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•Hepatic arterial infusion was proven to be an effective and safe treatment in advanced HCC.•Hepatic arterial infusion therapy was an independent factor for PFS and OS.•Hepatic ...arterial infusion therapy provided a potential benefit of survival in patients with advanced HCC.
To compare the overall survival (OS) and disease progression free survival (PFS) in patients with advanced hepatocellular carcinoma (Ad-HCC) who are undergoing hepatic arterial infusion (HAI) of oxaliplatin, fluorouracil/leucovorin (FOLFOX) treatment vs. sorafenib.
This retrospective study was approved by the ethical review committee, and informed consent was obtained from all patients before treatment. HAI of FOLFOX (HAIF) was recommended as an alternative treatment option for patients who refused sorafenib. Of the 412 patients with Ad-HCC (376 men and 36 women) between Jan 2012 to Dec 2015, 232 patients were treated with sorafenib; 180 patients were given HAIF therapy. The median age was 51 years (range, 16–82 years). Propensity-score matched estimates were used to reduce bias when evaluating survival. Survival curves were calculated by performing the Kaplan-Meier method and compared by using the log-rank test and Cox regression models.
The median PFS and OS in the HAIF group were significantly longer than those in the sorafenib group (PFS 7.1 vs. 3.3 months RECIST/7.4 vs. 3.6 months mRECIST, respectively; OS 14.5 vs. 7.0 months; p <0.001 for each). In the propensity-score matched cohorts (147 pairs), both PFS and OS in the HAIF group were longer than those in the sorafenib group (p <0.001). At multivariate analysis, HAIF treatment was an independent factor for PFS (hazard ratio HR 0.389 RECIST/0.402 mRECIST; p <0.001 for each) and OS (HR 0.129; p <0.001).
HAIF therapy may improve survival compared to sorafenib in patients with Ad-HCC. A prospective randomized trial is ongoing to confirm this finding.
We compared the hepatic arterial infusion of FOLFOX (a combination chemotherapy) with sorafenib (a tyrosine kinase inhibitor) in patients with advanced hepatocellular carcinoma, retrospectively. It was found that hepatic arterial infusion of FOLFOX therapy may improve both progression free and overall survival in patients with advanced hepatocellular carcinoma.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Hepatocellular carcinoma (HCC) remains one of the most common malignant tumors with poor survival. Pyroptosis is a kind of programmed cell death that can regulate the proliferation, invasion, and ...metastasis of tumor cells. However, the expression levels of pyroptosis-related genes (PRGs) in HCC and their relationship with prognosis are still unclear.
Our study identified 35 PRGs through bioinformatics analysis that were differentially expressed between tumor samples and nontumor samples. According to these differentially expressed genes, HCC patients could be divided into two groups, cluster 1 and cluster 2. The least absolute shrinkage and selection operator (LASSO) Cox regression method was performed to construct a 10-gene signature that classified HCC patients in the cancer genome atlas (TCGA) database into low-risk and high-risk groups.
The results showed that the survival rate of HCC patients in the low-risk group was significantly higher than that in the high-risk group (p < 0.001). The validation cohort, the Gene Expression Omnibus (GEO) cohort, was divided into two risk groups based on the median risk score calculated by the TCGA cohort. The overall survival (OS) of the low-risk group was significantly better than that of the high-risk group (p = 0.007). Univariate and multivariate Cox regression analyses revealed that the risk score was an independent factor in predicting OS in HCC patients. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that immune-related high-risk groups were rich in genes and had reduced immune status.
PRGs play a significant role in tumor immunity and have the potential capability to predict the prognosis of HCC patients.
Background Hepatocellular carcinoma (HCC) is one of the most lethal cancers, with a poor prognosis. Prognostic biomarkers for HCC patients are urgently needed. We aimed to establish a nomogram ...prediction system that combines a gene signature to predict HCC prognosis. Methods Differentially expressed genes (DEGs) were identified from publicly available Gene Expression Omnibus (GEO) datasets. The Cancer Genome Atlas (TCGA) cohort and International Cancer Genomics Consortium (ICGC) cohort were regarded as the training cohort and testing cohort, respectively. First, univariate and multivariate Cox analyses and least absolute shrinkage and selection operator (LASSO) regression Cox analysis were performed to construct a predictive risk score signature. Furthermore, a nomogram system containing a risk score and other prognostic factors was developed. In addition, a correlation analysis of risk group and immune infiltration was performed. Finally, we validated the expression levels using real-time PCR. Results Ninety-five overlapping DEGs were identified from four GEO datasets, and we constructed a four-gene-based risk score predictive model (risk score = EZH2 * 0.075 + FLVCR1 * 0.086 + PTTG1 * 0.015 + TRIP13 * 0.020). Moreover, this signature was an independent prognostic factor. Next, the nomogram system containing risk score, sex and TNM stage indicated better predictive performance than independent prognostic factors alone. Moreover, this signature was significantly associated with immune cells, such as regulatory T cells, resting NK cells and M2 macrophages. Finally, RT-PCR confirmed that the mRNA expressions of four genes were upregulated in most HCC cell lines. Conclusion We developed and validated a nomogram system containing the four-gene risk score, sex, and TNM stage to predict prognosis. Keywords: Hepatocellular carcinoma, Signature, Nomogram, Prognosis, Immune infiltration
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Microvascular invasion (MVI) is a risk factor for tumor recurrence after hepatectomy in hepatocellular carcinoma (HCC) patients.
Objective
This study aimed to investigate the efficacy and ...safety of postoperative adjuvant transarterial infusion chemotherapy (TAI) with the FOLFOX regimen for HCC patients with MVI.
Methods
In this prospective, phase III, randomized, open-label, controlled clinical trial, HCC patients with histologically confirmed MVI were randomly assigned (1:1) after hepatectomy to receive either one to two cycles of adjuvant TAI (AT group) or follow-up without any adjuvant treatment (FU group). The primary endpoint was disease-free survival (DFS), while secondary endpoints were overall survival (OS) and safety.
Results
Between June 2016 and April 2019, 127 patients were randomly assigned to the AT group (
n
= 63) or FU group (
n
= 64). Clinicopathological characteristics of the two groups were well-balanced. The 6-, 12-, and 18-month OS rates for the AT group were 100.0%, 97.7%, and 97.7%, respectively, and 94.5%, 89.6%, and 78.5% for the FU group, respectively. The 6-, 12-, and 18-month DFS rates for the AT and FU groups were 84.7%, 61.8%, and 58.7%, and 62.9%, 48.1%, and 38.6%, respectively. OS and DFS were significantly better in the AT group than in the FU group (
p
= 0.037 and 0.023, respectively). No patients in the AT group experienced grade 3 or more severe adverse events.
Conclusions
Adjuvant TAI after hepatectomy may bring survival benefits to HCC patients with MVI.
Trial registration
Trial number: NCT03192618.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background/Aims: Although endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) and fine needle biopsy (FNB) are widely used for tissue acquisition of pancreatic solid mass, the optimal ...strategy of this procedure has not been established yet. The aim of this nationwide study was to investigate the current practice patterns of EUS-FNA/FNB for pancreatic solid mass in Korea. Methods: The Policy-Quality Management of the Korean Pancreatobiliary Association (KPBA) developed a questionnaire containing 22 questions. An electronic survey consisting of the questionnaire was distributed by e-mail to members registered to the KPBA. Results: A total of 101 respondents completed the survey. Eighty respondents (79.2%) performed preoperative EUS-FNA/FNB for operable pancreatic solid mass. Acquire needles (60.4%) were used the most, followed by ProCore needles (47.5%). In terms of need size, most respondents (>80%) preferred 22-gauge needles regardless of the location of the mass. Negative suction with a 10-mL syringe (71.3%) as sampling technique was followed by stylet slow-pull (41.6%). More than three needle passes for EUS-FNA/FNB was performed by most respondents (>80%). The frequency of requiring repeated procedure was significantly higher in respondents with a low individual volume (<5 per month, p=0.001). Prophylactic antibiotics were routinely used in 39 respondents (38.6%); rapid on-site pathologic evaluation was used in 6.1%. Conclusions: According to this survey, practices of EUS-FNA/FNB for pancreatic solid mass varied substantially, some of which differed considerably from the recommendations present in existing guidelines. These results suggest that the development of evidence-based quality guidelines fitting Korean clinical practice is needed to establish the optimal strategy for this procedure.
Immune checkpoint blockade has demonstrated remarkable efficacy in hepatocellular carcinoma (HCC) but is also commonly accompanied by immune‐related adverse events (irAEs). However, the association ...between irAEs and antitumor efficacy in HCC patients remains unknown. All patients with HCC treated with anti‐PD‐1 antibodies from July 2018 to November 2019 were analyzed and divided into different groups according to their irAEs' status. In total, 101 HCC patients, including 21 (20.8%) patients who presented with irAEs (irAEs+), were enrolled. Among the adverse events, rash (n = 9, 8.9%) was the most frequent irAE, followed by mucositis (n = 3, 3.0%) and thyroiditis (n = 3, 3.0%). Patients in the irAEs+ group showed a higher tumor response rate than those in the irAEs− group (overall response rate: 28.6% vs 6.3%, P = .011; disease control rate: 85.7% vs 60.0%, P = .028). The median progression‐free survival (PFS) times were 14.8 months in the irAEs+ group and 4.1 months in the irAEs− group (P < .001). Further analysis based on the presence or absence of rash showed that the PFS of the patients in the irAEs+/rash+ group was better than that of those in the irAEs+/rash− or irAEs− group (all P < .05). Multivariate analysis showed that irAEs were an independent prognostic factor for PFS (hazard ratio HR: 0.22, P = .002). Thus, the occurrence of irAEs, especially rash, was associated with markedly improved PFS. Awareness of irAEs may help classify the subtype of HCC patients with an unprecedented survival benefit from anti‐PD‐1 antibodies.
What's new?
While anti‐program death receptor‐1 (anti‐PD‐1) antibodies produce clinical responses in patients with hepatocellular carcinoma (HCC), variations in efficacy and in the occurrence of adverse events present significant challenges in the clinical management of HCC. In the present study, the authors show that in HCC patients treated with anti‐PD‐1 antibodies, the development of immune‐related adverse events (irAEs), notably rash, is associated with improved progression‐free survival. The marked association between irAEs and treatment response suggests that irAEs could be used to predict survival in anti‐PD‐1 antibody‐treated HCC patients and could facilitate HCC subtype classification in patients who experience striking survival benefits.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background
The level of C‑reactive protein (CRP) and alpha‑fetoprotein (AFP) in immunotherapy (CRAFITY) score was associated with the prognosis of hepatocellular carcinoma (HCC) patients treated with ...immunotherapy. Based on the CRAFITY score, this study aimed to investigate the efficacy and safety of locoregional-immunotherapy for treating HCC patients.
Methods
HCC patients who received locoregional-immunotherapy were consecutively recruited at Sun Yat-sen University Cancer Center in 2019. CRAFITY 0 score was defined as the AFP level below 100 ng/ml and a CRP level of less than 1 mg/dl, CRAFITY 1 score was defined as the AFP level of at least 100 ng/ml or the CRP level of at least 1 mg/dl, and CRAFITY 2 score was defined as both the AFP level over 100 ng/ml and the CRP level of more than 1 mg/dl. The primary outcomes were progression-free survival (PFS) and overall survival (OS). The second outcomes were tumor response rate and treatment-related adverse events (AEs).
Results
The median PFS for HCC patients with the CRAFITY 0 score was not estimable. The PFS was 11.0 months 95% confidence interval (CI) 7.2–14.9 and 6.0 months (95% CI 4.2–7.8) for patients with CRAFITY 1 and 2 scores, respectively, with a significant difference between the two groups (
p
< 0.001). HCC patients with CRAFITY 0, 1, and 2 scores had 3 years OS rates of 63.8%, 60.8%, and 32.1%, respectively, with statistical differences among the three groups (
p
< 0.001). Patients with the CRAFITY 2 score were more likely to experience fever than those with other scores (
p
< 0.05). A greater CRAFITY score was correlated with a higher incidence of grade 3 and above liver injury (
p
< 0.01).
Conclusions
The CRAFITY score is a superior predictor of prognosis and treatment-related AEs in HCC patients treated with locoregional-immunotherapy.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The prediction of mechanical properties of cold-rolled steel is very important for the quality control, process optimization, and cost control of cold-rolled steel, but it is still a challenging task ...to predict accurately. For the existing graph structure of graph attention networks, it is difficult to effectively establish the complex coupling relationship and nonlinear causal relationship between variables. At the same time, it is considered that the process of cold-rolled steel has typical full-flow process characteristics and the graph attention network makes it difficult to extract the path information between the central node and its higher-order neighborhood. The neural Granger causality algorithm is used to extract the latent relationship between variables, and the basic graph structure of mechanical property prediction data is constructed. Secondly, the node embedding layer is added before the graph attention network, which leverages the symmetry nature of Node2vec method by incorporating both breadth-first and depth-first exploration strategies. This ensures a balanced exploration of diverse paths in the graph, capturing not only local structures but also higher-order relationships. The combined graph attention networks are then able to effectively capture the symmetry path information between nodes and dependencies between variables. The accuracy and superiority of this method are verified by experiments in real cold-rolled steel production cases.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
There is a lack of effective treatment to improve the prognosis of intrahepatic cholangiocarcinoma (ICC). Programmed cell death protein-1 (PD-1)-targeted immunotherapy has shown promising results in ...a variety of malignant tumours. However, in patients with advanced ICC, the safety and efficacy of anti-PD-1 agents remain unclear.
Forty-two advanced ICC patients treated with anti-PD-1 agents from August 2018 to December 2020 were retrospectively analyzed. Tumour response, overall survival (OS), progression-free survival (PFS), and time to tumour progression (TTP) were evaluated. Adverse events were also recorded.
The median duration of follow-up was 12.1 months, and the median time of treatment was 6.7 months for all patients. The median OS, median PFS, and median TTP for the whole cohort were 19.3 months, 11.6 months, and 11.6 months, respectively. The overall response rate (ORR) and disease control rate (DCR) for the whole cohort were 23.8% and 85.7%, respectively. Of the 42 evaluable individuals, two (4.8%) had hyperprogressive disease. The most common adverse events (AEs) were pain (n = 6; 14.3%), anorexia (n = 4; 9.5%), hypertension (n = 4; 9.5%), pyrexia (n = 3; 7.1%), cough (n = 3; 7.1%), and hypothyroidism (n = 3; 7.1%). The median OS of patients with albumin-bilirubin (ALBI) grade 1 was longer than that of patients with ALBI grade 2 (19.3 months vs. 14.7 months). The median PFS did not show a significant difference between ALBI grade 1 and grade 2 patients (13.6 months vs. 6.9 months).
PD-1-targeted immunotherapy showed promising efficacy and safety in advanced ICC patients.
Key messages
PD-1-targeted immunotherapy is a safe and effective treatment for advanced ICC patients.
This study provides therapeutic strategy for advanced ICC patients.
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