Recognizing and Managing Adverse Events in Y-90 Radioembolization.

Transarterial radioembolization using yttrium-90 (Y-90) microspheres is an important therapy in the management of unresectable primary liver tumors or hepatic metastases. While radioembolization is generally well-tolerated, it is not free from adverse events, and familiarity with the prevention and treatment of radioembolization-specific complications is an important component of patient care. This article aims to review radioembolization-specific toxicities stratified by hepatic, extrahepatic, and systemic effects, with a focus on preventing and mitigating radioembolization-induced morbidity.

Inferior vena cava filter tilting between placement and retrieval is associated with caval diameter and need for complex retrieval techniques.

PURPOSE: Inferior vena cava (IVC) filter tilt may lead to apex embedment and need for advanced retrieval techniques. This study assesses factors associated with filter tilt change over time and need for complex retrieval procedures. MATERIALS AND METHODS: 252 consecutive patients underwent retrievable IVC filter placement and removal at a single academic institution over 58 months. 182 (72.2%) patients met inclusion criteria. IVC filters included 168 (92.3%) Gunther Tulip and 14 (7.7%) Option filters. The primary outcome was medial-to-lateral IVC filter tilt change between placement and retrieval. Secondary outcomes included advanced retrieval technique use and multiple retrieval attempts. Independent variables included demographics, IVC diameter, filter hook position relative to the renal veins, and dwell time. Associations were determined using student's t-tests, ANOVA, and linear and logistic regressions. RESULTS: Mean IVC diameter at placement was 19.2 ± 3.3 mm. Mean filter tilts at placement and retrieval were 6.1 ± 4.9° and 5.2 ± 5.0°, respectively. Mean tilt change was 5.0 ± 5.0°. Larger IVC diameter was associated with greater filter tilt change (p = 0.0004). While IVC diameter did not independently predict retrieval difficulty, greater tilt change and prolonged dwell time were associated with increased advanced retrieval technique use (p = 0.01 and 0.002, respectively). Results were unchanged in a subgroup analysis of patients treated with Gunther Tulip filters. CONCLUSION: Larger IVC diameter predicts increased filter tilt change, which in turn is associated with challenging retrievals. Attention to IVC diameter during filter placement may anticipate tilt-related complications.

Hepatic artery aneurysm in the setting of focal nodular hyperplasia.

Hepatic artery aneurysms (HAA) are rare and may be seen in the setting of infection and vascular disease. Clinical presentation is variable but many are found incidentally during imaging studies. The association of HAA with focal nodular hyperplasia (FNH) is rarely reported in literature. We present the case of a 68-year-old woman found to have a hepatic artery aneurysm and hepatic mass, both within the same liver segment. FNH and hepatic adenomas share similar imaging features but have different treatments due to malignant potential of the latter, and biopsy should be performed when adenoma cannot be excluded. In this case biopsy of the mass revealed it to be FNH and the aneurysm was treated with embolization rather than surgery.

Life and Limb: Current Concepts in Endovascular Treatment of Extremity Trauma.

Traumatic injury is the leading cause of death worldwide in younger patient populations and extremity trauma with associated vascular injury accounts for many trauma-related deaths. Iatrogenic injury is also a common cause of extremity vascular trauma and the incidence of iatrogenic injury will likely increase as endovascular techniques continue to become more ubiquitous. For many vascular injuries involving the extremities, surgical repair is viewed as the standard of care. Historically, endovascular techniques did not play a role in the treatment of these vascular injuries, rather they were utilized only as part of the diagnostic assessment; however, there is an increasing trend toward endovascular management of extremity vascular trauma. No validated, widely implemented algorithm to select patients for endovascular intervention exists. Transcatheter techniques, however, play an important role in the management of these patients. For arterial injuries, embolization can be used to rapidly achieve hemostasis if the vessel can be sacrificed. More advanced endovascular techniques such as stent-graft placement may be best employed in the context of isolated, proximal extremity injuries, although there is increasing literature supporting the use of advanced techniques for more distal arterial injuries. The management of peripheral venous trauma remains controversial; however, there is growing data describing successful endovascular management of some peripheral venous injuries. The purpose of this article is to review extremity vascular trauma, concepts of injury triage, endovascular techniques, and intraprocedural considerations.

Yttrium-90 Radioembolization for the Treatment of Solitary, Unresectable HCC: The LEGACY Study.

BACKGROUND AND AIMS: Locoregional therapies, including yttrium-90 radioembolization, play an important role in the treatment of unresectable HCC. The aim of the LEGACY (Local radioEmbolization using Glass Microspheres for the Assessment of Tumor Control with Y-90) study was to evaluate objective response rate (ORR) and duration of response (DoR) in patients with solitary unresectable HCC treated with yttrium-90 glass microspheres. APPROACH AND RESULTS: LEGACY is a multicenter, single-arm, retrospective study conducted at three sites that included all eligible, consecutive patients with HCC treated with radioembolization between 2014 and 2017. Eligibility criteria included solitary HCC ≤ 8 cm, Child-Pugh A cirrhosis, and Eastern Cooperative Oncology Group performance status 0-1. Primary endpoints were ORR and DoR based on modified Response Evaluation Criteria in Solid Tumors in the treated area (localized), as evaluated by blinded, independent, central review. Radioembolization was performed with intent of ablative-level dosimetry in a selective fashion when possible. Overall survival was evaluated using Kaplan-Meier and multivariate Cox proportional hazards. Among the 162 patients included, 60.5% were Eastern Cooperative Oncology Group 0, and the median tumor size was 2.7 cm (range: 1-8) according to blinded, independent, central review. Radioembolization served as neoadjuvant therapy for transplantation or resection in 21.0% (34 of 162) and 6.8% (11 of 162) of patients, respectively, and as primary treatment for all others. Median follow-up time was 29.9 months by reverse Kaplan-Meier. ORR (best response) was 88.3% (CI: 82.4-92.4), with 62.2% (CI: 54.1-69.8) exhibiting a DoR ≥ 6 months. Three-year overall survival was 86.6% for all patients and 92.8% for those neoadjuvant patients with resected or transplanted liver. CONCLUSIONS: In this multicenter study of radioembolization, clinical meaningful response rates and prolonged DoR were observed in the treatment of unresectable, solitary HCC ≤ 8 cm.

Yttrium-90 radiation segmentectomy for hepatic metastases: A multi-institutional study of safety and efficacy.

BACKGROUND AND OBJECTIVES: This study assessed the outcomes of Yttrium-90 (90 Y) radiation segmentectomy for hepatic metastases unamenable to resection or ablation. MATERIALS AND METHODS: Over 6 years, 36 patients with 53 tumors underwent segmental radioembolization. Patients were not candidates for surgical resection or thermal ablation. Malignancies included metastases from colorectal cancer (31%), neuroendocrine tumors (28%), sarcoma (19%), and others (22%). Eighty-one percent of patients had undergone prior treatment with systemic chemotherapy. Ongoing systemic chemotherapy was continued. Toxicity, tumor response, tumor progression, and survival were assessed. RESULTS: The median tumor size was 3.6 cm (range 1.2-6.1 cm). Adverse event rates were low, with no hepatic-related Common Terminology Criteria for Adverse Events Grade 3 or 4 toxicity. Target tumor Response Evaluation Criteria in Solid Tumors disease control rate was 92% (28% partial response, 64% stable disease). For patients with enhancing tumors (n = 14), modified Response Evaluation Criteria in Solid Tumors target tumor objective response rate was 100%. During a median follow-up of 12 months, target tumor progression occurred in 28% of treated tumors. Overall survival was 96% and 83% at 6 and 12 months, respectively. CONCLUSIONS: 90 Y radiation segmentectomy for hepatic metastases demonstrates high rates of tumor control and minimal toxicity. Radiation segmentectomy should be considered for patients with metastatic hepatic malignancy who are not candidates for surgical resection.

Correlation of Y90-absorbed radiation dose to pathological necrosis in hepatocellular carcinoma: confirmatory multicenter analysis in 45 explants.

PURPOSE: To study the correlation between absorbed perfused liver dose using Y90 radioembolization and degree of hepatocellular carcinoma (HCC) necrosis in liver explants in a multicenter cohort analysis METHODS: A retrospective analysis of 45 HCC patients treated between 2014 and 2017 is presented. Inclusion criteria were treatment-naïve solitary HCC ≤ 8 cm and Child-Pugh A liver status using the radiation segmentectomy approach. All patients underwent liver resection or transplantation (LT). Liver explants were examined per institutional routine protocols to assess histopathological viability of HCC. Tumor pathological necrosis was classified into complete (100% necrosis), extensive (> 50% and ≤ 99%) necrosis, and partial (< 50%) necrosis. Absorbed perfused liver doses were estimated using MIRD calculations. Associations between dose and degree of necrosis were studied. RESULTS: Thirty-four (76%) patients underwent LT, and 11 (24%) patients underwent hepatic resection. Median radiation dose was 240 (IQR: 136-387) Gy. Thirty (67%) patients had complete pathologic necrosis (CPN) at explant, while 10 (22%) and 5 (11%) had extensive and partial necrosis, respectively. There were significant differences among perfused liver doses that exhibited partial, extensive, and complete necrosis (p = 0.001). Twenty-four out of twenty-eight (86%) patients who had dose > 190 Gy achieved CPN, while 11/17 (65%) who had < 190 Gy did not (Fisher's exact test; p = 0.001). Using binary logistic regression, only absorbed radiation dose was significantly associated with CPN (p = 0.01), while tumor size was not (p = 0.35). All patients receiving > 400 Gy exhibited CPN. CONCLUSION: Radiation segmentectomy for early HCC with ablative dosing > 400 Gy results in CPN. This represents the new standard target dose for radiation segmentectomy.

Transarterial Yttrium-90 Radioembolization of Hepatocellular Carcinoma Perfused by the Cystic Artery: Multi-institutional Feasibility Study.

PURPOSE: To assess the safety and efficacy of transarterial yttrium-90 radioembolization via the cystic artery for patients with hepatocellular carcinoma (HCC) adjacent to the gallbladder with cystic artery supply. MATERIALS AND METHODS: This retrospective study included 17 patients treated at 4 institutions. Patients with HCC perfused by the cystic artery who received ablative-dose radioembolization were included. Median tumor size was 3.8 cm (range, 2.0-8.8 cm). Fourteen patients (82%) had Child-Pugh class A cirrhosis and 3 (18%) had class B cirrhosis. Adverse events, tumor response, and time to progression were analyzed. RESULTS: Median dose to the tissue perfused by the cystic artery was 340 Gy (range, 200-720 Gy). There were no occurrences of acute cholecystitis warranting invasive intervention. Four patients (24%) experienced transient right upper quadrant pain, with symptom resolution within 3 mo. Six patients (35%) exhibited gallbladder wall edema on follow-up imaging. Two (12%) and 0 grade 3/4 increases in alkaline phosphatase and bilirubin were observed, respectively. Follow-up imaging demonstrated complete response in 13 target tumors (76%) and partial response in 4 (24%). There were no cases of target tumor progression during a median follow-up of 9 mo (range, 3-72 mo). CONCLUSIONS: Direct infusion of 90Y microspheres via the cystic artery appears to have an acceptable safety profile, without resulting in acute cholecystitis warranting invasive intervention. In selected patients with HCC in whom other treatments may be contraindicated and the tumor is supplied via the cystic artery, treatment with selective ablative radioembolization can be considered.

Transjugular intrahepatic portosystemic shunt creation via isolated persistent left superior vena cava: a case series.

BACKGROUND: Isolated persistent left superior vena cava (PLSVC) is a rare vascular anatomic variant, which can be an incidental finding at the time of an endovascular procedure. CASE PRESENTATION: This report describes the technical success, adverse events, and clinical outcomes of transjugular intrahepatic portosystemic shunt (TIPS) creation via isolated PLSVC. Three adult patients with cirrhosis and isolated PLSVC underwent TIPS placement successfully with one major adverse event. Two patients required TIPS revision within 90 days. There were no deaths within 90 days. CONCLUSIONS: TIPS creation via isolated PLSVC is feasible using standard techniques with a left jugular vein approach. Caution is warranted during the procedure to assess for any aberrant drainage pattern to the left atrium and to prepare for potentially challenging instrument navigation through the coronary sinus.

Fluoroscopically-guided interventions with radiation doses exceeding 5000 mGy reference point air kerma: a dosimetric analysis of 89,549 interventional radiology, neurointerventional radiology, vascular surgery, and neurosurgery encounters.

PURPOSE: To quantify and categorize fluoroscopically-guided procedures with radiation doses exceeding 5000 mGy reference point air kerma (Ka,r). Ka,r > 5000 mGy has been defined as a "significant radiation dose" by the Society of Interventional Radiology. Identification and analysis of interventions with high radiation doses has the potential to reduce radiation-induced injuries. MATERIALS AND METHODS: Radiation dose data from a dose monitoring system for 19 interventional suites and 89,549 consecutive patient encounters from January 1, 2013 to August 1, 2019 at a single academic institution were reviewed. All patient encounters with Ka,r > 5000 mGy were included. All other encounters were excluded (n = 89,289). Patient demographics, medical specialty, intervention type, fluoroscopy time (minutes), dose area product (mGy·cm2), and Ka,r (mGy) were evaluated. RESULTS: There were 260 (0.3%) fluoroscopically-guided procedures with Ka,r > 5000 mGy. Of the 260 procedures which exceeded 5000 mGy, neurosurgery performed 81 (30.5%) procedures, followed by interventional radiology (n = 75; 28.2%), neurointerventional radiology (n = 55; 20.7%), and vascular surgery (n = 49; 18.4%). The procedures associated with the highest Ka,r were venous stent reconstruction performed by interventional radiology, arteriovenous malformation embolization performed by neurointerventional radiology, spinal hardware fixation by neurosurgery, and arterial interventions performed by vascular surgery. Neurointerventional radiology had the highest mean Ka,r (7,799 mGy), followed by neurosurgery (7452 mGy), vascular surgery (6849 mGy), and interventional radiology (6109 mGy). The mean Ka,r for interventional radiology performed procedures exceeding 5000 mGy was significantly lower than that for neurointerventional radiology, neurosurgery, and vascular surgery. CONCLUSIONS: Fluoroscopically-guided procedures with radiation dose exceeding 5000 mGy reference point air kerma are uncommon. The results of this study demonstrate that a large proportion of cases exceeding 5000 mGy were performed by non-radiologists, who likely do not receive the same training in radiation physics, radiation biology, and dose reduction techniques as radiologists.

The inferior vena cava: a pictorial review of embryology, anatomy, pathology, and interventions.

The inferior vena cava (IVC) is the largest venous conduit below the diaphragm. Although this structure is often overlooked both clinically and radiographically, it can be involved in many different pathologic processes. A thorough understanding of the IVC will assist the radiologist in recognizing anatomic variants, identifying abnormalities, and providing accurate differential diagnoses. In this comprehensive pictorial review of the IVC, we depict embryology behind anatomic variants, present a wide range of pathology with a focus on diagnostic imaging, and describe relevant endovascular interventions.

Hepatotoxic Dose Thresholds by Positron-Emission Tomography After Yttrium-90 Radioembolization of Liver Tumors: A Prospective Single-Arm Observational Study.

PURPOSE: To define a threshold radiation dose to non-tumoral liver from 90Y radioembolization that results in hepatic toxicity using pair-production PET. MATERIALS AND METHODS: This prospective single-arm study enrolled 35 patients undergoing radioembolization. A total of 34 patients (27 with HCC and 7 with liver metastases) were included in the final analysis. Of 27 patients with underlying cirrhosis, 22 and 5 patients were Child-Pugh A and B, respectively. Glass and resin microspheres were used in 32 (94%) and 2 (6%) patients, respectively. Lobar and segmental treatment was done in 26 (76%) and 8 (24%) patients, respectively. Volumetric analysis was performed on post-radioembolization time-of-flight PET imaging to determine non-tumoral parenchymal dose. Hepatic toxicity was evaluated up to 120 days post-treatment, with CTCAE grade ≤ 1 compared to grade ≥ 2. RESULTS: The median dose delivered to the non-tumoral liver in the treated lobe was 49 Gy (range 0-133). A total of 15 patients had grade ≤ 1 hepatic toxicity, and 19 patients had grade ≥ 2 toxicity. Patients with a grade ≥ 2 change in composite toxicity (70.7 vs. 43.8 Gy), bilirubin (74.1 vs. 43.3 Gy), albumin (84.2 vs. 43.8 Gy), and AST (94.5 vs. 47.1 Gy) have significantly higher non-tumoral parenchymal doses than those with grade ≤ 1. Liver parenchymal dose and Child-Pugh status predicted grade ≥ 2 toxicity, observed above a dose threshold of 54 Gy. CONCLUSION: Increasing delivered 90Y dose to non-tumoral liver measured by internal pair-production PET correlates with post-treatment hepatic toxicity. The likelihood of toxicity exceeds 50% at a dose threshold of 54 Gy. ClinicalTrials.gov identifier: NCT02848638.

Prospective Trial Using Internal Pair-Production Positron Emission Tomography to Establish the Yttrium-90 Radioembolization Dose Required for Response of Hepatocellular Carcinoma.

PURPOSE: To prospectively assess the threshold dose for objective response of hepatocellular carcinoma (HCC), using 90Y internal pair-production positron emission tomography (PET) to quantify the radiation dose delivered to hepatic tumors after radioembolization. METHODS AND MATERIALS: A prospective study was performed under institutional review board approval from 2012 to 2014. Thirty-five patients with primary and secondary liver tumors undergoing 90Y treatment were recruited. Eight patients did not meet inclusion criteria, and 27 patients with HCC were included for analysis. Time-of-flight PET imaging was performed immediately after radioembolization and voxel values converted into 90Y activity. The radioembolization dose was calculated from PET images, and image segmentation was performed with volumetric analysis of dose deposition within tumors. Radiographic response was assessed on follow-up imaging. RESULTS: Treated HCC showed 84% objective response, 11% stable disease, and 5% progressive disease according to modified RECIST 1.1 response criteria. Responders had a higher median 90Y tumor dose than nonresponders (225 Gy vs 83 Gy, P < .01). Logistic regression models show tumor dose (P = .002) strongly predicted objective response. All nonresponders had tumor dose <200 Gy. No statistical difference for patient age, tumor volume, multifocal or extrahepatic disease, portal vein invasion, or injected 90Y activity was found between responders and nonresponders. CONCLUSIONS: Hepatocellular carcinoma that resulted in objective response after radioembolization had a greater median tumor dose of 225 Gy, compared with 83 Gy in nonresponders. Delivered tumor dose can be assessed by PET and significantly impacts treatment response in HCC.

An Interventionalist's Guide to Hemoptysis in Cystic Fibrosis.

Massive hemoptysis occurs in a minority of patients with cystic fibrosis, with an annual incidence of 1%. Although rare, massive hemoptysis can be a severe and potentially fatal complication of this disease. Beyond the acute life-threatening event, hemoptysis in patients with cystic fibrosis has been associated with faster decline in lung function, accelerated need for lung transplant, and increased mortality. The bronchial arteries are the culprit vessels in over 90% of cases of hemoptysis. This normally quiescent vascular system undergoes remarkable hypertrophy, collateralization, and angiogenesis before the onset of hemoptysis, introducing numerous pitfalls for the interventionalist. However, in experienced hands, bronchial artery embolization is a safe and potentially lifesaving therapy. Preprocedural noninvasive imaging, specifically computed tomographic angiography, has been repeatedly validated for helping to localize the likely site of bleeding, characterizing pertinent arterial anatomy, and promoting efficient and effective intervention; it has been recommended for all stable patients with hemoptysis. Success in the angiographic suite requires a thorough understanding of normal and variant bronchial arterial anatomy, appropriate patient selection, and a meticulous embolization technique. A meticulous approach to imaging and intervention, conscientious of both visualized and nonvisualized collateral pathways and nontarget vessels, can minimize potentially devastating complications. This review summarizes the current literature, modern procedural techniques, and emerging controversies, serving to guide an evolving approach to management of patients with cystic fibrosis and hemoptysis. ©RSNA, 2018.

Toward consensus reporting of radiation-induced liver toxicity in the treatment of primary liver malignancies: Defining clinically relevant endpoints.

BACKGROUND: Our purpose was to define the most clinically relevant "nonclassic" radiation-induced liver disease (RILD) endpoints in cirrhotic patients receiving stereotactic body radiation therapy or proton beam therapy for primary liver cancer. METHODS AND MATERIALS: We retrospectively collected pretreatment, detailed toxicity (≤6 months posttreatment), and outcomes data from 48 patients. Deaths were examined for association with RILD. Univariate and multivariate Cox models defined significant predictors of overall survival (OS)/RILD-specific survival (RILD-SS). RESULTS: With median follow-up of 13 months, 23 patients (48%) had an increase in Child-Pugh (CP) score (≥2, 25%) and 3 (6%) had ≥G3 transaminase elevation. Of 18 deaths, 6 were potentially ascribed to RILD. Univariate analysis showed that CP score increases of ≥1 and ≥2 and CP class change predicted OS, as did ≥G3 aspartate transaminase (AST) elevation and ≥1 Common Terminology Criteria for Adverse Events (CTCAE) AST toxicity grade change. On multivariate analysis, CP score increase of ≥2 and ≥1 CTCAE AST toxicity grade change were the strongest independent nonclassic RILD predictors of OS. For RILD-SS, CP score increases of ≥2, ≥grade 3 CTCAE alanine transaminase, and ≥grade 2 bilirubin elevations were predictive. CONCLUSIONS: Increased CP score ≥2 strongly predicts for both OS and RILD-SS and should be reported in future studies along with transaminase elevations, which are also predictive of outcomes.