Yttrium-90 Resin Microspheres Research Articles

Multicenter evaluation of the safety and efficacy of selective internal radiation therapy with yttrium-90 resin microspheres in Taiwan: data from the RESIN registry.

The REgistry of Selective Internal radiation therapy in AsiaNs (RESIN) was a multicenter, single-arm, prospective, observational study of 90Y resin microspheres in patients with hepatocellular carcinoma (HCC) or metastatic colorectal cancer (mCRC) from Taiwan. RESIN is the first real-life clinical study of this therapy in an Asian cohort. Study objectives were to evaluate the safety and efficacy of 90Y resin microspheres. Adults with HCC or mCRC scheduled to receive SIRT with 90Y resin microspheres were included. Primary endpoints were best overall response rate (ORR), adverse events, and changes from baseline in liver function. Secondary efficacy endpoints included overall survival (OS). Of 107 enrolled patients, 83 had HCC, and 24 had mCRC. ORR was 55.41% (HCC) and 33.33% (mCRC). Of 58 HCC patients with 6-month post-SIRT data, 13.79% (n=8) had resection, transplantation, transarterial chemoembolization, or radiofrequency ablation as the result of down-staging or down-sizing of their lesions. One hundred and ten treatment emergent adverse events (TEAEs) were reported in 51 patients, and five serious adverse events (SAEs) were reported in five patients. The most frequent TEAEs were abdominal pain, nausea and decreased appetite (HCC), and abdominal pain, decreased appetite, fatigue, and vomiting (mCRC). Two deaths due to SAEs (probably related to SIRT) were reported, both in patients with extensive HCC, active hepatitis infection, and other comorbidities. Median OS was 24.07 (HCC) and 12.66 (mCRC) months. Safety and efficacy outcomes with the routine use of SIRT with 90Y resin microspheres in Taiwan are consistent with published data.

The Influence of Additional Treatments on the Survival of Patients Undergoing Transarterial Radioembolization (TARE).

The aim of this study was to present our preliminary experience with transarterial radioembolization (TARE) using Yttrium-90 (90Y), compare the cancer-specific survival (CSS) of patients with hepatocellular carcinoma (HCC) and colorectal cancer (CRC) liver metastases undergoing TARE, and investigate the influence of additional treatments on CSS. Our database was interrogated to retrieve patients who had undergone TARE using Yttrium-90 (90Y) glass or resin microspheres. Kaplan-Meier curves and the log-rank test were employed to conduct survival analysis for the different groups (p < 0.05). Thirty-nine patients were retrieved (sex: 27 M, 12 F; mean age: 63.59 ± 15.66 years): twenty-three with hepatocellular carcinoma (HCC) and sixteen with CRC liver metastasis. Globally, the patients with HCC demonstrated a significantly longer CSS than those with CRC liver metastasis (22.64 ± 2.7 vs. 7.21 ± 1.65 months; p = 0.014). Among the patients with CRC liver metastasis, those receiving TARE and additional concomitant treatments (n = 10) demonstrated a longer CSS than the CRC patients receiving only TARE (9.97 ± 2.21 vs. 2.59 ± 0.24 months; p = 0.06). In the HCC group, there was a trend of a longer CSS in patients (n = 8) receiving TARE and additional treatments (27.89 ± 3.1 vs. 17.69 ± 3.14 months; p = 0.15). Patients with HCC seem to achieve a longer survival after TARE compared to patients with CRC liver metastases. In patients with CRC liver metastases, the combination of TARE and additional concomitant treatments may improve survival.

Selective Internal Radiation Therapy Using Y-90 Resin Microspheres for Metastatic Colorectal Cancer: An Updated Systematic Review and Network Meta-Analysis.

This literature review and exploratory network meta-analysis (NMA) aimed to compare the clinical effectiveness and tolerability of selective internal radiation therapy (SIRT) using yttrium-90 (Y-90) resin microspheres, regorafenib (REG), trifluridine-tipiracil (TFD/TPI), and best supportive care (BSC) in adult patients with chemotherapy-refractory or chemotherapy-intolerant metastatic colorectal cancer (mCRC). In light of recently published data, the literature was searched to complement and update a review published in 2018. Studies up to December 2022 comparing two or more of the treatments and reporting overall survival (OS), progression-free survival (PFS), or incidence of adverse events (AE) were included. The NMA compared hazard ratios (HRs) for OS and PFS using Markov chain Monte Carlo techniques. Fifteen studies were included, with eight studies added (none addressing SIRT). All active treatments improved OS in relation to BSC. SIRT had the longest OS among all treatments, although without statistically significant differences (HR [95% credible interval] for SIRT, 0.48 [0.27, 0.87]; TFD/TPI, 0.62 [0.46, 0.83]; REG, 0.78 [0.57, 1.05]) in a fixed effects model. Information regarding SIRT was insufficient for PFS analysis, and TFD/TPI was the best intervention (HR 2.26 [1.6, 3.18]). One SIRT study reported radioembolization-induced liver disease in > 10% of the sample; this was symptomatically managed. Non-haematological AEs (hand-foot skin reaction, fatigue, diarrhoea, hypertension, rash or desquamation) were more common with REG, while haematological events (neutropoenia, leukopenia, and anaemia) were more common with TFD/TPI. Current evidence supports SIRT treatment in patients with chemotherapy-refractory or chemotherapy-intolerant mCRC compared to newer oral agents, with comparable OS and low incidence of AEs.

Factors Impacting Survival After Transarterial Radioembolization in Patients with Unresectable Intrahepatic Cholangiocarcinoma: A Combined Analysis of the Prospective CIRT Studies

PurposeTransarterial radioembolization (TARE) with Yttrium-90 resin microspheres is a treatment option for patients with intrahepatic cholangiocarcinoma (ICC). However, optimising the timing of TARE in relation to systemic therapies and patient selection remains challenging. We report here on the effectiveness, safety, and prognostic factors associated with TARE for ICC in a combined analysis of the prospective observational CIRT studies (NCT02305459 and NCT03256994).MethodsA combined analysis of 174 unresectable ICC patients enrolled between 2015 and 2020 was performed. Patient characteristics and treatment-related data were collected at baseline; adverse events and time-to-event data (overall survival [OS], progression-free survival [PFS] and hepatic PFS) were collected at every follow-up visit. Log-rank tests and a multivariable Cox proportional hazard model were used to identify prognostic factors.ResultsPatients receiving a first-line strategy of TARE in addition to any systemic treatment had a median OS and PFS of 32.5 months and 11.3 months. Patients selected for first-line TARE alone showed a median OS and PFS of 16.2 months and 7.4 months, whereas TARE as 2nd or further treatment-line resulted in a median OS and PFS of 12 and 9.3 months (p = 0.0028), and 5.1 and 3.5 months (p = 0.0012), respectively. Partition model dosimetry was an independent predictor for better OS (HR 0.59 [95% CI 0.37–0.94], p = 0.0259). No extrahepatic disease, no ascites, and < 6.1 months from diagnosis to treatment were independent predictors for longer PFS.ConclusionThis combined analysis indicates that in unresectable ICC, TARE in combination with any systemic treatment is a promising treatment option.Level of evidence: level 3, Prospective observationalGraphic

Predictive Dosimetry and Outcomes of Hepatocellular Carcinoma Treated by Yttrium-90 Resin Microsphere Radioembolization: A Retrospective Analysis Using Technetium-99m Macroaggregated Albumin SPECT/CT and Planning Software

PurposeTo characterize estimated mean absorbed tumor dose (ADT), objective response (OR), and estimated target dose of hepatocellular carcinoma (HCC) after resin microsphere yttrium-90 (90Y) radioembolization using partition dosimetry. Materials and MethodsIn this retrospective, single-center study, multicompartment dosimetry of index tumors receiving 90Y radioembolization between October 2015 and June 2022 was performed using a commercial software package and pretreatment technetium-99m macroaggregated albumin single photon emission computed tomography (SPECT)/computed tomography (CT). In total, 101 patients with HCC underwent 102 treatments of 127 index tumors. Patients underwent imaging every 2–3 months after treatment to determine best response per modified Response Evaluation Criteria in Solid Tumors (mRECIST). Best response was defined as the greatest response category per mRECIST and categorized as OR or nonresponse (NR). A Cox proportional hazards model evaluated the probability of tumor OR and progression-free survival using ADT. ResultsThe median follow-up period was 148 days (interquartile range [IQR], 92–273 days). The median ADT of OR was 141.9 Gy (IQR, 89.4–215.8 Gy) compared with the median ADT of NR treatments of 70.8 Gy (IQR, 42.0–135.3 Gy; P < .001). Only ADT was predictive of response (hazard ratio = 2.79 [95% confidence interval {CI}: 1.44–5.40]; P = .003). At 6 months, an ADT of 157 Gy predicted 90.0% (95% CI: 41.3%–98.3%) probability of OR. At 1 year, an ADT of 157 Gy predicted 91.6% (95% CI: 78.3%–100%) probability of progression-free survival. Partition modeling and delivered activity were predictive of progression (P = .021 and P = .003, respectively). ConclusionsFor HCC treated with resin microspheres, tumors receiving higher ADT exhibited higher rates of OR. An ADT of 157 Gy predicted 90.0% OR at 6 months.

Comparison of absorbed doses to the tumoral and non-tumoral liver in HCC patients undergoing 99mTc-MAA and 90Y-microspheres radioembolization.

This study aimed to determine the absorbed doses in the tumoral-liver and non-tumoral liver of hepatocellular carcinoma (HCC) patients undergoing radioembolization with Yttrium-90 (90Y) resin microspheres, and compared with those derived from 99mTc-MAA using the partition model. A total of 42 HCC patients (28 males and 14 females, mean age 65 ± 11.51years) who received 45 treatment sessions with 90Y-microspheres between 2016 and 2021 were included. Pre-treatment 99mTc-MAA and post-treatment 90Y-bremsstrahlung SPECT/CT were acquired for each patient. Semi-automated segmentation of regions of interest (ROIs) was performed using MIM Encore software to determine the tumor-liver ratio (TLR) encompassing the liver volume, tumoral-liver, and lungs, and verified by both nuclear medicine physician and interventional radiologist. A partition dosimetry model was used to estimate the administered activity of 90Y-microspheres and the absorbed doses to the tumoral-liver and non-tumoral liver. The student's paired t test and Bland-Altman plot were used for the statistical analysis. The mean TLR values obtained from 99mTc-MAA SPECT/CT and 90Y-bremsstrahlung SPECT/CT were 4.78 ± 3.51 and 2.73 ± 1.18, respectively. The mean planning administered activity of 90Y-microspheres based on 99mTc-MAA SPECT/CT was 1.56 ± 0.80GBq, while the implanted administered activity was 2.53 ± 1.23GBq (p value < 0.001). The mean absorbed doses in the tumoral-liver estimated from 99mTc-MAA and 90Y-bremsstrahlung SPECT/CT were 127.44 ± 4.36Gy and 135.98 ± 6.30Gy, respectively. The corresponding mean absorbed doses in the non-tumoral liver were 34.61 ± 13.93Gy and 55.04 ± 16.36Gy. This study provides evidence that the administered activity of 90Y-microspheres, as estimated from 90Y-bremsstrahlung SPECT/CT, was significantly higher than that estimated from 99mTc-MAA SPECT/CT resulted in increased absorbed doses in both the tumoral-liver and non-tumoral liver. However, 99mTc-MAA SPECT/CT remains a valuable planning tool for predicting the distribution of 90Y-microspheres in liver cancer treatment.

Partition Dosimetry and Outcomes of Metastatic Neuroendocrine Tumors after Yttrium-90 Resin Microsphere Radioembolization

PurposeTo characterize estimated mean tumor-absorbed dose (ADT) and objective response of metastatic neuroendocrine tumor (NET) after resin microsphere yttrium-90 (90Y) hepatic radioembolization using partition dosimetry. Materials and MethodsIn this retrospective, single-center study, multicompartment dosimetry of index tumors receiving 90Y radioembolization between 2013 and 2022 involved the use of Sureplan (MIM Software, Cleveland, Ohio) and technetium-99m macroaggregated albumin single photon emission computed tomography (SPECT) combined with computed tomography. Thirty-six patients with NET underwent treatment of 56 index tumors. Patients underwent imaging every 3–6 months after treatment to determine best response per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and modified RECIST (mRECIST) criteria. Responses were categorized as objective response (OR) or nonresponse (NR). Wilcoxon rank sum test evaluated differences in continuous variables, and Pearson χ2 test evaluated differences in categorical variables. ResultsMedian follow-up was 582 days (IQR, 187–1,227 days). Per RECIST 1.1, 27 patients (75%) experienced OR and 9 patients experienced (25%) NR. Of the 36 patients, 33 (92%) showed hypervascular, mRECIST-evaluable tumors. Among them, 28 patients (85%) showed mRECIST OR and 5 patients (15%) showed NR. The mRECIST OR group received a higher ADT than the NR group (median, 107 Gy; IQR, 95.1–154 Gy vs median, 70.4 Gy; IQR, 62.9–87.6 Gy; P = .048). All tumors receiving at least 120 Gy showed mRECIST OR. ConclusionsIn hypervascular metastatic NET treated by 90Y resin microsphere radioembolization, higher tumor dose was associated with better tumor response per mRECIST. Doses of ≥120 Gy led to OR.

Predictive Partition Dosimetry and Outcomes after Yttrium-90 Resin Microsphere Radioembolization of Colorectal Cancer Metastatic to the Liver: A Retrospective Analysis

PurposeTo characterize estimated absorbed tumor dose (ADT), objective response (OR), and estimated target dose of liver metastatic colorectal cancer (mCRC) after resin microsphere yttrium-90 (90Y) radioembolization using partition dosimetry. Materials and MethodsIn this retrospective, single-center study, multicompartment dosimetry of index tumors undergoing 90Y radioembolization from October 2013 to July 2022 was performed using MIM SurePlan and pretreatment technetium-99m macroaggregated albumin infusion data. Thirty-eight patients with mCRC underwent treatments for 59 index tumors. Patients were imaged every 2–3 months after treatment and then every 3–6 months after disease control to determine the best response per Response Evaluation Criteria in Solid Tumors 1.1. Responses were categorized as OR or nonresponse (NR). A Cox proportional hazards model evaluated the probability of tumor OR and local progression–free survival (LPFS) based on ADT. ResultsPatients had a median follow-up of 116 days (interquartile range [IQR], 69–231 days). The ADT was higher for OR patients than for NR patients (median, 130.8 [IQR, 85.6–239.0] vs 40.6 [IQR, 26.0–66.3] Gy; P < .001). A greater percentage of OR than NR patients were treated with activities calculated by partition modeling (54% vs 12%; P = .005). Only ADT predicted response (P = .032). At 6 months, an ADT of 120 Gy predicted a 55% (95% CI, 0.0%–89%) probability of OR. Only ADT (P = .010) and female sex (P = .014) predicted LPFS. At 1 year, an ADT of 120 Gy predicted a 70% (95% CI, 35%–100%) probability of LPFS. ConclusionsTumor dose was the strongest predictor of OR for mCRC. Administration of an estimated 120 Gy to mCRC predicted 55% OR with 90Y resin microspheres at 6 months.

Evaluation of the pharmacokinetics, dosimetry, and therapeutic efficacy for the α-particle-emitting transarterial radioembolization (αTARE) agent [225Ac]Ac-DOTA-TDA-Lipiodol® against hepatic tumors

BackgroundThe liver is a common site for metastatic disease for a variety of cancers, including colorectal cancer. Both primary and secondary liver tumors are supplied through the hepatic artery while the healthy liver is supplied by the portal vein. Transarterial radioembolization (TARE) using yttrium-90 glass or resin microspheres have shown promising results with reduced side-effects but have similar survival benefits as chemoembolization in patients with hepatocellular carcinoma (HCC). This highlights the need for new novel agents against HCC. Targeted alpha therapy (TAT) is highly potent treatment due to the short range (sparing adjacent normal tissue), and densely ionizing track (high linear energy transfer) of the emitted α-particles. The incorporation of α-particle-emitting radioisotopes into treatment of HCC has been extremely limited, with our recent publication pioneering the field of α-particle-emitting TARE (αTARE). This study focuses on an in-depth evaluation of the αTARE-agent [225Ac]Ac-DOTA-TDA-Lipiodol® as an effective therapeutic agent against HCC regarding pharmacokinetics, dosimetry, stability, and therapeutic efficacy.Results[225Ac]Ac-DOTA-TDA was shown to be a highly stable with bench-top stability at ≥ 95% radiochemical purity (RCP) over a 3-day period and serum stability was ≥ 90% RCP over 5-days. The pharmacokinetic data showed retention in the tumor of [225Ac]Ac-DOTA-TDA-Lipiodol® and clearance through the normal organs. In addition, the tumor and liver acted as suppliers of the free daughters, which accumulated in the kidneys supplied via the blood. The dose limiting organ was the liver, and the estimated maximum tolerable activity based on the rodents whole-body weight: 728–3641 Bq/g (male rat), 396–1982 Bq/g (male mouse), and 453–2263 Bq/g (female mouse), depending on an RBE-value (range 1–5). Furthermore, [225Ac]Ac-DOTA-TDA-Lipiodol® showed significant improvement in survival for both the male and female mice (median survival 47-days) compared with controls (26-days untreated, and 33–35-days Lipiodol® alone).ConclusionsThis study shows that [225Ac]Ac-DOTA-TDA-Lipiodol® is a stable compound allowing for centralized manufacturing and distribution world-wide. Furthermore, the result of this study support the continue development of evaluation of the αTARE-agent [225Ac]Ac-DOTA-TDA-Lipiodol® as a potential treatment option for treating hepatic tumors.

Impact of sex on the efficacy of first-line mFOLFOX6 (plus or minus bevacizumab) versus mFOLFOX6 (plus or minus bevacizumab) plus Y90-radioembolization in patients with metastatic colorectal cancer: An exploratory, retrospective analysis of the phase III SIRFLOX trial.

3564 Background: Clinical trials in metastatic colorectal cancer (mCRC) investigating systemic and local treatment options are usually conducted irrespective of sex. However, sex-associated differences relating to safety and efficacy in the treatment of mCRC are of gaining interest. Methods: The SIRFLOX trial investigated the efficacy and safety of adding radioembolization using yttrium-90 resin microspheres (SIRT) to standard fluorouracil, leucovorin, and oxaliplatin (FOLFOX)–based chemotherapy in patients with previously untreated mCRC comparing it to standard treatment with FOLFOX-based chemotherapy. In this post-hoc analysis, the study population was stratified for sex (male versus female) using Propensity Score Matching (PSM) with baseline variables with difference (p-value &lt; 0.20) in a gender specific comparison serving as matching covariates (age, BSA, sidedness, bilirubin). Groups were matched in a 1:1 ratio, with the nearest calculated propensity logit, with a caliper width of ≤0.20 of the SD of the propensity score logit. Evaluated efficacy endpoints were progression-free survival (PFS, primary endpoint of the trial) and overall survival (OS). Results: 356 (67.2%) male and 173 (32.6%) female patients were randomized and treated in the SIRFLOX trial. In the overall study population, there was no difference regarding PFS or OS between male and female patients. No difference in PFS and OS between male (n = 101) and female (n = 101) patients could be observed independently of treatment arm. After PSM, female patients showed significant benefit regarding PFS from SIRT + chemotherapy compared to chemotherapy alone (12.2 [9.9-17] vs. 9.9 [7.5-12.7], p = 0.047) that translated into a trend to longer OS (27.3 [25.6-36.5] vs. 23.7 [17.8-28.8] months, p = 0.094, HR 0.68 [0.43-1.10]) while male patients did not show a difference regarding PFS and OS between treatment arms (p = 0.170, HR 1.41 [0.87-2.10]). In the experimental arm, female patients had significantly longer OS compared to male patients (27.3 [25.6-36.5] vs. 21.0 [17.9-26.7] months, p = 0.031, HR 0.64 [0.42-0.96]). Sex did not impact on OS in the chemotherapy arm (p = 0.410, HR 1.22 [0.76-2.02]). Conclusions: In the SIRFLOX trial, female patients seem to benefit from the addition of SIRT to chemotherapy regarding PFS and OS. This was not observed in male patients. To our knowledge, this is the first analysis to show sex-differences in the application of SIRT in patients with mCRC. Our results support the development of specific protocols according to sex. Clinical trial information: NCT00724503 .

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.

Abstract No. 129 Histopathological Analysis after Transarterial Radioembolization with Yttrium-90 Resin Microspheres

Abstract No. 129 Histopathological Analysis after Transarterial Radioembolization with Yttrium-90 Resin Microspheres

Survival and Toxicities after Yttrium-90 Transarterial Radioembolization of Cholangiocarcinoma in the RESiN Registry

PurposeTo report outcomes in patients with intrahepatic cholangiocarcinoma treated with yttrium-90 resin microspheres (transarterial radioembolization [TARE]) from a multicenter, prospective observational registry. Materials and MethodsNinety-five patients (median age, 67 years [interquartile range {IQR}, 59–74]; 50 men) were treated in 27 centers between July 2015 and August 2020. Baseline demographic characteristics included imaging findings, performance status, and previous systemic or locoregional treatments. Dosimetry method was tracked. Overall survival (OS) and progression-free survival were calculated using the Kaplan-Meier method. The best imaging response was calculated using the Response Evaluation Criteria in Solid Tumors v1.1. Grade ≥3 toxicities were assessed using Common Terminology Criteria for Adverse Events v5. Cox regression analysis was performed. ResultsFifty-two of 86 (60%) patients had multifocal tumors, and 24/89 (27%) had extrahepatic tumors. The median index tumor diameter was 7.0 cm (IQR, 4.9–10 cm). The activity calculation method was reported in 59/95 (62%) patients, with body surface area being the most frequently used method (45/59, 76%). Median OS for the cohort was 14 months (95% confidence interval, 12–22). OS at 3, 6, 12, and 24 months was 94%, 80%, 63%, and 34%, respectively. Median OS was longer in patients without cirrhosis (19.1 vs 12.2 months, P = .05). Cirrhosis, previous chemotherapy (OS, 19.1 vs 10.6 months for treatment-naïve; P = .07), and imaging response at 6 months (OS, 16.4 vs 9.5 months for no response; P = .06) underwent regression analysis. Imaging response predicted OS at regression (hazard ratio, 0.39; P = .008). Grade 3–4 bilirubin toxicities were noted in 5 of 72 (7%) patients. Grade 3 albumin toxicity was noted in 1 of 72 (1.4%) patients. ConclusionsObjective response at 6 months predicted longer OS after TARE for intrahepatic cholangiocarcinoma. The incidence of liver function toxicity was <10%.

Factors impacting survival after transarterial radioembolization in patients with hepatocellular carcinoma: Results from the prospective CIRT study

Transarterial radioembolization (TARE) with Yttrium-90 resin microspheres is an established treatment option for patients with hepatocellular carcinoma (HCC). However, optimising treatment application and patient selection remains challenging. We report here on the effectiveness, safety and prognostic factors, including dosing methods, associated with TARE for HCC in the prospective observational CIRT study. We analysed 422 patients with HCC enrolled between Jan 2015 and Dec 2017, with follow-up visits every 3 months for up to 24 months after first TARE. Patient characteristics and treatment-related data were collected at baseline; adverse events and time-to-event data (overall survival [OS], progression-free survival [PFS] and hepatic PFS) were collected at every 3-month follow-up visit. We used the multivariable Cox proportional hazard model and propensity score matching to identify independent prognostic factors for effectiveness outcomes. The median OS was 16.5 months, the median PFS was 6.1 months, and the median hepatic PFS was 6.7 months. Partition model dosimetry resulted in improved OS compared to body surface area calculations on multivariable analysis (hazard ratio 0.65; 95% CI 0.46-0.92; p= 0.0144), which was confirmed in the exact matching propensity score analysis (hazard ratio 0.56; 95% CI 0.35-0.89; p= 0.0136). Other independent prognostic factors for OS were ECOG-performance status >0 (p= 0.0018), presence of ascites (p= 0.0152), right-sided tumours (p= 0.0002), the presence of portal vein thrombosis (p= 0.0378) and main portal vein thrombosis (p= 0.0028), ALBI grade 2 (p= 0.0043) and 3 (p= 0.0014). Adverse events were recorded in 36.7% of patients, with 9.7% of patients experiencing grade 3 or higher adverse events. This large prospective observational dataset shows that TARE is an effective and safe treatment in patients with HCC. Using partition model dosimetry was associated with a significant improvement in survival outcomes. Transarterial radioembolization (TARE) is a form of localised radiation therapy and is a potential treatment option for primary liver cancer. We observed how TARE was used in real-life clinical practice in various European countries and if any factors predict how well the treatment performs. We found that when a more complex but personalised method to calculate the applied radiation activity was used, the patient responded better than when a more generic method was used. Furthermore, we identified that general patient health, ascites and liver function can predict outcomes after TARE. NCT02305459.

PET/CT calibration for post-treatment standard body scan acquisition with yttrium-90 resin micro-SPHERES

IntroductionAmong the objectives in treatments with yttrium-90 spheres, is to demonstrate that the tumoricidal dose is achieved and that hepatotoxic doses are avoided, as well as that there is no extrahepatic deposition. Material and methodsWe use different amounts of yttrium-90 resin micro-spheres and a NEMA NU2-2007 phantom to check if the scanner maintains a response that allows real dosimetric calculations. ResultsThe Gemini tomograph responds linearly in a wide range of activities with R2 = 0.9983. ConclusionThe detection capacity of the PET equipment allows us to carry out standard body studies with dosimetric purposes with times of five minutes per bed. It also make possible to verify the absence of extrahepatic deposition of significant amounts of yttrium 90 spheres.

Prognostic Factors for Effectiveness Outcomes After Transarterial Radioembolization in Metastatic Colorectal Cancer: Results From the Multicentre Observational Study CIRT

BackgroundTransarterial radioembolisation (TARE) with Yttrium-90 resin microspheres is a treatment option for patients with metastatic colorectal cancer in the liver (mCRC). A better understanding of the prognostic factors and treatment application can improve survival outcomes. MethodsWe analysed the safety and effectiveness of 237 mCRC patients included in the prospective observational study CIRSE Registry for SIR-Spheres Therapy (CIRT) for independent prognostic factors for overall survival (OS), progression-free survival (PFS) and hepatic progression-free survival (hPFS) using the Cox proportional-hazard model. ResultsThe median OS was 9.8 months, median PFS was 3.4 months and median hPFS was 4.2 months. Independent prognostic factors for an improved overall survival were the absence of extra-hepatic disease (P= .0391), prior locoregional procedures (P= .0037), an Aspartate transaminase to Platelet Ratio Index (APRI) value of ≤0.40 (P< .0001) and International Normalized Ratio (INR) ≤1 (P= .0078). Partition model dosimetry resulted in improved OS outcomes compared to the body surface area model (P = .0120). Independent predictors for PFS were APRI >0.40 (P = .0416) and prior ablation (P = .0323), and for hPFS these were 2 to 5 tumor nodules (P = .0148), Albumin-bilirubin (ALBI) grade 3 (P = .0075) and APRI >0.40 (P = .0207). During the study, 95 of 237 (40.1%) patients experienced 197 adverse events, with 28 of 237 (11.8%) patients having a grade 3 or higher adverse events. ConclusionIncluding easy-to-acquire laboratory markers INR, APRI, ALBI and using partition model dosimetry can identify mCRC patients that may benefit from TARE.

ALBI grade for outcome prediction in patients affected by hepatocellular carcinoma treated with transarterial radioembolization

Introduction and aimDiagnosis of hepatocellular carcinoma (HCC) often occurs when the disease is unresectable and therapeutic options are limited. The extent of disease and liver function according to Child-Pugh (C-P) classification are the main prognostic factors guiding clinicians in the management of HCC. The integration of albumin-bilirubin (ALBI) grade is emerging to assess liver function on account of its objectivity and reproducibility. Our aim was to investigate the value of the ALBI grade in predicting the outcome in patients treated with transarterial radioembolization (TARE).MethodsWe retrospectively enrolled patients with advanced and unresectable HCC treated with TARE in our institution. All patients underwent a preliminary dosimetric study before Yttrium-90 resin microsphere TARE. Barcelona Clinic Liver Cancer (BCLC), C-P, and ALBI scores were established at the time of TARE. Overall survival (OS), progression-free survival (PFS), and survival after TARE were assessed with the Kaplan-Meier method. Survival analyses were stratified according to ALBI grade, C-P, and BCLC classification. Univariate and multivariate Cox proportional regression models determined the association between prognostic factors and clinical outcomes.ResultsIn total, 72 patients were included in the study, showing an OS of 51 months. The ALBI grade identified groups of patients with different prognoses both in the whole cohort and within the C-P classes, especially between ALBI 1 and ALBI 2. This result is confirmed also within BCLC classes. In treatment naïve patients, the ALBI grade was not able to predict outcomes, whereas the presence and degree of portal vein thrombosis (PVT) significantly affected prognosis.ConclusionsThe ALBI grade provided a more accurate prognostic stratification than the C-P classification in patients with intermediate and advanced HCC treated with TARE. However, the outcome of HCC is affected not only by liver function but also by disease-related characteristics, such as disease burden and degree of PVT. Including the ALBI grade in clinical guidelines may improve the management of patients affected by HCC.

Calibración de PET/TC para adquisición de estudio de cuerpo estándar postratamiento con esferas de resina de ytrio-90

IntroductionAmong the objectives in treatments with yttrium-90 spheres is to demonstrate that the tumoricidal dose is achieved and that hepatotoxic doses are avoided, as well as that there is no extrahepatic deposition. Material and methodsWe use different amounts of yttrium-90 resin micro-spheres and a NEMA NU2-2007 phantom to check if the scanner maintains a response that allows real dosimetric calculations. ResultsThe Gemini tomograph responds linearly in a wide range of activities with R2=0.9983. ConclusionThe detection capacity of the PET equipment allows us to carry out standard body studies with dosimetric purposes with times of five minutes per BED. It also make possible to verify the absence of extrahepatic deposition of significant amounts of yttrium 90 spheres.

Toxicity comparison of yttrium-90 resin and glass microspheres radioembolization.

To investigate the clinical, hematological and biochemical toxicity differences between glass and resin yttrium-90 (90Y)-microspheres radioembolization treatment of primary and metastatic liver disease. Between May 2014 and November 2016 all consecutive glass and resin 90Y microspheres radioembolization treatments were retrospectively analyzed. Biochemical, hematological and clinical data were collected at treatment day, two weeks, one month and three months follow-up. Post-treatment 90Y PET/CTs were assessed for the absorbed doses in non-tumorous liver volume (DNTLV) and tumor volume (DTV). Biochemical, hematological and clinical toxicity were compared between glass and resin using chi square tests and repeated ANOVA measures. Biochemical and clinical toxicity was correlated with DNTLV,total by means of Pearson correlation and independent T-tests. A total of 85 patients were included (n=44 glass, n=41 resin). Clinical toxicity the day after treatment (i.e. abdominal pain (p=0.000), nausea (p=0.000) and vomiting (p=0.003)) was more prevalent for resin. Biochemical and hematological toxicities were similar for both microspheres. The DNTLV,total was significantly higher in patients with REILD grade ≥3 in the resin group (43.5 versus 33.3 Gy (p=0.050)). A similar non-significant trend was seen in the glass group: 95.0 versus 69.0 Gy (p=0.144). The clinical, hematological and biochemical toxicity of radioembolization treatment with glass and resin is comparable, however, post-embolization syndrome related complaints are more common for resin.

Abstract No. 562 Evaluation of a method for calculating yttrium-90 resin microsphere particle load

Y-90 microsphere vendors enable personalization of patient dose prescription with flexible ordering options available for treatment. We aim to evaluate a method for Y-90 resin microsphere particle load calculation to determine the amount of microspheres delivered to treatment regions.