Hepatocellular carcinoma with macrovascular invasion: need a personalized medicine for this complicated event
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ABSTRACT:
SUBMITTER: Hwang H
PROVIDER: S-EPMC10839729 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:Over the past several years, the success of genome-wide association studies (GWAS) and pharmacogenomics has gradually begun to enable personalized medicine in some fields. In the field of liver diseases, host genetic factors are now very useful in clinical practice for predicting treatment outcome and adverse reactions for pegylated interferon plus ribavirin combination therapy against chronic hepatitis C virus (HCV) infection. Recently, three virus-related hepatocellular carcinoma (HCC) GWAS were reported from Asia. One study examined hepatitis B virus-related HCC in China, where hepatitis B is very prevalent, and the other two examined HCV-related HCC in Japan. We identified a common variant in the DEPDC5 locus associated with HCV-related HCC, and another group identified an association involving the MICA locus. In this review, we compare the results of these GWAS and earlier candidate gene studies. Further research is needed to determine the role of these single nucleotide polymorphisms on HCC risk, but identification of these markers could make it possible to assess the magnitude of the risk of cancer based on each patient's genetic background. Consideration of the genetic background of the patients will likely play a role in personalized medicine for HCC, and understanding the mechanism underlying the association could suggest novel promising therapeutic targets in the future.
| S-EPMC7659374 | biostudies-literature
Project description:BackgroundTumoral macrovascular invasion (MVI) of hepatic and/or portal vein branches is a common phenomenon in hepatocellular carcinoma (HCC) and is associated with poorer prognosis when compared to HCC without MVI.SummaryCurrent international guidelines for the management of HCC recommend sorafenib as the only treatment option in case of MVI. Despite guideline recommendations, several alternative options have been tested to manage HCC with MVI: surgery, transarterial chemoembolization, external or internal radiation, hepatic arterial infusion chemotherapy, percutaneous treatment, cryotherapy, or the combination of two or more of these strategies, with or without sorafenib. Here we will provide a comprehensive state-of-the-art review for the management of this challenging clinical entity based on the most recent available data.Key messagesThere is a growing body of evidence suggesting that alternative strategies to standard-of-care sorafenib might improve survival in patients with advanced HCC with MVI but the level of evidence remains weak. Randomized phase III trials are ongoing and will hopefully provide information leading towards a more personalized treatment algorithm.
| S-EPMC5704715 | biostudies-literature
Project description:Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality in Taiwan. Some patients with HCC are diagnosed with macrovascular invasion (MVI), which is associated with a poorer prognosis. In Taiwan, sorafenib is the first-line therapy for patients with advanced HCC. However, the efficacy of adjuvant sorafenib therapy remains unclear for the subset of patients with HCC and MVI who are eligible for surgery. Therefore, we investigated the potential benefit of adjuvant sorafenib therapy for patients with HCC and MVI after surgery. Our study showed that the lack of improved PFS or OS of adjuvant sorafenib challenged the therapeutic benefit of postoperative sorafenib. Alcohol consumption and an α-fetoprotein level of ≥400 ng/mL were independent predictors of overall survival (OS); however, adjuvant sorafenib therapy was not a predictor of progression-free survival (PFS) or OS. In conclusion, our study indicated that adjuvant sorafenib therapy did not provide PFS or OS benefits in patients with HCC and MVI.
| S-EPMC10742418 | biostudies-literature
Project description:BackgroundThe indications for liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) continue to evolve. The aim of this study was to report outcomes in patients who underwent living donor liver transplantation (LDLT) for HCC outside traditional criteria including macrovascular invasion (MVI).MethodsWe reviewed outcomes in patients who met the University of California San Francisco (UCSF) criteria (n = 159) and our center-specific criteria (UCSF+) (largest tumor diameter ≤ 10 cm, any tumor number, AFP ≤ 1000 ng/ml) (n = 58). We also assessed outcomes in patients with MVI (n = 27).ResultsThe median follow was 28 (10.6-42.7) months. The 5 year overall survival and risk of recurrence (RR) in the UCSF and UCSF + group was 71% vs 69% (P = 0.7) and 13% vs 36% (P = 0.1) respectively. When patients with AFP > 600 ng/ml were excluded from the UCSF + group, RR was 27% (P = 0.3). Among patients with MVI who had downstaging (DS), 4/5(80%) in low-risk group (good response and AFP ≤ 100 ng/ml) and 2/10 (20%) in the high-risk group (poor response or AFP > 100 ng/ml) were alive at the last follow-up. When DS was not feasible, 3/3 (100%) in the low-risk group (AFP ≤ 100 ng/ml + Vp1-2 MVI) and 1/9 (9.1%) in the high-risk group (AFP > 100 or Vp3 MVI) were alive. The 5 year OS in the low-risk MVI group was 85% (P = 0.003).ConclusionWith inclusion of AFP, response to downstaging and degree of MVI, acceptable survival can be achieved with LDLT for HCC outside traditional criteria.
| S-EPMC8752562 | biostudies-literature
Project description:Vascular invasion is considered as the critical risk factors for tumor recurrence of hepatocellular carcinoma (HCC). To reveal the molecular mechanisms underlying macrovascular invasion (MaVI) and metastasis in HCC, we performed an iTRAQ based proteomic study to identify notably dysregulated proteins in 53 HCC patients with differential vascular invasion. In patients with MaVI, 47 proteins were significantly down-regulated in HCC tumor tissue. More importantly, 30 of them were not changed in HCC without MaVI. Gene ontology analysis of these 47 proteins shows the top 3 enriched pathways are urea cycle, gluconeogenesis and arginine biosynthetic process. We validated 9 remarkably dysregulated candidates in HCC patients with MaVI by Western blot, including 8 down-regulated proteins (CPS1, ASS1, ASL, ARG1, BHMT, DMGDH, Annexin A6 and CES1) and 1 up-regulated protein (CKAP4). Furthermore, dysregulation of CPS1, ASL and ARG1, key enzymes involved in urea cycle, together with Annexin A6 and CES1, major proteins in regulating cholesterol homeostasis and fatty acid ester metabolism were verified using immunohistochemical staining. The significant down-regulation of urea cycle generates clinically relevant proteomic signature in HCC patients with macrovascular invasion, which may provide possible insights into the molecular mechanisms of metastasis and new therapeutic targets of HCC.
2022-03-02 | PXD011846 | Pride
Project description:The study aimed to investigate the potential of traditional Chinese medicine (TCM) in reducing the risk of macrovascular invasion (MVI) in Chinese patients with hepatocellular carcinoma (HCC). This retrospective analysis involved 2,267 HCC patients treated at our hospital. Propensity score (PS) matching was used to compare TCM users (n = 485) with non-users (n = 485) in terms of age, Barcelona Clinic Liver Cancer (BCLC) staging, type of treatment, and AFP. The impact of TCM on the hazard ratio (HR) of MVI was evaluated using a Cox multivariate regression model. The efficacy of TCM therapy on MVI was further examined using the log-rank test. The analysis revealed that TCM medication was a significant protective factor for MVI in HCC patients, as evidenced by the Cox analysis (adjusted HR = 0.496, 95% CI: 0.387-0.635, p < 0.001). After PS matching, the Kaplan-Meier curve demonstrated a lower occurrence rate of MVI in TCM users compared to non-users. The study findings suggest that TCM treatment has the potential to decrease the incidence of MVI in HCC patients, irrespective of etiology, BCLC staging, liver function, or treatment type. Notably, as the use of TCM increased, the percentage of MVI in patients showed a gradual decrease, indicating the potential of TCM therapy as a successful strategy for preventing MVI.
| S-EPMC10923102 | biostudies-literature
Project description:BackgroundModels predicting future macrovascular invasion in hepatocellular carcinoma are constructed to assist timely interventions.MethodsA total of 366 HCC cases were retrospectively collected from five Chinese hospitals between April 2007 and November 2016: the training dataset comprised 281 patients from four hospitals; the external validation dataset comprised 85 patients from another hospital. Multi-task deep learning network-based models were constructed to predict future macrovascular invasion. The discrimination, calibration, and decision curves were compared to identify the best model. We compared the time to macrovascular invasion and overall survival using the best model and related image heterogeneity scores (H-score). Then, we determined the need for a segmentation subnet or the replacement deep learning algorithm by logistic regression in screening clinical/radiological factors. Finally, an applet was constructed for future application.FindingsThe best model combined clinical/radiological factors and radiomic features. It achieved best discrimination (areas under the curve: 0·877 in the training dataset and 0·836 in the validation dataset), calibration, and decision curve. Its performance was not affected by the treatments and disease stages. The subgroups had statistical significance for time to macrovascular invasion (training: hazard ratio [HR] = 0·073, 95% confidence interval [CI]: 0·032-0·167, p < 0·001 and validation: HR = 0·090, 95%CI: 0·022-0·366, p < 0·001) and overall survival (training: HR = 0·344, 95%CI: 0·246-0·547, p < 0·001 and validation: HR = 0·489, 95%CI: 0·279 - 0·859, p = 0·003). Similar results were achieved when the patients were subdivided by the H-score. The subnet for segmentation and end-to-end deep learning algorithms improved the performance of the model.InterpretationOur multi-task deep learning network-based model successfully predicted future macrovascular invasion. In high-risk populations, besides the current first-line treatments, more therapies may be explored for macrovascular invasion.
| S-EPMC8668827 | biostudies-literature
Project description:Background: The purpose of our dynamic nomogram is to help clinical select hepatocellular carcinoma (HCC) patients with transarterial chemoembolization (TACE) treatment advantages. Methods: In total, 1,135 patients with HCC admitted to the Beijing Ditan Hospital of Capital Medical University were enrolled in this study. We used a 7:3 random splits between a training set (n=796) and a validation set (n=339). The dynamic nomogram was established by multiple logistic regression and evaluated by the C-indices. We generated calibration plots, decision analysis curve and a clinical impact curve to assess the clinical usefulness of the nomogram. Macrovascular invasion (MVI) incidence curves were constructed using the Kaplan-Meier method and compared by the log-rank test. Results: Multivariate logistic regression analysis identified six risk factors independently associated with MVI: BCLC staging B vs 0-A (hazard ratio (HR): 2.350, 95% confidence interval (CI): 1.222-4.531; P = 0.010) and staging C vs 0-A (HR: 3.652, 95% CI: 1.212-11.184; P = 0.022), treatment -TACE (HR: 2.693, 95%CI: 1.824-3.987; P < 0.001), tumour size ≥3cm (HR: 2.239, 95%CI: 1.452-3.459; P < 0.001), ɣ-GGT ≥60 (HR: 1.685, 95%CI: 1.100-2.579; P = 0.016), AFP ≥400 (HR: 2.681, 95%CI: 1.692-4.248; P < 0.001) and CRP ≥5 (HR: 3.560, 95%CI: 2.361-5.388; P < 0.001). The C-indices was 0.817 and 0.829 in the training and validation sets, respectively. The calibration curves showed good agreement between the predicted probability and the actual probability by the dynamic nomogram. Conclusions: Our study developed and validated a dynamic nomogram including BCLC staging, treatment modality, tumour size, and three laboratory parameters (ɣ-GGT, AFP and CRP). It has good discrimination and accuracy, and provides a simple and reliable basis for clinical decision-making.
| S-EPMC8990408 | biostudies-literature
Project description:Macroscopic vascular invasion (MVI) is a poor prognostic factor in hepatocellular carcinoma (HCC). Hepatic arterial infusion chemotherapy (HAIC) is a promising treatment in MVI-HCC. However, it is not clear which regimens are suitable for HAIC. In this study, we aimed to compare the therapeutic effects between New FP (a fine-powder cisplatin suspended with lipiodol plus 5-fluorouracil) and low dose FP (LFP/cisplatin plus 5-fluorouracil) in the treatment of MVI-HCC patients with Child-Pugh class A. New FP is a regimen that consists of a fine-powder cisplatin suspended with lipiodol and 5-fluorouracil. Fifty-one patients were treated with LFP, and 99 patients were New FP. We compared the therapeutic effects of LFP and New FP and assessed factors that associated with the therapeutic effects. The median survival and progression-free survival times of LFP and New FP were 16.1/24.7 and 5.4/8.8 months, respectively (p < 0.05, p < 0.05). The complete response (29%) and objective response rate (76%) of New FP were significantly higher than those of LFP (p < 0.001, p < 0.01). Factors associated with better therapeutic response were better ALBI-grade and New FP treatment choice. New FP is a more powerful regimen than LFP in HAIC for MVI-HCC. New FP represents a recommended HAIC regimen for the treatment of patients with MVI-HCC.
| S-EPMC8431395 | biostudies-literature
Project description:Introduction: Transarterial chemoembolization (TACE) is an optional treatment for hepatocellular carcinoma (HCC) patients with macrovascular invasion (MVI) and without extrahepatic metastasis (EHM). As a recently emerging approach, the efficacy of hepatic arterial infusion chemotherapy (HAIC) compared with TACE in this group of patients is unclear. Methods: Between December 2016 and June 2020, patients diagnosed with HCC with MVI and without EHM who underwent TACE (n=91) or HAIC (n=190) as their initial treatment were included. Propensity score matching (PSM) was used to reduce selection bias and other imbalances. The objective response rate (ORR), overall survival (OS), progression-free survival (PFS), rate of subsequent resection, and safety were compared between groups. Results: Seventy-seven pairs of patients were matched after PSM. The ORR was higher in the HAIC group than that in the TACE group (29.9% vs. 9.1%, P = 0.013). The median PFS of patients in the HAIC group was longer than that of the patients in the TACE group (4.7 vs. 1.4 months, P = 0.002), but there was no significant difference in the median OS between the groups (19.6 vs. 18.1 months, P = 0.122). HAIC also showed a better safety profile than TACE. Conclusions: HAIC is an effective and safe option for treating HCC patients with MVI and without EHM compared to TACE.
| S-EPMC11898842 | biostudies-literature