Clinical outcomes and safety of external beam radiotherapy with extensive intrahepatic targets for advanced hepatocellular carcinoma: A single institutional clinical experience.

Background: This study observed the clinical outcome of radiotherapy to extensive intrahepatic targets for advanced hepatocellular carcinoma (HCC) in a single institution.

Methods: From September 2009 to July 2021, patients who underwent fractionated radiotherapy to a planning target volume (PTV) of over 100 ml with biological effective dose >30 Gy10 for advanced HCC were enrolled. Overall survival (OS) and radiation-induced liver toxicity (RILD) were evaluated. RILD was defined as an increase in Child-Pugh (CP) score ≥2 or liver function tests ≥2.5 times at 3 months after the end of radiotherapy.

Results: A total of 136 patients were evaluated. Eighty-nine patients had portal vein tumor thrombus (PVTT), 37 patients were in CP B stage, and the median radiation dose to PTV was 48.8 Gy10. The median OS was 12.3 months. The factors most affecting OS were PVTT (P = 0.001), PTV (>500 ml, P = 0.001), incomplete coverage of the intrahepatic tumor (P = 0.004), and CP B (P = 0.006) in Cox regression. RILD occurred in 22.4% of the patients and was affected by PVTT (P = 0.003), PTV (P = 0.010), pretreatment bilirubin levels (>1.5 mg/ml, P = 0.016), and the mean normal liver dose (MNLD) (≥ EQD2 18 Gy3, P = 0.021) in binary logistic regression. As the PTV was in excess of >500 ml, RILD developed in 30.2% of patients and the prognostic importance of pretreatment bilirubin levels (P = 0.006) and the MNLD (P = 0.014) increased.

Conclusions: As PTV is more extensive, the bilirubin level and the MNLD have to be taken into consideration for safe radiotherapy, in addition to the traditional prognostic factors.