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.
Hepatic ischemia-reperfusion injury (HIRI) and induced systemic inflammation is a time-dependent multistage process which poses a risk of causing direct hepatic dysfunction and multiorgan failure. Real-time in situ comprehensive visualization assessment is important and scarce for imaging-guided therapeutic interventions and timely efficacy evaluation. Here, a logically activatable nanoreporter (termed QD@IR783-TK-FITC) is developed for time-phase imaging quantification of HIRI and induced systemic inflammation. The nanoreporters could be used for in vivo ratiometric NIR-IIb fluorescence sensing of reactive oxygen species (ROS), which can depict the in situ hepatic ROS fluctuation for the early diagnosis of HIRI in the initial 3 h. Meanwhile, the ROS-specific reaction releases renal-clearable fluorophore fragments from nanoreporters for monitoring the systematic inflammation induced by HIRI via longitudinal urinalysis. In addition, a functional relationship between digitized signal outputs (NIR-IIb ratios, urinary fluorescence) with hepatic injury scores has been established, realizing precise prediction of HIRI severity and preassessment of therapeutic efficacy. Such a time-phased modular toolbox can dynamically report HIRI-induced systemic inflammation in vivo, providing an efficient approach for HIRI treatment.
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.
Enhancer of zeste homolog 2 (EZH2) is implicated in promoting HNSCC malignant progression. However, EZH2 inhibitors, when used alone, increase the number of myeloid-derived suppressor cells (MDSCs), which are responsible for enhancing tumor stemness and promoting tumor immune escape. We aimed to determine whether combining tazemetostat (an EZH2 inhibitor) and sunitinib (an MDSC inhibitor) can improve the response rate to an immune-checkpoint-blocking (ICB) therapy. We evaluated the efficacy of the above treatment strategies by bioinformatics analysis and animal experiments. EZH2 overexpression and abundant MDSCs in patients with HNSCC are associated with tumor progression. Tazemetostat treatment alone had limited inhibitory effect on HNSCC progression in the mouse models, accompanied by a surge in the number of MDSCs in the tumor microenvironment. Conversely, the combined use of tazemetostat and sunitinib reduced the number of MDSCs and regulatory T cell populations, promoting intratumoral infiltration of T cells and inhibiting of T cell exhausting, regulating of wnt/β-catenin signaling pathway and tumor stemness, promoting the intratumoral PD-L1 expression and improved the response rate to anti-PD-1 therapy. The combined use of EZH2 and MDSC inhibitors effectively reverses HNSCC-specific immunotherapeutic resistance and is a promising strategy for overcoming resistance to ICB therapy.
Abstract Background Few biomarkers can predict the efficiency of PD-1 blockade in patients with hepatocellular carcinoma (HCC). This study aimed to investigate the prognostic role of AFP and PIVKA-II in HCC patients receiving anti-PD-1 immunotherapy. Methods A total of 235 HCC patients treated with PD-1 blockade were enrolled. Serum AFP and PIVKA-II levels were collected before and after treatments. The patients were divided into groups based on the reduction in AFP and PIVKA-II: AFP reduction ≤50% vs AFP reduction > 50% and PIVKA-II reduction ≤50% vs PIVKA-II reduction > 50%. The primary endpoints included objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). Binary logistic regression analyses were used to explore the related factors of ORR. A Cox proportional hazards model was employed to identify the potential prognostic factors of PFS and OS. Results Among all the patients, 34.9% (82/235) achieved a complete or partial response. There was a positive correlation between AFP reduction > 50% or PIVKA-II reduction> 50% and the ORR of PD-1 blockade ( P < 0.001 and = 0.003). PFS was significantly improved in patients with AFP reduction > 50% and PIVKA-II reduction > 50% ( p < 0.001 and = 0.021). In addition, AFP reduction > 50% and PIVKA-II reduction> 50% were positively correlated with longer OS ( p = 0.003 and 0.006). Conclusion Early reductions in AFP and PIVKA-II can be predictors of the efficacy of PD-1 blockade in HCC patients.
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