Yttrium-90 Radioembolization Research Articles

Yttrium-90 radioembolization treatment strategies for management of hepatocellular carcinoma

Yttrium-90 radioembolization treatment strategies for management of hepatocellular carcinoma

Durvalumab-Induced Immune Thrombocytopenia in Patients with Advanced Cholangiocarcinoma Undergoing Yttrium-90 Radioembolization

Introduction: Immune thrombocytopenia (ITP) secondary to durvalumab, a programmed cell death ligand 1 inhibitor, is a rare but clinically significant immune-related adverse event. Herein, we present 2 patients with cholangiocarcinoma who developed ITP immediately post-yttrium-90 radioembolization (Y90-RE) while on durvalumab-based systemic therapy. We hypothesize that given the timing, the immunotherapy and the radioembolization combination led to this event. It is not uncommon given the approval of immunotherapy and its role in locoregional therapies, that patients are treated with a combination of systemic immunotherapy and radioembolization or other forms of radiation, thus signifying the importance of potential complications. Case Presentation: Two patients, a 67-year-old female and a 60-year-old man, with biopsy-proven advanced unresectable cholangiocarcinoma, received a combination of systemic therapy with durvalumab, gemcitabine, and cisplatin and subsequently Y90-RE. Both patients developed ITP following in the immediate post-Y90-RE period. All other causes of ITP were comprehensively ruled out and treatment for ITP was initiated in the form of high-dose steroid and intravenous immunoglobulins. Durvalumab was discontinued, and only gemcitabine/cisplatin-based chemotherapy was continued thereafter. Due to recurrence, one of the patients required longer courses of steroids as well as thrombopoietin receptor agonists. Conclusion: Immunotherapy in the form of durvalumab and now pembrolizumab alongside chemotherapy is an approved first-line standard of care. Furthermore, it is not uncommon for patients to receive Y90-RE to improve patient outcomes. This report highlights the development of ITP in 2 patients who received durvalumab alongside Y90-RE. Awareness of this as a potential immune-mediated event is important to allow for close monitoring of platelet counts and for early intervention/management when this occurs.

Systemic Immunological Changes After Yttrium-90 Radioembolization: A Pilot Prospective Observational Study-Clinical Insights.

To prospectively investigate levels of circulating cytokines, changes in frequencies of various immune cell subsets and expression of proliferation and checkpoint molecules on T cells in the peripheral blood after yttrium-90 radioembolization (TARE) of colorectal cancer liver metastases (CLM). We prospectively collected, isolated, and froze peripheral blood mononuclear cells (PBMC) and plasma samples from 15 patients immediately before, immediately after, 3 and 6 weeks post-TARE of CLM. Plasma samples were assessed for various cytokines using a multiplex immunoassay platform. PBMC samples were analyzed in a monocyte/dendritic cell (DC)/B cell flow panel and a T cell activation/exhaustion flow phenotyping panel. We compared the levels at the respective time points using Wilcoxon signed rank test. IFN-g significantly decreased immediately after (mean 1.62 vs. 3.02 at baseline, p = 0.04) and increased at 6weeks compared to the immediately post-TARE nadir (mean 9.42 vs. 1.62, p = 0.04). IL-10 decreased at 3weeks (mean 0.36 vs. 1.75, p = 0.025) post-TARE compared to baseline. Increased CD3+T cells (mean 78.24 vs. 60.8, p = 0.002) and decreased CTLA-4+CD4+T cells (mean 2.58 vs. 4.41, p = 0.033) were observed at 3weeks compared to baseline. Increased Ki-67+ proliferating CD8+T cells at 3 and 6weeks (mean 7.28 and 9.06, respectively, vs. 3.93 at baseline, p = 0.02 and 0.03) were recorded. A shift toward a favorable antitumoral cytokinic and immune cells response was observed after TARE. Significant changes were in specialized immune cells subsets playing important roles in the activation of the immune system. These results support trials combining TARE with immunotherapy for patients with CLM.

7040 Embolization Of Hepatic Metastases Is Effective For Palliative Management Of Severe Cushing Syndrome

Abstract Disclosure: S. Zhang: None. C. Musonza: None. A. Pillai: None. M. Ramos-Roman: None. J. Abramowitz: None. S. Mirfakhraee: None. P. Polanco: None. A.P. Dackiw: None. S. Al Mutar: None. A. Mallik: None. L. Jia: None. O. Hamidi: None. Background: Cushing syndrome (CS) due to metastatic endocrine neoplasms poses substantial treatment challenges. Arterial embolization and Yttrium-90 (Y-90) radioembolization for hepatic metastases are effective in the management of metastases due to neuroendocrine tumors (NETs). However, data are scarce on the role of embolization of liver metastases in patients with CS. Here, we report two cases of severe CS due to bulky hepatic metastases treated with embolization techniques. Case 1 A 49-year-old woman presented with severe ectopic CS and a 15-cm hepatic metastatic conglomerate. Liver biopsy showed NET of unknown primary. Treatment with subcutaneous octreotide and metyrapone (total daily dose 3000mg) resulted in modest improvement of serum cortisol from 89.8 to 45.8 mcg/dL. She was not a candidate for bilateral adrenalectomy or hepatectomy due to bulky hepatic metastases and subsequently underwent bland embolization to the hepatic conglomerate. Cortisol decreased from 63.9 mcg/dL to 13.8 mcg/dL after the initial procedure, but then rebounded to 35.8 mcg/dL. Serum cortisol decreased to 19.4 mcg/dL following additional embolization, and she was discharged on metyrapone 500mg three times daily. CS remained controlled 12 weeks after the procedure. Interval imaging showed a decrease in size of the dominant hepatic mass (9.7 cm). The patient is currently undergoing chemotherapy with carboplatin and etoposide. Case 2: A 40-year-old man presented to an outside institution with CS due to a 6.9 cm right adrenal mass and underwent adrenalectomy. Pathology showed oncocytic neoplasm of uncertain malignant potential. A year later, he presented to our hospital with recurrent CS and was found to have a 10.2 cm liver lesion, confirming stage IV adrenocortical carcinoma. FDG PET/CT did not show additional lesions. He was treated with osilodrostat and mitotane but his hypercortisolism remained uncontrolled. Mitotane was discontinued after a few doses due to side effects. Metastasectomy was attempted but halted due to extensive peritoneal carcinomatosis noted in the operating room. He was subsequently treated with Y-90 radioembolization to the liver metastasis. Afterwards, osilodrostat was held and serum cortisol decreased from 49.6 to 6.9 mcg/dL on day 14 post-procedure. Hydrocortisone was initiated for treatment of adrenal insufficiency. He received cisplatin, doxorubicin, and etoposide, but stopped after the first cycle due to side effects. Recent imaging showed a decrease in the hepatic lesion to 6.5 cm. Presently, the patient continues to have persistent adrenal insufficiency confirming remission of CS. Conclusion: These cases illustrate the potential efficacy of bland embolization and Y-90 radioembolization for palliative treatment of severe CS in patients with hepatic metastases. Presentation: 6/2/2024

Conversion Therapy to Transplant or Surgical Resection in Patients with Unresectable Hepatocellular Carcinoma Treated with Boosted Dose of Yttrium-90 Radiation Segmentectomy.

The aim of this study was to assess the efficacy of boosted dose yttrium-90 radioembolization (TARE) as a modality for conversion therapy to transplant or surgical resection in patients with unresectable hepatocellular carcinoma (HCC). In this single-center retrospective study, all patients with a diagnosis of HCC who were treated with boosted dose TARE (>190 Gy) between January 2013 and December 2023 were reviewed. Treatment response and decrease in tumor size were assessed with the RECIST v1.1 and mRECIST criteria. Milan and University of California, San Francisco (UCSF), criteria were used to determine transplant eligibility, and Barcelona Clinic Liver Cancer (BCLC) surgical resection recommendations were used to evaluate tumor resectability. Thirty-eight patients with primary HCC who were treated with boosted dose TARE were retrospectively analyzed. The majority of the patients were Child-Pugh A (n = 35; 92.1%), BCLC C (n = 17; 44.7%), and ECOG performance status 0 (n = 25; 65.8%). The mean sum of the target lesions was 6.0 cm (standard deviation; SD = 4.0). The objective response rate (ORR) was 31.6% by RECIST and 84.2% by mRECIST. The disease control rate (DCR) was 94.7% by both RECIST and mRECIST. Among patients outside of Milan or UCSF, 13/25 (52.0%, Milan) and 9/19 (47.4%, UCSF) patients were successfully converted to within transplant criteria. Of patients who were initially unresectable, conversion was successful in 7/26 (26.9%) patients. This study provides further real-world data demonstrating that boosted-dose TARE is an effective modality for conversion of patients with unresectable HCC to transplant or resection.

The role of immune checkpoint inhibitors and/or Yttrium-90 radioembolization in the management of hepatocellular carcinoma: challenges of treatment sequence

The role of immune checkpoint inhibitors and/or Yttrium-90 radioembolization in the management of hepatocellular carcinoma: challenges of treatment sequence

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.

Imageable Radioembolization Microspheres for Treatment of Unresectable Hepatocellular Carcinoma: Interim Results from a First-in-Human Trial

PurposeTo determine 6-month interim safety, effectiveness, and multimodal imageability of imageable glass microsphere yttrium-90 (90Y) radioembolization for unresectable hepatocellular carcinoma (HCC) in a first-in-human trial. Materials and MethodsImageable microspheres (Eye90 Microspheres; ABK Biomedical, Halifax, Nova Scotia, Canada), a U.S. Food and Drug Administration (FDA) Breakthrough-Designated Device consisting of glass radiopaque 90Y microspheres visible on computed tomography (CT) and single photon emission CT (SPECT), were used to treat 6 subjects with unresectable HCC. Patients underwent selective (≤2 segments) treatment in a prospective open-label pilot trial. Key inclusion criteria included liver-only HCC, performance status ≤1, total lesion diameter ≤9 cm, and Child-Pugh A status. Prospective partition dosimetry was utilized. Safety (measured by Common Terminology Criteria for Adverse Events [CTCAE] v5), multimodal imageability on CT and SPECT, and 3- and 6-month imaging response by modified Response Evaluation Criteria in Solid Tumors on magnetic resonance (MR) imaging were evaluated. ResultsSeven tumors in 6 subjects were treated and followed to 180 days. Administration success was 100%. Microsphere distribution measured by radiopacity on CT correlated with SPECT. Ninety-day target lesion complete response (CR) was observed in 3 of 6 subjects (50%) and partial response (PR) in 2 (33.3%). At 180 days, target lesion CR was maintained in 3 subjects (50%) and PR in 1 (16.7%). Two subjects could not be reassessed, having undergone intervening chemoembolization. All subjects reported adverse events (AEs), and 5 reported AEs related to treatment. There were no treatment-related Grade ≥3 AEs. ConclusionsRadioembolization using imageable microspheres was safe and effective in 6 subjects with unresectable HCC at 6-month interim analysis. Microsphere distribution by radiopacity on CT correlated with radioactivity distribution by SPECT, providing previously unavailable CT-based tumor targeting information.

Advancements in Interventional Radiology for Managing Hepatic Encephalopathy: A Comprehensive Review.

Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome resulting from liver dysfunction, leading to cognitive, behavioral, and motor impairments. The management of HE has traditionally relied on pharmacological treatments, dietary modifications, and liver transplantation. However, recent advancements in interventional radiology (IR) have introduced minimally invasive procedures that offer promising alternatives. This comprehensive review explores the latest IR techniques, including transjugular intrahepatic portosystemic shunt (TIPS), balloon-occluded retrograde transvenous obliteration (BRTO), portal vein embolization (PVE), and Yttrium-90 (Y90) radioembolization. The efficacy, clinical outcomes, and potential complications of these techniques are examined through an analysis of current studies and trials. The review highlights the benefits of IR in reducing portal hypertension and improving hepatic blood flow, ultimately alleviating HE symptoms. Additionally, it underscores the importance of multidisciplinary collaboration, ongoing research, and the development of clear patient selection criteria to optimize the use of IR in HE management. By integrating these advancements into clinical practice, healthcare providers can enhance the quality of care and improve outcomes for patients with HE.

An international phantom study of inter-site variability in Technetium-99m image quantification: analyses from the TARGET radioembolization study

BackgroundPersonalised multi-compartment dosimetry based on [99mTc]Tc-MAA is a valuable tool for planning 90Y radioembolization treatments. The establishment and effective application of dose–effect relationships in yttrium-90 (90Y) radioembolization requires [99mTc]Tc-MAA SPECT quantification ideally independent of clinical site. The purpose of this multi-centre phantom study was to evaluate inter-site variability of [99mTc]Tc-MAA imaging and evaluate a standardised imaging protocol. Data was obtained from the TARGET study, an international, retrospective multi-centre study including 14 sites across 8 countries. The impact of imaging related factors was estimated using a NEMA IQ phantom (representing the liver), and a uniformly filled cylindrical phantom (representing the lungs). Imaging was performed using site-specific protocols and a standardized protocol. In addition, the impact of implementing key image corrections (scatter and attenuation correction) in the site-specific protocols was investigated. Inter-site dosimetry accuracy was evaluated by comparing computed Lung Shunt Fraction (LSF) measured using planar imaging of the cylindrical and NEMA phantom, and contrast recovery coefficient (CRC) measured using SPECT imaging of the NEMA IQ phantom.ResultsRegarding the LSF, inter-site variation with planar site-specific protocols was minimal, as determined by comparing computed LSF between sites (interquartile range 9.6–10.1%). A standardised protocol did not improve variation (interquartile range 8.4–9.0%) but did improve mean accuracy compared to the site-specific protocols (5.0% error for standardised protocol vs 8.8% error for site-specific protocols). Regarding the CRC, inter-system variation was notable for site-specific SPECT protocols and could not be improved by the standardised protocol (CRC interquartile range for 37 mm sphere 0.5–0.7 and 0.6–0.8 respectively), however the standardised protocol did improve accuracy of sphere:background determination. Implementation of key image corrections did improve inter-site variation (CRC interquartile range for 37 mm sphere 0.6–0.7).ConclusionEliminating sources of variability in image corrections between imaging protocols reduces inter-site variation in quantification. A standardised protocol was not able to improve consistency of LSF or CRC but was able to improve accuracy.

Implications of lung shunt fraction calculation discrepancy in Y-90 radioembolization treatment from 2D planar vs 3D SPECT imaging

Abstract The safety and efficacy of Yttrium-90 (Y-90) radio-embolization therapy is partly dependent on the lung shunt fraction (LSF). There may be a notable disparity between LSF when calculated using 2D planar imaging vs 3D SPECT; this can affect the total allowable Y-90 dose delivered and therefore change the effectiveness of the procedure. The case presented demonstrates an 81% decrease in LSF when calculated by SPECT as compared to 2D planar imaging. This case highlights the importance of considering the imaging technique and the potential discrepancies that can arise between planar and SPECT imaging in LSF assessment.

Quantitative evaluation of 90Y-PET/CT and 90Y-SPECT/CT-based dosimetry following Yttrium-90 radioembolization.

Following yttrium-90 radioembolization (90Y-RE), 90Y-PET/CT and 90Y-SPECT/CT imaging provide the means to calculate the voxelized absorbed dose distribution. Given the widespread use of the two imaging modalities and lack of well-established standardized dosimetry protocols for 90Y-RE, there is a clinical need to systematically investigate and evaluate differences in the performance of voxel-based dosimetry between 90Y-PET/CT and 90Y-SPECT/CT. To quantitatively analyze and compare 90Y-PET/CT and 90Y-SPECT/CT-based dosimetry following 90Y-RE. 90Y-PET/CT and90Y-SPECT/CT imaging was acquired for 35 patients following 90Y-RE with TheraSphere for the treatment of unresectable hepatocellular carcinoma. Dosimetry was performed using the local deposition method with known activity and the mean dose (Dmean) was calculated for perfused liver volumes (PV), tumors (T), and perfused normal livers (NL). Additionally, the absorbed dose to x% of the volume (Dx, x [5%, 10%, …, 90%, 95%]) and the volume receiving y Gy (Vy, y [10Gy, 20Gy, …, 190Gy, 200Gy]) were calculated for T and NL, respectively. Dose metrics were compared using linear regression, Bland-Altman analysis, and statistical testing. Both 90Y-SPECT/CT and 90Y-PET/CT-based tumor Dmean were strongly correlated (R2 ≥ 0.90) with Dx, excluding metrics on the extrema. Intra-modality comparisons of various Dx and Vy metrics yielded statistically significant differences (ANOVA, p<0.001) for both90Y-PET/CT and90Y-SPECT/CT. Based on statistical testing, only Dx metrics separated by greater than 20%-30% coverage, and only Vy metrics separated by greater than 40-70Gy, reported significant differences. For PV, there was a strong correlation (R2 ≥ 0.99) between Dmean derived separately from 90Y-PET/CT and 90Y-SPECT/CT imaging. The strength of the correlation was slightly reduced for T and NL with R2=0.91 and R2=0.95, respectively. For PV, the mean bias±standard error (SE) and 95% limits of agreement (LOA) between Dmean from the two modalities was effectively zero with -0.8±0.4% (±2.5%). For T and NL, the mean bias±SE (±LOA) was -14.5±3.7% (±24%) and 9.4±4.7% (±27%), respectively. The strong correlation between Dmean and Dx suggests information from multiple dose metrics (e.g., D70 and Dmean) is largely redundant when establishing dose-response relationships in 90Y-RE. Dmean is highly correlated between 90Y-PET/CT and 90Y-SPECT/CT-based dosimetry, for all liver VOIs. Relative to 90Y-SPECT/CT, 90Y-PET/CT, on average, yielded higher Dmean to tumors (14%) and lower Dmean to perfused normal livers (9%). Absorbed dose differences for perfused liver volumes between 90Y-SPECT/CT and 90Y-PET/CT were negligible.

A comparison of methods for in vivo activity and absorbed dose quantification with PET/CT following yttrium-90 radioembolization.

Yttrium-90 (90Y) positron emission tomography (PET)/computed tomography (CT) imaging is increasingly being used to perform tumor (T) and normal liver (NL) voxel dosimetry after 90Y-radioembolization (90Y-RE). Yet, the accuracy of in vivo 90Y-PET/CT imaging, subject to motion blur and co-registration inaccuracies, and 90Y-PET/CT dose quantification, subject to availability of different voxel dosimetry algorithms, are not well understood. The purpose of this study was to investigate the accuracy of 90Y-PET/CT-based activity estimates following 90Y-RE and characterize differences between 90Y-PET/CT-based voxel dosimetry algorithms. Thirty-five patients underwent 90Y-PET/CT imaging after 90Y-RE with TheraSphere. The net administered 90Y activity (Aadmin) was determined using a dose calibrator and pre- and post-procedure exposure rate measurements. The summation of image-based activity (Aimage) was extracted from perfused volume (PV) and 3D-isotropically 2-cm expanded PV contour (PV+2cm). Absorbed doses were calculated using voxel S-value (VSV), local deposition method (LDM), and LDM with known activity (LDMKA) dosimetry algorithms. Linear regression and Bland-Altman analysis quantified the relationship between Aimage and Aadmin and between mean dose estimates (DLDM, DVSV, DLDM-KA) for PV, T, and perfused NL volumes. While Aadmin and Aimage in PV were highly correlated (R2>0.95), the mean bias±standard error (SE) and (95% limits of agreement, LOA) was significantly non-zero with -22.7±4.7% (±28.4%). In PV+2cm, the mean bias±SE (±LOA) decreased to 1.3±3.4% (±18.0%) consistent with zero mean error. DLDM and DVSV were highly correlated (R2>0.99) for all volumes of interest (VOIs) and the meanbias±SE(±LOA) was 2.2±0.2% (±1.0%), 0.7±0.4% (±2.8%), and 3.2±0.5% (±2.8%) for PV, T, and NL, respectively. DLDM-KA and DVSV were correlated with R2=0.86, 0.80, and 0.86 for PV, T, and NL, respectively. The meanbias±SE(±LOA) between DLDM-KA and DVSV was significantly non-zero with -19.6±5.1% (±31.0%), -20.8±4.4% (±29.0%), and -18.1±5.3% (±31.1%) for PV, T, and NL, respectively. The summation of Aimage in PV was underestimated relative to Aadmin. Only by accounting for respiratory motion, limited spatial resolution, and PET/CT co-registration errors through VOI expansion was Aimage, on average, equal to Aadmin. The differences between DLDM and DVSV were not clinically relevant, though DLDM-KA was approximately 20% greater than DVSV. Given the high quantitative accuracy of dose calibrators and challenges associated with accurate 90Y-PET/CT quantification, LDMKA is the preferred algorithm for accurate 90Y-PET/CT-based dosimetry following 90Y-RE.

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.

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.

O 20 - Safety and efficacy of proton beam therapy in high-risk hepatocellular carcinoma patients previously treated with Yttrium-90 Radioembolization

O 20 - Safety and efficacy of proton beam therapy in high-risk hepatocellular carcinoma patients previously treated with Yttrium-90 Radioembolization

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.