Treatment strategies for hepatocellular carcinoma with extrahepatic metastasis.
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ABSTRACT:
SUBMITTER: Long HY
PROVIDER: S-EPMC8316954 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Identification of extrahepatic metastases (EHM) of hepatocellular carcinoma (HCC) has been paradoxically increasing due to an increase in the survival of HCC patients. However, metastasis of HCC to the skeletal muscle tissue is extremely rare. We describe a unique case of HCC metastasizing to the paravertebral muscle. A 55-year-old man with a history of hepatitis B cirrhosis underwent partial liver resection with complete removal of HCC. Three months later, a computed tomography (CT) scan showed intrahepatic recurrence. The tumors were treated with yttrium-90 microspheres, trans-catheter arterial chemoembolization, and sorafenib. Six months later, a CT scan showed an enhancing lesion of the left paravertebral muscle that on biopsy were consistent with metastatic HCC. The tumor was treated with stereotactic hypo-fractionated image-guided radiation therapy (SHFRT). A follow-up scan 3 mo post-radiotherapy revealed a stable appearance of the paravertebral muscle metastasis. Because of the progression in the intrahepatic tumors, the patient was treated with capecitabine, which was changed to dasatinib 6 mo later. The patient passed away three years after the primary surgical resection. Management of EHM poses an extreme challenge. This is the first case of HCC with EHM to the paravertebral muscle in which stability of disease was achieved using SHFRT. This case highlights the importance of early detection of hepatitis B viral infection and initiation of anti-viral therapy to decrease recurrence of HCC and prevent EHM.
| S-EPMC5550763 | biostudies-other
Project description:Background and aimExtrahepatic metastasis (EHM) of hepatocellular carcinoma (HCC) leads to a worse prognosis. We aimed to develop a nomogram based on noninvasive pretreatment clinical data to predict EHM of HCC sooner.MethodsThree cohorts containing 1820, 479, and 988 HCC patients were enrolled from three hospitals in different regions in Taiwan and served as the training and validation cohorts. Pretreatment clinical data were analyzed by Cox regression modeling for independent risk factors of EHM.ResultsPlatelet count ≥ 200 × 103/μL, serum alfa-fetoprotein ≥ 100 ng/dL, tumor size ≥ 3 cm, tumor number > 1, and macrovascular invasion were independent risk factors for EHM and were used to develop a nomogram. This nomogram had concordance indices of 0.733 (95% confidence interval [CI]: 0.688-0.778) and 0.739 (95% CI: 0.692-0.787) for the prediction of EHM during a 5-year follow-up duration in the training and validation cohorts, respectively. A nomogram score > 61 implied a high risk of EHM (hazard ratio [HR] = 3.83; 95% CI: 2.77-5.31, P < 0.001).ConclusionWe have developed a nomogram that could accurately predict EHM of HCC and be readily available for formulating individualized treatment for all individual HCC patients to improve therapeutic efficacy.
| S-EPMC6386739 | biostudies-literature
Project description: Not available
| S-EPMC10432283 | biostudies-literature
Project description:Hepatocellular carcinoma (HCC) is the most frequent liver cancer with high lethality and low five-year survival rates leading to a substantial worldwide burden for healthcare systems. HCC initiation and progression are favored by different etiological risk factors including hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, non-/and alcoholic fatty liver disease (N/AFLD), and tobacco smoking. In molecular pathogenesis, endogenous alteration in genetics (TP53, TERT, CTNNB1, etc.), epigenetics (DNA-methylation, miRNA, lncRNA, etc.), and dysregulation of key signaling pathways (Wnt/β-catenin, JAK/STAT, etc.) strongly contribute to the development of HCC. The multitude and complexity of different pathomechanisms also reflect the difficulties in tailored medical therapy of HCC. Treatment options for HCC are strictly dependent on tumor staging and liver function, which are structured by the updated Barcelona Clinic Liver Cancer classification system. Surgical resection, local ablative techniques, and liver transplantation are valid and curative therapeutic options for early tumor stages. For multifocal and metastatic diseases, systemic therapy is recommended. While Sorafenib had been the standalone HCC first-line therapy for decades, recent developments had led to the approval of new treatment options as first-line as well as second-line treatment. Anti-PD-L1 directed combination therapies either with anti-VEGF directed agents or with anti-CTLA-4 active substances have been implemented as the new treatment standard in the first-line setting. However, data from clinical trials indicate different responses on specific therapeutic regimens depending on the underlying pathogenesis of hepatocellular cancer. Therefore, histopathological examinations have been re-emphasized by current international clinical guidelines in addition to the standardized radiological diagnosis using contrast-enhanced cross-sectional imaging. In this review, we emphasize the current knowledge on molecular pathogenesis of hepatocellular carcinoma. On this occasion, the treatment sequences for early and advanced tumor stages according to the recently updated Barcelona Clinic Liver Cancer classification system and the current algorithm of systemic therapy (first-, second-, and third-line treatment) are summarized. Furthermore, we discuss novel precautional and pre-therapeutic approaches including therapeutic vaccination, adoptive cell transfer, locoregional therapy enhancement, and non-coding RNA-based therapy as promising treatment options. These novel treatments may prolong overall survival rates in regard with quality of life and liver function as mainstay of HCC therapy.
| S-EPMC9775527 | biostudies-literature
Project description:BackgroundResistance to therapy remains a major cause of the failure of cancer treatment. A major challenge in cancer therapy is to design treatment strategies that circumvent the higher-level homeostatic functions of the robust cellular network that occurs in resistant cells. There is a lack of understanding of mechanisms responsible for the development of cancer and the basis of therapy-resistance mechanisms. Cellular signaling networks have an underlying architecture guided by universal principles. A robust system, such as cancer, has the fundamental ability to survive toxic anticancer drug treatments or a stressful environment mainly due to its mechanisms of redundancy. Consequently, inhibition of a single component/pathway would probably not constitute a successful cancer therapy.ResultsWe developed a computational method to study the mechanisms of redundancy and to predict communications among the various pathways based on network theory, using data from gene expression profiles of hepatocellular carcinoma (HCC) of patients with poor and better prognosis cancers. Our results clearly indicate that immune system pathways tightly regulate most cancer pathways, and when those pathways are targeted by drugs, the network connectivity is dramatically changed. We examined the main HCC targeted treatments that are currently being evaluated in clinical trials. One prediction of our study is that Sorafenib combined with immune system treatments will be a more effective combination strategy than Sorafenib combined with any other targeted drugs.ConclusionsWe developed a computational framework to analyze gene expression data from HCC tumors with varying degrees of responsiveness and non-tumor samples, based on both Gene and Pathway Co-expression Networks. Our hypothesis is that redundancy is one of the major causes of drug resistance, and can be described as a function of the network structure and its properties. From this perspective, we believe that integration of the redundant variables could lead to the development of promising new methodologies to selectively identify and target the most significant resistance mechanisms of HCC. We describe three mechanisms of redundancy based on their levels of generalization and study the possible impact of those redundancy mechanisms on HCC treatments.
| S-EPMC4236726 | biostudies-literature
Project description:The majority of hepatocellular carcinoma (HCC) cases are diagnosed at an advanced stage. Currently, there are only a few therapeutic methods available for patients with advanced HCC and extrahepatic metastasis (EHM). Systemic chemotherapy, such as FOLFOX4 (infusions of fluorouracil, leucovorin, and oxaliplatin), has been reported for treating advanced HCC with EHM, but its effectiveness is very poor. In this randomized, double-blind, placebo-controlled study, we aimed to assess the efficacy and safety of FOLFOX4 with all-trans-retinoic acid (ATRA) as a palliative treatment for HCC patients with EHM, compared to FOLFOX4 with a placebo. The primary endpoint was overall survival (OS), and subsequently, an exploratory model was developed based on bioinformatics to predict the efficacy of FOLFOX4-ATRA treatment. A total of 108 patients were randomly assigned in a 1:1 ratio to receive either FOLFOX4-ATRA or FOLFOX4-placebo. The intention-to-treat (ITT) population showed a median OS of 16.2 months for the FOLFOX4-ATRA group, compared with 10.7 months for the FOLFOX4-placebo group (HR 0.56, 95% CI 0.33-0.93; p = 0.025). The median progression-free survival (PFS) was 7.1 months for the FOLFOX4-ATRA group and 4.2 months for the FOLFOX4-placebo group (HR 0.62, 95% CI 0.41-0.94; p = 0.024). A panel of proteins with unique upregulation during complete response (CR) (SOD3, TTR, SSC5D, GP5, IGKV1D-33) and partial response (PR) (TGFB1, GSS, IGHV5-10-1) effectively predicted CR and PR in patients treated with FOLFOX4-ATRA, as compared to FOLFOX4-placebo. The results suggest that FOLFOX4-ATRA is a safe and effective treatment for patients with advanced HCC and EHM in eastern China.
| S-EPMC10522582 | biostudies-literature
Project description:PurposeTo develop and validate a radiomics machine learning (Rad-ML) model based on preoperative MRI to predict extrahepatic metastasis (EHM) in hepatocellular carcinoma (HCC) patients receiving transarterial chemoembolization (TACE) treatment.MethodsA total of 355 HCC patients who received multiple TACE procedures were split at random into a training set and a test set at a 7:3 ratio. Radiomic features were calculated from tumor and peritumor in arterial phase and portal venous phase, and were identified using intraclass correlation coefficient, maximal relevance and minimum redundancy, and least absolute shrinkage and selection operator techniques. Cox regression analysis was employed to determine the clinical model. The best-performing algorithm among eight machine learning methods was used to construct the Rad-ML model. A nomogram combining clinical and Rad-ML parameters was used to develop a combined model. Model performance was evaluated using C-index, decision curve analysis, calibration plot, and survival analysis.ResultsIn clinical model, elevated neutrophil to lymphocyte ratio and alpha-fetoprotein were associated with faster EHM. The XGBoost-based Rad-ML model demonstrated the best predictive performance for EHM. When compared to the clinical model, both the Rad-ML model and the combination model performed better (C-indexes of 0.61, 0.85, and 0.86 in the training set, and 0.62, 0.82, and 0.83 in the test set, respectively). However, the combined model's and the Rad-ML model's prediction performance did not differ significantly. The most influential feature was peritumoral waveletHLL_firstorder_Minimum in AP, which exhibited an inverse relationship with EHM risk.ConclusionsOur study suggests that the preoperative MRI-based Rad-ML model is a valuable tool to predict EHM in HCC patients treated with TACE.
| S-EPMC10859286 | biostudies-literature
Project description:BackgroundVascular invasion (VI) indicates highly invasive tumor biological behavior and is a major determining factor of poor survival and high risk of metastasis in hepatocellular carcinoma (HCC). Epidemiological evidence of the association between pretherapeutic platelet count (PLT) and the risk of VI and extrahepatic metastasis in HCC remains controversial.MethodsA systematic retrieval was executed in databases of PubMed, Embase, and Web of Science until Dec 2022. Effect size and 95% confidence interval (CI) were extracted or estimated to synthetically investigate the effects of pretherapeutic PLT on VI and extrahepatic metastasis. Meta-analyses were performed by using a random or a fixed effects model.ResultsFinally, the current meta-analysis included 15 studies with a total of 12,378 HCC patients. It was shown that, patients with a higher pretherapeutic level of PLT had a significantly increased risk of VI (11 studies,8,759 patients; OR = 1.44, 95%CI: 1.02-2.02) and extrahepatic metastasis (6 studies,8, 951 patients; OR = 2.51, 95% CI: 2.19-2.88) in comparison with patients with a lower PLT. Funnel plots and Begg's tests indicated that there were no significant publication biases.ConclusionThis meta-analysis shows that pretherapeutic elevated PLT is associated with an increased risk of VI and extrahepatic metastasis in HCC.
| S-EPMC10966694 | biostudies-literature
Project description:Abstract Liver cancer is highly malignant, has a low sensitivity to chemotherapy, and is associated with poor patient prognosis. The last 3 years have seen the emergence of promising targeted therapies for the treatment of hepatocellular carcinoma (HCC). For over 10 years, before the discovery of lenvatinib, sorafenib was only first-line therapeutic agent available for the treatment of advanced HCC. However, several clinical studies have shown that a considerable proportion liver cancer patients are insensitive to sorafenib. Very few patients actually substantially benefit from treatment with sorafenib, and the overall efficacy of the drug has not been satisfactory; therefore, sorafenib has attracted considerable research attention. This study, which is based on previous studies and reports, reviews the potential mechanisms underlying sorafenib resistance and summarizes combination therapies and potential drugs that can be used to sensitize HCC cells to sorafenib.
| S-EPMC9939808 | biostudies-literature
Project description:Fibrolamellar hepatocellular carcinoma (FL-HCC) is a rare primary liver tumor that typically presents at an advanced stage in early adolescents and adults with no underlying liver disease. Surgical resection is the first-line treatment, and patients who are not surgical candidates face limited treatment options with poor long-term outcomes. Herein we report the first documented, technically successful treatment of FL-HCC with extrahepatic spread using transarterial radioembolization (TARE) in a 16-year-old male patient with surgically unresectable disease. Subsequent imaging revealed tumor necrosis and a 20% reduction in size, and the patient survived 20 months post-treatment, a marked improvement relative to historical data in the literature. Further research should examine the potential role of yttrium-90 TARE in the treatment of FL-HCC patients with metastatic disease.
| S-EPMC7566208 | biostudies-literature