Cholangiocarcinoma 2020: the next horizon in mechanisms and management

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2020, Volume and Issue: 17(9), P. 557 - 588

Published: June 30, 2020

Abstract Cholangiocarcinoma (CCA) includes a cluster of highly heterogeneous biliary malignant tumours that can arise at any point the tree. Their incidence is increasing globally, currently accounting for ~15% all primary liver cancers and ~3% gastrointestinal malignancies. The silent presentation these combined with their aggressive nature refractoriness to chemotherapy contribute alarming mortality, representing ~2% cancer-related deaths worldwide yearly. current diagnosis CCA by non-invasive approaches not accurate enough, histological confirmation necessary. Furthermore, high heterogeneity CCAs genomic, epigenetic molecular levels severely compromises efficacy available therapies. In past decade, efforts have been made understand complexity develop new diagnostic tools therapies might help improve patient outcomes. this expert Consensus Statement, which endorsed European Network Study Cholangiocarcinoma, we aim summarize critically discuss latest advances in CCA, mostly focusing on classification, cells origin, genetic abnormalities, alterations, biomarker discovery treatments. horizon next decade from 2020 onwards highlighted.

Language: Английский

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Cholangiocarcinoma

Nature Reviews Disease Primers, Journal Year: 2021, Volume and Issue: 7(1)

Published: Sept. 9, 2021

Cholangiocarcinoma (CCA) is a highly lethal adenocarcinoma of the hepatobiliary system, which can be classified as intrahepatic, perihilar and distal. Each anatomic subtype has distinct genetic aberrations, clinical presentations therapeutic approaches. In endemic regions, liver fluke infection associated with CCA, owing to oncogenic effect chronic biliary tract inflammation. other CCA inflammation choledocholithiasis, cholelithiasis, or primary sclerosing cholangitis, but most CCAs have no identifiable cause. Administration anthelmintic drug praziquantel decreases risk from flukes, reinfection common future vaccination strategies may more effective. Some patients are eligible for potentially curative surgical options, such resection transplantation. Genetic studies provided new insights into pathogenesis two aberrations that drive non-fluke-associated intrahepatic fibroblast growth factor receptor 2 fusions isocitrate dehydrogenase gain-of-function mutations, therapeutically targeted. desmoplastic cancer targeting tumour immune microenvironment might promising approach. remains disease further scientific needed improve patient outcomes. system often This Primer reviews epidemiology, pathophysiological mechanisms, diagnosis management cholangiocarcinoma, highlights experience directions.

Language: Английский

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Biliary tract cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up

Annals of Oncology, Journal Year: 2022, Volume and Issue: 34(2), P. 127 - 140

Published: Nov. 10, 2022

Language: Английский

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Systemic therapies for intrahepatic cholangiocarcinoma

Journal of Hepatology, Journal Year: 2020, Volume and Issue: 72(2), P. 353 - 363

Published: Jan. 15, 2020

Language: Английский

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Advances in the treatment of intrahepatic cholangiocarcinoma: An overview of the current and future therapeutic landscape for clinicians

CA A Cancer Journal for Clinicians, Journal Year: 2022, Volume and Issue: 73(2), P. 198 - 222

Published: Oct. 19, 2022

Abstract Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver tumor and remains a fatal malignancy in majority of patients. Approximately 20%–30% patients are eligible for resection, which considered only potentially curative treatment; and, after median survival 53 months has been reported when sequenced with adjuvant capecitabine. For 70%–80% who present locally unresectable or distant metastatic disease, systemic therapy may delay progression, but limited to approximately 1 year. past decade, doublet chemotherapy gemcitabine cisplatin effective first‐line regimen, results from recent use triplet regimens even immunotherapy shift paradigm. More treatment strategies, including those that combine locoregional therapies like radioembolization hepatic artery infusion, have also developed. Molecular therapies, target fibroblast growth factor receptor isocitrate dehydrogenase, recently received US Food Drug Administration approval defined role as second‐line up 40% harboring these actionable genomic alterations, whether they should be setting under investigation. Furthermore, oncology field seeks expand indications immunotherapy, data demonstrated combining durvalumab standard cytotoxic improved ICC. This review focuses on current future strategies ICC treatment, summary literature each modality an algorithm can used drive personalized multidisciplinary approach this challenging malignancy.

Language: Английский

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Global Trends in Incidence Rates of Primary Adult Liver Cancers: A Systematic Review and Meta-Analysis

Frontiers in Oncology, Journal Year: 2020, Volume and Issue: 10

Published: Feb. 28, 2020

Background: Primary liver cancer is a leading cause of deaths worldwide. Global burden varies, reflecting geographical distribution viral hepatitis. Our objective was to perform systematic review and meta-analysis published current trends in incidence adult cancers histological types Methods: This study used searches PubMed, Embase, CINAHL, Web Science databases for English-language peer-reviewed articles from 1 January 2008 01 September 2019. Inclusion criteria were population-based studies patients with quantitative estimates temporal and/or types. For multiple the same area, only publication that reported most recent type population subgroup included. Review conducted per PRISMA guidelines. Two authors independently extracted data critically assessed studies. Proposed contributors observed included articles. Study-specific annual percentage change (APC) rates 95% confidence intervals (CIs) pooled using random-effects models. Heterogeneity measured I2 statistics bias evaluated funnel plots Egger's tests. Results: Overall, 53 met inclusion criteria, which 31 meta-analysis. APC +0.8 (95% CI -0.3, +2.0) combined, +2.6 +1.2, +4.0) hepatocellular carcinoma (HCC), +4.3 +2.5, +6.1) intrahepatic cholangiocarcinoma. Subgroup analyses indicated increasing (APC +3.2, +3.9) HCC +3.6, +2.9, +4.4) region North America/Europe/Australia, whereas corresponding decreasing -1.7, -2.2, -1.1) stable -0.7, -1.9, +0.5) Asia, respectively. Conclusions: Incidence Western countries, are Asian region, although still remaining high. findings highlight importance hepatitis control lifestyle interventions reduce global burden. Ongoing surveillance also vital detect early shifts trends.

Language: Английский

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Targeting FGFR inhibition in cholangiocarcinoma

Cancer Treatment Reviews, Journal Year: 2021, Volume and Issue: 95, P. 102170 - 102170

Published: Feb. 26, 2021

Cholangiocarcinomas (CCAs) are rare but aggressive tumours of the bile ducts, which often diagnosed at an advanced stage and have poor outcomes on systemic therapy. Somatic alterations with therapeutic implications been identified in almost half CCAs, particular intrahepatic CCA (iCCA), subtype arising from ducts within liver. Among patients CCA, fibroblast growth factor receptor 2 (FGFR2) fusions or rearrangements occur exclusively iCCA, where they estimated to be found up 10-15% patients. Clinical trials for selective FGFR kinase inhibitors shown consistent activity these agents previously treated iCCA harbouring alterations. Current show differences their structure, mechanisms target engagement, specificities FGFR1, 2, 3 4 other related kinases. These offer potential improve FGFR-driven impact variations molecular profiles efficacy, safety, acquired resistance mechanisms, patients' health-related quality life remains fully characterized. The most common adverse event associated is hyperphosphatemia, on-target off-tumour effect FGFR1 inhibition, strategies manage this include dose adjustment, chelators, use a low phosphate diet. As targeted enter clinic testing actionable mutations monitoring emergence will essential.

Language: Английский

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Updated Trends in Cancer in Japan: Incidence in 1985–2015 and Mortality in 1958–2018—A Sign of Decrease in Cancer Incidence

Journal of Epidemiology, Journal Year: 2021, Volume and Issue: 31(7), P. 426 - 450

Published: Feb. 5, 2021

Background: Unlike many North American and European countries, Japan has observed a continuous increase in cancer incidence over the last few decades. We examined most recent trends population-based mortality Japan.

Language: Английский

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Practical considerations in screening for genetic alterations in cholangiocarcinoma

Annals of Oncology, Journal Year: 2021, Volume and Issue: 32(9), P. 1111 - 1126

Published: April 28, 2021

Cholangiocarcinoma (CCA) encompasses diverse epithelial tumors historically associated with poor outcomes due to an aggressive disease course, late diagnosis, and limited benefit of standard chemotherapy for advanced disease. Comprehensive molecular profiling has revealed a landscape genomic alterations as oncogenic drivers in CCA. TP53 mutations, CDKN2A/B loss, KRAS mutations are the most common genetic However, intrahepatic CCA (iCCA) extrahepatic (eCCA) differ substantially frequency many alterations. This includes actionable alterations, such isocitrate dehydrogenase 1 (IDH1) large variety FGFR2 rearrangements, which found up 29% ∼10% patients iCCA, respectively, but rare eCCA. rearrangements currently only alteration targeted therapy, fibroblast growth factor receptor 1-3 inhibitor pemigatinib, been approved. favorable phase III results IDH1-targeted therapy ivosidenib iCCA have published, numerous other by therapies approved indications. Recent advances next-generation sequencing (NGS) led development assays that allow comprehensive gene panels within 2-3 weeks, including vitro diagnostic tests United States. These vary regarding acceptable source material (tumor tissue or peripheral whole blood), library construction (DNA RNA), target selection technology, panel size, type detectable While some commercial laboratories offer rapid services based on proprietary assay platforms, clinical centers may use kits designed research develop their own customized laboratory-developed tests. Large-scale NGS allows detailed precise diagnosis provides important opportunity improved treatment plans tailored individual patient's signature.

Language: Английский

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Mitochondrial oxidative metabolism contributes to a cancer stem cell phenotype in cholangiocarcinoma

Journal of Hepatology, Journal Year: 2021, Volume and Issue: 74(6), P. 1373 - 1385

Published: Jan. 21, 2021

Language: Английский

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