Efficacy and Safety of the Melphalan/Hepatic Delivery System in Patients with Unresectable Metastatic Uveal Melanoma: Results from an Open-Label, Single-Arm, Multicenter Phase 3 Study.

BACKGROUND: Uveal melanoma (UM) has a poor prognosis once liver metastases occur. The melphalan/Hepatic Delivery System (melphalan/HDS) is a drug/device combination used for liver-directed treatment of metastatic UM (mUM) patients. The purpose of the FOCUS study was to assess the efficacy and safety of melphalan/HDS in patients with unresectable mUM. METHODS: Eligible patients with mUM received treatment with melphalan (3.0 mg/kg ideal body weight) once every 6 to 8 weeks for a maximum of six cycles. The primary end point was the objective response rate (ORR). The secondary end points included duration of response (DOR), overall survival (OS), and progression-free survival (PFS). RESULTS: The study enrolled 102 patients with mUM. Treatment was attempted in 95 patients, and 91 patients received treatment. In the treated population (n = 91), the ORR was 36.3 % (95 % confidence interval [CI], 26.44-47.01), including 7.7 % of patients with a complete response. Thus, the study met its primary end point because the lower bound of the 95 % CI for ORR exceeded the upper bound (8.3 %) from the benchmark meta-analysis. The median DOR was 14 months, and the median OS was 20.5 months, with an OS of 80 % at 1 year. The median PFS was 9 months, with a PFS of 65 % at 6 months. The most common serious treatment-emergent adverse events were thrombocytopenia (15.8 %) and neutropenia (10.5 %), treated mostly on an outpatient basis with observation. No treatment-related deaths were observed. CONCLUSION: Treatment with melphalan/HDS provides a clinically meaningful response rate and demonstrates a favorable benefit-risk profile in patients with unresectable mUM (study funded by Delcath; ClinicalTrials.gov identifier: NCT02678572; EudraCT no. 2015-000417-44).

Radioembolization with Yttrium-90 Glass Microspheres as a First-Line Treatment for Unresectable Intrahepatic Cholangiocarcinoma-A Prospective Feasibility Study.

PURPOSE: To evaluate the safety and effectiveness of yttrium-90 (90Y) radioembolization as first-line treatment for unresectable intrahepatic cholangiocarcinoma (ICC). MATERIALS AND METHODS: This prospective study enrolled patients who had never received chemotherapy, liver embolization, and radiation therapy. The tumors were solitary in 16 patients, multiple in 8 patients, unilobar in 14 patients, and bilobar in 10 patients. Patients underwent transarterial radioembolization with 90Y-labeled glass microspheres. The primary end point was hepatic progression-free survival (HPFS). Secondary end points were overall survival (OS), tumor response, and toxicity. RESULTS: Twenty-four patients (age, 72.3 years ± 9.3; 12 women) were included in the study. The median delivered radiation dose was 135.5 Gy (interquartile range, 77.6 Gy). The median HPFS was 5.5 months (95% CI, 3.9-7.0 months). Analysis failed to identify any prognostic factor associated with HPFS. Imaging response at 3 months showed 56% disease control, and the best radiographic response was 71% disease control. The median OS from the radioembolization treatment was 19.4 months (95% CI, 5.0-33.7). Patients with solitary ICC had significantly longer median OS than patients with multifocal ICC: 25.9 months (95% CI, 20.8-31.0 months) versus 10.7 months (95% CI, 8.0-13.4 months) (P = .02). Patients with progression on the 3-month imaging follow-up had significantly shorter median OS than patients who had stable disease at 3 months: 10.7 months (95% CI, 0.7-20.7 months) versus 37.3 months (95% CI, 16.5-58.1 months) (P = .003). Two (8%) Grade 3 toxicities were reported. CONCLUSIONS: First-line treatment of ICC with radioembolization showed promising OS and minimal toxicity, especially in patients with solitary tumor. Radioembolization may be considered as a first-line treatment option for unresectable ICC.

Unresectable Intrahepatic Cholangiocarcinoma Treated with Radiation Segmentectomy/Lobectomy Using Yttrium 90-labeled Glass Microspheres.

Background: There is no curative treatment option for patients with unresectable intrahepatic, cholangiocarcinoma (IHC). The aim of this study was to evaluate the efficacy of; radiation segmentectomy/lobectomy using Y90-labeled glass microspheres in patients with; unresectable IHC. Methods: This IRB-approved, single-center study included, 16 patients (age: 67 ± 7.7 years) with IHC who received radiation segmentectomy or lobectomy, treatment using Y90-labeled glass microspheres between May 2009 and October 2019. Radiation, segmentectomy/lobectomy was defined as at least 190 Gy dose delivered into treated liver; volume. Results: The median OS from IHC diagnosis was 22.7 months (95% CI: 13.9-66.1) and from, radioembolization it was 7 months (95% CI: 4.33-54.17). Patients who did not receive, chemotherapy before the radioembolization had significantly longer median OS (26.8 vs. 5.9, months, P = 0.03). Four patients had >20 months survival after radioembolization, including 2, patients with survival of 42 and 54 months. There was no 30-day mortality and no severe, complications. Conclusion: Radiation segmentectomy/lobectomy is safe with minimal side effects. The median, OS of the study group is modest; however, 4 patients (25%) showed excellent survival. These results suggest a need for a larger study to define the IHC patient group who could, most benefit from this procedure.

Transarterial Yttrium-90 Glass Microsphere Radioembolization of Chemotherapy-Refractory Breast Cancer Liver Metastases: Results of a Single Institution Retrospective Study.

PURPOSE: Our purpose was to retrospectively evaluate the safety and efficacy of transarterial hepatic radioembolization (TARE) treatment with yttrium-90 labeled glass microspheres in patients with chemotherapy-refractory breast cancer with liver-dominant metastatic disease. METHODS AND MATERIALS: This retrospective single-institution study evaluated 31 female patients (mean age of 59.6 ± 13.2 years) who were treated with TARE. All patients received and progressed on systemic chemotherapy before TARE. Twenty-one patients also had extrahepatic metastases, including 13 patients who had metastases in bones only besides the liver. Survival data were analyzed by Kaplan-Meier method and compared using log-rank test. Imaging response to treatment was determined by Response Evaluation Criteria in Solid Tumors. RESULTS: Median overall survival (OS) from the TARE was 13 months (95% confidence interval, 9.1-16.9 months). The survival probability at 1, 2, and 3 years was 60.1%, 36.7%, and 24.5%, respectively. The median hepatic progression-free survival was 7 months (95% confidence interval, 6.1-7.9 months). There was no 30-day mortality and 3 patients (9.4%) had grade 3 toxicity. Estrogen receptor (ER) positive status predicted prolonged survival (14 months for ER+ vs 9 months for ER-; P = .028). Patients who had bone-only extrahepatic disease had higher OS than patients with extraosseous metastases (23 vs 8 months, P = .02). At the 3-month follow-up the radiographic objective response rate was 46.6% and disease control rate was 70%. CONCLUSIONS: The treatment of patients with liver-dominant chemotherapy-refractory breast cancer metastases with TARE using yttrium-90 labeled glass microspheres is safe and led to promising hepatic disease control and OS especially in patients with ER+ tumors and in patients without extrahepatic extraosseous metastases.

Role of Radioembolization in the Management of Liver-Dominant Metastatic Renal Cell Carcinoma: A Single-Center, Retrospective Study.

PURPOSE: The management of Renal cell carcinoma (RCC) patients with liver metastases is challenging. Liver-directed therapy, such as Transarterial radioembolization (TARE), is a reasonable option for these patients; however, its safety and efficacy are not well characterized. This study evaluated the safety and efficacy of TARE in patients with liver-dominant metastatic RCC. MATERIALS AND METHODS: This is a retrospective, single-center study. Thirty-eight patients' medical records were reviewed who underwent TARE between January 1, 2009, and December 31, 2019, in a tertiary cancer center. Two were excluded from further analysis. Thirty-six patients received 51 TARE treatments. Median follow-up time was 18.2 months. Imaging data were evaluated using mRECIST or RECIST 1.1 criteria. Toxicities, treatment responses, liver progression-free survival (LPFS), and median overall survival (OS) were calculated. Univariate and multivariate analyses were conducted to reveal predictors of OS. RESULTS: Median OS from TARE was 19.3 months (95% CI, 22.6-47.4) and from diagnosis of liver metastases was 36.5 months (95% CI: 26.4-49.8). Mild, grade 1 or 2, biochemical toxicity developed in 27 patients (75%). Grade 3-4 toxicity was noted in two patients (5.5%). The objective response rate was 89%; the disease control rate was 94% (21 complete response, 11 partial response, two stable disease, and two progressive disease). Univariate and multivariate analyses showed longer survival in patients who had objective response, lower lung shunt fraction, and better baseline liver function. CONCLUSIONS: TARE is safe and effective and led to promising overall survival in patients with liver-dominant metastatic RCC. LEVEL OF EVIDENCE: Level 3, retrospective cohort study.

Intraoperative Localization Using an Implanted Radar Reflector Facilitates Resection of Non-Palpable Trunk and Extremity Sarcoma.

BACKGROUND: Resecting non-palpable soft tissue tumors presents a unique challenge, particularly with recurrent disease in which surrounding tissue has been surgically manipulated and often irradiated. SAVI SCOUT® is a radar-based localization device that was developed for breast tumor localization and was recently FDA-approved for localization of soft tissue tumors. Application of this technology to soft tissue sarcoma has not been previously reported. METHODS: We assembled a single-institution retrospective case series of patients with trunk and extremity sarcomas resected by five sarcoma surgeons using SAVI SCOUT® from December 2018 to May 2020. Reflectors were placed preoperatively using image-guidance, and the radar detector was used intraoperatively to localize the target lesion. Clinical variables were abstracted from the electronic medical record including treatment history, pathology, and early oncologic outcomes. Using a focused review, we compared margin status and recurrence rates with previously published cohorts. RESULTS: Ten SAVI SCOUT®-localized sarcoma resections were performed. Eight were for locally recurrent disease, of which seven (83%) had prior radiation. The remaining lesions became non-palpable after neoadjuvant chemotherapy. SAVI SCOUT® facilitated resection in all cases with a margin-negative resection rate (77%) comparable to prior cohorts. In this high-risk population with a median follow-up of 14 months, only one patient recurred locally 7.5 months after SAVI SCOUT®-localized resection, requiring re-resection. CONCLUSION: SAVI SCOUT® technology facilitated resection of non-palpable recurrent sarcoma of the trunk and extremities in all ten cases attempted. In a high-risk patient population, the pattern of recurrence has been primarily distant with one instance of local tumor recurrence.

Liver tumor ablation in difficult locations: Microwave ablation of perivascular and subdiaphragmatic hepatocellular carcinoma.

AIM: To assess the safety and efficacy of CT-guided microwave ablation (MWA) of hepatocellular carcinoma (HCC) near large blood vessels and the diaphragm by analyzing procedural complications and local tumor progression (LTP). METHODS: From October 2013 through January 2019, 80 patients (54 males and 26 females) with 136 tumors who underwent CT-guided MWA of HCC were included in this retrospective analysis. MWA was performed on 43 perivascular HCC (≤5 mm from a vessel measuring ≥5 mm in diameter), 38 subdiaphragmatic HCC (≤5 mm from diaphragm), and 64 control HCC. Risk factors for local tumor progression (LTP), overall survival, and complications were analyzed using the Chi-square and Cox proportional hazards model methods. RESULTS: The technical success rate of MWA was 100%. Complication incidence was not significantly different between perivascular and control tumors (20.9% vs 10.9%; p = 0.155) or between subdiaphragmatic and control tumors (21.1% vs 10.9%; p = 0.163). The effect of lesion location on LTP disappeared while controlling for age and lesion size. There was no significant difference in median survival time between patients who had only control tumors (38.8 months) compared to patients with at least one perivascular or subdiaphragmatic tumor (42.5 months; p = 0.098). CONCLUSION: CT-guided percutaneous MWA of perivascular and subdiaphragmatic HCC tumors is safe and effective. The local tumor recurrence and survival was not significantly different compared to control tumors.

Over 12 Years Single Institutional Experience Performing Percutaneous Hepatic Perfusion for Unresectable Liver Metastases.

Patients with unresectable hepatic metastases, from uveal or ocular melanoma, are challenging to treat with an overall poor prognosis. Although over the past decade significant advances in systemic therapies have been made, metastatic disease to the liver, especially from uveal melanoma, continues to be a poor prognosis. Percutaneous hepatic perfusion (PHP) is a safe, viable treatment option for these patients. PHP utilizes high dose chemotherapy delivered directly to the liver while minimizing systemic exposure and can be repeated up to 6 times. Isolation of the hepatic vasculature with a double-balloon catheter allows for high concentration cytotoxic therapy to be administered with minimal systemic adverse effects. A detailed description of the multidisciplinary treatment protocol used at an institution with over 12 years of experience is discussed and recommendations are given. A dedicated team of a surgical or medical oncology, interventional radiology, anesthesiology and a perfusionist allows PHP to be repeatedly performed as a safe treatment strategy for unresectable hepatic metastases.

Transarterial Radioembolization Treatment of Pancreatic Cancer Patients with Liver-Dominant Metastatic Disease Using Yttrium-90 Glass Microspheres: A Single-Institution Retrospective Study.

PURPOSE: To retrospectively evaluate the safety and efficacy of transarterial radioembolization (TARE) with yttrium-90 (90Y)-labeled glass microspheres in pancreatic adenocarcinoma patients with liver-dominant metastatic disease. MATERIALS AND METHODS: This retrospective, single-center study evaluated 26 patients (12 men and 14 women; mean age, 65.5 ± 11.2 years) with liver-dominant metastatic pancreatic cancer who were treated with TARE from April 2010 to September 2017. All patients received systemic chemotherapy before TARE, and 19 received systemic therapy after embolization. Nineteen patients had extrahepatic disease at the time of TARE. Response to treatment was determined by Response Evaluation Criteria in Solid Tumors at 3 months. RESULTS: Median overall survival (OS) from pancreatic cancer diagnosis was 33.0 months (range, 8.5-87.5 months); median OS from diagnosis of liver metastasis was 21.8 months (range, 2.0-86.2 months); and median OS from TARE treatment was 7.0 months (range, 1.0-84.1 months). Grade 1-2 clinical toxicities were noted in 21 patients (80.8%), and 24 patients (92.3%) had grade 1-2 biochemical toxicities. Four patients (15.4%) had grade 3 clinical toxicities, and 6 patients (23.1%) had grade 3 biochemical toxicities. Imaging was available in 22 patients (84.6%) and demonstrated partial response in 1 patient, stable disease in 9 patients, and progressive disease in 12 patients. Improved hepatic progression-free survival was associated in patients younger than 65 years and in those whose carbohydrate antigen 19-9 level decreased or remained stable after treatment. CONCLUSIONS: TARE with 90Y-labeled glass microspheres is safe and led to promising OS in liver-dominant metastatic pancreatic cancer.

COMPLIANCE TESTING FOR HUMAN BODY MODEL EXPOSURE TO ELECTROMAGNETIC FIELDS FROM A HIGH-POWER WIRELESS CHARGING SYSTEM FOR DRONES.

Recently, a wireless charging system (WCS) for drones has been extensively studied, although standards for compliance testing of a WCS for drones have yet to be established. In this study, we propose methods for human exposure assessments of a WCS for drones by comprehensively considering the various positions of the system and the postures of human body models. The electromagnetic fields from a WCS are modeled and the internal quantities of the human body models, consisting of current density, internal electric field and specific absorption rate, are calculated. The incident fields around the WCS and the internal quantities are analyzed at 140 kHz, which is the operating frequency of the WCS applied. Results of an exposure assessment based on the confirmed worst-case scenario are presented. In addition, the internal quantities depending on the human body models and the material characteristics of the simplified models are also discussed using four different anatomical and simplified human body models.

Partial Splenic Artery Embolization in 35 Cancer Patients: Results of a Single Institution Retrospective Study.

PURPOSE: To evaluate the safety and efficacy of partial splenic embolization (PSE) in cancer patients with different etiologies of splenomegaly/hypersplenism. MATERIALS AND METHODS: The medical records of 35 cancer patients who underwent 39 PSE procedures were analyzed. The splenomegaly/hypersplenism was due to chemotherapy (n = 17), portal hypertension (n = 10), or hematologic malignancy (n = 8). After the first 11 PSEs, celiac plexus neurolysis, corticosteroids, and non-steroid anti-inflammatory drugs (NSAIDs) were included in the post-procedural management. RESULTS: PSE led to 59 ± 16% (mean ± standard deviation) splenic infarcts. The infarct volume per 1 mL 300-500 µm tris-acryl gelatin microspheres was not significantly different between the chemotherapy-induced group (264 ± 89 cm3) and the portal hypertension group (285 ± 139 cm3) but was significantly higher in the hematology group (582 ± 345 cm3). Platelet count increased from 65.7 ± 19.7 k/µl to a peak platelet count of 221 ± 83 k/µl at 2 weeks after PSE. Patients with a follow-up period of more than 1 year had the most recent platelet count of 174 ± 113 k/µl. Platelet count increase was significantly higher in the chemotherapy-induced group than the portal hypertension group. Adding celiac plexus neurolysis, corticosteroids, and NSAIDs to the post-procedural management resulted in a decreased rate of major complications from 73% to 46% and a decrease in the rate of moderate or severe pain from 92% to 20%. CONCLUSIONS: PSE improved platelet counts in cancer patients despite different etiologies of splenomegaly. The addition of celiac plexus neurolysis, corticosteroids, and NSAIDS to the post-PSE treatment protocol reduced complications. Data from this study could help to predict the amount of 300-500 µm tris-acryl gelatin microspheres required to achieve a planned infarct size.

Semiautomated Measure of Abdominal Adiposity Using Computed Tomography Scan Analysis.

BACKGROUND: The obesity epidemic has prompted the need to better understand the impact of adipose tissue on human pathophysiology. However, accurate, efficient, and replicable models of quantifying adiposity have yet to be developed and clinically implemented. We propose a novel semiautomated radiologic method of measuring the visceral fat area (VFA) using computed tomography scan analysis. MATERIALS AND METHODS: We obtained a cohort of 100 patients with rectal adenocarcinoma, with a median age of 60.9 y (age range: 35-87 y) and an average body mass index of 28.8 kg/m2 ± 6.56 kg/m2. The semiautomated quantification method of adiposity was developed using a commercial imaging suite. The method was compared to two manual delineations performed using two different picture archiving communication systems. We quantified VFA, subcutaneous fat area (SFA), total fat area (TFA), and visceral-to-subcutaneous fat ratio (V/S ratio) on computed tomography axial slices that were at the L4-L5 intervertebral level. RESULTS: The semiautomated method was comparable to manual measurements for TFA, VFA, and SFA with intraclass correlation (ICC) of 0.99, 0.97, and 0.96, respectively. However, the ICC for the V/S ratio was only 0.44, which led to the identification of technical outliers that were identified using robust regression. After removal of these outliers, the ICC improved to 0.99 for TFA, VFA, and SFA and 0.97 for the V/S ratio. Measurements from the manual methodology highly correlated between the two picture archiving communication system platforms, with ICC of 0.98 for TFA, 0.98 for VFA, 0.96 for SFA, and 0.95 for the V/S ratio. CONCLUSIONS: This semiautomated method is able to generate precise and reproducible results. In the future, this method may be applied on a larger scale to facilitate risk stratification of patients using measures of abdominal adiposity.

Using the Albumin-Bilirubin (ALBI) grade as a prognostic marker for radioembolization of hepatocellular carcinoma.

BACKGROUND: The Child-Pugh (CP) class is a commonly used scoring system to measure liver function in patients with hepatocellular carcinoma (HCC). We correlate the Albumin-Bilirubin (ALBI) grading system and CP to overall survival in our HCC patients receiving radioembolization. METHODS: We retrospectively evaluated patients who received radioembolization for HCC between the years 2009-2014. We evaluated the albumin and bilirubin levels in our patients prior to receiving their first (n=124) radioembolization. The ALBI grades were calculated from these data with the formula (log10 bilirubin ×0.66) + (albumin × -0.085) and correlated to outcomes using Mantel-Cox Log analysis. These statistical comparisons were duplicated with CP classes. RESULTS: Median survival differences between CP class A and B and between ALBI grade 1 and 2 were 4.7 and 9.9 months, respectively. A subset of ALBI grades 1 and 2 were identified within our CP class A patients with a median survival difference of 9.9 months. CONCLUSIONS: ALBI is a more sensitive marker of liver function than CP in the setting of mild dysfunction. Using ALBI, we identified a subset of patients that have significantly better outcomes from Y-90 radioembolization than previously identified with CP.

Viral hepatitis associated hepatocellular carcinoma outcomes with yttrium-90 radioembolization.

BACKGROUND: Viral associated (VA) malignancies have recently been correlated with improved outcomes. We sought to evaluate outcomes of patients with hepatocellular carcinoma (HCC) with and without viral hepatitis (hepatitis B and C) treated with lobar yttrium-90 radioembolization (Y-90 RE). METHODS: After IRB approval, an institutional database of patients with HCC who received RE between 2009-2014 was queried and 99 patients were identified that received a total of 122 lobar RE. Charts were reviewed to capture previous treatments, viral hepatitis status, α-fetoprotein values (AFP), Child-Pugh class (CP), albumin-bilirubin score (ALBI), portal vein thrombosis (PVT), volumes treated and doses delivered. Comparison was made with Chi-square and Mann-Whitney U test. Intrahepatic control (IHC), extrahepatic control (EHC), progression free survival (PFS), and overall survival (OS) were calculated according to the Kaplan-Meier method stratified by cause of underlying liver disease (viral vs. non-viral) and survival differences were assessed via the log-rank test. Hazard ratios were calculated using Cox regression. RESULTS: Median follow up for VA HCC and non-VA (NVA) HCC patients was 10.9 months (range, 0.8-46.7 months) and 11.8 months (range, 1.1-62.8 months), respectively. Patients with VA HCC (n=44) were younger (P<0.001) and had smaller pretreatment liver volumes (P<0.001); however, there was no difference with respect to gender, pre-treatment AFP, CP, ALBI, PVT, extrahepatic disease, previous treatment, or dose delivered. Median doses for VA and NVA HCC patients were 129.5 Gy (range, 90-215.8 Gy) and 131 Gy (range, 100.9-265 Gy), respectively (P=0.75). One year IHC showed a strong trend to better control for VA HCC at 67% versus 34% for NVA HCC (P=0.067) but 1 year EHC was significantly worse at 63% for VA HCC versus 86% for NVA HCC (P=0.027). There were no significant differences in survival, with a 1-year PFS of 45% for VA HCC versus 31% for NVA HCC (P=0.56) and 1 year OS of 46% versus 55% (P=0.55). Patients that received salvage treatments, CP A, no PVT, and those without extrahepatic disease had improved OS. CONCLUSIONS: Patients with VA HCC had a trend to improved IHC and significantly worse EHC. Prospective investigation of novel systemic therapies following Y-90 RE in patients with VA HCC is warranted to potentially further extend survival in VA HCC patients by addressing extra-hepatic disease.

Intrahepatic Cholangiocarcinoma Treated with Transarterial Yttrium-90 Glass Microsphere Radioembolization: Results of a Single Institution Retrospective Study.

PURPOSE: To evaluate the efficacy and safety of transarterial yttrium-90 glass microsphere radioembolization in patients with unresectable intrahepatic cholangiocarcinoma (ICC). MATERIALS AND METHODS: Retrospective review of 85 consecutive patients (41 men and 44 women; age, 73.4 ± 9.3 years) was performed. Survival data were analyzed by the Kaplan-Meier method, Cox regression models, and the log-rank test. RESULTS: Median overall survival (OS) from diagnosis was 21.4 months (95% confidence interval [CI]: 16.6-28.4); median OS from radioembolization was 12.0 months (95% CI: 8.0-15.2). Seven episodes of severe toxicity occurred. At 3 months, 6.2% of patients had partial response, 64.2% had stable disease, and 29.6% had progressive disease. Median OS from radioembolization was significantly longer in patients with Eastern Cooperative Oncology Group (ECOG) scores of 0 and 1 than patients with an ECOG score of 2 (18.5 vs 5.5 months, P = .0012), and median OS from radioembolization was significantly longer in patients with well-differentiated histology than patients with poorly differentiated histology (18.6 vs 9.7 months, P = .012). Patients with solitary tumors had significantly longer median OS from radioembolization than patients with multifocal disease (25 vs. 6.1 months, P = .006). The absence of extrahepatic metastasis was associated with significantly increased median OS (15.2 vs. 6.8 months, P = .003). Increased time from diagnosis to radioembolization was a negative predictor of OS. The morphology of the tumor (mass-forming or infiltrative, hyper- or hypo-enhancing) had no effect on survival. Post-treatment increased cancer antigen 19-9 level, increased international normalized ratio, decreased albumin, increased bilirubin, increased aspartate aminotransferase, and increased Model for End-Stage Liver Disease score were significant predictors of decreased OS. CONCLUSIONS: These data support the therapeutic role of radioembolization for the treatment of unresectable ICC with good efficacy and an acceptable safety profile.

Hepatic Progression-free and Overall Survival After Regional Therapy to the Liver for Metastatic Melanoma.

OBJECTIVES: Regional therapy for metastatic melanoma to the liver represents an alternative to systemic therapy. Hepatic progression-free survival (HPFS), progression-free survival (PFS), and overall survival (OS) were evaluated. MATERIALS AND METHODS: A retrospective review of patients with liver metastases from cutaneous or uveal melanoma treated with yttrium-90 (Y90), chemoembolization (CE), or percutaneous hepatic perfusion (PHP) was conducted. RESULTS: Thirty patients (6 Y90, 10 PHP, 12 CE, 1 PHP then Y90, 1 CE then PHP) were included. Multivariate analysis showed improved HPFS for PHP versus Y90 (P=0.004), PHP versus CE (P=0.02) but not for CE versus Y90. PFS was also significantly different: Y90 (54 d), CE (52 d), PHP (245 d), P=0.03. PHP treatment and lower tumor burden were significant predictors of prolonged PFS on multivariate analysis. Median OS from time of treatment was longest, but not significant, for PHP at 608 days versus Y90 (295 d) and CE (265 d), P=0.24. Only PHP treatment versus Y90 and lower tumor burden had improved OS on multivariate analysis (P=0.03, 0.03, respectively). CONCLUSIONS: HPFS and PFS were significantly prolonged in patients treated with PHP versus CE or Y90. Median OS in PHP patients was over double that seen in Y90 or CE patients but was significant only between PHP and Y90.

Percutaneous hepatic perfusion with melphalan in uveal melanoma: A safe and effective treatment modality in an orphan disease.

BACKGROUND: Metastatic uveal melanoma (UM) carries a poor prognosis; liver is the most frequent and often solitary site of recurrence. Available systemic treatments have not improved outcomes. Melphalan percutaneous hepatic perfusion (M-PHP) allows selective intrahepatic delivery of high dose cytotoxic chemotherapy. METHODS: Retrospective analysis of outcomes data of UM patients receiving M-PHP at two institutions was performed. Tumor response and toxicity were evaluated using RECIST 1.1 and Common Terminology Criteria for Adverse Events (CTCAE) v4.03, respectively. RESULTS: A total of 51 patients received 134 M-PHP procedures (median of 2 M-PHPs). 25 (49%) achieved a partial (N = 22, 43.1%) or complete hepatic response (N = 3, 5.9%). In 17 (33.3%) additional patients, the disease stabilized for at least 3 months, for a hepatic disease control rate of 82.4%. After median follow-up of 367 days, median overall progression free (PFS) and hepatic progression free survival (hPFS) was 8.1 and 9.1 months, respectively and median overall survival was 15.3 months. There were no treatment related fatalities. Non-hematologic grade 3-4 events were seen in 19 (37.5%) patients and were mainly coagulopathic (N = 8) and cardiovascular (N = 9). CONCLUSIONS: M-PHP results in durable intrahepatic disease control and can form the basis for an integrated multimodality treatment approach in appropriately selected UM patients.

Multimodality Management of "Borderline Resectable" Pancreatic Neuroendocrine Tumors: Report of a Single-Institution Experience.

BACKGROUND: Pancreatic neuroendocrine tumors (PanNETs) constitute approximately 3% of pancreatic neoplasms. Like patients with pancreatic ductal adenocarcinoma (PDAC), some of these patients present with "borderline resectable disease." For these patients, an optimal treatment approach is lacking. We report our institution's experience with borderline resectable PanNETs using multimodality treatment. METHODS: We identified patients with borderline resectable PanNETs who had received neoadjuvant therapy at our institution between 2000 and 2013. The definition of borderline resectability was based on National Comprehensive Cancer Network criteria for PDAC. Neoadjuvant regimen, radiographic response, pathologic response, surgical margins, nodal retrieval, number of positive nodes, and recurrence were documented. Statistics were descriptive. RESULTS: Of 112 patients who underwent surgical resection for PanNETs during the study period, 23 received neoadjuvant therapy, 6 of whom met all inclusion criteria and had borderline resectable disease. These 6 patients received at least 1 cycle of temozolomide and capecitabine, with 3 also receiving radiation. All had radiographic evidence of treatment response. Four (67%) had negative-margin resections. Four patients had histologic evidence of a moderate response. Follow-up (3.0-4.3 years) indicated that all patients were alive, with 5/6 free of disease (1 patient with metastatic disease still on treatment without progression). CONCLUSIONS: A multimodality treatment strategy (neoadjuvant temozolomide and capecitabine ± radiation) can be successfully applied to patients with PanNETs who meet NCCN borderline resectable criteria for PDAC. To our knowledge, this is the first report of the use of a multimodality protocol in the treatment of patients with borderline resectable PanNETs.

Liver-Directed Therapies for Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma.

Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (IHC) are primary liver cancers where all or most of the tumor burden is usually confined to the liver. Therefore, locoregional liver-directed therapies can provide an opportunity to control intrahepatic disease with minimal systemic side effects. The English medical literature and clinical trials were reviewed to provide a synopsis on the available liver-directed percutaneous therapies for HCC and IHC. Locoregional liver-directed therapies provide survival benefit for patients with HCC and IHC compared to best medical treatment and have lower comorbid risks compared to surgical resection. These treatment options should be considered, especially in patients with unresectable disease.