Genicular Artery Embolization: A Review of Essential Anatomic Considerations.

Genicular artery embolization is increasingly recognized as a safe and effective treatment option for symptomatic knee osteoarthritis and recurrent hemarthrosis after total knee arthroplasty. Genicular arteries are an essential contributor to vascular supply for the knee joint and demonstrate considerable variability. Familiarity with the anatomy and common variations is critical for preprocedural planning, accurate target selection, and minimizing adverse events in transarterial embolization procedures. This review aimed to provide a detailed discussion of the genicular artery anatomy that is relevant to interventional radiologists performing genicular artery embolization.

Genicular Artery Embolization for Treatment of Knee Osteoarthritis: Interim Analysis of a Prospective Pilot Trial Including Effect on Serum Osteoarthritis-Associated Biomarkers.

PURPOSE: To characterize the safety, efficacy, and potential role of genicular artery embolization (GAE) as a disease-modifying treatment for symptomatic knee osteoarthritis (OA). MATERIALS AND METHODS: This is an interim analysis of a prospective, single-arm clinical trial of patients with symptomatic knee OA who failed conservative therapy for greater than 3 months. Sixteen patients who underwent GAE using 250-µm microspheres and had at least 1 month of follow-up were included. Six patients completed the 12-month follow-up, and 10 patients remain enrolled. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was evaluated at baseline and at 1, 3, and 12 months. Serum and plasma samples were collected for biomarker analysis. The primary end point was the percentage of patients who achieved the minimal clinically important difference (MCID) for WOMAC pain score at 12 months. Baseline and follow-up outcomes were analyzed using the Wilcoxon matched-pairs signed-rank test. RESULTS: Technical success of the procedure was 100%, with no major adverse events. The MCID was achieved in 5 of the 6 (83%) patients at 12 months. The mean WOMAC pain score decreased from 8.6 ± 2.7 at baseline to 4.9 ± 2.7 (P = .001), 4.4 ± 2.8 (P < .001), and 4.7 ± 2.7 (P = .094) at 1, 3, and 12 months, respectively. There was a statistically significant decrease in nerve growth factor (NGF) levels at 12 months. The remaining 8 biomarkers showed no significant change at 12 months. CONCLUSIONS: GAE is a safe and efficacious treatment for symptomatic knee OA. Decreased NGF levels after GAE may contribute to pain reduction and slowing of cartilage degeneration.

Safety and Effectiveness of Yttrium-90 Radioembolization around the Time of Immune Checkpoint Inhibitors for Unresectable Hepatic Metastases.

PURPOSE: To assess the safety and effectiveness of yttrium-90 radioembolization and checkpoint inhibitor immunotherapy within a short interval for the treatment of unresectable hepatic metastases. MATERIALS AND METHODS: This single-institution retrospective study included 22 patients (12 men; median age, 65 y ± 11) with unresectable hepatic metastases and preserved functional status (Eastern Cooperative Oncology Group performance status 0/1) who received immunotherapy and radioembolization within a 15-month period (median, 63.5 d; interquartile range, 19.7-178.2 d) from February 2013 to March 2018. Primary malignancies were uveal melanoma (12 of 22; 54.5%), soft tissue sarcoma (3; 13.6%), cutaneous melanoma (3; 14%), and others (4; 18.2%). Studies were reviewed to March 2019 to assess Common Terminology Criteria for Adverse Events grade 3/4 toxicities, disease progression, and death. RESULTS: There were no grade 4 toxicities within 6 mo of radioembolization. Grade 3 hepatobiliary toxicities occurred in 3 patients (13.6%) within 6 months, 2 from rapid disease progression and 1 from a biliary stricture. Two patients (9.1%) experienced clinical toxicities, including grade 4 colitis at 6 months and hepatic abscess at 3 months. Median overall survival (OS) from first radioembolization was 20 mo (95% confidence interval [CI], 12.5-27.5 mo), and median OS from first immunotherapy was 23 months (95% CI, 15.9-30.1 mo). Within the uveal melanoma subgroup, the median OS from first radioembolization was 17.0 months (95% CI, 14.2-19.8 mo). Median time to progression was 7.8 months (95% CI, 3.3-12.2 mo), and median progression-free survival was 7.8 mo (95% CI, 3.1-12.4 mo). CONCLUSIONS: Checkpoint immunotherapy around the time of radioembolization is safe, with a low incidence of toxicity independent of primary malignancy.

Yttrium-90 Radioembolization in the Office-Based Lab.

PURPOSE: To evaluate the feasibility and benefits of performing yttrium-90 radioembolization in an office-based lab (OBL) compared to a hospital setting. MATERIALS AND METHODS: A radioembolization program was established in March 2019 in an OBL that is managed by the radiology department of a tertiary care center. Mapping and treatment angiograms performed in the OBL from March 2019 through January 2020 were compared to mapping and treatment angiograms performed in the hospital during the same time period. RESULTS: One hundred seventy-six mapping and treatment angiograms were evaluated. There was no difference in the proportion of mapping versus treatment angiograms performed at each site, the proportion of lobar versus selective dose vial administrations, or the mean number of dose vials administered per treatment procedure. Procedure start delays were longer in the hospital than in the OBL (28.6 minutes vs 0.8 minutes; P < .0001), particularly for procedures that were not scheduled as the first case of the day (hospital later case delay, 38.8 minutes vs OBL later case delay, 0.5 minutes; P < .0001). Procedures performed in the hospital took longer on average than procedures performed in the OBL (2 hours, 1.8 minutes vs 1 hour, 44.4 minutes; P = .0004), particularly for procedures that were not scheduled as the first case of the day (hospital later case duration, 2 hours, 7.4 minutes vs OBL later case duration, 1 hour, 43 minutes; P = .0006). CONCLUSIONS: Establishing a radioembolization program within an OBL is feasible and might provide more efficient procedure scheduling than the hospital setting.

Comparative Analysis of Safety and Efficacy of Transarterial Chemoembolization for the Treatment of Hepatocellular Carcinoma in Patients with and without Pre-Existing Transjugular Intrahepatic Portosystemic Shunts.

PURPOSE: To compare the safety and efficacy of transarterial chemoembolization for hepatocellular carcinoma (HCC) in patients with and without transjugular intrahepatic portosystemic shunts (TIPS). MATERIALS AND METHODS: This single-institution study included a retrospective review of 50 patients who underwent transarterial chemoembolization for HCC between January 2010 and April 2017. Twenty-five patients had preexisting TIPS, and 25 patients were selected to control for age, sex, and target tumor size. Baseline median Model for End-Stage Liver Disease (MELD; 13 TIPS, 9 control; P < .001) and albumin-bilirubin (ALBI; 3 TIPS, 2 control; P < .001) differed between groups. Safety was assessed on the basis of Common Terminology Criteria for Adverse Events (CTCAE) and change in MELD and ALBI grade assessed between 3 and 6 months. Efficacy was assessed by tumor response and time to progression (TTP). RESULTS: There was 1 severe adverse event (CTCAE grade >2) in the TIPS group. There was no difference in the change in MELD or ALBI grade. Although there was no difference in tumor response (P = .19), more patients achieved a complete response in the control group (19/25, 76%) than in the TIPS group (13/25, 52%). There was no difference in TTP (P = .82). At 1 year, 2 patients in the control group and 3 patients in the TIPS group received a liver transplant. Seven patients died in the TIPS group. CONCLUSIONS: Transarterial chemoembolization is as safe and effective in patients with TIPS as in patients without TIPS, despite worse baseline liver function. Severe adverse events are rare and may be transient.

Safety of Combined Yttrium-90 Radioembolization and Immune Checkpoint Inhibitor Immunotherapy for Hepatocellular Carcinoma.

PURPOSE: To investigate the safety of yttrium-90 radioembolization in combination with checkpoint inhibitor immunotherapy for the treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This single-center retrospective study included 26 consecutive patients with HCC who received checkpoint inhibitor immunotherapy within 90 days of radioembolization from April 2015 to May 2018. Patients had preserved liver function (Child-Pugh scores A-B7) and either advanced HCC due to macrovascular invasion or limited extrahepatic disease (21 patients) or aggressive intermediate stage HCC that resulted in earlier incorporation of systemic immunotherapy (5 patients). Clinical documentation, laboratory results, and imaging results at 1- and 3-month follow-up intervals were reviewed to assess treatment-related adverse events and treatment responses. RESULTS: The median follow-up period after radioembolization was 7.8 months (95% confidence interval [CI], 5.6-11.8). There were no early (30-day) mortality or grades 3/4 hepatobiliary or immunotherapy-related toxicities. Delayed grades 3/4 hepatobiliary toxicities (1-3 months) occurred in 2 patients in the setting of HCC disease progression. One patient developed pneumonitis. The median overall survival from first immunotherapy was 17.2 months (95% CI, 10.9-23.4). The median overall survival from first radioembolization was 16.5 months (95% CI, 6.6-26.4). From first radioembolization, time to tumor progression was 5.7 months (95% CI, 4.2-7.2), and progression-free survival was 5.7 months (95% CI, 4.3-7.1). CONCLUSIONS: Radioembolization combined with checkpoint inhibitor immunotherapy in cases of HCC appears to be safe and causes limited treatment-related toxicity. Future prospective studies are needed to identify the optimal combination treatment protocols and evaluate the efficacy of combination therapy.

Radioembolization for hepatocellular carcinoma: Statistical confirmation of improved survival in responders by landmark analyses.

Does imaging response predict survival in hepatocellular carcinoma (HCC)? We studied the ability of posttherapeutic imaging response to predict overall survival. Over 14 years, 948 patients with HCC were treated with radioembolization. Patients with baseline metastases, vascular invasion, multifocal disease, Child-Pugh > B7, and transplanted/resected were excluded. This created our homogeneous study cohort of 134 patients with Child-Pugh ≤ B7 and solitary HCC. Response (using European Association for Study of the Liver [EASL] and Response Evaluation Criteria in Solid Tumors 1.1 [RECIST 1.1] criteria) was associated with survival using Landmark and risk-of-death methodologies after reviewing 960 scans. In a subanalysis, survival times of responders were compared to those of patients with stable disease (SD) and progressive disease (PD). Uni/multivariate survival analyses were performed at each Landmark. At the 3-month Landmark, responders survived longer than nonresponders by EASL (hazard ratio [HR], 0.46; confidence interval [CI], 0.26-0.82; P = 0.002) but not RECIST 1.1 criteria (HR, 0.70; CI, 0.37-1.32; P = 0.32). At the 6-month Landmark, responders survived longer than nonresponders by EASL (HR, 0.32; CI, 0.15-0.77; P < 0.001) and RECIST 1.1 criteria (HR, 0.50; CI, 0.29-0.87; P = 0.021). At the 12-month Landmark, responders survived longer than nonresponders by EASL (HR, 0.34; CI, 0.15-0.77; P < 0.001) and RECIST 1.1 criteria (HR, 0.52; CI 0.27-0.98; P = 0.049). At 6 months, risk of death was lower for responders by EASL (P < 0.001) and RECIST 1.1 (P = 0.0445). In subanalyses, responders lived longer than patients with SD or PD. EASL response was a significant predictor of survival at 3-, 6-, and 12-month Landmarks on uni/multivariate analyses. CONCLUSION: Response to radioembolization in patients with solitary HCC can prognosticate improved survival. EASL necrosis criteria outperformed RECIST 1.1 size criteria in predicting survival. The therapeutic objective of radioembolization should be radiologic response and not solely to prevent progression. (Hepatology 2018;67:873-883).

Institutional decision to adopt Y90 as primary treatment for hepatocellular carcinoma informed by a 1,000-patient 15-year experience.

Yttrium-90 transarterial radioembolization (TARE) is a locoregional therapy (LRT) for hepatocellular carcinoma (HCC). In this study, we present overall survival (OS) outcomes in a 1,000-patient cohort acquired over a 15-year period. Between December 1, 2003 and March 31, 2017, 1,000 patients with HCC were treated with TARE as part of a prospective cohort study. A comprehensive review of toxicity and survival outcomes was performed. Outcomes were stratified by baseline Child-Pugh (CP) class, United Network for Organ Sharing (UNOS), and Barcelona Clinic Liver Cancer (BCLC) staging systems. Albumin and bilirubin laboratory toxicities were compared to baseline. OS outcomes were reported using censoring and intention-to-treat methodologies. All treatments were outpatient, with a median one treatment per patient. Five hundred six (51%) were CP A, 450 (45%) CP B, and 44 (4%) CP C. Two hundred sixty-three (26%) patients were BCLC A, 152 (15%) B, 541 (54%) C, and 44 (4%) D. Three hundred sixty-eight (37%) were UNOS T1/T2, 169 (17%) T3, 147 (15%) T4a, 223 (22%) T4b, and 93 (9%) N/M. In CP A patients, censored OS for BCLC A was 47.3 (confidence interval [CI], 39.5-80.3) months, BCLC B 25.0 (CI, 17.3-30.5) months, and BCLC C 15.0 (CI, 13.8-17.7) months. In CP B patients, censored OS for BCLC A was 27 (CI, 21-30.2) months, BCLC B 15.0 (CI, 12.3-19.0) months, and BCLC C 8.0 (CI, 6.8-9.5) months. Forty-nine (5%) and 110 (11%) patients developed grade 3/4 albumin and bilirubin toxicities, respectively. CONCLUSION: Based on our experience with 1,000 patients over 15 years, we have made a decision to adopt TARE as the first-line transarterial LRT for patients with HCC. Our decision was informed by prospective data and incrementally reported demonstrating outcomes stratified by BCLC, applied as either neoadjuvant or definitive treatment. (Hepatology 2017).

Radiation Segmentectomy: Potential Curative Therapy for Early Hepatocellular Carcinoma.

Purpose To report long-term outcomes of radiation segmentectomy (RS) for early hepatocellular carcinoma (HCC). The authors hypothesized that outcomes are comparable to curative treatments for patients with solitary HCC less than or equal to 5 cm and preserved liver function. Materials and Methods This retrospective study included 70 patients (median age, 71 years; range, 22-96 years) with solitary HCC less than or equal to 5 cm not amenable to percutaneous ablation who underwent RS (dose of >190 Gy) between 2003 and 2016. Patients who underwent subsequent curative liver transplantation were excluded to eliminate this confounding variable affecting survival. Radiologic response of time to progression and median overall survival were estimated by using the Kaplan-Meier method per the guidelines of the European Association for the Study of the Liver (EASL) and the World Health Organization (WHO). Results Seventy patients were treated with RS over 14 years. Sixty-three patients (90%) showed response by using EASL criteria, of which 41 (59%) showed complete response. Fifty patients (71%) achieved response by using WHO criteria, of which 11 (16%) achieved complete response. Response rates at 6 months were 86% and 49% by using EASL and WHO criteria, respectively. Median time to progression was 2.4 years (95% confidence interval: 2.1, 5.7), with 72% of patients having no target lesion progression at 5 years. Median overall survival was 6.7 years (95% confidence interval: 3.1, 6.7); survival probability at 1, 3, and 5 years was 98%, 66%, and 57%, respectively. Overall survival probability at 1, 3, and 5 years was 100%, 82%, and 75%, respectively, in patients with baseline tumor size less than or equal to 3 cm (n = 45) and was significantly longer than in patients with tumors greater than 3 cm (P = .026). Conclusion RS provides response rates, tumor control, and survival outcomes comparable to curative-intent treatments for selected patients with early-stage HCC who have preserved liver function. © RSNA, 2018 Online supplemental material is available for this article.

Perceptions of Quality in Interventional Oncology.

PURPOSE: To inductively characterize perceptions of quality in interventional oncology (IO) based on values and experiences of patients and referring providers. MATERIALS AND METHODS: Brief ethnographic interviews were completed with referring providers and patients before and after a variety of liver-directed procedures about their experiences, concerns, and perceptions of IO services at a single institution. Constructivist grounded theory was used to systematically analyze interview transcripts for themes until thematic saturation was achieved. All transcripts were analyzed by a reviewer with 3-years of experience performing such analyses, and 50% were randomly selected to be coded by 2 additional blinded reviewers. Interreviewer agreement was assessed via Cohen κ. RESULTS: Interviews with 22 patients (mean age, 65 y ± 13; 9 women) and 12 providers (mean age, 54 y ± 9; 6 women) were required to reach and confirm thematic saturation. Interreviewer agreement for interview themes was excellent (κ = 0.78; P < .001). Perceptions of high-quality IO care relied on interventional radiologists being responsive, friendly, and open; engaging in multidisciplinary collaboration; having thoughtful, dedicated support staff; and facilitating well-coordinated care after procedures and follow-up more than technical expertise and periprocedural comfort. Patient and provider perceptions of quality differed, but disjointed care after procedures was the most common critique among both groups. CONCLUSIONS: An inductive qualitative approach effectively characterized specific aspects of perceptions of high-quality IO care among patients and referring providers.

Y90 Radioembolization Significantly Prolongs Time to Progression Compared With Chemoembolization in Patients With Hepatocellular Carcinoma.

BACKGROUND & AIMS: Conventional transarterial chemoembolization (cTACE) is used to treat patients with hepatocellular carcinoma (HCC). Radioembolization is a minimally invasive procedure that involves implantation of radioactive micron-sized particles loaded with yttrium-90 (Y90) inside the blood vessels that supply a tumor. We performed a randomized, phase 2 study to compare the effects of cTACE and Y90 radioembolization in patients with HCC. METHODS: From October 2009 through October 2015, we reviewed patients with HCC of all Barcelona Clinic Liver Cancer (BCLC) stages for eligibility. Of these, 179 patients with BCLC stages A or B met our enrollment criteria and were candidates for cTACE or Y90 therapy. Patients were assigned randomly to groups that received Y90 therapy (n = 24; 50% Child-Pugh A) or cTACE (n = 21; 71% Child-Pugh A). The primary outcome was time to progression (TTP), evaluated by intention-to-treat analysis. Secondary outcomes included safety, rate of response (based on tumor size and necrosis criteria), and Kaplan-Meier survival time. We performed inverse probability of censoring weighting and competing risk analyses. RESULTS: Patients in the Y90 radioembolization group had significant longer median TTP (>26 mo) than patients in the cTACE group (6.8 mo; P = .0012) (hazard ratio, 0.122; 95% confidence interval [CI], 0.027-0.557; P = .007). This was confirmed by competing risk and inverse probability of censoring weighting analyses accounting for transplantation or death. A significantly greater proportion of patients in the cTACE group developed diarrhea (21%) than in the Y90 group (0%; P = .031) or hypoalbuminemia (58% in the cTACE group vs 4% in the Y90 group; P < .001). Similar proportions of patients in each group had a response to therapy, marked by necrosis (74% in the cTACE group vs 87% in the Y90 group) (P = .433). The median survival time, censored to liver transplantation, was 17.7 months for the cTACE group (95% CI, 8.3-not calculable) vs 18.6 months for the Y90 group (95% CI, 7.4-32.5) (P = .99). CONCLUSIONS: In a randomized phase 2 study of patients with HCC of BCLC stages A or B, we found Y90 radioembolization to provide significantly longer TTP than cTACE. Y90 radioembolization provides better tumor control and could reduce drop-out from transplant waitlists. ClinicalTrials.gov no. NCT00956930.

Interventional radiology in the management of the liver transplant patient.

Liver transplantation (LT) is commonly used to treat patients with end-stage liver disease. The evolution of surgical techniques, endovascular methods, and medical care has led to a progressive decrease in posttransplant morbidity and mortality. Despite these improvements, a multidisciplinary approach to each patient remains essential as the early diagnosis and treatment of the complications of transplantation influence graft and patient survival. The critical role of interventional radiology in the collaborative approach to the care of the LT patient will be reviewed. Liver Transplantation 23 1328-1341 2017 AASLD.

Immuno-oncology and Its Opportunities for Interventional Radiologists: Immune Checkpoint Inhibition and Potential Synergies with Interventional Oncology Procedures.

Immunotherapy, specifically the use of immune checkpoint inhibitors, offers a new approach to fighting cancer. Although the results of treatment with immune checkpoint inhibition alone have been remarkable for certain cancers, these results are not universal. Preclinical and early clinical studies indicate the potential for synergistic effects when immune checkpoint inhibition is combined with immunogenic local therapies such as ablation and embolization. This review offers an overview of immunology as it relates to immune checkpoint inhibition and the possibilities for synergy when combined with interventional radiology treatments.

Pretransplantation Portal Vein Recanalization and Transjugular Intrahepatic Portosystemic Shunt Creation for Chronic Portal Vein Thrombosis: Final Analysis of a 61-Patient Cohort.

PURPOSE: To report the final analysis of the safety and efficacy of portal vein (PV) recanalization (PVR) and transjugular intrahepatic portosystemic shunt (TIPS) creation (PVR-TIPS) in patients with PV thrombosis (PVT) in need of liver transplantation. MATERIALS AND METHODS: Sixty-one patients with cirrhosis and PVT underwent PVR-TIPS to improve transplantation candidacy. Median patient age was 58 years (range, 22-75 y), and median pre-TIPS Model for End-Stage Liver Disease score was 14 (range, 7-42). The most common etiologies of cirrhosis were nonalcoholic fatty liver disease in 18 patients (30%) and hepatitis C in 13 patients (21%). Twenty-seven patients (44%) had partial PVT, and 34 patients (56%) had complete thrombosis. Forty-nine patients (80%) had Yerdel grade 2 PVT, and 12 (20%) had Yerdel grade 3 PVT. Twenty-nine patients (48%) had cavernous transformation of the PV. RESULTS: PVR-TIPS was technically successful in 60 of 61 patients (98%). PV/TIPS patency was maintained in 55 patients (92%) at a median follow-up of 19.2 months (range, 0-105.9 mo). Recurrent PV/TIPS thrombosis occurred in 5 patients (8%), all of whom initially presented with complete PVT. The most common adverse events were TIPS stenosis in 13 patients (22%) and transient encephalopathy in 11 patients (18%). Twenty-four patients (39%) underwent transplantation, 23 of whom (96%) received an end-to-end anastomosis. There were no cases of recurrent PVT following transplantation, with a median imaging follow-up of 32.5 months (range, 0.4-75.4 mo). Five-year overall survival rate was 82%. CONCLUSIONS: PVR-TIPS is a safe, effective, and durable treatment option for patients with chronic PVT who need liver transplantation.

Same-day 90Y radioembolization: implementing a new treatment paradigm.

PURPOSE: To assess the feasibility of conducting pretreatment mesenteric angiography, coil embolization, 99mTc macroaggregated albumin (99mTc-MAA) scintigraphy, and 90Y radioembolization treatment in a single, same-day, combined outpatient encounter. METHODS: This was a retrospective study of 78 patients treated during the period 2008 - 2015 who were managed in a single outpatient encounter under the guidance of the Interventional Radiology Department and The Nuclear Medicine Department. Pretreatment planning was performed by reviewing baseline imaging and estimated perfused liver volume bearing the tumor. The region of interest was estimated using 3-D software; this value was used for dosimetry planning. Maximum lung shunting fractions of 10 % for hepatocellular carcinoma and 5 % for liver metastases were assumed. Subsequently, hepatic angiography and 99mTc-MAA scintigraphy were performed followed by 90Y treatment in one outpatient encounter. Total in-room procedure time was recorded. RESULTS: All patients underwent same-day angiography, 99mTc-MAA scintigraphy and 90Y radioembolization. Of the 78 patients, 16 received multiple segmental treatments to both lobes, 44 received treatment to the right lobe, and 18 received treatment to the left lobe. The median dose was 106 Gy. The median number of 90Y vials needed was two (range one to six). The median in-room time was 160 min (75 - 250 min). The residential status of the patients was as follows, 18 % (14/78) were local residents, 55 % (43/78) traveled from outside the city limits, 18 % (14/78) were from out-of-state, and 9 % (7/78) were resident abroad. Of the 78 patients, 61 (77 %) had hepatocellular carcinoma, and 17 (22 %) had liver metastases. The median lung dose was 3.5 Gy. CONCLUSION: This study demonstrated the feasibility of same-day 90Y evaluation and treatment while maintaining the principles of safe and effective 90Y infusion including tumoricidal dosimetry (lobar, segmentectomy), minimization of nontarget flow, and minimization of lung dose. This paradigm translates into expeditious cancer care and significant cost savings.

Types of Research Bias Encountered in IR.

Bias is a systemic error in studies that leads to inaccurate deductions. Relevant biases in the field of IR and interventional oncology were identified after reviewing articles published in the Journal of Vascular and Interventional Radiology and CardioVascular and Interventional Radiology. Biases cited in these articles were divided into three categories: preinterventional (health care access, participation, referral, and sample biases), periinterventional (contamination, investigator, and operator biases), and postinterventional (guarantee-time, lead time, loss to follow-up, recall, and reporting biases).

Angiogenic Response following Radioembolization: Results from a Randomized Pilot Study of Yttrium-90 with or without Sorafenib.

PURPOSE: To compare the regulation of serum angiogenic factors in patients with unresectable early hepatocellular carcinoma (HCC) treated with yttrium-90 ((90)Y) radioembolization alone vs with sorafenib. MATERIALS AND METHODS: In a single-center pilot study, 23 patients with unresectable HCC awaiting orthotopic liver transplantation were prospectively randomized to receive radioembolization alone (n = 12) or radioembolization with sorafenib (n = 11). Serum angiogenic markers (angiopoietin-2 [Ang-2], hepatocyte growth factor, interleukin [IL]-6, IL-8, c-reactive protein, platelet-derived growth factor [PDGF], and vascular endothelial growth factor [VEGF]) were assayed at baseline and at 2 and 4 weeks after radioembolization ((90)Y alone, n = 6; (90)Y plus sorafenib, n = 7). RESULTS: In the (90)Y-alone group, all growth factors were elevated above baseline levels at 2 and 4 weeks: VEGF increased 36% vs baseline at 2 weeks and 22% at 4 weeks, and PDGF increased 24% at 2 weeks and 3% at 4 weeks. In the (90)Y/sorafenib arm, Ang-2 and PDGF decreased at 2 weeks and the remainder increased. By 4 weeks, only PDGF remained below baseline levels. VEGF increased 49% at 2 weeks and 28% at 4 weeks, and PDGF decreased 31% at 2 weeks and 39% at 4 weeks. Differences were statistically significant for hepatocyte growth factor (P = .03) and PDGF (P = .02) at 2 weeks and for IL-6 (P = .05) at 4 weeks. CONCLUSIONS: Radioembolization is associated with a mild increase in angiogenic markers. The addition of sorafenib blunts PDGF response; other factors such as VEGF remain unaffected. The predominant effect of sorafenib may be through downregulation of PDGF and not VEGF.

Single- versus Triple-Drug Chemoembolization for Hepatocellular Carcinoma: Comparing Outcomes by Toxicity, Imaging Response, and Survival.

PURPOSE: To determine the efficacy of single- versus triple-drug chemoembolization for the treatment of hepatocellular carcinoma, as measured by toxicity, tumor response, time to progression (TTP), and overall survival (OS). MATERIALS AND METHODS: A single-center retrospective review was performed on 337 patients who underwent chemoembolization over a 14-year period; 172 patients underwent triple-drug conventional transarterial chemoembolization, and 165 patients underwent single-agent doxorubicin chemoembolization. Imaging characteristics and clinical follow-up after conventional transarterial chemoembolization were evaluated to determine TTP. Imaging response was determined per World Health Organization and European Association for the Study of Liver criteria. OS from time of first chemoembolization was calculated. RESULTS: Median TTP was similar between groups: 7.9 months (95% confidence interval [CI], 7.1-9.4) and 6.8 months (95% CI, 4.6-8.6) for triple- and single-drug regimens, respectively (P > .05). For single-agent conventional transarterial chemoembolization, median OS varied significantly by Barcelona Clinic for Liver Cancer (BCLC) stage: A, 40.8 months; B, 36.4 months; C, 10.9 months (P < .01). Median OS for triple-drug therapy also varied significantly by BCLC: A, 28.9 months; B, 18.1 months; C, 9.0 months (P < .01). Single-drug conventional transarterial chemoembolization demonstrated longer median OS compared with triple-drug therapy (P < .05) for BCLC A/B patients. CONCLUSIONS: Single-agent chemoembolization with doxorubicin and ethiodized oil demonstrates acceptable efficacy as measured by TTP and OS. Results compare favorably with traditional triple-drug therapy.