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Background: Assessment of hepatocellular carcinoma (HCC) treatment response after transarterial radioembolization (TARE) is challenging, as response by conventional imaging criteria may not become ...

PURPOSE To study the impact of transarterial Yttrium-90 radioembolization (TARE) in combination with second-line systemic chemotherapy for colorectal liver metastases (CLM). METHODS In this international, multicenter, open-label phase III trial, patients with CLM who progressed on oxaliplatin- or irinotecan-based first-line therapy were randomly assigned 1:1 to receive second-line chemotherapy with or without TARE. The two primary end points were progression-free survival (PFS) and hepatic PFS (hPFS), assessed by blinded independent central review. Random assignment was performed using a web- or voice-based system stratified by unilobar or bilobar disease, oxaliplatin- or irinotecan-based first-line chemotherapy, and KRAS mutation status. RESULTS Four hundred twenty-eight patients from 95 centers in North America, Europe, and Asia were randomly assigned to chemotherapy with or without TARE; this represents the intention-to-treat population and included 215 patients in the TARE plus chemotherapy group and 213 patients in the chemotherapy alone group. The hazard ratio (HR) for PFS was 0.69 (95% CI, 0.54 to 0.88; 1-sided P = .0013), with a median PFS of 8.0 (95% CI, 7.2 to 9.2) and 7.2 (95% CI, 5.7 to 7.6) months, respectively. The HR for hPFS was 0.59 (95% CI, 0.46 to 0.77; 1-sided P < .0001), with a median hPFS of 9.1 (95% CI, 7.8 to 9.7) and 7.2 (95% CI, 5.7 to 7.6) months, respectively. Objective response rates were 34.0% (95% CI, 28.0 to 40.5) and 21.1% (95% CI, 16.2 to 27.1; 1-sided P = .0019) for the TARE and chemotherapy groups, respectively. Median overall survival was 14.0 (95% CI, 11.8 to 15.5) and 14.4 months (95% CI, 12.8 to 16.4; 1-sided P = .7229) with a HR of 1.07 (95% CI, 0.86 to 1.32) for TARE and chemotherapy groups, respectively. Grade 3 adverse events were reported more frequently with TARE (68.4% v 49.3%). Both groups received full chemotherapy dose intensity. CONCLUSION The addition of TARE to systemic therapy for second-line CLM led to longer PFS and hPFS. Further subset analyses are needed to better define the ideal patient population that would benefit from TARE.

Purpose Performing a systematic review and meta-analysis to assess the evidence of intra-arterial therapies in liver metastatic breast cancer (LMBC) patients. Methods A systemic literature search was performed in PubMed, EMBASE, SCOPUS for studies regarding intra-arterial therapies in LMBC patients. Full text studies of LMBC patients (n >= 10) published between January 2010 and December 2020 were included when at least one outcome among response rate, adverse events or survival was available. Response rates were pooled using generalized linear mixed models. A weighted estimate of the population median overall survival (OS) was obtained under the assumption of exponentially distributed survival times. Results A total of 26 studies (1266 patients) were included. Eleven articles reported on transarterial radioembolization (TARE), ten on transarterial chemoembolization (TACE) and four on chemo-infusion. One retrospective study compared TARE and TACE. Pooled response rates were 49% for TARE (95%CI 32-67%), 34% for TACE (95%CI 22-50%) and 19% for chemo-infusion (95%CI 14-25%). Pooled median survival was 9.2 months (range 6.1-35.4 months) for TARE, 17.8 months (range 4.6-47.0) for TACE and 7.9 months (range 7.0-14.2) for chemo-infusion. No comparison for OS was possible due to missing survival rates at specific time points (1 and 2 year OS) and the large heterogeneity. Conclusion Although results have to be interpreted with caution due to the large heterogeneity, the superior response rate of TARE and TACE compared to chemo-infusion suggests first choice of TARE or TACE in chemorefractory LMBC patients. Chemo-infusion could be considered in LMBC patients not suitable for TARE or TACE.

Purpose of Review This review describes recent data supporting locoregional ablative radiation in the treatment of oligometastatic colorectal cancer liver metastases. Recent Findings Stereotactic body radiotherapy (SBRT) demonstrates high rates of local control in colorectal cancer liver metastases when a biologically equivalent dose of > 100 Gy is delivered. Future innovations to improve the efficacy of SBRT include MRI-guided radiotherapy (MRgRT) to enhance target accuracy, systemic immune activation to treat extrahepatic disease, and genomic customization. Selective internal radiotherapy (SIRT) with y-90 is an intra-arterial therapy that delivers high doses to liver metastases internally which has shown to increase liver disease control in phase 3 trials. Advancements in transarterial radioembolization (TARE) dosimetry could improve local control and decrease toxicity. Summary SBRT and SIRT are both promising options in treating unresectable metastatic colorectal cancer liver metastases. Identification of oligometastatic patients who receive long-term disease control from either therapy is essential. Future advancements focusing on improving radiation design and customization could further improve efficacy and toxicity.

To compare transarterial chemoembolization (TACE), transarterial radioembolization using Yttrium-90 (TARE), and transarterial ethanol ablation (TEA) for huge hepatocellular carcinoma (HCC) in treatment responses and long-term survival outcomes. In this retrospective study approved by institutional committee, inclusion criteria were tumour ≥ 10 cm, newly diagnosed, treatment naive, Child A, Performance Score 0 or 1, no venous invasion or extrahepatic disease on contrast-enhanced CT or MRI. There were 107 patients (Supportive Care [SC] 17, TACE 54, TARE 17, TEA 19). Survival outcomes of SC and TACE were compared (TACE selected as benchmark for transarterial treatments). Tumour response and overall survival (OS) of the three groups were compared. OS of TACE (vs. SC) was significantly longer (9.9 [5.9, 24.1] months versus 2.8 [1.5, 10.2], p = 0.001). Complete response of TEA was significantly better (TEA 10/19 [52.6%] versus TARE 2/17 [12.5%], p = 0.013, versus TACE 9/54 [16.7%], p = 0.002). OS of TEA (vs. TACE) was significantly longer (21.6 [12, 41] months versus 9.9 [5.9, 24.1], p = 0.014, hazard ratio 0.6 (0.3, 1). OS of TEA (vs. TARE) was longer (21.6 [12, 41] months versus 11.9 [7, 28.7], p = 0.082, hazard ratio 0.6 (0.3, 1.3) in favour of TEA). In patients with huge HCC, transarterial treatment as represented by TACE had a survival benefit over supportive care. In this retrospective analysis, TEA was associated with better tumour response and survival outcome as compared to TACE or TARE; therefore, transarterial treatment could be useful for prolonging patient survival, and TEA could be a preferred option.

Transarterial radioembolization (TARE) with yttrium 90 has increasingly been performed to treat hepatocellular carcinoma (HCC). TARE was historically used as a palliative lobar therapy for patients with advanced HCC beyond surgical options, ablation, or transarterial chemoembolization, but recent advancements have led to its application across the Barcelona Clinic Liver Cancer staging paradigm. Newer techniques, termed radiation lobectomy and radiation segmentectomy, are being performed before liver resection to facilitate hypertrophy of the future liver remnant, before liver transplant to bridge or downstage to transplant, or as a definite curative treatment. Imaging assessment of therapeutic response to TARE is challenging as the intent of TARE is to deliver local high-dose radiation to tumors through microembolic microspheres, preserving blood flow to promote radiation injury to the tumor. Because of the microembolic nature, early imaging assessment after TARE cannot rely solely on changes in size. Knowledge of the evolving methods of TARE along with the tools to assess posttreatment imaging and response is essential to optimize TARE as a therapeutic option for patients with HCC. ©RSNA, 2021.

Objective Transarterial radioembolization (TARE) offers a minimally invasive and safe treatment option for primary and metastatic hepatic malignancies. The benefits of TARE are manifold including prolonged overall survival, low associated morbidities, and improved time to progression allowing prolonged treatment-free intervals. The rapid development of new systemic therapies including immunotherapy has radically changed the treatment landscape for primary and metastatic liver cancer. Given the current climate, it is critical for interventional oncologists to understand the benefits of TARE relative to these other therapies. Therefore, this report aims to review quality-of-life outcomes and the cost comparisons of TARE as compared with systemic therapies.

Hepatocellular carcinoma (HCC) with portal vein tumoral thrombosis (PVTT) represents a major concern especially in the field of deceased donor liver transplantation (DDLT). However, when receiving transarterial radioembolization (TARE), a considerable percentage of such patients are able to achieve a radiologic complete response with adequate survival rates. In this pilot prospective study, we evaluated the effect of TARE in downstaging HCC patients with PVTT to meet criteria for DDLT. Between May 2013 and November 2016, patients were evaluated to be enrolled into our “Superdownstaging” protocol. Patients received yttrium-90 TARE and were enlisted for DDLT in case of complete and sustained (6months) radiological response. Patients with tumor thrombus in the main trunk and/or in the contralateral portal vein branch were excluded. TARE was effective in downstaging and receiving DDLT in 5/17 patients (29.4%). The 5-year overall survival was significantly higher in patients who underwent DDLT compared with those who were not transplanted (60.0% versus 0.0%, P=0.03). Three out of 5 patients developed recurrence within 1year after LT. The current series showed a clear survival gain in those patients who were able to receive DDLT after TARE but careful selection for DDLT is however advised.

Background The aim of this ancillary study of the SARAH trial is to compare health-related quality of life (HRQoL) in patients with locally advanced or inoperable hepatocellular carcinoma (HCC) treated with transarterial radioembolisation (TARE) or sorafenib. Methods This study included randomised patients who received either TARE or at least one dose of sorafenib with no major deviation in the protocol and who had at least one QoL follow-up assessment in addition to the baseline evaluation. QoL was assessed from the date of randomisation using the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire, until disease progression or other reasons for stopping study participation. Data were analysed using linear mixed and time-dependent models. Results A total of 285 patients were included (122 and 163, in the TARE and sorafenib groups, respectively). Questionnaire completion rates were similar (77.5% versus 80.4%, in the TARE and sorafenib groups, respectively, p = 0.25). Longitudinal HRQoL analysis showed a significant treatment and time effects for fatigue and global health status, and significant treatment, time and treatment by time interaction effects for appetite loss, diarrhoea and social functioning. The median time to deterioration for the global health status was 3.9 months (95% confidence interval [CI] 3.7–4.3) versus 2.6 months (95% CI 2.0–3.0) in the TARE and sorafenib groups, respectively. Conclusions HRQoL was preserved longer with TARE than with sorafenib in locally advanced HCC. These data could be used to optimise management of patients with advanced or inoperable HCC.

Purpose To use time-drive activity-based costing (TDABC) to characterize and compare costs of transarterial chemoembolization (TACE), transarterial radioembolization (TARE), and ablation. Methods This three-part study involved (1) prospective observation to record resources used during TACE, TARE, and ablation and statistical evaluation of interobserver and interprocedure variability; (2) Bland-Altman analysis of prospective measurements and medical record time stamps to establish practicality of using retrospective data in place of direct observation; (3) retrospective time stamp assessment for 117 ablations, 61 TACE procedures, and 61 TARE procedures to reveal variability drivers. Results Ablation costs were lowest ($3,744), which were 74% of TACE costs ($5,089) and 18% of TARE costs ($20,818). Consumables were the greatest cost contributor, accounting for 65% of ablation, 58% of TACE, and 90% of TARE costs. A single consumable contributed to most of the overall costs: the ablation probe (42%), ethiodized oil for TACE (30%), and yttrium-90 microspheres for TARE (80%). Bland-Altman analysis showed agreement between retrospective time stamps and prospective measurements. Ablation costs increased from $3,288 to $4,245 to $4,461 for one, two, or three tumors treated. TACE cost increased from $5,051 to $5,296 for lobar versus selective approaches. Conclusion A bottom-up costing approach using TDABC is feasible to assess true costs of hepatocellular carcinoma treatments and demonstrates ablation costs are significantly less than those of TACE and TARE. Replication of these methods at other institutions can facilitate development of a bundled payment model to promote utilization of locoregional therapies for hepatocellular carcinoma.

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. 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. 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. 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.

Hepatocellular carcinoma (HCC) is the fastest-growing cancer worldwide, causing significant morbidity and mortality. Surgical resection, ablation, or transplantation is the best treatment option for patients with HCC. However, only about one-fifth of patients are suitable for such primary curative treatments due to underlying liver disease or rapid extension of the tumor. Image-guided locoregional therapies may prove an important alternative in this scenario, particularly transarterial radioembolization (TARE) with yttrium-90 (Y-90). Based on many studies, TARE can be considered a curative treatment option for patients with early-stage HCC, a bridge to transplantation, and a method for downstaging tumors to give patients with unresectable HCC a chance to potentially receive a curative treatment. TARE can be also combined with other treatment modalities to provide a better quality of life in patients when compared with systemic therapy in patients with unresectable HCC. Here, we discuss the use of TARE in the approach to HCC patients who are in early, intermediate, or advanced stages.

Purpose To evaluate the safety and efficacy of 2 locoregional therapies (LRTs) including hepatic artery embolization (HAE) and transarterial radioembolization (TARE) in the treatment of patients with metastatic ovarian cancer to the liver. Material and Methods From October 2010 to May 2019, the data of 15 consecutive patients (median age, 54 years ± 9.8; range, 35–78 years) with hepatic metastatic ovarian cancer who were treated with either HAE (n = 6; 40%) or TARE (n = 9; 60%) were reviewed. The most common histopathologic type was epithelial ovarian carcinoma (80%). The most common chemotherapy regimens used prior to embolization included carboplatin, paclitaxel, cisplatin, and bevacizumab. Patients received a mean of 4 lines ± 3 (range, 1–9) of chemotherapy. All patients with serous carcinoma were resistant to platinum at the time of embolization. Indications for embolization were progression of disease to the liver while receiving chemotherapy in 14 (93.3%) patients and palliative pain control in 1 patient. Results The overall response rates at 1, 3, and 6 months were 92.4%, 85.6%, and 70%, respectively. Median overall survival from the time of LRT was 9 (95% confidence interval [CI], 4–14) months. Median local tumor progression was 6.4 months ± 5.03 (95% CI, 3.3–9.5). No grade 3–5 adverse events were detected in either group. Conclusions HAE and TARE were well tolerated in patients with metastatic ovarian cancer to the liver and possibly ensured prolonged disease control in heavily treated, predominantly in patients resistant to platinum. Larger numbers are needed to verify these data.

Transarterial radioembolization (TARE) is a locoregional radiopharmaceutical therapy based on the delivery of radioactive (90)Y microspheres to liver tumors. The importance of personalized dosimetry to make TARE safer and more effective has been demonstrated in recent clinical studies, stressing the need for quantification of the dose–response relationship to ultimately optimize the administered activity before treatment and image it after treatment. (90)Y dosimetric studies are challenging because of the lack of accurate and precise methods but are best realized with PET combined with Monte Carlo simulations and other image modalities to calculate a segmental dose distribution. The aim of this study was to assess the suitability of imaging (90)Y PET patients with the total-body PET/CT uEXPLORER and to investigate possible improvements in TARE (90)Y PET-based dosimetry. The uEXPLORER is the first commercially available ultra-high-resolution (171 cps/kBq) total-body digital PET/CT device with a 194-cm axial PET field of view that enables the whole body to be scanned at a single bed position. Methods: Two PET/CT scanners were evaluated in this study: the Biograph mCT and the total-body uEXPLORER. Images of a National Electrical Manufacturers Association (NEMA) image-quality phantom and 2 patients were reconstructed using our standard clinical oncology protocol. A late portal phase contrast-enhanced CT scan was used to contour the liver segments and create corresponding volumes of interest. To calculate the absorbed dose, Monte Carlo simulations were performed using Geant4 Application for Tomographic Emission (GATE). The absorbed dose and dose–volume histograms were calculated for all 6 spheres (diameters ranging from 10 to 37 mm) of the NEMA phantom, the liver segments, and the entire liver. Differences between the phantom doses and an analytic ground truth were quantified through the root mean squared error. Results: The uEXPLORER showed a higher signal-to-noise ratio at 10- and 13-mm diameters, consistent with its high spatial resolution and system sensitivity. The total liver-absorbed dose showed excellent agreement between the uEXPLORER and the mCT for both patients, with differences lower than 0.2%. Larger differences of up to 60% were observed when comparing the liver segment doses. All dose–volume histograms were in good agreement, with narrower tails for the uEXPLORER in all segments, indicating lower image noise. Conclusion: This patient study is compelling for the use of total-body (90)Y PET for liver dosimetry. The uEXPLORER scanner showed a better signal-to-noise ratio than mCT, especially in lower-count regions of interest, which is expected to improve dose quantification and tumor dosimetry.

Transarterial radioembolization (TARE) using β-emitting yttrium-90 microspheres has been used for decades in patients with liver-dominant unresectable metastatic neuroendocrine tumors (mNETs). TARE is one of the embolotherapies supported by the National Comprehensive Cancer Network, among other guidelines, for progressive or symptomatic liver-dominant mNETs. Initial studies with relatively short-term follow-up have indicated that TARE is likely to be at least as effective in controlling symptoms and/or disease progression in the liver as bland or chemoembolization. However, more recent data have shed new light on the risk of long-term hepatotoxicity in patients with mNETs treated with TARE. In this article, we will discuss rationale for TARE, clinical indications, outcomes, and toxicity, as well as new strategies to enhance efficacy of TARE while reducing its toxicity in the treatment of liver-dominant mNETs.

Transarterial radioembolization with yttrium-90 microspheres is an established therapy for hepatocellular carcinoma. Post-procedural imaging is important for the assessment of both treatment response and procedural complications. A variety of challenging treatment-specific imaging phenomena complicate imaging assessment, such as changes in tumoral size, tumoral and peritumoral enhancement, and extrahepatic complications. A review of the procedural steps, emerging variations, and timelines for post-treatment tumoral and extra-tumoral imaging changes are presented, which may aid the reporting radiologist in the interpretation of post-procedural imaging. Furthermore, a description of post-procedural complications and their significance is provided.

Systemic therapy remains the recommended first-line treatment for hepatocellular carcinoma (HCC) with macrovascular invasion (MVI). Transarterial radioembolization (TARE) is a promising alternative treatment, given its potential to impart a superior quality of life. The aims of this study were, first, to characterize trends and correlates for TARE as a first-line treatment for HCC patients with MVI in the United States and, second, to compare survival after TARE versus systemic therapy. Methods: We used the U.S. National Cancer Database to identify patients with T3BN0M0 HCC during 2010–2017. We performed multivariable logistic regression to identify factors associated with use of TARE versus systemic therapy and Cox proportional-hazards regression to identify factors associated with overall survival. Results: Of 11,259 patients with T3BN0M0 HCC, 1,454 (12.9%) and 3,915 (34.7%) were treated with TARE and systemic therapy, respectively. The proportion of patients who received TARE increased from 13.0% in 2010 to 37.0% in 2017. Older age, white race, and receiving care at an academic cancer program were associated with receipt of TARE, whereas lack of insurance, higher model-for-end-stage-liver-disease score, Charlson comorbidity index of at least 3, and Northeast region were associated with receipt of systemic therapy. TARE was associated with reduced mortality compared with systemic therapy (adjusted hazard ratio, 0.74; 95% CI, 0.68–0.80), with consistent results observed in propensity-weighted analysis and across all examined subgroups. Conclusion: Use of TARE as first-line therapy for HCC with MVI has increased in the United States. Patient characteristics, region, and medical center type affected the use of TARE. TARE was associated with reduced mortality compared with systemic therapy for HCC patients with MVI.

Purpose This article presents our experience regarding survival benefits in inoperable intermediate stage hepatocellular carcinoma (HCC) and advanced stage HCC treated with 131I-lipiodol. Materials and Methods This is a retrospective study of intermediate stage HCC (Barcelona Clinic Liver Cancer [BCLC] stage B) not responding to prior treatment and/or advanced stage HCC (BCLC stage C) treated with 131I-lipiodol. 131I-lipiodol was injected into the hepatic artery through transfemoral route. Postprocedure, the patient was isolated for 5 to 7 days. All patients underwent tumor response evaluation after 4 weeks. Survival of patients was calculated up to either death or conclusion of the study. Results A total of 55 patients (52 males [94.5%], 3 females [5.4%]) were given intra-arterial 131I-lipiodol therapy. The median overall survival after transarterial radioembolization (TARE) was 172 ± 47 days (95% confidence limit, 79–264 days). The overall survival at 3, 6, 9, and 12 months was 69, 47, 32, and 29%, respectively. A multivariate Cox regression analysis showed the presence of treatment prior to TARE to most significantly influence survival (B = 2.161, p ≤ 0.001). This was followed by size of the lesion which was second in line (B = 0.536, p = 0.034). Among 45 patients, 14 patients (31.1%) showed a partial response, 11 patients (24.4%) showed stable disease, and 20 patients (44.4%) showed progressive diseases. Conclusion TARE with 131I-lipiodol can be a safe and effective palliative treatment in advanced stage HCC and in patients with poor response to prior treatments like transarterial chemoembolization.

Background Neoadjuvant yttrium-90 transarterial radioembolization (TARE) is increasingly being used as a strategy to facilitate resection of otherwise unresectable tumors due to its ability to generate both tumor response and remnant liver hypertrophy. Perioperative outcomes after the use of neoadjuvant lobar TARE remain underinvestigated. Methods A single center retrospective review of patients who underwent lobar TARE prior to major hepatectomy for primary or metastatic liver cancer between 2007 and 2018 was conducted. Baseline demographics, radioembolization parameters, pre- and post-radioembolization volumetrics, intra-operative surgical data, adverse events, and post-operative outcomes were analyzed. Results Twenty-six patients underwent major hepatectomy after neoadjuvant lobar TARE. The mean age was 58.3 years (17-88 years). 62% of patients (n=16) had primary liver malignancies while the remainder had metastatic disease. Liver resection included right hepatectomy or trisegmentectomy, left or extended left hepatectomy, and sectorectomy/segmentectomy in 77% (n=20), 8% (n=2), and 15% (n=4) of patients, respectively. The mean length of stay was 8.3 days (range, 3-33 days) and there were no grade IV morbidities or 90-day mortalities. The incidence of post hepatectomy liver failure (PHLF) was 3.8% (n=1). The median time to progression after resection was 4.5 months (range, 3.3-10 months). Twenty-three percent (n=6) of patients had no recurrence. The median survival was 28.9 months (range, 16.9-46.8 months) from major hepatectomy and 37.6 months (range, 25.2-53.1 months) from TARE. Conclusions Major hepatectomy after neoadjuvant lobar radioembolization is safe with a low incidence of PHLF.

Purpose Preoperative hypertrophy induction of future liver remnant (FLR) reduces the risk of postoperative liver insufficiency after partial hepatectomy. One of the most commonly used methods to induce hypertrophy of FLR is portal vein embolization (PVE). Recent studies have shown that transarterial radioembolization (TARE) also induces hypertrophy of the contralateral liver lobe. The aim of our study was to evaluate contralateral hypertrophy after TARE versus after PVE taking into account the effect of cirrhosis. Methods Forty-nine patients undergoing PVE before hemihepatectomy and 24 patients with TARE as palliative treatment for liver malignancy were retrospectively included. Semi-automated volumetry of the FLR/contralateral liver lobe before and after intervention (20 to 65 days) was performed on CT or MRI, and the relative increase in volume was calculated. Cirrhosis was evaluated independently by two radiologists on CT/MRI, and interrater reliability was calculated. Results Hypertrophy after PVE was significantly more pronounced than after TARE (25.3% vs. 7.4%; p p = 0.002), whereas in patients with cirrhosis, the difference was not statistically significant (18.2% vs. 7.4%; p = 0.212). After PVE, hypertrophy in patients without cirrhosis was more pronounced than in patients with cirrhosis (25.9% vs. 18.2%; p = 0.203), while after TARE, hypertrophy was comparable in patients with and without cirrhosis (7.4% vs. 8.6%; p = 0.928). Conclusion TARE induces less pronounced hypertrophy of the FLR compared to PVE. Cirrhosis seems to be less of a limiting factor for hypertrophy after TARE, compared to PVE. Graphic abstract

Background Children with unresectable hepatocellular carcinoma (HCC) have a poor prognosis and limited treatment options. Transarterial radioembolization (TARE) using Yttrium-90 (Y90) has emerged as a potential bridge therapy to hepatic resection or transplantation for HCC with very limited studies in children. Observations Here we present the clinical course of 2 children successfully treated with TARE Y90 for initially unresectable fibrolamellar HCC (FL-HCC) and bridged to partial hemihepatectomy with >1-year overall survival post-TARE. Conclusion Although there have been prior published reports of pediatric patients with HCC being treated with TARE Y90 and some being able to undergo subsequent orthotopic liver transplantation, this is the first report of pediatric HCC patients treated with TARE Y90 as a bridge to nontransplant resections and going on to have >1-year overall survival.

Purpose: Intrahepatic cholangiocarcinoma (ICC) has a poor prognosis, when unresectable; therefore, intra-arterial therapies (IAT) such as trans-arterial chemoembolization (TACE) and trans-arterial radioembolization (TARE) have been employed. With the present systematic review and meta-analysis, we aimed to analyse published studies to understand if one IAT can be superior to the alternative. Materials and methods: A systematic search of PubMed and Web of Science databases was performed for articles published until 1 March 2020 relevant to IAT for ICC. Overall survival was the primary end point. Occurrence of clinical adverse events and tumour overall response were secondary outcome measures. Results: A total of 31 articles (of 793, n.1695 patients) were selected for data extraction, 13 were on TACE (906 patients) and 18 were on TARE (789 patients). Clinical and tumour characteristics showed moderate heterogeneity between the two groups. The median survival after TACE was 14.2months while after TARE was 13.5months (95%C.I.: 11.4–16.1). The survival difference was small (d = 0.112) at 1year and negligible at 2years (d = 0.028) and at 3years (d = 0.049). The radiological objective response after TACE was 20.6% and after TARE was 19.3% (d = 0.032). Clinical adverse events occurred in 58.5% after TACE, more frequently than after TARE (43.0%, d = 0.314). Conclusion: In conclusion, IATs are promising treatments for improving outcomes for patients with unresectable ICC. To date, TACE and TARE provide similar good outcomes, except for adverse events. Therefore, the decision about techniques is determined by ability to utilize these resources and patient specific factors (liver function or lesion dimension).

Introduction and objective Neuroendocrine tumors (NETs) debut in 75% of cases with liver metastases (LMNETs), whose therapeutic approach includes surgical resection and liver transplantation, while liver radioembolization with 90Y-microspheres (TARE) is reserved for non-operable patients usually due to high tumor burden. We present the accumulated experience of 10 years inTARE treatment of LMNETs in order to describe the safety and the effectiveness of the oncological response in terms of survival, as well as to detect the prognostic factors involved. Material and methods Of 136 TARE procedures, performed between January 2006 and December 2016, 30 LMNETs (11.1%) were retrospectively analyzed. The study measures were: Tumor response, time to liver progression, survival at 3 and 5 years, overall mortality and mortality associated with TARE. The radiological response assessment was assessed using RECIST 1.1 and mRECIST criteria. Results An average activity of 2.4 ± 1.3 GBq of 90Y was administered. No patient presented postembolization syndrome or carcinoid syndrome. There were also no vascular complications associated with the procedure. According to RECIST 1.1 criteria at 6 months, 78.6% presented partial response and 21.4% stable disease, there was no progression or complete response (1 by mRECIST). Survival at 3 and 5 years was 73% in both cases. Conclusion TARE treatment with 90Y-microspheres in LMNETs, applied within a multidisciplinary approach, is a safe procedure, with low morbidity, capable of achieving a high rate of radiological response and achieving lasting tumor responses.

Background Resection is the foundation for cure for colorectal cancer (CRC) liver metastases; however, only 20% of patients are suitable for surgery. Those suitable would be considered for resection or local therapies before being considered for regional therapies. Noncurative treatment is usually systemic chemotherapy. For patients with liver-only or liver-predominant metastases that are unresectable, regional therapies [conventional transarterial chemoembolization (cTACE), drug-eluting bead transarterial chemoembolization (DEB-TACE), and transarterial radioembolization (TARE)] may be considered. We review the current evidence for regional therapies for CRC liver metastases. Patients and Methods Literature searches (January 2000 to March 2019 or January 2010 to March 2019 depending on the specific systematic review question) were conducted, including Medline, Embase, Cochrane Library, and 2018 American Society of Clinical Oncology (ASCO) abstracts. Results A total of 4100 articles were identified; 15 studies were included in the review. There were no comparative data regarding the resectable population. There was either insufficient evidence (cTACE or DEB-TACE) or evidence against (TARE) the addition of regional therapies to systemic therapy in the first line in the unresectable population. There was either no evidence (cTACE) or weak evidence (DEB-TACE or TARE) for the addition of regional therapies with or without systemic therapy in the second line or later in the unresectable population. Conclusion Limited evidence supports the delivery of percutaneous regional therapies in patients with unresectable CRC liver metastases. There are strong data demonstrating positive effects of TARE within the liver, but they do not translate to a benefit in patient-important outcomes. DEB-TACE appears to offer a survival benefit in the second-line setting, although the evidence is limited by small sample size and larger trials are needed.

Purpose: The careful evaluation of MDCT is an essential step for the treatment planning in pre-treatment imaging work-up for Trans-Arterial Radio Embolization (TARE). It may provide unique volumetric data (CTVs), which are information useful for an effective and safe TARE. The purpose of this study is to demonstrate that the radiographer is able to calculate CTVs of TARE simulation with the same precision as the interventional radiologist. Methods: This study retrospectively considers 17 consecutive patients (8 males, 9 females; mean age 66.3 ± 13.2 years) who underwent pre-treatment work-up for TARE, between May 2019 and February 2020 (trial ID:2234 - protocol). For each patient, four specific parameters are evaluated from MDCT achieved during treatment simulation: healthy liver volume (HLV), the whole hepatic parenchyma (THV = healthy liver and TTV = tumour) involved by TARE, and whole liver volume (WLV). Four independent observers—R1 (expert interventional radiologist), T1, T2, and T3 (radiographers, with different experiences in the field of interventional radiology)—are involved in the imaging analysed. Results: All the 4 observers detected the same number of hepatic lesion(s) per patient. Regarding the three radiographers, the intra-observer reliability for CTVs is very high 0.997 to 1.000 (95%CI). Also inter-observer reproducibility between radiographers is excellent regarding CTVs, 0.965 to 0.999 (95%CI). The accuracy of radiographer evaluation is very high 0.964 to 0.999 (95%CI). Conclusions and implications for practice: The high intra- and inter-observer reproducibility shows that a properly trained radiographers might have the same accuracy as interventional radiologists, in assessing liver CTV data for planning TARE.

Background: Trans-arterial radioembolization (TARE) has shown promising results in treating hepatocellular carcinoma (HCC). We identified independent predictors of radiological complete response (CR) in patients with intrahepatic HCC who were treated with TARE. Methods: Patients with intrahepatic HCC treated with TARE between 2011 and 2017 were recruited. CR was defined according to the modified Response Evaluation Criteria in Solid Tumors. Cox regression analysis was used to determine independent predictors of CR. Results: The median age of study participants (83 men and 19 women) was 64.3 years. The mean survival after TARE was 55.5 months, and 21 (20.6%) patients died during the study period. Patients who achieved CR (14 patients, 13.7%) had significantly higher serum albumin level (median 4.1 vs. 3.9 g/dL), lower total bilirubin level (median 0.6 vs. 0.7 mg/dL), lower aspartate aminotransferase level (median 30.0 vs. 43.0 IU/L), lower alkaline phosphatase level (median 79.0 vs. 103.0 IU/L), lower alpha-fetoprotein level (median 12.7 vs. 39.9 ng/mL), lower des-gamma-carboxyprothrombin level (median 575.5 vs. 2772.0 mAU/mL), lower model for end-stage liver disease (MELD) score (median 6.0 vs. 7.0), and smaller maximal tumor diameter (median 6.3 vs. 9.0 cm) compared to those who did not achieve CR (all p &lt, 0.005). Multivariate Cox regression analysis showed that lower MELD score (hazard ratio (HR) = 0.436, p = 0.015) and maximal tumor size &lt, 9 cm (HR = 11.180, p = 0.020) were independent predictors of an increased probability of radiological CR after TARE. Conclusions: Low MELD score and small maximal tumor size were independently associated with an increased probability of CR after TARE in patients with intrahepatic HCC.

Purpose Liver metastasis in genitourinary (GU) malignancies signifies a poor prognosis and has a negative effect on patient survival. Selected patients with metastatic GU malignancies have liver-dominant disease. Liver-directed therapies (LDT) with conventional transarterial chemoembolization (cTACE) and transarterial radioembolization (TARE) have been well studied in primary liver cancer and metastatic hepatic disease and proven to be safe and efficacious in selected populations. Materials and Methods From 2005 to 2016, 32 patients with metastatic renal, bladder, or prostate cancer and liver-dominant metastases treated with cTACE or TARE were identified. Retrospective review of patient records was performed to assess baseline characteristics, imaging treatment response, survival, and treatment toxicity. Results The median survival from diagnosis of liver metastasis was 37 months in renal cell carcinoma (RCC), 8 months in transitional cell carcinoma (TCC), and 6 months in prostate carcinoma. 90% of patients with RCC maintained their ECOG performance status one-month post-treatment, as did 64% of the bladder and prostate groups. LDT was well tolerated for the most part. Conclusion LDT in patients with metastatic GU cancer is well tolerated and can lead to improved survival for some patients. Further studies are necessary to determine which patients may benefit the most.

BACKGROUND: US contrast agents are gas-filled microbubbles (MBs) that can be locally destroyed by using external US. Among other bioeffects, US-triggered MB destruction, also known as UTMD, has been shown to sensitize solid tumors to radiation in preclinical models through localized insult to the vascular endothelial cells. PURPOSE: To evaluate the safety and preliminary efficacy of combining US-triggered MB destruction and transarterial radioembolization (TARE) in participants with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: In this pilot clinical trial, participants with HCC scheduled for sublobar TARE were randomized to undergo either TARE or TARE with US-triggered MB destruction 1–4 hours and approximately 1 and 2 weeks after TARE. Enrollment took place between July 2017 and February 2020. Safety of US-triggered MB destruction was evaluated by physiologic monitoring, changes in liver function tests, adverse events, and radiopharmaceutical distribution. Treatment efficacy was evaluated by using modified Response Evaluation Criteria in Solid Tumors (mRECIST) on cross-sectional images, time to required next treatment, transplant rates, and overall survival. Differences across mRECIST reads were compared by using a Mann-Whitney U test, and the difference in prevalence of tumor response was evaluated by Fisher exact test, whereas differences in time to required next treatment and overall survival curves were compared by using a log-rank (Mantel-Cox) test. RESULTS: Safety results from 28 participants (mean age, 70 years ± 10 [standard deviation]; 17 men) demonstrated no significant changes in temperature (P = .31), heart rate (P = .92), diastolic pressure (P = .31), or systolic pressure (P = .06) before and after US-triggered MB destruction. No changes in liver function tests between treatment arms were observed 1 month after TARE (P > .15). Preliminary efficacy results showed a greater prevalence of tumor response (14 of 15 [93%; 95% CI: 68, 100] vs five of 10 [50%; 95% CI: 19, 81]; P = .02) in participants who underwent both US-triggered MB destruction and TARE (P = .02). CONCLUSION: The combination of US-triggered microbubble destruction and transarterial radioembolization is feasible with an excellent safety profile in this patient population and appears to result in improved hepatocellular carcinoma treatment response. © RSNA, 2020

Background/aim To evaluate the predictive value of metabolic activity assessed by 18 F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in patients with hepatocellular carcinoma (HCC) undergoing Yttrium-90 (Y-90) transarterial radioembolization (TARE). Methods Between 2009 and 2013, a total of 40 patients with HCC were treated with Y-90 TARE. Before each treatment, 18 F-FDG PET/CT was performed. Maximum standardized uptake value (SUVmax) and tumor-to-non-tumorous liver uptake ratio (TLR; tumor SUVmax/non-tumorous liver mean SUV) were measured for each patient. Tumor response was evaluated in accordance with modified RECIST criteria at 3-month intervals after Y-90 TARE. Statistical analysis was performed using the chi-squared test, Kaplan-Meier analysis, and the Cox proportional hazards model. Results The median patient age was 56.5 years. Twenty-nine patients (72.5%) were men; 36 patients (90.0%) were classified as Child-Pugh class A. Thirty-three patients (82.5%) showed disease control in treated lesions at 3 months after Y-90 TARE. Eleven patients (27.5%) showed progression-free survival. However, low and high TLR (relative to the median value of 2.1) did not affect rates of disease control, progression-free survival, or overall survival. No predictive factors could be identified for disease progression or death in patients with HCC undergoing Y-90 TARE. Conclusions TLR-based stratification is a simple method, but it may not be useful in treatment planning for HCC patient undergoing Y-90 TARE. Further studies with large number of patients are needed.

Transarterial radioembolization (TARE) with yttrium-90 (90Y) microspheres is a liver-directed treatment for primary and secondary hepatic malignancies. Personalized dosimetry aims for maximum treatment effect and reduced toxicity. We aimed to compare pre-treatment voxel-based dosimetry from 99mTc macroaggregated albumin (MAA) SPECT/CT with post-treatment 90Y PET/CT for absorbed dose values, and to evaluate image quality of 90Y SiPM-based PET/CT. Forty-two patients (28 men, 14 women, mean age: 67 ± 11 years) with advanced hepatic malignancies were prospectively enrolled. Twenty patients were treated with glass and 22 with resin microspheres. Radiation absorbed doses from planning 99mTc-MAA SPECT/CT and post-therapy 90Y PET/CT were assessed. 90Y PET/CT images were acquired for 20 min and reconstructed to produce 5-, 10-, 15-, and 20-min datasets, then evaluated using the 5-point Likert scale. The mean administered activity was 3.44 ± 1.5 GBq for glass and 1.62 ± 0.7 GBq for resin microspheres. The mean tumor absorbed doses calculated from 99mTc-MAA SPECT/CT and 90Y PET/CT were 175.69 ± 113.76 Gy and 193.58 ± 111.09 Gy (P = 0.61), respectively for glass microspheres; they were 60.18 ± 42.20 Gy and 70.98 ± 49.65 Gy (P = 0.37), respectively for resin microspheres. The mean normal liver absorbed doses from 99mTc-MAA SPECT/CT and 90Y PET/CT were 32.70 ± 22.25 Gy and 30.62 ± 20.09 Gy (P = 0.77), respectively for glass microspheres; they were 18.33 ± 11.08 Gy and 24.32 ± 15.58 Gy (P = 0.17), respectively for resin microspheres. Image quality of 90Y PET/CT at 5-, 10-, 15-, and 20-min scan time showed a Likert score of 3.6 ± 0.54, 4.57 ± 0.58, 4.84 ± 0.37, and 4.9 ± 0.3, respectively. 99mTc-MAA SPECT/CT demonstrated great accuracy for treatment planning dosimetry. SiPM-based PET/CT scanner showed good image quality at 10-min scan time, acquired in one bed position. A PET/CT scan time of 5 min showed acceptable image quality and suffices for dosimetry and treatment verification. This allows for inclusion of 90Y PET/CT in busy routine clinical workflows. Studies with larger patient cohorts are needed to confirm these findings.

Transarterial radioembolization (TARE) is one of the therapeutic options for hepatocellular carcinoma (HCC). This study aimed to investigate the predictors and prognostic values of achieving curative treatments after TARE. Overall, 143 patients with intrahepatic HCC treated with TARE between 2011 and 2017 were recruited from two Korean tertiary institutes. Twenty-seven patients received curative treatments after TARE. Younger age than 65 years and AFP of ≤200 ng/mL independently predicted the increased probability of achieving curative treatment after TARE, and the curative treatment after TARE provided a survival benefit in patients with intrahepatic HCC.

Studies have shown intra-arterial therapies to be effective in controlling neuroendocrine liver metastases (NELMs), but the evidence supporting the selection of specific methods is limited. This meta-analysis is the first to compare survival outcomes between transarterial chemoembolization (TACE) and transarterial radioembolization (TARE) in the treatment of NELM. A systematic search according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in PubMed and Embase databases was conducted in February 2020 for published studies comparing survival outcomes between TACE and TARE in the treatment of NELM. Six eligible cohort studies with a total of 643 patients were identified. The TACE and TARE groups were similar in terms of age, sex, hepatic tumor burden, tumor grade, and Eastern Cooperative Oncology Group (ECOG) score. The patients treated with TACE had significantly better overall survival (odds ratio [OR], 1.92; 95% confidence interval [CI] 1.14–3.22, p = 0.014) than those treated with TARE. Overall survival ranged from 16.8 to 81.9 months with TACE and from 14.5 to 66.8 months with TARE. No significant differences in hepatic progression-free survival (OR, 1.01; 95% CI 0.75–1.35; p = 0.96) or tumor response were observed within the first 3 months (OR, 2.87; 95% CI 0.81–10.21; p = 0.10) or thereafter (OR, 0.98; 95% CI 0.12–7.86; p = 0.99). The complication rates were similar between the two groups, with 6.9% of the TACE patients versus 8.5% of TARE patients reporting major complications (OR, 1.16; 95% CI 0.54–2.48; p = 0.71) and respectively 44.6% and 58.8% of the TACE and TARE patients reporting minor adverse events (OR, 1.08; 95% CI 0.39–2.99; p = 0.88). Despite similar tumor responses, an overall survival benefit was associated with TACE treatment of NELM compared with TARE treatment. Randomized controlled trials are warranted to confirm this finding and clarify whether certain subpopulations benefit from different transarterial methods.

Infiltrative-appearance hepatocellular carcinoma presents a challenge to clinicians as diagnostic criteria continue to evolve and evidence-based treatment guidelines have yet to be established. While transarterial radioembolization has shown efficacy in hepatocellular carcinoma, many studies exclude infiltrative-appearance HCC in their analysis. The purpose of this study was to describe imaging features of infiltrative-appearance hepatocellular carcinoma and evaluate effects of radioembolization on survival. In a retrospective review, infiltrative HCC patients treated from 2008 to 2017 were identified. Patients were divided into two groups: TARE versus systemic therapy/palliative care. Demographics, dates of diagnosis/expiry, albumin, international normalized ratio (INR), sodium, alpha-fetoprotein (AFP), creatinine, Child-Pugh class, model for end-stage liver disease (MELD) score, bilirubin, radiation dose and volume were collected. Patients with bilirubin > 3 were excluded. Mann–Whitney U test and Fisher’s exact test assessed differences between groups. Kaplan–Meier survival and Cox proportional hazard analyses were performed. Fifty-three patients were identified, 15 underwent TARE while 38 served as control. Mean age was 60, 43 patients were male. The mean overall survival was 16.2 months for the TARE group and 5.3 months for the control group (Log-rank p

Treatment for hepatocellular carcinoma (HCC) has experienced major advancements since the last update of the official Barcelona Clinic Liver Cancer (BCLC) prognosis and treatment strategy published in 2018. Advancements in the field have emerged in all areas, but in this manuscript, we present those that have primed a change in the strategy and comment why some encouraging data in select interventions are still considered immature and in need of further research to gain their incorporation into an evidence-based model for clinicians and researchers. Finally, we describe the critical insight and expert knowledge that is needed to take clinical decisions in individual patients so that the recommendation takes into account all the needed parameters to allow a personalised approach.

To analyze hepatobiliary specific contrast agent (HBA) dynamic MRI signal intensity (SI) differences between treated liver (TL) and untreated liver (UL) parenchyma in patients following transarterial radioembolization (TARE) for hepatocellular carcinoma (HCC) using yttrium-90 containing glass microspheres. This was a single institution retrospective study of patients with HCC treated with lobar or segmental TARE who received pre- and post-treatment HBA multiphase MRI within a 3-year period. Patients with prior locoregional therapies or multiple TAREs were excluded. SI was obtained by drawing a 2D ROI on T1-weighted non-contrast, arterial (25 s.), portal venous (60 s.), transitional (180 s.), and hepatobiliary (HB) (1200 s.) phase sequences in the (TL) angiosome and UL. HB phase signal enhancement characteristics were correlated with TARE dose thresholds ( 190 Gy) using the medical internal radiation dose (MIRD) methodology. 282 patients received TARE using glass microspheres during the study period and 58 patients who met inclusion criteria were analyzed. Median dose was 141.5 Gy MIRD [IQR 122.0, 161.5; range 100–540 Gy]). Statistically significant differences were present between treated and non-treated liver on non-contrast (− 28.0, p = 0.003), arterial (38.5, p = 0.013), and HB phases (− 95.8, p ≤ 0.001). Median follow-up time to furthest post-treatment MRI was 6 months (range 3-11 months). There was no significant SI difference on portal venous or transitional phases. HB phase SI changes in the TL compared to UL were significant at all TARE dose thresholds (p < 0.05). SI differences between treated and untreated liver after TARE are most significant on the HB phase and present at all evaluated dose levels at a median of 6 months after treatment. These findings support the parenchymal ablative potential for TARE and the necessity to consider liver function loss within targeted liver volumes.

Backgrounds/aims To evaluate our initial experience of bridging role of trans-arterial radio-embolization (TARE) before major hepatectomy for hepatocellular carcinoma (HCC) in risky patients with small expected remnant liver volume (ERLV). Methods We reviewed the data of patients with HCC who underwent major hepatectomy after TARE during the period between March and December 2017. Patients included had uni-lobar large HCC (＞5 cm) requiring major hepatectomy with small ERLV. Results Five patients were included in our study. All patients were Child Pugh class A. A single session of TARE was applied in all patients. None developed any adverse events related to irradiation. The mean tumor size at baseline was 8.4 cm and 6.1 cm after TARE (p=0.077). The mean % of tumor shrinkage was 24.5%. ERLV improved from 354.6 ml at baseline to 500.8 ml after TARE (p=0.012). ERLV percentage improved from 27.2% at baseline to 38.1% after TARE (p=0.004). The mean % of ERLV was 39.5%. The mean interval time between TARE and resection was 99.6 days. Four patients (80%) underwent right hemi-hepatectomy and one patient (20%) underwent extended right hemi-hepatectomy. The mean operation time was 151 minutes, and mean blood loss was 56 ml. The mean hospital stay was 13.8 days, and one patient (20%) developed postoperative morbidity. After a mean follow-up of 15 months, all patients were alive with no recurrence. Conclusions Yttrium-90 TARE can play a bridging role before major hepatectomy for borderline resectable HCC in risky patients with small ERLV.

The evolution of locoregional therapies in the last decade has been refined with improved patient selection and a development of a more personalized approach. In doing so, there has been associated improved outcomes and less toxicity. With the rapidly changing landscape of systemic therapy, the role of locoregional therapies alone or in combination for downstaging and curative intent will continue to evolve.

Atypical meningioma (AM) (WHO-II) has a recurrence rate of 28% after gross total resection (GTR) with limited salvage options. Transarterial therapies may provide treatment opportunities in AM patients who exhausted standard-of-care therapy. In cases where favorable tumor vasculature and particle simulation demonstrate acceptable target dose, Yttrium-90 trans-arterial radioemobilization (TARE) could theoretically provide salvage therapy. A 67-year-old man presented with recurrent AM post gross total resection with adjuvant radiotherapy in 2012, 2014, and 2016. The patient was deemed a poor candidate for additional therapies. Tumor vasculature mapping was performed to determine TARE candidacy. Super-selective angiography and contrast-enhanced cone-beam computed tomography angiosomes demonstrated predominant pial collaterals and minor supply from a middle meningeal artery branch. Particle simulation was performed by infusing 0.3 mCi of 99mTc-macroaggregated albumin (99mTc-MAA). SPECT/CT-MRI fusion demonstrated conformal activity solely within the tumor volume perfused by the middle meningeal artery branch with a lung shunt fraction of 54.7%. The patient subsequently received off-label Nivolumab (PD-1 inhibitor). Mapping angiography for AM using 99mTc-MAA is feasible. It may identify candidates for TARE and potential AM patients with favorable blood supply. The potential for conformal intracranial vascular brachytherapy is intriguing, however, altered arterial supply in recurrent tumors is challenging.

A mechatronic rail vehicle with reduced tare weight, two axles and only one level of suspension is proposed with the objective of reducing investment and maintenance costs. A wheelset to carbody connection frame in composite material will be used both as structural and as suspension element. Active control is introduced to steer the wheelsets and improve the curving performance. A feedforward control approach for active curve steering based on non-compensated lateral acceleration and curvature is proposed to overcome stability issues of a feedback approach. The feedforward approach is synthesised starting from the best achievable results of selected feedback approaches in terms of wheel energy dissipation and required actuation force. A set of 357 running cases (embracing 7 curves, 17 speeds per curve and 3 conicities) is used to design the controller. The controller is shown to perform well for conicity and track geometry variations and under the presence of track irregularities. QC 20201007

Purpose To compare the manifestations of chronic liver injury following transarterial chemoembolization with those of transarterial radioembolization (TARE) in patients with neuroendocrine tumor (NET). Materials and Methods This study consisted of an Institutional Review Board-approved single-institution retrospective analysis of NET patients who received transarterial chemoembolization from 2006 to 2016 and TARE from 2005 to 2014 and survived at least 1 year from the initial treatment. Patients receiving only transarterial chemoembolization (n = 63) or TARE (n = 28) were evaluated for the presence or absence of durable hepatic toxicities occurring at least 6 months after initial treatment. The definitions and grades of liver injury were adapted from Common Terminology Criteria for Adverse Events version 4.0 and were characterized by the presence of laboratory or clinical toxicities of Grade 3 or above. Results Chronic hepatic toxicity occurred in 14 of 63 transarterial chemoembolization patients (22%) with a total of 26 Grade 3-4 events, in whom elevation of bilirubin was the most common toxicity, compared to 8 of 28 TARE patients (29%) with a total of 16 Grade 3-4 and 2 Grade 5 events, in whom ascites were the most frequent toxicity. There were more laboratory toxicities in the transarterial chemoembolization group (65% vs 38%, P = .11) and fewer Grade 4–5 injuries (6% vs 27% of patients, P = .06). There was also a significantly higher number of patients who experienced intrahepatic progression of disease in the transarterial chemoembolization cohort than in the TARE patients (75% vs 43%, respectively; P = .005). Conclusions Delayed hepatotoxicity from transarterial chemoembolization and TARE occurred in 22% and 29% of patients, respectively, from 6 months to several years following treatment. Transarterial chemoembolization-related toxicities on average were less severe and manifested primarily as laboratory derangements, compared to TARE toxicities which consisted of clinical hepatic decompensation.

Fibrolamellar hepatocellular carcinoma (FL-HCC) is a rare primary liver tumor that typically presents at an advanced stage in early adolescents and adults with no underlying liver disease. Surgical resection is the first-line treatment, and patients who are not surgical candidates face limited treatment options with poor long-term outcomes. Herein we report the first documented, technically successful treatment of FL-HCC with extrahepatic spread using transarterial radioembolization (TARE) in a 16-year-old male patient with surgically unresectable disease. Subsequent imaging revealed tumor necrosis and a 20% reduction in size, and the patient survived 20 months post-treatment, a marked improvement relative to historical data in the literature. Further research should examine the potential role of yttrium-90 TARE in the treatment of FL-HCC patients with metastatic disease.

Transarterial radioembolization (TARE) with yttrium-90 microspheres has become widely utilized in managing hepatocellular carcinoma (HCC). The utility of TARE is expanding with new insights through experiences from real-world practice and clinical trials, and recently published data suggest that TARE in combination with sorafenib may improve the overall survival in selected patients. Here, we report a case of advanced stage HCC that was successfully treated with TARE and sorafenib. The patient achieved complete response (CR) at 12 months after the initial treatment with TARE and sorafenib, followed by additional transarterial chemoembolization and proton beam therapy for local tumor recurrence at 19-month post-TARE. The patient was followed up every 3 months thereafter and still achieved CR both biochemically and radiologically for the following 12 months. A combination strategy of TARE and systemic therapy may be a useful alternative treatment option for selected patients with advanced stage HCC. (J Liver Cancer 2020;20:160-166)

Purpose To assess the overall survival (OS) and progression-free survival (PFS) of unresectable hepatocellular carcinoma (HCC) patients undergoing yttrium-90 glass-microsphere transarterial radioembolization (TARE) with and without concurrent sorafenib. Methods OS and PFS were analyzed in 55 patients with an intrahepatic tumor (IHT) ≤50% without advanced or aggressive disease features (ADFs), which was referred to presence of infiltrative/ill-defined HCC, macrovascular invasion, or extrahepatic disease treated with only TARE (TARE_alone) and in 74 patients with IHT ≤50% with ADFs or IHT >50% treated with TARE and sorafenib (TARE_sorafenib). Prognostic factors for OS and PFS were identified using univariate and multivariate analyses. Results Median OS and PFS of TARE_alone patients were 21.6 (95% CI 6.1-37.1) and 9.1(95% CI 5.2-13.0) months, respectively, and for TARE_sorafenib patients 12.4 (95% CI 9.1-15.6) and 5.1 (95% CI 2.6-7.5) months, respectively. Better OS was associated with serum AFP

Background Little is known about factors that influence the efficacy of transarterial radioembolization (TARE). Purpose To determine the relationship between tumor radiation-absorbed dose and survival and tumor response in locally advanced inoperable hepatocellular carcinoma treated with TARE. Materials and Methods This was a secondary analysis of prospectively acquired data (between December 2011 and March 2015) from participants who received TARE in the Sorafenib versus Radioembolization in Advanced Hepatocellular Carcinoma (SARAH) trial (ClinicalTrials.gov identifier: NCT01482442). Tumor-absorbed dose was computed using technetium 99m (99mTc) macroaggregated human albumin (MAA) SPECT/CT. Visual agreement among CT, 99mTc-MAA SPECT/CT, and yttrium 90 (90Y) SPECT/CT or PET/CT was scored as optimal, suboptimal, or not optimal. Overall survival (OS) and tumor response at 6-month follow-up CT (Response Evaluation Criteria in Solid Tumors, version 1.1) were assessed. OS was evaluated using Kaplan-Meier tests. A propensity score comparing participants receiving a tumor dose greater than or equal to 100 Gy (best cut-off according to the receiver operating characteristic curve and median tumor radiation-absorbed dose values in the study groups) with those receiving sorafenib was calculated. Results One hundred twenty-one participants (median age, 67 years; interquartile range [IQR]: 61-73 years; 110 men) were evaluated in the dose-survival group, and 109 (median age, 66 years; IQR: 61-71 years; 100 men) were evaluated in the dose-tumor response group. In the dose-survival group, median OS was 9.3 months (95% confidence interval [CI]: 6.7 months, 10.7 months), and median tumor radiation-absorbed dose was 112 Gy (IQR: 68-220 Gy). Participants who received at least 100 Gy (n = 67) had longer survival than those who received less than 100 Gy (median, 14.1 months [95% CI: 9.6 months, 18.6 months] vs 6.1 months [95% CI: 4.9 months, 6.8 months], respectively; P < .001), and those with optimal agreement (n = 24) had the longest median OS (24.9 months; 95% CI: 9.6 months, 33.9 months). In the dose-tumor response group, tumor radiation-absorbed dose was higher in participants with disease control versus those with progressive disease (median, 121 Gy [IQR: 86-190 Gy] vs 85 Gy [IQR: 58-164 Gy]; P = .02). The highest disease control rate was observed in 31 of 40 participants (78%) with a tumor radiation-absorbed dose greater than or equal to 100 Gy and optimal agreement. Conclusion Higher tumor radiation-absorbed dose computed at technetium 99m macroaggregated human albumin SPECT/CT was associated with better overall survival and disease control in hepatocellular carcinoma treated with transarterial radioembolization with yttrium 90 in the Sorafenib versus Radioembolization in Advanced Hepatocellular Carcinoma trial. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Sofocleous and Kamarinos in this issue.

In this review we summarize the current evidence on the role of PET/CT with different probes for radioembolization therapy monitoring in HCC patients. Typical clinical examples are also provided to underline the utility of choline PET in this context. PubMed database was searched from 2000 until March 2020. Overall, 11C-acetate and radiolabeled choline PET have a higher sensitivity in the diagnosis of primary or recurrent HCC as compared to 18F-FDG. On the other hand, 18F-FDG PET/CT can provide useful prognostic information, especially for palliative treatments. Radiolabeled choline better predicts response to loco-regional treatment and provides a better differentiation of disease recurrence from treatment-related changes, as compared to other morphological imaging. HCC staging is better performed with PET/CT, thus allowing for a more adequate selection of patients candidate to transarterial radioembolization.

Background Transarterial radioembolization (TARE) is a locoregional minimally invasive therapeutic strategy to treat primary and secondary hepatic neoplasia. Aim The objective was to assess TARE-induced immuno-oncological effects and its perspective for potential therapy improvement by using a combinatory strategy with immune checkpoint inhibitors (ICI). Results Yttrium-90 (90Y) TARE is used in patients with persisting liver function as the first- and second-line treatment for cholangiocarcinoma and hepatocellular carcinoma and chemotherapy refractory liver metastasis of different primaries. Combination therapy with 90Y TARE and ICI may synergistically improve antitumoral immunity and patient outcome. Currently, there are no clinical studies with published data regarding this combination therapy and the subsequently induced immunological effects. Clinical data on other isotopes, e.g., holmium-166 (166Ho), are also lacking. Conclusion The clinical evidence of combined treatment with TARE and ICI must be considerably improved. This innovative therapy concept must be studied in new trials assessing the immunological data, including cellular phenotypes, activation, functions, and biomarkers. This may provide valid, sensitive, and specific models in order to evaluate the optimal therapy concept and/or the therapy combination for the best patient outcome.

OBJECTIVE. Treatment options for hepatocellular carcinoma (HCC) continue to expand. However, given the complexity of the patients including factors such as codominant cirrhosis or portal hypertension and transplant status, it can be difficult to know which treatment is most advantageous. The choice of HCC treatment is perhaps most complex in the setting of HCCs that are 3-5 cm. This article reviews the evidence for locoregional therapies in treating 3- to 5-cm HCCs. CONCLUSION. Combination therapy with transarterial chemoembolization (TACE) and ablation has the most robust and highest level of evidence to support its efficacy and therefore should be considered first-line therapy for nonresectable HCCs that measure 3-5 cm. The studies support that TACE followed by ablation is superior to either TACE alone or ablation alone. Data for transarterial radioembolization (TARE) to treat HCCs in this specific size range are very limited. Additional data are needed about the comparative effectiveness of TACE-ablation combination and TARE and how the TACE-ablation combination compares with surgical resection.

Objectives Yttrium-90 transarterial radioembolization (TARE) is a safe, effective modality of locoregional therapy for intermediate and advanced-stage hepatocellular carcinoma (HCC). We aim to identify novel predictors of important outcomes of TARE therapy. Methods A single-center retrospective study of 166 patients treated with TARE for HCC at Mayo Clinic Rochester between 2005-2015 and followed until December 2017. Multivariate logistic and stepwise regression analysis models were used to identify variables associated with overall survival (OS) and progression-free survival (PFS). Results The median OS and the median PFS were12.9 (95% CI: 11.0-17.3), and 8 months (95% CI: 6-11), respectively. Macrovascular invasion (HR: 1.9 [1.3-2.8]), Child-Pugh score (CPS) B or C vs. A (HR: 1.8 [1.2-2.7]), Eastern Cooperative Oncology Group Performance status (ECOG-PS) 2 or 1 vs. 0 (HR: 1.6 [1.1-2.4]) and activity (A) of administered radiation dose (HR: 1.005[1.00-1.010), independently correlated with poorer OS. Infiltrative HCC (HR: 2.4 [1.3-4.5), macrovascular invasion (HR: 1.6 [1.1-2.7]), and high activity of administered radiation dose (HR: 1.005 [1.00-1.010) were associated with worse PFS. Conclusion In HCC patients treated with TARE; macrovascular invasion, the activity of radiation dose, CPS, ECOG-PS, and infiltrative HCC predict OS and PFS.

Background & Aims Pre-treatment Tc-99m macroaggregated albumin (MAA) scans are routinely performed prior to transarterial radioembolization (TARE) to estimate lung shunt fraction (LSF) and lung dose. In this study, we investigate LSF observed in early hepatocellular carcinoma (HCC) and provide the scientific rationale for eliminating this step from routine practice. Methods Patients with HCC who underwent Y90 from 2004 to 2018 were reviewed. Inclusion criteria were early stage HCC (UNOS T1/T2/Milan criteria: solitary ≤5 cm, 3 nodules ≤3 cm). LSF was determined using MAA in all patients. Associations between LSF and baseline characteristics were investigated. A “no-MAA” paradigm was then proposed based on a homogenous group that expressed very low LSF. Results Of 1,175 patients with HCC treated with TARE, 448 patients met inclusion criteria. Mean age was 65.6 years and 303 (68%) were males. A total of 352 (79%) had solitary lesions and 406 (91%) unilobar disease. Two-hundred and forty-three (54%), 178 (40%) and 27 (6%) patients were Child-Pugh class A, B and C, respectively. Median LSF was 3.9% (IQR 2.4–6%). Median administered activity was 0.9 GBq (IQR 0.6–1.4), for a median segmental volume of 170 cm3 (range: 60–530). Median lung dose was 1.9 Gy (IQR: 1.0–3.3). The presence of a transjugular intrahepatic portosystemic shunt (TIPS; n = 38) was associated with LSF >10% (odds ratio 12.2; 95% CI 5.2–28.6; p Conclusion LSF is clinically negligible in patients with UNOS T1/T2 HCC without TIPS. When segmental injections are planned, this step can be eliminated, thereby reducing time-to-treatment, number of procedures, and improving convenience for patients traveling from faraway. Lay summary Transarterial radioembolization is a microembolic transarterial treatment for hepatocellular carcinoma. In our study, we found that early stage patients, where segmental injections are planned, exhibited low lung shunting, effectively eliminating the risk of radiation pneumonitis. We propose that the lung shunt study be eliminated in this subgroup, thus leading to fewer procedures, a cost reduction and improved convenience for patients.

Transarterial radioembolization (TARE) is, by all standards, a radiation therapy. As such, according to Euratom Directive 2013/59, it should be optimized by a thorough treatment plan based on the distinct evaluation of absorbed dose to the lesions and to the non-tumoural liver (two-compartment dosimetry). Since the dosimetric prediction with 99mTc albumin macro-aggregates (MAA) of non-tumoural liver is much more accurate than the same prediction on lesions, treatment planning should focus on non-tumoural liver rather than on lesion dosimetry. The aim of this study was to determine a safety limit through the analysis of pre-treatment dosimetry with 99mTc-MAA single photon emission computed tomography (SPECT/CT), in order to deliver the maximum tolerable absorbed dose to non-tumoural liver. Data from intermediate/advanced hepato-cellular carcinoma (HCC) patients treated with 90Y glass microspheres were collected in this single-arm retrospective study. Injection was always lobar, even in case of bilobar disease, to avoid treating the whole liver in a single session. A three-level definition of liver decompensation (LD) was introduced, considering toxicity only in cases of liver decompensation requiring medical action (LD type C, LDC). We report LDC rates, receiver operating characteristic (ROC) analysis between LDC and NO LDC absorbed dose distributions, normal tissue complication probability (NTCP) curves and uni- and multivariate analysis of risk factors associated with toxicity. A 6-month timeline was defined as necessary to capture all treatment-related toxicity events. Previous transarterial chemoembolization (TACE), presence or extension of portal vein tumoural thrombosis (PVTT) and tumour pattern (nodular versus infiltrative) were not associated with tolerance to TARE. On the contrary, at the multivariate analysis, the absorbed dose averaged over the whole non-tumoural liver (including the non-injected lobe) was a prognostic indicator correlated with liver decompensation (odds ratio = 4.24). Basal bilirubin > 1.1 mg/dL was a second even more significant risk factor (odds ratio = 6.35). NTCP analysis stratified with this bilirubin cut-off determined a 15% liver decompensation risk at 50 Gy/90 Gy for bilirubin >/