Effect of external beam radiation therapy versus transcatheter arterial chemoembolization for non-diffuse hepatocellular carcinoma (≥ 5 cm): a multicenter experience over a ten-year period.

Background: The optimal local treatment for HCC with tumor diameter ≥ 5 cm is not well established. This research evaluated the effectiveness of external beam radiation therapy (EBRT) versus transcatheter arterial chemoembolization (TACE) for HCC with tumor diameter ≥ 5 cm. Methods: A total of 1210 HCC patients were enrolled in this study, including 302 and 908 patients that received EBRT and TACE, respectively. Propensity score matching (PSM) was used to identify patient pairs with similar baseline characteristics. Overall survival (OS) was the primary study endpoint. Results: We identified 428 patients using 1:1 PSM for survival comparison. Compared with the TACE group, the EBRT group had a significantly longer median OS (mOS) before (14.9 vs. 12.3 months, p = 0.0085) and after (16.8 vs. 11.4 months, p = 0.0026) matching. In the subgroup analysis, compared with the TACE group, the EBRT group had a significantly longer mOS for HCC with tumor diameters of 5-7 cm (34.1 vs. 14.3 months, p = 0.04) and 7-10 cm (34.4 vs. 10 months, p = 0.00065), whereas for HCC with tumor diameters ≥ 10 cm, no significant difference in mOS was observed (11.2 vs. 11.2 months, p = 0.83). In addition, the multivariable Cox analysis showed that Child-A, alkaline phosphatase < 125 U/L, and EBRT were independent prognostic indicators for longer survival. Conclusion: EBRT is more effective than TACE as the primary local treatment for HCC with tumor diameter ≥ 5 cm, especially for HCC with tumor diameter of 5-10 cm.

PD-1 Inhibitors Combined with Antiangiogenic Therapy with or Without Transarterial Chemoembolization in the Treatment of Hepatocellular Carcinoma: A Propensity Matching Analysis.

Background: At present, it is not known whether targeting plus immunotherapy combined with transarterial chemoembolization (TACE) can improve the efficacy of hepatocellular carcinoma (HCC). The aim of this retrospective experiment was to explore the difference in clinical efficacy between antiangiogenic drugs plus PD-1 inhibitors combined with and without TACE. Methods: Clinical data of 145 patients with HCC who received anti-angiogenesis therapy plus PD-1 inhibitor combined with TACE (TACE-P-T) (n = 62) or anti-angiogenesis therapy combined with PD-1 inhibitor (P-T) (n = 83) in China from October 2018 to December 2022 were collected and reviewed. We used propensity matching (PSM) to create two groups with comparable baseline scores, compared their median survival time (mOS) and median progression-free survival time (mPFS), and performed subgroup analysis. Results: Before PSM, the mOS and mPFS of patients were 20.3 and 5.0 months in the triple therapy group and 13.6 and 7.4 months in the control group, respectively. After PSM, the mOS and mPFS of patients were 19.7 and 6.6 months in the triple treatment group and 10.5 and 3.7 months in the control group, respectively. Therefore, the TACE-P-T group showed better survival outcomes than P-T. In the subgroup analysis, compared with the control group, the mOS was 10.7 vs 20.3 months in the alpha fetoprotein (AFP) (≥ 400ng/mL/<400ng/mL) group, 29.3 vs 7.4 months in the alkaline phosphatase (ALP) (≥ 125u/L/< 125u/L) group and 10.5 vs 20.0 months in the Portal vein invasion (PVTT) group. Conclusion: Antiangiogenic therapy combined with PD-1 inhibitors combined with TACE has significant survival benefits for HCC patients.

Thymidine kinase 1 appears to be a marker for the prognosis of hepatocellular carcinoma based on a large-scale, multicenter study.

INTRODUCTION: The aim of this study was to investigate the role of thymidine kinase 1 (TK1) levels in hepatocellular carcinoma (HCC) prognosis and to develop a nomogram for predicting HCC prognosis. METHOD: In this study, 1066 HCC patients were enrolled between August 2018 and April 2022. TK1 levels were measured within one week before enrollment, and the relationship with HCC prognosis was evaluated. Next, all patients were randomly assigned to the training set (70%, n = 746) and the validation set (30%, n = 320). We used multivariate Cox analysis to find independent prognostic factors in the training set to construct a nomogram. The predictive power of the nomogram was assessed using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). The optimal critical value of TK1 was determined as 2.35 U/L using X-tile software. RESULT: Before and after propensity score matching (PSM), the median overall survival (mOS) of the low-TK1 group (< 2.35 U/L) remained significantly longer than that of the high-TK1 group (≥ 2.35 U/L) (48.1 vs 16.5 months, p < 0.001; 75.7 vs 19.8 months, p = 0.001). Moreover, multivariate Cox analysis showed that the low TK1 level was an independent positive prognostic indicator. Additionally, the area under the ROC curve for predicting the 1-year, 2-year, and 3-year survival rates was 0.770, 0.758, and 0.805, respectively. CONCLUSIONS: TK1 could serve as a prognostic marker for HCC. In addition, the nomogram showed good predictive capability for HCC prognosis.

A propensity score matching study on survival benefits of radiotherapy in patients with inoperable hepatocellular carcinoma.

With the advancements in radiotherapy (RT) in recent years, several studies have shown that RT can significantly prolong the survival of patients with hepatocellular carcinoma (HCC). As a noninvasive treatment option, the application of RT for the treatment of HCC is garnering increasing attention. In this retrospective study, we included data from 13,878 patients with HCC from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2019 and 325 patients with HCC treated in three tertiary hospitals in China between 2015 and 2021. Patient data were divided into RT and non-RT groups based on whether the patients underwent RT. Propensity score matching analysis was performed to minimize the deviation between the RT and non-RT groups, and the Kaplan-Meier method, Cox proportional hazard model, and nomogram were used to assess the efficacy of undergoing RT. The median overall survival (mOS) of the RT group was significantly longer compared with that of the non-RT group for the SEER data (16 months versus 9 months, p < 0.01). Similarly, the survival benefit was more significant in the RT group than in the non-RT group at our hospitals (34.1 months versus 15.4 months, p < 0.01). Furthermore, multivariate Cox analysis revealed that factors, including tumor (T) stage, patient age, tumor grade, serum AFP level, and chemotherapy, also affected patient survival. Moreover, these factors were also used to construct a nomogram. Subgroup analysis of these factors showed that RT was effective in prolonging patient survival in different populations. RT significantly improves the survival time of patients with inoperable HCC, thereby providing a basis for selecting HCC patients who can benefit from RT.

Construction and validation of a nomogram for HBV-related hepatocellular carcinoma: A large, multicenter study.

INTRODUCTION AND OBJECTIVES: We initiated this multicenter study to integrate important risk factors to create a nomogram for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) for clinician decision-making. PATIENTS AND METHODS: Between April 2011 and March 2022, 2281 HCC patients with an HBV-related diagnosis were included. All patients were randomly divided into two groups in a ratio of 7:3 (training cohort, n = 1597; validation cohort, n = 684). The nomogram was built in the training cohort via Cox regression model and validated in the validation cohort. RESULTS: Multivariate Cox analyses revealed that the portal vein tumor thrombus, Child-Pugh class, tumor diameter, alanine aminotransferase level, tumor number, extrahepatic metastases, and therapy were independent predictive variables impacting overall survival. We constructed a new nomogram to predict 1-, 2-, and 3-year survival rates based on these factors. The nomogram-related receiver operating characteristics (ROC) curves indicated that the area under the curve (AUC) values were 0.809, 0.806, and 0.764 in predicting 1-, 2-, and 3-year survival rates, respectively. Furthermore, the calibration curves revealed good agreement between real measurements and nomogram predictions. The decision curve analyses (DCA) curves demonstrated excellent therapeutic application potential. In addition, stratified by risk scores, low-risk groups had longer median OS than medium-high-risk groups (p < 0.001). CONCLUSIONS: The nomogram we constructed showed good performance in predicting the 1-year survival rate for HBV- related HCC.

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.

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.