Frozen Hybrid Kernelised Expectation Maximisation For Bremsstrahlung SPECT Reconstruction

Background: Selective internal radiation therapy with Yttrium-90 microspheres is an effective therapy for liver cancer and liver metastases. Yttrium-90 is mainly a high-energy beta particle emitter. These beta particles emit Bremsstrahlung radiation during their interaction with tissue making post-therapy imaging of the radioactivity distribution feasible. Nevertheless, image quality and quantification is difficult due to the continuous energy spectrum which makes resolution modelling, and attenuation and scatter estimation challenging. Methods: In this study, a modified hybrid kernelised expectation maximisation is used to improve resolution and contrast and reduce noise. The iterative part of the kernel was frozen at the 72nd sub-iteration to avoid over-fitting of noise and background. A NEMA phantom with spherical inserts was used for the optimisation and validation of the algorithm, and data from 5 patients treated with Selective internal radiation therapy were used as proof of clinical relevance of the method. Results: The results suggest a maximum improvement of 56% for region of interest mean recovery coefficient at fixed coefficient of variation and better identification of the hot volumes in the NEMA phantom. Similar improvements were achieved with patient data, showing 47% mean value improvement over the gold standard used in hospitals. Conclusions: Such quantitative improvements could facilitate improved dosimetry calculations with SPECT when treating patients with Selective internal radiation therapy, as well as provide a more visible position of the cancerous lesions in the liver.

Selective internal radiation therapy for hepatic metastases of uveal melanoma: a systematic review

Objective: Uveal melanoma (UM) commonly metastasizes to the liver. Treatment usually consists of liver-directed therapies, such as selective internal radiation therapy (SIRT). This review aimed to assess the effectiveness and safety of SIRT for hepatic metastases from UM. Methods: The study protocol is available at OSF ( https://osf.io/vhyct/ ). EMBASE and MEDLINE were searched until July 2020, using terms related to SIRT and hepatic metastases from UM. Studies reporting outcomes of SIRT in patients with UM and at least one hepatic metastasis were included. Data on overall survival (OS), hepatic progression free survival (hPFS) or tumor response were collected. The Newcastle-Ottawa Scale (NOS) was used to assess risk of bias. Results: 11 studies were included, reporting outcomes for 268 patients with hepatic metastases from UM. Most studies (n = 9, 81.8%) were retrospective. Disease control was achieved in 170 patients (67.5%) and the median OS from time of SIRT was 12.3 months. Median hPFS was 5.4 months. Low-grade side-effects were common but serious complications were infrequent. There were two treatment-related deaths. The median NOS score was 6 (moderate risk of bias). Conclusion: SIRT appears to be a safe and effective treatment for patients with unresectable hepatic metastases from UM. The certainty of our results is unclear due to predominantly retrospective data with moderate risk of bias. Further prospective studies are required to explore the role of SIRT in UM. Advances in knowledge: SIRT appears to be a safe treatment for patients with unresectable hepatic metastases from UM. Further prospective work is required.

Development of an MRI-Guided Approach to Selective Internal Radiation Therapy Using Holmium-166 Microspheres

Selective internal radiation therapy (SIRT) is a treatment modality for liver tumours during which radioactive microspheres are injected into the hepatic arterial tree. Holmium-166 (166Ho) microspheres used for SIRT can be visualized and quantified with MRI, potentially allowing for MRI guidance during SIRT. The purpose of this study was to investigate the MRI compatibility of two angiography catheters and a microcatheter typically used for SIRT, and to explore the detectability of 166Ho microspheres in a flow phantom using near real-time MRI. MR safety tests were performed at a 3 T MRI system according to American Society for Testing of Materials standard test methods. To assess the near real-time detectability of 166Ho microspheres, a flow phantom was placed in the MRI bore and perfused using a peristaltic pump, simulating the flow in the hepatic artery. Dynamic MR imaging was performed using a 2D FLASH sequence during injection of different concentrations of 166Ho microspheres. In the safety assessment, no significant heating (ΔTmax 0.7 °C) was found in any catheter, and no magnetic interaction was found in two out of three of the used catheters. Near real-time MRI visualization of 166Ho microsphere administration was feasible and depended on holmium concentration and vascular flow speed. Finally, we demonstrate preliminary imaging examples on the in vivo catheter visibility and near real-time imaging during 166Ho microsphere administration in an initial patient case treated with SIRT in a clinical 3 T MRI. These results support additional research to establish the feasibility and safety of this procedure in vivo and enable the further development of a personalized MRI-guided approach to SIRT.

Liver Decompensation as Late Complication in HCC Patients with Long-Term Response following Selective Internal Radiation Therapy

Selective internal radiation therapy (SIRT) is used as a treatment for hepatocellular carcinoma (HCC). The aim of this study was to assess long-term liver-related complications of SIRT in patients who had not developed radioembolization-induced liver disease (REILD). The primary outcome was the percentage of patients without REILD that developed Child-Pugh (CP) ≥ B7 liver decompensation after SIRT. The secondary outcomes were overall survival (OS) and tumor response. These data were compared with a matched cohort of patients treated with sorafenib. Eighty-five patients were included, of whom 16 developed REILD. Of the remaining 69 patients, 38 developed liver decompensation CP ≥ B7. The median OS was 18 months. In patients without REILD, the median OS in patients with CP ≥ B7 was significantly shorter compared to those without CP ≥ B7; 16 vs. 31 months. In the case-matched analysis, the median OS was significantly longer in SIRT-treated patients; 16 vs. 8 months in sorafenib. Liver decompensation CP ≥ B7 occurred significantly more in SIRT when compared to sorafenib; 62% vs. 27%. The ALBI score was an independent predictor of liver decompensation (OR 0.07) and OS (HR 2.83). After SIRT, liver decompensation CP ≥ B7 often developed as a late complication in HCC patients and was associated with a shorter OS. The ALBI score was predictive of CP ≥ B7 liver decompensation and the OS, and this may be a valuable marker for patient selection for SIRT.

Management of Liver Tumors during the COVID-19 Pandemic: The Added Value of Selective Internal Radiation Therapy (SIRT)

Background: In the context of the coronavirus disease 2019 (COVID-19) pandemic, liver-directed therapies (LDTs) may offer minimally invasive integrative tools for tumor control. Among them, selective internal radiation therapy (SIRT) represents a safe, flexible and effective treatment. Purpose of this study is to present our experience with SIRT during the first wave of COVID-19 pandemic and provide an overview of the indications and challenges of SIRT in this scenario. Methods: We retrospectively analyzed the number of patients evaluated by Multidisciplinary Liver Tumor Board (MLTB) and who were undergoing LDTs between March and July 2020 and compared it with 2019. For patients treated with SIRT, clinical data, treatment details and the best radiological response were collected. Results: Compared to 2019, we observed a 27.5% reduction in the number of patients referred to MLTB and a 28.3% decrease in percutaneous ablations; transarterial chemoembolizations were stable, while SIRT increased by 64%. The majority of SIRT patients (75%) had primary tumors, mostly HCC. The best objective response and disease control rates were 56.7% and 72.2%, respectively. Conclusion: The first wave of the COVID-19 pandemic was characterized by an increased demand for SIRT, which represents a safe, flexible and effective treatment, whose manageability will further improve by simplifying the treatment workflow, developing user-friendly and reliable tools for personalized dosimetry and improving interdisciplinary communication.

Comparison of the Uptake of Hepatocellular Carcinoma on Pre-Therapeutic MDCT, CACT, and SPECT/CT, and the Correlation with Post-Therapeutic PET/CT in Patients Undergoing Selective Internal Radiation Therapy

(1) Background: To comparatively analyze the uptake of hepatocellular carcinoma (HCC) on pre-therapeutic imaging modalities, the arterial phase multi-detector computed tomography (MDCT), the parenchymal phase C-arm computed tomography (CACT), the Technetium99m-macroaggregates of human serum albumin single-photon emission computed tomography/computed tomography (SPECT/CT), and the correlation to the post-therapeutic Yttrium90 positron emission tomography/computed tomography (PET/CT) in patients with selective internal radiation therapy (SIRT). (2) Methods: Between September 2013 and December 2016, 104 SIRT procedures were performed at our institution in 74 patients with HCC not suitable for curative surgery or ablation. Twenty-two patients underwent an identical sequence of pre-therapeutic MDCT, CACT, SPECT/CT, and post-therapeutic PET/CT with a standardized diagnostic and therapeutic protocol. In these 22 patients, 25 SIRT procedures were evaluated. The uptake of the HCC was assessed using tumor-background ratio (TBR). Therefore, regions of interest were placed on the tumor and the adjacent liver tissue on MDCT (TBRMDCT), CACT (TBRCACT), SPECT/CT (TBRSPECT/CT), and PET/CT (TBRPET/CT). Comparisons were made with the Friedman test and the Nemenyi post-hoc test. Correlations were analyzed using Spearman’s Rho and the Benjamini–Hochberg method. The level of significance was p < 0.05. (3) Results: TBR on MDCT (1.4 ± 0.3) was significantly smaller than on CACT (1.9 ± 0.6) and both were significantly smaller compared to SPECT/CT (4.6 ± 2.0) (pFriedman-Test < 0.001; pTBRMDCT/TBRCACT = 0.012, pTBRMDCT/TBRSPECT/CT < 0.001, pTBRCACT/TBRSPECT/CT < 0.001). There was no significant correlation of TBR on MDCT with PET/CT (rTBRMDCT/TBRPET/CT = 0.116; p = 0.534). In contrast, TBR on CACT correlated to TBR on SPECT/CT (rTBRCACT/TBRSPECT/CT = 0.489; p = 0.004) and tended to correlate to TBR on PET/CT (rTBRCACT/TBRPET/CT =0.365; p = 0.043). TBR on SPECT/CT correlated to TBR on PET/CT (rTBRSPECT/CT/TBRPET/CT = 0.706; p < 0.001) (4) Conclusion: The uptake assessment on CACT was in agreement with SPECT/CT and might be consistent with PET/CT. In contrast, MDCT was not comparable to CACT and SPECT/CT, and had no correlation with PET/CT due to the different application techniques. This emphasizes the value of the CACT, which has the potential to improve the dosimetric assessment of the tumor and liver uptake for SIRT.

Selective Internal Radiation Therapy in Breast Cancer Liver Metastases: Outcome Assessment Applying a Prognostic Score

Selective internal radiation therapy (SIRT) is a therapy option in patients with breast cancer liver metastasis (BCLM). This analysis aimed at identifying a prognostic score regarding overall survival (OS) after SIRT using routine pretherapeutic parameters. Retrospective analysis of 38 patients (age, 59 (39–84) years) with BCLM and 42 SIRT procedures. Cox regression for OS included clinical factors (age, ECOG and prior treatments), laboratory parameters, hepatic tumor load and dose reduction due to hepatopulmonary shunt. Elevated baseline ALT and/or AST was present if CTCAE grade ≥ 2 was fulfilled (>3 times the upper limit of normal). Median OS after SIRT was 6.4 months. In univariable Cox, ECOG ≥ 1 (hazard ratio (HR), 3.8), presence of elevated baseline ALT/AST (HR, 3.8), prior liver surgery (HR, 10.2), and dose reduction of 40% (HR, 8.1) predicted shorter OS (each p < 0.05). Multivariable Cox confirmed ECOG ≥ 1 (HR, 2.34; p = 0.012) and elevated baseline ALT/AST (HR, 4.16; p < 0.001). Combining both factors, median OS decreased from 19.2 months (0 risk factors; n = 14 procedures) to 5.9 months (1 factor; n = 20) or 2.2 months (2 factors; n = 8; p < 0.001). The proposed score may facilitate pretherapeutic identification of patients with unfavorable OS after SIRT. This may help to balance potential life prolongation with the hazards of invasive treatment and hospitalization.