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JHEP Reports : Innovation in Hepatology Oct 2021Hepatocellular carcinoma (HCC) usually arises in the context of a chronically damaged liver. Liver functional estimation is of paramount importance in clinical decision... (Review)
Review
Hepatocellular carcinoma (HCC) usually arises in the context of a chronically damaged liver. Liver functional estimation is of paramount importance in clinical decision making. The Child-Pugh score (CPS) can be used to categorise patients into 3 classes (A to C) based on the severity of liver functional impairment according to 5 parameters (albumin, bilirubin, prothrombin time, presence of ascites and hepatic encephalopathy). The albumin-bilirubin (ALBI) grade has emerged as an alternative, reproducible and objective measure of liver functional reserve in patients with HCC, defining worsening liver impairment across 3 grades (I to III). The ALBI score can identify different subgroups of patients with different prognoses across the diverse Barcelona Clinic Liver Cancer stages and CP classes, making it an appealing clinical predictor. In patients treated with potentially curative approaches (resection, transplantation, radiofrequency ablation, microwave ablation), ALBI grade has been shown to correlate with survival, tumour relapse, and post-hepatectomy liver failure. ALBI grade also predicts survival, toxicity and post-procedural liver failure in patients treated with transarterial chemoembolisation, radioembolisation, external beam radiotherapy as well as multi-kinase inhibitors (sorafenib, lenvatinib, cabozantinib, regorafenib) and immune checkpoint inhibitor therapy. In this review, we summarise the body of evidence surrounding the role of ALBI grade as a biomarker capable of optimising patient selection and therapeutic sequencing in HCC.
PubMed: 34505035
DOI: 10.1016/j.jhepr.2021.100347 -
Gut Aug 2020This trial compared the efficacy and safety of transarterial chemoembolisation (TACE) plus sorafenib with TACE alone using a newly established TACE-specific endpoint and... (Randomized Controlled Trial)
Randomized Controlled Trial
Randomised, multicentre prospective trial of transarterial chemoembolisation (TACE) plus sorafenib as compared with TACE alone in patients with hepatocellular carcinoma: TACTICS trial.
OBJECTIVE
This trial compared the efficacy and safety of transarterial chemoembolisation (TACE) plus sorafenib with TACE alone using a newly established TACE-specific endpoint and pre-treatment of sorafenib before initial TACE.
DESIGN
Patients with unresectable hepatocellular carcinoma (HCC) were randomised to TACE plus sorafenib (n=80) or TACE alone (n=76). Patients in the combination group received sorafenib 400 mg once daily for 2-3 weeks before TACE, followed by 800 mg once daily during on-demand conventional TACE sessions until time to untreatable (unTACEable) progression (TTUP), defined as untreatable tumour progression, transient deterioration to Child-Pugh C or appearance of vascular invasion/extrahepatic spread. Co-primary endpoints were progression-free survival (PFS), which is not a conventional one but defined as TTUP, or time to any cause of death plus overall survival (OS). Multiplicity was adjusted by gatekeeping hierarchical testing.
RESULTS
Median PFS was significantly longer in the TACE plus sorafenib than in the TACE alone group (25.2 vs 13.5 months; p=0.006). OS was not analysed because only 73.6% of OS events were reached. Median TTUP (26.7 vs 20.6 months; p=0.02) was also significantly longer in the TACE plus sorafenib group. OS at 1 year and 2 years in TACE plus sorafenib group and TACE alone group were 96.2% and 82.7% and 77.2% and 64.6%, respectively. There were no unexpected toxicities.
CONCLUSION
TACE plus sorafenib significantly improved PFS over TACE alone in patients with unresectable HCC. Adverse events were consistent with those of previous TACE combination trials.
TRIAL REGISTRATION NUMBER
NCT01217034.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Combined Modality Therapy; Disease Progression; Female; Humans; Liver Neoplasms; Male; Middle Aged; Progression-Free Survival; Prospective Studies; Sorafenib; Survival Rate
PubMed: 31801872
DOI: 10.1136/gutjnl-2019-318934 -
JHEP Reports : Innovation in Hepatology Aug 2022Hepatocellular carcinoma (HCC) accounts for 90% of liver tumours and is one of the leading causes of mortality. Cirrhosis due to viral hepatitis, alcohol or... (Review)
Review
Hepatocellular carcinoma (HCC) accounts for 90% of liver tumours and is one of the leading causes of mortality. Cirrhosis due to viral hepatitis, alcohol or steatohepatitis is the major risk factor, while liver dysfunction due to cirrhosis is a deciding factor in its treatment. The treatment modalities for HCC include liver transplant, hepatectomy, radiofrequency ablation, transarterial chemoembolisation, transarterial radioembolisation, targeted therapy, immunotherapy, and radiation therapy. The role of radiation therapy has been refined with the increasing use of stereotactic body radiation therapy (SBRT). Trials over the past two decades have shown the efficacy and safety of SBRT in recurrent and definitive HCC, leading to its acceptance and adoption in some more recent guidelines. However, high quality level I evidence supporting its use is currently lacking. Smaller randomised trials of external beam radiation therapy suggest high efficacy of radiation therapy compared to other treatments for patients with unresectable HCC, and phase III trials comparing SBRT with other modalities are ongoing. In this review, we discuss the rationale for SBRT in HCC and present evidence on its efficacy, associated toxicity, and technological advances.
PubMed: 35860434
DOI: 10.1016/j.jhepr.2022.100498 -
Cancers Jul 2019Although transcatheter arterial chemoembolization (TACE) is the standard of care for intermediate-stage hepatocellular carcinoma (HCC), this is a largely heterogeneous...
Lenvatinib as an Initial Treatment in Patients with Intermediate-Stage Hepatocellular Carcinoma Beyond Up-To-Seven Criteria and Child-Pugh A Liver Function: A Proof-Of-Concept Study.
Although transcatheter arterial chemoembolization (TACE) is the standard of care for intermediate-stage hepatocellular carcinoma (HCC), this is a largely heterogeneous disease that includes a subgroup of patients who do not benefit from TACE. The treatment strategy for this subgroup of patients currently remains an unmet need in clinical practice. Here, we performed a proof-of-concept study that lenvatinib may be a more favorable treatment option over TACE as an initial treatment in intermediate-stage HCC patients with large or multinodular tumours exceeding the up-to-seven criteria. This proof-of-concept study included 642 consecutive patients with HCC initially treated with lenvatinib or conventional TACE (cTACE) between January 2006 and December 2018. Of these patients, 176 who received lenvatinib or cTACE as an initial treatment and met the eligibility criteria (unresectable, beyond the up-to-seven criteria, no prior TACE/systemic therapy, no vascular invasion, no extrahepatic spread and Child-Pugh A liver function) were selected for the study. Propensity score matching was used to adjust for patient demographics. After propensity-score matching, the outcome of 30 patients prospectively treated with lenvatinib (14 in clinical trials, one in an early access program and 15 in real world settings) and 60 patients treated with cTACE as the initial treatment was compared. The change of albumin-bilirubin (ALBI) score from baseline to the end of treatment were -2.61 to -2.61 for 30 patients in the lenvatinib group ( = 0.254) and -2.66 to -2.09 in the cTACE group ( < 0.01), respectively. The lenvatinib group showed a significantly higher objective response rate (73.3% vs. 33.3%; < 0.001) and significantly longer median progression-free survival than the cTACE group (16.0 vs. 3.0 months; < 0.001). Overall survival was significantly longer in the lenvatinib group than in the cTACE group (37.9 vs. 21.3 months; hazard ratio: 0.48, < 0.01). In patients with large or multinodular intermediate-stage HCC exceeding the up-to-seven criteria with Child-Pugh A liver function, who usually do not benefit from TACE, lenvatinib provides a more favorable outcome than TACE.
PubMed: 31370183
DOI: 10.3390/cancers11081084 -
World Journal of Gastroenterology Mar 2014Transarterial chemoembolization (TACE) is the first line treatment for patients with intermediate stage hepatocellular carcinoma but is also increasingly being used for... (Review)
Review
Transarterial chemoembolization (TACE) is the first line treatment for patients with intermediate stage hepatocellular carcinoma but is also increasingly being used for patients on the transplant waiting list to prevent further tumor growth. Despite its widespread use, TACE remains an unstandardized procedure, with variation in type and size of embolizing particles, type and dose of chemotherapy and interval between therapies. Existing evidence from randomized controlled trials suggest that bland transarterial embolization (TAE) has the same efficacy with TACE. In the current article, we review the use of TACE and TAE for hepatocellular carcinoma and we focus on the evidence for their use.
Topics: Angiography; Antineoplastic Agents; Arteries; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Combined Modality Therapy; Embolization, Therapeutic; Humans; Liver Neoplasms; Neoadjuvant Therapy; Portal Vein; Prognosis; Randomized Controlled Trials as Topic; Treatment Outcome; Venous Thrombosis; Waiting Lists
PubMed: 24695579
DOI: 10.3748/wjg.v20.i12.3069 -
Contemporary Oncology (Poznan, Poland) 2017The liver is an organ that, due to vascularisation and functions, is prone to metastases. Most liver metastases are observed in cases of gastrointestinal cancers in:... (Review)
Review
The liver is an organ that, due to vascularisation and functions, is prone to metastases. Most liver metastases are observed in cases of gastrointestinal cancers in: stomach, colon, gallbladder, and bile ducts. Metastatic lesions are also observed in lung, breast, thyroid, kidney, and pancreatic cancer. One of the best known and most effective ways of liver lesion treatment is Metastasectomy. Unfortunately, lesions are frequently inoperable. Apart from chemotherapy, it is possible to apply local treatment such as TACE (trans-arterial chemoembolisation), RFA (Radio Frequency Ablation), and SBRT (Stereotactic Body Radiation Therapy). One of the newest methods of inoperable lesion treatment is radioembolisation (SIRT). Intravascular administration of microspheres containing radioisotope 90Y allows delivery of a higher dose of radiation directly to the tumour than traditional radiation with an external beam, while maintaining a small dose to healthy liver methods. Conducted clinical studies confirm the efficacy and safety of SIRT. It is an interesting alternative to other ways of treatment.
PubMed: 29416432
DOI: 10.5114/wo.2017.72153 -
Journal of Hepatology May 2015Transarterial chemoembolization (TACE) is the standard of care for patients with intermediate stage hepatocellular carcinoma (BCLC B). Further improvement of the use of... (Review)
Review
Transarterial chemoembolization (TACE) is the standard of care for patients with intermediate stage hepatocellular carcinoma (BCLC B). Further improvement of the use of TACE was the subject of intense clinical research over the past years. The introduction of DEB-TACE brought more technical standardization and reduction of TACE related toxicity. The use of dynamic radiologic response evaluation criteria (EASL, mRECIST), uncovered the prognostic significance of objective tumor response. Finally, new approaches for better patient selection for initial and subsequent TACE treatment schedules will limit the use of TACE to some extent but have the potential to improve outcome for patients at risk for TACE-induced harm.
Topics: Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Humans; Liver; Liver Neoplasms; Outcome Assessment, Health Care; Patient Selection; Prognosis; Radiography; Risk Adjustment
PubMed: 25681552
DOI: 10.1016/j.jhep.2015.02.010 -
Hepatic Oncology Apr 2015This review discusses the current data on Hepasphere™ in the treatment of hepatocellular carcinoma. HepaSphere is a drug-loadable microsphere that can be bound with... (Review)
Review
This review discusses the current data on Hepasphere™ in the treatment of hepatocellular carcinoma. HepaSphere is a drug-loadable microsphere that can be bound with doxorubicin, epirubicin, cisplatin or oxaliplatin. and studies confirm lower systemic exposure to the drug and fewer systemic doxorubicin-related side effects. Studies suggest that this technique is better tolerated than conventional lipiodol-based chemoembolization (c-TACE). In intermediate and early stage hepatocellular carcinoma - nonresponsive to curative treatments - complete response and partial response rates range from 22.2 to 48% and 43.7 to 51%, respectively. Studies with survival as an end-point are needed and head-to-head comparisons with other drug-eluting beads are necessary.
PubMed: 30190994
DOI: 10.2217/hep.15.2