Hepatic artery infusion chemotherapy (HAIC) and anti-programmed cell death protein-1 (PD-1) immunotherapy have shown promising outcomes in patients with advanced hepatocellular carcinoma (HCC), respectively. However, the combination of the two treatments has not been reported. In this study, we compared the efficacy of HAIC combined with anti-PD-1 immunotherapy (HAICAP) and HAIC in patients with advanced HCC.Between November 2018 and December 2019, advanced HCC patients that were treated with either HAICAP or HAIC were retrospectively recruited and reviewed for eligibility. Efficacy was evaluated according to tumor response and survival.As a result, 229 patients were included in this study. Patients were divided into HAICAP group (n = 81) and HAIC group (n = 148) accordingly. The follow-up time ranged from 1.0 to 21.6 months, with a median of 11.0 months. The median overall survival was 18.0 months in the HAICAP group and 14.6 months in the HAIC group (p = 0.018; HR = 0.62; 95% CI 0.34-0.91). The median progression-free survival was 10.0 months in the HAICAP group and 5.6 months in the HAIC group (p = 0.006; HR = 0.65; 95% CI 0.43-0.87). The disease control rate in overall response (83% vs 66%; p = 0.006) and intrahepatic response (85% vs 74%, respectively; p = 0.045) were higher in the HAICAP group than in the HAIC group.In comparison to HAIC, HAICAP was associated with a better treatment response and survival benefits for patients with advanced HCC.
Abstract Purpose For hepatocellular carcinoma (HCC) located in the left lateral lobe, the optimal surgical procedure is still controversial. This study aimed to optimize surgical strategies and to construct a nomogram to predict the postoperative survival of patients with HCC. Methods Between 1 January 2005 and 30 September 2018, a total of 493 patients were enrolled. Propensity score matching (PSM) was performed between the left lateral lobectomy (LLL) and left hepatectomy (LH) groups (1:1). The study endpoints were overall survival (OS), recurrence‐free survival (RFS), and safety. A nomogram was generated using a multivariate Cox proportional hazards model. The discriminative ability and calibration of the nomogram were evaluated using C‐statistics and calibration plots. Results After matching, 87 pairs were included. The LH group had better 1‐, 3‐, and 5‐year OS rates than the LLL group (88%, 73%, and 69% vs. 73%, 57%, and 49%, respectively; p = 0.017). The 1‐, 3‐, and 5‐year RFS rates of the LH group were similar to those of the LLL group (64%, 49%, and 46% vs. 63%, 51%, and 42%, respectively; p = 0.652). There were no significant differences in postoperative complications. Eight factors were integrated into the nomogram and it had good discriminative ability and calibration. Conclusion Our data revealed that compared to LLL, LH may result in better OS and have similar postoperative complications for HCC. The nomogram may serve as a practical tool for the individual prognostic evaluation of patients with HCC.
AbstractPurpose Existing prognostic staging systems depend on expensive manual extraction by pathologists, potentially overlooking hidden information, or use black-box deep learning models, which limits their clinical acceptance.This study introduces a novel deep learning-assisted paradigm for creating interpretable, multi-view risk scores to stratify prognostic risk in hepatocellular carcinoma (HCC) patients. Methods 510 HCC patients were enrolled in an internal dataset (SYSUCC) as training and validation cohorts to develop the Hybrid Deep Score (HDS): The Attention Activator (ATAT) was designed to heuristically identify tissues associated with high prognostic risk, and a multi-view risk scoring system based on ATAT established HDS from microscopic to macroscopic levels. The HDS was also validated on an external testing cohort (TCGA-LIHC) with 341 HCC patients. We assessed the prognostic significance using Cox regression and the concordance index (c-index). Results The ATAT first heuristically identified regions where necrosis, lymphocytes, and tumor tissues converge, particularly focusing on their junctions in high-risk patients. From this, this study developed three independent risk factors: microscopic morphological, co-localization, and deep global indicators, ultimately predicting HDS for each patient. The HDS outperformed existing clinical prognostic staging systems, showing higher hazard ratios (HR 3.24, 95% CI 1.91-5.43 in SYSUCC; HR 2.34, 95% CI 1.58-3.47 in TCGA-LIHC) and c-index (0.751 in SYSUCC; 0.729 in TCGA-LIHC) for Disease-Free Survival (DFS). Conclusion This novel paradigm, from identifying high-risk tissues to constructing prognostic risk scores, offers fresh insights into HCC research. It more precisely stratifies HCC patients into high- and low-risk groups for DFS and Overall Survival (OS) compared to existing clinical risk staging systems.
Background A combination of hepatic arterial infusion chemotherapy (HAIC), lenvatinib, and immune checkpoint inhibitors (ICIs) yields a high tumor response rate and survival benefit in unresectable hepatocellular carcinoma (uHCC). However, the selection criteria for different ICIs remain unclear. This study aims to compare the efficacy and safety of PD-1/PD-L1 antibodies combined with HAIC and lenvatinib. Methods This retrospective study included 184 patients with uHCC treated with HAIC+lenvatinib+PD-1/PD-L1 antibody from June 2019 to January 2022. We utilized propensity score matching (PSM) to select and match 60 patients treated with HAIC + durvalumab + lenvatinib (HDL) against 60 patients treated with HAIC + PD-1 antibodies + lenvatinib (HPL) to compare the efficacy and safety profiles of these two groups. Results After PSM, the baseline characteristics were well-balanced between the HDL and HPL groups. The overall survival (p = 0.293) and progression-free survival (p = 0.146) showed no significant difference. The objective response rate (ORR) was higher in the HDL group compared to the HPL group according to modified RECIST (74.1% vs. 53.6%, p = 0.022) and RECIST 1.1 (60.3% vs. 41.1%, p = 0.040), respectively. The incidence of grade 3 or 4 adverse events (AEs) was 10.0% and 18.3% (p = 0.191) in the HDL and HPL groups, respectively. Conclusions PD-L1 antibody appears to be a preferable companion in the combination therapy of HAIC + ICIs + lenvatinib compared to PD-1 antibody, showing higher ORR and relatively lower incidence of severe AEs. Further prospective studies involving a larger patient population are warranted.
4023 Background: The efficacy of operation, as the only radical option for resectable BCLC stage A/B hepatocellular carcinoma (HCC) patients beyond Milan criteria, is still unsatisfactory. This study aimed to investigate to efficacy and safety of preoperative neoadjuvant hepatic arterial infusion chemotherapy (HAIC) with FOLFOX regimen for these patients. Methods: In this multi-center, prospective, phase 3, randomized, open-labeled, controlled clinical trial, resectable BCLC stage A/B HCC patients beyond Milan criteria were randomly assigned (1:1) before hepatectomy to receive either neoadjuvant HAIC (treatment group) or operation directly without any neoadjuvant treatment (control group). The primary endpoint was overall survival (OS), the secondary endpoints are progression-free survival (PFS) and safety. Results: Between March 2016 and August 2022, a total of 487 patients were screened from seven Chinese hospitals, and 392 patients were randomly assigned to receive neoadjuvant FOLFOX-HAIC before hepatectomy (treatment group, n = 195), or operation directly without any neoadjuvant treatment (control group, n = 197) and were included in the ITT population. Among them, 14 patients from the treatment group and 13 patients from the control group were excluded from the PP population. In the ITT population, the OS rates at 1-, 2-, and 3-year were 97.7%, 86.3%, and 77.1%, respectively, for the treatment group and were 90.0%, 80.9%, and 70.6%, respectively, for the control group. The median PFS of the treatment and control groups was 17.4 months (95% CI, 9.0-25.8) and 9.8 months (8.2-11.4), respectively, in the ITT population. The OS and PFS were significantly better in treatment group than in control group (p = 0.032 and < 0.001, respectively) in ITT population. In the PP population, the OS rates at 1-, 2-, and 3-year were 98.7%, 91.1%, and 79.7%, respectively, for the treatment group and were 89.2%, 79.3%, and 67.7%, respectively, for the control group. The median PFS of the treatment and control groups was 22.7 months (95% CI, 10.9-34.5) and 10.2 months (8.4-12.1), respectively, in the PP population. The OS and PFS were significantly better in treatment group than in control group (p = 0.001 and < 0.001, respectively) in PP population. In treatment group of ITT population, the complete regression (CR) rate, object response rate (ORR), disease control rate (DCR) was 11.3%, 61.5%, and 97.4%, respectively. Safety analysis showed HAIC was quite safe, 191 (97.9%) patients had mild HAIC related adverse events (HRAEs) (grade 0-2). The operation related adverse events (ORAEs) were similar between two groups (p = 0.265). Conclusions: Neoadjuvant HAIC with FOLFOX regimen before hepatectomy may bring survival benefits for resectable BCLC stage A/B HCC patients beyond Milan criteria. Clinical trial information: NCT03851913 .
Abstract Background The predictive value of vessels encapsulating tumor clusters (VETC) in recurrent early‐stage hepatocellular carcinoma (HCC) remains unclear. Therefore, the aim of the present study was to investigate the prognostic significance of VETC in patients with recurrent early‐stage HCC after repeat hepatic resection (RHR) or radiofrequency ablation (RFA). Methods From December 2005 to December 2016, 138 patients receiving RHR and 188 patients receiving RFA were recruited. VETC was evaluated by immunohistochemical staining for CD34. The survival outcomes of patients with VETC pattern or not were investigated. Results There was no significant difference between the RHR and RFA groups in disease‐free survival (DFS) or overall survival (OS) as determined by the univariate analysis of the whole cohort. In the subgroup analysis of the VETC‐positive cohort, the patients in the RHR group showed a longer median DFS time in contrast to those in the RFA group (15.0 vs. 5.0 months, p = 0.001). Similarly, the patients in the RHR group showed a longer median OS time in contrast to those in the RFA group (39.5 vs. 19 months, p = 0.001). In the VETC‐negative cohort, no significant differences in DFS and OS rates between the RHR and RFA groups were observed ( p > 0.05). Conclusions The results of our study suggested that RHR was relatively safe and superior to RFA in improving survival outcomes for recurrent early‐stage HCC after initial hepatectomy. Furthermore, the VETC pattern may represent a reliable marker for selecting HCC patients who may benefit from RHR.
Background: Macroscopic vascular invasion (MVI) commonly occurs in patients with advanced hepatocellular carcinoma (HCC) for which resection and sorafenib are the common therapies prescribed. Here, we aimed to compare the survival outcomes of these two therapies in HCC patients with MVI. Methods: In total, 496 patients diagnosed with HCC and MVI without extrahepatic metastasis, treated with resection (resection-based group, n = 388) and sorafenib (sorafenib-based group, n = 108) were included in this study. A one-to-one propensity score-matching analysis (PSM) was performed to minimize the effect of potential confounders. Results: The median OS in the resection- and sorafenib-based group was 20.7 months (95% CI: 16.9-24.5) and 11.6 months (95% CI: 8.4-14.9) (p < 0.001), respectively. The median PFS was 4.7 months (95% CI: 3.8-5.5) in the resection-based group and 4.4 months (95% CI: 3.6-5.2) in the sorafenib-based group (p < 0.001). After PSM, 72 patients from each group were matched. The median OS was 27.2 months (95% CI: 16.4-38.0) in the resection-based group and 13.0 months (95% CI: 9.6-16.3) in the sorafenib-based group (p < 0.001). The median PFS was 5.3 months (95% CI: 3.2-7.4) in the resection-based group and 4.8 months (95% CI: 3.6-6.0) in the sorafenib-based group (p = 0.061). Conclusion: Findings from this study showed that, compared with sorafenib-based treatment, surgical resection might be associated with better survival benefits to HCC patients with MVI.
Abstract Background. The vessels encapsulating tumor clusters (VETC) pattern is an effective predictor of survival in patients with hepatocellular carcinoma (HCC) after resection. The predictive value of VETC in recurrent early-stage HCC remains unclear. Therefore, the aim of the present study was to investigate the prognostic significance of VETC in patients with recurrent early-stage HCC after repeat hepatic resection (RHR) or radiofrequency ablation (RFA). Methods. From December 2005 to December 2016, 138 patients who underwent RHR and 188 patients who underwent RFA were enrolled. VETC was evaluated by immunohistochemical staining for CD34. The survival outcomes of treatment for patients with or without the VETC pattern was investigated. Results. Among VETC-positive HCC patients, 50 patients underwent RHR, and 69 patients underwent RFA; among VETC-negative HCC patients, 88 patients underwent RHR, and 119 patients underwent RFA. There was no significant difference between the RHR and RFA groups in disease-free survival (DFS) or overall survival (OS) as determined by univariate analysis of the whole cohort. In the subgroup analysis of the VETC-positive cohort, the patients in the RHR group had a longer median DFS time compared to those in the RFA group (15.0 vs 5.0 months, P= 0.001). Similarly, the patients in the RHR group had a longer median OS time compared to those in the RFA group (39.5 vs 19 months, P= 0.001). In the VETC-negative cohort, there was no significant difference in DFS and OS rates between the RHR and RFA groups ( P >0.05). Conclusions. The results of our study suggested that RHR was relatively safe and superior to RFA in improving survival outcomes for recurrent early-stage HCC after initial hepatectomy. Furthermore, the VETC pattern may represent a reliable marker for selecting HCC patients who may benefit from RHR.
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