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Background: To develop and validate a novel administration device for holmium-166 transarterial radioembolisation (TARE) with the purpose of facilitating controlled fractional microsphere administration for a more flexible and image-guided TARE procedure. Methods: A Controlled Administration Device (CAD) was developed using MR-conditional materials. The CAD contains a rotating syringe to keep the microspheres in suspension during administration. Different rotational speeds were tested ex vivo to optimise the homogeneity of microsphere fractions administered from the device. The technical performance, accuracy, and safety was validated in three patients in a clinical TARE setting by administering a standard clinical dose in 5 fractions (identifier: NCT05183776). MRI-based dosimetry was used to validate the homogeneity of the given fractions in vivo, and serious adverse device event ((S)A(D)E) reporting was performed to assess safety of the CAD. Results: A rotational speed of 30 rpm resulted in the most homogeneous microsphere fractions with a relative mean deviation of 1.1% (range: -9.1-8.0%). The first and last fraction showed the largest deviation with a mean of -26% (std. 16%) and 7% (std. 13%). respectively. In the three patient cases the homogeneity of the microsphere fractions was confirmed given that MRI-based dosimetry showed near linear increase of mean absorbed target liver dose over the given fractions with R2 values of 0.98, 0.97 and 0.99. No (S)A(D)E's could be contributed to the use of the CAD. Conclusions: The newly developed CAD facilitates safe and accurate fractional microsphere administration during TARE, and can be used for multiple applications in the current and future workflows of TARE. [ABSTRACT FROM AUTHOR]

This study compares various methodologies for lung dosimetry in radioembolization using Monte Carlo (MC) simulations. A voxelized anthropomorphic phantom, created from a real patient's CT scan, preserved the actual density distribution of the lungs. Lung dosimetry was evaluated for five lung-shunt (LS) cases using traditional methods: the mono-compartmental organ-level approach (MIRD), local energy deposition (LED), and convolution with voxel S-values, either with local density corrections (SVOX_L) or without (SVOX_ST). Additionally, a novel voxel S-value (VSV) kernel for lung tissue with an ICRU density of 0.296   g / c m 3 was developed. Calculations were performed using either the ICRU lung density (Lung_296), the average lung density of the phantom (Lung_221), or the local density (Lung_L). The comparison revealed significant underestimations in the mean absorbed dose (AD) for the classical approaches: approximately − 40 % for MIRD, − 27 % for LED, − 28 % for SVOX_L, and − 88 % for SVOX_ST. Similarly, calculations with the lung VSV kernel showed underestimations of about − 62 % for Lung_296, − 50 % for Lung_221, and − 35 % for Lung_L. Given the high heterogeneity of lung tissue, traditional dosimetric methods fail to provide accurate estimates of the mean AD for the lungs. Therefore, MC dosimetry based on patient images is recommended as the preferred method for precise assessment of lung AD during radioembolization. [ABSTRACT FROM AUTHOR]

The influence of the interventional treatment approach for transarterial radioembolization (TARE) on the incidence of extrahepatic microsphere depositions and to angiographic complications was evaluated. In total, 398 TARE cycles were analyzed. Interventional treatment approaches were classified as single treatment position (TP) with interventional occlusion (IO), multiple TPs without IO, and multiple TPs with IO. Correlations with extrahepatic microsphere depositions, angiographic complications, and periprocedural clinical events were performed. Alternative treatment strategies were evaluated. Applications from multiple TPs could have ensured the safe application of microspheres in 48.2% of cases that were originally performed from a single TP after IO. Extrahepatic microsphere accumulations were detected after 5.2%, 5.3%, and 1.5% of TARE procedures from a single TP without IO, a single TP with IO, and multiple TPs without IO, respectively. Applications from multiple TPs did not increase angiographic complications. During the 30-day follow-up, nausea/vomiting and upper abdominal discomfort were observed more frequently in the group with IO than in the group without IO (7.9%/4.6% and 9.2%/5.9%, respectively). In many TARE procedures, the same target liver can be treated from multiple TPs instead of a single TP, reducing the need for the interventional occlusion of aberrant arteries and potential extrahepatic microsphere depositions. [ABSTRACT FROM AUTHOR]

Selective internal radiation therapy (SIRT) is a novel intervention for both primary and metastatic malignant liver lesions. Adrenocortical carcinoma (ACC) is rare with limited treatment options; evidence for SIRT in ACC liver metastases consists of case reports only. Selective internal radiation therapy (SIRT) was employed to treat recurrent liver metastases in a 49-year-old gentleman with ACC, who previously underwent a left-sided hepatectomy. The patient opted for SIRT after reviewing the literature regarding mitotane chemotherapy and its toxicities. Selective internal radiation therapy (SIRT) provided several months of progression-free survival (PFS), with no toxicity and an excellent radiological response. The patient re-presented 12 years after the initial diagnosis with skeletal metastases and sadly died in September 2022. Substantial unmet need exists for effective treatments in ACC, with 75% of patients presenting with incurable disease. Developing widespread disease, SIRT offered 2 years’ PFS in our patient; this was well tolerated with minimal residual liver impairment. Its use in ACC liver-limited disease warrants investigation.Selective internal radiation therapy (SIRT) is a novel intervention for both primary and metastatic malignant liver lesions. Adrenocortical carcinoma (ACC) is rare with limited treatment options; evidence for SIRT in ACC liver metastases consists of case reports only. Selective internal radiation therapy (SIRT) was employed to treat recurrent liver metastases in a 49-year-old gentleman with ACC, who previously underwent a left-sided hepatectomy. The patient opted for SIRT after reviewing the literature regarding mitotane chemotherapy and its toxicities. Selective internal radiation therapy (SIRT) provided several months of progression-free survival (PFS), with no toxicity and an excellent radiological response. The patient re-presented 12 years after the initial diagnosis with skeletal metastases and sadly died in September 2022. Substantial unmet need exists for effective treatments in ACC, with 75% of patients presenting with incurable disease. Developing widespread disease, SIRT offered 2 years’ PFS in our patient; this was well tolerated with minimal residual liver impairment. Its use in ACC liver-limited disease warrants investigation.

Abstract Background Dosimetry-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. Results The 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

Abstract Background Sirtuins have an important role in the regulation of metabolic and biological processess. Thus, we hypothesized that foods that could activate sirtuins, known as “sirtfood”, may improve health status. So, this study was aimed at investigating the association between the amount of sirtfood intake and the risk of major adverse cardiovascular events (MACE). Methods In this cohort study, 2918 adults who had no history of MACE at the start of the study (2006–2008) participated and were followed up on until 2018. The amount of sirtfoods intake (servings per week) was computed using a validated food frequency questionnaire. Each patient’s medical records were evaluated to detect MACE. The Cox proportional hazards model was applied to assess the association between the amount of sirtfood intake and the risk of MACE. Results The median duration of the study was 10.6 years. The hazard ratio (HR) for the risk of MACE was 0.70 for the second (95% CI: 0.50, 0.98) and 0.60 (95% CI: 0.42, 0.86) for the third tertile of sirtfoods intake compared with the first tertile. This association was nonlinear, and sirtfoods consumption of more than five servings per week did not result in a lower risk of MACE. In addition, there was a significant interaction between age (P-interaction

Transarterial radioembolization (TARE) with 166Ho-loaded microspheres is an established locoregional treatment for hepatocellular carcinoma (HCC), introduced in 2010. This study evaluates the clinical outcome of patients with HCC who underwent 166Ho-TARE with personalized dosimetry. Twenty-seven patients with 36 TARE procedures were analyzed. Treatment planning, execution, and evaluation was possible without complications in all cases. At the 3-month follow-up, disease control in the treated liver was achieved in 81.8% of patients (complete remission, partial remission, and stable disease in 36.4%, 31.8%, and 13.6%, respectively). The median overall survival (OS) was 17.2 months, and progression-free survival (PFS) in the treated liver was 11 months. Statistically significant positive correlations were observed between the achieved radiation dose for the tumor and both PFS (r = 0.62, p < 0.05) and OS (r = 0.48, p < 0.05), suggesting a direct dose–response relationship. The calculated achieved dose was 8.25 Gy lower than the planned dose, with relevant variance between planned and achieved doses in individual cases. These results confirm the efficacy of the 166Ho-TARE holmium platform and underscore the potential of voxel-based, personalized dosimetry to improve clinical outcomes. [ABSTRACT FROM AUTHOR]

• Combined microwave/optic approach for detection and characterization of detachments of wall paintings. • Risk falling assessment of the detachments and their classification in "stable", "almost-stable" and "unstable". • Reconstruction of wall painting stratigraphy by non-destructive techniques. • Proof of concept of the proposed tool on the wall paintings masterpiece of Masolino, Masaccio and Filippino Lippi in the Brancacci chapel in Florence, with the support of laboratory tests on proper mock-ups. This paper evaluates the improvements in wall paintings diagnostic achievable by the synergistic combination of DHSPI, SIRT and MWR techniques. These innovative portable and non-destructive techniques for in-situ diagnostic were tested in laboratory on mock-ups mimicking the real conditions of wall painting defects (such as detachments, cavities and cracks), and on the frescoes painted by Masolino, Masaccio and Filippino Lippi (between 1422 and 1475) in the Brancacci Chapel in the church of Santa Maria del Carmine in Florence, Italy. This research activity was part of the Brancacci Chapel diagnostic and monitoring project, where the assessment of the state of conservation is a mandatory prerequisite for planning the subsequent restoration work. In common practice, restorers make the preliminary evaluation on the state of conservation of the wall paintings by visual and tactile inspection, without the use of any special scientific instrumentation. Cracks, cavities, lack of material, detachments, out-of-plumb and deformation of (non-)structural elements are reported in a condition report to document the state of conservation at a given point in time. In particular, the detachments are recognized by the tap test, but this is a discretionary and highly subjective method. Thus, there is a strong demand for the development of a portable and non-destructive approach that refines this preliminary survey with objective data. Here, we present the results produced by the combination of MWR (useful for the dimensional characterization of hidden defects in the wall) and DHSPI-SIRT to identify the extent of deformations induced by thermal stimulus, providing an objective confirmation of the preliminary investigation performed by restorers, in which the detachments were indicated as "stable", "not very stable" and "unstable", i.e. , close to falling. The integrated use of these techniques in situ , supported by a laboratory study on ad-hoc prepared mock-ups, proved to be suitable for a quantitative evaluation of damage risk to guide restoration strategy accordingly. [ABSTRACT FROM AUTHOR]

Simple Summary: Y-90 Selective Internal Radiotherapy (SIRT) uses injectable radioactive microspheres to treat inoperable liver metastases. It is poorly understood how the effective local control of small-volume metastatic disease with Y-90 SIRT may improve patient survival. Here, we demonstrate that failure to locally control liver metastases with ytrritum-90 (Y-90) SIRT is associated with worse 1-year overall survival for patients with ≤5 metastases, emphasizing the importance of disease control in those with early metastatic disease. 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. [ABSTRACT FROM AUTHOR]

Background: Dosimetry-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. Results: The 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 ≈ 10% of the time. Conclusions: This work demonstrates the feasibility and accuracy of physics-inspired cropping layouts for patch-based Monte Carlo simulations. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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

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

Background: Sirtuins have an important role in the regulation of metabolic and biological processess. Thus, we hypothesized that foods that could activate sirtuins, known as "sirtfood", may improve health status. So, this study was aimed at investigating the association between the amount of sirtfood intake and the risk of major adverse cardiovascular events (MACE). Methods: In this cohort study, 2918 adults who had no history of MACE at the start of the study (2006–2008) participated and were followed up on until 2018. The amount of sirtfoods intake (servings per week) was computed using a validated food frequency questionnaire. Each patient's medical records were evaluated to detect MACE. The Cox proportional hazards model was applied to assess the association between the amount of sirtfood intake and the risk of MACE. Results: The median duration of the study was 10.6 years. The hazard ratio (HR) for the risk of MACE was 0.70 for the second (95% CI: 0.50, 0.98) and 0.60 (95% CI: 0.42, 0.86) for the third tertile of sirtfoods intake compared with the first tertile. This association was nonlinear, and sirtfoods consumption of more than five servings per week did not result in a lower risk of MACE. In addition, there was a significant interaction between age (P-interaction < 0.001) and sirtfoods intake in relation to MACE occurrence. When assessing sirtfood components, compared with the lowest intake, the highest amount of soy (HR: 0.74, 95% CI: 0.56, 0.99) and parsley (HR: 0.62, 95% CI: 0.47, 0.83) intake was related to a lower risk of MACE. Conclusion: Our results indicated an inverse association between a higher amount of sirtfood intake and a lower risk of MACE incidents. This association was nonlinear, and having more than five servings of sirtfood per week did not reduce the risk of MACE any further. [ABSTRACT FROM AUTHOR]

Abstract Background The administration of a 166Ho scout dose is available as an alternative to 99mTc particles for pre-treatment imaging in Selective Internal Radiation Therapy (SIRT). It has been reported that the 166Ho scout dose may be more accurate for the prediction of microsphere distribution and the associated therapy planning. The aim of the current study is to compare the scintigraphic imaging characteristics of both isotopes, considering the objectives of the pre-treatment imaging using clinically geared phantoms. Methods Planar and SPECT/CT images were obtained using a NEMA image quality phantom in different phantom setups and another body-shaped phantom with several inserts. The influence of collimator type, count statistics, dead time effects, isotope properties and patient obesity on spatial resolution, contrast recovery and the detectability of small activity accumulations was investigated. Furthermore, the effects of the imaging characteristics on personalized dosimetry are discussed. Results The images with 99mTc showed up to 3 mm better spatial resolution, up to two times higher contrast recovery and significantly lower image noise than those with 166Ho. The contrast-to-noise ratio was up to five times higher for 99mTc than for 166Ho. Only when using 99mTc all activity-filled spheres could be distinguished from the activity-filled background. The measurements mimicking an obese patient resulted in a degraded image quality for both isotopes. Conclusions Our measurements demonstrate better scintigraphic imaging properties for 99mTc compared to 166Ho in terms of spatial resolution, contrast recovery, image noise, and lesion detectability. While the 166Ho scout dose promises better prediction of the microsphere distribution, it is important to consider the inferior imaging characteristics of 166Ho, which may affect individualized treatment planning in SIRT.

Background: Introduced in the latest BCLC 2022, endovascular trans-arterial radioembolization (TARE) has an important role in the treatment of unresectable hepatocellular carcinoma (HCC) as a "bridge" or "downstaging" of disease. The evolution of TARE technology allows a more flexible and personalized target treatment, based on the anatomy and vascular characteristics of each HCC. The flex-dose delivery program is part of this perspective, which allows us to adjust the dose and its radio-embolizing power in relation to the size and type of cancer and to split the therapeutic dose of Y90 in different injections (split-bolus). Methods: From January 2020 to January 2022, we enrolled 19 patients affected by unresectable HCC and candidates for TARE treatment. Thirteen patients completed the treatment following the flex-dose delivery program. Response to treatment was assessed using the mRECIST criteria with CT performed 6 and 9 months after treatment. Two patients did not complete the radiological follow-up and were not included in this retrospective study. The final cohort of this study counts eleven patients. Results: According to mRECIST criteria, six months of follow-up were reported: five cases of complete response (CR, 45.4% of cases), four cases of partial response (PR, 36.4%), and two cases of progression disease (PD, 18.2%). Nine months follow-up reported five cases of complete response (CR, 45.4%), two cases of partial response (PR, 18.2%), and four cases of progression disease (PD, 36.4%). No intra and post-operative complications were described. The average absorbed doses to the hepatic lesion and to the healthy liver tissue were 319 Gy (range 133–447 Gy) and 9.5 Gy (range 2–19 Gy), respectively. Conclusions: The flex-dose delivery program represents a therapeutic protocol capable of "saving" portions of healthy liver parenchyma by designing a "custom-made" treatment for the patient. [ABSTRACT FROM AUTHOR]

Background: The administration of a 166Ho scout dose is available as an alternative to 99mTc particles for pre-treatment imaging in Selective Internal Radiation Therapy (SIRT). It has been reported that the 166Ho scout dose may be more accurate for the prediction of microsphere distribution and the associated therapy planning. The aim of the current study is to compare the scintigraphic imaging characteristics of both isotopes, considering the objectives of the pre-treatment imaging using clinically geared phantoms. Methods: Planar and SPECT/CT images were obtained using a NEMA image quality phantom in different phantom setups and another body-shaped phantom with several inserts. The influence of collimator type, count statistics, dead time effects, isotope properties and patient obesity on spatial resolution, contrast recovery and the detectability of small activity accumulations was investigated. Furthermore, the effects of the imaging characteristics on personalized dosimetry are discussed. Results: The images with 99mTc showed up to 3 mm better spatial resolution, up to two times higher contrast recovery and significantly lower image noise than those with 166Ho. The contrast-to-noise ratio was up to five times higher for 99mTc than for 166Ho. Only when using 99mTc all activity-filled spheres could be distinguished from the activity-filled background. The measurements mimicking an obese patient resulted in a degraded image quality for both isotopes. Conclusions: Our measurements demonstrate better scintigraphic imaging properties for 99mTc compared to 166Ho in terms of spatial resolution, contrast recovery, image noise, and lesion detectability. While the 166Ho scout dose promises better prediction of the microsphere distribution, it is important to consider the inferior imaging characteristics of 166Ho, which may affect individualized treatment planning in SIRT. [ABSTRACT FROM AUTHOR]

Pressure-Enabled Drug Delivery (PEDD), a method using pressure to advance catheter-delivered drug distribution, can improve treatment for hepatocellular carcinoma (HCC) and liver metastases, but real-world evidence is limited. We compared baseline patient characteristics, clinical complexity, and post-procedure healthcare resource utilization (HRUs) and clinical complications for PEDD and non-PEDD procedures. This study used a retrospective, longitudinal, cohort design of claims data from Clarivate's Real World Data Repository, which includes 98% of US payers with over 300 million unique patients from all US states. We identified patients with a trans-arterial chemoembolization (TACE) or trans-arterial radioembolization (TARE) from 1 January 2019 to 31 December 2022. Subsamples grouped patients with HCC receiving a TARE procedure at their first embolization and patients with metastatic colorectal cancer (CRC) that received a TARE procedure. We reported descriptive comparisons of our full sample of patients with HCC and liver metastases receiving PEDD versus non-PEDD procedures. We then conducted a matching-adjusted comparison of HRUs and clinical complications for PEDD and non-PEDD patients among our subsamples (HCC receiving a TARE procedure at their first embolization and patients with metastatic CRC that received a TARE procedure). Matching was based on baseline demographic and clinical characteristics using coarsened exact matching and propensity-score matching. HRUs included inpatient, outpatient, and emergency department visits. Clinical complications included ascites, cholecystitis, fatigue, gastric ulcer, gastritis, jaundice, LFT increase, lymphopenia, portal hypertension, and post-embolization syndrome. PEDD procedures were used on patients with worse baseline disease burdens: baseline Charlson comorbidity index (mean of 6.5 vs. 5.8), any prior clinical complication related to underlying disease (33.7 vs. 31.0%), and prior systemic therapy (22.1% vs. 16.2%). PEDD patients had a greater number of procedural codes indicative of technical complexity for TACE (PEDD mean = 226.3; non-PEDD mean = 134.5; p value <.01) and TARE (PEDD mean = 205.56; non-PEDD mean = 94.8; p value <0.01). Matching-adjusted analyses of patients with HCC and CRC demonstrated comparable HRU and clinical complications for PEDD and non-PEDD procedures post-index. Despite higher baseline disease burden and complexity, post-procedure HRU and clinical complications for PEDD patients were similar to non-PEDD patients. The complex baseline clinical profile may reflect selection of challenging cases for PEDD use. Future studies should validate the benefits observed with PEDD embolization in larger samples with greater statistical power. [ABSTRACT FROM AUTHOR]

About 80% of hepatocellular carcinoma (HCC) patients are in advanced stages and ineligible for curative surgery. Palliative treatments just maintained limited survival, thus an effective downstaging therapy is badly needed. Here we report an initially unresectable patient who underwent radical hepatectomy after successful downstaging with selective internal radiation therapy (SIRT). A 34‐year‐old man was diagnosed with China Liver Cancer Staging (CNLC) IIIa HCC. Due to insufficient future liver remnant and vascular involvement, the patient was suggested to be unresectable. SIRT with yttrium‐90 resin microspheres was given. At three months post‐SIRT, a complete response was achieved. The tumor was downstaged to CNLC Ia stage. The patient underwent anatomical hepatectomy 5 months after SIRT. Histopathological examination of the resected specimen showed 4% viable tumor cells inside a necrotic mass. To our knowledge, this is the first case who underwent SIRT with yttrium‐90 resin microspheres in China mainland. The success of the downstaging in this case renders a possible cure to be achieved in an initially unresectable patient. In addition, the nearly complete tumor necrosis in the resected specimen indicates a good prognosis post‐surgery. This is the first case who underwent SIRT with yttrium‐90 resin microspheres in China mainland. SIRT followed by anatomical hepatectomy is a potentially curative strategy for unresectable HCC, which deserves a confirmative trial in the future. [ABSTRACT FROM AUTHOR]

Introduction: This literature review and exploratory network meta-analysis (NMA) aimed to compare the clinical effectiveness and tolerability of selective internal radiation therapy (SIRT) using yttrium-90 (Y-90) resin microspheres, regorafenib (REG), trifluridine–tipiracil (TFD/TPI), and best supportive care (BSC) in adult patients with chemotherapy-refractory or chemotherapy-intolerant metastatic colorectal cancer (mCRC). Methods: In light of recently published data, the literature was searched to complement and update a review published in 2018. Studies up to December 2022 comparing two or more of the treatments and reporting overall survival (OS), progression-free survival (PFS), or incidence of adverse events (AE) were included. The NMA compared hazard ratios (HRs) for OS and PFS using Markov chain Monte Carlo techniques. Results: Fifteen studies were included, with eight studies added (none addressing SIRT). All active treatments improved OS in relation to BSC. SIRT had the longest OS among all treatments, although without statistically significant differences (HR [95% credible interval] for SIRT, 0.48 [0.27, 0.87]; TFD/TPI, 0.62 [0.46, 0.83]; REG, 0.78 [0.57, 1.05]) in a fixed effects model. Information regarding SIRT was insufficient for PFS analysis, and TFD/TPI was the best intervention (HR 2.26 [1.6, 3.18]). One SIRT study reported radioembolization-induced liver disease in > 10% of the sample; this was symptomatically managed. Non-haematological AEs (hand-foot skin reaction, fatigue, diarrhoea, hypertension, rash or desquamation) were more common with REG, while haematological events (neutropoenia, leukopenia, and anaemia) were more common with TFD/TPI. Conclusion: Current evidence supports SIRT treatment in patients with chemotherapy-refractory or chemotherapy-intolerant mCRC compared to newer oral agents, with comparable OS and low incidence of AEs. [ABSTRACT FROM AUTHOR]

Surgical resection remains the cornerstone of curative treatment for intrahepatic cholangiocarcinoma (iCCA), but this option is only available to a small percentage of patients. For patients with unresectable iCCA, systemic therapy with gemcitabine and platinum-based agents represents the mainstay of treatment; however, the armamentarium has grown to include targeted molecular therapies (e.g., FGFR2 inhibitors), use of adjuvant therapy, liver transplantation in select cases, immunotherapy, and locoregional liver-directed therapies. Despite advances, iCCA remains a challenge due to the advanced stage of many patients at diagnosis. Furthermore, given the improving options for systemic therapy and the fact that the majority of iCCA patients succumb to disease progression in the liver, the role of locoregional therapies has increased. This review will focus on the expanding role of interventional radiology and liver-directed therapies in the treatment of iCCA. [ABSTRACT FROM AUTHOR]

Background: Selective internal radiation therapy (SIRT) using a suitable β−-emitting radionuclide is a promising treatment modality for unresectable liver carcinoma. Yttrium-90 (90Y) [T1/2 = 64.2 h, Eβ(max) = 2.28 MeV, no detectable γ-photon] is the most preferred radioisotope for SIRT owing to its favorable decay characteristics. Objective: The present study describes indigenous development and evaluation of intrinsically radiolabeled [90Y]yttria alumino silicate ([90Y]YAS) glass microsphere, a formulation biosimilar to "TheraSphere" (commercially available, U.S. FDA-approved formulation), for SIRT of unresectable liver carcinoma in human patients. Methods: YAS glass microspheres of composition 40Y2O3-20Al2O3-40SiO2 (w/w) and diameter ranging between 20 and 36 μm were synthesized with almost 100% conversion efficiency and >99% sphericity. Intrinsically labeled [90Y]YAS glass microspheres were produced by thermal neutron irradiation of cold YAS glass microspheres in a research reactor. Subsequent to in vitro evaluations and in vivo studies in healthy Wistar rats, customized doses of [90Y]YAS glass microspheres were administered in human patients. Results: [90Y]YAS glass microspheres were produced with 137.7 ± 8.6 MBq/mg YAS glass (∼6800 Bq per microsphere) specific activity and 99.94% ± 0.02% radionuclidic purity at the end of irradiation. The formulation exhibited excellent in vitro stability in human serum and showed >97% retention in the liver up to 7 d post-administration when biodistribution studies were carried out in healthy Wistar rats. Yttrium-90 positron emission tomography scans recorded at different time points post-administration of customized dose of [90Y]YAS glass microspheres in human patients showed near-quantitative retention of the formulation in the injected lobe. Conclusions: The study confirmed the suitability of indigenously prepared [90Y]YAS glass microspheres for clinical use in the treatment of unresectable hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Sirtuins (SIRTs) are stress-responsive proteins that regulate several post-translational modifications, partly by acetylation, deacetylation, and affecting DNA methylation. As a result, they significantly regulate several cellular processes. In essence, they prolong lifespan and control the occurrence of spontaneous tumor growth. Members of the SIRT family have the ability to govern embryonic, hematopoietic, and other adult stem cells in certain tissues and cell types in distinct ways. Likewise, they can have both pro-tumor and anti-tumor effects on cancer stem cells, contingent upon the specific tissue from which they originate. The impact of autophagy on cancer stem cells, which varies depending on the specific circumstances, is a very intricate phenomenon that has significant significance for clinical and therapeutic purposes. SIRTs exert an impact on the autophagy process, whereas autophagy reciprocally affects the activity of certain SIRTs. The mechanism behind this connection in cancer stem cells remains poorly understood. This review presents the latest findings that position SIRTs at the point where cancer cells and autophagy interact. Our objective is to highlight the various roles of distinct SIRTs in cancer stem cell-related functions through autophagy. This would demonstrate their significance in the genesis and recurrence of cancer and offer a more precise understanding of their treatment possibilities in relation to autophagy. [ABSTRACT FROM AUTHOR]

The sirtuins (SIRT) protein family and the mechanistic/mammalian target of rapamycin (mTOR) are intracellular molecules that have been involved in the regulation of several biological processes, as well as in various aging-related processes. This pilot study, in small scale, aimed to analyze the effects of an 8-week physical exercise program on SIRT3 and mTOR levels in lymphocytes, as well as on lipid peroxidation in middle aged and older men. A total of 9 participants aged between 56 and 73 years were enrolled in an 8-week physical exercise program comprising cardiovascular and high-intensity interval training. The program involved three sessions per week, each lasting 45–60 min, conducted on non-consecutive days. Tests were conducted before and after the experimental period (pre- and post-training). Assessments included a vertical jump, 20 m velocity, ball throwing, and an aerobic capacity test. Lipid peroxidation (MDA) was measured in plasma as an oxidative stress biomarker. Additionally, sirtuin 3 (SIRT3/β-actin) and mTOR (mTOR/β-actin) levels were measured in isolated lymphocytes extracted from venous blood. Following the exercise training period, our results demonstrated a significant improvement in aerobic capacity (pre-training: 615.4 ± 45.3 m; post-training: 687.2 ± 34.6 m; t = −2.521; p = 0.012) and 20 m velocity (pre-training: 4.6 ± 0.5 s; post-training: 4.3 ± 0.3 s; t = −2.023; p = 0.04). Concerning blood variables, there was a significant decrease in mTOR levels (pre-training: 0.857 ± 0.593; post-training: 0.214 ± 0.097; t = −2.547; p = 0.011), while no changes were observed in SIRT3 (pre-training: 0.608 ± 0.404; post-training: 0.516 ± 0.390; t = 0.533; p = 0.594) and MDA (pre-training: 8420 ± 4615; post-training: 8800 ± 3163; t = −0.533; p = 0.594). The notable reduction in mTOR levels in lymphocytes following the 8-week physical exercise program suggests a potential role of exercise in modulating immune cell dynamics, particularly in middle-aged and older individuals. Furthermore, the exercise regimen resulted in improvements in physical function, including enhanced aerobic capacity and walking velocity. [ABSTRACT FROM AUTHOR]

Inflammation is a complex physiological phenomenon, which is the body's defensive response, but abnormal inflammation can have adverse effects, and many diseases are related to the inflammatory response. AMPK, as a key sensor of cellular energy status, plays a crucial role in regulating cellular energy homeostasis and glycolipid metabolism. In recent years, the anti-inflammation effect of AMPK and related signalling cascade has begun to enter everyone's field of vision – not least the impact on metabolic diseases. A great number of studies have shown that anti-inflammatory drugs work through AMPK and related pathways.Herein, this article summarises recent advances in compounds that show anti-inflammatory effects by activating AMPK and attempts to comment on them.

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.

To evaluate the safety and efficacy of combining yttrium-90 radioembolization (Y90-RE) with immune checkpoint inhibitor therapy, consecutive advanced unresectable hepatocellular carcinoma (HCC) patients treated between 2016 and 2022 with atezolizumab/bevacizumab or nivolumab within three-months pre- and post-Y90-RE were retrospectively evaluated. Tumor response and treatment-related clinical/laboratory adverse events (AE) were assessed at 1 and 6 months, as well as differences in clinical and laboratory variables and median overall survival (OS) from initial treatment (whether it was Y90-RE or systemic therapy) between the two cohorts. A total of 19 patients (10 atezolizumab/bevacizumab; 9 nivolumab), comprising 84% males with median age 69 years, met the inclusion criteria. Compared to the atezolizumab/bevacizumab group, there were less males (100% vs. 67%; p = 0.02) and more ECOG ≥ 2 patients in the nivolumab group (0% vs. 33%; p = 0.02). Baseline characteristics or incidence of 6-month post-treatment any-grade AE (60% vs. 56%; p = 0.7), grade ≥ 3 AE (0% vs. 11%; p = 0.3), objective response (58% total, 60% vs. 56%; p = 0.7), and complete response (16% total; 10% vs. 22%; p = 0.8) were similar between the atezolizumab/bevacizumab and the nivolumab cohorts. Median OS was 12.9 months for the whole cohort, 16.4 months for nivolumab, and 10.7 months for atezolizumab/bevacizumab. Among patients with advanced unresectable HCC, the utilization of Y90-RE concurrently or within 90 days of nivolumab or atezolizumab/bevacizumab immunotherapy, appears to be well-tolerated and with a low incidence of severe AE.

Abstract Background Radioembolization is one therapeutic option for the treatment of locally early-stage hepatocellular carcinoma. The aim of this study was to evaluate the distribution of Lipiodol® ultra-fluid and microspheres and to simulate their effectiveness with different beta emitters (90Y, 188Re, 32P, 166Ho, 131I, and 177Lu) on VX2 tumors implanted in the liver of 30 New Zealand rabbits. Results Twenty-three out of 30 rabbits had exploitable data: 14 in the group that received Lipiodol® ultra-fluid (group L), 6 in the group that received microspheres (group M), and 3 in the control group (group C). The histologic analysis showed that the Lipiodol® ultra-fluid distributes homogeneously in the tumor up to 12 days after injection. The X-ray μCT images showed that Lipiodol® ultra-fluid has a more distal penetration in the tumor than microspheres. The entropy (disorder of the system) in the L group was significantly higher than in the M group (4.06 vs 2.67, p = 0.01). Equivalent uniform biological effective doses (EUBED) for a tumor-absorbed dose of 100 Gy were greater in the L group but without statistical significance except for 177Lu (p = 0.03). The radionuclides ranking by EUBED (from high to low) was 90Y, 188Re, 32P, 166Ho, 131I, and 177Lu. Conclusions This study showed a higher ability of Lipiodol® ultra-fluid to penetrate the tumor that translated into a higher EUBED. This study confirms 90Y as a good candidate for radioembolization, although 32P, 166Ho, and 188Re can achieve similar results.

This study compares various methodologies for lung dosimetry in radioembolization using Monte Carlo (MC) simulations. A voxelized anthropomorphic phantom, created from a real patient’s CT scan, preserved the actual density distribution of the lungs. Lung dosimetry was evaluated for five lung-shunt (LS) cases using traditional methods: the mono-compartmental organ-level approach (MIRD), local energy deposition (LED), and convolution with voxel S-values, either with local density corrections (SVOX_L) or without (SVOX_ST). Additionally, a novel voxel S-value (VSV) kernel for lung tissue with an ICRU density of 0.296 g/cm3 was developed. Calculations were performed using either the ICRU lung density (Lung_296), the average lung density of the phantom (Lung_221), or the local density (Lung_L). The comparison revealed significant underestimations in the mean absorbed dose (AD) for the classical approaches: approximately −40% for MIRD, −27% for LED, −28% for SVOX_L, and −88% for SVOX_ST. Similarly, calculations with the lung VSV kernel showed underestimations of about −62% for Lung_296, −50% for Lung_221, and −35% for Lung_L. Given the high heterogeneity of lung tissue, traditional dosimetric methods fail to provide accurate estimates of the mean AD for the lungs. Therefore, MC dosimetry based on patient images is recommended as the preferred method for precise assessment of lung AD during radioembolization.

The influence of the interventional treatment approach for transarterial radioembolization (TARE) on the incidence of extrahepatic microsphere depositions and to angiographic complications was evaluated. In total, 398 TARE cycles were analyzed. Interventional treatment approaches were classified as single treatment position (TP) with interventional occlusion (IO), multiple TPs without IO, and multiple TPs with IO. Correlations with extrahepatic microsphere depositions, angiographic complications, and periprocedural clinical events were performed. Alternative treatment strategies were evaluated. Applications from multiple TPs could have ensured the safe application of microspheres in 48.2% of cases that were originally performed from a single TP after IO. Extrahepatic microsphere accumulations were detected after 5.2%, 5.3%, and 1.5% of TARE procedures from a single TP without IO, a single TP with IO, and multiple TPs without IO, respectively. Applications from multiple TPs did not increase angiographic complications. During the 30-day follow-up, nausea/vomiting and upper abdominal discomfort were observed more frequently in the group with IO than in the group without IO (7.9%/4.6% and 9.2%/5.9%, respectively). In many TARE procedures, the same target liver can be treated from multiple TPs instead of a single TP, reducing the need for the interventional occlusion of aberrant arteries and potential extrahepatic microsphere depositions.

Purpose: To evaluate the effect of reconstruction and noise removal algorithms on the accuracy and precision of iodine concentration (CI) quantified with subtracted micro-computed tomography (micro-CT). Procedures: Two reconstruction algorithms were evaluated: a filtered backprojection (FBP) algorithm and a simultaneous iterative reconstruction technique (SIRT) algorithm. A 3D bilateral filter (BF) was used for noise removal. A phantom study evaluated and compared the image quality, and the accuracy and precision of CI in four scenarios: filtered FBP, filtered SIRT, non-filtered FBP, and non-filtered SIRT. In vivo experiments were performed in an animal model of chemically-induced mammary cancer. Results: Linear relationships between the measured and nominal CI values were found for all the scenarios in the phantom study (R2 > 0.95). SIRT significantly improved the accuracy and precision of CI compared to FBP, as given by their lower bias (adj. p-value = 0.0308) and repeatability coefficient (adj. p-value < 0.0001). Noise removal enabled a significant decrease in bias in filtered SIRT images only; non-significant differences were found for the repeatability coefficient. The phantom and in vivo studies showed that CI is a reproducible imaging parameter for all the scenarios (Pearson r > 0.99, p-value < 0.001). The contrast-to-noise ratio showed non-significant differences among the evaluated scenarios in the phantom study, while a significant improvement was found in the in vivo study when SIRT and BF algorithms were used. Conclusions: SIRT and BF algorithms improved the accuracy and precision of CI compared to FBP and non-filtered images, which encourages their use in subtracted micro-CT imaging. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

To evaluate the safety and efficacy of combining yttrium-90 radioembolization (Y90-RE) with immune checkpoint inhibitor therapy, consecutive advanced unresectable hepatocellular carcinoma (HCC) patients treated between 2016 and 2022 with atezolizumab/bevacizumab or nivolumab within three-months pre- and post-Y90-RE were retrospectively evaluated. Tumor response and treatment-related clinical/laboratory adverse events (AE) were assessed at 1 and 6 months, as well as differences in clinical and laboratory variables and median overall survival (OS) from initial treatment (whether it was Y90-RE or systemic therapy) between the two cohorts. A total of 19 patients (10 atezolizumab/bevacizumab; 9 nivolumab), comprising 84% males with median age 69 years, met the inclusion criteria. Compared to the atezolizumab/bevacizumab group, there were less males (100% vs. 67%; p = 0.02) and more ECOG ≥ 2 patients in the nivolumab group (0% vs. 33%; p = 0.02). Baseline characteristics or incidence of 6-month post-treatment any-grade AE (60% vs. 56%; p = 0.7), grade ≥ 3 AE (0% vs. 11%; p = 0.3), objective response (58% total, 60% vs. 56%; p = 0.7), and complete response (16% total; 10% vs. 22%; p = 0.8) were similar between the atezolizumab/bevacizumab and the nivolumab cohorts. Median OS was 12.9 months for the whole cohort, 16.4 months for nivolumab, and 10.7 months for atezolizumab/bevacizumab. Among patients with advanced unresectable HCC, the utilization of Y90-RE concurrently or within 90 days of nivolumab or atezolizumab/bevacizumab immunotherapy, appears to be well-tolerated and with a low incidence of severe AE. [ABSTRACT FROM AUTHOR]

Summary: This review aims to present contemporary data for SIRT in the treatment of secondary hepatic malignancies including colorectal, neuroendocrine, breast and uveal melanoma. [ABSTRACT FROM AUTHOR]

Background: Radioembolization is one therapeutic option for the treatment of locally early-stage hepatocellular carcinoma. The aim of this study was to evaluate the distribution of Lipiodol® ultra-fluid and microspheres and to simulate their effectiveness with different beta emitters (90Y, 188Re, 32P, 166Ho, 131I, and 177Lu) on VX2 tumors implanted in the liver of 30 New Zealand rabbits. Results: Twenty-three out of 30 rabbits had exploitable data: 14 in the group that received Lipiodol® ultra-fluid (group L), 6 in the group that received microspheres (group M), and 3 in the control group (group C). The histologic analysis showed that the Lipiodol® ultra-fluid distributes homogeneously in the tumor up to 12 days after injection. The X-ray μCT images showed that Lipiodol® ultra-fluid has a more distal penetration in the tumor than microspheres. The entropy (disorder of the system) in the L group was significantly higher than in the M group (4.06 vs 2.67, p = 0.01). Equivalent uniform biological effective doses (EUBED) for a tumor-absorbed dose of 100 Gy were greater in the L group but without statistical significance except for 177Lu (p = 0.03). The radionuclides ranking by EUBED (from high to low) was 90Y, 188Re, 32P, 166Ho, 131I, and 177Lu. Conclusions: This study showed a higher ability of Lipiodol® ultra-fluid to penetrate the tumor that translated into a higher EUBED. This study confirms 90Y as a good candidate for radioembolization, although 32P, 166Ho, and 188Re can achieve similar results. [ABSTRACT FROM AUTHOR]

Background: PET imaging after yttrium-90 (Y-90) radioembolization is challenging because of the low positron fraction of Y-90 (32 × 10−6). The resulting low number of events can be compensated by the high sensitivity of long axial field-of-view (LAFOV) PET/CT scanners. Nevertheless, the reduced event statistics require optimization of the imaging protocol to achieve high image quality (IQ) and quantification accuracy sufficient for post-treatment dosimetry. Methods: Two phantoms (NEMA IEC and AbdoMan phantoms, mimicking human liver) filled with Y-90 and a 4:1 sphere (tumor)-to-background ratio were scanned for 24 h with the Biograph Vision Quadra (Siemens Healthineers). Eight patients were scanned after Y-90 radioembolization (1.3–4.7 GBq) using the optimized protocol (obtained by phantom studies). The IQ, contrast recovery coefficients (CRCs) and noise were evaluated for their limited and full acceptance angles, different rebinned scan durations, numbers of iterations and post-reconstruction filters. The s-value-based absorbed doses were calculated to assess their suitability for dosimetry. Results: The phantom studies demonstrate that two iterations, five subsets and a 4 mm Gaussian filter provide a reasonable compromise between a high CRC and low noise. For a 20 min scan duration, an adequate CRC of 56% (vs. 24 h: 62%, 20 mm sphere) was obtained, and the noise was reduced by a factor of 1.4, from 40% to 29%, using the full acceptance angle. The patient scan results were consistent with those from the phantom studies, and the impacts on the absorbed doses were negligible for all of the studied parameter sets, as the maximum percentage difference was −3.89%. Conclusions: With 2i5s, a 4 mm filter and a scan duration of 20 min, IQ and quantification accuracy that are suitable for post-treatment dosimetry of Y-90 radioembolization can be achieved. [ABSTRACT FROM AUTHOR]

Background: The calculation of the net administered activity (Aadmin) in patients undergoing 90Y‐radioembolization is essential for dosimetry and radiation safety, yet current methods for measuring residual 90Y activity are often associated with high uncertainty. Therefore, an accurate, robust, and clinically viable method for the determination of Aadmin across approved 90Y microsphere devices is desirable. Purpose: We report on a novel method to determine Aadmin by leveraging the quantitative capabilities of SPECT/CT to measure 90Y‐emission in vivo from patients following 90Y‐radioembolization with glass or resin microspheres. Methods: 90Y‐SPECT/CT attenuation‐corrected count data from 147 sequential 90Y‐radioembolization patients was used for this analysis. Aadmin was calculated as part of routine clinical practice via the exposure rate differences between the initial 90Y‐vial and the 90Y‐residual jar. This served as our gold standard measure of Aadmin. Patient data for each microsphere device were separated into training and testing cohorts to first develop regression models and then to independently assess model performance. The training cohorts were divided into four groups: first, based on the microsphere device (glass or resin), and second, based on the SPECT volume used to calculate counts (the full SPECT field of view (FOV) or liver only (VOIliver)). Univariate linear regression models were generated for each group to predict Aadmin based on 90Y‐SPECT data from the training cohorts. Leave‐one‐out cross validation was implemented to estimate variability in model parameters. To assess performance, linear models derived from the training cohort were applied to 90Y‐SPECT data from the testing cohort. A comparison of the models between microspheres devices was also performed. Results: Linear models derived from the glass and resin training cohorts demonstrated a strong, positive correlation between 90Y‐SPECT image counts and Aadmin for VOIliver and FOV with R2 > 0.98 in all cases. In the glass training cohort, model accuracy (100%—absolute mean prediction error) and precision (95% prediction intervals of mean prediction error) were 99.0% and 15.4% for the VOIliver and 99.7% and 17.5% for the FOV models, respectively. In the resin training cohort, the corresponding values were 98.6% and 16.7% for VOIliver and > 99.9% and 11.4% for the FOV models, respectively. The application of these linear models to 90Y‐SPECT data from the testing cohort showed Aadmin prediction errors to have high accuracy and precision for both microsphere devices. For the glass testing cohort, accuracy (precision) was 96.9% (19.6%) and 98.8% (21.1%) for the VOIliver and FOV models, respectively. The corresponding values for the resin training cohort were 97.3% (26.2%) and 98.5% (25.7%) for the VOIliver and FOV models, respectively. The slope of the linear models between the two microsphere devices was observed to be significantly different with resin microspheres generating 48%–49% more SPECT counts for equivalent 90Y activity based on each device manufacturer's activity calibration process. Conclusion: 90Y‐SPECT image counts can reliably predict (accuracy > 95% and precision < 18%) Aadmin after 90Y‐radioembolization, with performance characteristics essentially equivalent for both glass and resin microspheres. There is a clear indication that activity calibrations are fundamentally different between the two microsphere devices. [ABSTRACT FROM AUTHOR]

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Metastases of uveal melanoma (UM) spread predominantly to the liver. Due to low response rates to systemic therapies, liver-directed therapies (LDT) are commonly used for tumor control. The impact of LDT on the response to systemic treatment is unknown. A total of 182 patients with metastatic UM treated with immune checkpoint blockade (ICB) were included in this analysis. Patients were recruited from prospective skin cancer centers and the German national skin cancer registry (ADOReg) of the German Dermatologic Cooperative Oncology Group (DeCOG). Two cohorts were compared: patients with LDT (cohort A, n = 78) versus those without LDT (cohort B, n = 104). Data were analyzed for response to treatment, progression-free survival (PFS), and overall survival (OS). The median OS was significantly longer in cohort A than in cohort B (20.1 vs. 13.8 months; P = 0.0016) and a trend towards improved PFS was observed for cohort A (3.0 vs. 2.5 months; P = 0.054). The objective response rate to any ICB (16.7% vs. 3.8%, P = 0.0073) and combined ICB (14.1% vs. 4.5%, P = 0.017) was more favorable in cohort A. Our data suggest that the combination of LDT with ICB may be associated with a survival benefit and higher treatment response to ICB in patients with metastatic UM. [ABSTRACT FROM AUTHOR]

• Full-field thermomechanical data and pointwise moisture profiling of mural paintings can be achieved on-site using DHSPI, SIRT, NMR, and THz. • DHSPI and SIRT represent first-line on-field structural diagnostic techniques of large painted surfaces. • DHSPI-SIRT full-field scanning of mural paintings can guide techniques based on point-wise scanning. This paper explores the potential synergy of DHSPI, SIRT, THz and NMR combined application. These innovative non-destructive diagnostic techniques for on-field examination were implemented in a study performed on the famous Giotto frescoes in San Antonio Cathedral of Padova, Italy. In this on-field work the aim was to investigate on the enigma represented by a missing fresco by the Master in the chapel house hidden under a Baroque plaster, as it is assumed that portions of Giotto's original fresco may still be present. In general, to this goal, the research coordinated by the CIRCe center of the University of Padua implemented various NDT techniques with additional scientific and technical support by the instrumentation and staff of the advanced mobile laboratory (MOLAB). Here, we present data extracted from surface/subsurface to identify deformations (provided by portable interferometry system, DHSPI), along with in-depth data from thermal diffusion inside the fresco layers by thermography (SIRT), combined with relevant NMR and THz spectroscopy. Thus, this study provides an exemplar application of a novel diagnostic approach based on the mentioned complementary techniques. [ABSTRACT FROM AUTHOR]

Abstract Objective Advances in hepatic radioembolization are based on a selective approach with radical intent and the use of multicompartment dosimetric analysis. The objective of this study is to assess the utility of voxel-based dosimetry in the quantification of actual absorbed doses in radiation segmentectomy procedures and to establish cutoff values predictive of response. Methods Ambispective study in hepatocarcinoma patients treated with radiation segmentectomy. Calculated dosimetric parameters were mean tumor-absorbed dose, maximum tumor AD, minimal tumor AD in 30, 50, and 70% of tumor volume and mean AD in non-tumor liver. The actual absorbed dose (aAD) was calculated on the Y-90-PET/CT image using 3D voxel-based dosimetry software. To assess radiological response, localized mRECIST criteria were used. The objective response rate (ORR) was defined as CR or PR. Results Twenty-four HCC patients, BCLC 0 (5), A (17) and B (2) were included. The mean yttrium-90 administered activity was 1.38 GBq in a mean angiosome volume of 206.9 cc and tumor volume 56.01 cc. The mean theoretical AD was 306.3 Gy and aAD 352 Gy. A very low concordance was observed between both parameters (rho_c 0.027). ORR at 3 and 6 m was 84.21% and 92.31%, respectively. Statistically significant relationship was observed between the maximum tumor-absorbed dose and complete radiological response at 3 m (p 0.022). Conclusion A segmental approach with radical intention leads to response rates greater than 90%, being the tumor maximum absorbed dose the dosimetric parameter that best predicts radiological response in voxel-based dosimetry.

Sirtuins (SIRTs) are stress-responsive proteins that regulate several post-translational modifications, partly by acetylation, deacetylation, and affecting DNA methylation. As a result, they significantly regulate several cellular processes. In essence, they prolong lifespan and control the occurrence of spontaneous tumor growth. Members of the SIRT family have the ability to govern embryonic, hematopoietic, and other adult stem cells in certain tissues and cell types in distinct ways. Likewise, they can have both pro-tumor and anti-tumor effects on cancer stem cells, contingent upon the specific tissue from which they originate. The impact of autophagy on cancer stem cells, which varies depending on the specific circumstances, is a very intricate phenomenon that has significant significance for clinical and therapeutic purposes. SIRTs exert an impact on the autophagy process, whereas autophagy reciprocally affects the activity of certain SIRTs. The mechanism behind this connection in cancer stem cells remains poorly understood. This review presents the latest findings that position SIRTs at the point where cancer cells and autophagy interact. Our objective is to highlight the various roles of distinct SIRTs in cancer stem cell-related functions through autophagy. This would demonstrate their significance in the genesis and recurrence of cancer and offer a more precise understanding of their treatment possibilities in relation to autophagy.

Surgical resection remains the cornerstone of curative treatment for intrahepatic cholangiocarcinoma (iCCA), but this option is only available to a small percentage of patients. For patients with unresectable iCCA, systemic therapy with gemcitabine and platinum-based agents represents the mainstay of treatment; however, the armamentarium has grown to include targeted molecular therapies (e.g., FGFR2 inhibitors), use of adjuvant therapy, liver transplantation in select cases, immunotherapy, and locoregional liver-directed therapies. Despite advances, iCCA remains a challenge due to the advanced stage of many patients at diagnosis. Furthermore, given the improving options for systemic therapy and the fact that the majority of iCCA patients succumb to disease progression in the liver, the role of locoregional therapies has increased. This review will focus on the expanding role of interventional radiology and liver-directed therapies in the treatment of iCCA.