Radioembolization Research Articles

90Y SPECT scatter estimation and voxel dosimetry in radioembolization using a unified deep learning framework

Purpose90Y SPECT-based dosimetry following radioembolization (RE) in liver malignancies is challenging due to the inherent scatter and the poor spatial resolution of bremsstrahlung SPECT. This study explores a deep-learning-based absorbed dose-rate estimation method for 90Y that mitigates the impact of poor SPECT image quality on dosimetry and the accuracy–efficiency trade-off of Monte Carlo (MC)-based scatter estimation and voxel dosimetry methods.MethodsOur unified framework consists of three stages: convolutional neural network (CNN)-based bremsstrahlung scatter estimation, SPECT reconstruction with scatter correction (SC) and absorbed dose-rate map generation with a residual learning network (DblurDoseNet). The input to the framework is the measured SPECT projections and CT, and the output is the absorbed dose-rate map. For training and testing under realistic conditions, we generated a series of virtual patient phantom activity/density maps from post-therapy images of patients treated with 90Y-RE at our clinic. To train the scatter estimation network, we use the scatter projections for phantoms generated from MC simulation as the ground truth (GT). To train the dosimetry network, we use MC dose-rate maps generated directly from the activity/density maps of phantoms as the GT (Phantom + MC Dose). We compared performance of our framework (SPECT w/CNN SC + DblurDoseNet) and MC dosimetry (SPECT w/CNN SC + MC Dose) using normalized root mean square error (NRMSE) and normalized mean absolute error (NMAE) relative to GT.ResultsWhen testing on virtual patient phantoms, our CNN predicted scatter projections had NRMSE of 4.0% ± 0.7% on average. For the SPECT reconstruction with CNN SC, we observed a significant improvement on NRMSE (9.2% ± 1.7%), compared to reconstructions with no SC (149.5% ± 31.2%). In terms of virtual patient dose-rate estimation, SPECT w/CNN SC + DblurDoseNet had a NMAE of 8.6% ± 5.7% and 5.4% ± 4.8% in lesions and healthy livers, respectively; compared to 24.0% ± 6.1% and 17.7% ± 2.1% for SPECT w/CNN SC + MC Dose. In patient dose-rate maps, though no GT was available, we observed sharper lesion boundaries and increased lesion-to-background ratios with our framework. For a typical patient data set, the trained networks took ~ 1 s to generate the scatter estimate and ~ 20 s to generate the dose-rate map (matrix size: 512 × 512 × 194) on a single GPU (NVIDIA V100).ConclusionOur deep learning framework, trained using true activity/density maps, has the potential to outperform non-learning voxel dosimetry methods such as MC that are dependent on SPECT image quality. Across comprehensive testing and evaluations on multiple targeted lesions and healthy livers in virtual patients, our proposed deep learning framework demonstrated higher (66% on average in terms of NMAE) estimation accuracy than the current “gold-standard” MC method. The enhanced computing speed with our framework without sacrificing accuracy is highly relevant for clinical dosimetry following 90Y-RE.

Trends in Selective Internal Radiation Therapy (SIRT) for Treating Hepatocellular Carcinoma, Cholangiocarcinoma, and Liver Metastasis: A Total Population Analysis from 2006 to 2021 in Germany.

The aim of this study was to investigate trends in selective internal radiation therapy (SIRT) for hepatocellular carcinoma (HCC), cholangiocarcinoma (CCC), and liver metastasis in Germany. We analyzed the nationwide German hospital billing database from 2006 to 2019 for the diagnosis of HCC, CCC or liver metastasis in combination with SIRT. For analyses of SIRT on the hospital level, we used the reimbursement.INFO tool based on German hospitals' quality reports from 2008 to 2021. Linear regression analysis was performed to detect changes over time. We included a total of 14,165 SIRT procedures. The annual numbers increased from 99 in 2006 to 1605 in 2015 (p < 0.001; increase by 1521%), decreasing to 1175 cases in 2019 (p < 0.001). In 2008, 6 of 21 hospitals (28.6%) performed more than 20 SIRTs per year, which increased to 19 of 53 (35.8%) in 2021. The share of SIRT for HCC increased from 29.8% in 2006 to 44.7% in 2019 (p < 0.001) and for CCC from 0% in 2006 to 9.5% in 2019 (p < 0.001), while the share of SIRT for liver metastasis decreased from 70.2% in 2006 to 45.7% in 2019 (p < 0.001). In-hospital mortality was 0.2% after the SIRT procedure. Gastritis (2.7%), liver failure (0.4%), and sepsis (0.3%) were the most common in-hospital complications reported. We observed an increase in SIRT procedures in Germany, with the number of hospitals offering the procedure going up from 21 in 2008 to 53 in 2021. While the treatment of liver metastasis remains the most common indication, SIRT for HCC and CCC increased significantly over the last few years. The mortality and complication rates show that SIRT is a relatively safe procedure.

Efficacy of Selective Internal Radiation Therapy for Hepatocellular Carcinoma Post-Incomplete Response to Chemoembolization.

Hepatocellular carcinoma (HCC) is one of the most common neoplasms worldwide and the third most common cause of cancer-related death. Several liver-targeted intra-arterial therapies are available for unresectable HCC, including selective internal radiation therapy (SIRT) and trans-arterial chemoembolization (TACE). Those two are the most used treatment modalities in localized non-operable HCC. TACE is the treatment option for patients with stage B, according to the BCLC staging system. In contrast, SIRT does not have an official role in the treatment algorithm, but recent studies showed promising outcomes in patients treated with SIRT. Although TACE is globally a safe procedure, it might provoke several vascular complications such as spasms, inflammatory constriction, and, in severe cases, occlusion, dissection, or collateralization. Hence, it is acclaimed that those complications could restrain the targeted response of the radio-embolization when we use it as second-line therapy post TACE. In this study, we will assess the efficacity of SIRT using Yttrium 90 Microspheres post incomplete or failure response to TACE. In our retrospective study, we had 23 patients who met the inclusion criteria. Furthermore, those patients have been followed radiologically and biologically. Then, we evaluated the therapeutic effect according to the mRECIST criteria, in addition to the personalized dose analysis. We found 8 patients were treated with TheraSphere®, with a median tumor absorbed dose of 445 Gy, while 15 received SIR-Spheres® treatment with a mean tumor dose of 268 Gy. After radiological analysis, 56.5% of the patients had a complete response, and 17.3% showed partial response, whereas 13% had stable disease and 13% had progressive disease. For patients treated with SIRT after an incomplete response or failure to TACE, we found an objective response rate of 73.8%. Despite the known vascular complications of TACE, SIRT can give a favorable response.

Enfortumab vedotin as a salvage option as 5th line therapy for metastatic urothelial bladder cancer

Abstract A 67-year-old female patient with a muscle-invasive, non-metastatic urothelial bladder cancer (UC) (pT2 G3 cN0 cM0) developed metachronous metastases within 6 months after radical cystectomy with ileal conduit urinary diversion. After a good primary response to platinum-based chemotherapy, treatment was switched to the immune checkpoint inhibitor (ICI) pembrolizumab due to progressive disease. Subsequently the patient underwent selective internal radiotherapy (SIRT) of the liver and received vinflunine as well as a re-challenge with pembrolizumab. Two years after the initial diagnosis, rapid disease progression ultimately led to a switch to 5th line therapy with enfortumab vedotin (EV), which had only been approved in the United States at that time. The antibody-drug conjugate was well tolerated by the patient after dose reduction to 1.0 mg/ kg body weight. Simultaneous irradiation of newly occurring precardiac, hepatic and cerebral metastases were necessary. After 10 months of therapy with EV, tumour regression was observed accompanied with good symptom control. The presented case illustrates the efficacy and tolerability of EV in a heavily pre-treated patient with metastatic UC (mUC).

Efficacy of transarterial radioembolization using Y-90 resin microspheres versus atezolizumab-bevacizumab in unresectable hepatocellular carcinoma: A matching-adjusted indirect comparison

IntroductionNo head-to-head trials compared the efficacy of transarterial radioembolization (TARE, also known as selective internal radiation therapy) to combination immunotherapy in hepatocellular carcinoma (HCC). The analysis objective was to compare effectiveness outcomes of TARE using Y-90 resin microspheres and atezolizumab-bevacizumab (AB) in advanced unresectable HCC. MethodsPatient-level data from SARAH randomized controlled trial for TARE and aggregate real-world data from AB-real study were used in an unanchored matching-adjusted indirect comparison. The basecase analysis used per-protocol data from SARAH; intention-to-treat data were used in sensitivity analyses. The following prognostic variables and effect modifiers were identified from literature: cause of disease, macrovascular invasion, Eastern Cooperative Oncology Group Performance Status, alpha-fetoprotein level and albumin-bilirubin score. Weights were assigned to patients from SARAH to balance baseline characteristics across studies and reflect characteristics of AB-real patients. Overall survival (OS), progression-free survival (PFS) and response rates (overall response rates [ORR]) were calculated and compared. ResultsThe analysis of OS and PFS included 140 patients receiving TARE and 131 for the analysis of response rates, compared to 202 receiving AB. Median OS was 15.0 and 14.9 months for TARE and AB, respectively (HR=0.980; 95% confidence interval [CI]: 0.658–1.461; p-value=0.922). Median PFS was 4.4 and 6.8 months for TARE and AB, respectively (HR=0.745; 95%CI: 0.544–1.022; p-value=0.068). ORR were 19.8% and 25% with TARE and AB, respectively (OR for AB=1.386, 95%CI: 0.746–2.668; p-value=0.306). Sensitivity analyses generated similar results. ConclusionIn HCC patients receiving treatment, TARE using Y-90 resin microspheres may achieve comparable effectiveness outcomes compared with AB.

157P T/N ratio and radiation dose delivered do not correlate with the development of Radioembolization-Induced Liver Disease (REILD) in Hepatocellular Carcinoma (HCC) following Y90 selective internal radiation therapy (Y90-SIRT): A retrospective, single tertiary centre cohort study

157P T/N ratio and radiation dose delivered do not correlate with the development of Radioembolization-Induced Liver Disease (REILD) in Hepatocellular Carcinoma (HCC) following Y90 selective internal radiation therapy (Y90-SIRT): A retrospective, single tertiary centre cohort study

Embryology, anatomy and physiology of the liver: Review

The liver, located within the peritoneal cavity, is in the right upper quadrant of the abdomen. Additionally, it should be noted that the liver holds the distinction of being the largest gland within the human body, as well as the most extensive visceral tissue situated within the abdominal cavity. One of the factors contributing to the early migration of the developing intestines to an extracoelomic location during fetal development is their relatively bigger size in children, weighing between 1400 and 1800 g in adults. It contributes to the development of a distended abdomen in pediatric populations. The liver is situated in the right upper quadrant of the abdomen and spans across the midline to the left upper quadrant. The heart remains susceptible to regular injuries despite the protective presence of ribs and cartilage. The liver, functioning as an accessory organ in digestion, undertakes several metabolic processes, including drug metabolism, bile production, and bilirubin synthesis, alongside numerous other functions. For a considerable period, medical professionals and anatomists have encountered challenges in comprehending the complex functions of the liver. Significant advancements in the comprehension of liver anatomy have contributed significantly to the notable progress observed in various surgical and interventional radiologic procedures involving hepatic artery infusion pumps, liver ablation, transplantation, transarterial chemoembolization, selective internal radiation therapy, and portal vein embolization. The existence of hepatic structure is crucial for developing and implementing gradual therapies. This page aims to provide an academic overview of the embryology, anatomy, and function of the liver.

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

To evaluate safety and effectiveness of selective internal radiation therapy (SIRT) using yttrium-90 for localized and locally advanced intrahepatic cholangiocarcinoma (iCCA). 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. 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), andobjective radiologic response (p=0.014) are associated with OS. Two ≥grade 3 hyperbilirubinemia, anemia, and one pleuro-biliary fistula occurred post-SIRT. SIRT for localized iCCA is safe and effective in achieving radiological response, downstaging to surgery and transplant, and resulting in pathologic necrosis. Selective internal radiation therapy should be considered for patients with localized and locally advanced intrahepatic cholangiocarcinoma. • 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, andradiologic response are associated with survival. • Radioembolization should be considered for patients with localized and locally advanced iCCA.

S2988 Gastric Ulcer Due to Yttrium-90 Selective Internal Radiation Therapy

S2988 Gastric Ulcer Due to Yttrium-90 Selective Internal Radiation Therapy

Measurement of the Tumor-to-Normal Ratio for Radioembolization of Hepatocellular Carcinoma: A Prospective Study Comparing 2-Dimensional Perfusion Angiography, Technetium-99m Macroaggregated Albumin, and Yttrium-90 SPECT/CT

PurposeTo calculate the preradioembolic tumor-to-normal (T:N) ratio in hepatocellular carcinoma (HCC) using 2-dimensional (2D) perfusion angiography and compare it with that calculated using technetium-99m macroaggregated albumin (99mTc MAA) single-photon emission computed tomography (SPECT)/computed tomography (CT). Materials and MethodsThis prospective single-arm study enrolled 15 participants with HCC who underwent 2D perfusion angiography immediately before the enrollment and with the microcatheter located at the same location as 99mTc MAA injection, after which SPECT/CT was performed. Quantitative digital subtraction angiography was used to calculate the area under the curve for the tumor and normal hepatic parenchyma and subsequently calculate the T:N ratio. The T:N ratio was calculated from the 99mTc MAA SPECT/CT and post–yttrium-90 bremsstrahlung SPECT/CT using dosimetry software. ResultsThe mean participant age was 64.1 years ± 9.8, and the study included 14 (93%) men and 1 (7%) woman. The mean tumor size was 4.1 cm (SD ± 2.4), and all participants received segmental treatments with glass microspheres. The mean T:N ratio calculated by 99mTc MAA SPECT/CT was 2.28 (SD ± 0.89) vs 2.25 (SD ± 0.99) calculated by 2D perfusion angiography (P = .45). For the 13 participants who underwent selective internal radiation therapy (transarterial radioembolization), there was no significant difference between the T:N ratios calculated by 2D perfusion angiography and post-90Y SPECT/CT (2.25 [SD ± 1.05] vs 1.91 [SD ± 0.39]; P = .12). ConclusionsThe T:N ratio calculated by 2D perfusion angiography correlated well with that calculated by 99mTc MAA SPECT/CT.

Deep-Learning Based Auto-Segmentation for Liver Yttrium-90 Selective Internal Radiation Therapy

In resin Yttrium-90 (Y-90) selective internal radiation therapy (SIRT), liver volume sizes are needed for Y-90 activity calculations using the body-surface-area method, which are obtained from contours that are manually delineated in 3D images. The aim was to apply a deep-learning based auto-segmentation method for liver delineation for Y-90 SIRT. A deep-learning-based liver segmentation method was applied using the U-Net3D architecture, which is a 3D convolutional neural network (CNN) extended from the original 2D U-Net architecture for 3D objects in medical imaging. The segmentation model was trained on the Liver Tumor Segmentation (LiTS) dataset. The training data set contained 130 CT scans, and the test data set contained 70 CT scans. The model was deployed in the clinic using DICOM communication. Auto-segmentation of liver in the CT images of 18 SIRT patients was studied. The CT images were exported from clinical database to the segmentation model's DICOM location, where a monitoring software detected the incoming data and automatically ran the liver segmentation. The results were then returned to the original DICOM location where the CT images were stored. Auto-segmented liver contours were compared with physician manually-delineated contours. Dice similarity coefficient (DSC), mean distance to agreement (MDA), ratio of volume (RV), and ratio of activity (RA, ratio of activity calculated using an auto-segmented liver contour to the accurate activity calculated using a manually-delineated contour), were assessed. DSC, MDA, and RV are 0.942±0.014 (range: 0.908-0.959), 1.902±0.503 mm (range: 1.043-2.956 mm), and 0.988±0.039 (range: 0.901-1.045), respectively. RA is 1.001±0.003 (range: 0.993-1.007), which indicates that the activities calculated using the auto-segmented liver contours are close to the accurate activities. The segmentation model was able to successfully identify and segment livers in the CT images, and provide accurate and reliable results. The proposed method is beneficial for clinical use as it can process large amounts of data quickly and efficiently, and can be easily deployed in a clinical environment using DICOM communication.

Locoregional Therapy for Intrahepatic Cholangiocarcinoma: The Role of Intra-Arterial Therapies.

Intrahepatic cholangiocarcinoma (ICC) is a rare disease with a rising incidence. While surgical resection is the only curative option, the disease process is often identified in advanced stages, as this malignancy often remains clinically silent in early development. Only one-third of patients are eligible for resection at the time of diagnosis. For patients who cannot undergo resection, intra-arterial therapies are reasonable palliative treatment options; in rare occasions, these may be bridging therapies, as well. The premise of bland embolization and most chemoembolization intra-arterial therapies is that the arterial supply of the tumor is occluded to induce tumor necrosis, while radioembolization utilizes the arterial flow of the tumor to deliver radiation therapy. In this review, we discuss the use of transarterial embolization, transarterial chemoembolization, and selective internal radiation therapy for the treatment of ICC. Phase III randomized controlled clinical trials are difficult to tailor to this extremely rare and aggressive disease, but ultimately, further investigation should be pursued to define the patient population that will derive the greatest benefit from each modality.

Vascular Interventions in Oncology

Vascular interventions are an important and established tool in the management of the oncology patient. The goal of these procedures may be curative, palliative or adjunctive in nature. Some of the common vascular interventions used in oncology include transarterial embolisation or chemoembolisation, selective internal radiation therapy, chemosaturation, venous access lines, superior vena cava stenting and portal vein embolisation. We provide an overview of the principles, technology and approach of vascular techniques for tumour therapy in both the arterial and venous systems. Arterial interventions are currently mainly used in the management of hepatocellular carcinoma. Transarterial embolisation, chemoembolisation and selective internal radiation therapy deliver targeted catheter-delivered treatments with the aim of reducing tumour burden, controlling tumour growth or increasing survival in patients not eligible for transplantation. Chemosaturation is a regional chemotherapy technique that delivers high doses of chemotherapy directly to the liver via the hepatic artery, while reducing the risks of systemic effects. Venous interventions are more adjunctive in nature. Venous access lines are used to provide a means of delivering chemotherapy and other medications directly into the bloodstream. Superior vena cava stenting is a palliative procedure that is used to relieve symptoms of superior vena cava obstruction. Portal vein embolisation is a procedure that allows hypertrophy of a healthy portion of the liver in preparation for liver resection.Interventional radiology-led vascular interventions play an essential part of cancer management. These procedures are minimally invasive and provide a safe and effective adjunct to traditional cancer treatment methods. Appropriate work-up and discussion of each patient-specific problem in a multidisciplinary setting with interventional radiology is essential to provide optimum patient-centred care.

Clinically Translatable Phosphonated Silica Microspheres for Selective Internal Radiation Therapy of Hepatocellular Carcinoma

Selective internal radiation therapy (SIRT) is used as a locoregional therapy for hepatocellular carcinoma (HCC) to delay the progression of HCC. Thus far, various kinds of radioactive microspheres with different materials and radionuclides have been developed to be utilized in SIRT, but they remain unsatisfactory in some ways. Herein, using a facile method, phosphonated silica microspheres (PSMs) are prepared and further radiolabeled with 177Lu in a rapid and effective manner. The results suggest that the radiolabeling efficiency is higher than 99%, and the specific activity of the product is 10 kBq per microsphere. 177Lu‐PSM exhibits outstanding in vivo radiolabeling stability, excellent antitumor activity, and single‐photon‐emission computed tomography–computed tomography (SPECT/CT) imaging capability. In addition, it is shown that PSM can be produced in large quantities at a relatively low cost. The results indicate that 177Lu‐PSM might hold considerable potential for translation to clinical applications.

Prognostic role of radiomics-based body composition analysis for the 1-year survival for hepatocellular carcinoma patients.

Parameters of body composition have prognostic potential in patients with oncologic diseases. The aim of the present study was to analyse the prognostic potential of radiomics-based parameters of the skeletal musculature and adipose tissues in patients with advanced hepatocellular carcinoma (HCC). Radiomics features were extracted from a cohort of 297 HCC patients as post hoc sub-study of the SORAMIC randomized controlled trial. Patients were treated with selective internal radiation therapy (SIRT) in combination with sorafenib or with sorafenib alone yielding two groups: (1) sorafenib monotherapy (n=147) and (2) sorafenib and SIRT (n=150). The main outcome was 1-year survival. Segmentation of muscle tissue and adipose tissue was used to retrieve 881 features. Correlation analysis and feature cleansing yielded 292 features for each patient group and each tissue type. We combined 9 feature selection methods with 10 feature set compositions to build 90 feature sets. We used 11 classifiers to build 990 models. We subdivided the patient groups into a train and validation cohort and a test cohort, that is, one third of the patient groups. We used the train and validation set to identify the best feature selection and classification model and applied it to the test set for each patient group. Classification yields for patients who underwent sorafenib monotherapy an accuracy of 75.51% and area under the curve (AUC) of 0.7576 (95% confidence interval [CI]: 0.6376-0.8776). For patients who underwent treatment with SIRT and sorafenib, results are accuracy=78.00% and AUC=0.8032 (95% CI: 0.6930-0.9134). Parameters of radiomics-based analysis of the skeletal musculature and adipose tissue predict 1-year survival in patients with advanced HCC. The prognostic value of radiomics-based parameters was higher in patients who were treated with SIRT and sorafenib.

99mTc-macroaggregated albumin SPECT/CT predictive dosimetry and dose-response relationship in uveal melanoma liver metastases treated with first-line selective internal radiation therapy

First-line selective internal radiation therapy (SIRT) showed promising outcomes in patients with uveal melanoma liver metastases (UMLM). Patient survival depends on liver’s disease control. SIRT planning is essential and little is known about dosimetry. We investigated whether 99mTc-MAA-SPECT/CT dosimetry could predict absorbed doses (AD) evaluated on 90Y-PET/CT and assess the dose–response relationship in UMLM patients treated with first-line SIRT. This IRB-approved, single-center, retrospective analysis (prospectively collected cohort) included 12 patients (median age 63y, range 43–82). Patients underwent MRI/CT, 18F-FDG-PET/CT before and 3–6 months post-SIRT, and 90Y-PET/CT immediately post-SIRT. Thirty-two target lesions were included. AD estimates in tumor and non-tumor liver were obtained from 99mTc-MAA-SPECT/CT and post-SIRT 90Y-PET/CT, and assessed with Lin’s concordance correlation coefficients (ρc and Cb), Pearson’s coefficient correlation (ρ), and Bland–Altman analyses (mean difference ± standard deviation; 95% limits-of-agreement (LOA)). Influence of tumor characteristics and microsphere type on AD was analyzed. Tumor response was assessed according to size-based, enhancement-based and metabolic response criteria. Mean target lesion AD was 349 Gy (range 46–1586 Gy). Concordance between 99mTc-MAA-SPECT/CT and 90Y-PET/CT tumor dosimetry improved upon dose correction for the recovery coefficient (RC) (ρ = 0.725, ρc = 0.703, Cb = 0.969) with good agreement (mean difference: − 4.93 ± 218.3 Gy, 95%LOA: − 432.8–422.9). Without RC correction, concordance was better for resin microspheres (ρ = 0.85, ρc = 0.998, Cb = 0.849) and agreement was very good between predictive 99mTc-MAA-SPECT/CT and 90Y-PET/CT dosimetry (mean difference: − 4.05 ± 55.9 Gy; 95%LOA: − 113.7–105.6). After RC correction, 99mTc-MAA-SPECT/CT dosimetry overestimated AD (− 70.9 ± 158.9 Gy; 95%LOA: − 382.3–240.6). For glass microspheres, concordance markedly improved with RC correction (ρ = 0.790, ρc = 0.713, Cb = 0.903 vs without correction: ρ = 0.395, ρc = 0.244, Cb = 0.617) and 99mTc-MAA-SPECT/CT dosimetry underestimated AD (148.9 ± 267.5 Gy; 95%LOA: − 375.4–673.2). For non-tumor liver, concordance was good between 99mTc-MAA-SPECT/CT and 90Y-PET/CT dosimetry (ρ = 0.942, ρc = 0.852, Cb = 0.904). 99mTc-MAA-SPECT/CT slightly overestimated liver AD for resin (3.4 ± 3.4 Gy) and glass (11.5 ± 13.9 Gy) microspheres. Tumor AD was not correlated with baseline or post-SIRT lesion characteristics and no dose–response threshold could be identified. 99mTc-MAA-SPECT/CT dosimetry provides good estimates of AD to tumor and non-tumor liver in UMLM patients treated with first-line SIRT.

In Patients Treated by Selective Internal Radiotherapy, Cellular In Vitro Immune Function Is Predictive of Survival.

In patients with liver malignancies, the cellular immune function was impaired in vitro after selective internal radiotherapy (SIRT). Because immunosuppression varied substantially, in the current study, we investigated in 25 SIRT patients followed up for ten years whether the lymphocyte function was correlated with survival. Peripheral blood mononuclear cells were stimulated with four microbial antigens (tuberculin, tetanus toxoid, Candida albicans and CMV) before therapy and at four time points thereafter, and lymphocyte proliferation was determined by H3-thymidine uptake. The median sum of the responses to these four antigens decreased from 39,464 counts per minute (CPM) increment (range 1080-204,512) before therapy to a minimum of 700 CPM increment on day 7 after therapy (0-93,187, p < 0.0001). At all five time points, the median survival in patients with weaker responses was 2- to 3.5-fold shorter (p < 0.05). On day 7, the median survival in patients with responses below and above the cutoff of a 2 CPM increment was 185 and 523 days, respectively (χ2 = 9.4, p = 0.002). In conclusion, lymphocyte function could be a new predictor of treatment outcome after SIRT.

Two Birds with One Stone: Hepatocellular Carcinoma and Small Cell Lung Cancer Imaged with [18F]Fluorocholine Positron Emission Tomography/Computed Tomography.

We describe the case of a 67-year-old male patient with a moderately differentiated hepatocellular carcinoma (HCC) of the right liver lobe who underwent [18F]fluorocholine positron emission tomography/computed tomography (PET/CT) for staging due to a suspicious lung lesion at previous CT scan. [18F]fluorocholine PET/CT showed increased radiopharmaceutical uptake in a liver lesion corresponding to the known HCC. Furthermore, a right pulmonary hilar lesion suspicious for metastatic spread of HCC showed increased radiopharmaceutical uptake. Surprisingly, the histological assessment of the thoracic lesion demonstrated the presence of small cell lung cancer (SCLC). The patient underwent treatment with radiation therapy and chemotherapy for the SCLC and selective internal radiation therapy (SIRT) for the HCC. The patient died after one year due to progressive SCLC. This case demonstrates that coexisting tumors showing increased cell membrane turnover, including SCLC, can be detected by [18F]fluorocholine PET/CT. In our case, [18F]fluorocholine PET/CT findings influenced the patient management in terms of histological verification and different treatment of the detected lesions.

Selective Internal Radiotherapy Alters the Profiles of Systemic Extracellular Vesicles in Hepatocellular Carcinoma.

Incidence of hepatocellular carcinoma (HCC) is increasing globally. Radioembolization (RE)/selective internal radiotherapy (SIRT) is a promising treatment for inoperable HCC. RE triggers an immune response, involving extracellular vesicles (EVs) which are crucial for cell communication and tumor development. This study explores EV immune profiles and origins in patients with inoperable HCC before and after SIRT/RE. Blood samples from 50 HCC-patients treated with SIRT/RE were collected before and after therapy to determine cytokines and isolate EVs using size exclusion chromatography. The dynamic range and EV quality required for detecting variations in surface markers were assessed. Thirty-seven EV surface markers were analyzed using flow cytometry and correlated with clinical parameters. Several immunological markers (CD4, CD2, CD40, CD45, CD49e, CD69, CD209-EVs) were present in the circulation of HCC patients. These markers positively correlated with therapy response and survival. Conversely, B cell CD20, endothelial cell CD146, platelet CD49e, and CD41b EV markers negatively correlated with 60-day survival. Elevated levels of IL-6 and IL-8 before therapy correlated negatively with patient survival, coinciding with a positive correlation with CD20-positive EVs. Plasma EVs from HCC patients exhibit immunological, cancer, and coagulation markers, including potential biomarkers (CD4, CD20, CD49e, CD146). These may enhance our understanding of cancer biology and facilitate SIRT therapy monitoring.

TIPS-17 A FIRST-IN-HUMAN FEASIBILITY STUDY TO EVALUATE THE SAFETY OF SELECTIVE INTRA-ARTERIAL YTTRIUM-90 MICROSPHERE TREATMENT IN PATIENTS WITH RECURRENT GLIOBLASTOMA (THE FRONTIER TRIAL)

Abstract BACKGROUND: Glioblastoma (GBM) is the most aggressive primary brain tumor that virtually always recurs with no established standard therapy at recurrence. Median survival after recurrence is 7-12 months. Selective internal radiation therapy (SIRT) with Yttrium-90 (Y90) glass microspheres (TheraSphere™, Boston Scientific, Marlborough, MA) is an FDA approved standard treatment for hepatocellular carcinoma, and represents a novel strategy to treat regionally localized brain tumors. We are conducting a first-in-human clinical trial (under IDE) using Y90 microspheres modified to treat tumors in the brain. The goal of selectively delivering Y90 intra-arterially is to achieve higher tumoral absorbed doses while limiting non-target exposure. DESIGN: The primary objective is to evaluate the safety of Y90 microspheres treatment. Target enrollment is 12 patients at 5 participating medical centers. Key inclusion criteria include: 1st or 2nd recurrence of GBM , size 1-5cm, located in the non-dominant hemisphere in a non-eloquent region, accessible neurovascular anatomy for single intra-arterial treatment based on a diagnostic cerebral angiogram. After consent, patients will undergo screening angiography and imaging that be reviewed by the trial steering committee to determine treatment suitability. Treatment consists of Y90 microspheres administered intra-arterially to deliver 40Gy ± 10% to the treatment volume. Post-administration Y90 PET and MRI images allow assessment of dose distribution and acute safety. Following overnight admission, patients will be followed as outpatients weekly x 4, and then monthly up to month 6. Primary endpoints include treatment-related limiting toxicities, dose limiting toxicity defined as non-hematological toxicities ≥ grade 3, CNS toxicity ≥ grade 3 (eg. symptomatic ischemia or edema) related to non-target embolization, occurring through 30 days post procedure. Secondary endpoints include: treatment-related serious adverse events, change in post-treatment neurological function, technical success, objective response rate, progression-free survival, and overall survival. The study is registered with clinicaltrials.gov, number: NCT05303467.