Loading...

Table of Content

    30 December 2024, Volume 11 Issue 4
    Special topic
    Progress summary clinical trials of new drugs for liver cancer
    Sun Jiayang, Hu Wei, Tang Yu
    2024, 11(4):  1-5. 
    Asbtract ( 5 )   PDF (1948KB) ( 4 )  
    References | Related Articles | Metrics
    Objective: To summarize the development trend of global clinical trials of primary hepatic cancer(HCC) from 2020 to June 2024.
    Methods: Based on the Trialtrove database developed by Informa Pharma Intelligence (London, UK), the clinical trials of liver cancer and the related medicines launched from 2020 to 2024 were extracted. The annual growth rate, the characteristics of trials and tested products were analyzed.
    Results: During the statistical period, a total of 356 clinical trials for HCC were carried out worldwide, accounting for 4.3% of all anti-cancer clinical trials. Among them, 189 (53.1%) were initiated by domestic companies. The number of clinical trials for HCC peaked in 2022 (101 trials). Phase I(including phase Ⅰ/Ⅱ) clinical trials were the most common trial phase type (266 trials, 74.7%). In terms of trial indications, drug development for advanced HCC accounted for the highest proportion (324 trials, 91.0%). Among all the investigational drugs, the types of drugs involved mainly included antibody drugs (48.0%), small molecule targeted drugs (25.4%), cell and gene therapy (15.4%) and antibody-drug conjugate (5.0%). Thirty-two clinical trials focused on first line treatment for late-stage HCC. Among them, the main investigational treatment modality was combined immunotherapy based on immune checkpoint inhibitors. A total of 262 clinical trials were conducted for patients with advanced HCC progressed after previous treatment, of which 32 trials (12.2%) were carried out in patients failed immunotherapy. All the 32 trials were in phase Ⅰ/Ⅱ trials, involving a variety of experimental drug types.
    Conclusions: The clinical development of liver cancer drugs is active in the world, and domestic enterprises play an important role. In liver cancer, immunotherapy is the most active field of drug development. While in the clinical trials including heavily treated HCC patients, cell and gene therapy is also an important clinical research area. It is suggested that domestic enterprises should increase investment in the development of novel drugs for liver cancer, explore more new targets and drugs with new mechanisms, and broaden the possible directions of liver cancer treatment.
    Combination therapy with TIGIT monoclonal antibody in the first-line treatment of advanced hepatocellular carcinoma: a commentary based on the results of two phase-Ⅱ clinical studies
    Jiang Ning, Li Xuchu, Huang Huiyao, Sun Chao, Fang Hong, Ma Hailan, Jia Shuopeng, Wu Dawei, Tang Yu, Li Ning
    2024, 11(4):  6-12. 
    Asbtract ( 4 )   PDF (2958KB) ( 2 )  
    References | Related Articles | Metrics
    Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer worldwide. Despite significant progress in the early diagnosis and treatment of HCC in recent years, the prognosis for patients with advanced HCC remains poor. Emerging immunotherapies for HCC, such as programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors, have demonstrated some clinical efficacy, but issues with resistance persist. Monoclonal antibodies targeting T cell immunoreceptor with Ig and ITIM domains (TIGIT), as a novel immune checkpoint inhibitor, have the potential to enhance anti-tumor immune responses when used in combination with PD-1/PD-L1 inhibitors. This article, based primarily on the results of the AdvanTIG-206 and MORPHEUS-Liver Phase II clinical trials, summarizes the current efficacy and safety of TIGIT monoclonal antibody combination therapy as a first-line treatment for patients with advanced HCC. Additionally, it explores the potential and possible challenges of combining TIGIT antibodies with PD-1/PD-L1 inhibitors and targeted therapies, with the aim of identifying new directions for first-line therapy in advanced HCC.
    Research advance of oncolytic virus in liver cancer
    Xiang Guilin, Song Shuhui, Duan Shijie, Fang Hong, Tang Yu, Liu Funan
    2024, 11(4):  13-18. 
    Asbtract ( 3 )   PDF (1660KB) ( 0 )  
    References | Related Articles | Metrics
    Liver cancer is a major global health concern whose clinical treatment means are limited, facing a series of challenges such as high postoperative recurrence rates, high transplant failure rates and resistance to chemotherapy drugs, and the overall clinical benefit is unsatisfactory. In recent years, with the rapid development of immunotherapy, major breakthroughs have been achieved in the treatment of multiple malignant tumors. As a new biological immunotherapy agent, oncolytic virus (OV) kills tumors by highly selective infecting and lysing tumor cells, activating the body's immune response, improving the tumor microenvironment and other mechanisms, and numerous clinical studies have been carried out in the treatment of liver cancer. The preliminary data show an encouraging application prospects. Herein, this review systematically introduces the mechanism of action of OV while comprehensively summarizes the latest clinical research progress of OV in liver cancer, Particularly,we emphasize the innovative products of OV in the treatment of liver cancer and its research and development design strategy, as well as sorts out the combination therapy of OV, which will provide potential directions for the future treatment of liver cancer with OV.
    Original article
    A network calculator based on lymphocyte ratio-associated immune-inflammatory response score predicts survival in patients with hepatocellular carcinoma
    Shi Limin, Zhang Mingxing, Cai Siqi, Yang Yueyi, Yang Chunyi, Zhang Wenqiong
    2024, 11(4):  19-26. 
    Asbtract ( 4 )   PDF (7030KB) ( 3 )  
    References | Related Articles | Metrics
    Objective: To develop a lymphocyte ratio-associated immune-inflammatory response score (IRS) and construct a network calculator to predict prognostic risk in patients with hepatocellular carcinoma (HCC).
    Method: HCC patients who were surgically treated in Shanghai Public Health Clinical Center between January 2018 and December 2023 were selected. Neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), monocyte to lymphocyte ratio (MLR) and C-reactive protein to lymphocyte ratio (CLR) were collected. IRS was constructed using multifactorial Cox risk regression. Univariate and multifactorial Cox regression models were used to analyse risk factors for mortality in HCC patients. Constructed and assessed nomogram prediction accuracy using R packages such as rms, foreign, readxl, Hmisc and rmda. Development of a mortality risk network calculator for HCC patients using the DynNom package.
    Result: 154 patients were followed up from 1 month to 60 months, with a median follow-up of 17 months, in which the 1-, 3- and 5-year mortality rates were 30.5%, 50.6% and 61.0%, respectively. IRS=0.213 × NLR+0.005×PLR+0.042×CLR was constructed based on the multifactorial Cox risk regression coefficient β. IRS was significantly higher in patients who died than in those who survived (P<0.05). Patients in the high-risk group (IRS≥2.88) had significantly lower survival than patients in the low-risk group (IRS<2.88) (P<0.05). Time- receiver operating characteristic (ROC) curves showed areas under the curve (AUCs) of 0.829 (95% confidence interval [95%CI]: 0.760-0.885), 0.901 (95%CI: 0.842-0.943), and 0.898 (95%CI: 0.839-0.941) for 1-year, 3-year, and 5-year risk of death among patients with IRS prediction, respectively. The results of multifactorial Cox risk regression analysis showed that maximum tumour diameter, γ-glutamyl transferase (GGT), alkaline phosphatase (ALP), alpha-fetoprotein (AFP) and IRS were independent factors for the risk of death in HCC patients (P<0.05). Nomogram were constructed based on IRS to predict the risk of death in HCC patients at 1, 3 and 5 years. The calibration curves showed that the C-index of the nomogram predicting the risk of death at 1, 3 and 5 years was 0.836 (95%CI: 0.818-0.912), 0.903 (95%CI: 0.882-0.961) and 0.847 (95%CI: 0.817-0.932), respectively, respectively, and time-decision curve analysis (DCA) revealed that the nomogram provided a significant meaningful clinical net benefit for risk thresholds in the range of 0-1. The web calculator interface is available at https://nomogramdynamic.shinyapps.io/DynNomapp/.
    Conclusion: The risk of death in HCC patients can be effectively predicted by evaluating and localising the IRS. The network calculator of the risk of death in HCC patients constructed by the IRS combined with the maximum diameter of the tumour, GGT, ALP, and AFP can provide a more positive basis for the treatment of patients with a poorer prognosis.
    Exploration of the guiding significance of protein regulating cytokinesis 1 in the management of gastrointestinal tumors
    Liu Yifeng, Ran Yihong, Che Xu
    2024, 11(4):  27-35. 
    Asbtract ( 4 )   PDF (3724KB) ( 0 )  
    References | Related Articles | Metrics
    Objective: Analyzing the expression, biological role, and prognostic impact of protein regulating cytokinesis 1 (PRC1) in gastrointestinal tumors through bioinformatics tools, and subsequently guide clinical treatment.
    Method: Based on a public database analysis, the expression level of PRC1 in gastrointestinal tumors, co-expressed genes, biological mechanisms of action, immunological regulatory characteristics, interpretation of gene mutation sites, prognostic impact on various tumors, and the prognostic impact of gene mutations on gastrointestinal tumors are analyzed.
    Result: PRC1 was highly expressed in cholangiocarcinoma, colon cancer, liver cancer, pancreatic cancer, rectal cancer, and gastric cancer, and highly co-expressed with PRC1 related genes, which together affected the biological process of gastrointestinal tumors. The PRC1 and related gene sets were mainly enriched in mitotic related items in gene ontology (GO) enrichment analysis. In terms of immune promotion, PRC1 plays a regulatory role in B, CD4+, CD8+ and other immune cells in gastric and pancreatic cancer. PRC1 affects the biological process of gastrointestinal tumors in various forms of deep deletion, shallow deletion, diploid mutation, and amplification. The main mutation forms of each point on the PRC1 segment are missense mutations and truncations, which affect the translation and expression of PRC1, thereby affecting the biological process of gastrointestinal tumors. The high expression of PRC1 affects the prognosis of gastric cancer and pancreatic cancer. PRC1 mutation group indicates a poor prognosis of gastrointestinal tumors.
    Conclusion: The high expression and mutation of PRC1 in gastrointestinal tumors are high-risk factors for malignant progression and poor prognosis of gastrointestinal tumors, further guiding clinical treatment strategies.
    The application value of contrast-enhanced ultrasound on the differentiation of colorectal cancer liver metastasis and atypical hepatic hemangioma
    Chen Yuxiang, Yan Ji, Zhang Chenxue, Yu Haitao, Wu Xueliang, Wang Likun
    2024, 11(4):  36-41. 
    Asbtract ( 4 )   PDF (3622KB) ( 0 )  
    References | Related Articles | Metrics
    Objective: To explore the clinical application value of contrast-enhanced ultrasound (CEUS) in differentiating between colorectal cancer liver metastasis (CCLM) and atypical hepatic hemangioma (AHH).
    Method: A retrospective analysis was conducted on patients diagnosed with 76 cases of CCLM and 80 cases of AHH between 2020 and 2022, who underwent CEUS and received pathological confirmation at our institution. The ultrasonographic characteristics of both groups were compared. The diagnostic sensitivity, specificity, accuracy, and receiver operating characteristic (ROC) curves were analyzed for conventional ultrasound alone and in combination with CEUS.
    Result: The results indicated significant differences in ultrasound enhancement features between CCLM and AHH, with statistically significant differences in tumor lesion internal and surrounding blood flow signals (P<0.05). Conventional ultrasound combination with CEUS significantly improved the specificity and accuracy in diagnosing CCLM compared to conventional ultrasound alone. Furthermore, the area under the curve for conventional ultrasound combination with CEUS was significantly higher than that for conventional ultrasound.
    Conclusion: CEUS is an effective method for enhancing the ultrasound differentiation capability between CCLM and AHH.
    Meta-analysis of long-term survival in patients with spontaneous rupture of hepatocellular carcinoma after hepatectomy
    Zhang Jing, Huang Xiaozhun, Huang Zhangkan, Xu Lin, Yin Xin, Bi Xinyu, Che Xu, Ni Yong
    2024, 11(4):  42-49. 
    Asbtract ( 3 )   PDF (5904KB) ( 1 )  
    References | Related Articles | Metrics
    Objective: Spontaneous rupture of hepatocellular carcinoma (HCC) is associated with high mortality rates, and hepatic resection can provide better outcomes than other available treatments. However, whether HCC rupture affects tumor recurrence and patient survival remains controversial.
    Method: From inception to January 14, 2020. The electronic databases of PubMed, OVID, Web of Science, Embase, and the Cochrane Library were searched from the date of database inception until January 14, 2020, and studies reporting survival outcomes with comparison between rupture HCC (rHCC) and non-rupture HCC (nrHCC) were included. The reported data were statistically summarized using Review Manager V5.3.
    Result: A total of 3 144 patients from nine cohort studies were included. The overall survival (OS) and disease-free survival (DFS) were lower in the rHCC group than in the nrHCC group. The subgroup analysis of high-quality propensity-matched analyses to investigate the true impact of rupture on DFS and OS between the rHCC and nrHCC groups with no heterogeneity. The 1, 3, and 5 years hazard ratios (HR) of OS were 5.30 (95% confidence interval [95%CI]: 3.42-8.22), 5.76 (95%CI: 4.24-7.81), and 4.20 (95%CI: 3.20-5.51), respectively. The HR of 1, 3 and 5 years DFS were 3.68 (95%CI: 2.67- 5.07), 3.87 (95%CI: 2.99- 5.02) and 3.72 (95%CI: 2.93- 4.72), respectively.
    Conclusion: The present Meta-analysis demonstrated that the DSF and OS were significantly lower in the rHCC group than in the nrHCC group and that spontaneous HCC rupture was a predictor of poor survival outcomes.
    Review
    Research progress of locoregional therapies combined with systemic therapies in unresectable hepatocellular carcinoma
    Jing Congmin, Zhang Yubao
    2024, 11(4):  50-53. 
    Asbtract ( 4 )   PDF (1534KB) ( 3 )  
    References | Related Articles | Metrics
    Liver cancer ranks fifth in the incidence of malignant tumors and second in the causes of cancer-related death in China. Most of the patients have already developed to the middle and late stages when characteristic symptoms appear, have missed the best time for surgery, so palliative therapy plays a central role in the treatment of hepatocellular carcinoma. Locoregional treatment is one of the main therapeutic options for patients with unresectable hepatocellular carcinoma (uHCC), and immunotherapy and targeted systemic therapy have also made substantial progress in recent years, but the effect of interventional therapy alone or monotherapy is limited. Several combination therapy options have been actively explored in clinical studies, with encouraging efficacy and brought hope for the treatment of uHCC patients. Among them,the new combination of locoregional combined with systemic therapy is expected to be a potential therapeutic modality for intermediate and advanced hepatocellular carcinoma. This review provides an overview of the current status of research on locoregional combined with systemic therapy, aim to provide more treatment strategies for uHCC patients.
    Research progress on hand-foot skin reaction in targeted therapy for hepatocellular carcinoma
    Ning Yanting, Xia Juan, Wu Shu, Zhang Qi, Li Xiaoqing, Che Xu, Zhan Zhengyin
    2024, 11(4):  54-59. 
    Asbtract ( 5 )   PDF (1822KB) ( 1 )  
    References | Related Articles | Metrics
    Targeted drugs, as an important means in the treatment of liver cancer, have significantly improved the overall survival rate of liver cancer patients. However, some side effects inevitably occur during treatment. Hand-foot skin reaction is one of the common adverse reactions, which not only affects the patient's quality of life, but may also force the patient to reduce the dosage of the drug or interrupt treatment. , thus affecting the therapeutic effect. This article comprehensively analyzes the current research status of hand-foot skin reactions related to targeted drugs at home and abroad, discusses its pathogenesis, clinical manifestations, and grading standards, and compares the differences in chemotherapy-related hand-foot syndrome. In addition, this article also focuses on the prevention and care strategies, health education, traditional Chinese and Western medicine treatments for hand-foot skin reactions, etc, aiming to reduce patients' symptoms, improve their quality of life, and improve their treatment compliance. At the same time, the existing problems and future development trends of hand-foot skin reactions in liver cancer targeted therapy are summarized, with a view to providing a comprehensive reference basis for clinicians and nursing workers, and for the prevention and management of hand-foot skin reactions related to liver cancer targeted drug treatment.