EASL-EORTC clinical practice guidelines : management of hepatocellular carcinoma

Cancer incidence and deaths in the United States were projected for the most common cancer types for the years 2020 and 2030 based on changing demographics and the average annual percentage changes in incidence and death rates. Breast, prostate, and lung cancers will remain the top cancer diagnoses throughout this time, but thyroid cancer will replace colorectal cancer as the fourth leading cancer diagnosis by 2030, and melanoma and uterine cancer will become the fifth and sixth most common cancers, respectively. Lung cancer is projected to remain the top cancer killer throughout this time period. However, pancreas and liver cancers are projected to surpass breast, prostate, and colorectal cancers to become the second and third leading causes of cancer-related death by 2030, respectively. Advances in screening, prevention, and treatment can change cancer incidence and/or death rates, but it will require a concerted effort by the research and healthcare communities now to effect a substantial change for the future.

https://cancerres.aacrjournals.org/content/canres/74/11/2913.full.pdf

Projecting Cancer Incidence and Deaths to 2030: The Unexpected Burden of Thyroid, Liver, and Pancreas Cancers in the United States

https://aasldpubs.onlinelibrary.wiley.com/doi/epdf/10.1002/hep.25762

The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association

Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial.

Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial

Since the publication of the American Association for the Study of Liver Diseases (AASLD) practice guidelines on the management of hepatocellular carcinoma (HCC) in 2005, new information has emerged that requires that the guidelines be updated. The full version of the new guidelines is available on the AASLD Web site at http://www.aasld.org/practiceguidelines/ Documents/Bookmarked%20Practice%20Guidelines/ HCCUpdate2010.pdf. Here, we briefly describe only new or changed recommendations.

/pdf/aasld-practice-guideline-management-of-hepatocellular-51bocalv0r.pdf

AASLD PRACTICE GUIDELINE Management of Hepatocellular Carcinoma: An Update

EASL–EORTC Clinical Practice Guidelines (CPG) on the management of hepatocellular carcinoma (HCC) define the use of surveillance, diagnosis, and therapeutic strategies recommended for patients with this type of cancer. This is the first European joint effort by the European Association for the Study of the Liver (EASL) and the European Organization for Research and Treatment of Cancer (EORTC) to provide common guidelines for the management of hepatocellular carcinoma. These guidelines update the recommendations reported by the EASL panel of experts in HCC published in 2001 [1]. Several clinical and scientific advances have occurred during the past decade and, thus, a modern version of the document is urgently needed. The purpose of this document is to assist physicians, patients, health-care providers, and health-policy makers from Europe and worldwide in the decision-making process according to evidencebased data. Users of these guidelines should be aware that the recommendations are intended to guide clinical practice in circumstances where all possible resources and therapies are available. Thus, they should adapt the recommendations to their local regulations and/or team capacities, infrastructure, and cost– benefit strategies. Finally, this document sets out some recommendations that should be instrumental in advancing the research and knowledge of this disease and ultimately contribute to improve patient care. The EASL–EORTC CPG on the management of hepatocellular carcinoma provide recommendations based on the level of evidence and the strength of the data (the classification of evidence is adapted from National Cancer Institute [2]) (Table 1A) and the strength of recommendations following previously reported systems (GRADE systems) (Table 1B).

http://www.bclc.cat/download/easl-guidelines.pdf

EASL-EORTC Clinical Practice Guidelines: Management of hepatocellular carcinoma European Association for the Study of the Liver ⇑ , European Organisation for Research and Treatment of Cancer

BACKGROUND & AIMS
Cholangiocarcinoma, the second most common liver cancer, can be classified as intrahepatic cholangiocarcinoma (ICC) or extrahepatic cholangiocarcinoma. We performed an integrative genomic analysis of ICC samples from a large series of patients.


METHODS
We performed a gene expression profile, high-density single-nucleotide polymorphism array, and mutation analyses using formalin-fixed ICC samples from 149 patients. Associations with clinicopathologic traits and patient outcomes were examined for 119 cases. Class discovery was based on a non-negative matrix factorization algorithm and significant copy number variations were identified by Genomic Identification of Significant Targets in Cancer (GISTIC) analysis. Gene set enrichment analysis was used to identify signaling pathways activated in specific molecular classes of tumors, and to analyze their genomic overlap with hepatocellular carcinoma (HCC).


RESULTS
We identified 2 main biological classes of ICC. The inflammation class (38% of ICCs) is characterized by activation of inflammatory signaling pathways, overexpression of cytokines, and STAT3 activation. The proliferation class (62%) is characterized by activation of oncogenic signaling pathways (including RAS, mitogen-activated protein kinase, and MET), DNA amplifications at 11q13.2, deletions at 14q22.1, mutations in KRAS and BRAF, and gene expression signatures previously associated with poor outcomes for patients with HCC. Copy number variation-based clustering was able to refine these molecular groups further. We identified high-level amplifications in 5 regions, including 1p13 (9%) and 11q13.2 (4%), and several focal deletions, such as 9p21.3 (18%) and 14q22.1 (12% in coding regions for the SAV1 tumor suppressor). In a complementary approach, we identified a gene expression signature that was associated with reduced survival times of patients with ICC; this signature was enriched in the proliferation class (P < .001).


CONCLUSIONS
We used an integrative genomic analysis to identify 2 classes of ICC. The proliferation class has specific copy number alterations, activation of oncogenic pathways, and is associated with worse outcome. Different classes of ICC, based on molecular features, therefore might require different treatment approaches.

https://www.gastrojournal.org/article/S0016-5085(13)00002-4/pdf

BASIC AND TRANSLATIONAL—BILIARY Integrative Molecular Analysis of Intrahepatic Cholangiocarcinoma Reveals 2 Classes That Have Different Outcomes

Special article Clinical Management of Hepatocellular Carcinoma. Conclusions of the Barcelona-2000 EASL Conference

Background & Aims: IGF signaling has a relevant role in a variety of human malignancies. We analyzed the underlying molecular mechanisms of IGF signaling activation in early hepatocellular carcinoma (HCC; BCLC class 0 or A) and assessed novel targeted therapies blocking this pathway. Methods: An integrative molecular dissection of the axis was conducted in a cohort of 104 HCCs analyzing gene and miRNA expression, structural aberrations, and protein activation. The therapeutic potential of a selective IGF-1R inhibitor, the monoclonal antibody A12, was assessed in vitro and in a xenograft model of HCC. Results: Activation of the IGF axis was observed in 21% of early HCCs. Several molecular aberrations were identified, such as overexpression of IGF2 –resulting from reactivation of fetal promoters P3 and P4-, IGFBP3 downregulation and allelic losses of IGF2R (25% of cases). A gene signature defining IGF-1R activation was developed. Overall, activation of IGF signaling in HCC was significantly associated with mTOR signaling (p = 0.035) and was clearly enriched in the Proliferation subclass of the molecular classification of HCC (p = 0.001). We also found an inverse correlation between IGF activation and miR-100/miR-216 levels (FDR < 0.05). In vitro studies showed that A12-induced abrogation of IGF-1R activation and downstream signaling significantly decreased cell viability and proliferation. In vivo, A12 delayed tumor growth and prolonged survival, reducing proliferation rates and inducing apoptosis. Conclusions: Integrative genomic analysis showed enrichment of activation of IGF signaling in the Proliferation subclass of HCC. Effective blockage of IGF signaling with A12 provides the rationale for testing this therapy in clinical trials. Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver.

https://www.journal-of-hepatology.eu/article/S0168-8278(10)00023-1/pdf

Jordi Bruix

Papers

AASLD PRACTICE GUIDELINE Management of Hepatocellular Carcinoma: An Update

EASL-EORTC Clinical Practice Guidelines: Management of hepatocellular carcinoma European Association for the Study of the Liver ⇑ , European Organisation for Research and Treatment of Cancer

BASIC AND TRANSLATIONAL—BILIARY Integrative Molecular Analysis of Intrahepatic Cholangiocarcinoma Reveals 2 Classes That Have Different Outcomes

Special article Clinical Management of Hepatocellular Carcinoma. Conclusions of the Barcelona-2000 EASL Conference

IGF activation in a molecular subclass of hepatocellular carcinoma and pre-clinical efficacy of IGF-1R blockage q