A Pilot Study of Pembrolizumab in Combination With Y90 Radioembolization in Subjects With Poor Prognosis Hepatocellular Carcinoma.

BACKGROUND: Combination checkpoint inhibition therapy with yttrium-90 (Y90) radioembolization represents an emerging area of interest in the treatment of advanced hepatocellular carcinoma (HCC). HCRN GI15-225 is an open-label, single-arm multicenter, pilot study (NCT03099564). METHODS: Eligible patients had poor prognosis, localized HCC defined as having portal vein thrombus, multifocal disease, and/or diffuse disease that were not eligible for liver transplant or surgical resection. Patients received pembrolizumab 200 mg intravenously every 3 weeks in conjunction with glass yttrium-90 (Y90) radioembolization TheraSphere. Primary endpoint was 6-month progression-free survival (PFS6) per RECIST 1.1. Secondary endpoints included time to progression (TTP), objective response rate (ORR), overall survival (OS), and safety/tolerability. RESULTS: Between October 23, 2017 and November 24, 2020, 29 patients were enrolled: 2 were excluded per protocol. Fifteen of the remaining 27 patients were free of progression at 6 months (55.6%; 95% CI, 35.3-74.5) with median PFS 9.95 months (95% CI, 4.14-15.24) and OS 27.30 months (95% CI, 10.15-39.52). One patient was not evaluable for response due to death; among the remaining 26 patients, ORR was 30.8% (95% CI, 14.3-51.8) and DCR was 84.6% (95% CI, 65.1-95.6). CONCLUSION: In patients with localized, poor prognosis HCC, pembrolizumab in addition to glass Y90 radioembolization demonstrated promising efficacy and safety consistent with prior observations (ClinicalTrials.gov Identifier: NCT03099564; IRB Approved: 16-3255 approved July 12, 2016).

Optimal patient selection for yttrium-90 glass plus chemotherapy in the treatment of colorectal liver metastases: additional quality of life, efficacy, and safety analyses from the EPOCH study.

BACKGROUND: Evaluating transarterial radioembolization (TARE) in patients with metastatic colorectal carcinoma of the liver who have progressed on first-line chemotherapy (EPOCH) demonstrated superior outcomes using yttrium-90 glass microspheres plus chemotherapy (TARE/Chemo) vs chemotherapy (Chemo) to treat colorectal liver metastases. Additional exploratory analyses were undertaken to assess the impact of TARE/Chemo on efficacy, safety, time to subsequent therapy, time to deterioration in quality of life (QoL), and identify criteria for improved patient selection. METHODS: Time to deterioration in QoL was analyzed for the primary study population. Subsequently, a post hoc analysis was undertaken to identify subgroups for which time to deterioration in QoL was improved with TARE/Chemo vs Chemo. Progression-free survival (PFS), hepatic (h)PFS, time to subsequent therapy, and safety outcomes were compared between treatments. RESULTS: The primary population showed no significant difference in time to deterioration in QoL between treatment arms; however, significance was seen in 2 identified subgroups, namely: Subgroup A (N = 303) which excluded patients with both Eastern Cooperative Oncology Group (ECOG) 1 and baseline CEA ≥ 35 ng/mL from both treatment arms; subgroup B (N = 168) additionally excluded patients with KRAS (Kirsten rat sarcoma) mutation. In subgroup A, TARE/Chemo patients (N = 143) demonstrated superior outcomes vs Chemo (N = 160): PFS (9.4 vs. 7.6 months, hazard ratio (HR): 0.64; 1-sided P = .0020), hPFS (10.8 vs. 7.6 months, HR: 0.53; 1-sided P < .0001), time to deterioration in QoL (5.7 vs. 3.9 months, HR: 0.65; 1-sided P = .0063), and time to subsequent therapy (21.2 vs. 10.5 months, HR: 0.52; 1-sided P < .0001). Subgroup B patients showed similar but larger significant differences between treatment arms. Median PFS, hPFS, and time to deterioration in QoL were numerically greater for TARE/Chemo in both subgroups vs the primary population, with the greatest magnitude of difference in subgroup B. Both subgroups exhibited higher percentage of CEA responders and improved ORR with TARE/Chemo vs chemo alone. Safety (reported as event rate/100 patient-years) was higher with Chemo in all populations. Additional efficacy analyses in the primary population are also reported. CONCLUSIONS: Careful patient selection, including consideration of the prognostic factors ECOG, baseline CEA, and KRAS status, sets outcome expectations in patients with colorectal liver metastases suitable for TARE/Chemo as second-line treatment (Trial Registry Number: NCT01483027).

Transarterial Radioembolization for Management of Hepatocellular Carcinoma.

Transarterial radioembolization (TARE) with Yttrium-90 (Y90) is a growing area of study due to its benefits in early-, intermediate-, and late-stage hepatocellular carcinoma. Treatment intent, including curative therapy, bridging to transplant, and downstaging disease, informs treatment approach and dosimetry goals. Radiation lobectomy (RL) and radiation segmentectomy (RS) are the 2 main forms of Y90 administration which have shown improved survival outcomes with the development of personalized dosimetry. RS aims to achieve complete pathological necrosis with dose escalation and RL aims for local disease control as well as induction of contralateral lobe hypertrophy to improve hepatic reserve. Furthermore, TARE has been validated in head-to-head comparison to other locoregional and systemic therapies. Lastly, early potential exists for combination therapy between TARE and immune checkpoint inhibitors for advanced stage disease.

Dose-effect relationships in neuroendocrine tumour liver metastases treated with [166Ho]-radioembolization.

PURPOSE: Aim of this study was to investigate a dose-response relationship, dose-toxicity relationship, progression free survival (PFS) and overall survival (OS) in neuroendocrine tumour liver metastases (NELM) treated with holmium-166-microspheres radioembolization ([166Ho]-radioembolization). MATERIALS AND METHODS: Single center, retrospective study included patients with NELM that received [166Ho]-radioembolization with post-treatment SPECT/CT and CECT or MRI imaging for 3 months follow-up. Post-treatment SPECT/CT was used to calculate tumour (Dt) and whole liver healthy tissue (Dh) absorbed dose. Clinical and laboratory toxicity was graded by Common Terminology Criteria for Adverse Events (CTCAE), version 5 at baseline and three-months follow-up. Response was determined according to RECIST 1.1. The tumour and healthy doses was correlated to lesion-based objective response and patient-based toxicity. Kaplan Meier analyses were performed for progression free survival (PFS) and overall survival (OS). RESULTS: Twenty-seven treatments in 25 patients were included, with a total of 114 tumours. Median follow-up was 14 months (3 - 82 months). Mean Dt in non-responders was 68 Gy versus 118 Gy in responders, p = 0.01. ROC analysis determined 86 Gy to have the highest sensitivity and specificity, resp. 83% and 81%. Achieving a Dt of ≥ 120 Gy provided the highest likelihood of response (90%) for obtaining response. Sixteen patients had grade 1-2 clinical toxicity and only one patient grade 3. No clear healthy liver dose-toxicity relationship was found. The median PFS was 15 months (95% CI [10.2;19.8]) and median OS was not reached. CONCLUSION: This study confirms the safety and efficacy of [166Ho]-radioembolization in NELM in a real-world setting. A clear dose-response relationship was demonstrated and future studies should aim at a Dt of ≥ 120 Gy, being predictive of response. No dose-toxicity relationship could be established.

Utility of pre-procedural [99mTc]TcMAA SPECT/CT Multicompartment Dosimetry for Treatment Planning of 90Y Glass microspheres in patients with Hepatocellular Carcinoma: comparison of anatomic versus [99mTc]TcMAA-based Segmentation.

PURPOSE: Pre-treatment [99mTc]TcMAA-based radioembolization treatment planning using multicompartment dosimetry involves the definition of the tumor and normal tissue compartments and calculation of the prescribed absorbed doses. The aim was to compare the real-world utility of anatomic and [99mTc]TcMAA-based segmentation of tumor and normal tissue compartments. MATERIALS AND METHODS: Included patients had HCC treated by glass [90Y]yttrium microspheres, ≥ 1 tumor, ≥ 3 cm diameter and [99mTc]TcMAA SPECT/CT imaging before treatment. Segmentation was performed retrospectively using dedicated dosimetry software: (1) anatomic (diagnostic CT/MRI-based), and (2) [99mTc]TcMAA threshold-based (i.e., using an activity-isocontour threshold). CT/MRI was co-registered with [99mTc]TcMAA SPECT/CT. Logistic regression and Cox regression, respectively, were used to evaluate relationships between total perfused tumor absorbed dose (TAD) and objective response rate (ORR) and overall survival (OS). In a subset-analysis pre- and post-treatment dosimetry were compared using Bland-Altman analysis and Pearson's correlation coefficient. RESULTS: A total of 209 patients were enrolled. Total perfused tumor and normal tissue volumes were larger when using anatomic versus [99mTc]TcMAA threshold segmentation, resulting in lower absorbed doses. mRECIST ORR was higher with increasing total perfused TAD (odds ratio per 100 Gy TAD increase was 1.22 (95% CI: 1.01-1.49; p = 0.044) for anatomic and 1.19 (95% CI: 1.04-1.37; p = 0.012) for [99mTc]TcMAA threshold segmentation. Higher total perfused TAD was associated with improved OS (hazard ratio per 100 Gy TAD increase was 0.826 (95% CI: 0.714-0.954; p = 0.009) and 0.847 (95% CI: 0.765-0.936; p = 0.001) for anatomic and [99mTc]TcMAA threshold segmentation, respectively). For pre- vs. post-treatment dosimetry comparison, the average bias for total perfused TAD was + 11.5 Gy (95% limits of agreement: -227.0 to 250.0) with a strong positive correlation (Pearson's correlation coefficient = 0.80). CONCLUSION: Real-world data support [99mTc]TcMAA imaging to estimate absorbed doses prior to treatment of HCC with glass [90Y]yttrium microspheres. Both anatomic and [99mTc]TcMAA threshold methods were suitable for treatment planning. TRIAL REGISTRATION NUMBER: NCT03295006.

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

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

Voxel-based tumor dose correlates to complete pathologic necrosis after transarterial radioembolization for hepatocellular carcinoma.

PURPOSE: The transarterial radioembolization (TARE) dose is traditionally calculated using the single-compartment Medical Internal Radiation Dose (MIRD) formula. This study utilized voxel-based dosimetry to correlate tumor dose with explant pathology in order to identify dose thresholds that predicted response. METHODS: All patients with HCC treated with TARE using yttrium-90 [90Y] glass microspheres at a single institution between January 2015 - June 2023 who underwent liver transplantation were eligible. The [90Y] distribution and dose-volume histograms were determined using Simplicity90 (Mirada Medical, Oxford UK) with a Bremsstrahlung SPECT/CT. A complete response was assigned if explant pathology showed complete necrosis and the patient had not undergone additional treatments to the same tumor after TARE. Logistic regression and receiver operator characteristic (ROC) curves were constructed to evaluate dose thresholds correlated with response. RESULTS: Forty-one patients were included. Twenty-six (63%) met criteria for complete response. Dose to 95% (D95), 70% (D70), and 50% (D50) of the tumor volume were associated with likelihood of complete response by logistic regression (all p < 0.05). For lesions with complete response versus without, the median D95 was 813 versus 232 Gy, D70 was 1052 versus 315 Gy, and D50 was 1181 versus 369 Gy (all p < 0.01). A D95 > 719 Gy had the highest accuracy at 68% (58% sensitivity, 87% specificity) for predicting complete response. Median percent of tumor volume receiving at least 100 Gy (V100), 200 Gy (V200), 300 Gy (V300), and 400 Gy (V400) also differed by pathologic response: the median V100, V200, V300, and V400 was 100% versus 99%, 100% versus 97%, 100% versus 74%, and 100% versus 43% in the complete response versus non-complete response groups, respectively (all p < 0.05). CONCLUSION: Voxel-based dosimetry was well-correlated with explant pathology. The D95 threshold had the highest accuracy, suggesting the D95 may be a relevant target for multi-compartment dosimetry.

The role of biomarkers and dosimetry parameters in overall and progression free survival prediction for patients treated with personalized 90Y glass microspheres SIRT: a preliminary machine learning study.

BACKGROUND: Overall Survival (OS) and Progression-Free Survival (PFS) analyses are crucial metrics for evaluating the efficacy and impact of treatment. This study evaluated the role of clinical biomarkers and dosimetry parameters on survival outcomes of patients undergoing 90Y selective internal radiation therapy (SIRT). MATERIALS/METHODS: This preliminary and retrospective analysis included 17 patients with hepatocellular carcinoma (HCC) treated with 90Y SIRT. The patients underwent personalized treatment planning and voxel-wise dosimetry. After the procedure, the OS and PFS were evaluated. Three structures were delineated including tumoral liver (TL), normal perfused liver (NPL), and whole normal liver (WNL). 289 dose-volume constraints (DVCs) were extracted from dose-volume histograms of physical and biological effective dose (BED) maps calculated on 99mTc-MAA and 90Y SPECT/CT images. Subsequently, the DVCs and 16 clinical biomarkers were used as features for univariate and multivariate analysis. Cox proportional hazard ratio (HR) was employed for univariate analysis. HR and the concordance index (C-Index) were calculated for each feature. Using eight different strategies, a cross-combination of various models and feature selection (FS) methods was applied for multivariate analysis. The performance of each model was assessed using an averaged C-Index on a three-fold nested cross-validation framework. The Kaplan-Meier (KM) curve was employed for univariate and machine learning (ML) model performance assessment. RESULTS: The median OS was 11 months [95% CI: 8.5, 13.09], whereas the PFS was seven months [95% CI: 5.6, 10.98]. Univariate analysis demonstrated the presence of Ascites (HR: 9.2[1.8,47]) and the aim of SIRT (segmentectomy, lobectomy, palliative) (HR: 0.066 [0.0057, 0.78]), Aspartate aminotransferase (AST) level (HR:0.1 [0.012-0.86]), and MAA-Dose-V205(%)-TL (HR:8.5[1,72]) as predictors for OS. 90Y-derived parameters were associated with PFS but not with OS. MAA-Dose-V205(%)-WNL, MAA-BED-V400(%)-WNL with (HR:13 [1.5-120]) and 90Y-Dose-mean-TL, 90Y-D50-TL-Gy, 90Y-Dose-V205(%)-TL, 90Y-Dose- D50-TL-Gy, and 90Y-BED-V400(%)-TL (HR:15 [1.8-120]) were highly associated with PFS among dosimetry parameters. The highest C-index observed in multivariate analysis using ML was 0.94 ± 0.13 obtained from Variable Hunting-variable-importance (VH.VIMP) FS and Cox Proportional Hazard model predicting OS, using clinical features. However, the combination of VH. VIMP FS method with a Generalized Linear Model Network model predicting OS using Therapy strategy features outperformed the other models in terms of both C-index and stratification of KM curves (C-Index: 0.93 ± 0.14 and log-rank p-value of 0.023 for KM curve stratification). CONCLUSION: This preliminary study confirmed the role played by baseline clinical biomarkers and dosimetry parameters in predicting the treatment outcome, paving the way for the establishment of a dose-effect relationship. In addition, the feasibility of using ML along with these features was demonstrated as a helpful tool in the clinical management of patients, both prior to and following 90Y-SIRT.

Adjuvant holmium-166 radioembolization after radiofrequency ablation in early-stage hepatocellular carcinoma patients: a dose-finding study (HORA EST HCC trial).

PURPOSE: The aim of this study was to investigate the biodistribution of (super-)selective trans-arterial radioembolization (TARE) with holmium-166 microspheres (166Ho-MS), when administered as adjuvant therapy after RFA of HCC 2-5 cm. The objective was to establish a treatment volume absorbed dose that results in an absorbed dose of ≥ 120 Gy on the hyperemic zone around the ablation necrosis (i.e., target volume). METHODS: In this multicenter, prospective dose-escalation study in BCLC early stage HCC patients with lesions 2-5 cm, RFA was followed by (super-)selective infusion of 166Ho-MS on day 5-10 after RFA. Dose distribution within the treatment volume was based on SPECT-CT. Cohorts of up to 10 patients were treated with an incremental dose (60 Gy, 90 Gy, 120 Gy) of 166Ho-MS to the treatment volume. The primary endpoint was to obtain a target volume dose of ≥ 120 Gy in 9/10 patients within a cohort. RESULTS: Twelve patients were treated (male 10; median age, 66.5 years (IQR, [64.3-71.7])) with a median tumor diameter of 2.7 cm (IQR, [2.1-4.0]). At a treatment volume absorbed dose of 90 Gy, the primary endpoint was met with a median absorbed target volume dose of 138 Gy (IQR, [127-145]). No local recurrences were found within 1-year follow-up. CONCLUSION: Adjuvant (super-)selective infusion of 166Ho-MS after RFA for the treatment of HCC can be administered safely at a dose of 90 Gy to the treatment volume while reaching a dose of ≥ 120 Gy to the target volume and may be a favorable adjuvant therapy for HCC lesions 2-5 cm. TRIAL REGISTRATION: Clinicaltrials.gov NCT03437382 . (registered: 19-02-2018).

Ultrastable PLGA-Coated 177Lu-Microspheres for Radioembolization Therapy of Hepatocellular Carcinoma.

Transarterial radioembolization (TARE) is a highly effective localized radionuclide therapy that has been successfully used to treat hepatocellular carcinoma (HCC). Extensive research has been conducted on the use of radioactive microspheres (MSs) in TARE, and the development of ideal radioactive MSs is crucial for clinical trials and patient treatment. This study presents the development of a radioactive MS for TARE of HCC. These MSs, referred to as 177Lu-MS@PLGA, consist of poly(lactic-co-glycolic acid) (PLGA) copolymer and radioactive silica MSs, labeled with 177Lu and then coated with PLGA. It has an extremely high level of radiostability. Cellular experiments have shown that it can cause DNA double-strand breaks, leading to cell death. In vivo radiostability of 177Lu-MS@PLGA is demonstrated by microSPECT/CT imaging. In addition, the antitumor study has shown that TARE of 177Lu-MS@PLGA can effectively restrain tumor growth without harmful side effects. Thus, 177Lu-MS@PLGA exhibits significant potential as a radioactive MS for the treatment of HCC.

Selective internal radiation therapy using yttrium-90 microspheres for treatment of localized and locally advanced intrahepatic cholangiocarcinoma.

OBJECTIVES: To evaluate safety and effectiveness of selective internal radiation therapy (SIRT) using yttrium-90 for localized and locally advanced intrahepatic cholangiocarcinoma (iCCA). METHODS: A retrospective review was performed of patients with localized iCCA treated with SIRT at a single institution. Overall survival (OS), local tumor response, progression-free survival (PFS), and toxicity were collected. Stratified analysis was performed based on surgical resection. Predictor analysis of OS was performed using the Fine-Grey regression analysis model with patients bridged to surgery regarded as competing events. RESULTS: A total of 28 consecutive patients with localized iCCA were treated with a total of 38 sessions of SIRT (17 segmental, 13 lobar, and 8 combined deliveries) and a mean dominant target dose per session of 238.4 ± 130.0 Gy. The cumulative radiologic response rate was 16/28 (57.1%) with a median PFS of 265 days. Median survival time (MST) was 22.9 months for the entire cohort with 1-year and 3-year survival of 78.4% and 45.1%, respectively. Ten patients (34.5%) were downstaged to surgical intervention (7 resection, 3 transplant) and showed longer OS (p = 0.027). The 1-year and 3-year OS for patients who received surgery were 100% and 62.5% (95% CI: 14.2-89.3%), respectively. Age (p = 0.028), Eastern Cooperative Oncology Group performance status (p = 0.030), and objective radiologic response (p=0.014) are associated with OS. Two ≥grade 3 hyperbilirubinemia, anemia, and one pleuro-biliary fistula occurred post-SIRT. CONCLUSIONS: SIRT for localized iCCA is safe and effective in achieving radiological response, downstaging to surgery and transplant, and resulting in pathologic necrosis. CLINICAL RELEVANCE STATEMENT: Selective internal radiation therapy should be considered for patients with localized and locally advanced intrahepatic cholangiocarcinoma. KEY POINTS: • The effectiveness of radioembolization for intrahepatic cholangiocarcinoma (iCCA) can be underestimated given the inclusion of extrahepatic disease. • Radioembolization is safe and effective for local and locally advanced iCCA. Age, Eastern Cooperative Oncology Group performance status, and radiologic response are associated with survival. • Radioembolization should be considered for patients with localized and locally advanced iCCA.

Locoregional Therapies for Primary and Metastatic Breast Cancer: AJR Expert Panel Narrative Review.

Minimally invasive locoregional therapies have a growing role in the multidisciplinary treatment of primary and metastatic breast cancer. Factors contributing to the expanding role of ablation for primary breast cancer include earlier diagnosis, when tumors are small, and increased longevity of patients whose condition precludes surgery. Cryoablation has emerged as the leading ablative modality for primary breast cancer owing to its wide availability, the lack of need for sedation, and the ability to monitor the ablation zone. Emerging evidence suggests that in patients with oligometastatic breast cancer, use of locoregional therapies to eradicate all disease sites may confer a survival advantage. Evidence also suggests that transarterial therapies-including chemoembolization, chemoperfusion, and radioembolization-may be helpful to some patients with advanced liver metastases from breast cancer, such as those with hepatic oligoprogression or those who cannot tolerate systemic therapy. However, the optimal modalities for treatment of oligometastatic and advanced metastatic disease remain unknown. Finally, locoregional therapies may produce tumor antigens that in combination with immunotherapy drive anti-tumor immunity. Although key trials are ongoing, additional prospective studies are needed to establish the inclusion of interventional oncology in societal breast cancer guidelines to support further clinical adoption and improved patient outcomes.

Advances in Radionuclide Therapies for Patients with Neuro-endocrine Tumors.

PURPOSE OF REVIEW: To provide insights into the role of peptide receptor radionuclide therapy (PRRT) in patients with advanced neuroendocrine tumors (NET) and an overview of possible strategies to combine PRRT with locoregional and systemic anticancer treatments. RECENT FINDINGS: Research on combining PRRT with other treatments encompasses a wide variety or treatments, both local (transarterial radioembolization) and systemic therapies, chemotherapy (i.e., capecitabine and temozolomide), targeted therapies (i.e., olaparib, everolimus, and sunitinib), and immunotherapies (e.g., nivolumab and pembrolizumab). Furthermore, PRRT shows promising first results as a treatment prior to surgery. There is great demand to enhance the efficacy of PRRT through combination with other anticancer treatments. While research in this area is currently limited, the field is rapidly evolving with numerous ongoing clinical trials aiming to address this need and explore novel therapeutic combinations.

Chemoembolization, Radioembolization, and Percutaneous Ablation: New Opportunities for Treating Ovarian Cancer Liver Metastasis.

OPINION STATEMENT: Parenchymal liver metastases from ovarian cancer, occurring in 2-12.5% of cases, significantly worsen prognosis. While surgery and systemic treatments remain primary options, unresectable or chemotherapy-resistant multiple liver metastases pose a significant challenge. Recent advances in liver-directed therapies, including radiofrequency ablation, microwave ablation, cryoablation, transarterial chemoembolization (TACE), and radioembolization, offer potential treatment alternatives. However, the efficacy of these techniques is limited by factors such as tumor size, number, and location. The ideal candidate for tumor ablation is a patient with paucifocal disease, a single tumor up to 5 cm or up to 3 tumors smaller than 3 cm and tumors 1 cm away from major bile ducts and high-flow vessels. Transarterial chemoembolization could be performed in patients with less than 70% tumor load. Differently, radioembolization is available with less limitation on the sites or number of liver cancers. Radioembolization techniques are also able to downsize liver metastases. However, there are limited data regarding the outcomes of loco-regional therapy in patients with hepatic metastases from ovarian cancer. Advancing liver-directed therapies through interventional oncology, combined with robust data on the oncological efficacy of these local treatments, will validate their potential as effective locoregional therapies for liver metastases. This could offer a promising treatment option for patients with ovarian cancer and unresectable hepatic metastases.

Prognostic factors influencing outcomes in hepatocellular carcinoma patients undergoing selective internal radiation therapy.

Selective internal radiation therapy (SIRT) has emerged as a viable endovascular treatment strategy for hepatocellular carcinoma (HCC). According to the Barcelona Clinic Liver Cancer (BCLC) classification, SIRT is currently recommended for early- and intermediate-stage HCC that is unsuitable for alternative locoregional therapies. Additionally, SIRT remains a recommended treatment for patients with advanced-stage HCC and portal vein thrombosis (PVT) without extrahepatic metastasis. Several studies have shown that SIRT is a versatile and promising treatment with a wide range of applications. Consequently, given its favourable characteristics in various scenarios, SIRT could be an encouraging treatment option for patients with HCC across different BCLC stages. Over the past decade, an increasing number of studies have focused on better understanding the prognostic factors associated with SIRT to identify patients who derive the most benefit from this treatment or to refine the optimal technical procedures of SIRT. Several variables can influence treatment decisions, with a growing emphasis on a personalised approach. This review, based on the literature, will focus on the prognostic factors associated with the effectiveness of radioembolization and related complications. By comprehensively analysing these factors, we aimed to provide a clearer understanding of how to optimise the use of SIRT in managing HCC patients, thereby enhancing outcomes across various clinical scenarios.

AAPM Medical Physics Practice Guideline 14.a: Yttrium-90 microsphere radioembolization.

Radioembolization using Yttrium-90 (90 Y) microspheres is widely used to treat primary and metastatic liver tumors. The present work provides minimum practice guidelines for establishing and supporting such a program. Medical physicists play a key role in patient and staff safety during these procedures. Products currently available are identified and their properties and suppliers summarized. Appropriateness for use is the domain of the treating physician. Patient work up starts with pre-treatment imaging. First, a mapping study using Technetium-99m (Tc-99m ) is carried out to quantify the lung shunt fraction (LSF) and to characterize the vascular supply of the liver. An MRI, CT, or a PET-CT scan is used to obtain information on the tumor burden. The tumor volume, LSF, tumor histology, and other pertinent patient characteristics are used to decide the type and quantity of 90 Y to be ordered. On the day of treatment, the appropriate dose is assayed using a dose calibrator with a calibration traceable to a national standard. In the treatment suite, the care team led by an interventional radiologist delivers the dose using real-time image guidance. The treatment suite is posted as a radioactive area during the procedure and staff wear radiation dosimeters. The treatment room, patient, and staff are surveyed post-procedure. The dose delivered to the patient is determined from the ratio of pre-treatment and residual waste exposure rate measurements. Establishing such a treatment modality is a major undertaking requiring an institutional radioactive materials license amendment complying with appropriate federal and state radiation regulations and appropriate staff training commensurate with their respective role and function in the planning and delivery of the procedure. Training, documentation, and areas for potential failure modes are identified and guidance is provided to ameliorate them.

The Future of Interventions for Stage IV Colorectal Cancers.

Future options for the management of stage IV colorectal cancer are primarily focused on personalized and directed therapies. Interventions include precision cancer medicine, utilizing nanocarrier platforms for directed chemotherapy, palliative pressurized intraperitoneal aerosol chemotherapy (PIPAC), adjunctive oncolytic virotherapy, and radioembolization techniques. Comprehensive genetic profiling provides specific tumor-directed therapy based on individual genetics. Biomimetic magnetic nanoparticles as chemotherapy delivery systems may reduce systemic side effects of traditional chemotherapy by targeting tumor cells and sparing healthy cells. PIPAC is a newly emerging option for patients with peritoneal metastasis from colorectal cancer and is now being used internationally, showing promising results as a palliative therapy for colorectal cancer. Oncolytic virotherapy is another emerging potential treatment option, especially when combined with standard chemotherapy and/or radiation, as well as immunotherapy. And finally, radioembolization with yttrium-90 ( 90 Y) microspheres has shown some success in treating patients with unresectable liver metastasis from colorectal cancer via selective arterial injection.

Direct comparison and reproducibility of two segmentation methods for multicompartment dosimetry: round robin study on radioembolization treatment planning in hepatocellular carcinoma.

PURPOSE: Investigate reproducibility of two segmentation methods for multicompartment dosimetry, including normal tissue absorbed dose (NTAD) and tumour absorbed dose (TAD), in hepatocellular carcinoma patients treated with yttrium-90 (90Y) glass microspheres. METHODS: TARGET was a retrospective investigation in 209 patients with < 10 tumours per lobe and at least one tumour ≥ 3 cm ± portal vein thrombosis. Dosimetry was compared using two distinct segmentation methods: anatomic (CT/MRI-based) and count threshold-based on pre-procedural 99mTc-MAA SPECT. In a round robin substudy in 20 patients with ≤ 5 unilobar tumours, the inter-observer reproducibility of eight reviewers was evaluated by computing reproducibility coefficient (RDC) of volume and absorbed dose for whole liver, whole liver normal tissue, perfused normal tissue, perfused liver, total perfused tumour, and target lesion. Intra-observer reproducibility was based on second assessments in 10 patients ≥ 2 weeks later. RESULTS: 99mTc-MAA segmentation calculated higher absorbed doses compared to anatomic segmentation (n = 209), 43.9% higher for TAD (95% limits of agreement [LoA]: - 49.0%, 306.2%) and 21.3% for NTAD (95% LoA: - 67.6%, 354.0%). For the round robin substudy (n = 20), inter-observer reproducibility was better for anatomic (RDC range: 1.17 to 3.53) than 99mTc-MAA SPECT segmentation (1.29 to 7.00) and similar between anatomic imaging modalities (CT: 1.09 to 3.56; MRI: 1.24 to 3.50). Inter-observer reproducibility was better for larger volumes. Perfused normal tissue volume RDC was 1.95 by anatomic and 3.19 by 99mTc-MAA SPECT, with corresponding absorbed dose RDC 1.46 and 1.75. Total perfused tumour volume RDC was higher, 2.92 for anatomic and 7.0 by 99mTc-MAA SPECT with corresponding absorbed dose RDC of 1.84 and 2.78. Intra-observer variability was lower for perfused NTAD (range: 14.3 to 19.7 Gy) than total perfused TAD (range: 42.8 to 121.4 Gy). CONCLUSION: Anatomic segmentation-based dosimetry, versus 99mTc-MAA segmentation, results in lower absorbed doses with superior reproducibility. Higher volume compartments, such as normal tissue versus tumour, exhibit improved reproducibility. TRIAL REGISTRATION: NCT03295006.

Clinical, dosimetric, and reporting considerations for Y-90 glass microspheres in hepatocellular carcinoma: updated 2022 recommendations from an international multidisciplinary working group.

PURPOSE: In light of recently published clinical reports and trials, the TheraSphere Global Dosimetry Steering Committee (DSC) reconvened to review new data and to update previously published clinical and dosimetric recommendations for the treatment of hepatocellular carcinoma (HCC). METHODS: The TheraSphere Global DSC is comprised of health care providers across multiple disciplines involved in the treatment of HCC with yttrium-90 (Y-90) glass microsphere-based transarterial radioembolization (TARE). Literature published between January 2019 and September 2021 was reviewed, discussed, and adjudicated by the Delphi method. Recommendations included in this updated document incorporate both the results of the literature review and the expert opinion and experience of members of the committee. RESULTS: Committee discussion and consensus led to the expansion of recommendations to apply to five common clinical scenarios in patients with HCC to support more individualized efficacious treatment with Y-90 glass microspheres. Existing clinical scenarios were updated to reflect recent developments in dosimetry approaches and broader treatment paradigms evolving for patients presenting with HCC. CONCLUSION: Updated consensus recommendations are provided to guide clinical and dosimetric approaches for the use of Y-90 glass microsphere TARE in HCC, accounting for disease presentation, tumor biology, and treatment intent.

Defining textbook outcome for selective internal radiation therapy of hepatocellular carcinoma: an international expert study.

BACKGROUND: A textbook outcome (TO) is a composite indicator covering the entire intervention process in order to reflect the "ideal" intervention and be a surrogate for patient important outcomes. Selective internal radiation therapy (SIRT) is a complex multidisciplinary and multistep intervention facing the challenge of standardization. This expert opinion-based study aimed to define a TO for SIRT of hepatocellular carcinoma. METHODS: This study involved two steps: (1) the steering committee (4 interventional radiologists) first developed an extensive list of possible relevant items reflecting an optimal SIRT intervention based on a literature review and (2) then conducted an international and multidisciplinary survey which resulted in the final TO. This survey was online, from February to July 2021, and consisted three consecutive rounds with predefined settings. Experts were identified by contacting senior authors of randomized trials, large observational studies, or studies on quality improvement in SIRT. This study was strictly academic. RESULTS: A total of 50 items were included in the first round of the survey. A total of 29/40 experts (73%) responded, including 23 interventional radiologists (79%), three nuclear medicine physicians (10%), two hepatologists, and one oncologist, from 11 countries spanning three continents. The final TO consisted 11 parameters across six domains ("pre-intervention workup," "tumor targeting and dosimetry," "intervention," "post-90Y imaging," "length of hospital stay," and "complications"). Of these, all but one were applied in the institutions of > 80% of experts. CONCLUSIONS: This multidimensional indicator is a comprehensive standardization tool, suitable for routine care, clinical round, and research.