3430 - Hepatobiliary Toxicity following Ablative Radiation for Centrally Located Hepatocellular Carcinoma (HCC)

Purpose/Objective(s): Multiple radiotherapy (RT) regimens using protons or photons are employed for the treatment of HCC with the goal of delivering an ablative RT dose in 5-25 fractions. However, in patients with centrally located tumors, hepatobiliary toxicity associated with various ablative RT methods is poorly characterized.

Materials/Methods: A retrospective review of patients treated with ablative RT (EQD2 > 80 Gy) for HCC from 2014-2024 was performed at a single institution. A Central Hepatobiliary Tree (CHBT) structure was retrospectively defined in all patients as a 1 cm expansion of the portal vein, from origin to bifurcation, to serve as a surrogate for the biliary ducts. Tumors were classified as central if the PTV overlapped with the CHBT structure. Standardized max point doses (EQD2, a/b=3) for the Portal Vein and CHBT were collected. Baseline patient characteristic data including age, tumor stage, Child-Pugh (CP) Score, ALBI Score, and cirrhosis etiology were collected. Central hepatobiliary toxicity events were classified according to CTCAE Version 6.0 and changes in ALBI Scores collected during follow-up.

Results: A total of 46 patients met criteria for central tumors with a median follow-up duration of 21 months (range 4-67). The dose / fractionation for central tumors included 50 Gy / 5 fractions (n=13, 28%), 58.05-70.2 Gy /15 fractions (n=28, 61%) and 75 Gy / 25 fractions (n=4, 9%) using protons (n=27, 59%) or photons (n= 19, 41%). Baseline CP scores were available in 35 patients and included CP A (n=24, 67%), CP B (n=10, 28%) and CP C (n=1, 3%). Average baseline ALBI Score was -2.36. Baseline ALBI grades included Grade 1 (n=17, 27%), Grade 2 (n=25, 54%) and Grade 3 (n=3, 7%). Seven (15%) patients received liver transplants at a median of 10.2 months (range 11 days – 17.5 months) after RT. The median for the EQD2 DMax (a/b=3) was 111 Gy (range 80-188) for the CHBT and 100 Gy (range 4-187) for the Portal Vein. No occurrences of biliary stricture attributable to radiation were identified. A single patient with CHBT EQD2 Dmax of 104 Gy and Portal Vein EQD2 DMax of 100 Gy developed portal vein thrombosis potentially attributable to RT 26 months after RT. Increase in ALBI Grade within 6 months of RT was seen in 15 (33%) patients. ALBI increase was seen in 8/13 (62%) SBRT patients and in 7/33 (21%) fractionated patients (p=0.009).

Conclusion: The incidence of central hepatobiliary toxicity following ablative radiation for centrally located HCC is very low. Central location of HCC tumors should not preclude consideration of ablative radiation, particularly with hypofractionated courses using > 5 fractions.