Transarterial Radioembolization Treatment Research Articles

Y-90 Radioembolization and PD-1 Inhibitor as Neoadjuvant Treatment in Hepatocellular Carcinoma.

This study showcases a comprehensive treatment protocol for high-risk hepatocellular carcinoma (HCC) patients, focusing on the combined use of Y-90 transarterial radioembolization (TARE) and Programmed Cell Death-1 (PD-1) inhibitors as neoadjuvant therapy. Highlighted through a case report, it offers a step-by-step reference for similar therapeutic interventions. A retrospective analysis was conducted on a patient who underwent hepatectomy following Y-90 TARE and PD-1 inhibitor treatment. Key demographic and clinical details were recorded at admission to guide therapy selection. Y-90 TARE suitability and dosage calculation were based on Technetium-99m (Tc-99m) macroaggregated albumin (MAA) perfusion mapping tests. Lesion coverage by Y-90 microspheres was confirmed through single photon emission computed tomography/computed tomography (SPECT/CT) fusion imaging, and adverse reactions and follow-up outcomes were meticulously documented. The patient, with a 7.2 cm HCC in the right hepatic lobe (T1bN0M0, BCLC A, CNLC Ib) and an initial alpha-fetoprotein (AFP) level of 66,840 ng/mL, opted for Y-90 TARE due to high recurrence risk and initial surgery refusal. The therapy's parameters, including the lung shunting fraction (LSF) and non-tumor ratio (TNR), were within therapeutic limits. A total of 1.36 GBq Y-90 was administered. At 1 month post-therapy, the tumor shrank to 6 cm with partial necrosis, and AFP levels dropped to 21,155 ng/mL, remaining stable for 3 months. After 3 months, PD-1 inhibitor treatment led to further tumor reduction to 4 cm and AFP decrease to 1.84 ng/mL. The patient then underwent hepatectomy; histopathology confirmed complete tumor necrosis. At 12 months post-surgery, no tumor recurrence or metastasis was observed in follow-up sessions. This protocol demonstrates the effective combination of Y-90 TARE and PD-1 inhibitor as a bridging strategy to surgery for HCC patients at high recurrence risk, providing a practical guide for implementing this approach.

Role of Flex-Dose Delivery Program in Patients Affected by HCC: Advantages in Management of Tare in Our Experience.

Background: Introduced in the latest BCLC 2022, endovascular trans-arterial radioembolization (TARE) has an important role in the treatment of unresectable hepatocellular carcinoma (HCC) as a "bridge" or "downstaging" of disease. The evolution of TARE technology allows a more flexible and personalized target treatment, based on the anatomy and vascular characteristics of each HCC. The flex-dose delivery program is part of this perspective, which allows us to adjust the dose and its radio-embolizing power in relation to the size and type of cancer and to split the therapeutic dose of Y90 in different injections (split-bolus). Methods: From January 2020 to January 2022, we enrolled 19 patients affected by unresectable HCC and candidates for TARE treatment. Thirteen patients completed the treatment following the flex-dose delivery program. Response to treatment was assessed using the mRECIST criteria with CT performed 6 and 9 months after treatment. Two patients did not complete the radiological follow-up and were not included in this retrospective study. The final cohort of this study counts eleven patients. Results: According to mRECIST criteria, six months of follow-up were reported: five cases of complete response (CR, 45.4% of cases), four cases of partial response (PR, 36.4%), and two cases of progression disease (PD, 18.2%). Nine months follow-up reported five cases of complete response (CR, 45.4%), two cases of partial response (PR, 18.2%), and four cases of progression disease (PD, 36.4%). No intra and post-operative complications were described. The average absorbed doses to the hepatic lesion and to the healthy liver tissue were 319 Gy (range 133-447 Gy) and 9.5 Gy (range 2-19 Gy), respectively. Conclusions: The flex-dose delivery program represents a therapeutic protocol capable of "saving" portions of healthy liver parenchyma by designing a "custom-made" treatment for the patient.

MIDOS: a novel stochastic model towards a treatment planning system for microsphere dosimetry in liver tumors.

Transarterial radioembolization (TARE) procedures treat liver tumors by injecting radioactive microspheres into the hepatic artery. Currently, there is a critical need to optimize TARE towards a personalized dosimetry approach. To this aim, we present a novel microsphere dosimetry (MIDOS) stochastic model to estimate the activity delivered to the tumor(s), normal liver, and lung. MIDOS incorporates adult male/female liver computational phantoms with the hepatic arterial, hepatic portal venous, and hepatic venous vascular trees. Tumors can be placed in both models at user discretion. The perfusion of microspheres follows cluster patterns, and a Markov chain approach was applied to microsphere navigation, with the terminal location of microspheres determined to be in either normal hepatic parenchyma, hepatic tumor, or lung. A tumor uptake model was implemented to determine if microspheres get lodged in the tumor, and a probability was included in determining the shunt of microspheres to the lung. A sensitivity analysis of the model parameters was performed, and radiation segmentectomy/lobectomy procedures were simulated over a wide range of activity perfused. Then, the impact of using different microspheres, i.e., SIR-Sphere®, TheraSphere®, and QuiremSphere®, on the tumor-to-normal ratio (TNR), lung shunt fraction (LSF), and mean absorbed dose was analyzed. Highly vascularized tumors translated into increased TNR. Treatment results (TNR and LSF) were significantly more variable for microspheres with high particle load. In our scenarios with 1.5 GBq perfusion, TNR was maximum for TheraSphere® at calibration time in segmentectomy/lobar technique, for SIR-Sphere® at 1-3 days post-calibration, and regarding QuiremSphere® at 3 days post-calibration. This novel approach is a decisive step towards developing a personalized dosimetry framework for TARE. MIDOS assists in making clinical decisions in TARE treatment planning by assessing various delivery parameters and simulating different tumor uptakes. MIDOS offers evaluation of treatment outcomes, such as TNR and LSF, and quantitative scenario-specific decisions.

Influencing factors of lung shunt fraction in transarterial radioembolization treatment

Influencing factors of lung shunt fraction in transarterial radioembolization treatment

A personalized Monte Carlo study of tumor and critical organ doses for Trans-arterial Radioembolization patients.

Trans-arterial Radioembolization (TARE) is an intra-arterial treatment method for liver malignancies. In this procedure, the therapeutic tumor dose is significant for predicting the treatment effectiveness while the dose absorbed in an organ at risk provides an understanding of its tolerance to radiation. This study proposes a Monte Carlo (MC) approach for determining absorbed organ doses for patients undergoing TARE treatment. The technique is based on the use of a voxel-based partial body model generated for each patient from his/her anatomical image data to represent the critical body structures more realistically. These structures are first segmented from image slices to create an image block which is then incorporated into a radiation transport package (MCNP6.2) to perform MC simulations. When used along with the parameters specific to a patient's treatment, such as lung-shunt factor (LSF), tumor-to-normal liver ratio (TLR), fractional uptakes, and administered activity, this approach allowed more accurate simulation of radiation interactions and hence provided absorbed doses specific to a TARE patient. The MC method also calculated the absorbed doses in organs or tissues that were close to target tissues for which the MIRD formalism makes no predictions. MIRD calculations were found to overestimate the absorbed doses by as much as 11% in lungs, 5% in liver, and 20% in tumor volumes. This raises concerns about the treatment's efficacy when estimating the correct activity to be administered to a patient. When each patient simulation was repeated with a 90Y source spectrum to reflect the distribution of varying beta energies, the liver and the lungs were observed to receive relatively lower doses than those obtained with monoenergetic beta particles. Thus, it can be stated that the approach adopted in this study offers a more precise model of the patient's critical tissues and serves as a personalized dosimetric tool for TARE treatment planning.

Long-term Clinical Outcomes of Yttrium-90 Transarterial Radioembolization for Hepatocellular Carcinoma: A 5-Year Institutional Experience

To examine the clinical outcomes of yttrium-90 (Y90) transarterial radioembolization (TARE) for primary hepatocellular carcinoma (HCC) through the evaluation of a 5-year institutional experience. This retrospective study evaluated 88 consecutive patients with primary HCC receiving Y90 TARE treatment at an academic medical center from 2017 to 2021. Disease distribution was bilobar in 60.2% of patients with an average lesion diameter of 5.0±3.4cm and Barcelona Clinic Liver Cancer stage B or C in 77% of the participants. Clinical outcomes were elucidated by examination of complications, liver function tests, biochemical response, and radiographic response. Objective response ratio (ORR) and progression-free survival (PFS) were also calculated. The mean administered Y90 radiation dose was 127.8±20.2Gy. No significant complications or LFT elevations occurred post-therapy. Of the 73.9% of patients with α-fetoprotein-producing tumors, 67.8% experienced a complete or partial biochemical response 1 month post-treatment. The ORR was 83.3% on 6-month imaging and PFS was 9.6±8.5 months. Functional outcomes (Eastern Cooperative Oncology Group) were maintained or improved in 79.6% and 76.1% of patients by 6 months and 1 year post-treatment, respectively. The mean survival was 14.7±12.1 months. At 6 months post-treatment, 77.3% of patients were downstaged to or maintained Milan criteria, which was sustained for 74.4% and 70.0% of patients 1 year and 2 years after treatment, respectively. Y90-TARE is a safe and effective therapy for primary HCC. Enduring outcomes further act as a realistic bridge to liver transplantation, with a majority of patients maintaining Milan criteria and preserving their functional status long term.

Predictive Factors for Adverse Event Outcomes After Transarterial Radioembolization with Yttrium-90 Resin Microspheres in Europe: Results from the Prospective Observational CIRT Study

BackgroundUsing data collected in the prospective observational study CIRSE Registry for SIR-Spheres Therapy, the present study aimed at identifying predictors of adverse events (AEs) following transarterial radioembolization (TARE) with Yttrium-90 resin microspheres for liver tumours.MethodsWe analysed 1027 patients enrolled between January 2015 and December 2017 and followed up for 24 months. Four hundred and twenty-two patients with hepatocellular carcinoma (HCC), 120 with intrahepatic carcinoma (ICC), 237 with colorectal liver metastases and 248 with liver metastases from other primaries were included. Prognostic factors were calculated with a univariable analysis by using the overall AEs burden score (AEBS).ResultsAll-cause AEs were reported in 401/1027 (39.1%) patients, with AEs associated with TARE, such as abdominal pain (16.6%), fatigue (17%), and nausea (11.7%) reported most frequently. Grade 3 or higher AEs were reported in 92/1027 (9%) patients. Reports on grade ≥ 3 gastrointestinal ulcerations (0.4%), gastritis (0.3%), radiation cholecystitis (0.2%) or radioembolization-induced liver disease (0.5%) were uncommon. Univariable analysis showed that in HCC, AEBS increased for Eastern Cooperative Oncology Group (ECOG) 0 (p = 0.0045), 1 tumour nodule (0.0081), > 1 TARE treatment (p = 0.0224), no prophylactic embolization (p = 0.0211), partition model dosimetry (p = 0.0007) and unilobar treatment target (0.0032). For ICC, > 1 TARE treatment was associated with an increase in AEBS (p = 0.0224), and for colorectal liver metastases, ECOG 0 (p = 0.0188), > 2 prior systemic treatments (p = 0.0127), and 1 tumour nodule (p = 0.0155) were associated with an increased AEBS.ConclusionOur study confirms that TARE is a safe treatment with low toxicity and a minimal impact on quality of life.

The ROWAN study: Safety and efficacy of transarterial radioembolization with Y-90 glass microspheres and the STRIDE regimen in hepatocellular carcinoma.

TPS622 Background: In patients with early and intermediate hepatocellular carcinoma (HCC) who are ineligible for resection, thermal ablation, or liver transplant, transarterial radioembolization (TARE) with yttrium-90 glass microspheres has shown superior efficacy compared to transarterial chemoembolization; a subset of patients progress despite effective local therapy. Immunotherapy using the single tremelimumab regular interval durvalumab (STRIDE) regimen has demonstrated superior overall survival to sorafenib in advanced HCC. Recent work showed that TARE upregulates both the innate and adaptive immune systems. The possibility for TARE and STRIDE to have additive or synergistic effects when combined is of current scientific and clinical interest. The primary objective of the Phase II ROWAN Study is to assess the objective response rate and durability of local tumor control with TARE followed by STRIDE vs. TARE alone. Methods: ROWAN is a global, open-label, prospective, multicenter randomized controlled trial comparing treatment with TARE using glass microspheres followed by the STRIDE regimen (a single dose of 300 mg tremelimumab combined with 1500 mg monthly dose of durvalumab for 18 months) to TARE alone in HCC. ROWAN will include 150 patients across approximately 20 study sites in North America and Europe. Key inclusion criteria: HCC, diagnosed by radiographic imaging or histology; ineligible for or declined liver resection, thermal ablation, or transplantation; Child-Pugh A; ECOG 0; life expectancy ≥6 months; treatment naïve; unilobar tumor; measurable by mRECIST; tumor volume ≤25% of whole liver volume; and untreated future liver remnant volume ≥30% of whole liver volume. Key exclusion criteria: extrahepatic metastases; shunt fraction with a lung dose of >30 Gy; macrovascular invasion; infiltrative disease not evaluable by mRECIST; history of any organ allograph; autoimmune or inflammatory disorder; current use of immunosuppressive medication; history of malignancy other than HCC within past 3 years; and active infection. Patients will be randomized in a 1:1 ratio to two study arms (TARE followed by STRIDE or TARE alone) using two stratification factors (TARE treatment goal [ablative vs. non-ablative] and alpha fetoprotein level [>400 vs. ≤400 ng/mL]). Tumor and blood samples will be collected for correlative studies. Co-primary efficacy endpoints are objective response rate and duration of response (localized mRECIST). The primary safety endpoint is the number of adverse events (AEs) and serious AEs. Interim statistical analyses will be conducted after 25 patients have been randomized to each arm and completed the second imaging assessment 6 months post-randomization; final analysis will be after the last evaluable patient has completed the 18 months follow-up visit post-randomization or discontinued treatment. Clinical trial information: 05063565 .

Transarterial Radioembolization Planning and Treatment with Microspheres Containing Holmium-166: Determination of Renal and Intestinal Radionuclide Elimination, Effective Half-Life, and Regulatory Aspects

After transarterial radioembolization (TARE) with microspheres loaded with holmium-166, radioactivity is excreted from the body. The aim of this study was to evaluate radioactive renal and intestinal excretions after TARE planning and treatment procedures with holmium-166-loaded microspheres and to correlate the findings with the intratherapeutic effective half-life. Urinary and intestinal excretions of patients who underwent TARE procedures were collected during postinterventional intervals of 24 h (TARE planning) and 48 h (TARE treatment). Whole-body effective half-life measurements were performed. Calibrations of the 166Ho measuring system showed evidence of long-living nuclides. For excretion determination, 22 TARE planning procedures and 29 TARE treatment procedures were evaluated. Mean/maximum total excretion proportions of the injected 166Ho were 0.0038%/0.0096% for TARE planning procedures and 0.0061%/0.0184% for TARE treatment procedures. The mean renal fractions of all measured excretions were 97.1% and 98.1%, respectively. Weak correlations were apparent between the injected and excreted activities (R2 planning/treatment: 0.11/0.32). Mean effective 166Ho half-lives of 24.03 h (planning) and 25.62 h (treatment) confirmed low excretions. Radioactive waste disposal regulations of selected jurisdictions can be met but must be reviewed before implementing this method into clinical practice. Inherent long-living nuclide impurities should be considered.

Abstract No. 243 Treatment Timing and Overall Survival of Liver-Dominant Metastatic Colorectal Cancer Patients Treated with Glass Transarterial Radioembolization: Analyses from the EPOCH Trial

The EPOCH trial investigated the potential benefit of adding transarterial radioembolization (TARE) with yttrium-90 glass microspheres to second-line chemotherapy in patients with liver-dominant metastatic colorectal cancer (mCRC). Post-hoc analyses evaluated the effect of TARE treatment day post calibration on clinical and safety outcomes.

Radioembolization with chemotherapy for liver-dominant colorectal cancer: Analysis of patient subgroups in the EPOCH trial.

115 Background: The EPOCH trial evaluated potential benefit of second-line transarterial radioembolization (TARE) plus chemotherapy compared to chemotherapy alone in patients with liver-dominant metastatic colorectal disease (mCRC). Presented here are additional results from EPOCH of depth and duration of response (DoR), and progression-free survival (PFS) and hepatic progression-free survival (hPFS) subgroup analyses. Methods: EPOCH was a 1:1 randomized, open-label, global, multicenter phase 3 trial of second-line chemotherapy for liver-dominant mCRC comparing outcomes from chemotherapy with or without unilobar or same-day bilobar TARE treatment using glass microspheres. Primary study endpoints were PFS and hPFS. Pre-specified subgroup analyses of PFS and hPFS were performed. PFS, hPFS, DoR for patients with objective response, and depth of response (percent change from baseline to nadir in sum of longest diameters of target lesions) were based on blinded, independent central review using RECIST 1.1. The use of TheraSphere in the trial in the USA was under Investigational Device Exemption from FDA. Results: Both primary endpoints of PFS (HR = 0.69, 95% CI: 0.54, 0.88; 1-sided p=0.0013) and hPFS (HR = 0.59, 95% CI: 0.46, 0.77; 1-sided p<0.0001) were met in the EPOCH study. Median DoR in the 73 responders of the TARE arm was numerically longer, with 7.2 months by Kaplan-Meier analysis; in the 45 responders of the chemotherapy only arm, 6.6 months (HR = 0.79, 95% CI: 0.48, 1.30; 1-sided p = 0.178). Mean depth of response across all patients in the TARE arm with data available (N=196) was -25.6%, compared to -13.0% in the chemotherapy only arm (N=182; mean difference -12.6 percentage points; 95% CI: -18.9, -6.3; 1-sided p = 0.0001). Key subgroups of interest which showed improved PFS and/or hPFS in the TARE arm (ie, 95% CI for the HR entirely below 1) are as follows: Conclusions: These data suggest that liver-dominant mCRC patients in this trial benefitted in second-line treatment from a combination of TARE plus chemotherapy based upon improved PFS and hPFS over the full set of patients and in a number of subgroups. The addition of TARE to chemotherapy improves depth of response compared to chemotherapy alone. Clinical trial information: NCT01483027. [Table: see text]

Clinical and prognostic significance of CD14 (+) HLA-DR (-/low) myeloid-derived suppressor cells in patients with hepatocellular carcinoma received transarterial radioembolization with Yttrium-90.

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. For unresectable HCC, transarterial radioembolization (TARE) with Yttrium-90 is a widely used treatment. The aim of this study was to investigate whether monocytic myeloid-derived suppressor cells (M-MDSC) and CD39+ T cells can be non-invasive predictive biomarkers of radiological response and prognosis in patients with HCC treated with TARE. This study was conducted on 39 patients with HCC who were treated with TARE between August 2018 and December 2019 and the control group consisted of 23 healthy volunteers. CD4+, CD8+, CD39+ T cells, Natural killer (NK) cells, myeloid cells (MC) and M-MDSC parameters are examined in the course of TARE treatment with student t test and Kaplan-Meier method. There were statistically significant differences in M-MDSC, CD39+ T cells and MC values between healthy controls and HCC patients. A statistically significant difference was found in M-MDSC and CD4+ T cells values in the HCC patient group who responded to the treatment compared to those who did not. Survival analysis found that patients with lower frequencies (under 3.81%) of M-MDSC showed more prominent differences of overall survival (OS) compared to patients with all high groups. We found that M-MDSC in the peripheral blood might be a useful non-invasive biomarker to predict OS. We have shown for the first time that M-MDSC is correlated with treatment response in HCC patients treated with TARE. Additionally, we have found that the percentage of CD39+ T cells is high in HCC patients and these cells are positively correlated with M-MDSC.

The position of transarterial chemoembolization with drug-eluting beads and yttrium-90 transarterial radioembolization in patients with hepatocellular carcinoma: Consensus statements from a Delphi-method expert panel in Turkey.

Clinical studies conducted in different geographic regions using different methods to compare transarterial chemoembolization (TACE) and transarterial radioembolization (TARE) have demonstrated discordant results. Meta-analyses in this field indicate comparable overall survival (OS) with TACE and TARE, while reporting a longer time to progression and a higher downstaging effect with TARE treatment. In terms of isolated procedure costs, treatment with TARE is 2 to 3 times more, and in some countries even more, expensive than TACE. However, relevant literature indicates that TARE is more advantageous compared to TACE regarding the need for repeat procedures, costs of complication management, total hospital stay and quality of life. Heterogeneity of hepatocellular carcinoma (HCC) patients as well as the shortcomings of clinical classifications, randomized clinical trials and cost-effectiveness studies make it difficult to choose between treatment alternatives in this field. As in other countries, these challenges lead to differences in treatment choice across different centers in Turkey. The present expert panel used two round modified Delphi method to investigate the resources and clinical parameters referenced while selecting patients for drug-eluting beads (DEB)-TACE and TARE treatment modalities in Turkish clinical practice. The cost-effectiveness parameters and comparisons of these treatments have also been evaluated at a prediction level. The panelists stated that they most commonly use the BCLC staging system for the management of HCC patients in Turkey. However, they did not find any of the staging systems or treatment guidelines sufficient enough for their clinical practice in terms of covering the down-staging intent of treatments. Since living donor transplant preference is higher in Turkey than the rest of the Western countries, down-staging treatments are thought to be more prioritized in Turkey than that in other Western countries. The panelists reached a consensus that TARE may provide improved OS and reduce the number of repeat procedures compared to DEB-TACE in intermediate-stage patients with a single tumor spanning a diameter above 5 cm who experience recurrence after previous treatment with TACE and most TACE-naïve patient groups in intermediate stage. Based on the consensus on OS and the number of procedures, the panelists assumed that TARE would be more cost-effective than DEB-TACE in most groups of TACE-naïve patients in intermediate stage and in those with a single tumor spanning a diameter above 5 cm. It was also stated that the predicted cost-effectiveness advantage of TARE could be more pronounced in patients with a tumor diameter greater than 7 cm.

GATE Monte Carlo dosimetry in 90Y TARE planning: influence of simulation parameters and image resampling on dosimetric accuracy and optimization of computational times

Direct Monte Carlo (MC) simulation is considered the gold standard approach for internal dosimetry in nuclear medicine, and it is increasingly used in planning Trans-Arterial Radio-Embolization (TARE) of HepatoCellular Carcinoma (HCC) {and hepatic metastases}. However its computational times, longer with respect to other simplified approaches, constitute a limiting factor, especially when dealing with {large size and finely discretized voxelized volumes}. Aim of this work was the investigation of the influence of cuts on the production of secondary particles and of input CT images resamplings on dosimetric accuracy and computational time in patient-specific voxel-level MC simulations of 90 Y-labelled glass microspheres TARE treatment, to find optimal combinations of settings for speeding up such simulations. GATE GEANT4 interface was used to perform simulations employing CT and 99m Tc SPECT as input data, examining multiple CT resolutions (via CT resamplings characterized by voxel volume factors 2, 8, and 64 with respect to native one, and a CT resampling with SPECT resolution) and production cuts (0.01 mm, 0.05 mm, 0.1 mm, 0.5 mm and some more, specific for each resampling). Increasing cut length and reducing CT resolution produces an early rapid decrease followed by a late slow decrease of simulation time as a function of this two parameters. A reduction up to 30% with respect to reference simulation time, while preserving acceptable dosimetric accuracy, was obtained. The best combination of settings among the examined ones resulted the choice of CT resampling with 8 times the native voxel volume and of 0.1-0.5 mm cut, ensuring dosimetric agreement within 1% in liver-related VOIs, while reducing simulation time to 45%.

Real-world outcomes of patients with intrahepatic cholangiocarcinoma treated with trans-arterial radioembolization: Results from the CIRSE Registry for SIR-Spheres Therapy (CIRT), a large European prospective multi-center observational study.

308 Background: Trans-arterial radioembolization (TARE) is a treatment option for patients with intrahepatic cholangiocarcinoma (ICC). The CIRSE Registry for SIR-Spheres Therapy (CIRT) is the first European prospective multi-centre observational study designed to evaluate the clinical outcomes of patients treated with TARE with SIR-Spheres Y90 resin microspheres for ICC in the multi-institutional real-life clinical setting. The study was conducted by the Cardiovascular and Interventional Radiological Society of Europe (CIRSE). Methods: Patients were enrolled prospectively between Jan 2015 and 31 Dec 2017. Eligible patients were adults treated with TARE with Y90 resin microspheres for ICC. Data on baseline characteristics and treatment intention/clinical context and dosimetry were collected, as well as follow-up data (every 3 months; for 24 months after treatment), including overall survival (OS), (hepatic) progression-free survival [(h)PFS], safety and Global Health Status (GHS, using the European Organisation for the Research and Treatment of Cancer QLQ-C30). Results: 120 patients were included from 18 sites in 8 European countries. Median age was 63 years (range: 29-86) and 54.2% were male. Median tumour to liver percentage was 12.8%. Median prescribed activity was 1.32 GBq for whole liver treatments (n = 49), 1.20 GBq for right lobe treatments (n = 56) and 0.82 GBq for left lobe treatments (n = 51). 97.5% of the delivered activity was within 90% of the prescribed activity. TARE treatment as a first line (L1) global strategy was applied in 39.1%, 27.4% as second line (after systemic therapy). Treatment intention was predominantly palliative (69.2%) or tumour shrinkage (20.8%). Median OS was 14.7 months (95% confidence interval (CI) 10.9 – 17.9). Median PFS was 5.7 months (95% CI 3.9 – 7.5), whereas hPFS was 6.2 months (95% CI 4.1 – 8.5). Mean GHS was 59.3 at baseline, 61.0 after 3 months, 56.0 at 6 months, 54.4 at 9 months and 63.0 after 1 year. Severe adverse events (grade 3 and 4) were found in 13 (10.8%) patients: (abdominal pain 3.3%, fatigue 1.7%, gastrointestinal ulceration 0.8%, gastritis 0.8%, radiation cholecystitis 0.8%, radiation-induced liver disease 1.7%, other 5.8%). Detailed subgroup analyses are currently being performed. Updated data describing OS, PFS and hPFS for L1 TARE vs TARE after systemic chemotherapy, as well as prognostic factors for OS, PFS and hPFS will be shown. Conclusions: The results from this large prospective multi-centre observational study shows that in the real-world context, TARE is applied early and successfully in the treatment pathway. TARE is shown to be an effective and safe treatment with no meaningful deterioration of quality of life. Clinical trial information: NCT02305459.

Hybrid angiography-CT for transarterial radioembolization: a pictorial essay.

Although hybrid angiography-CT (Angio-CT) has a long history of use for interventional oncology procedures, its applications for transarterial radioembolization (TARE) are not as well described in the literature. This pictorial essay demonstrates a single-institution experience with the utilization of an Angio-CT system for TARE treatment of hepatocellular carcinoma. Procedural images and clinical data for twenty-four patients who underwent initial angiographic mapping with hepatopulmonary shunt fraction assessment and or administration of Yttrium-90 (Y-90) microspheres using the Angio-CT system to date were reviewed. Cases were reviewed for examples that highlight the specific utility of Angio-CT. Three representative TARE cases were selected which illustrate unique advantages and applications of the Angio-CT system when performing TARE. These include the ability to optimally delineate hepatic vascular anatomy, accurately calculate liver volumes for dosimetry, and improve the detection and characterization of equivocal lesions. Angio-CT has unique advantages which can be applied to TARE treatment of patients with HCC. The technology has potential to be an especially effective tool for those who aim to be at the cutting edge of the rapidly growing field of interventional oncology.

Chemoembolization Versus Radioembolization for Neuroendocrine Liver Metastases: A Meta-analysis Comparing Clinical Outcomes.

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 66.8months 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.

Computed tomographic perfusion imaging for the prediction of response transarterial radioembolization with Yttrium‑90 glass microspheres of hepatocellular carcinoma.

The present study aimed to estimate the clinical value of quantitative computed tomography perfusion imaging (CTPI) parameters in predicting early treatment response, as determined by the modified response evaluation criteria in solid tumours (mRECIST), in patients with HCC who underwent transarterial radioembolization (TARE). This retrospective cohort study included 54 patients with HCC who had TARE treatment between July 2018 and August 2019. Each patient was evaluated using CTPI before the procedure and in the first and third months after the procedure. In the third month, treatment response was determined based on mRECIST and used as a reference. ROC analysis was performed to determine the relationship between the CTPI parameters before treatment and one month after treatment and the treatment response. Significant cut-off values for three of the CTPI parameters - hepatic blood flow (BF), time to start (TTS) and hepatic perfusion index (HPI) - which were among the pre-treatment CTPI parameters, were found to predict progressive disease (PD). The TTS cut-off value was 1.29 (sensitivity: 86.7%; specificity: 6.7%), the BF cut-off value was 81.58 (sensitivity: 53.3%; specificity: 90%) and the HPI cut-off value was 88.26 (sensitivity: 33%; specificity: 96.7%). BV, TTS and HPI may be predictive for PD in HCC lesions in the third month after TARE treatment. In contrast, the CTPI parameters in the first month after TARE played no significant role in predicting the treatment response and determining the effects of TARE on the microvascular level.

Analysis of failed therapy evaluations in radioembolization of primary and secondary liver cancers

PurposeTo analyze patients’ characteristics and reasons for not performing planned transarterial radioembolization (TARE) in liver cancer after 99mTc-labeled macroaggregated albumin (99mTc-MAA) evaluation.MethodsIn this retrospective single-center cohort, all patients undergoing 99mTc-MAA evaluation prior to planned TARE for primary or secondary liver cancer between 2009 and 2018 were analyzed. Patients were assigned to either “TARE” or “no TARE” group. Patients’ characteristics, arising reasons for not performing the planned TARE treatment as well as predictive factors for occurrence of these causes were analyzed.Results436 patients [male = 248, female = 188, median age 62 (23–88) years] with 99mTc-MAA evaluation prior to planned TARE of primary or secondary liver cancer were included in this study. 148 patients (33.9%) did not receive planned TARE. Patients with a hepatic tumor burden > 50%, no liver cirrhosis, no previous therapies and a higher bilirubin were significantly more frequent in “no TARE” compared to “TARE” group. Main reasons for not performing TARE were extrahepatic tracer accumulation (n = 70, 40.5%), non-target accumulation of 99mTc-MAA (n = 27, 15.6%) or a hepatopulmonary shunt fraction of more than 20% (n = 23, 13.3%). Independent preprocedural parameters for not performing planned TARE were elevated bilirubin (p = 0.021) and creatinine (p = 0.018) and lower MELD score (p = 0.031).ConclusionA substantial number of patients are precluded from TARE following 99mTc-MAA evaluation, which is, therefore, implicitly needed to determine contraindications to TARE and should not be refrained from in pretreatment process. However, a preceding careful patient selection is needed especially in patients with high hepatic tumor burden and alteration in lab parameters.

Abstract 2350: Transarterial radioembolization versus systemic treatment for the management of hepatocellular carcinoma with vascular invasion: Analysis of the US National Cancer Database

Abstract Background and Aims: For hepatocellular carcinoma (HCC) with vascular invasion, systemic treatment is recommended but transarterial radioembolization (TARE) is often used in clinical practice. The aim of this study was to investigate the current usage of TARE vs. systemic therapy as a first-line treatment for HCC with vascular invasion in the United States (US). Method: We performed a retrospective cohort study using the National Cancer Database (NCDB), which represents more than 70 percent of newly diagnosed cancer cases nationwide. All HCC patients diagnosed between 2010 and 2015 with the tumor stage of T3BN0M0 according to the 7th edition of the American Joint Committee on Cancer TNM staging system (tumor involving a major branch of a large vein of the liver without lymph nodes or extrahepatic metastasis) and received TARE or systemic treatment as a first-line treatment were included. Multivariable logistic regression was used to estimate factors associated with the utilization of TARE vs. systemic therapy. Results: A total of 1979 patients who received systemic treatment and 524 patients who received TARE were included. The proportion of patients receiving TARE increased from 15.7% in 2010 to 31.4% in 2015 (P<0.01). The median tumor size of the largest lesion was comparable (7.0cm for TARE vs. 7.1 cm for systemic treatment, P=0.43). Factors independently associated with increased likelihood of receiving TARE over systemic treatment were: advanced age (Odds Ratio [OR]: 1.02, 95% confidence interval [CI]: 1.01 - 1.03, p=0.005), insurance status: private (OR: 3.06, 95% CI: 1.61 - 5.65, p<0.001), Medicaid/Medicare (OR: 2.91, 95% CI: 1.52 - 5.31, p<0.001), others (OR: 4.85, 95% CI: 1.90 - 11.62, p<0.001) vs. no insurance, and receiving care in the Midwest vs. Northeast region of the US (OR: 1.89, 95% CI: 1.38 - 2.53, p<0.001). Patients were significantly less likely to receive TARE if receiving treatment at community cancer program (OR: 0.24, 95% CI: 0.098 - 0.49, p<0.001) or comprehensive community cancer program (OR: 0.62, 95% CI: 0.48 - 0.82, p<0.001) vs. academic cancer program. Larger tumor size (OR per 1cm: 0.97, 95% CI: 0.95 - 1.00, p=0.03) and higher Charlson comorbidity index of ≥3 vs. 0 (OR: 0.53, 95% CI: 0.38 - 0.73, p<0.001) were inversely associated with receiving TARE. Recent HCC diagnosis year was associated with an increased likelihood of receiving TARE (OR: 1.23, 95% CI:1.16 - 1.32, p<0.001). Conclusion: The proportion of patients receiving TARE as a first-line treatment for HCC with macrovascular invasion has been increasing in the US. Age, comorbidities, insurance status, tumor size, and the type and location of cancer centers are associated with the usage of TARE vs. systemic treatment in HCC patients with vascular invasion. Citation Format: Joseph C. Ahn, Michael Luu, Walid Ayoub, Alexander Kuo, Andrew Hendifar, Jun Gong, Kambiz Kosari, Shelly Lu, Nicholas Nissen, Ju Dong Yang. Transarterial radioembolization versus systemic treatment for the management of hepatocellular carcinoma with vascular invasion: Analysis of the US National Cancer Database [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2350.