Multidisciplinary Delphi Consensus on Safety of Combining Transarterial Radioembolization with Yttrium-90 Microspheres with Systemic Anticancer Agents for the Treatment of Liver Malignancy.

PURPOSE: To provide guidance, via multidisciplinary consensus statements, on the safety interactions between systemic anticancer agents (such as radiosensitizing chemotherapy, immunotherapy, targeted therapy, and peptide receptor radionuclide therapy) and transarterial radioembolization (TARE) with yttrium-90 (90Y)-labeled microspheres in the treatment of primary and metastatic liver malignancies. MATERIALS AND METHODS: A literature search identified 59 references that informed 26 statements on the safety of 90Y TARE combined with systemic therapies. Modified Delphi method was used to develop consensus on statements through online anonymous surveys of the 12 panel members representing the fields of interventional radiology, medical oncology, surgical oncology, hepatology, and pharmacy, focusing on hepatocellular carcinoma (HCC), metastatic colorectal cancer (mCRC), neuroendocrine tumors, metastatic breast cancer, and intrahepatic cholangiocarcinoma. RESULTS: High-level evidence was limited. Level 1 data in patients with mCRC suggest that some radiosensitizing chemotherapies (eg, oxaliplatin) require temporary dose reduction when used concomitantly with 90Y TARE, and some targeted therapies (eg, vascular endothelial growth factor inhibitors and antiangiogenic tyrosine kinase inhibitors) should be avoided for at least 4 weeks before 90Y TARE. In patients with HCC, the feasibility of 90Y TARE and immunotherapy has been demonstrated with Level 4 evidence. Data are more limited for other primary and secondary liver malignancies, and consensus statements were driven by expert opinion (Level 5). CONCLUSIONS: Given the absence of evidence-based guidelines on the safety of 90Y TARE in combination with systemic anticancer therapy, these consensus statements provide expert guidance on the potential risks when considering specific combinations.

Safety and Efficacy of Radiosynoviorthesis: A Prospective Canadian Multicenter Study.

Radiosynoviorthesis is approved in several European countries and the United States to treat refractory synovitis in many inflammatory joint diseases, such as rheumatoid arthritis, spondyloarthropathies, and other arthritic joint diseases. No radiopharmaceuticals for radiosynoviorthesis are currently approved in Canada. The aim of this Health Canada-approved trial was to demonstrate the safety and efficacy of radiosynoviorthesis. Methods: Between July 2012 and November 2017, we conducted a multicenter, prospective, interventional Canadian trial. Patients (n = 360) with synovitis refractory to standard treatments after failing 2 intraarticular glucocorticoid injections were included. They were followed up at 3, 6, and 12 mo. Outcome measures included adverse events (AEs) and clinical signs of synovitis (pain, swelling, and joint effusion) measured with the Health Assessment Questionnaire Disability Index, the Disease Activity Score, and the Visual Analog Scale. Results: In total, 392 joints were treated, including those reinjected after 6 mo (n = 34). Of these, 83.4% (327/392) were injected with [90Y]Y-citrate for the knees and 9.9% (39/392) with [186Re]Re-sulfide for medium-sized joints. Of the joints treated, 82.7% (324/392) were knees. Fifty-five AEs, most of them of mild grade, occurred and resolved without sequelae and were not life-threatening. The incidence of radiosynoviorthesis-related AEs was 9.4% (34/360). The proportion of patients showing an improvement in synovitis symptoms after radiosynoviorthesis was significant at 3 mo and was maintained up to 12 mo (P < 0.001). Conclusion: This study confirmed the safety of radiosynoviorthesis in the treatment of patients with synovitis refractory to standard treatments. There is evidence of sustained clinical efficacy at 12 mo, suggesting that radiosynoviorthesis is an effective treatment for improving synovitis symptoms.

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

BACKGROUND AND AIM: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: Safety and efficacy outcomes with the routine use of SIRT with 90Y resin microspheres in Taiwan are consistent with published data.

Modified Radiation Lobectomy Strategy of Radioembolization for Right-Sided Unresectable Primary Liver Tumors.

PURPOSE: To assess the safety and effectiveness of using modified radiation lobectomy (mRL) to treat primary hepatic tumors located in the right hepatic lobe (Segments V-VIII) and to determine future liver remnant (FLR) hypertrophy. MATERIALS AND METHODS: A retrospective review was performed at a single institution to include 19 consecutive patients (7 females, 12 males) who underwent single-session mRL for right-sided primary hepatic tumors: 15 received segmentectomy plus lobectomy (segmental dose of >190 Gy and lobar dose of >80 Gy); 4 were treated with the double-segmental approach (dominant segments of >190 Gy and nondominant segments of >80 Gy). Treated tumors included 13 hepatocellular carcinoma (HCC), 4 cholangiocarcinoma (CCA), and 2 mixed-type HCC-CCA with a median dominant tumor size of 5.3 cm (interquartile range [IQR], 3.7-7.3 cm). FLR of the left hepatic lobe was measured at baseline, T1 (4-8 weeks), T2 (2-4 months), T3 (4-6 months), and T4 (9-12 months). RESULTS: Objective tumor response and tumor control were achieved in 17 of the 19 (89.5%) and 18 of the 19 (94.7%) patients, respectively. FLR hypertrophy was observed at T1 (median, 47.8%; P = .025), T2 (median, 48.4%; P = .012), T3 (median, 50.4%; P = .015), and T4 (median, 59.1%; P < .001). Patients without cirrhosis demonstrated greater hypertrophy by 6 months (median, 55.8% vs 47.2%; P = .031). One patient developed a Grade 3 adverse event (ascites requiring paracentesis) at 1-month follow-up. Grade ≥2 serum toxicities were associated with worse baseline Child-Pugh Score, serum albumin, and total bilirubin (P < .05). Among 7 patients who underwent neoadjuvant mRL, 2 underwent resection and 1 received liver transplant. CONCLUSIONS: mRL appears safe and effective for treatment of right-sided primary hepatic tumors with the benefit of promoting FLR hypertrophy.

Tumor Size and Watershed Area Correlate with Incomplete Treatment and Tumor Progression after Selective Radioembolization for Hepatocellular Carcinoma.

PURPOSE: To identify factors of incomplete treatment after segmental transarterial radioembolization (TARE) for treatment-naive and solitary hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A total of 75 consecutive patients (age, 68.5 years [SD ± 8.0]; 25/75 [33.3%] women) with treatment-naive, solitary HCC underwent segmental or subsegmental TARE with glass microspheres (tumor size, 3.8 cm [SD ± 2.2]; administered dose, 222.6 Gy [SD ± 123.9]) at a single institution from November 2015 to June 2022. Radiologic response and progression-free survival (PFS) were assessed as per modified Response Evaluation Criteria in Solid Tumors. RESULTS: Complete treatment was achieved in 48 of 75 (64.0%) patients (mean follow-up, 33.2 months [SD ± 27.4]). Patients with incomplete treatment (27/75, 36%) presented with larger tumor size (5.0 [SD ± 2.5] vs 3.1 [SD ± 1.6] cm; P = .0001), with more tumors located in the watershed zone (81.5% vs 41.7%; P = .001). These patients were less likely to be bridged to transplant or resection (22.2% vs 52.1%; P = .015). Watershed tumors demonstrated worse target tumor PFS (median PFS, 19 months vs not reached; P = .0104) and overall PFS (9.1 months vs not reached; P = .0077). Watershed location was associated with worse PFS among tumors >3 cm in size (8.4 months vs not reached; P = .035) but not in tumors ≤3 cm in size (52.2 months vs not reached; P = .915). CONCLUSIONS: Tumor size and watershed location were associated with incomplete treatment after segmental TARE for HCC. Watershed tumors were associated with worse PFS, particularly tumors larger than 3 cm. These tumors may require careful treatment planning and repeated treatments to ensure a durable response.

Radioembolization plus Immune Checkpoint Inhibitor Therapy Compared with Radioembolization plus Tyrosine Kinase Inhibitor Therapy for the Treatment of Hepatocellular Carcinoma.

PURPOSE: To investigate if combination therapy with immune checkpoint inhibitor (ICI) and yttrium-90 (90Y) radioembolization results in superior outcomes than those yielded by tyrosine kinase inhibitor (TKI) therapy and 90Y for the treatment of intermediate- to advanced-stage hepatocellular carcinoma (HCC). METHODS: A retrospective review of patients presented at an institutional multidisciplinary liver tumor board between January 1, 2012 and August 1, 2023 was conducted. In total, 44 patients with HCC who underwent 90Y 4 weeks within initiation of ICI or TKI therapy were included. Propensity score matching was conducted to account for baseline demographic differences. Kaplan-Meier analysis was used to compare median progression-free survival (PFS) and overall survival (OS), and univariate statistics identified disease response and control rate differences. Duration of imaging response was defined as number of months between the first scan after therapy and the first scan showing progression as defined by modified Response Evaluation Criteria in Solid Tumors (mRECIST) or immune Response Evaluation Criteria in Solid Tumors (iRECIST). Adverse events were analyzed per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. RESULTS: Patients in the 90Y+ICI therapy group had better objective response rates (ORRs) (89.5% vs 36.8%; P < .001) and disease control rates (DCRs) (94.7% vs 63.2%; P < .001) by mRECIST and iRECIST (ORR: 78.9% vs 36.8%; P < .001; DCR: 94.7% vs 63.2%; P < .001). Median PFS (8.3 vs 4.1 months; P = .37) and OS (15.8 vs 14.3 months; P = .52) were not statistically different. Twelve patients (63.1%) in the 90Y+TKI group did not complete systemic therapy owing to adverse effects compared with 1 patient (5.3%) in the 90Y+ICI group (P < .001). Grade 3/4 adverse events were not statistically different (90Y+TKI: 21.1%; 90Y+ICI: 5.3%; P = .150). CONCLUSIONS: Patients with HCC who received 90Y+ICI had better imaging response and fewer regimen-altering adverse events than those who received 90Y+TKI. No significant combination therapy adverse events were attributable to radioembolization.

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.

PURPOSE: To 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 METHODS: In 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. RESULTS: The 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). CONCLUSIONS: For 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.

Radiation Major Hepatectomy Using Ablative Dose Yttrium-90 Radioembolization in Patients with Hepatocellular Carcinoma 5 cm or Larger.

PURPOSE: To evaluate the safety and effectiveness of ablative radioembolization for large hepatocellular carcinoma (HCC) while preserving a small future liver remnant (FLR). MATERIALS AND METHODS: Twenty-five patients with large HCC of ≥5 cm requiring treatment for >60% of the total liver volume and having well-preserved liver function were treated with ablative glass microsphere radioembolization at a single institution from January 2017 to December 2021. Radioembolization was performed with a mean absorbed dose of >150 Gy, and the FLR per nontumor liver volume (NTLV) was set at >30%. Changes in liver function, adverse events, duration of response (DoR) in a treated area, time-to-progression (TTP), and overall survival (OS) were retrospectively investigated. RESULTS: The largest tumor diameter and planned dose per treated volume were 11.4 cm ± 3.9 and 242.3 Gy ± 63.6 (169.4 Gy ± 45.9 per whole liver volume), respectively. All patients remained at Child-Pugh Class A for 90 days. No patient experienced Grade 3‒4 hyperbilirubinemia or new ascites. One patient (lung dose, 27.8 Gy) developed radiation pneumonitis requiring transient steroid treatment. According to the posttreatment dosimetry, the tumorous and nontumorous liver absorbed doses were 418.8 Gy ± 227.4 and 69.0 Gy ± 32.1, respectively. The median DoR in a treated area and TTP were 22.0 and 17.1 months, respectively. The 5-year OS rate was 83.2%. CONCLUSIONS: Ablative radioembolization of large HCC of ≥5 cm can be performed safely and effectively in patients with preserved liver function when FLR/NTLV exceeds 30%.

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

PURPOSE: To 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 METHODS: This 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. RESULTS: Median 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). CONCLUSIONS: TARE has an acceptable safety profile for the treatment of LCML, with survival benefits best seen in LC tumors.

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

PURPOSE: To 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 METHODS: In 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. RESULTS: Patients 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. CONCLUSIONS: Tumor 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.

Segmental Yttrium-90 Radioembolization Using Glass Microspheres Greater than 400 Gray for the Treatment of Intrahepatic Cholangiocarcinoma: A Preliminary Experience.

Radiation segmentectomy with a dose of >190 Gy using yttrium-90 (90Y) glass microspheres for intrahepatic cholangiocarcinoma (iCCA) has been shown to be safe and effective. The present study further increased the dose to >400 Gy for treatment of iCCA as complete pathologic necrosis has been shown in hepatocellular carcinoma using this ablative approach. A total of 10 patients with 13 tumors (median size, 5.3 cm; range, 1.5-13.6 cm) at a single institution underwent >400-Gy segmental radioembolization. Objective response was achieved in all tumors (13 of 13, 100%). One patient developed a Grade 3 or greater major adverse event (stroke and hepatic decompensation). One patient was bridged to transplant (>95% pathologic necrosis), whereas another underwent resection (>99% necrosis). Contralateral hypertrophy was observed in 6 out of 6 patients treated with modified lobectomy dosing, with a functional liver reserve increase from a median of 31.5% to 57.1%. The present report suggests that segmental transarterial radioembolization with >400 Gy is feasible in terms of safety and effectiveness for treating iCCA.

A Phase I/IIa Trial of Yttrium-90 Radioembolization in Combination with Durvalumab for Locally Advanced Unresectable Hepatocellular Carcinoma.

PURPOSE: Synergistic effect of radiotherapy and immunotherapy for the treatment of hepatocellular carcinoma (HCC) has been reported. This phase I/IIa pilot trial evaluated preliminary efficacy and safety of combination of radioembolization with yttrium-90 microspheres (Y90-radioembolization) and durvalumab in patients with locally advanced unresectable HCC. PATIENTS AND METHODS: Patients with Child-Pugh score ≤ 7 and locally advanced HCC, defined as Barcelona Clinic Liver Cancer (BCLC) stage B HCC or BCLC-C disease without extrahepatic metastases, received Y90-radioembolization followed by intravenous durvalumab 1,500 mg 7 to 14 days after Y90-radioembolization and every 4 weeks thereafter. Primary endpoint was time to progression (TTP) assessed by modified RECIST (mRECIST). Secondary endpoints included overall survival (OS), progression-free survival (PFS), objective response rate (ORR) determined by mRECIST, and safety. RESULTS: All 24 patients enrolled received Y90-radioembolization and 23 received at least one dose of durvalumab. Median follow-up duration was 19.0 months (range, 2.2-24.2). Median TTP was 15.2 months [95% confidence interval (CI), 6.1-not estimated]. Median OS was not reached and 18-month OS rate was 58.3% (95% CI, 36.4-75.0). Median PFS was 6.9 months (95% CI, 5.4-15.2). Seven (29.2%) patients had a complete response and 13 (54.2%) had a partial response; ORR was 83.3% (95% CI, 62.6-95.3). Eleven (47.8%) patients experienced any-grade treatment-related adverse events. Two (8.7%) patients had grade 3 treatment-related adverse events (neutropenia and fever). None experienced any treatment-related serious adverse events. CONCLUSIONS: In patients with locally advanced unresectable HCC, the combination of Y90-radioembolization and durvalumab demonstrated promising efficacy and safety, warranting further evaluation in large-scale controlled trials.

Voxel-Based Dosimetry Predicts Hepatotoxicity in Hepatocellular Carcinoma Patients Undergoing Radioembolization with 90Y Glass Microspheres.

Personalized dosimetry holds promise to improve radioembolization treatment outcomes in hepatocellular carcinoma (HCC) patients. To this end, tolerance absorbed doses for nontumor liver tissue are assessed by calculating the mean absorbed dose to the whole nontumor liver tissue (AD-WNTLT), which may be limited by its neglect of nonuniform dose distribution. Thus, we analyzed whether voxel-based dosimetry could be more accurate in predicting hepatotoxicity in HCC patients undergoing radioembolization. Methods: In total, 176 HCC patients were available for this retrospective analysis; of these, 78 underwent partial- and 98 whole-liver treatment. Posttherapeutic changes in bilirubin were graded using the Common Terminology Criteria for Adverse Events. We performed voxel-based and multicompartment dosimetry using pretherapeutic 99mTc-labeled human serum albumin SPECT and contrast-enhanced CT/MRI and defined the following dosimetry parameters: AD-WNTLT; the nontumor liver tissue volume exposed to at least 20 Gy (V20), at least 30 Gy (V30), and at least 40 Gy (V40); and the threshold absorbed dose to the 20% (AD-20) and 30% (AD-30) of nontumor liver tissue with the lowest absorbed dose. Their impact on hepatotoxicity after 6 mo was analyzed using the area under the receiver-operating-characteristic curve; thresholds were identified using the Youden index. Results: The area under the curve for prediction of posttherapeutic grade 3+ increases in bilirubin was acceptable for V20 (0.77), V30 (0.78), and V40 (0.79), whereas it was low for AD-WNTLT (0.67). The predictive value could further be increased in the subanalysis of patients with whole-liver treatment, where a good discriminatory power was found for V20 (0.80), V30 (0.82), V40 (0.84), AD-20 (0.80), and AD-30 (0.82) and an acceptable discriminatory power was found for AD-WNTLT (0.63). The accuracies of V20 (P = 0.03), V30 (P = 0.009), V40 (P = 0.004), AD-20 (P = 0.04), and AD-30 (P = 0.02) were superior to that of AD-WNTLT but did not differ significantly from each other. The respective thresholds were 78% (V30), 72% (V40), and 43 Gy (AD-30). Statistical significance was not reached for partial-liver treatment. Conclusion: Voxel-based dosimetry may more accurately predict hepatotoxicity than multicompartment dosimetry in HCC patients undergoing radioembolization, which could enable dose escalation or deescalation with the intent to optimize treatment response. Our results indicate that a V40 of 72% may be particularly useful in whole-liver treatment. However, further research is warranted to validate these results.

Yttrium-90 Activity Quantification in PET/CT-Guided Biopsy Specimens from Colorectal Hepatic Metastases Immediately after Transarterial Radioembolization Using Micro-CT and Autoradiography.

PURPOSE: To evaluate the yttrium-90 (90Y) activity distribution in biopsy tissue samples of the treated liver to quantify the dose with higher spatial resolution than positron emission tomography (PET) for accurate investigation of correlations with microscopic biological effects and to evaluate the radiation safety of this procedure. MATERIALS AND METHODS: Eighty-six core biopsy specimens were obtained from 18 colorectal liver metastases (CLMs) immediately after 90Y transarterial radioembolization (TARE) with either resin or glass microspheres using real-time 90Y PET/CT guidance in 17 patients. A high-resolution micro-computed tomography (micro-CT) scanner was used to image the microspheres in part of the specimens and allow quantification of 90Y activity directly or by calibrating autoradiography (ARG) images. The mean doses to the specimens were derived from the measured specimens' activity concentrations and from the PET/CT scan at the location of the biopsy needle tip for all cases. Staff exposures were monitored. RESULTS: The mean measured 90Y activity concentration in the CLM specimens at time of infusion was 2.4 ± 4.0 MBq/mL. The biopsies revealed higher activity heterogeneity than PET. Radiation exposure to the interventional radiologists during post-TARE biopsy procedures was minimal. CONCLUSIONS: Counting the microspheres and measuring the activity in biopsy specimens obtained after TARE are safe and feasible and can be used to determine the administered activity and its distribution in the treated and biopsied liver tissue with high spatial resolution. Complementing 90Y PET/CT imaging with this approach promises to yield more accurate direct correlation of histopathological changes and absorbed dose in the examined specimens.

Radioembolization for Treatment of Hepatocellular Carcinoma: Current Evidence and Patterns of Utilization.

Primary liver malignancy, of which hepatocellular carcinoma (HCC) is the most common type, is the second most common cause of death due to cancer worldwide. Given the historically poor prognosis of liver cancer, there has been major research on its treatment options, with significant advancements over the last decade. Transarterial radioembolization (TARE) is a locoregional treatment option for HCC that involves transarterial delivery of the ß-emitter yttrium-90 via resin or glass microspheres to arterialized tumor vasculature, delivering a tumoricidal dose to the tumor. The recent 2022 update of the Barcelona Clinic Liver Cancer (BCLC) treatment algorithm features a more prominent role for locoregional treatment, including the incorporation of radioembolization for very-early-stage (BCLC-0) and early-stage (BCLC-A) diseases. This review provides a contemporary summary of the evolving role of TARE in treatment of HCC in light of recent and upcoming trials.

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

BACKGROUND: Using 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. METHODS: We 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). RESULTS: All-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. CONCLUSION: Our study confirms that TARE is a safe treatment with low toxicity and a minimal impact on quality of life.

Evolution of Personalized Dosimetry for Radioembolization of Hepatocellular Carcinoma.

Yttrium-90 transarterial radioembolization (TARE) has progressed from a salvage or palliative lobar or sequential bilobar regional liver therapy for patients with advanced disease to a versatile, potentially curative, and often highly selective local treatment for patients across Barcelona Clinic Liver Cancer stages. With this shift, radiation dosimetry has evolved to become more tailored to patients and target lesion(s), with treatment dose and distributions adapted for specific clinical goals (ie, palliation, bridging or downstaging to liver transplantation, converting to surgical resection candidacy, or ablative/curative intent). Data have confirmed that "personalizing" dosimetry yields real-world improvements in tumor response and overall survival while maintaining a favorable adverse event profile. In this review, imaging techniques used before, during, and after TARE have been reviewed. Historical algorithms and contemporary image-based dosimetry methods have been reviewed and compared. Finally, recent and upcoming developments in TARE methodologies and tools have been discussed.