Immunoembolization for the Treatment of Uveal Melanoma Hepatic Metastases.

Uveal melanoma is the most common primary intraocular tumor in adults. Approximately 50% of patients develop metastatic disease despite successful treatment of the primary eye tumor. The liver is the most common site of metastatic disease occurring in more than 90% of patients. Clinical prognosis is dependent on the ability to control the growth of liver tumors. Locoregional therapies play an important role in stabilizing liver metastases, prolonging survival for patients with metastatic uveal melanoma. As overall survival is prolonged, the development of extrahepatic disease becomes more common. Immunoembolization, a form of liver-directed therapy, not only focuses on treating hepatic metastases by stimulating the local immune system to suppress the growth of liver tumors, but it potentially generates a systemic immune response delaying the growth of extrahepatic metastases as well. The following article discusses immunoembolization for the treatment of metastatic uveal melanoma including the rationale, mechanism of action, indications, contraindications, outcomes, and associated toxicities.

Evaluation of Uterine Fibroid Vascularity Using Contrast-Enhanced Ultrasound in Comparison with Contrast-Enhanced Magnetic Resonance Imaging.

OBJECTIVE: The aim of the work described here was to assess uterine fibroid vascularity using contrast-enhanced ultrasound (CEUS) as compared with magnetic resonance imaging (MRI). METHODS: Forty women diagnosed with symptomatic uterine fibroids scheduled for uterine artery embolization (UAE) were enrolled in this institutional review board-approved study. Before UAE, participants underwent CEUS examination with an Aplio i800 scanner (Canon Medical Systems, Tustin, CA, USA) with curvilinear array (8C1). CEUS was performed using 2.0 mL of the ultrasound contrast agent Lumason (Bracco, Milan, Italy) administered intravenously. Digital CEUS clips were acquired and randomized offline, and fibroids were characterized as hyper- or hypovascular. MRI was used as reference standard for fibroid vascularity and compared with CEUS. Results were analyzed using McNemar's test. RESULTS: Forty participants were enrolled in the trial. One patient did not proceed with the UAE procedure and one patient refused pre-procedure MRI because of claustrophobia. Therefore, 38 participants underwent CEUS and MRI examinations before UAE. Hypervascular fibroids were seen on MRI and CEUS in 24 and 26 participants, respectively. Hypovascular fibroids were seen with MRI and CEUS in 14 and 12 participants, respectively. Fibroids characterized as hypovascular in two participants by MRI were characterized as hypervascular by CEUS. CEUS and MRI findings were similar in 36 of 38 participants, corresponding to an accuracy of 95% (p = 0.62). CONCLUSION: Contrast-enhanced ultrasound can accurately assess uterine fibroid vascularity, serving as a potential alternative to MRI in determination of the vascularity of uterine fibroids.

Randomized controlled trial of mechanical thrombectomy vs catheter-directed thrombolysis for acute hemodynamically stable pulmonary embolism: Rationale and design of the PEERLESS study.

BACKGROUND: The identification of hemodynamically stable pulmonary embolism (PE) patients who may benefit from advanced treatment beyond anticoagulation is unclear. However, when intervention is deemed necessary by the PE patient's care team, data to select the most advantageous interventional treatment option are lacking. Limiting factors include major bleeding risks with systemic and locally delivered thrombolytics and the overall lack of randomized controlled trial (RCT) data for interventional treatment strategies. Considering the expansion of the pulmonary embolism response team (PERT) model, corresponding rise in interventional treatment, and number of thrombolytic and nonthrombolytic catheter-directed devices coming to market, robust evidence is needed to identify the safest and most effective interventional option for patients. METHODS: The PEERLESS study (ClinicalTrials.gov identifier: NCT05111613) is a currently enrolling multinational RCT comparing large-bore mechanical thrombectomy (MT) with the FlowTriever System (Inari Medical, Irvine, CA) vs catheter-directed thrombolysis (CDT). A total of 550 hemodynamically stable PE patients with right ventricular (RV) dysfunction and additional clinical risk factors will undergo 1:1 randomization. Up to 150 additional patients with absolute thrombolytic contraindications may be enrolled into a nonrandomized MT cohort for separate analysis. The primary end point will be assessed at hospital discharge or 7 days post procedure, whichever is sooner, and is a composite of the following clinical outcomes constructed as a hierarchal win ratio: (1) all-cause mortality, (2) intracranial hemorrhage, (3) major bleeding, (4) clinical deterioration and/or escalation to bailout, and (5) intensive care unit admission and length of stay. The first 4 components of the win ratio will be adjudicated by a Clinical Events Committee, and all components will be assessed individually as secondary end points. Other key secondary end points include all-cause mortality and readmission within 30 days of procedure and device- and drug-related serious adverse events through the 30-day visit. IMPLICATIONS: PEERLESS is the first RCT to compare 2 different interventional treatment strategies for hemodynamically stable PE and results will inform strategy selection after the physician or PERT determines advanced therapy is warranted.

Improved Uveal Melanoma Copy Number Subtypes Including an Ultra-High-Risk Group.

Purpose: To evaluate the clinical relevance of low-frequency copy number aberrations (CNAs) in uveal melanoma (UM) and to discern residual genomic and clinical heterogeneity within established molecular subtypes based on genome-wide CNA profiling of 921 primary tumors. Design: Retrospective single-center case series. Participants: Patients with primary UM referred for genetic testing between 2008 and 2016 (n = 921). The Cancer Genome Atlas cohort with clinical outcome data available (n = 70) was used to validate findings. Methods: Genome-wide CNAs were generated for primary tumors from 921 patients and for 19 metastatic UM (mUM) in the liver. Of the 921 patients, metastatic outcome was known for 678 patients with a median time to metastasis of 4.5 years. The primary tumors were processed on the Affymetrix arrays SNP-5.0 (n = 140), SNP-6.0 (n = 359), or CytoScanHD (n = 422), and the metastatic tumors on the CytoScanHD array (n = 19). Recurrent CNAs were identified, and the prognostic effect of individual CNAs and multiple CNA clustering strategies, including more specific molecular subgroups with rare CNAs, were evaluated. Main Outcome Measures: CNA recurrence, and effect of CNAs and derived molecular subtypes on metastatic-free survival. Results: Genomic profiling revealed CNAs associated with risk of metastasis and demonstrated a strong association between chromosomal instability and patient prognosis. Using standard prognostic CNAs, 6 clusters were detected, and inclusion of chromosome 16q deletion revealed an additional cluster. Of these 7 genomic clusters, 5 patient groups showed distinct rates of metastasis, indicating that different genomic patterns can have similar patient outcomes. A small group of patients with a significantly higher rate of metastasis was characterized by monosomy 3, 8q amplification, and deletion of 1p or 16q. Although this ultra-high-risk group accounts for only 7% of this cohort, 88% demonstrated metastasis within 4 years, compared with 45% in the second-highest risk group. Conclusions: These results suggest that 1p and 16q deletion should be incorporated in clinical assays to assess prognosis at diagnosis and to guide enrollment in clinical trials for adjuvant therapies.

Investigation of Radiation Dose Estimates and Image Quality Between Commercially Available Interventional Fluoroscopy Systems for Fluoroscopically Guided Interventional Procedures.

RATIONALE AND OBJECTIVES: To investigate differences in radiation dose and image quality for single-plane flat-panel-detector based interventional fluoroscopy systems from two vendors using phantom study and clinical procedures. MATERIALS AND METHODS: AlluraClarityIQ (Philips) and Artis Q (Siemens-Healthineers) interventional fluoroscopy systems were evaluated. Phantom study included comparison of system-reported air-kerma rates (AKR) for clinical protocols with simulated patient thicknesses (20-40 cm). Differences in system-reported radiation dose estimates, cumulative-air-kerma (CAK) and kerma-area-product (KAP), for different clinical procedures were investigated. Subset analysis investigated differences in CAK, KAP and other factors affecting radiation dose when the same patients underwent repeat embolization procedures performed by the same physician on the two different fluoroscopy systems. Two blinded interventional radiologists reviewed image-quality for these procedures using a five-point scale (1-5; 5-best) for five parameters. RESULTS: Phantom study revealed that air-kerma rates was significantly higher for Artis Q system for 30-40cm of simulated patient thicknesses (p < 0.05). Overall data analysis from 4381 clinical cases revealed significant differences in CAK and KAP for certain procedures (p < 0.05); with significantly lower values for AlluraClarityIQ systems (median CAK lower by: 29%-58%). Subset analysis with 40 patients undergoing repeat embolization procedures on both systems revealed that median CAK and KAP were significantly lower for AlluraClarityIQ systems (p < 0.02) by 45% and 31%, respectively. Image quality scores for AlluraClarityIQ systems were significantly greater (mean difference range for five parameters: 1.3-1.6; p < 0.005). CONCLUSION: Radiation dose and image quality differences were observed between AlluraClarityIQ and Artis Q systems. AlluraClarityIQ systems showed lower radiation utilization and an increase in subjective perception of image quality.

Locoregional Therapies for the Treatment of Uveal Melanoma Hepatic Metastases.

Uveal melanoma is the most common primary intraocular malignant tumor in adults. Approximately 50% of patients develop metastatic disease of which greater than 90% of patients develop hepatic metastases. Following the development of liver tumors, overall survival is dismal with hepatic failure being the cause of death in nearly all cases. To prolong survival for patients with metastatic uveal melanoma, controlling the growth of hepatic tumors is essential. This article will discuss imaging surveillance following the diagnosis of primary uveal melanoma; locoregional therapies used to control the growth of hepatic metastases including chemoembolization, immunoembolization, radioembolization, percutaneous hepatic perfusion, and thermal ablation; as well as currently available systemic treatment options for metastatic uveal melanoma.

Surgical Pulmonary Embolectomy Outcomes for Acute Pulmonary Embolism.

BACKGROUND: Acute pulmonary embolism (PE) is associated with significant mortality. Surgical embolectomy is a viable treatment option; however, it remains controversial as a result of variable outcomes. This review investigates patient outcomes after surgical embolectomy for acute PE. METHODS: An electronic search was performed to identify articles reporting surgical embolectomy for treatment of PE. 32 studies were included comprising 936 patients. Demographic, perioperative, and outcome data were extracted and pooled for systematic review. RESULTS: Mean patient age was 56.3 years (95% confidence interval [CI], 52.5, 60.1), and 50% were male (95% CI, 46, 55); 82% had right ventricular dysfunction (95% CI, 62, 93), 80% (95% CI, 67, 89) had unstable hemodynamics, and 9% (95% CI, 5, 16) experienced cardiac arrest. Massive PE and submassive PE were present in 83% (95% CI, 43, 97)] and 13% (95% CI, 2, 56) of patients, respectively. Before embolectomy, 33% of patients (95% CI, 14, 60) underwent systemic thrombolysis, and 14% (95% CI, 8, 24) underwent catheter embolectomy. Preoperatively, 47% of patients were ventilated (95% CI, 26; 70), and 36% had percutaneous cardiopulmonary support (95% CI, 11, 71). Mean operative time and mean cardiopulmonary bypass time were 170 minutes (95% CI, 101, 239) and 56 minutes (95% CI, 42, 70), respectively. Intraoperative mortality was 4% (95% CI, 2, 8). Mean hospital and intensive care unit stay were 10 days (95% CI, 6, 14) and 2 days (95% CI, 1, 3), respectively. Mean postoperative systolic pulmonary artery pressure (sPAP) was significantly decreased from the preoperative period (sPAP 57.8, mm Hg; 95% CI, 53, 62.7) to the postoperative period (sPAP, 31.3 mm Hg; 24.9, 37.8); P < .01). In-hospital mortality was 16% (95% CI, 12, 21). Overall survival at 5 years was 73% (95% CI, 64, 81). CONCLUSIONS: Surgical embolectomy is an acceptable treatment option with favorable outcomes.

Recent Trends in Endovascular and Surgical Treatment of Peripheral Arterial Disease in the Medicare Population.

OBJECTIVE. Although radiologists developed endovascular treatment of peripheral arterial disease (PAD) in the 1960s, vascular surgeons and cardiologists have become increasingly involved in its application. The purpose of this study was to examine utilization trends in endovascular and surgical treatment of PAD in recent years in the Medicare population. CONCLUSION. Surgical treatment of PAD has decreased each year from 2011 to 2016, whereas endovascular treatment has increased each year. By 2016, Medicare patients who needed revascularization for PAD were more than four times as likely to undergo endovascular as they were to undergo surgical treatment. Between 2011 and 2016, radiologists, vascular surgeons, and cardiologists all increased their endovascular volume, but by 2016, vascular surgeons and cardiologists performed three of every four endovascular procedures for the Medicare population. While only 12% of the total endovascular procedures for PAD were performed in 2016, radiology has grown its procedural volume each year from 2011 through 2016.

An Outcome Assessment of a Single Institution's Longitudinal Experience with Uveal Melanoma Patients with Liver Metastasis.

There is no FDA-approved treatment for metastatic uveal melanoma (UM) and overall outcomes are generally poor for those who develop liver metastasis. We performed a retrospective single-institution chart review on consecutive series of UM patients with liver metastasis who were treated at Thomas Jefferson University Hospital between 1971-1993 (Cohort 1, n = 80), 1998-2007 (Cohort 2, n = 198), and 2008-2017 (Cohort 3, n = 452). In total, 70% of patients in Cohort 1 received only systemic therapies as their treatment modality for liver metastasis, while 98% of patients in Cohort 2 and Cohort 3 received liver-directed treatment either alone or with systemic therapy. Median Mets-to-Death OS was shortest in Cohort 1 (5.3 months, 95% CI: 4.2-7.0), longer in Cohort 2 (13.6 months, 95% CI: 12.2-16.6) and longest in Cohort 3 (17.8 months, 95% CI: 16.6-19.4). Median Eye Tx-to-Death OS was shortest in Cohort 1 (40.8 months, 95% CI: 37.1-56.9), and similar in Cohort 2 (62.6 months, 95% CI: 54.6-71.5) and Cohort 3 (59.4 months, 95% CI: 56.2-64.7). It is speculated that this could be due to the shift of treatment modalities from DTIC-based chemotherapy to liver-directed therapies. Combination of liver-directed and newly developed systemic treatments may further improve the survival of these patients.

First year experience of a pulmonary embolism response team with comparisons of outcomes between catheter directed therapy versus standard anticoagulation.

Objectives: The Pulmonary Embolism Response Team (PERT) model is now widely adopted in many institutions to provide multidisciplinary care for patients with acute pulmonary embolism (PE). However, descriptive experiences of PERT operations and studies on clinical outcomes remain limited.Methods: We performed a retrospective review of PERT activations at an academic tertiary care center, with secondary aims to study outcomes associated with performing catheter directed therapies (CDT).Results: The intermediate high-risk PE category was most frequent (n = 40, 76.9%) among the 52 total cases evaluated during the study period. There was one in-hospital mortality, associated with hospice admission for a non-PE diagnosis. Six patients (11.5%) experienced a bleeding complication of any severity. Anticoagulation (AC) alone was recommended in 30 patients (57.7%) and CDT was performed in 16 patients (30.8%). There were no significant differences in patient characteristics or disease severity between patients in the AC group versus the CDT group, except for a higher prevalence of malignancy in the AC group (p = 0.037). Patients who underwent CDT demonstrated a lower, albeit non-significant, median intensive care unit (ICU) length of stay (LOS) (3 vs. 4 days, p = 0.34) and hospital LOS (4 vs. 5 days, p = 0.25), as compared to patients receiving AC alone. Bleeding rates were similar between the two groups (6.7% vs. 6.3%, p = 1.0).Conclusions: Adoption of the PERT model at an academic tertiary care center was associated with acceptably low rates of mortality and bleeding, similar to other published studies. Performing CDT in select patients under PERT consultation may be associated with shorter ICU and hospital LOS; however, larger studies are needed to validate this finding.

Outcomes of extracorporeal life support for the treatment of acute massive pulmonary embolism: A systematic review.

BACKGROUND: Massive pulmonary embolism (PE) can cause hemodynamic instability leading to high mortality. Extracorporeal life support (ECLS) has been increasingly used as a bridge to definitive therapy. This systematic review investigates the outcomes of ECLS for the treatment of massive PE. METHODS: Electronic search was performed to identify all relevant studies published on ECLS use in patients with PE. 50 case series or reports were selected comprising 128 patients with acute massive PE who required ECLS. Patient-level data were extracted for statistical analysis. RESULTS: Median patient age was 50 [36, 63] years and 41.3% (50/121) were male. 67.2% (86/128) of patients presented with cardiac arrest. Median heart rate was 126 [118, 135] and median systolic pulmonary artery pressure (sPAP) was 55 [48, 69] mmHg. The majority of ECLS included veno-arterial ECLS [97.1% (99/102)]. Median ECLS time was 3 [2, 6] days. 43.0% (55/128) patients received systemic thrombolysis, 22.7% (29/128), received catheter-guided thrombolysis, and 37.5% (48/128) underwent surgical embolectomy. 85.1% (97/114) were weaned off ECLS. Post-ECLS complications included bleeding in 23.4% (30/128), acute renal failure in 8.6% (11/128), dialysis in 6.3% (8/128), heparin-induced thrombocytopenia in 3.1 (4/128), and extremity hypoperfusion in 2.3% (3/128). The most common cause of death was shock at 30.3% (10/33). The median length of hospital stay was 22 [11, 39] days including 8 [5, 13] intensive care unit (ICU) days. The 30-day mortality rate was 22% (20/91). CONCLUSIONS: ECLS is safe and effective therapy in unstable patients with acute massive pulmonary embolism and offers acceptable outcomes.

A Prospective Phase II Trial of Radioembolization for Treatment of Uveal Melanoma Hepatic Metastasis.

Background Overall survival (OS) for patients with uveal melanoma (UM) hepatic metastases is extremely poor. Therefore, stabilization of hepatic metastases is essential to prolonging OS. Purpose To assess the safety and effectiveness of radioembolization (RE) for treatment of UM hepatic metastases. Materials and Methods Enrollment for this prospective phase II trial began November 2011 and concluded January 2017. Treatment-naïve participants (group A) and participants who progressed after immunoembolization (group B) with hepatic tumor burden less than 50% underwent RE. Participants were followed for 1 month and every 3 months for acute and delayed toxicities, respectively. MRI, CT, and PET were performed every 3 months to evaluate for tumor response and extrahepatic disease. Participants were followed for at least 2 years or until death. Kaplan-Meier method and multivariable Cox proportional hazard models were used for data analysis. Results In group A, 24 participants (mean age ± standard deviation, 59 years ± 13; 13 men and 11 women) underwent unilobar (n = 7), fractionated whole-liver (n = 1), or sequential lobar (n = 16) RE. One participant was excluded from the trial. Complete response (n = 0), partial response (n = 9), or stable disease (n = 11) was achieved in 20 of 23 (87.0%; 95% confidence interval [CI]: 66.4%, 97.2%) participants. Median progression-free survival from liver metastasis was 8.1 months (95% CI: 6.4, 11.8; range, 3.3-33.7 months). Median OS was 18.5 months (95% CI: 11.3, 23.5; range, 6.5-73.7 months). In group B, 24 participants (mean age, 58 years ± 10; nine men and 15 women) underwent unilobar (n = 5) or sequential lobar (n = 19) RE. Complete response (n = 0), partial response (n = 8), or stable disease (n = 6) was achieved in 14 of 24 (58.3%; 95% CI: 36.3%, 77.9%) participants. Median progression-free survival from liver metastasis was 5.2 months (95% CI: 3.7, 9.8; range, 2.9-22.0 months). Median OS was 19.2 months (95% CI: 11.5, 24.0; range, 4.8-76.6 months). Grade 3 treatment-related toxicities included transient lymphopenia (group A, n = 1; group B, n = 1), pain (group A, n = 2) and nausea or vomiting (group A, n = 1). Conclusion Radioembolization is a promising treatment for patients with uveal melanoma hepatic metastases. © RSNA, 2019 Online supplemental material is available for this article.

Inferior Vena Cava Filter Placement and Retrieval Rates among Radiologists and Nonradiologists.

PURPOSE: To evaluate inferior vena cava (IVC) filter placement and retrieval rates among radiologists, vascular surgeons, cardiologists, other surgeons, and all other health care providers for Medicare fee-for-service beneficiaries in the years 2012-2015. MATERIALS AND METHODS: The nationwide Medicare Physician/Supplier Procedure Summary Master Files were used to determine the volume and utilization rate of IVC filter placement, IVC filter repositioning, and IVC filter retrieval, which correspond to procedure codes 37191, 37192, and 37193, respectively. Procedural code 37193 was not available before 2012, so data were reviewed for the years 2012-2015. RESULTS: The total volume of Medicare IVC filter placement decreased from 57,785 in 2012 to 44,378 in 2015, with radiologists responsible for 60% of all filter placements. Volume of IVC filter placement declined across all specialties, including radiologists, who placed 33,744 in 2012 and 27,957 in 2015. In contrast, total retrieval of IVC filters increased from 4,060 removals in 2012 to 6,166 in 2015. Retrieval rate per 100,000 Medicare beneficiaries increased from 11 in 2012 to 16 in 2015. Radiologists removed the bulk of the filters: 64% in both 2012 and 2015. Vascular surgeons, cardiologists, and other surgeons retrieved, respectively, 20%, 10%, and 5% of all IVC filters in 2012 and 22%, 9%, and 5% in 2015. CONCLUSIONS: From 2012 to 2015, IVC filter placement steadily decreased across all specialties. Retrieval rate of IVC filters continued to rise over the same period. Radiologists were responsible for the majority of IVC filter placements and retrievals.

Metastatic Liver Disease: Indications for Locoregional Therapy and Supporting Data.

Metastatic liver disease is a major cause of cancer-related morbidity and mortality. Surgical resection is considered the only curative treatment, yet only a minority is eligible. Patients who present with unresectable disease are treated with systemic agents and/or locoregional therapies. The latter include thermal ablation and catheter-based transarterial interventions. Thermal ablation is reserved for those with limited tumor burden. It is used to downstage the disease to enable curative surgical resection, as an adjunct to surgery, or in select patients it is potentially curative. Transarterial therapies are indicated in those with more diffuse disease. The goals of care are to palliate symptoms and prolong survival. The indications and supporting data for thermal ablation and transarterial interventions are reviewed, technical and tumor factors that need to be considered prior to intervention are outlined, and finally several cases are presented.

A Phantom Study and a Retrospective Clinical Analysis to Investigate the Impact of a New Image Processing Technology on Radiation Dose and Image Quality during Hepatic Embolization.

PURPOSE: To investigate changes in radiation dose and image quality using phantoms and hepatic embolization procedures performed with a new image processing technology (ClarityIQ) for a single-plane flat-detector-based interventional fluoroscopy system. MATERIALS AND METHODS: Phantom study was performed using acrylic sheets simulating different patient sizes. Air kerma rates (AKRs) were compared for different fluoroscopy modes and magnification modes without and with ClarityIQ. Repeat hepatic embolization procedures performed on the same lobe of the liver in the same patient by the same interventional radiologist between January 2013 and July 2014 without and with ClarityIQ were evaluated retrospectively. This included treatment of 33 hepatic lobes in 26 patients. Cumulative air kerma (CAK), kerma-area product (KAP), and factors affecting radiation dose were extracted from study metadata and compared. Blinded randomized image quality review was performed on arteriograms using a five-point scale. RESULTS: The phantom study revealed a significantly lower AKR (P < .005) with ClarityIQ. Repeated-measures analysis revealed a significant effect of ClarityIQ (P ≤ .001) on CAK and KAP, with reductions ranging between 9% and 85% (median, 67%) and between 5% and 89% (median, 75%), respectively, on a case-by-case basis. Mean reductions in CAK and KAP were 279 mGy and 134,030 mGy·cm(2), respectively. Image quality review scores were significantly lower (P ≤ .001) with ClarityIQ, effecting visualization of tumor vasculature and appearance of noise texture. CONCLUSIONS: ClarityIQ resulted in radiation dose reduction in the phantom study and in the hepatic embolization procedures, but with a decrease in subjective perceptions of image quality.

Uveal Melanoma Metastatic to the Liver: Chemoembolization With 1,3-Bis-(2-Chloroethyl)-1-Nitrosourea.

OBJECTIVE: The purpose of this study is to evaluate whether chemoembolization with 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) is a safe and effective treatment for bulky uveal melanoma liver metastasis. MATERIALS AND METHODS: Over a 7-year period, 63 treatment-naïve patients presented with uveal melanoma metastasis replacing 50% or more of the normal liver parenchyma. Patients with Eastern Cooperative Oncology Group 0-2 performance status, no extensive extrahepatic metastases, and adequate liver and renal function were treated with BCNU (200 mg) chemoembolization. Pretreatment tumor burdens were classified by MRI as 50-75% and more than 75%. Lactate dehydrogenase (LDH) levels were divided into less than or equal to 500 and more than 500 IU/L (i.e., more than twice the normal level). Treatment toxicity was assessed using Common Terminology Criteria for Adverse Events (version 4.0). CT and MRI were used to determine best radiologic response (Response Evaluation Criteria in Solid Tumors). Overall survival (OS) and progression-free survival (PFS) were compared with tumor burden and LDH levels. RESULTS: Fifty patients (31 men; mean age, 59.1 years; range, 30-88 years) met the inclusion criteria. A total of 271 chemoembolization procedures were performed. Grade 3 thrombocytopenia occurred in two patients, grade 3 hyperbilirubinemia (n = 2) was attributed to disease progression, and asymptomatic grade 4 transaminitis occurred after 16 treatments. Best radiologic response was as follows: partial response, n = 3; stable disease, n = 33; and disease progression, n = 12 (no follow-up imaging, n = 2). The median OS was 7.1 months (range, 1.2-32.3 months), and the median PFS was 5.0 months (range, 1.1-32.3 months). Eleven patients (22%) survived longer than 12 months (range, 12.2-32.3) with one patient alive at follow-up. Tumor burden and LDH levels showed no statistically significant effect on OS (p = 0.20 and p = 0.14, respectively) or PFS (p = 0.10 and p = 0.34, respectively). CONCLUSION: BCNU chemoembolization should be considered as a treatment option for patients with bulky uveal melanoma hepatic metastases.

Double-blinded, randomized phase II study using embolization with or without granulocyte-macrophage colony-stimulating factor in uveal melanoma with hepatic metastases.

PURPOSE: To investigate the effects of immunoembolization with granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with uveal melanoma (UM) with liver-only metastasis. MATERIALS AND METHODS: In this double-blind phase II clinical trial, patients were randomized to undergo immunoembolization or bland embolization (BE). Lobar treatment was performed with GM-CSF or normal saline solution mixed with ethiodized oil followed by embolization with gelatin sponge emulsified with iodinated contrast medium. Fifty-two patients (immunoembolization, n = 25; BE, n = 27) were enrolled. Response was assessed after every two treatments. The primary endpoint was overall response rate (ORR) of liver metastases. Progression-free survival (PFS), overall survival (OS), and immunologic responses were secondary endpoints. RESULTS: There were five partial responses in the immunoembolization group (ORR, 21.2%; 90% confidence interval [CI], 10.3%-30.5%) and three in the BE group (ORR, 16.7%; 90% CI, 6.3%-26.9%). Stable disease was seen in 12 patients in the immunoembolization group and 19 in the BE group. OS times were 21.5 months (95% CI, 18.5-24.8 mo) with immunoembolization and 17.2 months (95% CI, 11.9-22.4 mo) with BE. The degree of proinflammatory cytokine production was more robust after immunoembolization and correlated with time to "systemic" extrahepatic progression. In the immunoembolization group, interleukin (IL)-6 levels at 1 hour (P = .001) and IL-8 levels at 18 hours after the procedure (P < .001) were significant predictors of longer systemic PFS. Moreover, a dose-response pattern was evident between posttreatment serum cytokine concentrations and systemic PFS. CONCLUSIONS: Immunoembolization induced more robust inflammatory responses, which correlated with the delayed progression of extrahepatic systemic metastases.

Arterial Blood, Rather Than Venous Blood, is a Better Source for Circulating Melanoma Cells.

BACKGROUND: CTCs provide prognostic information and their application is under investigation in multiple tumor types. Of the multiple variables inherent in any such process, none is more important to outcome than the appropriateness of the sample source. To address this question, we investigated CTCs in paired peripheral venous and arterial blood specimens obtained from stage IV uveal melanoma patients. METHODS: Blood specimens were obtained from both common femoral arteries and antecubital veins in 17 uveal melanoma patients with multiple hepatic metastases for CTC measurements. FINDING: CTCs were detectable with greater frequency (100%) and in larger numbers (median 5, range 1 to 168) in all arterial blood specimens than in venous samples (52.9%; median 1, range 0 to 8). Patients with hepatic as well as extra-hepatic metastasis showed higher number of arterial CTCs, compared to patients with liver-only metastasis (p = 0.003). There was no significant association between the number of arterial CTCs and the tumor burden within the liver in patients who had liver-only metastases. INTERPRETATION: Our data indicate that arterial blood specimens might be a better source of circulating uveal melanoma cells. Although less conveniently processed, perhaps arterial blood should be evaluated as sample source for measurement of CTCs.

Early arterial stasis during resin-based yttrium-90 radioembolization: incidence and preliminary outcomes.

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.

Single-center comparison of three chemoembolization regimens for hepatocellular carcinoma.

PURPOSE: Transarterial chemoembolization regimens for hepatocellular carcinoma (HCC) vary, without a gold-standard method. The present study was performed to evaluate outcomes in patients with HCC treated with doxorubicin/ethiodized oil (DE), cisplatin/doxorubicin/mitomycin-c/ethiodized oil (CDM), or doxorubicin drug-eluting beads (DEBs). MATERIALS AND METHODS: Patients received the same regimen at all visits, without crossover. Groups were compared based on Child-Pugh disease status, tumor/node/metastasis stage, and Barcelona Clinic Liver Cancer stage. Imaging outcomes were assessed based on modified Response Evaluation Criteria in Solid Tumors to calculate tumor response (ie, sum of complete and partial response), progressive disease (PD), and time to progression (TTP). RESULTS: A total of 228 infusions were performed in 122 patients: 59 with DE, 30 with CDM, and 33 with DEBs. The groups had similar Child-Pugh status (P = .45), tumor/node/metastasis stages (P = .5), and Barcelona Clinic Liver Cancer scores (P = .22). Follow-up duration was similar among groups (P = .24). Patients treated with DE underwent significantly more treatments (2.3 ± 1.4) than those treated with CDM (1.6 ± 0.7; P = .004) or DEBs (1.4 ± 0.6; P<.0001). Compared with DE (51%), tumor response was significantly more common with CDM (84%; P = .003) or DEBs (82%; P = .004). PD was significantly more likely with DE (37%) than with CDM (13%; P = .02) or DEBs (9%; P = .004). TTP was similar between groups (P = .07). CDM and DEBs were similar in regard to disease progression (P = .6) and response (P = .83). CONCLUSIONS: During a similar follow-up period, patients treated with CDM or DEB chemoembolization showed a significantly higher response rate and a lower incidence of tumor progression, with fewer required treatment sessions, than those treated with DE chemoembolization.