Exploration of safety indicators for radiotherapy in hepatocellular carcinoma: A real-world study

Hepatocellular carcinoma (HCC) is the most common pathological subtype of primary liver cancer and is associated with high incidence and mortality. External beam radiation therapy (EBRT) is a widely used local treatment modality for HCC across different disease stages. In the era of precision radiotherapy, standardized safety evaluation indicators for HCC radiotherapy remain lacking. Normal liver tissue surrounding the tumor may lose hepatic function after high-dose irradiation. In this study, remnant functional liver volume (RFLV) was defined as the volume of liver tissue that retains normal function after irradiation, and the residual remnant functional liver volume after x Gy irradiation (rRFLV_x) was defined as the absolute liver volume receiving less than a given dose threshold (x Gy), and plans to explore the performance of rRFLV_x as a radiotherapy safety dose indicator based on real-world data, as well as to explore the safety and efficacy of EBRT in HCC.

A total of 113 HCC patients who received stereotactic body radiotherapy (a SBRT group, n=35) or intensity-modulated radiation therapy (a IMRT group, n=78) for liver lesions at the Third Xiangya Hospital of Central South University between 2015 and 2023 were prospectively collected and selected. The occurrence of radiation-induced liver diseases (RILDs) was recorded. Dosimetric parameters potentially associated with RILDs were analyzed using binary logistic regression with Hosmer-Lemeshow test, mainly including mean liver dose (MLD), remnant liver volume (RLV), standard liver volume (SLV), and rRFLV_x. Radiotherapy-related hepatitis virus reactivation and other radiotherapy-related toxicities were also observed. Progression-free survival (PFS) and overall survival (OS) were used to evaluate the efficacy of EBRT in HCC.

Among the 113 HCC patients, 12 were diagnosed with RILDs, including 11 in the IMRT group and only 1 in the SBRT group. Binary logistic regression with Hosmer-Lemeshow test results suggested that rRFLV₂₅, rRFLV₂₀, rRFLV₁₅, rRFLV₂₅/SLV, rRFLV₂₀/SLV, and rRFLV₁₅/SLV were significantly associated with the occurrence of RILDs in HCC patients in the IMRT group (all P<0.05), while MLD and RLV were not associated with the occurrence of RILDs (P=0.88). One patient without regular anti-hepatitis viral treatment was diagnosed with radiotherapy-related HBV clinical reactivation, and one patient was diagnosed with immunotherapy-related HBV clinical reactivation. The median PFS was 5.6 months in the IMRT group and 16.4 months in the SBRT group, and the best local control rates were 98.6% and 100.0%, respectively. The median OS was 12.2 months in the IMRT group and 33.5 months in the SBRT group. The 6-month, 1-year, and 2-year OS rates in the IMRT group were 77.1%, 52.6%, and 18.6%, respectively. The 1-year, 2-year, 3-year, 4-year, and 5-year OS rates in the SBRT group were 86.1%, 61.7%, 39.2%, 25.7%, and 18.3%, respectively.

EBRT is safe and effective for HCC patients at different stages. Compared with MLD and RLV, rRFLV_x and rRFLV_x/SLV may be more reliable for evaluating the occurrence of RILDs after IMRT treatment. For patients with hepatitis background, concurrent antiviral therapy during radiotherapy is relatively safe, but serum viral load should be closely monitored. Further research is needed to explore the efficacy and safety of radiotherapy combined with targeted and immunotherapy.