Combination makes strength: a narrative review of transarterial radioembolization plus immune checkpoint inhibitors for hepatocellular carcinoma.

BACKGROUND AND OBJECTIVE: Immune checkpoint inhibitors (ICIs) and transarterial radioembolization (TARE) are now regarded as promising and versatile therapies for hepatocellular carcinoma (HCC). Combining TARE and ICIs may offer synergistic antineoplastic effects by integrating local and systemic tumor control. This review critically discusses recent preclinical evidence supporting the TARE-ICI combination strategy, completed and ongoing clinical trials, and the challenges in identifying optimal target populations and treatment protocols. METHODS: A comprehensive literature search was conducted in multiple electronic databases (PubMed, Scopus, and Web of Science) from January 1999 to January 2024. The first part of the search was directed at identifying concluded studies regarding the TARE-ICIs combination. The second part aimed at identifying ongoing clinical trials exploring the Clinicaltrials.gov database. KEY CONTENT AND FINDINGS: The combination of TARE and ICIs is a promising strategy, supported by preclinical evidence of immune activation post-TARE and potential synergies with ICIs. Early-phase clinical trials have reported encouraging efficacy. However, significant heterogeneity exists among these studies, particularly concerning target populations and treatment schedules. CONCLUSIONS: The current evidence on TARE-ICI is favorable and promising in improving outcomes of patients with HCC. Further conclusive and higher levels of evidence are pending.

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

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

Impact of scatter correction on personalized dosimetry in selective internal radiotherapy using 166Ho-PLLA: a single-center study including Monte-Carlo simulation, phantom and patient imaging.

BACKGROUND: Developments in transarterial radioembolization led to the conception of new microspheres loaded with holmium-166 (166Ho). However, due to the complexity of the scatter components in 166Ho single photon emission computed tomography (SPECT), questions about image quality and dosimetry are emerging. The aims of this work are to investigate the scatter components and correction methods to propose a suitable solution, and to evaluate the impact on image quality and dosimetry including Monte-Carlo (MC) simulations, phantom, and patient data. METHODS: Dual energy window (DEW) and triple energy window (TEW) methods were investigated for scatter correction purposes and compared using Contrast Recovery Coefficients (CRC) and Contrast to Noise Ratios (CNR). First, MC simulations were carried out to assess all the scatter components in the energy windows used, also to confirm the choice of the parameter needed for the DEW method. Then, MC simulations of acquisitions of a Jaszczak phantom were conducted with conditions mimicking an ideal scatter correction. These simulated projections can be reconstructed and compared with real acquisitions corrected by both methods and then reconstructed. Finally, both methods were applied on patient data and their impact on personalized dosimetry was evaluated. RESULTS: MC simulations confirmed the use of k = 1 for the DEW method. These simulations also confirmed the complexity of scatter components in the main energy window used with a high energy gamma rays component of about half of the total counts detected, together with a negligible X rays component and a negligible presence of fluorescence. CRC and CNR analyses, realized on simulated scatter-free projections of the phantom and on scatter corrected acquisitions of the same phantom, suggested an increased efficiency of the TEW method, even at the price of higher level of noise. Finally, these methods, applied on patient data, showed significant differences in terms of non-tumoral liver absorbed dose, non-tumoral liver fraction under 50 Gy, tumor absorbed dose, and tumor fraction above 150 Gy. CONCLUSIONS: This study demonstrated the impact of scatter correction on personalized dosimetry on patient data. The use of a TEW method is proposed for scatter correction in 166Ho SPECT imaging.

Selective Internal Radiotherapy (SIRT) and Chemosaturation Percutaneous Hepatic Perfusion (CS-PHP) for Metastasized Uveal Melanoma: A Retrospective Comparative Study.

Even with liver-targeted therapies, uveal melanoma with hepatic metastasis remains a challenge. The aim of this study was to compare the outcome of patients treated with either SIRT or CS-PHP. We included 62 patients with hepatic metastasized uveal melanoma (n = 34 with SIRT, receiving 41 cycles; n = 28 with CS-PHP, receiving 56 cycles) that received their treatments between 12/2013 and 02/2020 at a single center. We evaluated their response according to the RECIST 1.1, as well as progression-free survival (PFS) and overall survival (OS), after the initiation of the first cycle of the liver-directed treatment using Cox regression, adjusted via propensity score analysis for confounders, including the amount of hepatic involvement. The disease control rate was 18% for SIRT and 30% for CS-PHP. The median (range) of PFS was 127.5 (19-1912) days for SIRT and 408.5 (3-1809) days for CS-PHP; adjusted Cox regression showed no significant difference (p = 0.090). The median (range) of OS was 300.5 (19-1912) days for SIRT and 516 (5-1836) days for CS-PHP; adjusted Cox regression showed a significant difference (p = 0.006). In our patient cohort, patients treated with CS-PHP showed a significantly longer OS than patients treated with SIRT. CS-PHP might therefore be preferable for patients with liver-dominant metastatic uveal melanoma.

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.

Clinical impact of 99mTc-MAA SPECT/CT-based personalized predictive dosimetry in selective internal radiotherapy: a real-life single-center experience in unresectable HCC patients.

BACKGROUND: Recent data demonstrated that personalized dosimetry-based selective internal radiotherapy (SIRT) is associated with better outcome for unresectable hepatocellular carcinoma (HCC). AIM: We aim to evaluate the contribution of personalized predictive dosimetry (performed with Simplicity90® software) in our population of HCC patients by comparing them to our historical cohort whose activity was determined by standard dosimetry. METHODS: This is a retrospective, single-center study conducted between February 2016 and December 2020 that included patients with HCC who received SIRT after simulation based on either standard dosimetry (group A) or, as of December 2017, on personalized dosimetry (group B). Primary endpoints were best overall response (BOR) and objective response rate (ORR) evaluated by mRECIST at 3 months. Safety and toxicity profiles were evaluated at 1- and 3-months post-treatment. For group A we compared the activity to be administered determined a posteriori using Simplicit90Y® and the activity actually administered determined by the standard approach. RESULTS: Between February 2016 and December 2020, 66 patients received 69 simulations leading to 40 treatments. The median follow-up time was equal for both groups, 21 months (range 3-55) in group A and 21 months (range 4-39) in group B. The per patient analysis revealed a significant benefit of personalized predictive dosimetry in terms of better overall response at 3 months (80% vs. 33.3%, p = 0.007) and at 6 months (77.8% vs. 22.2%, p = 0.06). This trend was found in the analysis by nodule with a response rate according to mRECIST of 87.5% for personalized dosimetry versus 68.4% for standard dosimetry at 3 months, p = 0.24. Only one grade 3 biological toxicity (hyperbilirubinemia) was noted in group A. The comparison between the administered activity and the recommended activity recalculated a posteriori using Simplicit90Y® showed that the vast majority of patients who progressed (83.33%) received less activity than that recommended by the personalized approach or an inadequate distribution of the administered activity. CONCLUSIONS: Our study aligns to recent literature and confirms that the use of personalized dosimetry allows a better selection of HCC patients who can benefit from SIRT, and consequently, improves the effectiveness of this treatment.

Selective internal radiotherapy in Germany: a review of indications and hospital mortality from 2012 to 2019.

Background and Aim: Selective internal radiotherapy (SIRT) is a minimal invasive tumor therapy for hepatocellular carcinoma (HCC), biliary tract cancer (BTC), and liver metastasis of extrahepatic tumors. Comprehensive data on past and current trends of SIRT as well as outcome parameters such as in-hospital mortality and adverse events in Germany are missing. Methods: We evaluated current clinical developments and outcomes of SIRT in Germany based on standardized hospital discharge data, provided by the German Federal Statistical Office from 2012 to 2019. Results: A total of 11,014 SIRT procedures were included in the analysis. The most common indication was hepatic metastases (54.3%; HCC: 39.7%; BTC: 6%) with a trend in favor of HCC and BTC over time. Most SIRTs were performed with yttrium-90 (99.6%) but the proportion of holmium-166 SIRTs increased in recent years. There were significant differences in the mean length of hospital stay between 90Y (3.67 ± 2 days) and 166Ho (2.9 ± 1.3 days) based SIRTs. Overall in-hospital mortality was 0.14%. The mean number of SIRTs/hospital was 22.9 (SD ± 30.4). The 20 highest case volume centers performed 25.6% of all SIRTs. Conclusion: Our study gives a detailed insight into indications, patient-related factors, and the incidence of adverse events as well as the overall in-hospital mortality in a large SIRT collective in Germany. SIRT is a safe procedure with low overall in-hospital mortality and a well-definable spectrum of adverse events. We report differences in the regional distribution of performed SIRTs and changes in the indications and used radioisotopes over the years. Relevance for Patients: SIRT is a safe procedure with very low overall mortality and a well-definable spectrum of adverse events, particularly gastrointestinal. Complications are usually treatable or self-limiting. Acute liver failure is a potentially fatal but exceptionally rare complication. 166Ho has promising beneficial bio-physical characteristics and 166Ho-based SIRT should be further evaluated against 90Y-based SIRT as the current standard of care.

The management of oligometastatic disease in colorectal cancer: Present strategies and future perspectives.

Oligometastatic disease has been described as an intermediate clinical state between localized cancer and systemically metastasized disease. Recent clinical studies have shown prolonged survival when aggressive locoregional approaches are added to systemic therapies in patients with oligometastases. The aim of this review is to outline the newest options to treat oligometastatic colorectal cancer (CRC), also considering its molecular patterns. We present an overview of the available local treatment strategies, including surgical procedures, stereotactic body radiation therapy (SBRT), thermal ablation, as well as trans-arterial chemoembolization (TACE) and selective internal radiotherapy (SIRT). Moreover, since imaging methods provide crucial information for the early diagnosis and management of oligometastatic CRC, we discuss the role of modern radiologic techniques in selecting patients that are amenable to potentially curative locoregional treatments.

Liver Tumor Enhancement at Hybrid Angio-CT and Comparison With Tumor and Hepatic Parenchymal Distribution of Yttrium-90 Microspheres by Positron Emission Tomography.

This single-center retrospective study evaluated patients who underwent treatment of a primary or secondary hepatic malignancy with injection of glass or resin yttrium-90 (90Y) microspheres with a corresponding hybrid angiography-computed tomography (angio-CT) and 90Y positron emission tomography (PET). Volumetric contours were defined by three independent observers and were used to calculate relative tumoral enhancement at angio-CT. This parameter was compared with the tumor-to-normal (T/N) activity ratio predicted by technetium-99m macro-aggregated albumin (99mTc-MAA) single photon emission computed tomography (SPECT) and microsphere activity distribution by 90Y PET. A similar correlation was observed for the enhancement ratio at angio-CT with observed microsphere distribution at 90Y PET (r=0.34) to that predicted by 99mTc-MAA SPECT (r=0.32). The enhancement ratio on angio-CT performed as well as 99mTc-MAA in the prediction of 90Y PET activity distribution. The technique could not be readily applied to tumors with large areas of hypoattenuation (necrosis) on angio-CT. With refinement and further study, this technique could be used as a quantitative adjunct to standard-of-care 99mTc-MAA SPECT for dosimetry calculations and prediction of microsphere distribution to maximize tumor response and minimize hepatotoxicity.

LiMAx Prior to Radioembolization for Hepatocellular Carcinoma as an Additional Tool for Patient Selection in Patients with Liver Cirrhosis.

BACKGROUND AND AIMS: Radioembolization (RE) has recently demonstrated a non-inferior survival outcome compared to systemic therapy for advanced hepatocellular carcinoma (HCC). Therefore, current guidelines recommend RE for patients with advanced HCC and preserved liver function who are unsuitable for transarterial chemoembolization (TACE) or systemic therapy. However, despite the excellent safety profile of RE, post-therapeutic hepatic decompensation remains a serious complication that is difficult to predicted by standard laboratory liver function parameters or imaging modalities. LiMAx® is a non-invasive test for liver function assessment, measuring the maximum metabolic capacity for 13C-Methacetin by the liver-specific enzyme CYP 450 1A2. Our study investigates the potential of LiMAx® for predicting post-interventional decompensation of liver function. PATIENTS AND METHODS: In total, 50 patients with HCC with or without liver cirrhosis and not amenable to TACE or systemic treatments were included in the study. For patients prospectively enrolled in our study, LiMAx® was carried out one day before RE (baseline) and 28 and 90 days after RE. Established liver function parameters were assessed at baseline, day 28, and day 90 after RE. The relationship between baseline LiMAx® and pre-and post-interventional liver function parameters, as well as the ability of LiMAx® to predict hepatic decompensation, were analyzed. RESULTS: We observed a strong association between baseline LiMAx® and bilirubin, albumin, ALBI grade, and MELD score. Patients presenting with Child-Pugh score B 28 days after RE or with a deterioration in Child-Pugh score by at least one point had a significantly lower baseline LiMAx® compared to those with Child-Pugh score A or with stable Child-Pugh score. The ability of LiMAx® to predict hepatic decompensation after RE was determined using ROC curve analysis and was compared to MELD score and ALBI grade. LiMAx® achieved a substantial AUC of 0.8117, comparable to MELD score and ALBI grade. CONCLUSION: Patients with lower LiMAx® values at baseline have a significantly increased risk for hepatic decompensation after RE, despite being categorized as Child-Pugh A. Therefore, LiMAx® can be used as an additional tool to identify patients at high risk of post-interventional hepatic failure.

Comparison of PMT-based TF64 and SiPM-based Vereos PET/CT systems for 90 Y imaging and dosimetry optimization: A quantitative study.

BACKGROUND: Selective internal radiotherapy based on transarterial radioembolization (TARE) with yttrium-90 (90 Y) microspheres is an established treatment for primary or metastatic liver disease. PURPOSE: The objective of this work is to optimize the dosimetry of patients treated with 90 Y TARE, using positron emission tomography (PET) images. METHODS: The NEMA 2012 PET phantom was filled with nearly 3.9 GBq of 90 Y activity and acquired at days 0, 3, 5, 7, and 9 on a classic time-of-flight PET/computed tomography (CT) scanner (Philips TF64) and on a silicon photomultiplier (SiPM)-based PET/CT scanner (Philips Vereos). Acquisitions were carried on following the guidelines proposed in a previously published multicentric trial and images were reconstructed by varying and combining the available parameters. Comparisons were performed to identify the best set(s) of parameters leading to the most accurate 90 Y-PET image(s), in terms of activity distribution. Then, for both scanners, the best images were analyzed with Simplicit90 Y, a personalized dosimetry software using multicompartmental Medical Internal Radiation Dose model. The comparison between measured and true doses allowed to identify the image granting the most consistent dose estimations and, therefore, to designate the set of parameters to be applied on patients' data for the reconstruction of optimized clinical images. Posttreatment dosimetry of four patients was then realized with Simplicit90 Y using optimized imaging datasets. RESULTS: Based on activity distribution comparisons and dose estimations over phantom and patients data, the SiPM-based PET/CT system appeared more suitable than the photomultiplier tube-based TF64 for 90 Y-PET imaging. With the SiPM-based PET/CT system, reconstructed images with a 2-mm voxel size combined with the application of the point spread function correction led to the most accurate results for quantitative 90 Y measures. CONCLUSIONS: For the SiPM-based PET/CT scanner, an optimized set of reconstruction parameters has been identified and applied on patients' data in order to generate the most accurate image to be used for an improved personalized 90 Y-PET dosimetry, ensuring a reliable evaluation of the delivered doses.

ArTisaN trial protocol: a single Centre, open-label, phase II trial of the safety and efficacy of TheraSphere selective internal radiation therapy (SIRT) in the treatment of inoperable metastatic (liver) neuroendocrine neoplasia (NENs).

BACKGROUND: Neuroendocrine neoplasias (NENs) are a rare type of malignancy that arise from the cells of the neuroendocrine system. Most patients present with advanced, unresectable disease, typically with metastases to the liver. The presence of liver metastases dictates prognosis and there has been a number of studies investigating therapies that reduce the burden of liver disease. Selective Internal Radiation Therapy (SIRT) allows the delivery of targeted high dose radiation directly to tumours, with relative sparing of the surrounding liver tissue. Here, we describe the design and rationale of ArtTisaN, a phase II study to assess efficacy and tolerability of SIRT using TheraSpheres for the management of liver metastases secondary to NENs. METHODS: Twenty-four eligible participants will be recruited to receive SIRT with TheraSpheres. The primary objective is to determine the objective response rate to treatment, defined as the rate of best overall response in the treated liver volume. In addition, total hepatic response and overall response will be assessed according to RECIST 1.1. The second co-primary objective is to determine the incidence of adverse and serious adverse device events. The secondary objectives are progression free survival, overall survival and quality of life. Additional exploratory objectives include investigation of circulating biomarkers of response and identification of a radiomic signature of response. DISCUSSION: This trial will provide prospective evidence on the efficacy of SIRT using TheraSpheres for the management of liver metastases. TRIAL REGISTRATION: NCT04362436 .

Same day yttrium-90 radioembolization with single photon emission computed tomography/computed tomography: An opportunity to improve care during the COVID-19 pandemic and beyond.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has made it more challenging for patients to undergo yttrium-90 (Y-90) radioembolization (RE). Same day Y-90 RE provides an opportunity to minimize logistical challenges and infection risk associated with COVID-19, thus improving patient access. AIM: To describe the use of same day Y-90 RE with routine single photon emission computed tomography/computed tomography (SPECT/CT) in order to optimize therapy. METHODS: All patients were selected for Y-90 RE through a multidisciplinary tumor board, and were screened and tested for COVID-19 infection per institutional protocol. A same day procedure was developed, consisting of angiography, imaging, and Y-90 resin particle delivery. Routine SPECT/CT after technetium-99m macroaggregated albumin (Tc-99m MAA) administration was performed for assessment of arterial supply, personalized dosimetry, and extrahepatic activity. Post-treatment Y-90 bremsstrahlung SPECT/CT was performed for confirmation of particle delivery, by utilization of energy windowing to limit signal from previously administered Tc-99m MAA particles. RESULTS: A total of 14 patients underwent same day Y-90 RE between March and June 2020. Mean lung shunt fraction was 6.13% (range 3.5%-13.1%). Y-90 RE was performed for a single lesion in 7 patients, while the remaining 7 patients had treatment of multifocal lesions. The largest lesion measured 8.3 cm. All patients tolerated the procedure well and were discharged the same day. CONCLUSION: Same day Y-90 RE with resin-based microspheres is feasible, and provides an opportunity to mitigate infection risk and logistical challenges associated with the COVID-19 pandemic and beyond. We recommend consideration of SPECT/CT, especially among patients with complex malignancies, for the potential to improve outcomes and eligibility of patients to undergo same day Y-90 RE.

Disease control and failure patterns of unresectable hepatocellular carcinoma following transarterial radioembolization with yttrium-90 microspheres and with/without sorafenib.

BACKGROUND: Impressive survival outcome of our previous study in unresectable hepatocellular carcinoma (HCC) patients undergoing yttrium-90 glass microspheres transarterial radioembolization (TARE) with/without sorafenib according to individuals' disease burden, i.e., intrahepatic tumor load (IHT) and adverse disease features (ADFs) might partly be confounded by other treatments and underlying hepatic function. Therefore, a dedicated study focusing on treatment response and assessment of failure patterns might be a way to improve treatment outcome in addition to patient selection based on the disease burden. AIM: To assess the tumor response, disease control and patterns of disease progression following TARE with/without sorafenib in unresectable HCC patients. METHODS: This retrospective study was conducted in successful TARE procedures with available pre- and post-treatment imaging studies (n = 169). Three treatment subgroups were (1) TARE only (TARE_alone) for IHT ≤ 50% without ADFs, i.e., macrovascular invasion, extrahepatic disease (EHD) and infiltrative/ill-defined HCC (n = 63); (2) TARE with sorafenib (TARE_sorafenib) for IHT > 50% and/or presence of ADFs (n = 81); and (3) TARE only for patients who could not receive sorafenib due to contraindication or intolerance (TARE_no_sorafenib) (n = 25). Objective response rate (ORR; consisted of complete response (CR) and partial response (PR)), disease control rate (DCR; consisted of CR, PR and stable disease) and failure patterns of treated, intrahepatic and extrahepatic sites were assessed using the modified response evaluation criteria in solid tumors. Time to progression (TTP) was calculated from TARE to the first radiologic progression at any site using Kaplan-Meier method. Identification of prognostic factors for TTP using the univariate Kaplan-Meier method and multivariate Cox proportional hazard model were performed in major population subgroups, TARE_alone and TARE_sorafenib. RESULTS: The median radiologic follow-up time was 4.4 mo (range 0.5-48.8). In treated area, ORR was highest in TARE_sorafenib (53.1%), followed by TARE_alone (41.3%) and TARE_no_sorafenib (16%). In intrahepatic area, DCR remained highest in TARE_sorafenib (84%), followed by TARE_alone (79.4%) and TARE_no_sorafenib (44%). The overall DCR was highest in TARE_alone (79.4%), followed by TARE_sorafenib (71.6%) and TARE_no_sorafenib (40%). Dominant failure patterns were intrahepatic for both TARE_alone (44.5%) and TARE_sorafenib (38.4%). Extrahepatic progression was more common in TARE_sorafenib (32%) and TARE_no_sorafenib (40%) than in TARE_alone (12.7%). TTP was longest in TARE_alone (8.6 mo; 95%CI: 3.4-13.8), followed by TARE_sorafenib (5.1 mo; 95%CI: 4.0-6.2) and TARE_no_sorafenib (2.7 mo; 95%CI: 2.2-3.1). Pre-existing EHD (HR: 0.37, 95%CI: 0.24-0.56, P < 0.001) was a sole prognostic factor for TTP in TARE_sorafenib with no prognostic factor for TTP in TARE_alone. CONCLUSION: TARE with/without sorafenib according to individuals' disease burden provided DCR approximately 70% with intrahepatic progression as dominant failure pattern. Extrahepatic progression was more common in procedures with initially high disease burden.

Anomalous Branch of the Left Hepatic Artery With Pericardial, Diaphragmatic, Splenic and Gastric Supply During Selective Internal Radiotherapy (SIRT).

Selective internal radiotherapy (SIRT) is an established modality for the treatment of hepatic malignancy. The procedure is normally carried out in two parts. The first part involves a planning or "work-up" angiogram to delineate anatomy and plan safe yttrium-90 (Y90) delivery, and the second part for the administration of the Y90 microspheres. The work-up angiogram has three main purposes including delineation of hepatic and tumor vascular anatomy, which might influence the administration of the microbeads, identification, and embolization of blood vessels, which may complicate treatment or contribute to non-target Y90 microsphere deposition and administration of technetium 99 (metastable) labeled macroaggregated albumin (99mTcMAA) at the planned administration points prior to the same day single-photon emission computed tomography (SPECT) or planar SPECT to identify sites of 99mTcMAA uptake. We present the case of a SIRT procedure that demonstrated an anomalous artery arising from the left hepatic artery with supply to the pericardium, diaphragm, fundus of the stomach, and spleen. This is a rare vascular variant that highlights the importance of thorough assessment of both the planning angiograms and SPECT CT for the presence of anatomical variants and abnormal extrahepatic 99mTcMAA uptake to help reduce the need to recall patients for repeat work-up procedures.

The multidisciplinary management of oligometastases from colorectal cancer: a narrative review.

In the United States of America, almost 150,000 people are estimated to be diagnosed with colorectal cancer in 2020 and up to 35% of those are expected to present with oligometastatic disease. The term 'oligometastasis' was first used in 1995, however surgical literature describing liver resection for colorectal cancer dates back to the 1940s. Five-year survival rates of up to 42% with surgery alone for solitary lesions are reported. Modern trials have demonstrated median overall survival rates of over 80 months for patients with colorectal liver metastases treated with perioperative chemotherapy. Colorectal liver metastases have accordingly been described as 'proof of concept' for the oligometastatic theory.

Evaluation of liver tumour response by imaging.

The goal of assessing tumour response on imaging is to identify patients who are likely to benefit - or not - from anticancer treatment, especially in relation to survival. The World Health Organization was the first to develop assessment criteria. This early score, which assessed tumour burden by standardising lesion size measurements, laid the groundwork for many of the criteria that followed. This was then improved by the Response Evaluation Criteria in Solid Tumours (RECIST) which was quickly adopted by the oncology community. At the same time, many interventional oncology treatments were developed to target specific features of liver tumours that result in significant changes in tumours but have little effect on tumour size. New criteria focusing on the viable part of tumours were therefore designed to provide more appropriate feedback to guide patient management. Targeted therapy has resulted in a breakthrough that challenges conventional response criteria due to the non-linear relationship between response and tumour size, requiring the development of methods that emphasize the appearance of tumours. More recently, research into functional and quantitative imaging has created new opportunities in liver imaging. These results have suggested that certain parameters could serve as early predictors of response or could predict later tumour response at baseline. These approaches have now been extended by machine learning and deep learning. This clinical review focuses on the progress made in the evaluation of liver tumours on imaging, discussing the rationale for this approach, addressing challenges and controversies in the field, and suggesting possible future developments.

Renal and Intestinal Excretion of 90Y and 166Ho After Transarterial Radioembolization of Liver Tumors.

OBJECTIVE. The aim of this study was to evaluate the amount of free radioactivity in renal and intestinal excretions during the first 48 hours after transarterial radioembolization (TARE) procedures on the liver. SUBJECTS AND METHODS. Urinary, intestinal, and biliary excretions of patients who underwent TARE with three different types of microspheres were collected during a postinterventional period of 48 hours (divided into two 24-hour intervals). Radioactivity measurements were performed. The detected amounts of activity were correlated to clinical and procedural characteristics, times of excretion, and microsphere types. RESULTS. Twenty-four patients were evaluated, 10 treated with 90Y-glass, 10 with 90Y-resin, and four with 166Ho-poly-L-lactic acid (PLLA) microspheres. Activity excretion occurred in all cases. The highest total excretion proportions of the injected activities were 0.011% for 90Y-glass, 0.119% for 90Y-resin, and 0.005% for 166Ho-PLLA microspheres. Intestinal excretion was markedly less than renal excretion (p < 0.001). Excretion after TARE with 90Y-resin was statistically significantly higher than with 90Y-glass or 166Ho-PLLA micro-spheres (p = 0.002). For each microsphere type, the excreted activity was independent of the activity of the injected microspheres. CONCLUSION. Renal and intestinal excretion of radioactivity after TARE is low but not negligible. The radiation risk for individuals interacting with patients can be minimized if contact with urine and bile is avoided, particularly during the first 24 hours after the procedure.

Liver Resection After Selective Internal Radiation Therapy with Yttrium-90: Safety and Outcomes.

INTRODUCTION: Selective internal radiotherapy (SIRT) with yttrium-90 (Y-90) is an intra-arterial therapy for hepatic malignancy in patients who are unsuitable for surgical resection. This treatment is considered palliative, although some patients can demonstrate a response that is adequate to facilitate surgical resection with curative intent. METHODS: All patients who underwent liver resection post SIRT were reviewed. Data gathered included patient demographics, tumor type, surgical details, and post-operative outcomes. RESULTS: Twelve patients underwent SIRT followed by liver resection (7 males and 5 females). Pathologies were hepatocellular carcinoma (n = 5), metastatic colorectal cancer (n = 5), and neuroendocrine tumor (n = 2). Lesional response (size, volume, and RECIST (response evaluation criteria in solid tumors)) was calculated and where appropriate functional liver remnant (FLR) is presented. Mean FLR increase was 264cm3 (range - 123 to 909), and all cases demonstrated a partial response according to RECIST with a mean largest lesion volume reduction of 475cm3 (range 14-1632). No post-SIRT complications were noted. Hepatectomy occurred at a mean of 322 days from SIRT treatment. Ninety-day morbidity was 67% (n = 6), complications post-surgery were analyzed according to the Clavien-Dindo classification scale; a total of 15 events occurred in 6 patients. Ninety-day mortality of 11% (n = 1). CONCLUSION: In selected cases, liver resection is possible post SIRT. As this can represent a potentially curative option, it is important to reconsider resection in the follow-up of patients undergoing SIRT. Post-operative complications are noted following major and extended liver resection. Therefore, further studies are needed to improve patient selection.

Catheter-Directed Computed Tomography Hepatic Angiography for Yttrium-90 Selective Internal Radiotherapy of Hepatocellular Carcinoma Reduces Prophylactic Embolization of Extrahepatic Vessels.

OBJECTIVES: To determine the rate of prophylactic embolization of extrahepatic vessels in patients undergoing yttrium-90 selective internal radiotherapy (90Y SIRT) for hepatocellular carcinoma (HCC) with the use of catheter-directed computed tomography hepatic angiography (CD-CTHA). MATERIALS AND METHODS: This retrospective study included 186 HCC patients who received 90Y SIRT from May 2010 to June 2015 in a single institution. All procedures were performed in a hybrid angiography-CT suite equipped with digital subtraction angiography (DSA) and CD-CTHA capabilities. CD-CTHA was performed during pre-treatment hepatic angiography. 90Y SIRT was administered approximately 2 weeks later. Selective prophylactic embolization of extrahepatic vessels was performed if extrahepatic enhancement was seen on CD-CTHA or if an extrahepatic vessel opacified on DSA/CD-CTHA despite the final microcatheter position for 90Y microsphere delivery being beyond the origin of this vessel. RESULTS: Thirty-five patients (18.8%) required selective embolization of extrahepatic vessels. Technical success of 90Y SIRT was 99.5%. Two patients (1.1%) developed radiation-induced gastrointestinal ulceration, and one (0.54%) developed radiation-induced pneumonitis. Extrahepatic uptake of 90Y microspheres was seen in the gallbladder of one patient without significant complications. CONCLUSION: The use of CD-CTHA in 90Y SIRT of HCC was associated with a low rate of prophylactic embolization of extrahepatic vessels while maintaining a high technical success rate of treatment and low rate of complications. LEVEL OF EVIDENCE: Level 4, case series.