Lijun Chen,1 Min Liu,2 Shenshen Chen,1 Yi Wu,1 Shichun Guan,1 Jianxu Li,1 Shixiong Liang1 

1Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, 530021, People’s Republic of China; 2Department of Oncology, Zhuzhou Central Hospital, Zhuzhou, 412000, People’s Republic of China

Correspondence: Shixiong Liang; Jianxu Li, Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, 530021, People’s Republic of China, Email sxiongliang@163.com; 1327542141@qq.com

Purpose: There is limited research data on the management of hepatocellular carcinoma (HCC) patients with Child-Pugh class B (CP-B). This study aimed to evaluate the clinical outcomes and radiation-induced hepatic toxicity (RIHT) of combined intensity modulated radiotherapy (IMRT) and programmed cell death protein 1 (PD-1) inhibitors in advanced HCC patients with CP-B.
Patients and Methods: This retrospective study screened 232 CP-B advanced HCC patients who had undergone IMRT, and the irradiation scopes were intrahepatic tumor lesions and/or venous tumor thrombosis. The propensity matching method (PSM) was used to reduce selection bias between the radiotherapy (RT) and RT+PD-1 groups. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoints included local progression-free survival (LPFS), out-of-field progression-free survival (outPFS), objective response rate (ORR), disease control rate (DCR), and RIHT.
Results: 50 and 39 patients with CP-B advanced HCC were included in the RT+PD-1 and RT groups. After PSM, 39 patients from each group were matched. The median follow-up duration was 15.53 months (95% CI, 13.83– 17.22). The median OS and median PFS of RT+PD-1 group were significantly prolonged than RT group (OS:14.27 months [95% CI, 10.53–not estimable] vs 7.57 months [95% CI, 6.57– 10.00], HR = 0.284; 95% CI, 0.153– 0.526; p < 0.001), (PFS:9.00 months [95% CI, 5.00–not estimable] vs 4.50 months [95% CI, 3.10– 6.00], HR = 0.349; 95% CI, 0.188– 0.648; p < 0.001). The ORR of RT+PD-1 group was improved than RT group, 43.6% (95% CI, 27.3– 59.9) vs 28.2% (95% CI, 13.4– 43.0) (p = 0.157). The incidence of RIHT did not differ between the groups except the RT+PD-1 group experienced increased total bilirubin (≥grade 1) more frequently (p = 0.021).
Conclusion: Combined IMRT and PD-1 inhibitors improved clinical outcomes with a comparable incidence of RIHT to radiotherapy alone in advanced HCC patients with CP-B. The individual combined IMRT and PD-1 inhibitors for CP-B could be cautiously applied weighing the survival benefits and the RIHT risks.

Keywords: Child-Pugh B, hepatocellular carcinoma, PD-1 inhibitors, hepatic toxicity, radiotherapy, immunotherapy