PD-1 inhibitors plus anti-angiogenic therapy with or without intensity-modulated radiotherapy for advanced hepatocellular carcinoma: A propensity score matching study.

Background: Whether intensity-modulated radiotherapy (IMRT) can enhance the efficacy of the programmed death (PD)-1 inhibitors combined with anti-angiogenic therapy for hepatocellular carcinoma (HCC) is unclear. Therefore, we conducted this multicenter retrospective study to investigate the efficacy of the combination of PD-1 inhibitors with anti-angiogenic therapy and IMRT. Methods: From April 2019 to March 2022, a total of 197 patients with HCC [combination of PD-1 inhibitors with anti-angiogenic therapy and IMRT (triple therapy group), 54; PD-1 inhibitors plus anti-angiogenic therapy (control group), 143] were included in our study. Propensity score matching (PSM) was applied to identify two groups with similar baselines. The objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) of the two groups were compared before and after matching. Results: Prior to PSM, the triple therapy group had higher ORR (42.6% vs 24.5%, P = 0.013) and more superior median OS (mOS) (20.1 vs 13.3 months, P = 0.009) and median PFS (mPFS) (8.7 vs 5.4 months, P = 0.001) than the control group. Following PSM, the triple therapy group still exhibited better mPFS (8.7 vs 5.4 months, P = 0.013) and mOS (18.5 vs 12.6 months, P = 0.043) than the control group. However, the ORR of the two groups was similar (40% vs 25%, P = 0.152). No significant difference was observed in the treatment-related adverse events between the two groups (P < 0.05 for all). Conclusions: The combination of PD-1 inhibitors with anti-angiogenic therapy and IMRT for HCC is a promising regimen.

PD-L1 expression on circulating tumor cells can be a predictive biomarker to PD-1 inhibitors combined with radiotherapy and antiangiogenic therapy in advanced hepatocellular carcinoma.

Aim: A programmed death 1 (PD-1) inhibitor coupled with radiotherapy and antiangiogenic therapy is a potential therapeutic strategy for advanced hepatocellular carcinoma (HCC). We aimed to determine if circulating tumor cells (CTCs) positive for programmed death-ligand 1 (PD-L1) could be employed as a predictive biomarker in HCC patients receiving triple therapy. Methods: In this study, HCC patients received a PD-1 inhibitor in combination with intensity-modulated radiotherapy (IMRT) and antiangiogenic therapy. Following IMRT, the PD-1 inhibitor was administrated once every 3 weeks, while the antiangiogenic drug was given once a day. Treatment was continued until the disease progressed. Two mL of peripheral blood was collected at baseline, 1 month, and 3 months after treatment for CTC enrichment using the CytoSorter® system with a CytoSorter™ CTC PD-L1 Kit (Watson Biotech., China). Result: A total of 47 HCC patients receiving the triple therapy were enrolled in this study. Patients with < 2 PD-L1+ CTCs at baseline had a higher objective response rate (ORR) and longer overall survival (OS) than those with ≥ 2 PD-L1+ CTCs (56.5% vs. 16.7%, p = 0.007; not reach vs. 10.8 months, p = 0.001, respectively). The count of PD-L1+ CTCs was found to be an independent predictive biomarker of OS. Furthermore, the objective response was more likely to be achieved in patients with a dynamic decrease in PD-L1+ CTC counts at 1 month after treatment. Conclusions: Our study demonstrated that PD-L1+ CTCs could be a predictive biomarker for HCC patients receiving PD-1 inhibitors in combination with IMRT and antiangiogenic therapy.

Heat-shock protein 90α is a potential prognostic and predictive biomarker in hepatocellular carcinoma: a large-scale and multicenter study.

BACKGROUND: Although the diagnostic value of plasma heat-shock protein 90α (HSP90α) in hepatocellular carcinoma (HCC) has been previously reported, the causal effect of the plasma HSP90α levels on HCC prognosis remains largely unclear. To this extent, we sought to assess whether the plasma HSP90α acts as a prognostic factor for HCC patients. METHODS: A total of 2150 HCC patients were included in this retrospective study between August 2016 and July 2021. Plasma HSP90α levels were tested within a week before treatment and their association with prognosis was assessed. RESULTS: An optimal cutoff value of 143.5 for the HSP90α based on the overall survival (OS) was determined using the X-tile software. HCC patients with HSP90α < 143.5 ng/mL (low HSP90α) before and after propensity score matching (PSM) indicated longer median OS (mOS) relative to those with HSP90α ≥ 143.5 ng/mL (high HSP90α) (37.0 vs. 9.0 months, p < 0.001; 19.2 vs. 9.6 months, p < 0.001; respectively). In addition, the high HSP90α plasma level is an independent poor prognostic factor for OS in HCC patients. In our subgroup analysis, including the supportive care group, surgery group, transarterial chemoembolization (TACE) group, adjuvant TACE group, an immune checkpoint inhibitor (ICI) plus targeted therapy group, and TACE plus ICI group, the high HSP90α group demonstrated better OS compared to the low HSP90α group. Moreover, in the supportive care, TACE, ICI plus targeted therapy, TACE plus ICI groups, and high HSP90α levels were also an independent poor prognostic factors for OS. CONCLUSIONS: Our study confirmed that the plasma HSP90α level can be used as a prognostic biomarker for HCC.

Gamma knife radiosurgery versus transcatheter arterial chemoembolization for hepatocellular carcinoma with portal vein tumor thrombus: a propensity score matching study.

BACKGROUND: The optimal locoregional treatment for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) is unclear. This study aimed to investigate the efficacy of Gamma knife radiosurgery (GKR) versus transcatheter arterial chemoembolization (TACE) in HCC patients with PVTT. METHODS: This retrospective study included 544 HCC patients with PVTT (GKR, 202; TACE, 342). Propensity score matching (PSM) analysis identified 171 matched pairs of patients. The primary endpoint was overall survival (OS). RESULTS: Before PSM, the GKR group exhibited longer median OS (mOS) than the TACE group (17.2 vs. 8.0 months, p < 0.001). We followed the Cheng's classification for PVTT. In the subgroup analysis, GKR was associated with significantly longer mOS for patients with PVTT II-IV (17.5 vs. 8.7 months, p < 0.001; 17.2 vs. 7.8 months, p = 0.001; 14.5 vs. 6.5 months, p = 0.001, respectively) and comparable OS for patients with PVTT I. After PSM, the GKR group had also a longer mOS than the TACE group (15.8 vs. 10.4 months, p < 0.001). In the subgroup analysis, the GKR group demonstrated superior mOS for patients with PVTT II-IV (all p < 0.05) and comparable OS for patients with PVTT I. CONCLUSIONS: GKR was associated better OS than TACE in HCC patients with PVTT, especially for patients with PVTT II-IV. CLINICAL TRIALS REGISTRATION: The study was registered in the Chinese Clinical Trials Registry under the registration number ChiCTR2100051057.