The last 5 years have witnessed relevant advances in the systemic treatment of hepatocellular carcinoma. New data have emerged since the development of the EASL Clinical Practice Guidelines on the ...management of hepatocellular carcinoma in 2018. Drugs licensed in some countries now include 4 oral multi-tyrosine kinase inhibitors (sorafenib, lenvatinib, regorafenib and cabozantinib), 1 anti-angiogenic antibody (ramucirumab) and 4 immune checkpoint inhibitors, alone or in combination (atezolizumab in combination with bevacizumab, ipilimumab in combination with nivolumab, nivolumab and pembrolizumab in monotherapy). Prolonged survival in excess of 2 years can be expected in most patients with sensitive tumours and well-preserved liver function that renders them fit for sequential therapies. With different choices available in any given setting, the robustness of the evidence of efficacy and a correct matching of the safety profile of a given agent with patient characteristics and preferences are key in making sound therapeutic decisions. The recommendations in this document amend the previous EASL Clinical Practice Guidelines and aim to help clinicians provide the best possible care for patients today. In view of several ongoing and promising trials, further advances in systemic therapy of hepatocellular carcinoma are foreseen in the near future and these recommendations will have to be updated regularly.
Linked color imaging (LCI) has been shown to be effective in multiple randomized controlled trials for enhanced colorectal polyp detection. Recently, artificial intelligence (AI) with deep learning ...through convolutional neural networks has dramatically improved and is increasingly recognized as a promising new technique for enhancing colorectal polyp detection.
This study aims to evaluate a newly developed computer-aided detection (CAD) system in combination with LCI for colorectal polyp detection.
First, a convolutional neural network was trained for colorectal polyp detection in combination with the LCI technique using a dataset of anonymized endoscopy videos. For validation, 240 polyps within fully recorded endoscopy videos in LCI mode, covering the entire spectrum of adenomatous histology, were used. Sensitivity (true-positive rate per lesion) and false-positive frames in a full procedure were assessed.
The new CAD system used in LCI mode could process at least 60 frames per second, allowing for real-time video analysis. Sensitivity (true-positive rate per lesion) was 100%, with no lesion being missed. The calculated false-positive frame rate was 0.001%. Among the 240 polyps, 34 were sessile serrated lesions. The detection rate for sessile serrated lesions with the CAD system used in LCI mode was 100%.
The new CAD system used in LCI mode achieved a 100% sensitivity per lesion and a negligible false-positive frame rate. Note that the new CAD system used in LCI mode also specifically allowed for detection of serrated lesions in all cases. Accordingly, the AI algorithm introduced here for the first time has the potential to dramatically improve the quality of colonoscopy.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Immune checkpoint inhibitors (ICIs) have reshaped cancer therapy. ICIs enhance T cell activation through various mechanisms and may help reverse the exhausted phenotype of tumour-infiltrating ...lymphocytes. However, disrupting the key role that checkpoint molecules play in immune homeostasis may result in autoimmune complications. A broad range of immune-related adverse events (irAEs) involve almost every organ but mostly affect the skin, digestive system, lung, endocrine glands, nervous system, kidney, blood cells, and musculoskeletal system. They are usually manageable but can be life-threatening. The incidence of irAEs is not very different in patients with hepatocellular carcinoma (HCC) compared to other tumour types, although there is a trend towards a higher incidence of hepatic irAEs. HCC usually develops on a background of cirrhosis with associated systemic manifestations. Extrahepatic organ dysfunction in cirrhosis may cause signs and symptoms that overlap with irAEs or increase their severity. Available guidelines for the management of irAEs have not specifically considered the assessment of toxicities in the context of patients with liver cancer and cirrhosis. This review addresses the toxicity profile of ICIs in patients with HCC, focusing on the challenges that the underlying liver disease poses to their diagnosis and management. Challenges include late recognition, inadequate work-up and delayed treatment, overdiagnosis and inappropriate interruption of ICIs, complications caused by immunosuppressive therapy, and increased cost. A specific algorithm for the management of hepatic irAEs is provided.
There have been major advances in the armamentarium for hepatocellular carcinoma (HCC) since the last official update of the Barcelona Clinic Liver Cancer prognosis and treatment strategy published ...in 2018. Whilst there have been advances in all areas, we will focus on those that have led to a change in strategy and we will discuss why, despite being encouraging, data for select interventions are still too immature for them to be incorporated into an evidence-based model for clinicians and researchers. Finally, we describe the critical insight and expert knowledge that are required to make clinical decisions for individual patients, considering all of the parameters that must be considered to deliver personalised clinical management.
Hepatocellular carcinoma (HCC) is one of the most common causes of cancer‐related deaths globally due, in part, to the majority of patients being diagnosed with intermediate or advanced stage ...disease. Our increased understanding of the heterogeneous molecular pathogenesis of HCC has led to significant developments in novel targeted therapies. Despite these advances, there remains a high unmet need for new treatment options. HCC is a complex disease with multiple pathogenic mechanisms caused by a variety of risk factors, making it difficult to characterize with a single biomarker. In fact, numerous biomarkers have been studied in HCC, but alpha‐fetoprotein (AFP) remains the most widely used and accepted serum marker since its discovery over 60 years ago. This review summarizes the most relevant studies associated with the regulation of AFP at the gene and protein levels; the pathophysiology of AFP as a pro‐proliferative protein; and the correlation of AFP with molecular HCC subclasses, the vascular endothelial growth factor pathway and angiogenesis. Also described are the historical and current uses of AFP for screening and surveillance, diagnosis, its utility as a prognostic and predictive biomarker and its role as a tumour antigen in HCC. Taken together, these data demonstrate the relevance of AFP for patients with HCC and identify several remaining questions that will benefit from future research.
IMbrave150 demonstrated that atezolizumab plus bevacizumab led to significantly improved overall survival (OS) and progression-free survival (PFS) compared with sorafenib in patients with ...unresectable hepatocellular carcinoma at the primary analysis (after a median 8.6 months of follow-up). We present updated data after 12 months of additional follow-up.
Patients with systemic treatment-naive, unresectable hepatocellular carcinoma were randomized 2:1 to receive 1,200 mg atezolizumab plus 15 mg/kg bevacizumab intravenously every 3 weeks or 400 mg sorafenib orally twice daily in this open-label, phase III study. Co-primary endpoints were OS and PFS by independently assessed RECIST 1.1 in the intention-to-treat population. Secondary efficacy endpoints included objective response rates and exploratory subgroup efficacy analyses. This is a post hoc updated analysis of efficacy and safety.
From March 15, 2018, to January 30, 2019, 501 patients (intention-to-treat population) were randomly allocated to receive atezolizumab plus bevacizumab (n = 336) or sorafenib (n = 165). On August 31, 2020, after a median 15.6 (range, 0-28.6) months of follow-up, the median OS was 19.2 months (95% CI 17.0–23.7) with atezolizumab plus bevacizumab and 13.4 months (95% CI 11.4–16.9) with sorafenib (hazard ratio HR 0.66; 95% CI 0.52-0.85; descriptive p <0.001). The median PFS was 6.9 (95% CI 5.7-8.6) and 4.3 (95% CI 4.0-5.6) months in the respective treatment groups (HR 0.65; 95% CI 0.53-0.81; descriptive p < 0.001). Treatment-related grade 3/4 adverse events occurred in 143 (43%) of 329 and 72 (46%) of 156 safety-evaluable patients in the respective groups, and treatment-related grade 5 events occurred in 6 (2%) and 1 (<1%) patients.
After longer follow-up, atezolizumab plus bevacizumab maintained clinically meaningful survival benefits over sorafenib and had a safety profile consistent with the primary analysis.
NCT03434379.
The primary analysis of IMbrave150 showed that atezolizumab plus bevacizumab had significantly greater benefits than sorafenib in patients with advanced hepatocellular carcinoma, but survival data were not yet mature. At this updated analysis done 12 months later, median overall survival was 5.8 months longer with atezolizumab plus bevacizumab than sorafenib, and the severity profile of treatment-related side effects remained similar. These updated results confirm atezolizumab plus bevacizumab as the first-line standard of care for advanced hepatocellular carcinoma.
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•Atezolizumab plus bevacizumab or sorafenib were given for unresectable HCC.•This updated analysis was performed 12 months after the primary analysis of IMbrave150.•Median OS was 5.8 months longer with atezolizumab plus bevacizumab than sorafenib.•ORR was 30% with atezolizumab plus bevacizumab (median duration of 18.1 months).•The safety profile was similar to the findings of the primary analysis.
The intermediate stage of hepatocellular carcinoma (HCC) comprises a highly heterogeneous patient population and therefore poses unique challenges for therapeutic management, different from the early ...and advanced stages. Patients classified as having intermediate HCC by the Barcelona Clinic Liver Cancer (BCLC) staging system present with varying tumor burden and liver function. Transarterial chemoembolization (TACE) is currently recommended as the standard of care in this setting, but there is considerable variation in the clinical benefit patients derive from this treatment.In April 2012, a panel of experts convened to discuss unresolved issues surrounding the application of current guidelines when managing patients with intermediate HCC. The meeting explored the applicability of a subclassification system for intermediate HCC patients to tailor therapeutic interventions based on the evidence available to date and expert opinion. The present report summarizes the proposal of the expert panel: four substages of intermediate HCC patients, B1 to B4.
In patients with unresectable hepatocellular carcinoma, the combination of atezolizumab and bevacizumab was associated with better progression-free and overall survival outcomes, response rate, and ...preservation of quality of life than sorafenib. Serious toxic effects were noted in 38% of patients, similar to that seen in previous studies of these agents.
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