Radioembolization Research Articles

166Ho-RadioEmbolizaTiOn Using personalized prediCtive dosimetry in patients with Hepatocellular carcinoma: A prospective, single-centre study (RETOUCH).

Holmium-166 (166Ho) radioembolization could offer a more individualized approach in terms of imaging and dosimetry. We aim to evaluate the feasibility and safety of 166Ho selective internal radiation therapy (SIRT) using a higher tumour dose than previously administered determined by 166Ho-scout as a surrogate marker in HCC patients. This is an open-label, prospective, non-randomized, single-centre pilot study that included patients with HCC that received 166Ho-SIRT if the work-up using 166Ho-scout showed a tumour-absorbed dose ≥150 Gy, a non-tumoural liver absorbed dose less than 60 Gy and a lung absorbed dose less than 30 Gy. Primary endpoints were feasibility and safety-toxicity profiles at 24-48 h and 1 month. Overall response rates (ORR) at 3 months (mRECIST, RECIST 1.1 and metabolic response by FDG and choline PET CT) and time to progression (TTP) represented the secondary endpoints. Fifteen patients with large tumours (mean diameter 55.67 ± 28.42 mm) received 17 166Ho-SIRT treatments between July 2020 and June 2022. All the attempted treatments were accomplished. Mean administered tumour dose was 183.18 ± 71.71 Gy, while non-tumour liver dose was 30.29 ± 14.56 Gy. Median time of follow-up was 12 months (IQR 9-16). Only grade 1-2 clinical and biological AEs were observed. There were no liver decompensations. At 3 months, objective response was achieved for all target lesions (CR 78.57%, PR 21.43% according to mRECIST). Median TTP was 18.8 (range 2.9; n.e.) months. Personalized 166Ho-SIRT with a tumour delivered dose ≥150 Gy was feasible and safe for HCC patients with promising response rates.

Unexpected Anti-tumor Effect of Selective Internal Radiation Therapy and Radiofrequency Ablation Followed by Immune Checkpoint Inhibitors for Hepatocellular Carcinoma

Introduction: Hepatocellular carcinoma (HCC) has become an increasingly serious health problem worldwide. Combining immune checkpoint inhibitors (ICIs) for HCC with local treatments can produce synergistic effects. Although the abscopal effect was noted in 1953, most studies on this phenomenon have been conducted in the context of external beam radiotherapy (EBRT). The incidence of the abscopal effect induced by selective internal radiation therapy (SIRT) alone is lower. This research reports a case of a patient with multifocal HCC who received SIRT plus radiofrequency ablation (RFA) followed by ICI therapy. During the subsequent course of ICI therapy, an anti-tumor effect was detected in the left hepatic lobe, far from the site targeted by the local treatments. Case Presentation: The abscopal effect has recently attracted widespread attention because ICIs can enhance this phenomenon. However, little is known about the relationship between inducing the abscopal effect and local treatment against HCC. A 76-year-old male patient presented with multifocal HCC. During hepatic angiography, MRI showed multiple HCCs in both lobes of the liver. Selective internal radiation therapy was performed on a tumor with a diameter of approximately 80 millimeters in the right lobe. A month later, RFA was conducted on another tumor in the right lobe, approximately 30 mm in diameter, and ICI therapy was administered on the second day post-RFA. Hepatic arterial phase imaging of contrast-enhanced magnetic resonance performed 10 months after SIRT showed the disappearance of the tumor in the left liver lobe. Conclusions: This case highlights that the combination of multiple local treatment methods with ICI therapy can enhance the anti-tumor immune response and benefit patients with multifocal

The experience of transarterial embolisation for metastsatic NET at queen Elizabeth Hospital Birmingham and future possible role of selective internal radiation therapy

The experience of transarterial embolisation for metastsatic NET at queen Elizabeth Hospital Birmingham and future possible role of selective internal radiation therapy

First-line chemotherapy with selective internal radiation therapy for intrahepatic cholangiocarcinoma: the French ACABi GERCOR PRONOBIL cohort

Background & AimsSelective internal radiation therapy (SIRT) is a promising option for liver-only unresectable intrahepatic cholangiocarcinoma (iCCA). The Real-SIRTCCA study retrospectively assessed the benefit of adding SIRT to chemotherapy in this setting within the French nationwide observational cohort ACABi-GERCOR-PRONOBIL. MethodsInclusion criteria were advanced iCCA with limited or no extrahepatic disease, treated with first-line gemcitabine plus platinum chemotherapy +/- concurrent SIRT. All patients treated by chemotherapy with concurrent SIRT were included. To ensure groups’ similarity, a rigorous selection was applied to the chemo-only group, with exclusion of patients with liver involvement >50% and extra-hepatic metastases. The primary outcome was progression-free survival (PFS). Secondary outcomes were overall survival (OS), objective response rate (ORR) and tumor resection rate. Propensity score and Inverse Probability of Treatment Weighting (IPTW) propensity approaches were used to address confounding factors between groups. ResultsBetween July 2007 and December 2023, 277 patients met the Real-SIRTCCA inclusion criteria, with 88 in the chemo-SIRT group and 189 in chemo-only group. Chemo-SIRT was associated with longer PFS (median=10.8 vs. 5.5 months, HR=0.54, 95% CI 0.41-0.71, p<0.0001), a trend for longer OS (median=22.5 vs. 15.1 months, HR=0.76, 95% CI 0.57-1.01), higher ORR (58.3% vs. 28.5%, OR=3.51, 95% CI 2.03-6.09, p<0.0001), and resection rate (18.7% vs 8.8%, p=0.0279) as compared to chemo-alone. After IPTW, superiority of chemo-SIRT was confirmed with better PFS (HR=0.55, 95% CI 0.45-0.66, p<0,0001), OS (HR=0.70, 95% CI 0.58-0.85, p=0.0004), ORR (OR=3.17, 95% CI 2.18-4.49, p<0.0001) and resection rate (OR=2.94, 95% CI 1.71-5.03, p<0.0001). ConclusionsAdding SIRT to first-line chemotherapy significantly improved survival outcomes, ORR, and secondary tumor resection in locally advanced iCCA. Prospective randomized data are needed to confirm these results. Clinical trial numberNCT04935853

Metastatic insulinoma—outcomes in the current era

Abstract Background Multimodal interventions in neuroendocrine tumors appear to have a beneficial impact on survival. Metastatic insulinoma is associated with hypoglycemia and, historically, a shortened life expectancy. Methods The authors retrospectively analyzed the clinical outcomes of patients with metastatic insulinomas treated at a tertiary care center between 2006 and 2023. Results Clinical data on 14 patients with metastatic insulinoma (metastases to the liver, skeleton, and lung) were reviewed in this descriptive study. The patients underwent various treatments including surgery; liver directed therapies (embolization, selective internal radiotherapy), somatostatin analogs; targeted agents (everolimus); systemic chemotherapy (capecitabine/temozolomide; carboplatin/etoposide); external beam radiation; and peptide receptor radiotherapy. Seven subjects died during follow-up. The time of the 7 deaths ranged from 2.5 to 10.4 years (median time to death was 8.2 years). This compares to previous reports of median survival of about 2 years. Seven subjects are alive 1.2-12.3 years after diagnosis. Hypoglycemia was well-controlled and did not cause the deaths. Conclusions Multimodal interventions in metastatic insulinoma can be effective in managing hypoglycemia. The patients on multimodal treatments also lived a long time when considering previous published reports of median survival of just 2 years. Our findings challenge previous assumptions regarding clinical outcomes in this patient population.

LI-RADS radiation-based treatment response algorithm for HCC: what to know and how to use it.

Locoregional treatments (LRT) continue to advance for hepatocellular carcinoma (HCC). Selective internal radiation therapy (SIRT) or transarterial radioembolization (TARE) with radioactive 90 Yttrium (Y90) microspheres is currently widely accepted, and external beam and stereotactic body radiation (EBRT/SBRT) are increasingly used as LRT1-5. Assessment of treatment response after these radiation-based therapies can be challenging, given that the adjacent liver also undergoes treatment related changes, inflammatory changes occur, and there is a variable time for response to develop. In 2017, the liver imaging reporting and data system (LI-RADS) workgroup initially developed a single algorithm for the imaging assessment of treatment response encompassing all types of locoregional therapies, the LI-RADS treatment response (LR-TR) algorithm. Recognizing that response and imaging patterns differ between radiation and non-radiation based therapies, the LR-TR working group recently updated the algorithm to reflect the unique characteristics of tumor response for therapies involving radiation. This article aims to elucidate the changes in the new version of the LI-RADS TR, with a guide for algorithm utilization and illustration of expected and unexpected findings post liver directed therapies for HCC.

Sequencing microsphere selective internal radiotherapy after external beam radiotherapy for hepatocellular carcinoma: proof of concept of a synergistic combination.

This study aims to explore the synergistic effects of combining Stereotactic Body Radiation Therapy (SBRT) and Selective Internal Radiation Therapy (SIRT) in that specific sequence for treating hepatocellular carcinoma (HCC), particularly in patients at high risk of radiation-induced liver disease (RILD). We analyzed a case of a patient with HCC who was treated with SBRT at our institution. A virtual 90Y dose distribution was added using our in-house -BLINDED FOR REVIEW- model to keep a minimum dose to the healthy liver tissue. BED and EUD metrics were calculated to harmonize the dose distributions of SBRT and SIRT. Our radiation biology-based models suggest that the combination of SBRT and SIRT could maintain effective tumor control while reducing the dose to normal liver tissue. Specifically, an SBRT plan of 10 Gy x 3 fractions combined with SIRT yielded comparable tumor control probability to an SBRT-only plan of 10 Gy x 5 fractions. The combination of SBRT and SIRT is a promising treatment strategy for HCC patients at high risk of RILD. While the LQ model and associated formalisms provide a useful starting point, further studies are needed to account for factors beyond these models. Nonetheless, the potential for significant dose reduction to normal tissue suggests that this combination therapy could offer substantial clinical benefits. This article presents a proposal to combine SBRT and SIRT, in this specific order, for HCC, discussing its advantages. A framework for future research into optimizing combination therapy for HCC is provided, utilizing a novel HCC vascular model to simulate 90Y doses.

The Impact of Radiation Dose and Tumour Burden on Outcomes in Hepatocellular Carcinoma: 11-Year Experience in a 413-Patient Cohort Treated with Yttrium-90 Resin Microsphere Radioembolisation

Introduction: Transarterial radioembolisation (RE) using yttrium-90 (Y-90) microspheres is a widely used locoregional therapy for a broad spectrum of hepatocellular carcinoma (HCC) given its favourable safety profile. We evaluated the real-world outcomes of unresectable HCC treated with resin Y-90 RE and the relationship between tumour absorbed dose and subsequent curative therapy with survival. Methods: Included were consecutive patients treated with Y-90 resin microspheres RE for unresectable HCC between January 2008 and May 2019 at the National Cancer Centre Singapore/Singapore General Hospital. The outcomes were stratified by tumour burden, distribution, presence of portal vein invasion (PVI) and liver function to improve prognostication. Results: The median overall survival (OS) evaluated on 413 included patients was 20.9 months (95% CI: 18.2–24.0). More than half of the patients (214/413, 51.8%) had HCC beyond up-to-seven criteria, and 37.3% had portal vein invasion (154/413, 37.3%). Majority (71.7%) had dosimetry calculated based on the partition model. Patients who received ≥150 Gy to tumour had significantly better outcomes (OS 32.2 months, 95% CI: 18.3–46.4) than those who did not (OS 17.5 months, 95% CI: 13.7–22.7, p < 0.001). Seventy patients (17%) received curative therapies after tumour was downstaged by Y-90 RE and had better OS of 79.7 months (95% CI: 40.4 – NE) compared to those who did not receive curative therapies (OS 17.1 months; 95% CI: 13.5–20.4, p < 0.001). RE-induced liver injury was observed in 5.08% of the patients while 3.2% of the patients had possible radiation pneumonitis but none developed Grade 3–4 toxicity. For HCC without PVI, OS differed significantly with performance status, albumin-bilirubin grade, tumour distribution, and radiation dose; for HCC with PVI, Child-Pugh class and AFP were significant predictors of survival. Conclusions: Treatment outcomes for unresectable HCC using Y-90 RE were favourable. Incorporating tumour burden and distribution improved prognostication. Patients who received tumour absorbed dose above 150 Gy had better OS. Patients who subsequently received curative therapies after being downstaged by Y-90 RE had remarkable clinical outcomes.

Use of selective internal radiation therapy with yttrium-90 as a bridge to liver resection: a 5-year single-center experience

Selective internal radiation therapy (SIRT) with yttrium-90 (Y-90) has been historically reserved for unresectable liver malignancy. Evidence is emerging for the use of SIRT to increase future liver remnant (FLR), allowing for the resection of previously inoperable disease. This was a 5-year retrospective review of all patients undergoing SIRT with Y-90 at a tertiary institute. Patient demographics, clinicopathologic data, surgical details, and postoperative outcomes were reviewed. The primary outcome, safety of liver resection after SIRT, was evaluated with 90-day morbidity and mortality. A total of 134 SIRT procedures were performed on 113 patients. Post-SIRT complications occurred in 18 patients (15.9%), with a single 30-day mortality. In addition, 17 patients underwent SIRT with the intent to augment FLR for liver resection. After SIRT, mean hepatic mebrofenin extraction and FLR increased from 2.5%/min/m2 and 30.5% to 4.2%/min/m2 and 52.5% (P=.01 and P<.0001, respectively). Ten patients underwent resection, and there were 2 intraoperative complications. The median time from SIRT to resection was 5.2 months. The 90-day postoperative morbidity was 20% (n=2), and complications were analyzed according to the Clavien-Dindo II classification scale. There was no 30-day or 90-day postoperative mortality. Post-SIRT liver resection is a challenging procedure with low postoperative mortality and morbidity.

CCL2 Predicts Survival in Patients with Inoperable Hepatocellular Carcinoma Undergoing Selective Internal Radiotherapy.

Hepatocellular carcinoma (HCC) is the largest subgroup of primary liver tumors. Ablative therapies, such as selective internal radiation therapy (SIRT), are used in late stages for patients with unresectable liver metastases and no response to other therapies. CCL2 (C-C motif chemokine ligand 2) is a potent monocyte chemoattractant. It is associated with tumor progression and metastasis. The role of circulating CCL2 as a biomarker in HCC undergoing selective internal radiation therapy remains unclear. A total of 41 patients (8 female, 33 male) suffering from HCC and undergoing SIRT were enrolled. Pre- and post-therapy changes in circulating CCL2 levels were determined by bead-based immunoassay and compared with clinical laboratory parameters and patient data. A total of 32 patients exhibited survival beyond 60 days. It was observed that levels of CCL2 correlated with scores indicating a higher likelihood of non-survival and with the severity of the disease. Moreover, a significant inverse correlation was discovered between CCL2 levels and the survival of patients over 60 days in relation to counts of leukocytes, granulocytes, monocytes, and C-reactive protein. CCL2 may serve as a potential marker for patient survival after SIRT. The prediction of which HCC patients are likely to benefit from SIRT may be helpful in guiding therapeutic management.

Radioembolization of HCC and secondary hepatic tumors: a comprehensive review.

Transarterial radioembolization (TARE), also called Selective Internal Radiation Therapy (SIRT), has emerged as an effective locoregional therapy for primary and secondary hepatic tumors, utilizing yttrium-90 (Y90) microspheres and other agents such as holmium-166 and rhenium-188. TARE has various applications in the management of HCC across different BCLC stages. Radiation segmentectomy, which involves administering high doses of Y90 (>190 Gy), can be both curative and ablative, achieving complete necrosis of the tumor. In contrast, radiation lobectomy involves administering a lower dose of Y90 (80-120 Gy) as a neoadjuvant treatment modality to improve local control and induce future liver remnant (FLR) hypertrophy in patients who are planned to undergo surgery but have insufficient FLR. Modified radiation lobectomy combines both techniques and offers several advantages over portal vein embolization (PVE). Y90 is also used in downstaging HCC patients outside liver transplantation criteria, as well as bridging those awaiting liver transplantation (LT). Multiple studies and combined analyses were described to highlight the outcomes of TARE and compare it with other treatment modalities, including TACE and sorafenib. Additionally, the review delves into the efficacy and safety of radioembolization in managing metastatic colorectal cancer and other metastatic tumors to the liver. Recent studies have emphasized the role of personalized dosimetry for improved outcomes, and thus we described the different methods used for this purpose. Pretherapy imaging, estimating lung shunt, selection of therapeutic radionuclides, adverse effects, and cost-effectiveness were all discussed as well.

Modern TARE 2023 - from palliative care to a curative treatment alternative

Selective internal radiotherapy (SIRT) or transarterial radioembolisation (TARE) is an alternative treatment for hepatocellular carcinoma (HCC) or hepatic metastatic colorectal carcinoma (mCRC) and is now anchored in many guidelines. The article summarises the current guidelines on SIRT/TARE in HCC and mCRC.

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

BackgroundOverall 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/MethodsThis 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.ResultsThe 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).ConclusionThis 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.

PET/CT-Based Absorbed Dose Maps in 90Y Selective Internal Radiation Therapy Correlate with Spatial Changes in Liver Function Derived from Dynamic MRI.

Functional liver parenchyma can be damaged from treatment of liver malignancies with 90Y selective internal radiation therapy (SIRT). Evaluating functional parenchymal changes and developing an absorbed dose (AD)-toxicity model can assist the clinical management of patients receiving SIRT. We aimed to determine whether there is a correlation between 90Y PET AD voxel maps and spatial changes in the nontumoral liver (NTL) function derived from dynamic gadoxetic acid-enhanced MRI before and after SIRT. Methods: Dynamic gadoxetic acid-enhanced MRI scans were acquired before and after treatment for 11 patients undergoing 90Y SIRT. Gadoxetic acid uptake rate (k1) maps that directly quantify spatial liver parenchymal function were generated from MRI data. Voxel-based AD maps, derived from the 90Y PET/CT scans, were binned according to AD. Pre- and post-SIRT k1 maps were coregistered to the AD map. Absolute and percentage k1 loss in each bin was calculated as a measure of loss of liver function, and Spearman correlation coefficients between k1 loss and AD were evaluated for each patient. Average k1 loss over the patients was fit to a 3-parameter logistic function based on AD. Patients were further stratified into subgroups based on lesion type, baseline albumin-bilirubin scores and alanine transaminase levels, dose-volume effect, and number of SIRT treatments. Results: Significant positive correlations (ρ = 0.53-0.99, P < 0.001) between both absolute and percentage k1 loss and AD were observed in most patients (8/11). The average k1 loss over 9 patients also exhibited a significant strong correlation with AD (ρ ≥ 0.92, P < 0.001). The average percentage k1 loss of patients across AD bins was 28%, with a logistic function model demonstrating about a 25% k1 loss at about 100 Gy. Analysis between patient subgroups demonstrated that k1 loss was greater among patients with hepatocellular carcinoma, higher alanine transaminase levels, larger fractional volumes of NTL receiving an AD of 70 Gy or more, and sequential SIRT treatments. Conclusion: Novel application of multimodality imaging demonstrated a correlation between 90Y SIRT AD and spatial functional liver parenchymal degradation, indicating that a higher AD is associated with a larger loss of local hepatocyte function. With the developed response models, PET-derived AD maps can potentially be used prospectively to identify localized damage in liver and to enhance treatment strategies.

Selective internal radiation therapy for unresectable HCC: The SIRT downstaging study.

Selective internal radiation therapy (SIRT) is recommended as a downstaging (DS) strategy for solitary unresectable HCC <8cm. The aim of this study was to report the results of acquired experience in a tertiary center for all unresectable HCCs. We conducted a retrospective, observational study using data collected from consecutive patients undergoing SIRT between October 2013 and June 2020. DS was considered achieved when a curative treatment could be proposed 6 months after SIRT. One hundred twenty-seven patients were included (male = 90%, 64 ± 11y), of whom 112 (n = 88%) had cirrhosis. HCC was classified as BCLC stage C in 64 patients (50%), with a median diameter of 61mm, an infiltrative pattern in 51 patients (40%), and portal vein invasion in 62 (49%) patients. Fifty patients (39%) achieved DS 6 months following SIRT, with 29 of them (23%) undergoing curative treatment in a median time of 4.3 months: 17 (13%) were transplanted, 11 (85%) had liver resection, and 1 patient had a radiofrequency ablation. The median overall survival of patients with or without DS was 51 versus 10 months, respectively (p < 0.001). In patients who achieved DS, progression-free survival was higher in patients who underwent surgery: 47 versus 11 months (p < 0.001). Four variables were independently associated with DS: age (OR: 0.96, 95% CI: [0.92, 0.99]; p = 0.032), baseline α-fetoprotein (OR: 1.00, 95% CI: [1.00, 1.00]; p = 0.034), HCC distribution (OR: 0.3, 95% CI: [0.11, 0.75]; p = 0.012), and ALBI grade (OR: 0.34. 95% CI: [0.14, 0.80]; p = 0.014). These results suggest that SIRT in patients with unresectable HCC could be an effective treatment: DS was achieved for around 39% of the patients and more than half of these then underwent curative treatment.

Imaging of Hypoxia in Liver Tumors With 18 F-FMISO PET Before Selective Internal Radiotherapy With 90 Y Microspheres.

Hypoxia is a known cause of resistance to radiotherapy and chemotherapy. Although there are multiple studies in external radiation therapies based on hypoxia PET, the effect of hypoxia in radioembolization is largely unknown. Here we present 2 cases of hepatocellular carcinoma patients from a prospective study with different lesion characteristics on pretreatment 18 F-FMISO PET and varying responses on 18 F-FDG PET.

The Impact of Local Control on Overall Survival after Y-90 Selective Internal Radiotherapy of Liver Metastases in Oligometastatic Cancer: A Retrospective Analysis.

Y-90 Selective Internal Radiotherapy (SIRT) is an ablative therapy used for inoperable liver metastasis. The purpose of this investigation was to examine the impact of local control after SIRT on overall survival (OS) in oligometastatic patients. A retrospective, single-institution study identified oligometastatic patients with ≤5 non-intracranial metastases receiving unilateral or bilateral lobar Y-90 SIRT from 2009 to 2021. The primary endpoint was OS defined from Y-90 SIRT completion to the date of death or last follow-up. Local failure was classified as a progressive disease at the target lesion(s) by RECIST v1.1 criteria starting at 3 months after SIRT. With a median follow-up of 15.7 months, 33 patients were identified who had a total of 79 oligometastatic lesions treated with SIRT, with the majority histology of colorectal adenocarcinoma (n = 22). In total, 94% of patients completed the Y-90 lobectomy. Of the 79 individual lesions treated, 22 (27.8%) failed. Thirteen patients received salvage liver-directed therapy following intrahepatic failure; ten received repeat SIRT. Median OS (mOS) was 20.1 months, and 12-month OS was 68.2%. Intralesional failure was associated with worse 1 y OS (52.3% vs. 86.2%, p = 0.004). These results suggest that intralesional failure following Y-90 may be associated with inferior OS, emphasizing the importance of disease control in low-metastatic-burden patients.

DosePatch: physics-inspired cropping layout for patch-based Monte Carlo simulations to provide fast and accurate internal dosimetry

BackgroundDosimetry-based personalized therapy was shown to have clinical benefits e.g. in liver selective internal radiation therapy (SIRT). Yet, there is no consensus about its introduction into clinical practice, mainly as Monte Carlo simulations (gold standard for dosimetry) involve massive computation time. We addressed the problem of computation time and tested a patch-based approach for Monte Carlo simulations for internal dosimetry to improve parallelization. We introduce a physics-inspired cropping layout for patch-based MC dosimetry, and compare it to cropping layouts of the literature as well as dosimetry using organ-S-values, and dose kernels, taking whole-body Monte Carlo simulations as ground truth. This was evaluated in five patients receiving Yttrium-90 liver SIRT.ResultsThe patch-based Monte Carlo approach yielded the closest results to the ground truth, making it a valid alternative to the conventional approach. Our physics-inspired cropping layout and mosaicking scheme yielded a voxel-wise error of < 2% compared to whole-body Monte Carlo in soft tissue, while requiring only ≈\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\approx$$\\end{document} 10% of the time.ConclusionsThis work demonstrates the feasibility and accuracy of physics-inspired cropping layouts for patch-based Monte Carlo simulations.

Safety and efficacy of Holmium-166 selective internal radiotherapy of primary and secondary liver cancer confirmed by real-world data.

Holmium-166 has emerged as a promising option for selective internal radiotherapy (SIRT) for hepatic malignancies, but data on routine clinical use are lacking. The purpose of this study was to describe the safety and effectiveness of Holmium-166 SIRT in real-world practice through retrospective analysis of a multicenter registry. Retrospective analysis was conducted on Holmium-166 SIRT procedures performed between July 15, 2019, and July 15, 2021, across seven European centers. Treatment planning, treatment realization and post-treatment follow-up were conducted according to routine local practice. Safety and effectiveness data were extracted from the patients' health records. Primary endpoint analysis was assessed for the entire study population with separate analysis for subgroups with hepatocellular carcinoma, metastatic colorectal cancer and intrahepatic cholangiocarcinoma. A total of 167 SIRT procedures in 146 patients (mean age 66 ± 11 years, 68% male) were retrospectively evaluated. Most common tumor entities were hepatocellular carcinoma (n=55), metastatic colorectal cancer (n=35), intrahepatic cholangiocarcinoma (n=19) and metastatic neuroendocrine tumors (n=10). Nine adverse events grade ≥ 3 according to Common Terminology Criteria for Adverse Events were recorded, including one fatal case of radioembolization-induced liver disease. Response rates and median overall survival for the above mentioned subgroups were comparable to results from previous Holmium-166 trials as well as to results from Yttrium-90 registries. This study confirms that the safety and effectiveness of Holmium-166 SIRT derived from prospective trials also applies in routine clinical practice, reinforcing its potential as a viable treatment option for primary and secondary liver cancer.

The safety and short-term efficacy of selective internal radiation therapy combined with systemic treatment for unresectable malignant hepatic tumors in Chinese patients.

e16247 Background: There are many systemic treatment options for patients with unresectable malignant hepatic tumors. In China, selective internal radiation therapy (SIRT) with yttrium-90 (Y90) resin microspheres was approved until 2022. The aim of this retrospective study was to investigate the safety and short-term efficacy of SIRT with Y90 resin microspheres followed by systemic treatment in Chinese patients. Methods: The study analyzed patients who received SIRT with Y90 combined with systemic treatment at our center between June 2022 and October 2023. The study's primary endpoint was to determine the objective response rate (ORR), while safety was the secondary endpoint. Response was measured based on modified Response Evaluation Criteria in Solid Tumors criteria (mRECIST) up to 90 days after the initial therapy. Safety was evaluated using the Common Terminology Criteria for Adverse Events Version 5.0. Results: 21 patients wereincluded, of whom 22 times of SIRT were performed. 18 patients had HCC, and 3 had mCRC.The baseline characteristics of the patients are shown in Table. The median age was 54 years (IQR, 48-59 years) and 90.5% of patients were male. According to Eastern Cooperative Oncology Group performance status, grade 0 and grade 1 were 81% and 19%, respectively, whereas Child-Pugh A represented 90.5% of cases. The proportion of patients with hepatitis B virus infection was 95.2%. Thirteen (61.9%) patients received different treatments before SIRT. The median number of tumors was 2.5 (IQR, 1-4.3), whereas the median diameter of the largest lesion was 100.4 mm (IQR, 68.3-127.7 mm). PVTT was classified as follows: Vp1 (n = 3), Vp2 (n = 2), Vp3 (n = 2) and Vp4 (n = 1). Median AFP was 33.2 ng/mL (IQR, 5.9-401 ng/mL). The median total radiation activity administered was 1.4 GBq (IQR, 0.9-2.7 GBq) and the median target tissue dose was 205 Gy (IQR, 155-242 Gy). Nine (43%) patients were downstaged to surgery. Four (19%) patients had a complete response, fifteen (71.4%) had a partial response and two (9.5%) had a progressive disease. ORR and disease control rate were 90.5% and 90.5%, respectively. None of the patients experienced grade 3 and higher adverse events. The most common treatment-related adverse events were fever and abdominal pain, which required no special treatment. Conclusions: SIRT with Y90 resin microspheres combined with systemic treatment is safe and effective in patients with unresectable malignant hepatic tumors, which resulted in encouraging ORR (90.5%) and a downstaging rate (43%). Clinical trial information: ChiCTR2300077524. [Table: see text]