Optimal timing of combining sorafenib with trans-arterial chemoembolization in patients with hepatocellular carcinoma: A meta-analysis

Dai, Yanmei; Jiang, Huijie; Jiang, Hao; Zhao, Sheng; Zeng, Xu; Sun, Ran; Zheng, Ruoshui

doi:10.1016/j.tranon.2021.101238

Cited by 16 publications

(15 citation statements)

References 28 publications

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“…For now, molecularly targeted drugs are still the main treatment strategy for advanced HCC (72)(73)(74). Among them, Sorafenib is the most widely used (75)(76)(77). In order to overcome the shortcomings of Sorafenib, newly molecular targeted drugs including Regorafenib, Lenvatinib and Cabozantinib have been approved for marketing one after another (78)(79)(80).…”

Section: Discussionmentioning

confidence: 99%

A Novel Microcrystalline BAY-876 Formulation Achieves Long-Acting Antitumor Activity Against Aerobic Glycolysis and Proliferation of Hepatocellular Carcinoma

et al. 2021

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BAY-876 is an effective antagonist of the Glucose transporter type 1 (GLUT1) receptor, a mediator of aerobic glycolysis, a biological process considered a hallmark of hepatocellular carcinoma (HCC) together with cell proliferation, drug-resistance, and metastasis. However, the clinical application of BAY-876 has faced many challenges. In the presence study, we describe the formulation of a novel microcrystalline BAY-876 formulation. A series of HCC tumor models were established to determine not only the sustained release of microcrystalline BAY-876, but also its long-acting antitumor activity. The clinical role of BAY-876 was confirmed by the increased expression of GLUT1, which was associated with the worse prognosis among advanced HCC patients. A single dose of injection of microcrystalline BAY-876 directly in the HCC tissue achieved sustained localized levels of Bay-876. Moreover, the single injection of microcrystalline BAY-876 in HCC tissues not only inhibited glucose uptake and prolonged proliferation of HCC cells, but also inhibited the expression of epithelial-mesenchymal transition (EMT)-related factors. Thus, the microcrystalline BAY-876 described in this study can directly achieve promising localized effects, given its limited diffusion to other tissues, thereby reducing the occurrence of potential side effects, and providing an additional option for advanced HCC treatment.

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Section: Discussionmentioning

confidence: 99%

A Novel Microcrystalline BAY-876 Formulation Achieves Long-Acting Antitumor Activity Against Aerobic Glycolysis and Proliferation of Hepatocellular Carcinoma

et al. 2021

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“…A recent study has shown that adding sorafenib to TACE significantly prolongs the recurrence of HCC [23]. In contrast, other trials (SPACE and TACE2) [24,25] did not show significant benefit initially; however, later subgroup analyses suggested that a longer duration of treatment with sorafenib in combination with TACE may improve clinical outcomes [26]. A meta-analysis of randomized trials conducted by Facciorusso et al [27] showed that after chemoembolization there was a statistically significant increase in severe toxicity (risk ratio: 1.44, 1.08-1.92, p = 0.01), though this outcome might be influenced by the heterogeneity of the procedures used.…”

Section: Introductionmentioning

confidence: 99%

Transarterial Chemoembolization (TACE) Plus Sorafenib Compared to TACE Alone in Transplant Recipients with Hepatocellular Carcinoma: An Institution Experience

Abdelrahim

Victor²,

Esmail

et al. 2022

Cancers

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Background: Hepatocellular carcinoma (HCC) is the sixth most common malignancy and the third most common cause of cancer-related mortality worldwide. Transarterial chemoembolization has shown survival benefits in patients with early to intermediate-stage HCC, becoming the standard of care and recommended treatment modality by most clinical practice guidelines. The most recent trials of the TACE plus sorafenib combined therapy in patients with unresectable HCC have yielded inconsistent outcomes. The purpose of this study was to compare the outcomes of HCC patients treated with the TACE sorafenib combination as opposed to TACE monotherapy. Methods: This retrospective study included all patients with unresectable HCC who underwent liver transplantation and were treated by either TACE alone or TACE plus sorafenib between July 2008–December 2019. Demographic and clinical data as well as HCC recurrence post-liver transplant (LT) were reported as frequencies and proportions for categorical variables and as the median and interquartile range (IQR) or mean. Chi-square or Fisher’s exact tests were performed for categorical variables and the Kruskal-Wallis test or unpaired test was performed for continuous variables. Kaplan-Meier curves present overall patient survival and HCC-free survival. Results: A total of 128 patients received LT, with a median (IQR) age of 61.4 (57.0, 66.3) years; most were males (77%). Within the TACE-only group, 79 (77%) patients met the Milan criteria and 24 (23%) were beyond the Milan criteria, while the TACE plus sorafenib group had a higher proportion of patients beyond the Milan criteria: 16 (64%) vs. 9 (36%); p = 0.01. The five-year disease-free survival (DFS) between the treatment groups approached significance, with 100% DFS in the TACE plus sorafenib group vs. 67.2% in the TACE-alone group, p = 0.07. Five-year patient survival was 77.8% in the TACE plus sorafenib group compared to 61.5% in the TACE-alone group (p = 0.51). However, in patients who met the beyond Milan criteria, those who received TACE alone had a lower average amount of (percent) tumor necrosis on explant pathology (43.8% ± 32%) compared to patients who received TACE plus sorafenib (69.6% ± 32.8%, p = 0.03).Conclusion: This study identified that using TACE plus sorafenib is generally well-tolerated and demonstrated improved overall survival compared to TACE only in transplant recipients with unresectable HCC. A multi-center and prospective randomized controlled trial is needed to substantiate these findings.

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“… 6 , 7 The combination therapy of trans-arterial chemoembolization (TACE) and sorafenib was confirmed to prolong survival for advanced HCC effectively. 8 Among all these therapies, TACE was the most common treatment for HCC patients.…”

Section: Introductionmentioning

confidence: 99%

Development of a Prognostic Nomogram in Hepatocellular Carcinoma with Portal Vein Tumor Thrombus Following Trans-Arterial Chemoembolization with Drug-Eluting Beads

Cheng¹,

Yu²,

Liu³

et al. 2021

CMAR

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Objective To develop and validate a prognostic nomogram in eastern patients with hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) receiving trans-arterial chemoembolization with drug-eluting beads (DEB-TACE). Methods This retrospective study included 200 patients with training cohort (n = 118) from institution 1 and test cohort (n = 82) from institution 2. All these patients received first-line DEB-TACE between October 2016 and October 2018. Multivariate Cox proportional hazard regression analysis was performed on the training cohort to reveal the independent prognostic factors, and then prognostic nomograms were developed. In order to evaluate the performance of the nomogram comprehensively in both the training and test cohorts, C-index, Kaplan–Meier curve with Log rank test, receiver operating characteristic curve (ROC), calibration plot, and decision curve analysis (DCA) were performed. Results Tumor number, serum γ-glutamyl transferase (GGT) level, and level of PVTT were independent risk factors of prognosis. A nomogram was constructed to predict 6-, 12- and 18-month overall survival (OS) based on these identified prognostic factors. C-indexes of the nomogram were 0.88 (95% confidence interval [CI], 0.79–0.97) in the training cohort and 0.87 (95% CI, 0.75–0.99) in the test cohort. The Kaplan–Meier curve analysis showed that the nomogram was able to separate patients into low- and high-risk subgroups. ROC curves for the nomogram at 6-, 12- and 18-month showed satisfied discrimination, with an AUC of 0.765, 0.803 and 0.809 in the training cohort, respectively, and 0.772, 0.724 and 0.746 in the test cohort, respectively. The calibration curve demonstrated good agreement between predicted and actual survival rates in the training and test cohorts. The decision curve showed good performance of the nomogram in terms of clinical application. Conclusion We developed and validated a nomogram that was accurate and clinically useful in eastern patients with HBV-associated HCC with PVTT who underwent DEB-TACE.

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Optimal timing of combining sorafenib with trans-arterial chemoembolization in patients with hepatocellular carcinoma: A meta-analysis

Cited by 16 publications

References 28 publications

A Novel Microcrystalline BAY-876 Formulation Achieves Long-Acting Antitumor Activity Against Aerobic Glycolysis and Proliferation of Hepatocellular Carcinoma

A Novel Microcrystalline BAY-876 Formulation Achieves Long-Acting Antitumor Activity Against Aerobic Glycolysis and Proliferation of Hepatocellular Carcinoma

Transarterial Chemoembolization (TACE) Plus Sorafenib Compared to TACE Alone in Transplant Recipients with Hepatocellular Carcinoma: An Institution Experience

Development of a Prognostic Nomogram in Hepatocellular Carcinoma with Portal Vein Tumor Thrombus Following Trans-Arterial Chemoembolization with Drug-Eluting Beads

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