Yttrium-90 Transarterial Radioembolization Research Articles

Yttrium-90 Induces an Effector Memory Response with Neoantigen Clonotype Expansion: Implications for Immunotherapy.

90Y can safely treat HCC; however, it causes transient lymphopenia. In this article, 90Y stimulates a peripheral effector memory response independent of initial treatment response. TCR sequencing revealed that polyclonal profiles in patients without an OR to treatment were associated with rapid progression rates 6 months after 90Y.

Outcomes Analysis of Yttrium-90 Radioembolization for Tumors Other Than Metastatic Colorectal Cancer from the Radiation-Emitting SIR-Spheres in Nonresectable (RESiN) Registry

PurposeTo characterize the response and survival outcomes of yttrium-90 (90Y) transarterial radioembolization (TARE) for unresectable, liver-dominant metastases from primary neoplasms other than colorectal carcinoma. Materials and MethodsThis study included 1,474 patients enrolled in the Radiation-Emitting Society of Interventional Radiology (SIR)–Spheres in Nonresectable Liver Tumor registry who received resin 90Y-TARE as part of their oncologic management for unresectable primary or secondary liver tumors (NCT 02685631). Of these patients, 33% (481/1,474) were treated for liver metastases of noncolorectal origin (m-non-CRC) compared with 34% (497/1,474) treated for metastatic colorectal cancer (mCRC) and 34% (496/1,474) treated for hepatocellular carcinoma. Treatment response and cancer survival probabilities were computed and compared for each primary cancer type. The Kaplan-Meier method and log-rank test were used to compare survival outcomes. ResultsRadiological responses were observed in 12 unique cancer types, mostly heavily pretreated malignancies refractory to multiple lines of systemic therapies. The overall use of resin 90Y-TARE in m-non-CRC resulted in better treatment outcomes in terms of duration of response, progression-free survival, time to progression, and overall survival (P = .04, P = .02, P = .01, and P = .04, respectively). Analyses of cancer cell types revealed that metastatic neuroendocrine tumor, sarcoma, and ovarian, renal, prostate, and breast cancers were associated with superior treatment outcomes, whereas worse treatment outcomes were observed in metastatic lung, gastric, pancreatic, and esophageal cancers. ConclusionsReal-world data demonstrate the use of resin 90Y-TARE in m-non-CRC refractory to standard chemotherapy. For some cell types, this expanded use achieved superior treatment outcomes relative to the reference standard of mCRC, suggesting the need for inquiry into broadened indications for 90Y-TARE.

Immune Modulation in Untreated, Contralateral Hepatic Metastases after Yttrium-90 Radioembolization of Microsatellite Stable Colorectal Cancer

PurposeTo assess immunogenic effects in unembolized contralateral tumor after single lobar yttrium-90 transarterial radioembolization (90Y-TARE) of colorectal liver metastases (CRLMs). Material and MethodsThe analysis comprised 10 patients with microsatellite stable (MSS) CRLM scheduled for staged treatment in the prospective AROMA trial. Eligibility criteria included bilobar metastatic disease with >5 lesions without any treatment within 3 weeks. Baseline biopsy was followed by initial 90Y-TARE treatment of 1 liver lobe, followed by a second biopsy of yet untreated tumors in the other liver lobe at a median of 13 days (range, 4–49 days) immediately before second treatment. Tumor biopsies and peripheral blood mononuclear cells (PBMCs) were collected before treatments for immune cell analysis. Patients were stratified into responders and nonresponders based on tumor control or progression during follow-up. ResultsAt baseline, responders (n = 4) displayed lower concentrations of FoxP3+ cells and colocation of CD4+FoxP3+ cells than nonresponders (both P = .02) in tumor tissues. At second biopsy, nonresponders showed a higher CD68+ macrophage density (P = .0014) than responders. Responders displayed fewer CD4+FoxP3+ T cells than CD8+ T cells at all time points (P = .02 and P = .0428). Nonresponders demonstrated a trending increase in CD68+ macrophages (P = .062), as well as a higher CD8+PD1+/CD8+ ratio (P = .062). PBMCs of nonresponders displayed lower CD8+PD1+ T cells and CD8+PD1+/CD8+ ratio at both time points. Conclusions90Y-TARE induces local immunogenic effects in nonexposed MSS CRLM, as well as systemic exhaustion of immune cells in nonresponders. Clinical implications such as a prognostic role or synergism of 90Y-TARE and checkpoint inhibition in MSS CRLM warrant further investigation.

Precision individual dosimetry in Yttrium-90 transarterial radioembolization in the presence of Au nanoparticles

Individual post-treatment dosimetry plays a crucial role in assessing the effectiveness of Y-90 transarterial radioembolization (TARE) treatment. Y-90 positron emission tomography (PET) imaging is widely regarded as the gold standard for post-TARE dosimetry. However, a major limitation of Y-90 PET imaging is the low positron yield of Y-90. This study aimed to address this limitation and improve individual dosimetry using Au nanoparticles (NPs)-induced pair production in Y-90 PET imaging. The GATE Monte Carlo platform was used to simulate post-TARE PET imaging. The study examined five levels of Au NP concentration in the liver tumor: 1%, 5%, 10%, 15%, and 20% by weight. The quality of the acquired PET images was evaluated by calculating the signal-to-background ratio (SBR) and contrast-to-noise ratio (CNR). The errors in PET-based dose volume histograms (DVHPET-based) and reference dose volume histograms (DVHrefrence) were evaluated through various metrics, including root-mean-square error (RMSE), mean absorbed dose (Dmean), and maximum absorbed dose (Dmax). The results showed that as the concentration of Au NPs increased in the tumor, the CNR and SBR values also increased. At concentrations 5 wt% and above, the difference in the values of Dmean and Dmax obtained from the reference dosimetry and PET-based dosimetry is less than 5%. The calculated RMSE values indicated that concentrations 5 wt% and above exhibited acceptable agreement between the DVHPET-based and DVHrefrence. When the concentration of Au NPs increases up to 5 wt%, the presence of Au NPs within the tumor does not significantly affect the Dmean. Conversely, with the presence of Au NPs, at concentrations of 10, 15, and 20 wt%, the Dmean within the tumor experiences reductions of approximately 6%, 10%, and 14%, respectively. The pair production was induced by simultaneously injecting Y-90 and Au NPs into the tumor. Our study demonstrated that dosimetry accuracy in TARE improved through induced positron PET imaging. As a consequence of the dose reduction phenomenon observed upon introducing Au NPs into the tumor, the optimal concentration of Au NPs for enhancing dosimetric precision was determined to be 5 wt%.

Predictors of Hepatic Decompensation after Yttrium90 Transarterial Radioembolization—Optimizing Patient Selection

Abstract Purpose Yttrium 90 (Y90) transarterial radioembolization (TARE) is effective for unresectable hepatocellular carcinoma (HCC) or to bridge/downstage before transplant; however, optimal patient selection is not well-described. This study aims to identify factors that increase risk of liver decompensation resulting in hospital admissions after TARE. Methods Patients who received Y90 as their first treatment during 2012 to 2022 were identified from a prospectively collected database of 1675 HCC patients. Clinically significant hepatic decompensation was defined as total bilirubin more than or equal to 3 mg/dL or any increase in Model for End-stage Liver Disease (MELD) score resulting in readmission within 60 days or death. Results Of 137 patients, 7 (5.1%) developed hepatic decompensation requiring admission within 30 days and an additional 8 (10.9%) within 60 days. Two of these patients (1.4%) died and two (1.4%) required urgent transplant within 2 months. Preprocedure albumin less than 3.5 gm/dL (p = 0.0207), international normalized ratio more than 1.2 (p = 0.017), ascites (p = 0.036), elevated MELD (p = 0.012), and Child-Pugh (p = 0.007) scores were significant predictors of decompensation, while creatinine and sodium were not. Patients with Child-Pugh B score were three to four times more likely to decompensate (28 vs. 8%) compared to Child-Pugh A. For every unit increase in Child-Pugh score more than 6, odds of decompensation increased by a factor of 2.15. Conclusion Y90 TARE is safe and effective; however, 10.9% patients require readmission for worsened liver function. Because ascites is a significant factor in predicting decompensation and all patients require adequate renal function to receive Y90 TARE, Child-Pugh score may be more useful than MELD for patient selection. Further risk stratification may be required for those with a Child-Pugh score more than or equal to 7.

Are survival outcomes dependent on the tumour dose threshold of 139 Gy in patients with chemorefractory metastatic colorectal cancer treated with yttrium-90 radioembolization using glass particles? A real-world single-centre study.

To compare the survival and objective response rate (ORR) of the patients receiving estimated tumour absorbed dose (ETAD) <140 Gy versus ETAD ≥140 Gy in patients with advanced chemorefractory colorectal carcinoma liver metastases (CRCLM) treated with yttrium-90 transarterial radioembolization (90Y TARE). Between August 2016 and August 2023 adult patients with unresectable, chemorefractory CRCLM treated with 90Y TARE using glass particles, were retrospectively enrolled. Primary outcomes were overall survival (OS) and hepatic progression free survival (hPFS). Secondary outcome was ORR. A total of 40 patients with a mean age of 66.2 ± 7.8 years met the inclusion criteria. Mean ETAD for group 1 (ETAD <140 Gy) and group 2 (ETAD ≥140) were 131.2 ± 17.4 Gy versus 195 ± 45.6 Gy, respectively. The mean OS and hPFS for group 1 versus group 2 were 12 ± 10.3 months and 8.1 ± 9.3 months versus 9.3 ± 3 months and 7.1 ± 8.4 months, respectively and there were no significant differences (P = .181 and P = .366, respectively). ORR did not show significant difference between the groups (P = .432). In real-world practice, no significant difference was found in OS, hPFS, and ORR between patients who received ETAD <140 Gy versus ETAD ≥140 Gy in patients with CRCLM, in this series. This study demonstrated that increased tumour absorbed doses in radioembolization may not provide additional significant advantage for OS and hPFS for patients with CRCLM.

Predictability of the radiological response to Yttrium-90 transarterial radioembolization by dynamic magnetic resonance imaging-based radiomics analysis in patients with intrahepatic cholangiocarcinoma

The study aims to investigate the predictability of the radiological response in intrahepatic cholangiocarcinoma (iCC) patients undergoing Yttrium-90 transarterial radioembolization (TARE) with a combined model built on dynamic magnetic resonance imaging (MRI)-based radiomics and clinical features. Thirty-six naive iCC patients who underwent TARE were included in this study. The tumor segmentation was performed on the axial T2-weighted (T2W) without fat suppression, axial T2W with fat suppression, and axial T1-weighted (T1W) contrast-enhanced (CE) sequence in equilibrium phase (Eq). At the sixth month MRI follow-up, all patients were divided into responders and non-responders according to the modified Response Evaluation Criteria in Solid Tumors. Subsequently, a radiomics score (rad-score) and a combined model of the rad-score and clinical features for each sequence were generated and compared between the groups. Thirteen (36.1%) patients were considered responders, and the remaining 23 (63.9%) were non-responders. Responders exhibited significantly lower rad-scores than non-responders (P < 0.050 for all sequences). The radiomics models showed good discriminatory ability with an area under the curve (AUC) of 0.696 [95% confidence interval (CI), 0.522–0.870] for the axial T1W-CE-Eq, AUC of 0.839 (95% CI, 0.709–0.970) for the axial T2W with fat suppression, and AUC of 0.836 (95% CI, 0.678–0.995) for the axial T2W without fat suppression. Radiomics models created by pre-treatment MRIs can predict the radiological response to Yttrium- 90 TARE in iCC patients with high accuracy. Combining radiomics with clinical features could increase the power of the test. Large-scale studies of multi-parametric MRIs with internal and external validations are needed to determine the clinical value of radiomics in iCC patients.

Contralateral Hypertrophy Post Yttrium-90 Transarterial Radioembolization in Patients With Hepatocellular Carcinoma and Portal Vein Tumor Thrombus.

Objectives Contralateral hypertrophy of non-irradiated liver following Yttrium-90 (90Y) transarterial radioembolization (TARE) is increasingly recognized as an option to facilitate curative surgical resection in patients that would otherwise not be surgical candidates due to a small future liver remnant (FLR). This study aimed to investigate the correlation between patient features and liver hypertrophy and identify potential predictors for liver growth in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) undergoing TARE. Methodology Twenty-three patients with HCC and PVTT were included. Contralateral liver hypertrophy was assessed at six months posttreatment based on CT or MRI imaging. Thirteen patient features were selected for statistical and prediction analysis. Univariate Spearman correlation and analysis of variance (ANOVA) tests were performed. Subsequently, four feature-selection methods based on multivariate analysis were used to improve model generalization performance. The selected features were applied to train linear regression models, with fivefold cross-validation to assess the performance of the predicted models. Results The ratio of disease-free target liver volume to spared liver volume and total liver volume showed the highest correlations with contralateral hypertrophy (P-values = 0.03 and 0.05, respectively). In three out of four feature-selection methods, the feature of disease-free target liver volume to total liver volume ratio was selected, having positive correlations with the outcome and suggesting that more hypertrophy may be expected when more volume of disease-free liver is irradiated. Conclusions Contralateral hypertrophy post-90Y TARE can be an option for facilitating surgical resection in patients with otherwise small FLR.

Imaging Considerations before and after Liver-Directed Locoregional Treatments for Metastatic Colorectal Cancer.

Colorectal cancer is a leading cause of cancer-related death. Liver metastases will develop in over one-third of patients with colorectal cancer and are a major cause of morbidity and mortality. Even though surgical resection has been considered the mainstay of treatment, only approximately 20% of the patients are surgical candidates. Liver-directed locoregional therapies such as thermal ablation, Yttrium-90 transarterial radioembolization, and stereotactic body radiation therapy are pivotal in managing colorectal liver metastatic disease. Comprehensive pre- and post-intervention imaging, encompassing both anatomic and metabolic assessments, is invaluable for precise treatment planning, staging, treatment response assessment, and the prompt identification of local or distant tumor progression. This review outlines the value of imaging for colorectal liver metastatic disease and offers insights into imaging follow-up after locoregional liver-directed therapy.

Histopathologic Changes after Yttrium-90 Radioembolization of Colorectal Liver Metastases: A Pilot Feasibility Study

PurposeTo evaluate the histopathologic changes and potential correlations of tumor absorbed dose (TAD) after yttrium-90 transarterial radioembolization (TARE) for colorectal liver metastases (CLMs). Materials and MethodsThis prospective pilot study assessed 12 patients with 13 CLMs through positron emission tomography (PET)/computed tomography (CT)–guided biopsies before, immediately after TARE (T0), and 3 weeks after TARE (T3). Subsequent sampling from the same location was enabled by fiducial placement. Biopsy samples were evaluated with hematoxylin and eosin, TUNEL, Ki67, OxPhos, caspase-3 (CC3), and pH2AX antibodies. Proliferation changes (Ki67) and double-strand DNA breaks (DSBs) were evaluated quantitatively. TAD was calculated on post-TARE PET/CT scan of the biopsy needle location at T0 and T3. ResultsMedian TAD at 3 weeks after TARE was 162 Gy (interquartile range (IQR), 92–211 Gy). DSBs decreased significantly from T0 (median, 77%; IQR, 75%–100%) to T3 (median, 14%; IQR, 0%–54%; P = .028). A decrease in Ki67 was also documented (median, 73%; IQR, 70%–80% at T0 vs median, 41%; IQR, 0%–66% at T3; P = .046). There was a strong positive correlation between TAD and DSBs at T0 (r[9] = 0.68) and a strong negative correlation at T3 (r[10] = −0.855; P = .042 and P = .002, respectively). There was a strong negative correlation between TAD and Ki67 at both T0 (r[9] = −0.733; P = .025) and T3 (r[10] = −0.681; P = .030). Tumors that exhibited caspase-3 activation (8/13, 62%) at either T0 or T3 time point were more likely to develop progression (7/8 [88%] vs 1/5 [20%]; P = .015). ConclusionsPost-TARE biopsy can be used to assess TAD and histopathologic changes. Significant decreases in DSBs and proliferation index were noted after TARE. Post-TARE CC3 activation deserves further exploration.

Outcomes in Patients with Macrotrabecular-Massive Subtype Hepatocellular Carcinoma Treated with Yttrium-90 Transarterial Radioembolization

PurposeTo compare the outcomes of yttrium-90 transarterial radioembolization (TARE) in patients with hepatocellular carcinoma (HCC) with and without macrotrabecular-massive (MTM) subtypes. Materials and MethodsForty-one consecutive patients with HCC (male, 90.3%; mean age, 65.3 years [SD ± 10.7]) who underwent yttrium-90 TARE between September 2014 and January 2022 were grouped into the MTM-HCC (n = 17, 41.5%) and non–MTM-HCC (n = 24, 58.5%) groups based on their histopathological subtypes. Demographic, clinical, and radiological characteristics were compared. Survival, univariate, and multivariate analyses were performed, and prognostic factors were evaluated. ResultsIn MTM-HCC group, the rates of moderately to poorly differentiated tumors were significantly higher (13/17 vs 8/16, P = .007), and new intrahepatic/extrahepatic metastases were detected more frequently (12/17 vs 15/24, P = .038). Median overall survival (OS) in the cohort was 29 months (range, 17.1–40.9 months), whereas patients with MTM-HCC had a significantly shorter median OS (20 vs 44 months, P = .014). In univariate analysis, MTM-HCC subtype (hazard ratio [HR], 2.690; P = .021), the presence of satellite nodules (HR, 3.810; P = .004), and macrovascular invasion (HR, 3.321; P = .012) were identified as significant prognostic factors. In multivariate analysis, MTM-HCC subtype and macrovascular invasion were determined as independent poor prognostic factors (P = .038 and P = .012, respectively). ConclusionsIn patients with HCC treated with yttrium-90 TARE, both the rates of moderately to poorly differentiated histopathological classes and the development of intrahepatic or extrahepatic metastases were significantly higher in the MTM-HCC subtype. OS was worse in patients with MTM-HCC, and macrovascular invasion and MTM-HCC subtype were identified as independent poor prognostic factors.

Radiomics-Based Prediction Model for Outcome of Radioembolization in Metastatic Colorectal Cancer.

To evaluate the benefit of a contrast-enhanced computed tomography (CT) radiomics-based model for predicting response and survival in patients with colorectal liver metastases treated with transarterial Yttrium-90 radioembolization (TARE). Fifty-one patients who underwent TARE were included in this single-center retrospective study. Response to treatment was assessed using the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) at 3-month follow-up. Patients were stratified as responders (complete/partial response and stable disease, n = 24) or non-responders (progressive disease, n = 27). Radiomic features (RF) were extracted from pre-TARE CT after segmentation of the liver tumor volume. A model was built based on a radiomic signature consisting of reliable RFs that allowed classification of response using multivariate logistic regression. Patients were assigned to high- or low-risk groups for disease progression after TARE according to a cutoff defined in the model. Kaplan-Meier analysis was performed to analyze survival between high- and low-risk groups. Two independent RF [Energy, Maximal Correlation Coefficient (MCC)], reflecting tumor heterogeneity, discriminated well between responders and non-responders. In particular, patients with higher magnitude of voxel values in an image (Energy), and texture complexity (MCC), were more likely to fail TARE. For predicting treatment response, the area under the receiver operating characteristic curve of the radiomics-based model was 0.75 (95% CI 0.48-1). The high-risk group had a shorter overall survival than the low-risk group (3.4 vs. 6.4months, p < 0.001). Our CT radiomics model may predict the response and survival outcome by quantifying tumor heterogeneity in patients treated with TARE for colorectal liver metastases.

Yttrium-90 Transarterial Radioembolization of Primary Lung Cancer Metastases to the Liver

PurposeTo assess whether yttrium-90 transarterial radioembolization (TARE) is safe and effective in the treatment of primary lung cancer metastases to the liver (LCML). Methods and MethodsThis retrospective study included 57 patients with LCML who were treated with 79 TARE treatments. Histology included non–small cell lung cancer (NSCLC) (n = 27), small cell lung cancer (SCLC) (n = 17), and lung carcinoid (LC) (n = 13). Survival was calculated using Kaplan–Meier method; differences between groups were estimated using log rank test. Cox proportional hazards model was used to determine factors influencing survival. Adverse events were graded using the Society of Interventional Radiology Adverse Events Classification. ResultsMedian overall survival (OS) was as follows: NSCLC, 8.3 months (95% confidence interval [CI], 6.3–16.4 months); SCLC, 4.1 months (95% CI, 1.9–6.6 months); and LC, 43.5 months (95% CI, 7.8–61.4 months). For NSCLC, presence of bilobar vs unilobar disease (hazard ratio [HR], 5.24; 95% CI, 1.64–16.79; P = .002); more tumors, 2–5 vs 1 (HR, 4.88; 95% CI, 1.17–20.37; P = .003) and >5 vs 1 (HR, 3.75; 95% CI, 0.95–6.92; P = .05); and lobar vs segmental treatment (HR, 2.56; 95% CI, 0–NA; P = .002) were negative predictors of OS. For SCLC, receipt of >2 lines of chemotherapy vs ≤2 lines (HR, 3.16; 95% CI, 0.95–10.47; P = .05) was a negative predictor of OS. For LC, tumor involvement of >50% was a negative predictor of OS (HR, 3.77 × 1015; 95% CI, 0–NA; P = .002). There were 11 of 79 severe or life-threatening adverse events within 30 days (abdominal pain, altered mental status, nausea/vomiting, acalculous/aseptic cholecystitis, hyponatremia, pancreatitis, renal failure, and death from pneumonia). ConclusionsTARE has an acceptable safety profile for the treatment of LCML, with survival benefits best seen in LC tumors.

Yttrium-90 transarterial radioembolization and capecitabine in hepatocellular carcinoma with portal vein involvement.

Hepatocellular carcinoma (HCC) with portal vein tumor thrombus is considered an advanced stage disease. Non-surgical local and systemic therapies are the only treatment options available. To analyze the survival and toxicity outcomes of systemic treatment concurrent with yttrium-90 transarterial radioembolization in HCC with liver-limited disease and portal vein involvement with Child-Pugh B liver reserve. The medical records of 22 patients who underwent yttrium-90 transarterial radioembolization concomitant with capecitabine chemotherapy as first-line treatment between 2014 and 2019 were retrospectively reviewed. Twenty-two patients were included in the study. Grade 3 to 4 side effects were evaluated, and hepatic encephalopathy developed in 1 patient after yttrium-90 transarterial radioembolization. In the fourth month of radiological evaluation, 11 patients had a partial response (50%), 5 patients had stable disease (22.7%), and 6 patients (27.3%) developed progressive disease. The median survival time was 21 months. Combined treatment with yttrium-90 transarterial radioembolization and capecitabine may be an effective and safe treatment option. Treatment was associated with a median overall survival of 21 months and a disease control rate of 72.7% at 4 months in patients with inoperable HCC.

Effect of Previous Transarterial Chemoembolization on Survival and Toxicity after Yttrium-90 Transarterial Radioembolization of Hepatocellular Carcinoma in the Radiation-Emitting SIR-Spheres in Nonresectable Liver Tumor Registry

PurposeTo determine overall survival (OS), best response, and toxicities in patients with hepatocellular carcinoma (HCC) previously treated with chemoembolization (TACE+) or yttrium-90 resin transarterial radioembolization (TARE) compared with those of TACE-naïve (T-N) participants. Materials and MethodsIn this prospective, observational study, 262 adult participants with HCC were divided into TACE+ (n = 93, 35%) or T-N (n = 169, 65%) groups, included from 36 centers in the United States. Overall survival (OS) was assessed using Kaplan-Meier analysis from the date of TARE. Best response at 6 months was evaluated using modified Response Evaluation Criteria in Solid Tumors. Six-month toxicities were reported using Common Terminology Criteria for Adverse Events, version 5. ResultsMedian OS for patients in the TACE+ and T-N groups was 22.3 months (95% CI: 17.2 to not reachable) and 21.5 months (95% confidence interval [CI]: 14.9–29.9), respectively (P = .6). Imaging at 6 months ± 2 weeks was available in 156 of 262 (60%) participants. Partial or complete response was seen in 27 of 55 patients (49%) in the TACE+ group and 65 of 101 patients (64%) in the T-N group (P = .2). Six-month toxicities were available in 69 of 93 patients (74%) in the TACE+ group and 135 of 167 patients (81%) in the T-N group. Attributable Grade 3 or greater liver function toxicities were similar between the study groups (all P > .05). ConclusionsOS and imaging response at 6 months in the TACE+ group was similar to that in the T-N group with similar toxicities. Radioembolization is an acceptable treatment option for patients with HCC previously treated with TACE.

Bilobar Radioembolization Carries the Risk of Radioembolization-Induced Liver Disease in the Treatment of Advanced Hepatocellular Carcinoma: Safety and Efficacy Comparison to Systemic Therapy with Atezolizumab/Bevacizumab.

Recommended treatment options for advanced-stage hepatocellular carcinoma (HCC) include systemic therapy (ST) and trans-arterial radioembolization (TARE) with Yttrium-90 (Y90). Before the approval of immune-checkpoint inhibitors, a similar safety profile was reported for TARE and ST with tyrosine kinase inhibitors (TKI). However, whole-liver treatment and underlying cirrhosis were identified as risk factors for potentially lethal radioembolization-induced liver disease (REILD). Therefore, the safety and efficacy of TARE and ST with atezolizumab/bevacizumab were compared in patients with advanced HCC involving at least both liver lobes in a retrospective real-world cohort. In total, 74 patients with new or recurrent advanced-stage HCC (BCLC stage B/C) were included if treated with either bilobar TARE (n = 33) or systemic combination therapy with atezolizumab plus bevacizumab (n = 41). Most patients had compensated liver function (90.5% were classified as Child-Pugh Score A, 73% as ALBI Grade 1) at baseline. Although not significant, patients treated with ST showed a more prolonged overall survival than those treated with Y90 TARE (7.1 months vs. 13.0 months, p = 0.07). While a similar disease control rate could be achieved with bilobar TARE and atezolizumab/bevacizumab, in the TARE group, overall survival was curtailed by the occurrence of REILD. In patients with underlying liver cirrhosis, the liver function at baseline was a predictor for REILD.

Resection Postradioembolization in Patients With Single Large Hepatocellular Carcinoma.

The aim of this study was to evaluate the efficacy of yttrium-90 transarterial radioembolization (TARE) to convert to resection initially unresectable, single, large (≥5cm) hepatocellular carcinoma (HCC). TARE can downsize cholangiocarcinoma to resection but its role in HCC resectability remains debatable. All consecutive patients with a single large HCC treated between 2015 and 2020 in a single tertiary center were reviewed. When indicated, patients were either readily resected (upfront surgery) or underwent TARE. TARE patients were converted to resection (TARE surgery) or not (TARE-only). To further assess the effect of TARE on the long-term and short-term outcomes, a propensity score matching analysis was performed. Among 216 patients, 144 (66.7%) underwent upfront surgery. Among 72 TARE patients, 20 (27.7%) were converted to resection. TARE-surgery patients received a higher mean yttrium-90 dose that the 52 remaining TARE-only patients (211.89±107.98 vs 128.7±36.52Gy, P <0.001). Postoperative outcomes between upfront-surgery and TARE-surgery patients were similar. In the unmatched population, overall survival at 1, 3, and 5 years was similar between upfront-surgery and TARE-surgery patients (83.0%, 60.0%, 47% vs 94.0%, 86.0%, 55.0%, P =0.43) and compared favorably with TARE-only patients (61.0%, 16.0% and 9.0%, P <0.0001). After propensity score matching, TARE-surgery patients had significantly better overall survival than upfront-surgery patients ( P =0.021), while disease-free survival was similar ( P =0.29). TARE may be a useful downstaging treatment for unresectable localized single large HCC providing comparable short-term and long-term outcomes with readily resectable tumors.

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.

Early Prediction of Response of Hepatocellular Carcinoma to Yttrium-90 Radiation Segmentectomy Using a Machine Learning MR Imaging Radiomic Approach

PurposeTo assess the accuracy of a machine learning (ML) approach based on magnetic resonance (MR) imaging radiomic quantification obtained before treatment and early after treatment for prediction of early hepatocellular carcinoma (HCC) response to yttrium-90 transarterial radioembolization (TARE). Materials and MethodsIn this retrospective single-center study of 76 patients with HCC, baseline and early (1–2 months) post-TARE MR images were collected. Semiautomated tumor segmentation facilitated extraction of shape, first-order histogram, and custom signal intensity–based radiomic features, which were then trained (n = 46) using a ML XGBoost model and validated on a separate cohort (n = 30) not used in training to predict treatment response assessed at 4–6 months (based on modified Response and Evaluation Criteria in Solid Tumors criteria). Performance of this ML radiomic model was compared with those of models comprising clinical parameters and standard imaging characteristics using area under the receiver operating curve (AUROC) analysis for prediction of complete response (CR). ResultsSeventy-six tumors with a mean (±SD) diameter of 2.6 cm ± 1.6 were included. Sixty, 12, 1, and 3 patients were classified as having CR, partial response, stable disease, and progressive disease, respectively, at 4–6 months posttreatment on the basis of MR images. In the validation cohort, the radiomic model showed good performance (AUROC, 0.89) for prediction of CR, compared with models comprising clinical and standard imaging criteria (AUROC, 0.58 and 0.59, respectively). Baseline imaging features appeared to be more heavily weighted in the radiomic model. ConclusionsThe use of ML modeling of radiomic data combining baseline and early follow-up MR imaging could predict HCC response to TARE. These models need to be investigated further in an independent cohort.

THU-154 - Improved identification of good candidates for the treatment of intermediate/advanced hepatocellular carcinoma by Yttrium-90 transarterial radioembolization

THU-154 - Improved identification of good candidates for the treatment of intermediate/advanced hepatocellular carcinoma by Yttrium-90 transarterial radioembolization