3016 - Rates of Hepatotoxicity Following Liver-Directed Ablative External Beam Radiotherapy and Transarterial Radioembolization for Hepatocellular Carcinoma

G. Lee¹, K. S. Lau-Min², E. P. Walsh², J. Franses³, P. D. Sutphin⁴, V. Wu⁴, H. J. Roberts⁵, T. S. Hong⁵, E. P. Wehrenberg-Klee⁴, and J. Y. Wo⁵; ¹Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, ²Division of Medical Oncology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, ³Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL, ⁴Department of Interventional Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, ⁵Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA

Purpose/Objective(s): This study aims to evaluate the safety of combining liver-directed ablative external beam radiotherapy (EBRT) and transarterial radioembolization (TARE) in the management of hepatocellular carcinoma (HCC), a multimodal approach that is increasingly utilized but lacks well established data concerning hepatotoxicity. Materials/

Methods: A retrospective review identified patients with HCC who received both liver-directed EBRT and TARE between 2015-2023 at a single institution. Hepatotoxicity was assessed based on CTCAE v5.0 grade =3 events for liver function tests (AST, ALT, ALP, bilirubin) and/or increase in Child Turcotte Pugh (CTP) score by =2. Predictors of hepatotoxicity were assessed via logistic and Cox regression analysis. Secondary endpoints analyzed were radiographic tumor response, local control (LC), progression free survival (PFS), and overall survival (OS).
Results: 21 patients were identified with a median follow up of 8 months: 12 received TARE first followed by EBRT with a median interval of 6 months and 9 received EBRT first followed by TARE with a median interval of 13 months. Baseline characteristics before 2^nd modality RT were: BCLC stage A in 10%, B in 33%, and C in 57%; tumor thrombus in 43%; median tumor size 5.4 cm; CTP class A in 52% and B in 48%; 52% with prior non-RT treatment. EBRT was stereotactic ablative (median dose 50 Gy) in 33% and moderately hypofractionated (median 48.8 Gy) in 67%. TARE was segmental in 24% and lobar in 76% (67% SirSpheres, 33% glass microsphere treatment) with a median dose of 35 mCi. Same lesion was treated in 57% and same hepatic lobe was treated in 86%. Post 2^nd modality RT, 17 (81%) patients experienced hepatotoxicity: 7 (33%) within 3 months and 10 (48%) within 6 months. Cumulative incidence of hepatotoxicity at 6 months was 48% which was reduced to 10% when hepatic disease progression (n=16, 76%) and any subsequent therapy (n=10, 48%) were incorporated as competing risk events. Pre-treatment characteristics including higher AST/ALT/ALP, lower albumin, greater tumor size, and CTP class B vs A were associated with increased risk for hepatotoxicity; RT characteristics had no significant association. Tumor response was complete in 24% for both and partial in 38% and 48% following each EBRT and TARE, respectively. Median LC, PFS, and OS were 32 (95% CI 3-NR), 3 (95% CI 1-4) and 8 (95% CI 3-13) months following 2^nd modality RT, respectively.
Conclusion: Patients who undergo both EBRT and TARE represent a high risk cohort of HCC patients. While rates of hepatotoxicity seem high following both RT modalities, there is significant confounding with hepatic progression and subsequent therapy. Worse baseline liver function and greater tumor burden are likely risk factors for treatment-related hepatotoxicity. Prospective studies are warranted to further evaluate the safety of multimodality liver-directed RT.