A preliminary study of optimal treatment response rates in patients undergoing hepatic arterial infusion chemotherapy combined with molecular targeting and immunotherapy.

Objectives: This study aimed to examine the effectiveness of the best response rate (BRR) as a surrogate for overall survival (OS), using the modified Response Evaluation Criteria in Solid Tumors (mRECIST), in patients with unresectable hepatocellular carcinoma (HCC) undergoing hepatic arterial infusion chemotherapy (HAIC) with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) combined with molecular targeting and immunotherapy. Methods: This study enrolled 111 consecutive patients who had complete imaging data. The median age of patients was 58 years (IQR 50.5-65.0). Among the patients, those with Barcelona Clinic Liver Cancer (BCLC) stage A, BCLC stage B, and BCLC stage C comprised 6.4%, 19.1%, and 73.6%, respectively. The optimal threshold of BRR can be determined using restricted cubic splines (RCS) and the rank sum statistics of maximum selection. Survival curves of patients in the high rating and low rating groups were plotted. We then used the change-in-estimate (CIE) method to filter out confounders and the inverse probability of treatment weighting (IPTW) to balance confounders between the two groups to assess the robustness of the results. Results: The median frequency of the combination treatment regimens administered in the overall population was 3 times (IQR 2.0-3.0). The optimal BRR truncation value calculated was -0.2. Based on this value, 77 patients were categorized as the low rating group and 34 as the high rating group. The differences in the OS between the high and low rating groups were statistically significant (7 months [95%CI 6.0-14.0] vs. 30 months [95%CI 30.0-]; p< 0.001). Using the absolute 10% cut-off value, the CIE method was used to screen out the following confounding factors affecting prognosis: successful conversion surgery, baseline tumor size, BCLC stage, serum total bilirubin level, number of interventional treatments, alpha-fetoprotein level, presence of inferior vena cava tumor thrombus, and partial thrombin activation time. The survival curve was then plotted again using IPTW for confounding factors, and it was found that the low rating group continued to have better OS than the high rating group. Finally, the relationship between BRR and baseline factors was analyzed, and inferior vena cava tumor thrombus and baseline tumor size correlated significantly with BRR. Conclusions: BRR can be used as a surrogate endpoint for OS in unresectable HCC patients undergoing FOLFOX-HAIC in combination with molecular targeting and immunotherapy. Thus, by calculating the BRR, the prognosis of HCC patients after combination therapy can be predicted. Inferior vena cava tumor thrombus and baseline tumor size were closely associated with the BRR.

In vitro characteristics of Epirubicin-loaded thermosensitive liquid embolic agent.

OBJECTIVE: To investigate the drug loading and release rate of epirubicin-loaded thermosensitive liquid embolic agents in vitro. MATERIALS AND METHODS: The drug loading and stability of epirubicin-loaded thermosensitive liquid embolic agents with or without iopromide were determined by high-performance liquid chromatography, and the same method was used to determine the drug release rate of thermosensitive liquid embolic agents at different time points. RESULTS: For epirubicin-loaded thermosensitive liquid embolic agents without iopromide, the average drug loading after filtration by membrane was (0.78 ± 0.02) mg and the drug loading rate was (16.1 ± 0.35)%, while the average drug loading without membrane was (0.73 ± 0.06) mg and the drug loading rate was (15.07 ± 1.17)%. After adding iopromide, the drug loading capacity was measured from 0 h-24 h solution and the drug loading was calculated indirectly and conclude that the drug loading capacity of thermosensitive liquid embolic agents decreased or disappeared. The sustained release rate of epirubicin from 0 to 48 hours was 42.65% in 48 hours. CONCLUSION: Epirubicin can be successfully loaded into the thermosensitive liquid embolic agents with good stability and sustained release. After adding iopromide, the drug loading capacity of thermosensitive liquid embolic agents decreased or disappeared.

Hepatic arterial infusion chemotherapy in hepatocellular carcinoma: A bibliometric and knowledge-map analysis.

Background: In recent years, hepatic arterial infusion chemotherapy (HAIC) has gained popularity in the treatment of hepatocellular carcinoma. Although several studies have been published, no bibliometric analysis have been conducted on this topic. Objectives: To understand the development status and future trends in the application of HAIC, we conducted bibliometric analysis to examine the cooperation and influence among countries, institutions, authors, and journals. Methods: All relevant articles and reviews on the use of HAIC in HCC treatment were retrieved from the Web of Science database. A bibliometric analysis of countries, institutions, journals, authors, and keywords related to this field was performed using R and VOSviewer software. The main aspects analyzed were the research status and key fields of HAIC in HCC treatment. Results: A total of 1026 articles published in 292 journals by 4937 authors from 959 institutions between 1974 and 2021 were retrieved. A rapid increase in articles published after 1990 was observed, which reached the peak in 2021. Japan had the most publications and citations. Yonsei University, Sun Yat-sen University, and Hiroshima University were the three leading institutions in research on this topic. Kwang-Hyub Han and Masatoshi Kudo have the greatest academic influence in this field. Most publications were made in the Hepato-Gastroenterology, whereas cancer had the most citations. The main aspects of HAIC treatment of HCC include HAIC and TACE, chemotherapy drug selection, HAIC and targeted therapy and immunotherapy, HAIC and surgery, and hepatotoxicity. Keywords such as FOLFOX, lenvatinib, hepatic arterial infusion chemotherapy are hot words in this field in recent years. Conclusion: The research on the use of HAIC in the treatment of HCC has been on the rise. Currently, HAIC combined with targeted therapy or immunotherapy has attracted significant attention.