Efficacy, Safety, and Potential Biomarkers of Sunitinib and Transarterial Chemoembolization (TACE) Combination in Advanced Hepatocellular Carcinoma (HCC)

Pokuri, Venkata; Tomaszewski, Garin; Ait‐Oudhia, Sihem; Groman, Adrienne; Lugade, Amit A.; Thanavala, Yasmin; Ashton, Edward A.; Grande, Catherine; Fetterly, Gerald J.; Iyer, Renuka

doi:10.1097/coc.0000000000000286

Cited by 16 publications

(7 citation statements)

References 37 publications

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“…Because of our interest in methodologies to support clinical testing of RA therapies, we used a compartment model to interpret DCE-MRI data because the model parameters are independent of the imaging and injection conditions and should be more robust in multicenter trials. The DCE-MRI quantitation techniques used in this study have been validated in several multicenter clinical trials in other indications[ 15 , 44 , 45 ]. The simple compartment model has one vascular compartment and one tissue compartment and the measured signal is used to derive the constant of proportionality in the leak of GBCA from capillaries to tissue, K trans [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

Magnetic resonance imaging of the hand and wrist in a randomized, double-blind, multicenter, placebo-controlled trial of infliximab for rheumatoid arthritis: Comparison of dynamic contrast enhanced assessments with semi-quantitative scoring

Beals

Baumgartner

Peterfy³

et al. 2017

PLoS ONE

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The objective of this study was to compare the scope and the discriminative power of Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) to those of semi-quantitative MRI scoring for evaluating treatments for rheumatoid arthritis (RA) in multicenter randomized clinical trials (RCTs). Sixty-one patients with active RA participated in a double-blind, parallel group, randomized, multicenter methodology study receiving infliximab or placebo through 14 weeks. The most symptomatic wrist and metacarpophalangeal joints (MCPs) were imaged using MRI. In addition to clinical assessments with DAS28(CRP), the severity of inflammation was measured as synovial leak of gadolinium based contrast agent (GBCA) using DCE-MRI (Ktrans, primary endpoint) at weeks 0, 2, 4, and 14. Two radiologists independently scored synovitis, osteitis and erosion using RA MRI Score (RAMRIS) and cartilage loss using a 9-point MRI scale (CARLOS). Infliximab showed greater decrease from baseline in DAS28(CRP), DCE-MRI Ktrans of wrist and MCP synovium, and RAMRIS synovitis and osteitis at all visits compared with placebo (p<0.001). Treatment effect sizes of infliximab therapy were similar for DAS28(CRP) (1.08; 90% CI (0.63–1.53)) and MRI inflammation endpoints: wrist Ktrans (1.00 (0.55–1.45)), RAMRIS synovitis (0.85 (0.38–1.28)) and RAMRIS osteitis (0.99 (0.52–1.43)). Damage measures of bone erosion (RAMRIS) and cartilage loss (CARLOS) were reduced with infliximab compared to with placebo at 14 weeks (p≤0.025). DCE-MRI and RAMRIS were equally sensitive and responsive to the anti-inflammatory effects of infliximab. RAMRIS and CARLOS showed suppression of erosion and cartilage loss, respectively, at 14 weeks. (ClinicalTrials.gov registration: NCT01313520)

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Section: Discussionmentioning

confidence: 99%

Magnetic resonance imaging of the hand and wrist in a randomized, double-blind, multicenter, placebo-controlled trial of infliximab for rheumatoid arthritis: Comparison of dynamic contrast enhanced assessments with semi-quantitative scoring

Beals

Baumgartner

Peterfy³

et al. 2017

PLoS ONE

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“…The median duration of sorafenib in the combination arm was 38.7 months [100]. The efficacy of associating of TKIs and LDTs [101] has yet to be proven. Although, there is another ongoing phase III clinical study (NCT03905967) to evaluate if adding TACE with lenvatinib Is better than lenvatinib alone as first-line therapy in advanced HCC, the enthusiasm of the combination strategy is waning in particular amongst patients with advanced BCLC-C HCC where growing number of systemic therapy options are emerging.…”

Section: Current State Of Liver Directed Therapies Associated Withmentioning

confidence: 99%

Current State of Liver-Directed Therapies and Combinatory Approaches with Systemic Therapy in Hepatocellular Carcinoma (HCC)

Viveiros

Riaz

Lewandowski

et al. 2019

Cancers

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The increasing set of liver-directed therapies (LDT) have become an integral part of hepatocellular carcinoma (HCC) treatment. These range from percutaneous ablative techniques to arterial embolization, and varied radiotherapy strategies. They are now used for local disease control, symptom palliation, and bold curative strategies. The big challenge in the face of these innovative and sometimes overlapping technologies is to identify the best opportunity of use. In real practice, many patients may take benefit from LDT used as a bridge to curative treatment such as resection and liver transplantation. Varying trans-arterial embolization strategies are used, and comparison between established and developing technologies is scarce. Also, radioembolization utilizing yttrium-90 (Y-90) for locally advanced or intermediate-stage HCC needs further evidence of clinical efficacy. There is increasing interest on LDT-led changes in tumor biology that could have implications in systemic therapy efficacy. Foremost, additional to its apoptotic and necrotic properties, LDT could warrant changes in vascular endothelial growth factor (VEGF) expression and release. However, trans-arterial chemoembolization (TACE) used alongside tyrosine-kinase inhibitor (TKI) sorafenib has had its efficacy contested. Most recently, interest in associating Y-90 and TKI has emerged. Furthermore, LDT-led differences in tumor immune microenvironment and immune cell infiltration could be an opportunity to enhance immunotherapy efficacy for HCC patients. Early attempts to coordinate LDT and immunotherapy are being made. We here review LDT techniques exposing current evidence to understand its extant reach and future applications alongside systemic therapy development for HCC.

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“…Sunitinib is an oral multi-target TKI whose main targets are VEGFR and PDGFR, among others. A phase II trial studied sunitinib in combination with transarterial chemoembolization for treatment of advanced HCC, and patients had a median progression-free survival of 8 months and an OS of 14.9 months ( Pokuri et al, 2018 ). Again, our data indicate that low-risk patients will be more sensitive to erlotinib and sunitinib.…”

Section: Discussionmentioning

confidence: 99%

Construction of a Necroptosis-Associated Long Non-Coding RNA Signature to Predict Prognosis and Immune Response in Hepatocellular Carcinoma

Wang

Zhang

et al. 2022

Front. Mol. Biosci.

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Background: Necroptosis is a form of programmed cell death, and studies have shown that long non-coding RNA molecules (lncRNAs) can regulate the process of necroptosis in various cancers. We sought to screen lncRNAs associated with necroptosis to predict prognosis and tumor immune infiltration status in patients with hepatocellular carcinoma (HCC).Methods: Transcriptomic data from HCC tumor samples and normal tissues were extracted from The Cancer Genome Atlas database. Necroptosis-associated lncRNAs were obtained by co-expression analysis. Necroptosis-associated lncRNAs were then screened by Cox regression and least absolute shrinkage and selection operator methods to construct a risk model for HCC. The models were also validated and evaluated by Kaplan-Meier analysis, univariate and multivariate Cox regression, and time-dependent receiver operating characteristic (ROC) curves. In addition, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes enrichment, gene set enrichment, principal component, immune correlation, and drug sensitivity analyses were applied to assess model risk groups. To further differentiate the immune microenvironment of different HCC subtypes, the entire dataset was divided into three clusters, based on necroptosis-associated lncRNAs, and a series of analyses performed.Results: We constructed a model comprising four necroptosis-associated lncRNAs: POLH-AS1, DUXAP8, AC131009.1, and TMCC1-AS1. Overall survival (OS) duration was significantly longer in patients classified as low-risk than those who were high-risk, according to our model. Univariate and multivariate Cox regression analyses further confirmed risk score stability. The analyzed models had area under the ROC curve values of 0.786, 0.713, and 0.639 for prediction of 1-, 3-, and 5-year OS, respectively, and risk score was significantly associated with immune cell infiltration and ESTIMATE score. In addition, differences between high and low-risk groups in predicted half-maximal inhibitory concentration values for some targeted and chemical drugs, providing a potential basis for selection of treatment approach. Finally, cluster analysis facilitated more refined differentiation of the immune microenvironment in patients with HCC and may allow prediction of the effectiveness of immune checkpoint inhibitors.Conclusions: This study contributes to understanding of the function of necroptosis-related lncRNAs in predicting the prognosis and immune infiltration status of HCC. The risk model constructed and cluster analysis provide a basis for predicting the prognosis of patients with HCC and to inform the selection of immunotherapeutic strategies.

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Efficacy, Safety, and Potential Biomarkers of Sunitinib and Transarterial Chemoembolization (TACE) Combination in Advanced Hepatocellular Carcinoma (HCC)

Abstract: Encouraging progression-free survival and overall survival were seen with acceptable toxicity in our study of sunitinib and TACE combination in advanced HCC. Potential imaging and serum biomarkers showed increased benefit with combination therapy.

Cited by 16 publications

References 37 publications

Magnetic resonance imaging of the hand and wrist in a randomized, double-blind, multicenter, placebo-controlled trial of infliximab for rheumatoid arthritis: Comparison of dynamic contrast enhanced assessments with semi-quantitative scoring

Magnetic resonance imaging of the hand and wrist in a randomized, double-blind, multicenter, placebo-controlled trial of infliximab for rheumatoid arthritis: Comparison of dynamic contrast enhanced assessments with semi-quantitative scoring

Current State of Liver-Directed Therapies and Combinatory Approaches with Systemic Therapy in Hepatocellular Carcinoma (HCC)

Construction of a Necroptosis-Associated Long Non-Coding RNA Signature to Predict Prognosis and Immune Response in Hepatocellular Carcinoma

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