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Cancers Jul 2023Hepatocellular cancer (HCC) and biliary tract cancers (BTCs) have poor survival rates and a low likelihood of a cure, especially in advanced-stage disease. Early... (Review)
Review
Hepatocellular cancer (HCC) and biliary tract cancers (BTCs) have poor survival rates and a low likelihood of a cure, especially in advanced-stage disease. Early diagnosis is crucial and can significantly improve survival rates through curative treatment approaches. Current guidelines recommend abdominal ultrasonography (USG) and alpha-fetoprotein (AFP) monitoring for HCC screening in high-risk groups, and abdominal USG, magnetic resonance imaging (MRI), and magnetic resonance cholangiopancreatography (MRCP) monitoring for biliary tract cancer. However, despite this screening strategy, many high-risk individuals still develop advanced-stage HCC and BTC. Blood-based biomarkers are being developed for use in HCC or BTC high-risk groups. Studies on AFP, AFP-L3, des-gamma-carboxy prothrombin, glypican-3 (GPC3), osteopontin (OPN), midkine (MK), neopterin, squamous cell carcinoma antigen (SCCA), Mac-2-binding protein (M2BP), cyclic guanosine monophosphate (cGMP), and interleukin-6 biomarkers for HCC screening have shown promising results when evaluated individually or in combination. In the case of BTCs, the potential applications of circulating tumor DNA, circulating microRNA, and circulating tumor cells in diagnosis are also promising. These biomarkers have shown potential in detecting BTCs in early stages, which can significantly improve patient outcomes. Additionally, these biomarkers hold promise for monitoring disease progression and evaluating response to therapy in BTC patients. However, further research is necessary to fully understand the clinical utility of these biomarkers in the diagnosis and management of HCC and BTCs.
PubMed: 37568696
DOI: 10.3390/cancers15153880 -
BMC Research Notes Nov 2023This study aims to describe the diagnostic performance of alpha-fetoprotein (AFP), alpha-fetoprotein L3 isoform (AFP-L3), protein induced by vitamin K absence II...
OBJECTIVE
This study aims to describe the diagnostic performance of alpha-fetoprotein (AFP), alpha-fetoprotein L3 isoform (AFP-L3), protein induced by vitamin K absence II (PIVKA-II), and combined biomarkers for non-B non-C hepatocellular carcinoma (NBNC-HCC).
RESULTS
A total of 681 newly-diagnosed primary liver disease subjects (385 non-HCC, 296 HCC) who tested negativity for the hepatitis B surface antigen (HBsAg) and hepatitis C antibody (anti-HCV) enrolled in this study. At the cut-off point of 3.8 ng/mL, AFP helps to discriminate HCC from non-HCC with an area under the curve (AUC) value of 0.817 (95% confidence interval [CI]: 0.785-0.849). These values of AFP-L3 (cut-off 0.9%) and PIVKA-II (cut-off 57.7 mAU/mL) were 0.758 (95%CI: 0.725-0.791) and 0.866 (95%CI: 0.836-0.896), respectively. The Bayesian Model Averaging (BMA) statistic identified the optimal model, including patients' age, aspartate aminotransferase, AFP, and PIVKA-II combination, which helps to classify HCC with better performance (AUC = 0.896, 95%CI: 0.872-0.920, P < 0.001). The sensitivity and specificity of the optimal model reached 81.1% (95%CI: 76.1-85.4) and 83.2% (95%CI: 78.9-86.9), respectively. Further analyses indicated that AFP and PIVKA-II markers and combined models have good-to-excellent performance detecting curative resected HCC, separating HCC from chronic hepatitis, dysplastic, and hyperplasia nodules.
Topics: Humans; Carcinoma, Hepatocellular; alpha-Fetoproteins; Liver Neoplasms; Vitamin K; Vitamins; Bayes Theorem; ROC Curve; Biomarkers; Biomarkers, Tumor
PubMed: 37932802
DOI: 10.1186/s13104-023-06600-y -
Hepatology Communications Nov 2023Alpha-fetoprotein (AFP) and des-gamma carboxyprothrombin (DCP), also known as protein induced by vitamin K absence-II (PIVKA-II [DCP]) are biomarkers for HCC with...
BACKGROUND
Alpha-fetoprotein (AFP) and des-gamma carboxyprothrombin (DCP), also known as protein induced by vitamin K absence-II (PIVKA-II [DCP]) are biomarkers for HCC with limited diagnostic value when used in isolation. The novel GAAD algorithm is an in vitro diagnostic combining PIVKA-II (DCP) and AFP measurements, age, and gender (biological sex) to generate a semi-quantitative result. We conducted prospective studies to develop, implement, and clinically validate the GAAD algorithm for differentiating HCC (early and all-stage) and benign chronic liver disease (CLD), across disease stages and etiologies.
METHODS
Patients aged ≥18 years with HCC or CLD were prospectively enrolled internationally into algorithm development [n = 1084; 309 HCC cases (40.7% early-stage) and 736 controls] and clinical validation studies [n = 877; 366 HCC cases (47.6% early-stage) and 303 controls]. Serum samples were analyzed on a cobas® e 601 analyzer. Performance was assessed using receiver operating characteristic curve analyses to calculate AUC.
RESULTS
For algorithm development, AUC for differentiation between early-stage HCC and CLD was 90.7%, 84.4%, and 77.2% for GAAD, AFP, and PIVKA-II, respectively. The sensitivity of GAAD for the detection of early-stage HCC was 71.8% with 90.0% specificity. Similar results were shown in the clinical validation study; AUC for differentiation between early-stage HCC and CLD was 91.4% with 70.1% sensitivity and 93.7% specificity. GAAD also showed strong specificity, with a lower rate of false positives regardless of disease stage, etiology, or region.
CONCLUSIONS
The GAAD algorithm significantly improves early-stage HCC detection for patients with CLD undergoing HCC surveillance. Further phase III and IV studies are warranted to assess the utility of incorporating the algorithm into clinical practice.
Topics: Humans; Adolescent; Adult; Carcinoma, Hepatocellular; Liver Neoplasms; Prospective Studies; alpha-Fetoproteins; Algorithms
PubMed: 37938100
DOI: 10.1097/HC9.0000000000000317 -
Journal of Digital Imaging Dec 2023This study aimed to explore the magnetic resonance imaging (MRI) features of dual-phenotype hepatocellular carcinoma (DPHCC) and their diagnostic value.The data of 208...
This study aimed to explore the magnetic resonance imaging (MRI) features of dual-phenotype hepatocellular carcinoma (DPHCC) and their diagnostic value.The data of 208 patients with primary liver cancer were retrospectively analysed between January 2016 and June 2021. Based on the pathological diagnostic criteria, 27 patients were classified into the DPHCC group, 113 patients into the noncholangiocyte-phenotype hepatocellular carcinoma (NCPHCC) group, and 68 patients with intrahepatic cholangiocarcinoma (ICC) were classified into the ICC group. Two abdominal radiologists reviewed the preoperative MRI features by a double-blind method. The MRI features and key laboratory and clinical indicators were compared between the groups. The potentially valuable MRI features and key laboratory and clinical characteristics for predicting DPHCC were identified by univariate and multivariate analyses, and the odds ratios (ORs) were recorded. In multivariate analysis, tumour without capsule (P = 0.046, OR = 9.777), dynamic persistent enhancement (P = 0.006, OR = 46.941), and targetoid appearance on diffusion-weighted imaging (DWI) (P = 0.021, OR = 30.566) were independently significant factors in the detection of DPHCC compared to NCPHCC. Serum alpha-fetoprotein (AFP) > 20 µg/L (P = 0.036, OR = 67.097) and prevalence of hepatitis B virus (HBV) infection (P = 0.020, OR = 153.633) were independent significant factors in predicting DPHCC compared to ICC. The differences in other tumour marker levels and imaging features between the groups were not significant. In MR enhanced and diffusion imaging, tumour without capsule, persistent enhancement and DWI targetoid findings, combined with AFP > 20 µg/L and HBV infection-positive laboratory results, can help to diagnose DPHCC and differentiate it from NCPHCC and ICC. These results suggest that clinical, laboratory and MRI features should be integrated to construct an AI diagnostic model for DPHCC.
Topics: Humans; alpha-Fetoproteins; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Carcinoma, Hepatocellular; Cholangiocarcinoma; Contrast Media; Liver Neoplasms; Magnetic Resonance Imaging; Phenotype; Retrospective Studies; Double-Blind Method
PubMed: 37578576
DOI: 10.1007/s10278-023-00888-9 -
Annals of Palliative Medicine Jan 2024Hepatocellular carcinoma (HCC) is a leading cause of morbidity and mortality in the United States. For certain patients, liver transplantation (LT) may be curative. The... (Review)
Review
BACKGROUND AND OBJECTIVE
Hepatocellular carcinoma (HCC) is a leading cause of morbidity and mortality in the United States. For certain patients, liver transplantation (LT) may be curative. The determination of which patients would benefit most from transplant and have the lowest risk of post-transplant recurrence has evolved as technology and treatments have expanded. We aim to review epidemiological changes in the HCC landscape, selection criteria for transplant, organ allocation, bridge therapies and post-transplant recurrence, and identify points for palliative care involvement.
METHODS
Literature review was performed using PubMed MeSH searches in addition to reference list review. Additional information was retrieved from government regulatory and procurement organizations.
KEY CONTENT AND FINDINGS
Metabolic and alcohol-associated liver diseases have surpassed hepatitis C as the leading causes of LT over the last decade, and have also risen as the underlying conditions seen in patients with HCC requiring LT. The United Network for Organ Sharing (UNOS) coordinates organ allocation, which includes disease severity, waitlist time, blood type, and distance from donor hospital. It has progressed to incorporate treatment response and alpha-fetoprotein into its listing criteria for patients with HCC, in addition to the well-established Milan Criteria (MC, one tumor <5 cm, ≤3 tumors ≤3 cm). Therapies to bridge patients until LT include locoregional therapies as well as immunotherapy. Dropout on the waitlist is seen up to 20% either due to decompensation or progression of disease. Recurrence of HCC post-transplant remains challenging. Given this, current guidelines recommend early palliative care involvement regardless of transplant listing status for both symptom management and advance care planning.
CONCLUSIONS
For patients with HCC with favorable tumor biology, LT can be curative. However, given the symptom burden while awaiting LT and the notable number of patients who are unable to receive a transplant, early palliative care is critical in appropriate management of HCC.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Liver Transplantation; Patient Selection; Retrospective Studies; Tissue Donors
PubMed: 38124475
DOI: 10.21037/apm-23-341 -
Cancer Immunology, Immunotherapy : CII Jun 2024Alpha-fetoprotein elevated gastric cancer (AFPGC) got growing interests for its aggressive nature and unfavorable prognosis. Here, a phase 1 dose escalation study was...
BACKGROUND
Alpha-fetoprotein elevated gastric cancer (AFPGC) got growing interests for its aggressive nature and unfavorable prognosis. Here, a phase 1 dose escalation study was conducted to evaluate safety and efficacy of zimberelimab (GLS-010, anti-PD-1) plus lenvatinib and chemotherapy (XELOX) as the first-line treatment for AFPGC.
METHODS
Histologically confirmed HER2-negative, advanced GC patients with elevated serum AFP level (≥ 20 ng/ml) were screened. Using a 3 + 3 dose escalation design, patients were administered varying doses of lenvatinib (12, 16, 20 mg) with GLS-010 and XELOX. The primary endpoints were safety and determination of recommended phase II dose (RP2D). Secondary endpoints included overall response rate (ORR), progression-free survival (PFS) and disease control rate.
RESULTS
Nine patients were enrolled with no dose-limiting toxicities observed. Most frequent treatment-related AEs were fatigue (55.6%), hand-foot syndrome (55.6%) and rash (55.6%), and no grade ≥ 4 AEs were reported. All patients exhibited disease control with ORR reaching 33.3%. The median PFS and OS reached 7.67 months (95% CI 4.07-11.27) and 13.17 months (95% CI 2.78-23.56), respectively. Serum AFP level was found correlated with therapeutic responses. Further 16s rRNA sequencing analysis demonstrated altered gut microbiota with elevated abundance of Lachnospiraceae bacterium-GAM79 and Roseburia hominis A2-183.
CONCLUSIONS
GLS-010 plus lenvatinib and XELOX demonstrated a manageable safety profile with promising efficacy for AFPGC. With RP2D of lenvatinib determined as 16 mg, further expansion cohort is now ongoing. Translational investigation suggested that serum AFP can be indictive for therapeutic responses and certain microbiota species indicating favorable responses to immunotherapy was elevated after the combinational treatment.
Topics: Humans; Quinolines; Male; Female; Middle Aged; Phenylurea Compounds; Antineoplastic Combined Chemotherapy Protocols; Stomach Neoplasms; Aged; alpha-Fetoproteins; Antibodies, Monoclonal, Humanized; Adult; Prognosis
PubMed: 38833154
DOI: 10.1007/s00262-024-03743-0 -
International Journal of Surgery... Nov 2023The treatment efficacy of transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) for huge single hepatocellular carcinoma (HCC) has not...
Hepatic arterial infusion chemotherapy versus transarterial chemoembolization, potential conversion therapies for single huge hepatocellular carcinoma: a retrospective comparison study.
BACKGROUND
The treatment efficacy of transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) for huge single hepatocellular carcinoma (HCC) has not been fully documented. The aim of this study was to compare TACE and HAIC for patients with solitary nodular HCCs greater than or equal to 10 cm without vascular invasion and metastasis.
METHODS
From July 2015 to June 2020, a total of 147 patients with single nodular HCC greater than or equal to 10 cm without vascular invasion and metastasis receiving TACE ( n =77) or HAIC ( n =70) were retrospectively enrolled. The tumor response, overall survival (OS), and progression-free survival (PFS) were investigated and compared. The treatment outcome of two transarterial interventional therapies was explored.
RESULTS
The objective response rate and PFS were higher in patients who received HAIC than in those who received TACE (44.3 vs. 10.4% and 8.9 vs. 4.2 months, respectively; P =0.001 and P =0.030), whereas the disease control rate and OS were not significantly different (92.9 vs. 84.4% and 21.3 vs. 26.6 months, respectively; P =0.798 and P =0.749). The decreased levels of alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II (PIVKA-II) in patients treated with HAIC were significantly higher than those treated with TACE ( P =0.038 and P <0.001). Multivariable analysis showed that the aspartate aminotransferase/platelet ratio index was associated with OS, whereas albumin-bilirubin grade and PIVKA-II were associated with PFS.
CONCLUSIONS
HAIC has better potential than TACE to control local tumors for huge single HCC without vascular invasion and metastasis and thus may be the preferred conversion therapy for these tumors.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Retrospective Studies; Chemoembolization, Therapeutic; Infusions, Intra-Arterial; Treatment Outcome
PubMed: 37578432
DOI: 10.1097/JS9.0000000000000654 -
Cancer Cell International Oct 2023Hepatocellular carcinoma (HCC) is the most predominant primary liver cancer, causing many illnesses and deaths worldwide. The insidious clinical presentation, difficulty... (Review)
Review
Hepatocellular carcinoma (HCC) is the most predominant primary liver cancer, causing many illnesses and deaths worldwide. The insidious clinical presentation, difficulty in early diagnosis, and the highly malignant nature make the prognosis of HCC extremely poor. The complex and heterogeneous pathogenesis of HCC poses significant challenges to developing therapies. Urine-based biomarkers for HCC, including diagnostic, prognostic, and monitoring markers, may be valuable supplements to current tools such as serum α-fetoprotein (AFP) and seem promising for progress in precision medicine. Herein, we reviewed the major urinary biomarkers for HCC and assessed their potential for clinical application. Molecular types, testing platforms, and methods for building multimolecule models in the included studies have shown great diversity, thus providing abundant novel tools for future clinical transformation and applications.
PubMed: 37833757
DOI: 10.1186/s12935-023-03092-5 -
Cancers Apr 2024Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death and the sixth most diagnosed malignancy worldwide. Serum alpha-fetoprotein (AFP) is the... (Review)
Review
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death and the sixth most diagnosed malignancy worldwide. Serum alpha-fetoprotein (AFP) is the traditional, ubiquitous biomarker for HCC. However, there has been an increasing call for the use of multiple biomarkers to optimize care for these patients. AFP, AFP-L3, and prothrombin induced by vitamin K absence II (DCP) have described clinical utility for HCC, but unfortunately, they also have well established and significant limitations. Circulating tumor DNA (ctDNA), genomic glycosylation, and even totally non-invasive salivary metabolomics and/or micro-RNAS demonstrate great promise for early detection and long-term surveillance, but still require large-scale prospective validation to definitively validate their clinical validity. This review aims to provide an update on clinically available and emerging biomarkers for HCC, focusing on their respective clinical strengths and weaknesses.
PubMed: 38672535
DOI: 10.3390/cancers16081453 -
Cancers Jul 2023Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Although alpha fetoprotein (AFP) remains a commonly used serological marker...
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Although alpha fetoprotein (AFP) remains a commonly used serological marker of HCC, the sensitivity and specificity of AFP in detecting HCC is often limited. Exosomal RNA has emerged as a promising diagnostic tool for various cancers, but its use in HCC detection has yet to be fully explored. Here, we employed Machine Learning on 114,602 exosomal RNAs to identify a signature that can predict HCC. The exosomal expression data of 118 HCC patients and 112 healthy individuals were stratified split into Training, Validation and Unseen Test datasets. Feature selection was then performed on the initial training dataset using permutation importance, and the predictive performance of the selected features were tested on the validation dataset using Support Vector Machine (SVM) Classifier. A minimum of nine features were identified to be predictive of HCC and these nine features were then evaluated across six different models in an unseen test set. These features, mainly in the immune, platelet/neutrophil and cytoskeletal pathways, exhibited good predictive performance with ROC-AUC from 0.79-0.88 in the unseen test set. Hence, these nine exosomal RNAs have potential to be clinically useful minimally invasive biomarkers for HCC.
PubMed: 37509410
DOI: 10.3390/cancers15143749