Arterially Directed Therapies for Hepatocellular Carcinoma

Shah, Rajesh P.; Brown, Karen T.; Sofocleous, Constantinos T.

doi:10.2214/ajr.11.7554

Cited by 22 publications

(26 citation statements)

References 81 publications

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“…In these interventions, catheter-based embolic agents are introduced into the hyperperfused tumor regions via the femoral artery and, ultimately, the hepatic artery branches (3).…”

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confidence: 99%

Early Dynamic ¹⁸F-FDG PET to Detect Hyperperfusion in Hepatocellular Carcinoma Liver Lesions

et al. 2013

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In addition to angiographic data on vascularity and vascular access, demonstration of hepatocellular carcinoma (HCC) liver nodule hypervascularization is a prerequisite for certain intrahepatic antitumor therapies. Early dynamic (ED) 18 F-FDG PET/ CT could serve this purpose when the current standard method, contrast-enhanced (CE) CT, or other CE morphologic imaging modalities are unsuitable. A recent study showed ED 18 F-FDG PET/CT efficacy in this setting but applied a larger-thanstandard 18 F-FDG activity and an elaborate protocol likely to hinder routine use. We developed a simplified protocol using standard activities and easily generated visual and descriptive or quantitative endpoints. This pilot study assessed the ability of these endpoints to detect HCC hyperperfusion and, thereby, evaluated the suitability in of the protocol everyday practice. Methods: Twenty-seven patients with 34 HCCs (diameter $ 1.5 cm) with hypervascularization on 3-phase CE CT underwent liver ED 18 F-FDG PET for 240 s, starting with 18 F-FDG (250-MBq bolus injection). Four frames at 15-s intervals, followed by 3 frames at 60-s intervals were reconstructed. Endpoints included focal tracer accumulation in the first 4 frames (60 s), subsequent focal washout, and visual and quantitative differences between tumor and liver regions of interest in maximum and mean ED standardized uptake value (ED SUVmax and ED SUVmean, respectively) 240-s time-activity curves. Results: All 34 lesions were identified by early focal 18 F-FDG accumulation and faster time-to-peak ED SUVmax or ED SUVmean than in nontumor tissue. Tumor peak ED SUVmax and ED SUVmean exceeded liver levels in 85% and 53%, respectively, of lesions. Nadir tumor signal showed no consistent pattern relative to nontumor signal. HCC had a significantly shorter time to peak and significantly faster rate to peak for both ED SUVmax and ED SUVmean curves and a significantly higher peak ED SUVmax but not peak ED SUVmean than the liver. Conclusion: This pilot study provided proof of principle that our simplified ED 18 F-FDG PET/CT protocol includes endpoints that effectively detect HCC hypervascularization; this finding suggests that the protocol can be used routinely.

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“…In these interventions, catheter-based embolic agents are introduced into the hyperperfused tumor regions via the femoral artery and, ultimately, the hepatic artery branches (3).…”

mentioning

confidence: 99%

Early Dynamic ¹⁸F-FDG PET to Detect Hyperperfusion in Hepatocellular Carcinoma Liver Lesions

et al. 2013

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“…While TACE carries a 1A recommendation for stage B disease (15), some institutions rely on bland embolization due to the overall cost versus TACE as well as conflicting studies comparing their efficacy (14,(16)(17)(18). Age has not been demonstrated as a factor that impacts outcome with TAE (19).…”

Section: Patient Selectionmentioning

confidence: 99%

“…The goal of catheter placement is to ensure complete vascular coverage of the tumor with sparing of as much normal parenchyma as possible, limiting the amount of normal tissue ischemia and post embolization syndrome. Embolic agents selection and composition varies, but small embolic material sizes generally range from 40-300 μm (15). One important consideration in catheter directed embolotherapy involves intra-tumoral arterial-venous shunts, which may result in inadvertent pulmonary arterial embolization if particle size is too small.…”

Section: Technique and Considerationsmentioning

confidence: 99%

Locoregional and systemic therapy for hepatocellular carcinoma

Gbolahan

Schacht

Beckley

et al. 2017

J. Gastrointest. Oncol.

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The management of hepatocellular carcinoma (HCC) remains challenging due to late presentation and the presence of accompanying liver dysfunction. As such, most patients are not eligible for curative resection and liver transplant. Management in this scenario depends on a number of factors including hepatic function, tumor burden, patency of hepatic vasculature and patients' functional status. Based on these, patients can be offered catheter based intra-arterial therapy for intermediate stage disease and in more advanced disease, sorafenib. Given recent data, regorafenib is now an option following failure of sorafenib.Catheter directed intra-arterial therapy takes advantage of tumor hypervascularity and the unique dual blood supply of the liver, as hepatic tumors receive arterial perfusion via the hepatic artery while the rest of the liver is supplied by the portal vein. This allows selective embolization and delivery of chemotherapeutic agents to the tumor. Compared to best supportive care, intra-arterial therapy offers a survival benefit in intermediate stage HCC and is the recommended approach for treatment. None of the catheter based approaches; including bland embolization, conventional trans-arterial chemoembolization (cTACE), drug eluting bead trans-arterial chemoembolization (DEB-TACE) or trans-arterial radioembolization (TARE) offers a clear advantage over the other, although DEB-TACE may be characterized by less systemic toxicity. All of these approaches are contraindicated in patients with portal vein thrombosis (PVT). On the other hand, intraarterial, radio embolization, with Yttrium-90 (Y90) can be offered to patients with PVT. The place of this modality in management of HCC is still being investigated. The role of sorafenib in advanced HCC is not in doubt, as until recently, it was the only systemic therapy approved for the management in this setting. This is despite multiple trials evaluating other agents. The addition of sorafenib to catheter-based therapy in intermediate stage disease has also failed to show any benefit. The modest survival benefit with sorafenib and the failure of other targeted agents suggest that it is important to look beyond inhibition of angiogenesis in advanced HCC. Identification of key drivers and mediators of HCC remains paramount for successful drug development. In line with this, it is refreshing that the excitement that has followed developments in cancer immunotherapy is finding its way to HCC with early trials of anti-PD1 monoclonal antibodies showing sufficient activity that phase III trials are now ongoing for Pembrolizumab and Nivolumab in advanced HCC. Future drug development efforts will focus on defining the feasibility of combining different treatment approaches targeting multiple important modulators of HCC.

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“…3 Hypoxia produces cell death if severe or prolonged, though cancer cells can survive by some genetic and adaptive changes in a mild or short time condition of hypoxia. [4][5][6] The standard TACE procedure has been established to deliver emulsion of anticancer agent and lipiodol followed by embolization material (e.g., gelatin sponge particles, polyvinyl alcohol (PVA) particles) with or without transarterial chemo-infusion. 3,6,7 The emulsion of lipiodol and anticancer agent is selectively retained within the tumor, which increases the exposure of the neoplastic cells to chemotherapy.…”

mentioning

confidence: 99%

“…[4][5][6] The standard TACE procedure has been established to deliver emulsion of anticancer agent and lipiodol followed by embolization material (e.g., gelatin sponge particles, polyvinyl alcohol (PVA) particles) with or without transarterial chemo-infusion. 3,6,7 The emulsion of lipiodol and anticancer agent is selectively retained within the tumor, which increases the exposure of the neoplastic cells to chemotherapy. Moreover, the embolization material (particles) blocks the tumoral blood supply and limits the washout of drugs, which helps the emulsion to remain inside the tumor.…”

mentioning

confidence: 99%

Cytotoxic Activity of Anticancer Drugs on Hepatocellular Carcinoma Cells in Hypoxic-Hyponutritional Culture

Zhu

Yang

et al. 2014

International Surgery

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To investigate which anticancer drugs and combination of dual drugs could further promote the inhibition of cell growth in vitro against HCC cell line (HepG2) in the hypoxic and hyponutritional culture medium (HHCM) mimicked the different scenarios of transcatheter arterial chemoembolization (TACE). The cells of hepatocellular carcinoma (HCC) treated by TACE suffered various hypoxia and hyponutrition. The cells were treated for 2 hours, 4 hours, 6 hours, and 24 hours, respectively, using 10 drugs including epirubicin (EPI), cisplatin (DDP), mitomycin-C (MMC), oxaliplatin (OXA), hydroxycamptothecin (HCPT), 5-fluorouracil (5-FU), gemcitabine (GEM), docetaxel (DTX), thiotepa (TSPA), and pemetrexed disodium (PEM) in 4 concentrations of HHCM (5%, 10%, 25%, and 50%, respectively) mimicking the scenario of TACE and were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cells treated with combinations of dual drugs for 24 hours were also tested. The sensitive drugs with inhibition rates more than 30% were EPI, MMC, HCPT, OXA, and PEM in 4 types of HHCMs. The sensitivity of the cells to treatment with drugs for 24 hours was significantly higher than the sensitivity of the cells to treatment with drugs for 2 hours in 5%, 10%, and 25% HHCM. The sensitivity of the combination of dual drugs was no more than the sensitivity of the single drug with higher sensitivity in 4 concentrations of HHCM. EPI, MMC, HCPT, OXA, and PEM exhibited cytotoxic activity against HepG2 cells in various hypoxia and hyponutrition states. Prolonging the time of exposure could increase the sensitivity of drug, and the combination of dual drugs cannot enhance the cytotoxic effect.

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Arterially Directed Therapies for Hepatocellular Carcinoma

Abstract: Chemoembolization, particle embolization, drug-eluting beads, and radioembolization have been used for locoregional control. This review discusses patient selection, techniques, safety, clinical outcomes, and imaging findings related to these therapies.

Cited by 22 publications

References 81 publications

Early Dynamic ¹⁸F-FDG PET to Detect Hyperperfusion in Hepatocellular Carcinoma Liver Lesions

Early Dynamic ¹⁸F-FDG PET to Detect Hyperperfusion in Hepatocellular Carcinoma Liver Lesions

Locoregional and systemic therapy for hepatocellular carcinoma

Cytotoxic Activity of Anticancer Drugs on Hepatocellular Carcinoma Cells in Hypoxic-Hyponutritional Culture

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Arterially Directed Therapies for Hepatocellular Carcinoma

Abstract: Chemoembolization, particle embolization, drug-eluting beads, and radioembolization have been used for locoregional control. This review discusses patient selection, techniques, safety, clinical outcomes, and imaging findings related to these therapies.

Cited by 22 publications

References 81 publications

Early Dynamic 18F-FDG PET to Detect Hyperperfusion in Hepatocellular Carcinoma Liver Lesions

Early Dynamic 18F-FDG PET to Detect Hyperperfusion in Hepatocellular Carcinoma Liver Lesions

Locoregional and systemic therapy for hepatocellular carcinoma

Cytotoxic Activity of Anticancer Drugs on Hepatocellular Carcinoma Cells in Hypoxic-Hyponutritional Culture

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Early Dynamic ¹⁸F-FDG PET to Detect Hyperperfusion in Hepatocellular Carcinoma Liver Lesions

Early Dynamic ¹⁸F-FDG PET to Detect Hyperperfusion in Hepatocellular Carcinoma Liver Lesions