Thermal ablation compared to stereotactic body radiation therapy for hepatocellular carcinoma: A multicenter retrospective comparative study.

BACKGROUND AIMS: Early-stage HCC can be treated with thermal ablation or stereotactic body radiation therapy (SBRT). We retrospectively compared local progression, mortality, and toxicity among patients with HCC treated with ablation or SBRT in a multicenter, US cohort. APPROACH RESULTS: We included adult patients with treatment-naïve HCC lesions without vascular invasion treated with thermal ablation or SBRT per individual physician or institutional preference from January 2012 to December 2018. Outcomes included local progression after a 3-month landmark period assessed at the lesion level and overall survival at the patient level. Inverse probability of treatment weighting was used to account for imbalances in treatment groups. The Cox proportional hazard modeling was used to compare progression and overall survival, and logistic regression was used for toxicity. There were 642 patients with 786 lesions (median size: 2.1 cm) treated with ablation or SBRT. In adjusted analyses, SBRT was associated with a reduced risk of local progression compared to ablation (aHR 0.30, 95% CI: 0.15-0.60). However, SBRT-treated patients had an increased risk of liver dysfunction at 3 months (absolute difference 5.5%, aOR 2.31, 95% CI: 1.13-4.73) and death (aHR 2.04, 95% CI: 1.44-2.88, p < 0.0001). CONCLUSIONS: In this multicenter study of patients with HCC, SBRT was associated with a lower risk of local progression compared to thermal ablation but higher all-cause mortality. Survival differences may be attributable to residual confounding, patient selection, or downstream treatments. These retrospective real-world data help guide treatment decisions while demonstrating the need for a prospective clinical trial.

Boosted-Dose Yttrium-90 Radiation Segmentectomy or Lobectomy for Hepatocellular Carcinoma Refractory to Prior Transarterial Embolization or Chemoembolization: A Single Institution Retrospective Case Series.

PURPOSE: To assess the tumor response rates and liver toxicity of boosted-dose transarterial radioembolization (TARE) for treatment of hepatocellular carcinoma (HCC) refractory to previous transarterial embolization (TAE) and/or chemoembolization (TACE). MATERIALS AND METHODS: All patients were identified who had HCC treated between 2017 and 2020 that had been refractory to prior TAE or TACE, then treated with boosted-dose segmental or lobar TARE. Tumor response was assessed by multiphasic CT or MRI using localized mRECIST imaging criteria and serological alpha-fetoprotein levels at three and six months after TARE, if available. Liver toxicity was evaluated using serial serological liver function tests, platelet counts, and clinical Child-Pugh and MELD scores. RESULTS: Twenty-four patients met inclusion criteria. Mean age was 68.7 years (54-89); 8 were females. Three (12.5%) patients had Barcelona Clinical Liver Cancer stage A, 4 (16.7%) stage B, and 17 (70.8%) stage C disease. Three months after TARE, 52% of patients had a complete response and 33% had a partial response. Mean AFP decreased from 33.2 ng/mL at baseline to 17 ng/mL at 3 months (p = 0.782). The median MELD-Na score increased from 11 at baseline to 16 at 6 months post-TARE (p = 0.044); the mean Child-Pugh score rose from 5 at baseline to 6 at 3 months post-TARE (p < 0.01). CONCLUSION: Boosted-dose TARE resulted in statistically significant favorable tumor responses by imaging criteria in 85% of patients previously refractory to TAE or TACE. TARE resulted in transient but acceptable deterioration of liver function and clinical scores.

Utility of Cone-Beam CT for Bronchial Artery Embolization and Chemoinfusion: A Single-Institution Retrospective Case Series.

PURPOSE: To describe the technique and document utility of adjunctive cone-beam CT (CBCT) in patients undergoing bronchial artery embolization (BAE) or chemoinfusion (BAC). MATERIALS AND METHODS: Between August 2010 and February 2021, 26 patients (62 bronchial arteries) were evaluated with CBCT in addition to the usual digital subtraction angiography (DSA) during BAE or BAC. 19 patients (43 arteries) underwent BAE for hemoptysis; 7 patients (19 arteries) had BAC for palliation of lung malignancy. Retrospective review of procedural reports and the archived DSA and CBCT images was assessed for (1) whether CBCT findings added unique diagnostic information prior to treatment of target arteries compared to DSA alone; and (2) whether these unique CBCT findings led to modification of embolization or chemoinfusion technique. RESULTS: In 61 of 62 (98%) interrogated bronchial arteries, CBCT provided additional unique diagnostic information over planar DSA, primarily cross-sectional assessment of the spinal canal for spinal arteries. In 46/62 (74%) of the bronchial arteries the unique information did not lead to a change in therapeutic technique. In 15 bronchial arteries (24%), the added information from CBCT led to change in embolization and/or chemoinfusion technique. Embolization of one small unrecognized spinal artery branch (1.6%), which was missed intra-procedurally but retrospectively seen on CBCT led to transient spinal cord ischemia. CONCLUSIONS: These results suggest that adjunctive use of CBCT technique may improve diagnostic confidence from information provided by DSA in nearly all cases of BAE and BAC leading to improved therapeutic targeting or change in technique of embolization or chemoinfusion.

Inline Balloon Occlusion-Assisted Delivery of Ethylene Vinyl Alcohol Copolymer for Peripheral Arterial Applications: A Multicenter Case Series.

PURPOSE: To assess the feasibility, safety, and efficacy of balloon-assisted delivery of ethylene vinyl alcohol copolymer (EVOH) for a range of peripheral arterial applications. MATERIALS AND METHODS: Six academic medical centers entered retrospective data on 46 consecutive patients (27 men, 19 women; ages, 11-94 y; mean age, 50.3 y) who underwent 60 balloon-assisted EVOH procedures. The cohort was restricted to procedures involving peripheral, nonneural arteries 1-5.5 mm in diameter. Clinical indications included a wide range of vascular pathologic conditions (most commonly arteriovenous malformations [n = 20], renal angiomyolipomas [n = 8], and acute hemorrhage [n = 9]) and targeted visceral and musculoskeletal peripheral arteries. Data collected included sex, age, clinical indication, arterial pathology, arteries embolized, type of occlusion balloon microcatheter, type and concentration of EVOH agent, effectiveness as an embolic backstop, vessels protected, adequacy of EVOH cast penetration, catheter extraction, nontarget embolization, and complications. RESULTS: Balloon occlusion prevented EVOH reflux in 59 of 60 procedures (98.3%). Nontarget EVOH embolization occurred in 2 procedures (3.3%). Adequate EVOH cast penetration and complete filling of the target pathologic structure were seen in 57 of 60 procedures (95%). Balloon deflation and uneventful extraction occurred in all procedures; small EVOH fragments detached into target arteries in 2 cases. One major (1.7%) and 2 minor (3.3%) complications occurred. CONCLUSIONS: Balloon-assisted EVOH embolization of peripheral arteries is feasible, safe, effective, and versatile. The primary advantage of balloon-assisted EVOH embolization is the ability to apply more injection pressure to advance the EVOH cast assertively into the pathologic structure(s).

The Beauty and Bane of Pressure-Directed Embolotherapy: Hemodynamic Principles and Preliminary Clinical Evidence.

OBJECTIVE: Particulate emboli are passive agents that follow blood flow. Deployed antireflux devices obstruct blood flow. CONCLUSION: The aim of this review is to describe the complex hemodynamic alterations to blood flow caused by the deployment of antireflux devices and the resulting changes to embolic distribution. The therapeutic goal is optimization of embolization safety and efficacy.

90Y Radioembolization for Hepatic Malignancy in Patients with Previous Biliary Intervention: Multicenter Analysis of Hepatobiliary Infections.

Purpose To determine the frequency of hepatobiliary infections after transarterial radioembolization (TARE) with yttrium 90 (90Y) in patients with liver malignancy and a history of biliary intervention. Materials and Methods For this retrospective study, records of all consecutive patients with liver malignancy and history of biliary intervention treated with TARE at 14 centers between 2005 and 2015 were reviewed. Data regarding liver function, 90Y dosimetry, antibiotic prophylaxis, and bowel preparation prophylaxis were collected. Primary outcome was development of hepatobiliary infection. Results One hundred twenty-six patients (84 men, 42 women; mean age, 68.8 years) with primary (n = 39) or metastatic (n = 87) liver malignancy and history of biliary intervention underwent 180 procedures with glass (92 procedures) or resin (88 procedures) microspheres. Hepatobiliary infections (liver abscesses in nine patients, cholangitis in five patients) developed in 10 of the 126 patients (7.9%) after 11 of the 180 procedures (6.1%; nine of those procedures were performed with glass microspheres). All patients required hospitalization (median stay, 12 days; range, 2-113 days). Ten patients required percutaneous abscess drainage, three patients underwent endoscopic stent placement and stone removal, and one patient needed insertion of percutaneous biliary drains. Infections resolved in five patients, four patients died (two from infection and two from cancer progression while infection was being treated), and one patient continued to receive suppressive antibiotics. Use of glass microspheres (P = .02), previous liver resection or ablation (P = .02), and younger age (P = .003) were independently predictive of higher infection risk. Conclusion Infectious complications such as liver abscess and cholangitis are uncommon but serious complications of transarterial radioembolization with 90Y in patients with liver malignancy and a history of biliary intervention.

Erratum to updated survival outcomes and analysis of long-term survivors from the MORE study on safety and efficacy of radioembolization in patients with unresectable colorectal cancer liver metastases.

[This corrects the article DOI: 10.21037/jgo.2017.03.10.].

Liver-directed therapy for hepatocellular carcinoma.

Liver-directed therapy is a critical component of treatment strategies for hepatocellular carcinoma. These therapies included percutaneous image-guided ablation, transarterial chemoembolization, and transarterial radioembolization, and are administered by interventional radiologists. Depending on the stage of disease, a particular treatment modality, or a combination thereof, is expected to be most efficacious in achieving the goals of treatment for a particular patient. This article seeks to review the various liver-directed treatment modalities for treatment of hepatocellular carcinoma, with attention to their efficacy and patient selection criteria.

Updated survival outcomes and analysis of long-term survivors from the MORE study on safety and efficacy of radioembolization in patients with unresectable colorectal cancer liver metastases.

BACKGROUND: The Metastatic colorectal cancer liver metastases Outcomes after RadioEmbolization (MORE) study was a retrospective analysis of 606 patients with unresectable colorectal liver metastases treated with radioembolization (RE) using 90Y-labeled resin microspheres. The first analysis of this study was completed with a last patient follow-up of 77.7 months. We now provide an updated survival analysis through September 15, 2016, with a last patient follow-up of 125 months. METHODS: 90Y-RE was considered for patients with advanced liver-only or liver-dominant metastatic colorectal cancer which was deemed not suitable for surgery, ablation, or systemic therapy, and which had progressed or become refractory to at least one line of systemic therapy. All patients with a diagnosis of metastatic colorectal cancer who had received at least 1 RE treatment and 1 follow-up visit were included in the analysis. Patients were treated between July 2002 and December 2011 at one of 11 U.S. tertiary care centers. Data were collected at baseline, on the day of the first 90Y-RE treatment (day 0), and at all subsequent visits or until death. Patient medical charts and/or public records were accessed to obtain dates of death. RESULTS: Dates of death were obtained for 574 out of a total of 606 patients, and overall survival (OS) data analyzed. Updated median OS was 10.0 months (95% CI: 9.2-11.8 months) at a median follow-up of 9.5 months versus the originally reported median OS of 9.6 months (95% CI: 9.0-11.1 months) at a follow-up of 8.6 months in the first MORE analysis. Patients received a median (range) of 2 (0 to 6) lines of chemotherapy. Baseline characteristics and factors significantly associated with patient survival (P<0.01) are consistent with those reported in the first safety analysis of the MORE study. These factors include poor ECOG performance status, markers of advanced disease such as increased extent of tumor-to-target liver involvement, poor baseline liver function, pre-treatment anemia, lung shunt fraction, and number of lines of prior chemotherapy. Patient age did not significantly affect survival outcomes. CONCLUSIONS: Long-term follow-up confirms that 90Y-RE treatment offers favorable survival benefits for patients with unresectable metastatic colorectal cancer, even among patients who received 3 or more prior lines of chemotherapy. Our analysis also supports earlier reported prognostic factors for survival after 90Y-RE. Overall, our updated analysis confirms that 90Y-RE treatment provided a meaningful response and survival advantage for MORE patients across all ages and across diverse community and academic centers in the U.S.

Pressure-Directed Embolization of Hepatic Arteries in a Porcine Model Using a Temporary Occlusion Balloon Microcatheter: Proof of Concept.

PURPOSE: The purpose of this project was to test the hypothesis that temporary hepatic artery balloon occlusion would favorably alter the distribution of particle emboli within the targeted and nontargeted downstream vascular compartments. MATERIALS AND METHODS: Five Yorkshire pigs underwent transfemoral placement of balloon microcatheters into selected segmental hepatic arteries. A collection catheter was surgically introduced into a downstream hepatic artery branch. Blood pressures at the femoral artery sheath and the collection catheter were obtained with the microcatheter balloon deflated and inflated. Identical quantities of calibrated 250- and 400-µm microspheres were injected via the balloon microcatheter when inflated, then deflated. Each animal underwent up to four paired microsphere embolizations. Microspheres collected from the intrahepatic collection catheter were counted manually by light microscopy. RESULTS: Inflation of the balloon microcatheter in the segmental hepatic artery resulted in a consistent and significant decrease in blood pressure (mean: 30 mmHg; range 23-43 mmHg; p < 0.05) in the downstream vascular compartment. The number of microspheres selectively delivered to the targeted intrahepatic collection catheter was significantly greater when the balloon microcatheter was inflated rather than deflated in all 20 paired embolic deliveries (by 2.4-fold, mean; p = 0.0002), despite delivery of the same total number of microspheres. CONCLUSION: Balloon occlusion significantly reduces blood pressure in the downstream vascular compartment, resulting in increased delivery of emboli to a targeted intrahepatic arterial collection catheter relative to other portions of the embolized vascular compartment, likely due to blood flowing into this compartment from neighboring hepatic and extrahepatic arteries.

Recommendations for radioembolisation after liver surgery using yttrium-90 resin microspheres based on a survey of an international expert panel.

INTRODUCTION: Guidelines on how to adjust activity in patients with a history of liver surgery who are undergoing yttrium-90 radioembolisation (90Y-RE) are lacking. The aim was to study the variability in activity prescription in these patients, between centres with extensive experience using resin microspheres 90Y-RE, and to draw recommendations on activity prescription based on an expert consensus. METHODS: The variability in activity prescription between centres was investigated by a survey of international experts in the field of 90Y-RE. Six representative post-surgical patients (i.e. comparable activity prescription, different outcome) were selected. Information on patients' disease characteristics and data needed for activity calculation was presented to the expert panel. Reported was the used method for activity prescription and whether, how and why activity reduction was found indicated. RESULTS: Ten experts took part in the survey. Recommendations on activity reduction were highly variable between the expert panel. The median intra-patient range was 44 Gy (range 18-55 Gy). Reductions in prescribed activity were recommended in 68% of the cases. In consensus, a maximum DTarget of 50 Gy was recommended. CONCLUSION: With a current lack of guidelines, large variability in activity prescription in post-surgical patients undergoing 90Y-RE exists. In consensus, DTarget ≤50 Gy is recommended. KEY POINTS: • BSA method does not account for a decreased remnant liver volume after surgery. • In post-surgical patients, a volume-based activity determination method is recommended. • In post-surgical patients, a mean D Target of ≤ 50Gy should be aimed for.

Baseline hemoglobin and liver function predict tolerability and overall survival of patients receiving radioembolization for chemotherapy-refractory metastatic colorectal cancer.

BACKGROUND: Patients with liver metastatic colorectal cancer (mCRC) often benefit from receiving 90Y-microsphere radioembolization (RE) administered via the hepatic arteries. Prior to delivery of liver-directed radiation, standard laboratory tests may assist in improving outcome by identifying correctable pre-radiation abnormalities. METHODS: A database containing retrospective review of consecutively treated patients of mCRC from July 2002 to December 2011 at 11 US institutions was used. Data collected included background characteristics, prior chemotherapy, surgery/ablation, radiotherapy, vascular procedures, 90Y treatment, subsequent adverse events and survival. Kaplan-Meier estimates compared the survival of patients across lines of chemotherapy. The following values were obtained within 10 days prior to each RE treatment: haemoglobin (HGB), albumin, alkaline phosphatase (Alk phosph), aspartate aminotransferase (AST), alanine transaminase (ALT), total bilirubin and creatinine. Common Terminology Criteria Adverse Events (CTCAEs) 3.0 grade was assigned to each parameter and analysed for impact on survival by line of chemotherapy. Consensus Guidelines were used to categorize the parameter grades as either within or outside guidelines for treatment. RESULTS: A total of 606 patients (370 male; 236 female) were studied with a median follow-up was 8.5 mo. (IQR 4.3-15.6) after RE. Fewer than 11% of patients were treated outside recommended RE guidelines, with albumin being the most common, 10.5% grade 2 (<3-2.0 g/dL) at time of RE. All seven parameters showed statistically significant decreased median survivals with any grade >0 (P<0.001) across all lines of prior chemotherapy. Compared to grade 0, grade 2 albumin decreased overall survival 67%; for grade 2 total bilirubin a 63% drop occurred, and grade 1 HGB resulted in 66% lower median survival. CONCLUSIONS: Review of pre-RE laboratory parameters may aid in improving median survivals if correctable grade >0 values are addressed prior to radiation delivery. HGB <10 g/dL is a well-known negative factor in radiation response and is easily corrected. Improving other parameters is more challenging. These efforts are important in optimizing treatment response to liver radiotherapy.

Hepatopulmonary Shunting: A Prognostic Indicator of Survival in Patients with Metastatic Colorectal Adenocarcinoma Treated with 90Y Radioembolization.

Purpose To determine if high lung shunt fraction (LSF) is an independent prognostic indicator of poor survival in patients who undergo yttrium 90 radioembolization for unresectable liver-dominant metastatic colorectal cancer. Materials and Methods Retrospective data were analyzed from 606 patients (62% men; mean age, 62 years) who underwent radioembolization to treat liver metastases from colorectal adenocarcinoma between July 2002 and December 2011 at 11 U.S. centers. Institutional review board exemptions were granted prior to the collection of data at each site. Overall survival was estimated by using Kaplan-Meier survival and univariate Cox proportional hazards models to examine the effect of LSF on survival and to compare this to other potential prognostic indicators. Multivariate analysis was also performed to determine whether LSF is an independent risk factor for poor survival. Results LSF higher than 10% was predictive of significantly decreased survival (median, 6.9 months vs 10.0 months; hazard ratio, 1.60; P < .001) and demonstrated a mild but significant correlation to serum carcinoembryonic antigen levels and tumor-to-liver volume ratio (Pearson correlation coefficients, 0.105 and 0.113, respectively; P < .05). A progressive decrease in survival was observed as LSF increased from less than 5% to more than 20% (P < .05). LSF did not correlate with the presence of extrahepatic metastases or prior administration of bevacizumab. Conclusion Increased LSF is an independent prognostic indicator of worse survival in patients undergoing radioembolization for liver-dominant metastatic colorectal adenocarcinoma. High LSF correlates poorly to other potential markers of tumor size, such as tumor-to-liver volume ratio or serum carcinoembryonic antigen level, and does not correlate to the presence of extrahepatic metastases. © RSNA, 2016 Online supplemental material is available for this article.

Prognostic value of post-Yttrium 90 radioembolization therapy 18F-fluorodeoxyglucose positron emission tomography in patients with liver tumors.

OBJECTIVE: This study assessed the benefit of post-therapy 18F-FDG PET/CT versus CT alone in identifying malignant liver tumor progression following radioembolization with Y-90 microspheres. METHODS: 24 patients with 44 liver tumors underwent CT imaging pre-radioembolization and PET/CT post-radioembolization. Predictive value of Response Evaluation Criteria in Solid Tumors (RECIST 1.1), The World Health Organization (WHO), mRECIST and European Association for the Study of the Liver (EASL) with PET/CT versus CT alone was assessed. RESULTS: Prediction of liver malignancy progression was improved (p<0.05) for tumors labeled as non-responding based on combined PET/CT with RECIST 1.1, WHO, mRECIST, and EASL criteria compared to assessment without PET. CONCLUSIONS: The addition of post-therapy PET to routine CT in patients with hepatic tumors undergoing radioembolization may improve identification of non-responding tumors.

Quantification of Blood Pressure Changes in the Vascular Compartment When Using an Anti-Reflux Catheter during Chemoembolization versus Radioembolization: A Retrospective Case Series.

PURPOSE: To assess whether blood pressure changes in the downstream vascular compartment are greater with transarterial chemoembolization than transarterial radioembolization (TARE) when using an anti-reflux catheter. MATERIALS AND METHODS: The Surefire Infusion System (Surefire Medical, Inc, Westminster, Colorado) was used for lobar and sublobar administration in 51 drug-eluting embolic transarterial chemoembolization and 55 TARE procedures (22 with resin microspheres [TARE/resin] and 33 with glass microspheres [TARE/glass]). Of patients receiving transarterial chemoembolization and TARE/glass, 97% had hepatocellular carcinomas; 87% of patients receiving TARE/resin had metastases. The absolute (mm Hg) and relative (%) changes in the systemic-hepatic arterial pressure difference (SHAPD) were calculated from simultaneous blood pressure measurements obtained from the femoral artery vascular sheath and the antireflux catheter before, after, and, when feasible, during transarterial chemoembolization or TARE. RESULTS: Transarterial chemoembolization was associated with a significant reduction in SHAPD compared with TARE (13 mm Hg ± 1.7 vs -4.3 mm Hg ± 1.5; P < .001). A reduction in SHAPD led to early termination of 55.6% of lobar and 53.3% of sublobar transarterial chemoembolization procedures compared with only 5.5% of lobar TARE/resin and no TARE/glass procedures. TARE/resin procedures were associated with a significantly greater change in SHAPD compared with TARE/glass procedures (0.9 mm Hg ± 2.7 vs -8.0 mm Hg ± 1.5; P = .0035). CONCLUSIONS: Hepatic arterial pressures in the treated vascular compartment increased more after transarterial chemoembolization than after TARE, suggesting that transarterial chemoembolization resulted in more embolic obstruction of the targeted vascular compartment than TARE.

Control of massive hemoptysis via a "back-door" approach through the pulmonary artery.

Bronchial artery embolization is an effective nonsurgical therapy for massive hemoptysis. Routine selection of the bronchial arteries from the aorta usually enables the interventionalist full interrogation and embolization of the culprit vascular abnormality. In problematic cases where bronchial artery access is difficult, a systemic-to-pulmonary arterial shunt can be exploited as a retrograde means of vascular intervention. A case is presented where inaccessibility of a tortuous left bronchial artery was circumvented by accessing the left pulmonary artery, leading to successful embolization and control of hemoptysis.

Intravascular Ultrasound in the Creation of Transhepatic Portosystemic Shunts Reduces Needle Passes, Radiation Dose, and Procedure Time: A Retrospective Study of a Single-Institution Experience.

PURPOSE: To assess whether intravascular ultrasound (US) guidance impacts number of needle passes, contrast usage, radiation dose, and procedure time during creation of transjugular intrahepatic portosystemic shunts (TIPS). MATERIALS AND METHODS: Intravascular US-guided creation of TIPS in 40 patients was retrospectively compared with conventional TIPS in 49 patients between February 2010 and November 2015 at a single tertiary care institution. Patient sex and age, etiology of liver disease (hepatitis C virus, alcohol abuse, nonalcoholic steatohepatitis), severity of liver disease (mean Model for End-Stage Liver Disease score), and indications for TIPS (variceal bleeding, refractory ascites, refractory hydrothorax) in conventional and intravascular US-guided cases were recorded. RESULTS: The two groups were well matched by sex, age, etiology of liver disease, Child-Pugh class, Model for End-Stage Liver Disease scores, and indication for TIPS (P range = .19-.94). Fewer intrahepatic needle passes were required in intravascular US-guided TIPS creation compared with conventional TIPS (2 passes vs 6 passes, P < .01). Less iodinated contrast material was used in intravascular US cases (57 mL vs 140 mL, P < .01). Radiation exposure, as measured by cumulative dose, dose area product, and fluoroscopy time, was reduced with intravascular US (174 mGy vs 981 mGy, P < .01; 3,793 µGy * m(2) vs 21,414 µGy * m(2), P < .01; 19 min vs 34 min, P < .01). Procedure time was shortened with intravascular US (86 min vs 125 min, P < .01). CONCLUSIONS: Intravascular US guidance resulted in fewer intrahepatic needle passes, decreased contrast medium usage, decreased radiation dosage, and shortened procedure time in TIPS creation.

Persistent Vascular Remodeling and Leakiness are Important Components of the Pathobiology of Re-bleeding in Hemophilic Joints: Two Informative Cases.

OBJECTIVE: It is unclear if vascular remodeling in hemophilic joints perpetuates bleeding because it is difficult to gauge leakiness in the setting of low clotting factor levels. Two patients provided the unique opportunity to demonstrate that vascular changes directly contribute to joint bleeding. APPROACH AND RESULTS: Two patients had severe hemophilic arthropathies; joint vascularity and bleeding were studied during periods of normalized plasma clotting factor activities with MSKUS and PD. One patient was "cured" of hemophilia with liver transplantation. Abnormal elbow vascularization persisted despite normalization of coagulation status and was associated with severe bleeding years after transplant. Dynamic vascular changes were detected prior to and during bleeding; angiography revealed enlarged, thickened vessels consistent with remodeling, and required arterial embolization. The second patient had continued knee bleeding and fluctuating vascular changes for months following knee replacement, unresponsive to intense daily factor treatment. Subsequently, new bleeds developed in other joints associated with similar vascular changes despite continued factor replacement. CONCLUSIONS: Vascular remodeling contributes to perpetuated hemophilic joint bleeding and therefore contributes to progressive arthropathy. Intra-articular or systemic administration of anti-angiogenic drugs, such as vascular endothelial growth factor antagonists, might be of benefit in such patients, but requires study.

Safety and Efficacy of Radioembolization in Elderly (≥ 70 Years) and Younger Patients With Unresectable Liver-Dominant Colorectal Cancer.

BACKGROUND: The effects of advancing age on clinical outcomes after radioembolization (RE) in patients with unresectable liver-dominant metastatic colorectal cancer (mCRC) are largely unknown. PATIENTS AND METHODS: This study was a retrospective analysis of 160 elderly (≥ 70 years) and 446 younger (< 70 years) consecutive patients from 11 US centers who received RE using ytrrium-90 ((90)Y) resin microspheres ((90)Y radioembolization [(90)Y-RE]) between July 2002 and December 2011. A further analysis was conducted in 98 very elderly patients (≥ 75 years). Statistical analyses of safety, tolerability, and overall survival were conducted. RESULTS: Mean ages (± standard deviation) in the younger (< 70 years), elderly (≥ 70 years), and very elderly (≥ 75 years) cohorts were 55.9 ± 9.4 years, 77.2 ± 4.8 years, and 80.2 ± 3.8 years, respectively. Overall survival was similar between elderly and younger patients: 9.3 months (95% confidence interval [CI], 8.0-12.1) and 9.7 months (95% CI, 9.0-11.4) (P = .335). There were no differences between cohorts for any grade adverse events (P = .433) or grade 3+ events (P = .482). Analysis of patients ≥ 75 years and < 75 years confirmed similar overall survival (median, 9.3 months vs. 9.6 months, respectively; P = .987) and grade 3+ events (P = .398) or any adverse event (P = .158) within 90 days of RE. CONCLUSION: For patients with unresectable liver-dominant mCRC who meet eligibility criteria for RE, (90)Y-RE microspheres appear to be effective and well-tolerated, regardless of age. Criteria for selecting patients for RE should not include age for exclusion from this potentially beneficial intervention.