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Advanced therapeutic modalities in hepatocellular carcinoma: Novel insights.

ABSTRACT: Hepatocellular carcinoma (HCC), the most common type of liver cancer, is usually a latent and asymptomatic malignancy caused by different aetiologies, which is a result of various aberrant molecular heterogeneity and often diagnosed at advanced stages. The incidence and prevalence have significantly increased because of sedentary lifestyle, diabetes, chronic infection with hepatotropic viruses and exposure to aflatoxins. Due to advanced intra- or extrahepatic metastasis, recurrence is very common even after radical resection. In this paper, we highlighted novel therapeutic modalities, such as molecular-targeted therapies, targeted radionuclide therapies and epigenetic modification-based therapies. These topics are trending headlines and their combination with cell-based immunotherapies, and gene therapy has provided promising prospects for the future of HCC treatment. Moreover, a comprehensive overview of current and advanced therapeutic approaches is discussed and the advantages and limitations of each strategy are described. Finally, very recent and approved novel combined therapies and their promising results in HCC treatment have been introduced.

SUBMITTER: Shokoohian B

PROVIDER: S-EPMC8435417 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Advanced therapeutic modalities in hepatocellular carcinoma: Novel insights.

Shokoohian Bahare B Negahdari Babak B Aboulkheyr Es Hamidreza H Abedi-Valugerdi Manuchehr M Baghaei Kaveh K Agarwal Tarun T Maiti Tapas Kumar TK Hassan Moustapha M Najimi Mustapha M Vosough Massoud M

Journal of cellular and molecular medicine 20210823 18

Hepatocellular carcinoma (HCC), the most common type of liver cancer, is usually a latent and asymptomatic malignancy caused by different aetiologies, which is a result of various aberrant molecular heterogeneity and often diagnosed at advanced stages. The incidence and prevalence have significantly increased because of sedentary lifestyle, diabetes, chronic infection with hepatotropic viruses and exposure to aflatoxins. Due to advanced intra- or extrahepatic metastasis, recurrence is very commo ...[more]

PMID: 34423899

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Project description:Methods83 patients with hepatocellular carcinoma (HCC) admitted to the interventional oncology department were randomly divided into two groups. Apatinib and camrelizumab were administered to 42 patients in group A, whereas sorafenib was administered to 41 patients in group B for three months. The clinical efficacy was evaluated in terms of objective response rate (ORR), and disease control rate (DCR). Certain tumor markers like alpha-fetoprotein (AFP), carbohydrate antigen 199 (CA199), carcinoembryonic antigen (CEA), hypoxia-inducible factor (HIF-1), immune function T lymphocyte subsets (CD3+, CD4+, CD8+, CD4+/CD8+) were determined before and after treatment. The serum levels of vascular endothelial growth factor (VEGF), osteopontin (OPN), aspartate aminotransferase (AST), and epidermal growth factor 7 (EGF7)] were observed. The survival time between the two groups was compared, such as progression-free survival (PFS) and median survival (MS). Finally, the toxicity and side effects data were also obtained.ResultsThe ORR and DCR of group A were 69.05% and 88.10%, respectively, which were significantly higher (P<0.05) than group B (ORR=53.66% and DCR=70.73%). After treatment, the AFP, CA199, CEA, and HIF-1 levels of both groups decreased significantly (P<0.05), and the respective biomarker levels of group A were lower than those of group B (P<0.05). Following treatment, CD3+, CD4+, CD4+/CD8+ index in group A significantly increased (P<0.05) while CD8+ level was significantly decreased (P<0.05). Compared to group B, a significant increase was observed in group A's CD3+, CD4+, and CD4+/CD8+ index. There were no significant changes in CD3+, CD4+, CD8+, CD4+/CD8+ indexes before and after treatment in group B (P>0.05). The serum level of VEGF, OPN, EGF-7 and AST indexes of group A&B were decreased significantly (P<0.05). Compared with group B, the VEGF, OPN, EGF7 and AST indexes of group A were significantly reduced (P<0.05). PFS and MS in group A were significantly higher than in group B (P<0.05). There was no significant difference between groups A and B in terms of toxicity and adverse effects (P>0.05).ConclusionIn treating HCC, combining apatinib and camrelizumab can reduce tumor markers, enhance the immune system and curative effect, and prolong patient survival. The underline mechanism is related to the down-regulation of VEGF, OPN and HIF-1 indexes.

Project description:BackgroundSpontaneous rupture of hepatocellular carcinoma (rHCC) poses a life-threatening complication with a mortality rate of 25-75%. Treatment aims at achieving hemostasis and includes options such as trans-arterial embolization, perihepatic packing, and hepatic resection. The optimal treatment remains a subject of debate. Our retrospective review evaluates these treatments and investigates imaging's role in prognosis for rHCC patients.PurposeWe aimed to compare survival outcomes among rHCC patients who received transarterial embolization (TAE), surgery (perihepatic packing, hepatectomy), or best supportive care (BSC), while also identifying predictive imaging factors in these patients.Materials and methodsAll patients diagnosed with rHCC and admitted to Maharaj Nakorn Chiangmai Hospital between January 2012 and December 2021 were included. We reviewed clinical features, imaging results, treatment modalities, and outcomes. In order to balance pretreatment confounders, inverse probability treatment weighting (IPTW) was employed. Flexible parametric survival regression was utilized to compare survival outcomes and identify imaging factors predicting the survival of rHCC patients. Hazard ratios (HR) and the difference in restricted mean survival time (RMST) were reported.ResultAmong the 186 rHCC patients included, we observed 90-day and 1-year mortality rates of 64% and 84%, respectively. Both the TAE and surgery groups exhibited significantly lower 1-year mortality rates compared to BSC. The HR were 0.56 (95% CI 0.33-0.96) for TAE and 0.52 (95% CI 0.28-0.95) for surgery compared to BSC. Both the TAE and surgery also significantly extended the 1-yeaar life expectancy post-initial treatment when compared to BSC, with an RMST difference of + 55.40 days (95% CI 30.18-80.63) for TAE vs. BSC and + 68.43 days (95% CI 38.77-98.09) for surgery vs. BSC. The presence of active contrast extravasation and bleeding in both lobes were independent prognostic factors for 1-year survival.ConclusionsTAE and surgical treatments provide comparable survival benefits for rHCC patients, extending survival time by approximately 2 months compared to best supportive care. We strongly recommend active management for all rHCC patients whenever possible.

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Advanced therapeutic modalities in hepatocellular carcinoma: Novel insights.

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Advanced therapeutic modalities in hepatocellular carcinoma: Novel insights.

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