Efficacy and safety of hepatic arterial infusion chemotherapy combined with lenvatinib and PD-1 inhibitors for advanced hepatocellular carcinoma with macrovascular invasion.

BACKGROUND AND AIMS: The prognosis of hepatocellular carcinoma (HCC) with macrovascular invasion(MaVI)is poor, and the treatment is limited. This study aims to explore the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC), combined with lenvatinib and programmed cell death-1(PD-1) inhibitor in the first-line treatment of HCC with MaVI. METHODS: From July 2020 to February 2022, we retrospectively analyzed consecutive patients with HCC with MaVI who received hepatic arterial infusion FOLFOX(oxaliplatin, 5-fluorouracil, and leucovorin)combined with lenvatinib and PD-1 inhibitor. The efficacy was evaluated by RECIST 1.1. Kaplan-Meier was used to explore the overall survival and progression-free survival (PFS), and the COX regression model was used to analyze the risk factors of PFS. Adverse events (AEs) were evaluated according to CTCAE5.0. RESULTS: Thirty-two patients with HCC complicated with MaVI were recruited from the Second Affiliated Hospital of Nanchang University. Among the patients treated with HAIC combined with lenvatinib and PD-1 inhibitor, ten patients (31.25%) got partial response, eighteen patients (56.25%) maintained stable disease and four patients (12.50%) suffered progressive disease during follow-up; and objective response rate was 31.25%, and disease control rate was 87.5%. The median PFS was 179 days. Univariate and multivariate Cox analysis showed that the extrahepatic metastases and Child-Pugh score were independent prognostic factors of PFS. Twenty-two (68.75%) patients suffered adverse reactions. The main AEs were elevated transaminase (46.87%), thrombocytopenia (40.63%), hypoalbuminemia (28.13%), nausea and vomiting (21.88%), leukopenia (18.76%), abdominal pain (15.63%), hypertension (15.63%) and fever (15.63%). There were seven cases (21.88%) that had grade 3 or above AEs; Among them, two cases with elevated transaminase (6.25%), leukopenia, thrombocytopenia, nausea and vomiting, abdominal pain, and diarrhea occurred in one case respectively. Moreover, no treatment-related death was observed. CONCLUSIONS: Hepatic arterial infusion of FOLFOX combined with lenvatinib and PD-1 inhibitor as the first-line treatment for HCC complicated with MaVI is effective, and adverse reactions are tolerable.

Network meta-analysis of adjuvant treatments for patients with hepatocellular carcinoma after curative resection.

PURPOSE: The prevention of recurrence for patients with hepatocellular carcinoma after curative resection is still a great challenge in clinical practice. There are numerous studies that trying to search for favorable strategies to decrease the recurrence and prolong life span for these patients, whereas no consensus is reached till now. Herein, we aim to compare the efficacy between different reported treatments by network meta-analysis(NMA). METHODS: We searched Pubmed, Web of Science and Cochrane Library for abstracts and full-text articles published from database inception through February 2023. All of the random controlled trials(RCTs) were evaluated and collected as eligible studies. The primary outcome was the prevention of recurrence between different procedures. The second outcomes were one-year survival, three-year survival and five-year survival. RESULTS: Thirty-two RCTs including 5783 patients were selected, and 12 treatments were classified. Most of the studies were high quality with low bias. Thirty-one studies including 5629 patients were recruited for recurrence analysis. The network meta-analysis showed benefits from transarterial chemoembolization(TACE) + portal vein chemotherapy(PVC)[OR, 2.84 (1.15,6.99)] and internal radiotherapy(IRT) [OR, 2.63 (1.41,4.91)] compared to non-adjuvant(NA) treatment when considering prevention of recurrence. Seventeen studies including 2047 patients were collected for one-year survival analysis. The network meta-analysis showed benefit from TACE[OR, 0.33 (0.14,0.75)] when considering one-year survival. Twenty-one studies including 2463 patients were collected for three-year survival analysis. The network meta-analysis showed TACE [OR, 0.51 (0.30,0.86)], IRT[OR, 0.41 (0.20,0.83)] and dendritic cell(DC) [OR, 0.09 (0.01,0.98)] were better than NA when considering three-year survival. Sixteen studies including 1915 patients were collected for five-year survival analysis. The network meta-analysis didn't show any benefit from different treatments when considering five-year survival. Other strategies including external radiotherapy(ERT), branched-chain amino acids(BCAA), hepatic artery infusion chemotherapy(HAIC), cytokine-induced killer(CIK), adoptive immunotherapy(AIT), Huaier, interferon(IFN), oral chemotherapy(OCT) and sorafenib(SOR) didn't show significant benefit regardless of prevention of recurrence or short-, long- time survival. CONCLUSION: This NMA found that TACE + PVC and IRT were considered as the procedures to decrease HCC recurrence rate. TACE, IRT and DC were preferred when considering the extending of life span for post-operative patients with HCC. Large scale of RCTs are needed to verify it.

Efficacy and Safety of Drug-Eluting Bead TACE in the Treatment of Primary or Secondary Liver Cancer.

Background: The drug-eluting beads transarterial chemoembolization (DEB-TACE) has already been used in hepatic malignancies. We aim to evaluate the efficacy and safety of DEB-TACE in treating primary or secondary liver cancer. Methods: We retrospectively evaluated 59 patients with hepatic malignancies, including 41 patients with primary liver cancer and 18 patients with secondary liver cancer, between September 2016 and February 2019. All patients were treated with DEB-TACE. Objective response rate (ORR) and disease control rate (DCR) were evaluated by mRECIST. The pain was assessed using a numerical rating scale (NRS) where 0 represented no pain, and a score of ten was unbearable. Adverse reactions were assessed according to Common Terminology Criteria for Adverse Events 4.0 (CTCAE4.0). Results: In the subgroup of primary liver cancer, 3 patients (7.32%) got complete response, 13 patients (31.71%) got partial response, 21 patients (51.22%) experienced stable disease, and 4 patients (9.76%) suffered progressive disease; ORR was 39.02% and DCR was 90.24%. In the subgroup of secondary liver cancer, 0 patients (0%) got complete response, 6 patients (33.33%) got partial response, 11 patients (61.11%) experienced stable disease, and 1 patient (5.56%) suffered progressive disease; ORR was 33.33% and DCR was 94.44%. We did not find any difference when comparing the efficacy between primary and secondary liver cancer (P=0.612). The one-year survival rate was 70.73% for primary liver cancer and 61.11% for secondary liver cancer. There was no significant difference between the two groups (P=0.52). For the patients with CR or PR, no factor could predict the efficacy of DEB-TACE. The most common treatment-related adverse reactions were short-term liver function disorders. The symptoms included fever (20.34%), abdomen pain (16.95%), and vomiting (5.08%), all patients with adverse reactions got remission after treatment. Conclusions: DEB-TACE has a promising effect in the treatment of primary or secondary liver cancer. The treatment-related adverse reactions are tolerable.

Comparison of Different First-Line Systemic Therapies in Advanced Biliary Tract Cancer Based on Updated Random Controlled Trials: A Systematic Review and Network Meta-Analysis.

Methods: We searched PubMed, Web of Science, and Cochrane Library for abstracts and full-text articles published from database inception through May 2022. All the random controlled trials (RCTs) were assessed and collected as eligible studies. The primary outcome was overall survival (OS). The second outcome was progression-free survival (PFS). Results: Seventeen studies, including 3632 patients, were selected from 1361 records. In the network meta-analysis for OS, gemcitabine + cisplatin (GemCis) + cediranib (HR, 0.11; 95% CI, 0.00-2.88), GemCis+durvalumab (HR, 0.27; 95% CI, 0.06-1.29), and GemCis + merestinib (HR, 0.37; 95% CI, 0.03-4.36) showed the trend of OS benefit over standard treatment (GemCis), although there was no significant difference. GemCis, GemOxa, and gemcitabine+S1 (GemS1) did not differ when comparing OS. In the network meta-analysis for PFS, GemCis+merestinib (HR, 0.67; 95% CI, 0.54-0.83) and GemCis+durvalumab (HR, 0.22; 95% CI, 0.08-0.62) showed PFS benefit over standard treatment (GemCis) with a significant difference. GemCis, GemOxa, and GemS1 did not differ when comparing PFS. Conclusion: GemCis+durvalumab might be the most promising regimen for advanced BTC when considering OS and PFS. GemOxa and GemS1 could be alternative options for advanced BTC patients with nontolerance to GemCis.

Multiwalled Carbon Nanotube/Graphite Powder Film for Wearable Pressure Sensors with High Sensing Performance.

With the continuous progress of artificial intelligence and other manufacturing technologies, there is promising potential for wearable piezoresistive sensors in human physiological signal detection and bionic robots. Here, we present a facile solution-mixing process to fabricate a multiwalled carbon nanotube/graphite powder (MWCNT@Gp) film, which has high sensitivity and great linearity and is more oriented to flexible piezoresistive sensors. The sensor consists of two parts: a spinosum microstructure shaped by a sandpaper template and polydimethylsiloxane (PDMS) as the top substrate and interdigital electrodes as the bottom substrate. The experiments we have conducted show that these two parts provide good protection to the MWCNTs@Gp film and improve sensor sensitivity. Additionally, the sensitivity of the optimal ratio of multiwalled carbon nanotubes and graphite powder is analyzed. The 5%MWCNT@5%Gp composites were found to have relatively good conductivity, which is convenient for the fabrication of conductive films of piezoresistive sensors. Finally, we conducted application experiments and found that the flexible piezoresistive sensor can detect minute signals of human motion and different pressure points. This indicates the feasibility of portable sensors in electronic skin and smart devices.