Search

Simple Summary: Various cancer therapies are often ineffective for advanced metastatic liver disease. While immunotherapy can be effective in some cases, it does not provide significant benefits for metastatic cancer in the liver. CBL0137 is an experimental drug that helps form a special type of DNA called Z-DNA, which may help boost the body's immune response against tumors. We investigated how CBL0137 affects metastatic liver tumor models from colon (CT26) and breast (4T1) cancers focusing on how it triggers immune responses. The results showed that CBL0137 hepatic arterial infusion (HAI) enhanced anti-tumor effects by depleting immune-suppressing cells while preserving effector T cells. Combining CBL0137 HAI with conventional immunotherapy improved survival in 4T1 tumors but not in CT26 tumors, highlighting the importance of targeting specific immune cell populations for effective treatment. Background: Surgery, chemotherapy, and radiation often have limited utility for advanced metastatic disease in the liver, and despite its promising activity in select cancers, PD-1 blockade therapy similarly has minimal benefit in this setting. Curaxin, CBL0137, is an experimental anti-cancer drug that disrupts the binding of DNA to histones, destabilizes chromatin, and induces Z-DNA formation which may stimulate anti-tumor immune responses. Methods: Murine cell lines of colon (CT26) and breast (4T1) cancer were interrogated for survival and CBL0137-associated DNA changes in vitro. Immunocompetent models of liver metastases followed by CBL0137 hepatic arterial infusion (HAI) were used to examine in vivo tumor cell DNA alterations, treatment responses, and the immune contexture associated with CBL0137, both alone and in combination with anti-PD-1 therapy. Results: CBL0137 induced immediate changes to favor tumor cell death in vitro and in vivo with an efficient tumor uptake via the HAI route. Toxicity to CBL0137 was minimal and anti-tumor treatment effects were more efficient with HAI compared to intravenous delivery. Immune effects were pronounced with CBL0137 HAI with concurrent depletion of a specific population of myeloid-derived suppressor cells and maintenance of effector T cell populations. Conclusions: Combination of CBL0137 HAI with PD-1 blockade improved survival in 4T1 tumors but not in CT26 tumors, and therapeutic efficacy relies on the finding of simultaneous and targeted depletion of myeloid-derived suppressor cells and skewing of T cell populations to produce synergy with PD-1 blockade therapy. [ABSTRACT FROM AUTHOR]

Background: Hepatic arterial infusion pump (HAIP) treatment is a technique used to treat liver localized malignancy with intra-arterial chemotherapy. Methylene blue is generally administered to verify hepatic perfusion and exclude inadvertent extrahepatic perfusion. The use of indocyanine green dye (ICG) combined with near-infrared (NIR) fluorescence imaging during robot-assisted HAIP placement may be an attractive alternative by providing high contrast without blue discoloration of the operative field. Methods: Data was collected retrospectively from 2 centers in the Netherlands. Intraoperative perfusion of the liver segments and extrahepatic perfusion were assessed using ICG/NIR as well as methylene blue on video imaging and correlated to postoperative 99 m-Tc perfusion scintigraphy. Results: 13 patients underwent robot-assisted surgery for HAIP placement; median length of stay was 4 days, complications occurred in 4 patients. Hepatic perfusion showed identical patterns when ICG was compared with methylene blue. In 1 patient, additional extrahepatic perfusion was found using ICG, leading to further vessel ligation. Intraoperative ICG perfusion was concordant with 99 m-Tc perfusion scintigraphy. Discussion: Liver and extrahepatic perfusion determined by ICG fluorescence imaging is concordant with blue dye perfusion and 99 m-Tc perfusion scintigraphy. Therefore, ICG fluorescence imaging is deemed a safe and reliable technique for perfusion testing during robot-assisted HAIP placement. [ABSTRACT FROM AUTHOR]

Peptide receptor radionuclide therapy (PRRT) confers significant progression-free survival advantage for patients with small bowel grade 1 and 2 well-differentiated neuroendocrine tumors (WD NET). PRRT may also be clinically beneficial for patients with NET of pancreatic, bronchial, and other sites of origin; patients with paragangliomas; as well as for patients with well-differentiated grade 3 NET. Direct intra-arterial (IA) administration of PRRT into the hepatic artery for patients with NET liver metastases may result in higher radiopharmaceutical dose and longer dwell time in the liver tumors while relatively sparing non-tumor liver tissue and other organs such as the kidneys and bone marrow when compared with intravenous (IV) administration. This review summarizes currently available data on IA and IV PRRT dose distribution, reports safety and efficacy of IA PRRT, and proposes future research questions. [ABSTRACT FROM AUTHOR]

Purpose: Identify risk factors for biliary toxicity in patients with colorectal liver metastases who received floxuridine (FUDR) via a surgically implanted hepatic artery infusion pump (HAIP). Describe the incidence of biliary toxicity and evaluate relevant patterns in the biliary toxicity cohort. Methods: A single center, retrospective, case-control study included adult colorectal cancer patients with liver metastases who received at least one cycle of FUDR via a surgically implanted HAIP from 1 January 2017, to 1 October 2021. Patients were excluded if they had incomplete records, cholangiocarcinoma diagnosis, or received concurrent mitomycin and FUDR. Biliary toxicity criteria derived from existing HAIP literature were utilized to determine whether patients experienced biliary toxicity. Multiple variables were compared by univariate statistical analysis between the biliary toxicity and non-biliary toxicity cohorts to identify potential risk factors for development of FUDR-induced biliary toxicity. Results: Out of 50 patients who had a HAIP implanted, 39 met the inclusion criteria. Five of the 39 patients (12.7%) included in the analysis met the pre-specified biliary toxicity criteria. No risk factors for biliary toxicity were identified. All five patients who developed biliary toxicity demonstrated elevations in alkaline phosphatase (ALP) prior to meeting the toxicity criteria. Conclusion: Biliary toxicity remains a significant and therapy-limiting consequence of FUDR administration. Rising ALP may be an early indicator of subsequent biliary toxicity. Future studies with more patients may identify risk factors that can facilitate risk mitigation strategies. [ABSTRACT FROM AUTHOR]

Simple Summary: Dedicated catheters for hepatic arterial infusion chemotherapy were removed from the market, leading to a decrease in the number of patients eligible for this therapy. The purpose of this study was to assess the results of a novel approach to overcome the shortage of dedicated catheters for hepatic arterial infusion chemotherapy in the treatment of colorectal cancer liver metastases. The main modification of our placement technique consisted of the use of an indwelling 5-Fr Vertebral catheter, on the tip of which we created a two-sided additional lateral hole. The catheter was connected to a pediatric port. Fourteen patients underwent 15 modified procedures. The primary success rate was 100%, and the secondary success rate was 93.3%. There were two late major complications, graded IIIa according to the Clavien–Dindo classification. Our experience suggests that the derived utilization of the devices used routinely in interventional radiology provides an effective solution that can compensate for the shortage of dedicated devices. Dedicated catheters for hepatic arterial infusion chemotherapy were removed from the market. The purpose of this study was to assess the results of a novel approach to overcome the shortage of dedicated catheters for hepatic arterial infusion chemotherapy in the treatment of colorectal cancer liver metastases. We retrospectively included patients who underwent a percutaneous placement of a hepatic intra-arterial port catheter in a single tertiary center from February 2021 to June 2022. We examined the patient baseline characteristics, technical features of the modified procedures, technical success rates, complications and oncological outcomes. Fourteen patients (median age: 60 years; q1 = 54; q3 = 70; range: 53–81 years) underwent 15 modified procedures. The main modification of our placement technique consisted of the use of an indwelling 5-Fr Vertebral catheter, on the tip of which we created a two-sided additional lateral hole. The catheter was connected to a pediatric port. The primary success rate was 100%, and the secondary success rate was 93.3%. There were two late major complications, graded IIIa according to the Clavien–Dindo classification. The median liver progression free survival was 6.1 months (q1 = 2.5; q3 = 7.2; range: 1.3–11.6). Our experience suggests that the derived utilization of the devices used routinely in interventional radiology provides an effective solution that can compensate for the shortage of dedicated devices. [ABSTRACT FROM AUTHOR]

Background: Hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin and 5-fluorouracil was effective in unresectable hepatocellular carcinoma (HCC). The program of FOLFOX-HAIC in HCC was performed for 1 day (HAIC 1d) or 2 days (HAIC 2d). We hereby retrospectively compared the efficacy and safety between these two treatment regimens and explored the predictive power of thymidylate synthase (TYMS), an enzyme involved in the DNA synthesis process and metabolism of fluorouracil.Methods: This study included patients with a primary diagnosis of unresectable HCC. These patients received HAIC for 1 day or 2 days. The overall survival (OS), progression-free survival (PFS), tumor response, and adverse events were compared. The propensity score matching (PSM) was used to reduce bias. Peripheral blood samples before the treatments were collected and used to measure the concentration of TYMS through enzyme-linked immunosorbent assay (ELISA). ELISA was performed according to the manufacturers' guidelines.Results: We included 368 patients for this study: 248 in the HAIC 1d group and 120 in the HAIC 2d group. There was no significant difference of OS between the two groups (14.5 for HAIC 1d vs 15.3 months for HAIC 2d, p=0.46). Compared with the HAIC 1d group, the HAIC 2d group did not prolong the PFS (7.3 vs 7.5 months, p=0.91) or elevate the tumor response (42.5% vs 39.1%, p=0.53) per RECIST 1.1. In the PSM cohort, the efficacy between the two groups was similar. The total frequencies of grade 3-4 events were higher with the HAIC 2d group than with the HAIC 1d group, especially in the PSM cohort (p=0.043). Additionally, patients with TYMS low level might benefit longer OS from the HAIC 2d group (18.7 vs 13.6 months, p=0.014).Conclusions: There was not much of a difference in efficacy between the two groups, but the HAIC for 1 day might be safer, which needed further research. The level of TYMS might be the predictive biomarkers. [ABSTRACT FROM AUTHOR]

Background: Hepatic arterial infusion chemotherapy delivers the drug directly to the liver. We aim to explore the benefits and tolerability of Hepatic arterial infusion chemotherapy plus regorafenib in advanced colorectal liver metastasis refractory to standard systemic chemotherapy.Methods: This study analyzed 47 patients treated with hepatic arterial infusion chemotherapy plus regorafenib after standard systemic oxaliplatin and/or irinotecan in combination with bevacizumab or cetuximab between Jan 2017 and Jun 2020. Regorafenib was given for only 3 weeks in a 4-week cycle.Results: Among 47 patients, 32 (68%) were males. The median age was 61 (29-75). With a median follow-up of 22.2 months (3.7-50.7 months). Before Hepatic arterial infusion chemotherapy administration in combination with regorafenib, 34 (72.3%) patients previously received ≥ 2 prior lines of systemic therapy and 37 (78.7%)patients previously received targeted biological treatment (anti-VEGF or anti-EGFR, or both). The initial doses of regorafenib were 40 mg/d (n = 1, 2.13%), 80 mg/d (n = 11, 23.43%), 120 mg/d (n = 2, 4.26%), and 160 mg/d (n = 23, 48.94%), while for 24.6% (n = 14) dose was unknown. Median Overall Survival was 22.2 months. Median Progression-Free Survival was 10.8 (95% CI: 9.0-13.7) months. Common Adverse Events were hand-foot skin reaction (12.77%), fatigue (6.38%), vomiting (6.38%), and decreased appetite (6.38%). Only 2 patients discontinued regorafenib due to Adverse Events.Conclusions: Regorafenib combined with Hepatic arterial infusion was effective and tolerable in patients with liver predominant metastasis of colorectal cancer. Hence, this therapy can be considered as an alternative for second- or subsequent lines of therapy in patients refractory to standard systemic chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Patients with hepatocellular carcinoma (HCC) and macrovascular invasion (MVI) who receive systemic chemotherapy have a poor prognosis. This study aimed to determine if one-shot cisplatin (CDDP) chemotherapy via hepatic arterial infusion (HAI) combined with radiation therapy (RT) prior to systemic chemotherapy could improve the outcomes of these patients.Methods: This study consisted of 32 HCC patients with the following eligibility criteria: (i) portal vein invasion 3/4 and/or hepatic vein invasion 2/3; (ii) received one-shot CDDP via HAI; (iii) received RT for MVI, (iv) a Child-Pugh score ≤ 7; and (v) an Eastern Clinical Oncology Group Performance Status score of 0 or 1. To determine the therapeutic effect, we collected information on patient characteristics and took contrast-enhanced computed tomography at the start of the therapy and every 2 to 4 months after the start of therapy. We evaluated the overall response of the tumor and tumor thrombosis according to modified Response Evaluation Criteria in Solid Tumors. We assessed patient data using the Mann-Whitney U and Fisher exact tests and evaluated overall survival and progression-free survival using the log-rank test.Results: The overall response rate at the first evaluation performed a median of 1.4 weeks after HAI was 16% for the main intrahepatic tumor and 59% for the MVI. The best responses were the same as those of the first-time responses. The duration of median survival was 8.6 months, and progression-free survival of the main intrahepatic tumor was 3.2 months. Predictive factors for overall survival were the relative tumor volume in the liver and the first therapeutic response of MVI. There were no severe adverse events or radiation-induced hepatic complications.Conclusions: One-shot CDDP via HAI and RT were well tolerated and showed immediate and favorable control of MVI. Thus, this combination shows potential as a bridging therapy to systemic chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Colorectal liver metastases (CRLM) are the most common cause of disease-specific mortality in patients with colorectal cancer. Hepatic artery infusion (HAI) combined with systemic chemotherapy improves survival for these patients. The safety of colorectal resection at the time of HAI pump placement has not been well established.Methods: Patients with CRLM who underwent combined HAI pump placement and colorectal (primary) resection or HAI pump placement alone were evaluated for perioperative outcomes, pump-specific complications, infectious complications, and time to treatment initiation. These outcomes were compared using comparative statistics.Results: Patients who underwent combined HAI pump placement and primary resection (n = 19) vs HAI pump placement alone (n = 13) had similar demographics and rates of combined hepatectomy. Combined HAI pump placement and primary resection group had similar operative time and blood loss (both p = NS), but longer length of stay (6 vs 4 days, p = 0.02) compared to pump placement alone. Overall postoperative complications (21% vs 8%) and pump-specific complications (16% vs 31%) were similar (both p = NS). Infection rates were not different between groups, nor was time to initiation of HAI therapy (19 vs 16 days p = NS), or systemic therapy (34 vs 35 days p = NS).Conclusion: Combining colorectal resection with HAI pump implantation is a safe surgical approach for management of unresectable CRLM. Postoperative complications, specifically infectious complications, were not increased, nor was there a delay to initiation of HAI or systemic chemotherapy. Investigation of long-term oncologic outcomes for HAI pump placement and primary tumor resection in patients with unresectable CRLM is ongoing. [ABSTRACT FROM AUTHOR]

Primary liver tumours (i.e. hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC)) are among the most frequent cancers worldwide. However, only 10–20% of patients are amenable to curative treatment, such as resection or transplant. Liver metastases are most frequently caused by colorectal cancer, which accounts for the second most cancer-related deaths in Europe. In both primary and secondary tumours, radioembolization has been shown to be a safe and effective treatment option. The vast potential of personalized dosimetry has also been shown, resulting in markedly increased response rates and overall survival. In a rapidly evolving therapeutic landscape, the role of radioembolization will be subject to changes. Therefore, the decision for radioembolization should be taken by a multidisciplinary tumour board in accordance with the current clinical guidelines. The purpose of this procedure guideline is to assist the nuclear medicine physician in treating and managing patients undergoing radioembolization treatment. Preamble: The European Association of Nuclear Medicine (EANM) is a professional non-profit medical association that facilitates communication worldwide among individuals pursuing clinical and research excellence in nuclear medicine. The EANM was founded in 1985. These guidelines are intended to assist practitioners in providing appropriate nuclear medicine care for patients. They are not inflexible rules or requirements of practice and are not intended, nor should they be used, to establish a legal standard of care. The ultimate judgment regarding the propriety of any specific procedure or course of action must be made by medical professionals taking into account the unique circumstances of each case. Thus, there is no implication that an approach differing from the guidelines, standing alone, is below the standard of care. To the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set out in the guidelines when, in the reasonable judgment of the practitioner, such course of action is indicated by the condition of the patient, limitations of available resources or advances in knowledge or technology subsequent to publication of the guidelines. The practice of medicine involves not only the science but also the art of dealing with the prevention, diagnosis, alleviation and treatment of disease. The variety and complexity of human conditions make it impossible to always reach the most appropriate diagnosis or to predict with certainty a particular response to treatment. Therefore, it should be recognised that adherence to these guidelines will not ensure an accurate diagnosis or a successful outcome. All that should be expected is that the practitioner will follow a reasonable course of action based on current knowledge, available resources and the needs of the patient to deliver effective and safe medical care. The sole purpose of these guidelines is to assist practitioners in achieving this objective. [ABSTRACT FROM AUTHOR]

Purpose: To compare the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) to transarterial chemoembolization/embolization (TACE/TAE) for the treatment of advanced hepatocellular carcinoma (HCC) with major portal vein tumor thrombosis (PVTT).Materials and Methods: Forty-six patients with advanced HCC with major PVTT who underwent HAIC or TACE/TAE between April 2013 and April 2017 were included. In the HAIC group (n = 22), oxaliplatin (35-40 mg/m2 for 2 h) and 5-fluorouracil (600-800 mg/m2 for 22 h) on days 1-3 every 4 weeks were administered for a maximum of six serial courses. In the TACE/TAE group (n = 24), an emulsion of epirubicin (40-60 mg) and lipiodol was administered followed by particles (cTACE), or particles alone embolization (TAE). Overall survival (OS), tumor response according to mRECIST, progression-free survival (PFS), and adverse events were investigated.Results: Median OS was 20.8 months in the HAIC group versus 4.0 months in the TACE/TAE group (P < 0.001; hazard ratio [HR], 0.17). The HAIC group showed higher tumor response rates than the TACE/TAE group (59.1% [13/22] vs. 22.7% [5/22]; P = 0.014) and a longer median PFS (9.6 vs. 1.5 months; P < 0.001; HR, 0.09). The Child-Pugh class (P = 0.007) and treatment method (P = 0.002) were independent risk factors of survival. The most frequent grade 3 or worse treatment-related adverse events were liver dysfunction (2 [9.1%] vs. 5 [20.8%]), hematological abnormalities (1 [4.5%] vs. 2 [8.3%]), and fever (1 [4.5%] vs. 4 [16.7%]). One treatment-related death due to acute liver failure occurred 3 days after TACE treatment.Conclusion: HAIC may significantly improve OS and provide better tumor control with mild side effects and preserved liver function in patients with advanced HCC with major PVTT compared to TACE/TAE treatment. [ABSTRACT FROM AUTHOR]

Introduction: Hepatic arterial infusion chemotherapy (HAIC) is a feasible treatment for patients with colorectal cancer (CRC) with unresectable liver metastases. Objective: The aim of this retrospective study was to assess HAIC of 5-fluorouracil (5FU) in patients with unresectable liver metastases from CRC refractory to standard systemic chemotherapy. Methods: A total of 137 patients (85 men, 52 women; median age, 62 years; with KRAS mutation, n = 57) were recruited from seven institutions from September 2008 to December 2015. These patients were refractory to systemic chemotherapy including three cytotoxic agents (fluoropyrimidine, oxaliplatin, and irinotecan) with two molecular-targeted agents (bevacizumab and epidermal growth factor receptor antibody [cetuximab or panitumumab]). All patients underwent HAIC of continuous 5FU for unresectable liver metastases. Overall survival time, time to treatment failure, objective response rate, disease control rate, and incidence of adverse events to HAIC were assessed retrospectively. Results: The median overall survival time was 4.8 months (95% confidence interval [CI], 4.0–5.7 months), whereas time to treatment failure was 2.4 months (95% CI, 2.0–2.8 months). The objective overall response rate and disease control rate were 12.4 and 64%, respectively. Grade 3 or 4 adverse events were observed in 2.9% of the patients (hyperbilirubinemia in 2, liver abscess in 1, and myelosuppression in 1). Conclusions: There were few incidences of severe adverse events to HAIC of 5FU for liver metastases from CRC refractory to standard systemic chemotherapy. Therefore, it might present as a treatment option as last-line chemotherapy. [ABSTRACT FROM AUTHOR]

Background: There is lack of data for identifying optimal local therapy for the management of recurrent hepatocellular carcinoma (HCC) after hepatic resection.Aims: A retrospective study was performed to compare the effectiveness of transarterial chemoembolization (TACE) plus radiofrequency ablation (RFA) with that of TACE alone for recurrent HCC.Methods: From 2007 to 2013, patients with recurrent HCC ≤ 5 cm were treated with either TACE plus RFA (n = 96) or TACE (n = 63). Inverse probability of treatment weighting was used to make allowances for imbalances in treatment assignment. The disease-free survival (DFS) and overall survival (OS) were retrospectively analyzed.Results: The TACE group had lower pretreatment Child-Pugh class (P = 0.025) and shorter pretreatment interval of recurrence (P = 0.028). The 1-, 3-, and 5-year DFS rates for the TACE-RFA group were 55.1%, 22.5%, and 9.7%, respectively, and 41.1%, 9.9%, and 4.9%, respectively, for the TACE group. The OS rates at 1, 3, and 5 years were 82.3%, 42.7%, and 16.5%, respectively, in the TACE-RFA group, and 75.9%, 30.7%, and 11.3%, respectively, in the TACE group. Cirrhosis was significantly associated with disease progression (hazard ratio [HR] 1.53; 95% CI 1.09-2.14; P = 0.014).Conclusions: In patients with recurrent HCC ≤ 5 cm, TACE-RFA shows better DFS than TACE alone as a first-line local therapy. [ABSTRACT FROM AUTHOR]

Background: Liver-directed hepatic arterial therapies are associated with improved survival and effective symptom control for patients with unresectable neuroendocrine liver metastases (NELM). Whether transarterial chemoembolization (TACE) or transarterial radioembolization (TARE) with yttrium-90 (y-90) are associated with improved short- or long-term outcomes is unknown.Study Design: A retrospective review was performed of all patients with NELM undergoing transarterial therapies, from 2000 to 2018, at 2 academic medical centers. Postoperative morbidity, radiographic response according to response evaluation criteria in solid tumors (RECIST) criteria, and long-term outcomes were compared between patients who underwent TACE vs TARE.Results: Among 248 patients with NELM, 197 (79%) received TACE and 51 (21%) received TARE. While patients who underwent TACE were more likely to have carcinoid syndrome, larger tumors, and higher chromogranin A levels, there was no difference in tumor differentiation, primary site, bilobar disease, or synchronous presentation. Nearly all TARE treatments (92%) were performed as outpatient procedures, while 99% of TACE patients spent at least 1 night in the hospital. There were no differences in overall morbidity (TARE 13.7% vs TACE 22.6%, p = 0.17), grade III/IV complication (5.9% vs 9.2%, p = 0.58), or 90-day mortality. The disease control rate (DCR) on first post-treatment imaging (RECIST partial/complete response or stable disease) was greater for TACE compared with TARE (96% vs 83%, p < 0.01). However, there was no difference in median overall survival (OS, 35.9 months vs 50.1 months, p = 0.3) or progression-free survival (PFS, 15.9 months vs 19.9 months, p = 0.37).Conclusions: In this retrospective multi-institutional analysis, both TACE and TARE with Y-90 were safe and effective liver-directed therapies for unresectable NELM. Although TARE was associated with a shorter length of hospital stay, TACE demonstrated improved short-term DCR, and both resulted in comparable long term outcomes. [ABSTRACT FROM AUTHOR]

Background: The aim of the study was to evaluate the safety and feasibility of intra-arterial mitomycin C (MMC) infusion after selective internal radiation therapy (SIRT) using Yttrium-90 (90Y) resin microspheres in liver metastatic breast cancer (LMBC) patients. Patients and methods: The prospective pilot study included LMBC patients from 2012–2018. Patients first received infusion of 90Y resin microspheres, after 6–8 weeks response to treatment was assessed by MRI, 18F-FDG PET/CT and laboratory tests. After exclusion of progressive disease, MMC infusion was administrated 8 weeks later in different dose cohorts; A: 6 mg in 1 cycle, B: 12 mg in 2 cycles, C: 24 mg in 2 cycles and D: maximum of 72 mg in 6 cycles. In cohort D the response was evaluated after every 2 cycles and continued after exclusion of progressive disease. Adverse events (AE) were reported according to CTCAE version 5.0. Results: Sixteen patients received 90Y treatment. Four patients were excluded for MMC infusion, because of extra hepatic disease progression (n = 3) and clinical and biochemical instability (n = 1). That resulted in the following number of patient per cohort; A: 2, B: 1, C: 3 and D: 6. In 4 of the 12 patients (all cohort D) the maximum dose of MMC was adjusted due biochemical toxicities (n = 2) and progressive disease (n = 2). One grade 3 AE occurred after 90Y treatment consisting of a gastrointestinal ulcer whereby prolonged hospitalization was needed. Conclusions: Sequential treatment of intra-arterial infusion of MMC after 90Y SIRT was feasible in 75% of the patients when MMC was administrated in different escalating dose cohorts. However, caution is needed to prevent reflux after 90Y SIRT in LMBC patients. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether baseline multiparametric MR imaging can predict overall survival (OS) and hepatic progression-free survival (HPFS) in patients with neuroendocrine liver metastases (NELMs) treated with transarterial chemoembolization (TACE).Methods: This retrospective study included 84 NELMs patients treated with TACE. Tumor volume and volumetric measurements of arterial enhancement (AE), venous enhancement (VE), and apparent diffusion coefficient (ADC) were performed on baseline MR imaging. A maximum of one, two, and five index lesions were selected in each patient. OS was the primary endpoint and HPFS was the secondary endpoint. Prognostic values of volumetric multiparametric MR parameters for predicting OS and HPFS considering a maximum of one, two, and five index lesions were assessed.Results: Prognostic values of volumetric multiparametric MR parameters for predicting OS and HPFS were similar regardless of the maximum number of index lesions. Multivariate survival analysis showed that baseline dominant tumor volume ≥ 73 cm3, volumetric mean AE ≥ 45%, and mean VE ≥ 73% were independent prognostic factors for OS (HR 2.73; 95% CI 1.45, 5.15; HR 0.32; 95% CI 0.17, 0.63; HR 0.35; 95% CI 0.17, 0.72, respectively) and HPFS (HR 2.30, 95% CI 1.38, 3.84; HR 0.46, 95% CI 0.25, 0.84; HR 0.36, 95% CI 0.19, 0.57, respectively). OS and HPFS were similar in patients with low and high volumetric mean ADC.Conclusion: Volumetric enhancement values and tumor volume of the dominant lesion on baseline MR imaging may act as prognostic factors for OS and HPFS in NELMs patients treated with TACE.Key Points: • High volumetric mean AE and VE, and low tumor volume of the dominant lesion on baseline MR imaging were associated with favorable OS and HPFS in NELMs patients treated with TACE. • Evaluation of multiple lesions does not provide additional information as compared to single lesion evaluation. [ABSTRACT FROM AUTHOR]

Background: In case of response to chemotherapy, unresectable liver metastases from colorectal cancer can be converted to resectable and thereby obtain a chance of cure. The primary aim of this trial was to evaluate the response rate with intrahepatic oxaliplatin in combination with systemic 5-FU +/– cetuximab. Secondary aims were to evaluate the conversion rate from unresectable to resectable liver metastases, median progression-free survival, median overall survival, and toxicity. Methods: Forty-five chemo-naïve patients with liver metastases from colorectal cancer were treated in a prospective phase II trial. Calcium folinate and 5-FU were delivered systemically while oxaliplatin was delivered alternating between systemic and intrahepatic administration. When oxaliplatin was delivered intrahepatic-ally, infusion time was reduced to 10 min followed by embolic material. In patients with KRAS wild-type tumors, cetuximab was added. Results: The treatment was well tolerated and only pain in the liver and a mild increase in liver enzymes were observed after intrahepatic oxaliplatin. The patients obtained a response rate of 82%. Further, 58% converted from having unresectable to resectable liver metastases. The median overall survival and progression-free survival were 38.7 months (95% confidence interval [CI] 33.0–44.3) and 12.9 months (95% CI 10.2–15.6), respectively. Conclusions: Intrahepatic infusion of oxaliplatin in 10 min with systemic 5-FU to patients with chemo-naïve colorectal cancer is feasible and with low toxicity. A high response rate and long median overall survival were obtained. [ABSTRACT FROM AUTHOR]

Purpose: To develop an implantable port in which a microcatheter can be inserted for a combination therapy of repeated transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) for advanced liver cancer.Materials and Methods: The design of a currently used implantable port was modified. A funnel part was constructed in the port. The septum was punctured by a 20-gauge indwelling needle, and 2.0-Fr non-tapered microcatheter was inserted into the port. In the in vitro studies, the advance of a microcatheter out of the funnel part was evaluated via seven different septum puncture sites. A 5-Fr indwelling catheter connected to the port was placed in a vascular model, and a microcatheter catheterization was evaluated. In an in vivo study, the port-catheter system was implanted in the hepatic artery in a pig. A microcatheter was percutaneously inserted through the port into the hepatic arterial branches, and embolization was performed.Results: In the in vitro studies, the microcatheter was smoothly advanced out of the port and catheterizations into the hepatic arteries were successful via all septum puncture sites. In the in vivo study, repeated selective embolization through the port was successfully conducted on 7, 14 and 21 days after the implantation.Conclusion: The developed implantable port can be used for repeated catheter insertion into the hepatic artery. The combination of repeated TACE and HAIC could be possible using this device. [ABSTRACT FROM AUTHOR]

Objectives: This study investigates whether quantitative image analysis of pretreatment CT scans can predict volumetric response to chemotherapy for patients with colorectal liver metastases (CRLM).Methods: Patients treated with chemotherapy for CRLM (hepatic artery infusion (HAI) combined with systemic or systemic alone) were included in the study. Patients were imaged at baseline and approximately 8 weeks after treatment. Response was measured as the percentage change in tumour volume from baseline. Quantitative imaging features were derived from the index hepatic tumour on pretreatment CT, and features statistically significant on univariate analysis were included in a linear regression model to predict volumetric response. The regression model was constructed from 70% of data, while 30% were reserved for testing. Test data were input into the trained model. Model performance was evaluated with mean absolute prediction error (MAPE) and R2. Clinicopatholologic factors were assessed for correlation with response.Results: 157 patients were included, split into training (n = 110) and validation (n = 47) sets. MAPE from the multivariate linear regression model was 16.5% (R2 = 0.774) and 21.5% in the training and validation sets, respectively. Stratified by HAI utilisation, MAPE in the validation set was 19.6% for HAI and 25.1% for systemic chemotherapy alone. Clinical factors associated with differences in median tumour response were treatment strategy, systemic chemotherapy regimen, age and KRAS mutation status (p < 0.05).Conclusion: Quantitative imaging features extracted from pretreatment CT are promising predictors of volumetric response to chemotherapy in patients with CRLM. Pretreatment predictors of response have the potential to better select patients for specific therapies.Key Points: • Colorectal liver metastases (CRLM) are downsized with chemotherapy but predicting the patients that will respond to chemotherapy is currently not possible. • Heterogeneity and enhancement patterns of CRLM can be measured with quantitative imaging. • Prediction model constructed that predicts volumetric response with 20% error suggesting that quantitative imaging holds promise to better select patients for specific treatments. [ABSTRACT FROM AUTHOR]

The efficacy and tolerability of hepatic arterial infusion (HAI) oxaliplatin plus systemic 5-fluorouracil and cetuximab as frontline treatment in patients with colorectal liver metastases (CRLM) are unknown. In this multicenter, single-arm phase II study, patients with CRLM not amenable to curative-intent resection or requiring complex/major liver resection, and no prior chemotherapy for metastatic disease, received HAI oxaliplatin and intravenous 5-fluorouracil, leucovorin and cetuximab, every two weeks until disease progression, limiting toxicity or at least 3 months after complete response or curative-intent resection/ablation. The primary endpoint was overall response rate (ORR). 35 patients, mostly with bilateral (89%), multiple CRLM (>4, 86%; >10, 46%) were enrolled in eight centers. The ORR was 88% (95% CI, 71%−96%) among evaluable patients (n = 32), and 95% (95% CI 70–100%) among the 22 wild-type RAS/BRAF evaluable patients. After a median follow-up of 8.8 years (95% CI, 8.7-not reached), median progression-free survival was 17.9 months (95% CI, 15–23) and median overall survival (OS) was 46.3 months (95% CI, 40.0-not reached). 23 of the 35 patients (66%), including 22 (79%) of the 25 patients with wild-type RAS tumor, underwent curative-intent surgical resection and/or ablation of CRLM. HAI catheter remained patent in 86% of patients, allowing for a median of eight oxaliplatin infusions (range, 1–19). Treatment toxicity was manageable, without toxic death. HAI oxaliplatin plus systemic 5-fluorouracil and cetuximab appears highly effective in the frontline treatment of patients with unresectable CRLM and should be investigated further. • First Phase 2 study of hepatic arterial oxaliplatin plus systemic LV5FU2-cetuximab. • Patients with colorectal liver metastases, unresectable or requiring major surgery. • ORR was 88% (95% in wild-type RAS/BRAF patients). • 66% of the patients had sufficient response to undergo secondary resection. • Median PFS and OS were 17.9 and 46.3 months. [ABSTRACT FROM AUTHOR]

Aim: This randomized phase III trial compared hepatic arterial infusion (HAI) chemotherapy with 5-fluorouracil (5-FU) followed by uracil/tegafur (UFT) and leucovorin (LV) versus UFT/LV alone for patients with curatively resected liver metastases from colorectal cancer (CRC).Methods: The study was designed to include 280 patients to be randomized to receive either HAI with 5-FU followed by UFT/LV (Arm A) or UFT/LV alone (Arm B) to assess whether HAI chemotherapy improved disease-free survival (DFS).Results: Forty-four patients were randomized. Three-year DFS was relatively worse in the experimental arm although this difference was not statistically significant (43.5% in Arm A vs. 58% in Arm B; hazard ratio [HR], 1.304; P = 0.534). The experimental arm also tended to have a worse 3-year overall survival rate (80.2% in Arm A vs. 85.2% in Arm B; HR, 2.255; P = 0.192). There was no significant difference in the frequency of Grade 3 or higher toxicities between the two arms.Conclusion: Although this study was limited by a small sample size after early study termination, our analysis found that HAI with 5-FU followed by UFT/LV did not improve the DFS of patients with curatively resected liver metastases from CRC compared with UFT/LV alone. The future studies are necessary to evaluate the survival benefit of HAI in combination with newer systemic chemotherapeutic agents for patients with resectable liver metastases from CRC. [ABSTRACT FROM AUTHOR]

Background: The impact of sarcopenia on the prognosis of patients with hepatocellular carcinoma (HCC) who receive transcatheter intra-arterial therapies, including transcatheter arterial chemoembolization and transcatheter arterial infusion chemotherapy, remains unclear. We investigated the prognostic value of skeletal muscle loss (SML) stratified by cutoffs for sarcopenia and rate of change in skeletal muscle mass over 6 months.Methods: We retrospectively evaluated 102 patients with HCC treated with transcatheter intra-arterial therapies between 2005 and 2015. Computed tomography images of the third lumbar vertebra (L3) were analyzed to obtain the skeletal muscle area normalized for the height squared, defined as the skeletal muscle index at L3 (L3 SMI), before and 6 months after treatment. Low or high SMI was defined using cutoff values of 42 cm2/m2 in men and 38 cm2/m2 in women. The rate of change in skeletal muscle mass (ΔL3 SMI) over 6 months was calculated. Overall survival (OS) was compared in groups classified by baseline L3 SMI and ΔL3 SMI; prognostic significance was assessed with univariate and multivariate analyses, using Cox proportional hazards models.Results: OS did not differ significantly between groups with low (n = 31) and high (n = 71) SMI at baseline (P = 0.172), but OS was significantly poorer in patients with SML (n = 41), defined as ΔL3 SMI < - 4.6% over 6 months than in those without SML (n = 61, P = 0.018). On multivariate analysis, SML (hazard ratio [HR], 1.675; 95% confidence interval [CI], 1.031-2.721; P = 0.037), serum alpha-fetoprotein ≥20 ng/mL (HR, 2.550; 95% CI, 1.440-4.515; P = 0.001), and maximum tumor diameter ≥ 30 mm (HR, 1.925; 95% CI, 1.166-3.179; P = 0.010) were independent predictors of poor OS. Baseline L3 SMI was not significantly associated with OS (HR, 1.405; 95% CI, 0.861-2.293; P = 0.174).Conclusions: ΔL3 SMI was an independent prognostic factor in patients with HCC treated with transcatheter intra-arterial therapies. Further study is required to reveal whether prevention of skeletal muscle depletion might be a new therapeutic strategy to contribute to improved clinical outcomes in patients with HCC. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate a pumping emulsification device that can improve the physiochemical properties and stability of lipiodol emulsion for conventional transarterial chemoembolization.Materials and Methods: A pumping emulsification device constructed of a glass membrane with a hydrophobic surface with pore size of 50 μm in diameter was placed between two syringe adaptors. Epirubicin solutions were mixed with lipiodol with pumping exchanges using the emulsification device or a three-way cock. The ratios of epirubicin solution to lipiodol were 1:2 or 1:1. A total of 120 emulsions were created.Results: The emulsification device showed significantly higher percentages of water-in-oil when compared with the three-way cock (97.9 % vs. 68.9 % in 1:2 ratio, and 82.1 % vs. 17.8 % in 1:1 ratio, p < .001). Droplet sizes in the emulsification device were more homogenous. Mean droplet sizes and viscosities in the emulsification device did not show any significant changes for 30 min after pumping, whereas in the three-way cock, the droplet sizes significantly enlarged and viscosities significantly decreased (p=.023 and p=.002).Conclusion: The emulsification device can form a high percentage of water-in-oil emulsion with stable droplets sizes and viscosities. This developed device is promising to increase therapeutic effects in conventional transarterial chemoembolization.Key Points: • We developed new device for transarterial chemoembolization for liver cancer. • The device can improve the physiochemical properties of lipiodol emulsion. • The device can increase the therapeutic effects in conventional transarterial chemoembolization. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether clinically relevant portal hypertension (CRPH) influences outcome and whether it may serve as a prognostic marker in patients treated with transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC).Methods: One hundred and forty-seven patients underwent conventional TACE as a first-line treatment for a single HCC. CRPH was graded as 0, 1, or 2. The influence of CRPH, together with other factors, on local tumour progression (LTP) and overall survival (OS) were analysed using Cox proportional hazards regression.Results: A higher CRPH grade (grade 1, p = 0.005, hazard ratio [HR] = 3.282; grade 2, p < 0.001, HR = 7.144) and less selective catheterization (p = 0.009, HR = 1.951) were significantly associated with early LTP. Regarding OS, older age, (p < 0.001, HR = 1.050), CRPH grade 2 (p = 0.024, HR = 2.058), and a larger tumour (p < 0.001, HR = 1.454) were significantly associated with early death.Conclusions: Portal hypertension was significantly associated with poor outcome after TACE, and non-invasive CRPH grading may be a useful prognostic marker of TACE.Key Points: • Portal hypertension was significantly associated with poor outcome after TACE. • Grading portal hypertension non-invasively can help predict TACE outcome in HCC patients. • CRPH grading can aid in selecting optimal candidates for TACE. [ABSTRACT FROM AUTHOR]

Background: Sorafenib is recommended for the first-line treatment of advanced hepatocellular carcinoma (HCC). However, the median progression-free survival (PFS) of patients with HCC and major portal vein tumor thrombosis treated with sorafenib monotherapy is no more than 3 months. A prospective single-arm phase II study was conducted to determine whether adding hepatic arterial infusion chemotherapy of oxaliplatin, 5-fluorouracil and leucovorin to sorafenib could improve on these results.Methods: Thirty five patients were treated with sorafenib 400 mg orally twice a day, oxaliplatin 85 mg/m2 HAI on day 1, leucovorin 400 mg/m2 HAI on days 1, and 5-fluorouracil 2800 mg/m2 on days 1 and 2, repeated every 21 days. The primary end point was the 3-month PFS rate.Results: The 3-, 6-, and 12-month PFS rates were 82.9, 51.4, and 22.9%, respectively. The median PFS and overall survival was 6.7 and 13.2 months, respectively. The objective response rate was 40%, and the disease control rate was 77.1% by RECIST criteria. Five (14.3%) patients achieved conversion to complete resection after the study treatment, and one of them experienced a pathological complete response. Treatment-related deaths did not occur. Grade 3-4 toxicities consisted of increases in aspartate aminotransferase (31.4%), hand-foot syndrome (17.1%), thrombocytopenia (14.3%), and neutropenia (8.6%).Conclusions: The combination treatment met the pre-specified end point of a 3-month progression free survival rate exceeding 65% and was clinical tolerable. The merits of this approach need to be established with a phase III trial. Clinical trial number http://ClinicalTrials.gov (No. NCT02981498). [ABSTRACT FROM AUTHOR]

Liver cancer continues to be a growing healthcare challenge worldwide. Both primary and secondary liver cancers are among the most commonly reported causes of cancer-related death, and the incidence rates of primary liver cancer, or hepatocellular carcinoma (HCC), are expected to grow in the United States and Europe. The majority of patients' cancers are diagnosed at stages that are not amenable to surgical or curative therapy. However, alternative options for the treatment of HCC have expanded greatly in recent years, mostly due to technical innovations in interventional oncology. Advancements in imaging capabilities have allowed the integration of innovative, image-guided, catheter-based, intra-arterial therapies into clinical practice. New modalities of these minimally invasive therapies have become widely adopted, which has allowed larger-scale studies to clarify their appropriate role in the multidisciplinary clinical management of patients. In parallel, basic and translational research continue to break new ground in therapy paradigms, including the introduction of new generations of drug-eluting beads and radioembolic microspheres. This review highlights the history of these therapies, and discusses the value of novel, emerging, image-guidance technologies as well as the most recently presented data from prospective trials on the combination of local tumor therapies with systemically administered anticancer agents. [ABSTRACT FROM AUTHOR]

Background: The most frequent pattern of recurrence is remnant liver after hepatectomy for gastric cancer liver metastases (GLM). The evidence of adjuvant hepatic artery infusion chemotherapy (HAIC) after hepatectomy for GLM is lacking. The aim of this study was to evaluate the efficacy of adjuvant HAIC after hemihepatectomy for GLM.Methods: Between 2001 and 2012, 14 patients who underwent hemihepatectomy for GLM were included in this study. Adjuvant HAIC to the remnant hemiliver was the FEM regimen (333 mg/m2 5-fluorouracil each week, 30 mg/m2 epirubicin once every 4 weeks, and 2.7 mg/m2 mitomycin-C once every 2 weeks) and was administered for 6 months after hemihepatectomy. Clinicopathological prognostic factors for survival were analyzed using a prospectively collected database.Results: Nine patients had solitary GLM, and 5 patients had multiple GLM before surgery. The median period from hemihepatectomy to HAIC was 30 days. The 6-month HAIC completion rate was 79% (n = 11/14). Reasons of HAIC failure included liver dysfunction (n = 1), catheter infection (n = 1), and development of multiple recurrence (n = 1). The median follow-up was 29 (range 8-166) months. Recurrences were detected in 8 patients (57%). The site of recurrences included lung (n = 1), lymph nodes (n = 1), peritoneal dissemination (n = 1), brain (n = 1), pleural (n = 1), and multiple sites (n = 3). The overall 5-year survival rate was 43%. The pathological T4 classification and the preoperative CEA ≥5 ng/mL were significant prognostic factors for overall survival.Conclusions: Adjuvant HAIC after hemihepatectomy for GLM prevents remnant liver recurrence and may contribute to long-term survival. [ABSTRACT FROM AUTHOR]

Background: The hepatic artery infusion (HAI) of irinotecan, oxaliplatin and 5-fluorouracil with intravenous cetuximab achieved outstanding efficacy in previously treated patients with initially unresectable liver metastases from colorectal cancer. This planned study aimed at the identification of pharmacogenetic predictors of outcomes.Methods: Circulating mononuclear cells were analysed for 207 single-nucleotide polymorphisms (SNPs) from 34 pharmacology genes. Single-nucleotide polymorphisms passing stringent Hardy-Weinberg equilibrium test were tested for their association with outcomes in 52 patients (male/female, 36/16; WHO PS, 0-1).Results: VKORC1 SNPs (rs9923231 and rs9934438) were associated with early and objective responses, and survival. For rs9923231, T/T achieved more early responses than C/T (50% vs 5%, P=0.029) and greatest 4-year survival (46% vs 0%, P=0.006). N-acetyltransferase-2 (rs1041983 and rs1801280) were associated with up to seven-fold more macroscopically complete hepatectomies. Progression-free survival was largest in ABCB1 rs1045642 T/T (P=0.026) and rs2032582 T/T (P=0.035). Associations were found between toxicities and gene variants (P<0.05), including neutropenia with ABCB1 (rs1045642) and SLC0B3 (rs4149117 and rs7311358); and diarrhoea with CYP2C9 (rs1057910), CYP2C19 (rs3758581), UGT1A6 (rs4124874) and SLC22A1 (rs72552763).Conclusion: VKORC1, NAT2 and ABCB1 variants predicted for HAI efficacy. Pharmacogenetics could guide the personalisation of liver-targeted medico-surgical therapies. [ABSTRACT FROM AUTHOR]

Background: Based on promising results from a Phase I study of hepatic arterial infusion chemotherapy using a combination of miriplatin and cisplatin powder (DDP-H) for unresectable hepatocellular carcinoma (UMIN-CTR000003541), a multicenter, open-label, randomized phase II study was conducted to evaluate the efficacy and safety of the combination therapy versus miriplatin monotherapy.Methods: Nineteen patients, five and fourteen Barcelona-Clinic Liver Cancer staging classification A and B cases, respectively, were randomly assigned to receive either miriplatin monotherapy (n = 9) or miriplatin/DDP-H combination therapy (n = 10). DDP-H and/or miriplatin were administered through the hepatic arteries supplying the lobes of the liver containing tumors, and progression free survival was analyzed as a primary end point in addition to other secondary endpoints. The corresponding therapy was repeated unless disease progression or severe adverse events were recorded.Results: The monotherapy or combination therapy was performed for 15 or 36 sessions in total, respectively. Although there were no significant differences between the two groups for treatment intervals (p = 0.96) or the dose of miriplatin used in each session (p = 0.99), the progression free survival and overall disease control rate were significantly better in the combination therapy group (91 vs 423 days, p = 0.025; 40.0 vs 77.8%, p = 0.0025, respectively). Consistent with these observations, a trend of a significantly slower increase in des-γ-carboxyprothrombin was observed, and the number of treatment sessions was nearly significantly larger in the combination therapy group (p < 0.0001, p = 0.057, respectively). Conversely, the median survival time did not show a significant difference (706 days, monotherapy vs 733 days, combination therapy; p = 0.40). A significant decrease in cholinesterase was observed during the course of treatment only in patients receiving combination therapy (r = -0.86, p < 0.0001). A few cases in both arms showed hematological and/or non-hematological toxicities that were categorized as grade 1 (NCI-CTCAE).Conclusions: The higher disease control effects with the combination of miriplatin and DDP-H indicate that it is a promising alternative treatment for cases with multiple HCCs, especially for those that can tolerate the treatment without experiencing a reduction in hepatic reserve.Trial Registration: This study was registered on 1 January 2012 with the University Hospital Medical Information Network Clinical Trials Registry ( http://www.umin.ac.jp/ctr/index.htm , UMIN000004691). [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to evaluate the pharmacokinetics and histopathological findings of transarterial chemoembolization (TACE) using cisplatin powder mixed with degradable starch microspheres (DSM) (Cis/DSM-TACE) compared with cisplatin arterial infusion (Cis-AI).Materials and Methods: Eighteen rabbits with VX2 liver tumors were divided into two groups: Cis/DSM-TACE (n = 9) and Cis-AI (n = 9) groups. In the Cis/DSM-TACE group, a mixture of cisplatin powder and DSM was injected until stasis of hepatic arterial flow was achieved. In the Cis-AI group, cisplatin solution was infused.Results: The platinum concentrations in VX2 tumors in the Cis/DSM-TACE group at 24 and 72 h were significantly elevated compared with those in the Cis-AI group (P = .016 and .019, respectively). There were no significant differences in the platinum concentrations in plasma. Histopathological examination revealed the presence of several microspheres inside the tumors at 1 h, which completely disappeared at 24 h. Tumor cell apoptosis at 1 h in the Cis/DSM-TACE group was more frequently observed compared with that in the Cis-AI group (P = .006).Conclusions: TACE using cisplatin powder mixed with DSM provides a higher drug concentration in tumors, thereby achieving stronger antitumor effects compared with arterial infusion of cisplatin solution. [ABSTRACT FROM AUTHOR]

Background: The feasibility and efficacy of adjuvant hepatic arterial infusion (HAI) in preventing the development of liver metastases in patients with advanced colon carcinoma have not been validated. The aim of this randomized controlled study was to compare the feasibility of HAI and the protective effect against liver metastasis after curative resection to those of systemic chemotherapy.Methods: Between July 2000 and June 2003, 91 patients were enrolled. Patients were randomly assigned to receive 5-fluorouracil (5-FU) via continuous venous infusion (CVI) or intra-hepatic arterial weekly high-dose 5-FU (WHF). The primary endpoint was overall survival (OS).Results: In the WHF group, the cumulative failure rate of hepatic arterial catheterization was 16.7% at 6 months. The occurrence of grade 3 adverse events was comparable between the groups. The 5-year OS rates were 59.0% in the CVI group and 34.9% in the WHF group (P = 0.164). CVI tended to show a protective effect against liver metastasis regarding the 5-year liver-specific cumulative recurrence rate: CVI, 45.0% vs. WHF, 68.3%; P = 0.037).Conclusion: HAI therapy has a certain protective effect against liver metastasis after curative resection in patients with colorectal cancer. However, this therapy did not contribute to any marked improvement in their overall survival. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) patients with hepatic vein tumor thrombosis (HVTT) extending to the inferior vena cava (IVC) have an extremely poor prognosis. Here we report a case of HCC with HVTT and renal dysfunction after hepatic arterial infusion chemotherapy (HAIC) successfully treated by liver resection and active veno-venous bypass.Case Presentation: A 77-year-old man was diagnosed to have a large HCC with intrahepatic metastases and HVTT extending to the IVC. Due to the advanced stage, HAIC with cisplatin was performed 13 times in a period of 17 months. As a consequence of this treatment, the size of the main HCC markedly decreased, and the advanced part of the HVTT went down to the root of the right hepatic vein (RHV). However, because of renal dysfunction, HAIC with cisplatin was discontinued and right hepatectomy with patch graft venoplasty of the root of the RHV was performed. Because progression of renal dysfunction had to be avoided, veno-venous bypass was activated during IVC clamping to prevent renal venous congestion and hypotension. Histological examination showed foci of a moderately differentiated HCC with extensive fibrosis and necrosis in the main HCC. Histologically, the HVTT in the RHV showed massive necrosis and tightly adhered to the vascular wall of the RHV. The postoperative function of the remnant liver was good, and no further deterioration of renal function was detected. The patient did not show signs of recurrence 15 month after surgery.Conclusion: In the present case, HAIC using cisplatin in combination with hepatic resection and patch graft venoplasty of the IVC provided a good long-term outcome with no HCC recurrence. Renal function was preserved by using active veno-venous bypass during IVC clamping to prevent renal venous congestion and hypotension. [ABSTRACT FROM AUTHOR]

Background: For patients with liver metastases from gastric cancer (LMGC), combination chemotherapy with fluoropyrimidines and platinum agents has been recognized as standard treatment. However, the prognosis of hepatic progression after first-line treatment failure remains poor. When hepatic progression occurs, hepatic arterial infusion (HAI) chemotherapy may be helpful for preventing disease progression.Purpose: To retrospectively assess the feasibility and efficacy of HAI chemotherapy using 5-fluorouracil, epirubicin, and mitomycin C (FEM) for patients with LMGC after failure of systemic S-1 plus cisplatin.Material and Methods: We reviewed the records of patients who received HAI chemotherapy using FEM for LMGC that progressed during systemic S-1 plus cisplatin treatment while extrahepatic disease was decreased or did not appear. HAI chemotherapy was given as second-line therapy using 5-fluorouracil (330 mg/m(2) weekly), epirubicin (30 or 40 mg/m(2) every 4 weeks), and mitomycin C (2.7 mg/m(2) biweekly).Results: Fourteen patients were analyzed. Toxicity of HAI chemotherapy was generally mild. The objective response rate was 42.9%, including a complete response rate of 14.3%. Median times to hepatic and extrahepatic progression were 9.2 and 7.4 months, respectively. Of 12 patients with documented progression after HAI chemotherapy, 10 patients (83.3%) received additional treatment, including irinotecan or taxanes. Overall, median survival was 12.7 months.Conclusion: Our findings suggest that HAI chemotherapy using FEM is a feasible and effective treatment for patients with LMGC after failure of systemic S-1 plus cisplatin. HAI chemotherapy employed in the second-line setting is useful for achieving long-term disease control of LMGC. [ABSTRACT FROM AUTHOR]

Purpose: Portal vein tumor thrombosis is a critical complication in patients with hepatocellular carcinoma (HCC). This prospective multicenter trial assessed the efficacy of hepatic arterial infusion chemoembolization therapy with cisplatin suspended in lipiodol combined with 5-fluorouracil for HCC patients with portal vein tumor thrombosis.Methods: We enrolled 52 HCC patients with portal vein tumor thrombosis. They received hepatic arterial infusion chemoembolization therapy with cisplatin suspension in lipiodol and 5-fluorouracil. The primary efficacy endpoint was progression-free survival (PFS), while the secondary endpoints were overall survival (OS), tumor response rate, safety, and tolerability. Independent factors for survival were also evaluated.Results: The median PFS and OS were 8.6 and 27.0 months, respectively. Ten patients showed complete response, while 29 had partial response (response rate, 75.0 %). The median survival time of 10 patients with complete response and 29 with partial response was 32 months, while that of 15 patients with partial response who later showed disappearance of HCC following additional therapies was 50 months. Multivariate analysis identified response to treatment and disappearance of viable HCC as independent predictors of survival. The treatment was well tolerated, and the only encountered Grade 3 toxicities were thrombocytopenia and hyperbilirubinemia.Conclusions: Hepatic arterial infusion chemoembolization therapy with cisplatin suspension in lipiodol combined with 5-fluorouracil is effective treatment for unresectable HCC with portal vein tumor thrombosis. [ABSTRACT FROM AUTHOR]

Purpose: Cancer patients with predominantly hepatic metastases have poor outcomes and limited options. Hepatic arterial infusion (HAI) of a therapeutic agent may be an appropriate option for producing increased drug concentrations at the tumor sites while reducing systemic adverse effects in normal tissues.Methods: Patients with predominantly hepatic metastases (n = 48) were placed in 6 groups according to nanoparticle albumin-bound paclitaxel (nab-paclitaxel) dose level using a 3 + 3 design plus dose expansion for responsive tumor types. We evaluated the toxicity, antitumor activity, and pharmacokinetics of nab-paclitaxel delivered via HAI.Results: Thirty-eight and ten patients underwent HAI over 1 and 4 h, respectively, at doses of up to 300 mg/m(2). The treatment was safe and exhibited antitumor activity. Pharmacokinetic analyses revealed that HAI of nab-paclitaxel over 4 h resulted in markedly lower peak drug concentrations (C max) and longer times to peak concentration (T max) than that over 1 h. The self-control pharmacokinetic studies showed that HAI of nab-paclitaxel led to much lower C max and areas under the curve (AUC), compared with intravenous infusion.Conclusions: HAI of nab-paclitaxel at up to 300 mg/m(2) over 4 h was well tolerated. Pharmacokinetic evaluation of C max, T max, and AUC implied that 4-h HAI enhanced hepatic extraction of nab-paclitaxel. Further preclinical and clinical studies are required to develop reliable methods of evaluation of hepatic extraction (clinicaltrials.gov registration number NCT00732836, first registered on August 8, 2008, and last updated on October 27, 2014). [ABSTRACT FROM AUTHOR]

Objective: To assess the methodological quality of clinical research on Chinese medicine (CM) applied by intra-arterial infusion in treating primary liver cancer (PLC). Methods: Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, and three Chinese databases, including Chinese BioMedical Database (CBM), China National Knowledge Infrastructure (CNKI) and China Academic Journal (VIP) were searched. Chinese articles were also searched manually in 16 journals. Two reviewers independently selected studies, the quality of literatures were assessed according to the Cochrane Collaboration method of quality assessment. Results: A total of 14 articles met the inclusion criteria for this review. Only three of these articles described the randomization method used. None of the studies was blinded. All of the articles didn't report the calculation of the sample size. Only six studies mentioned adverse reactions. All of the studies were of grade C according to the Cochrane Collaboration method. Six studies reported results of survival, and only two of these reported better efficacy in the treatment groups. Conclusions: The quality of studies concerned intra-arterial infusion of CM in treating with PLC was poor and the exact effect of these medicines still need evaluation. Well designed RCTs with large sample sizes, adequate follow-up data and reliable methods of assessment are needed to better appraise the real effect of CMs in the treatment of PLC patients. [ABSTRACT FROM AUTHOR]

Objectives This study was conducted to determine the incidence of early stasis in radioembolization using resin yttrium-90 (Y-90) microspheres, to evaluate potential contributing factors, and to review initial imaging outcomes. Methods Patients in whom early stasis occurred were compared with those in whom complete delivery was achieved for tumour type and vascularity, tumour : normal liver ratio ( T : N ratio) at technetium-99m-macroaggregated albumin ( Tc-99m- MAA) angiography, previous intra-arterial therapy, and infusion site (left, right or whole liver). Tumour response was evaluated at 3 months and defined according to whether a partial response and stable disease versus progressive disease were demonstrated. Results A total of 71 patients underwent 128 Y-90 infusions in which 26 (20.3%) stasis events occurred. Hypervascular and hypovascular tumours had similar rates of stasis (17.4% versus 27.8%; P = NS). The mean ± standard deviation T : N ratio was 3.03 ± 1.54 and 3.66 ± 2.79 in patients with and without stasis, respectively ( P = NS). Stasis occurred in 14 of 81 (17.3%) and 12 of 47 (25.5%) infusions following previous intra-arterial therapy and in therapy-naïve territories, respectively ( P = NS). Early stasis occurred in 15 of 41 (36.6%) left, 10 of 65 (15.4%) right and one of 22 (4.5%) whole liver infusions ( P < 0.001). Rates of partial response and stable disease were similar in the stasis (88.3%) and non-stasis (76.0%) groups ( P = NS). Conclusions Early stasis occurred in approximately 20% of infusions with similar incidences in hyper- and hypovascular tumours. Whole-liver therapy reduced the incidence of stasis. Stasis did not appear to affect initial imaging outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Treatment efficacy of intra-arterial radioembolization for liver tumors depends on the selective targeting of tumorous tissue. Recent investigations have demonstrated that tumors may receive inadequate doses of radioactivity after radioembolization, due to unfavorable tumor to non-tumor (T/N) uptake ratios of radioactive microspheres. Hepatic arterial infusion of the vasoconstrictor angiotensin II (AT-II) is reported to increase the T/N blood flow ratio. The purpose of this systematic review was to provide a comprehensive overview of the effect of hepatic arterial AT-II on T/N blood flow ratio in patients with hepatic malignancies, and determine its clinical value for radioembolization. Methods: This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A structured search was performed in the PubMed, EMBASE and Cochrane databases. Only studies that presented data on T/N ratios before and after infusion of AT-II into the hepatic artery, in human patients with hepatic malignancies, were selected. Median T/N ratios before, during and after AT-II infusion, and the median T/N ratio improvement factor were extracted from the selected articles. All data on systemic blood pressure measurements and clinical symptoms were also extracted. Results: The search identified 524 titles of which 5 studies, including a total of 71 patients were considered relevant. Median T/N ratios before infusion of AT-II ranged from 0.4 to 3.4. All studies observed a substantial improvement of the T/N ratio after AT-II infusion, with median improvement factors ranging from 1.8 to 3.1. A transitory increase of systemic blood pressure was observed during AT-II infusion. Conclusions: Infusion of AT-II into the hepatic artery leads to an increase of the tumor to non-tumor blood flow ratio, as measured by T/N uptake ratios. Clinical trials are warranted to assess safety aspects, optimal administration strategy and impact on treatment efficacy during radioembolization. [ABSTRACT FROM AUTHOR]

Despite successful treatment of the primary tumor, uveal melanoma has a propensity to metastasize to the liver. Prognosis is poor due to the very aggressive nature of these tumors. Because systemic therapies are relatively ineffective and patient survival correlates to disease control in the liver, locoregional therapies provide a means of prolonging survival. We review various techniques including chemoembolization, immunoembolization, radioembolization, arterial fotemustine infusion, and hepatic perfusion for the treatment of liver metastases from uveal melanoma. [ABSTRACT FROM AUTHOR]

Hepatic metastases, which are frequently seen in patients with neuroendocrine tumors (NETs), have a major adverse impact on the patient's quality of life and survival. Surgery is the treatment of choice for hepatic metastases but is possible in only a small percentage of patients. Systemic chemotherapy yields disappointing results. Somato-statin analogs are effective in controlling symptoms in many of these patients; however, the disease can become refractory to treatment. Transcatheter intra-arterial liver-directed therapies, such as hepatic artery embolization, chemoembolization, and radioembolization are frequently used in patients with NETs metastatic to the liver, especially in patients with refractory, unresectable, or recurrent disease. These treatments are effective in palliating the hormonal symptoms as well as achieving objective tumor responses. This review focuses on the technique, safety, and clinical efficacy of hepatic artery embolization, chemoembolization, and radioembolization in patients with metastatic NETs. [ABSTRACT FROM AUTHOR]

Background: Resection + radiofrequency ablation (RFA) + hepatic artery infusion (HAI) + systemic chemotherapy for patients with unresectable synchronous liver-only metastases from colorectal cancer was rarely used previously.Methods: We compared the outcomes of 42 patients underwent resection + RFA + HAI + systemic chemotherapy (RRHS) with that of 43 patients underwent resection + RFA + systemic chemotherapy (RRS).Results: The overall survival, the survival free of hepatic recurrence and the median survival in the RRHS group were all significantly higher than those in RRS group at 4 years. While the rates of adverse effects were similar in the two groups.Conclusion: For patients with unresectable synchronous liver-only metastases from colorectal cancer, RRHS not only decreases but also postpones hepatic recurrence and therefore improves overall survival at 4 years, as compared with RRS. [ABSTRACT FROM AUTHOR]

Rationale: The objective of this study was to retrospectively evaluate the efficacy of a combination of (32)P-glass microsphere-mediated intra-arterial internal radiation and chemoembolization for the treatment of hepatocellular carcinoma.Methods: Twenty-five consecutive patients with primary hepatocellular carcinoma referred for radiation therapy were treated with intra-arterial infusion of (32)P-glass microspheres followed by chemoembolization. beta-bremsstrahlung imaging was performed to monitor microsphere distribution. A partition model and a radiation dose equation were used for determination of radiation exposure in various tissues. Clinical response was evaluated using computed axial tomography scans.Results: The mean estimated absorption dose in tumor tissue was 137.42 +/- 56.69 Gy. A receiver operating characteristic curve was used to establish 90.65 Gy as the cutoff absorption dose with the best sensitivity and specificity for predicting response. The overall tumor response rate was 92%, while response in patients with radiation doses >90.65 Gy was 100%. Overall median patient survival was 15 months.Conclusion: beta-bremsstrahlung imaging following intra-arterial infusion of (32)P-glass microspheres and chemoembolization incorporates effective treatment with convenient dosimetry monitoring and manageable adverse events using a single surgical procedure. This approach is a safe and effective method for ameliorating hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Background: The prognosis of unresectable hepatic colorectal metastases is poor even if chemotherapy is administered. The purpose of this study was to evaluate the long-term efficacy of hepatic arterial infusion (HAI) chemotherapy and hepatectomy following HAI for such condition.Methods: Seventy-two patients with unresectable hepatic colorectal metastases received continuous HAI of 5-fluorouracil.Results: The overall response rate was 38%. The median survival of all patients was 18 months. The overall 3-year survival rate was 18%. Seven patients (10%) survived more than 58 months. Of the eight patients with a complete response, seven developed liver and/or lung metastases, and of these, one patient undergoing additional hepatectomy has been disease-free and the other six receiving chemotherapy died of disease. Another complete-response case died of liver abscess. Of the 19 patients with a partial response, six could undergo hepatectomy after HAI. The overall 5-year survival rate of seven patients undergoing hepatectomy was 71%, whereas for patients without hepatectomy, the rate was 0%.Conclusions: Most patients showing response after HAI for unresectable hepatic colorectal metastases had relapses. The long-term prognosis of patients undergoing hepatectomy after HAI was favorable. Therefore, when HAI makes liver metastases resectable, they should be resected. [ABSTRACT FROM AUTHOR]

Background: Patients with advanced hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT) have a particularly grave prognosis. In the current study, an attempt was made to localize chemoradiation therapy (CCRT) followed by hepatic arterial infusion chemotherapy (HAIC) in patients with locally advanced HCC with PVT and good reserve liver function. The objective of the current study was to evaluate the therapeutic effect of localized CCRT followed by HAIC as a new treatment modality for these patients.Methods: Between January 1998 and December 2003, 40 patients were recruited. Concurrent regional chemotherapy using an intra-arterial implanted port plus localized external beam radiotherapy was performed with a total of 45 gray (Gy) over 5 weeks with conventional fractionation and hepatic arterial infusion of 5-fluorouracil (5-FU), which was administered during the first and fifth weeks of radiotherapy. One month after localized CCRT, HAIC with 5-FU and cisplatin was administered every 4 weeks.Results: One month after localized CCRT, an objective response was observed on the intention-to-treat analysis in 18 of 40 patients (45%). The actuarial 3-year overall survival rate was 24.1% and the median survival time was 13.1 months from the start of radiation treatment. Responders after localized CCRT demonstrated significantly better survival (P = .033) than nonresponders.Conclusions: The substantial response rate as well as median survival time noted in the current study encourages the use of this new approach in patients with locally advanced HCC with PVT. [ABSTRACT FROM AUTHOR]

Herein we report the efficacy of embolization of small patent gastric or duodenal vessels for treating gastroduodenal complications after hepatic arterial infusion therapy (HAIC). Catheter ports were implanted percutaneously from a femoral approach in three cases or surgically in the gastroduodenal artery in two cases. Acute abdominal pain developed on average after four HAIC courses of 5FU-oxaliplatin, mytomycin, oxaliplatin or fotemustine. Esophagogastroduodenoscopy showed gastroduodenal lesions (gastroduodenitis with or without ulcerations) in all cases. Despite the interruption of the HAIC, symptoms persisted and led to selective hepatic arteriography showing a patent right gastric artery (n = 4) or a recanalized gastroduodenal artery (n = 1) responsible for gastroduodenal misperfusion. Successful embolizations of the arteries responsible for gastroduodenal misperfusion (right gastric artery in four cases and gastroduodenal artery in one case) using 0.018 platinium coils relieved the patients' symptoms and allowed the HAIC to continue. In gastroduodenal complications of HAIC, a selective hepatic arteriography should be performed to search any artery responsible for the misperfusion of the toxic agent in the gastroduodenal area. Embolization of these arteries allowed the HAIC to be restored. [ABSTRACT FROM AUTHOR]

The use of hepatic arterial infusion (HAI) for the delivery of chemotherapeutic agents to treat residual microscopic disease after curative hepatic resection for colorectal cancer metastases remains controversial. In recent years, a number of studies examining adjuvant HAI have shown conflicting results. A meta-analysis of prospective clinical trials was performed to determine if adjuvant HAI confers a survival benefit in this setting. Two reviewers independently performed a literature search of MEDLINE, PubMed, EMBASE, the Cochrane library, and the Cochrane Clinical Trials Registry. Prospective clinical trials comparing hepatic arterial chemotherapy after curative hepatic resection for colorectal cancer metastases against a control arm were included. Non–English-language publications were excluded. The outcome measure was survival difference at 1 and 2 years after surgery. Seven studies met the inclusion criteria, and all except one were randomized trials. The survival difference in months (positive values favoring the treatment arm) was 1.8 at 1 year (95% confidence interval, -4.9, 8.5) and 9.6 at 2 years (95% confidence interval, -2.2, 21.4). Neither was statistically significant (at 2 years, P=0.11). Based on these findings, routine adjuvant HAI after curative resection for colorectal cancer of the liver cannot be recommended. However, given the trend toward a survival benefit at 2 years, further study is recommended. [Copyright &y& Elsevier]

The treatment of hepatic tumors in cirrhotic and noncirrhotic patients still represents a major issue in decision making for oncologists and surgeons. The high mortality of open liver surgery, particularly in cirrhotic patients, has pushed physicians to research new modalities. In this review paper we summarize the available and alternative methods for the treatment of liver masses using new modalities and a minimally invasive approach, which will benefit the quality of life of the patients. We also outline therapeutic plan options. [ABSTRACT FROM AUTHOR]

The purpose of the present study is to evaluate the feasibility of a method developed to withdraw a port–catheter system that had been implanted with use of the fixed catheter tip technique. Withdrawal of an implanted catheter was required in four patients with advanced liver cancer in whom port–catheter systems had been implanted for performance of repeated hepatic arterial infusion. In all patients, port–catheter systems were successfully removed without complications. In conclusion, an implanted port–catheter system can be removed even when implanted with the fixed catheter tip technique. [Copyright &y& Elsevier]