for control of primary as well as metastatic liver tumors. Early reports for central hepatobiliary toxicity have been published. We reviewed all liver SBRT cases treated at our institution for incidence of central hepatobiliary toxicity and evaluated the relation with planned dosimetry to define predictors to limit toxicity for future patients. Methods: 43 consecutive patients treated with liver SBRT between 3/2017 to 7/2021 were included in the study. 40 patients were eligible for analysis as 3 were lost to followup. These included- 31 Hepatocellular Carcinoma (HCC), 6 cholangiocarcinoma (CC) and 3 metastatic lesions. They received 35-50 Gy in 3-5 fractions utilizing VMAT for radiation planning and treated on Truebeam in Bodyfix immobilization and 4D scans utilized to create ITV for motion management along with MRI fusion for target delineation. All patients were prospectively planned with CBD spared to max dose <50 Gy. All patients had LFTs evaluated at each fraction and then every 3 months after. Toxicity was assessed according to CTCAE v4.0. We retrospectively contoured central hepatobiliary tree (cHBT) defined as portal vein from confluence to division with 1.5 cm margin expansion. Dosimetry data was analyzed to correlate CBD, cHBT and PV max, CBD PV and cHBT 1cc, cHBT V30Gy and cHBTV40Gy with toxicity. Doses were converted to BED10 for analysis and reported as absolute dose for this study. Results: Median follow up for all patients was 8 months (3-38 months). Local control rates at primary sites of disease was 85% (34 patients). 35 patients with >3 mnth follow up were evaluated for subacute and chronic toxicity. Toxicity grades were grade 4- 3 patients (7.5%), grade 3 -5 patients (12.5%), < grade 2- 32 patients (80%). Local control rates at primary sites of disease were 34 patients (85%). 35 patients with >3 mnth follow up were evaluated for subacute and chronic toxicity. Median PTV volume was 241cc (21.5-1087.5cc). 6 (15%) patients had portal vein thrombosis. Median dose was 40 Gy in 5 fractions. There was no correlation between Dmax for CBD, PV and cHBT with toxicity. cHBT V30 and V40 showed trends towards statistical significance V30 and V40 for cHBT showed a trend towards statistical correlation (coeff 0.63) but no statistically significant dosimetric association. All patients that developed grade 4 toxicity had portal vein thrombosis or lesion involving the hilum. Conclusions: Central hepatobiliary toxicity is seen in 7.5% patients with Liver SBRT. The risk is higher in patients with portal vein thrombosis. Moderate doses 30-40 Gy seem to be a better predictor of toxicity and should be limited during planning especially in patients with portal vein thrombosis. This finding confirms the reported explant data from pathology reviews in the published literature. This data needs to be validated in a larger prospectively evaluated sample.