Intensity-modulated radiotherapy combined with systemic atezolizumab and bevacizumab in treatment of hepatocellular carcinoma with extrahepatic portal vein tumor thrombus: A preliminary multicenter single-arm prospective study

Abstract

Background and aimsThe efficacy and safety of systemic atezolizumab and bevacizumab (atezo/bev) in treatment of patients with unresectable hepatocellular carcinoma (HCC) have been demonstrated. However, the efficacy of this treatment in patients with HCC and extrahepatic portal vein tumor thrombus (ePVTT) is not satisfactory. This study aimed to study the efficacy and safety of combining intensity-modulated radiotherapy (IMRT) with systemic atezo/bev in treatment of these patients.MethodsThis multicenter prospective study included patients with ePVTT treated with IMRT combined with atezo/bev from March to September 2021 in three centers in China. The outcomes of this study included objective response rate (ORR), overall survival (OS), progression-free survival (PFS), time to progression (TTP), and association between response and tumor mutational burden (TMB). Treatment-related adverse events (TRAEs) were analyzed to assess safety.ResultsOf 30 patients in this study, the median follow-up was 7.4 months. Based on the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, the ORR was 76.6%, the median OS for the entire cohort was 9.8 months, the median PFS was 8.0 months, and the median TTP was not reached. This study failed to establish a significant correlation between TMB with any of the following outcomes, including ORR, OS, PFS or TTP. The most common TRAEs at all levels were neutropenia (46.7%), and the most common grade 3/4 TRAE was hypertension (16.7%). There was no treatment-related deaths.ConclusionsIMRT combined with atezo/bev showed encouraging treatment efficacy with an acceptable safety profile, making this treatment to be a promising option for HCC patients with ePVTT. Further studies are required to support the findings of this preliminary study.Clinical trial registrationhttp://www.chictr.org.cn, Identifier ChiCTR2200061793.

Outcome of Atezolizumab Plus Bevacizumab Combination Therapy in High-Risk Patients with Advanced Hepatocellular Carcinoma

“…Wang et al analyzed 30 patients with PVTT that were treated with a combination of ATE + BEV and radiotherapy. They reported that median OS and PFS were 9.8 and 8.0 months, and the ORR was 76.6% [23]. Manzar et al also analyzed the efficacy of 21 patients (of which 71.4% had PVTT) that were treated with a combination of ATE + BEV and radiotherapy; they reported that median OS was 16.1 months [24].…”

Transarterial chemoembolization combined with lenvatinib, programmed death-1 inhibitor, and iodine-125 seed brachytherapy for hepatocellular carcinoma with portal vein tumor thrombosis

“…Moreover, radiation therapy enhances antitumor T-cell response by stimulating effector phases, making it an excellent addition to PD-1 inhibitors 42 . Previous studies approved radiation plus PD-1 inhibitors therapy in HCC with PVTT 43,44 . Therefore, the combination therapy comprising lenvatinib, TACE, PD-1 inhibitor, and I 125 seed brachytherapy is expected to have a better therapeutic effect in the treatment of HCC, especially in patients with PVTT.…”

Tyrosine-kinase inhibitor combined with iodine-125 seed brachytherapy for hepatocellular carcinoma refractory to transarterial chemoembolization: a propensity-matched study

“…Currently, the treatment of HCC with vascular invasion is still a great challenge [ 6 , 38 ]. Our study found that TKI-I conferred a higher treatment response of tumor thrombosis compared with TKI alone.…”