Effectiveness of Vaccines and Monoclonal Antibodies Against Respiratory Syncytial Virus: Generic Protocol for Register-Based Cohort Study.

Several immunization products are currently being developed against respiratory syncytial virus (RSV) for children, pregnant females, and older adults, and some products have already received authorization. Therefore, studies to monitor the effectiveness of these products are needed in the following years. To assist researchers to conduct postmarketing studies, we developed a generic protocol for register-based cohort studies to evaluate immunization product effectiveness against RSV-specific and nonspecific outcomes. To conduct a study on the basis of this generic protocol, the researchers can use any relevant databases or healthcare registers that are available at the study site.

Effectiveness of Immunization Products Against Medically Attended Respiratory Syncytial Virus Infection: Generic Protocol for a Test-Negative Case-Control Study.

Monitoring the real-life effectiveness of respiratory syncytial virus (RSV) products is of major public health importance. This generic protocol for a test-negative design study aims to address currently envisioned approaches for RSV prevention (monoclonal antibodies and vaccines) to study effectiveness of these products among target groups: children, older adults, and pregnant women. The generic protocol approach was chosen to allow for flexibility in adapting the protocol to a specific setting. This protocol includes severe acute respiratory infection (SARI) and acute respiratory infection (ARI), both due to RSV, as end points. These end points can be applied to studies in hospitals, primarily targeting patients with more severe disease, but also to studies in general practitioner clinics targeting ARI.

Dose-response relationship after yttrium-90-radioembolization with glass microspheres in patients with neuroendocrine tumor liver metastases.

BACKGROUND: In radioembolization, response is achieved through the irradiation and damaging of tumor DNA. For hepatic metastases of neuroendocrine tumors, a dose-response relationship has not been established yet. This study assesses whether increasing tumor-absorbed doses lead to increased response rates. METHODS: We included all patients who underwent yttrium-90 (90Y) glass microspheres radioembolization in our center if both pre- and post-treatment contrast-enhanced CT and post-injection PET/CT were available. Up to five hepatic tumors and the healthy hepatic tissue were delineated, and absorbed dose was quantified using post-injection PET/CT. Response was measured according to RECIST 1.1 on patient and tumor level. Linear mixed models were used to study the relationship between absorbed dose and response on tumor level. Logistic regression analysis was used on patient level to study dose-response and hepatic dose-toxicity relationships. RESULTS: A total of 128 tumors in 26 patients (31 procedures) were included in the response analysis. While correcting for confounding by tumor volume, a significant effect of response on dose was found (p = 0.0465). Geometric mean of absorbed dose for responding tumors was 170 Gy, for stable disease 101 Gy, and for progressive disease 67 Gy. No significant dose-toxicity relationship could be identified. CONCLUSION: In patients with neuroendocrine tumor liver metastases, treated with 90Y-radioembolization, a clear dose-response relationship was found. We propose to perform 90Y-radioembolization with an absolute minimum planned tumor-absorbed dose of 150 Gy.

Use of an anti-reflux catheter to improve tumor targeting for holmium-166 radioembolization-a prospective, within-patient randomized study.

PURPOSE: The objective of this study was to investigate whether the use of an anti-reflux catheter improves tumor targeting for colorectal cancer patients with unresectable, chemorefractory liver metastases (mCRC) treated with holmium-166 (166Ho)-radioembolization. MATERIALS AND METHODS: In this perspective, within-patient randomized study, left and right hepatic perfusion territories were randomized between infusion with a Surefire® anti-reflux catheter or a standard microcatheter. The primary outcome was the difference in tumor to non-tumor (T/N) activity distribution. Secondary outcomes included the difference in infusion efficiency, absorbed doses, predictive value of 166Ho-scout, dose-response relation, and survival. RESULTS: Twenty-one patients were treated in this study (the intended number of patients was 25). The median T/N activity concentration ratio with the use of the anti-reflux catheter was 3.2 (range 0.9-8.7) versus 3.6 (range 0.8-13.3) with a standard microcatheter. There was no difference in infusion efficiency (0.04% vs. 0.03% residual activity for the standard microcatheter and anti-reflux catheter, respectively) (95%CI - 0.05-0.03). No influence of the anti-reflux catheter on the dose-response rate was found. Median overall survival was 7.8 months (95%CI 6-13). CONCLUSION: Using a Surefire® anti-reflux catheter did not result in a higher T/N activity concentration ratio in mCRC patients treated with 166Ho-radioembolization, nor did it result in improved secondary outcomes measures. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT02208804.

Evaluation of the Safety and Feasibility of Same-Day Holmium-166 -Radioembolization Simulation and Treatment of Hepatic Metastases.

PURPOSE: To evaluate the safety and feasibility of same-day treatment, including the simulation procedure for assessment of intrahepatic and extrahepatic distribution of the microspheres, with holmium-166 (166Ho)-radioembolization. MATERIALS AND METHODS: This was a secondary analysis of patients included in the 4 prospective studies (HEPAR I, HEPAR II, HEPAR PLuS, and SIM) on 166Ho-radioembolization. The technical success rate of the same-day treatment protocol, defined as the number of patients who completed the same-day treatment, was measured. Total in-room time, duration of the scout procedure, time to imaging, and duration of the treatment procedure were recorded. Reasons for discontinuation or adjustment of treatment were identified. Adverse events that occurred during the treatment day were recorded. RESULTS: One hundred five of 120 scheduled patients completed the same-day treatment with 166Ho-radioembolization (success rate, 88%). After the simulation procedure, treatment was cancelled in 15 patients because of extrahepatic deposition (n = 8), suboptimal tumor targeting (n = 1), unanticipated vascular anatomy (n = 5), and dissection (n = 1). In another 14 patients, the treatment plan was adjusted. The median total procedure time (ie, simulation, imaging, and treatment) was 6:39 hours:minutes (range, 3:58-9:17 hours:minutes). Back pain was a major same-day treatment-related complaint (n = 28). CONCLUSION: 166Ho-radioembolization as a same-day treatment procedure is feasible in most selected patients, although treatment was adjusted in 12% of patients and cancelled in 12% of patients. This approach might be beneficial for a select patient population, such as patients needing a radiation segmentectomy.

Open epididymal spermatozoa aspiration for obstructive azoospermia.

In men suffering from obstructive azoospermia (OA), surgical sperm retrieval (SR) can be performed for use with intracytoplasmic sperm injection (ICSI). Several techniques of surgical SR exist, with various results. In our facility, we have developed the open epididymal spermatozoa aspiration (OESA) procedure. The aim of this study was to report on the sperm retrieval rate (SRR), reproductive outcome and neonatal outcome of OESA followed by ICSI. In addition, we have investigated possible predictors of successful SR and clinical pregnancy. A total of 231 men who were treated with OESA were included in this retrospective analysis, together with their female partners. We found an overall SRR of 76.6%. Serum FSH was a significant negative predictor of successful SR (odds ratio 0.87; 95% CI 0.78-0.98; p = 0.021). Overall cumulative pregnancy rate was 50.8%. Higher age (odds ratio 0.90; p < 0.001) and frozen vs. fresh embryo transfer (odds ratio 0.56; p = 0.004) were negatively associated with clinical pregnancy in multivariable analysis. Reproductive and neonatal outcomes did not differ according to obstruction cause. We conclude that OESA is a reliable and safe method for surgical SR in men suffering from OA.

Factors associated with COVID-19 autumn 2022 booster uptake in the Netherlands among older adults aged ≥ 60 years and younger adults with chronic conditions.

BACKGROUND: A booster with bivalent COVID-19 vaccine was offered in the Netherlands in autumn, 2022. We aimed to investigate vaccine uptake during the autumn 2022 booster round among the population subgroups at risk for severe COVID-19 that were specifically targeted by this campaign: the medical risk group aged 18-59 years and individuals ≥ 60 years. We calculated booster uptake in both populations and analyzed determinants of booster uptake among those who had received at least one prior COVID-19 vaccination. METHODS: Having had an autumn 2022 booster dose was defined as having received a COVID-19 vaccination between 19 September 2022 and 7 March 2023. The study population included individuals who received at least one previous COVID-19 vaccination. National registries of sociodemographic determinants and COVID-19 vaccination were linked by a unique person identifier. Voting proportions for political parties were included at neighborhood level. Determinants of COVID-19 vaccine autumn booster uptake were ranked by importance by random forest analyses. RESULTS: Booster uptake was 68 % among those aged ≥ 60 and 30 % among those aged 18-59 years with a medical risk factor for severe disease. For both target groups the most important determinant for booster uptake was age (15 % in 18-29 years to 72 % in 80 + years). Voting proportions for progressive liberal political parties ranked second in the random forest analysis in both groups, with an increasing proportion of votes associated with higher uptake. In the 60 + group, household type ranked third, with highest vaccine uptake among married couples without children (72 %) and the lowest uptake among unmarried couples with children (47 %). In the medical risk group, migration status ranked third. Migrants with two parents born abroad had the lowest uptake (18 %), whereas migrants with both parents born in the Netherlands had the highest uptake (35 %). CONCLUSION: The target group of people aged ≥ 60 years was much better reached than the target group of people with a medical risk aged 18-59 years. Uptake varied considerably among subgroups in both target groups. The findings of this study can be used in future vaccination strategies as well as for further research to better understand the drivers and barriers of vaccine uptake among the subgroups with notably low uptake.

Determinants of COVID-19 Vaccine Uptake in The Netherlands: A Nationwide Registry-Based Study.

By September 2022, the uptake of at least one dose of COVID-19 vaccine in the Dutch adult population was 84%. Ecological studies have indicated a lower uptake in certain population groups. We aimed to investigate determinants of COVID-19 vaccine uptake in the Netherlands at individual level to evaluate and optimize implementation of the vaccination program and generate hypotheses for research on drivers of, and barriers to, vaccination. A retrospective database study was performed including the entire Dutch population ≥ 18. Vaccination data (5 January 2021-18 November 2021) were at individual levels linked to sociodemographic data. Random forest analyses ranked sociodemographic determinants of COVID-19 vaccine uptake. The most important determinant was age; uptake increased until the age of 80 (67% in 18-35 years, 92% in 67-79 years, and 88% in those > 80). Personal income and socioeconomic position ranked second and third, followed by migration status. Uptake was lower among individuals in the lowest income group (69%), those receiving social benefits (56%), and individuals with two parents born abroad (59%). Our finding that age is the most important determinant for uptake likely reflects the prioritisation of elderly in the programme and the general understanding of their increased vulnerability. However, our findings also reveal important other disparities in vaccine uptake. How to best address this inequity in future vaccination campaigns requires further research.

Effect of COVID-19 vaccination on mortality by COVID-19 and on mortality by other causes, the Netherlands, January 2021-January 2022.

BACKGROUND: We aimed to estimate vaccine effectiveness (VE) against COVID-19 mortality, and to explore whether an increased risk of non-COVID-19 mortality exists in the weeks following a COVID-19 vaccine dose. METHODS: National registries of causes of death, COVID-19 vaccination, specialized health care and long-term care reimbursements were linked by a unique person identifier using data from 1 January 2021 to 31 January 2022. We used Cox regression with calendar time as underlying time scale to, firstly, estimate VE against COVID-19 mortality after primary and first booster vaccination, per month since vaccination and, secondly, estimate risk of non-COVID-19 mortality in the 5 or 8 weeks following a first, second or first booster dose, adjusting for birth year, sex, medical risk group and country of origin. RESULTS: VE against COVID-19 mortality was > 90 % for all age groups two months after completion of the primary series. VE gradually decreased thereafter, to around 80 % at 7-8 months post-primary series for most groups, and around 60 % for elderly receiving a high level of long-term care and for people aged 90+ years. Following a first booster dose, the VE increased to > 85 % in all groups. The risk of non-COVID-19 mortality was lower or similar in the 5 or 8 weeks following a first dose compared to no vaccination, as well as following a second dose compared to one dose and a booster compared to two doses, for all age and long-term care groups. CONCLUSION: At the population level, COVID-19 vaccination greatly reduced the risk of COVID-19 mortality and no increased risk of death from other causes was observed.

Radioembolization-Induced Changes in Hepatic [18F]FDG Metabolism in Non-Tumorous Liver Parenchyma.

Background: [18F]FDG-PET/CT is increasingly used for response assessments after oncologic treatment. The known response criteria for [18F]FDG-PET/CT use healthy liver parenchyma as the reference standard. However, the [18F]FDG liver metabolism results may change as a result of the given therapy. The aim of this study was to assess changes in [18F]FDG liver metabolism after hepatic 90Y resin radioembolization. Methods: [18F]FDG-PET/CT scans prior to radioembolization and one and three months after radioembolization (consistent with the PERCIST comparability criteria), as well as 90Y-PET/CT scans, were analyzed using 3 cm VOIs. The FDG activity concentration and absorbed dose were measured. A linear mixed-effects logistic regression model and logistic mixed-effects model were used to assess the correlation between the FDG-activity concentration, absorbed dose, and biochemical changes. Results: The median SULVOI,liver at baseline was 1.8 (range = 1.2−2.8). The mean change in SULVOI,liver per month with an increase in time was 0.05 (95%CI 0.02−0.09) at p < 0.001. The median absorbed dose per VOI was 31.3 Gy (range = 0.1−82.3 Gy). The mean percent change in ΔSULVOI,liver for every Gy increase in the absorbed dose was −0.04 (95%CI −0.22−0.14) at p = 0.67. The SULblood and SULspleen results showed no increase. Conclusions: The [18F]FDG metabolism in the normal liver parenchyma is significantly but mildly increased after radioembolization, which can interfere with its use as a threshold for therapy response.

Dose-Response and Dose-Toxicity Relationships for Glass 90Y Radioembolization in Patients with Liver Metastases from Colorectal Cancer.

Radioembolization based on personalized treatment planning requires established dose-response and dose-toxicity relationships. The aim of this study was to investigate dose-response and dose-toxicity relationships in patients with colorectal liver metastases (CRLMs) treated with glass 90Y-microspheres. Methods: All CRLM patients treated with glass 90Y-microspheres in our institution were retrospectively analyzed. The tumor-absorbed dose was calculated for each measurable metastasis (i.e.,18F-FDG-positive and more than a 5-cm3 tumor volume) on posttreatment 90Y PET. Metabolic tumor response was determined on 18F-FDG PET/CT by measuring the total lesion glycolysis at baseline and at 3 mo after treatment. The relationship between tumor-absorbed dose and metabolic response was determined on a per-lesion and per-patient basis using a linear mixed-effects regression model. Clinical toxicity and laboratory toxicity were correlated with healthy liver-absorbed dose. Results: Thirty-one patients were included. The median tumor-absorbed dose of 85 measurable metastases was 133 Gy (range, 20-1001 Gy). Per response category, this was 196 Gy for complete response (CR), 177 Gy for partial response (PR), 72 Gy for stable disease, and 95 Gy for progressive disease (PD). A significant dose-response relationship was found on a tumor level, with a significantly higher tumor-absorbed dose in metastases with CR (+94%) and PR (+74%) than in metastases with PD (P < 0.001). A similar relationship was found on a patient level, with PR having a higher tumor-absorbed dose than did PD (+58%, P = 0.044). A tumor-absorbed dose of more than 139 Gy predicted a 3-mo metabolic response with the greatest accuracy (89% specificity and 77% sensitivity), whereas a tumor-absorbed dose of more than 189 Gy predicted response with 97% specificity and 45% sensitivity. The median healthy liver-absorbed dose was 63 Gy (range, 24-113 Gy). Toxicity was limited mostly to grades 1 and 2, with 1 case of radioembolization-induced liver disease in a patient who received the highest healthy liver-absorbed dose. A positive trend was seen for most laboratory parameters in our dose-toxicity analysis. Conclusion: A significant relationship was observed between dose and response in CRLM patients treated with glass 90Y radioembolization.

Dose-Effect Relationships of 166Ho Radioembolization in Colorectal Cancer.

Radioembolization is a treatment option for colorectal cancer (CRC) patients with inoperable, chemorefractory hepatic metastases. Personalized treatment requires established dose thresholds. Hence, the aim of this study was to explore the relationship between dose and effect (i.e., response and toxicity) in CRC patients treated with 166Ho radioembolization. Methods: CRC patients treated in the HEPAR II and SIM studies were analyzed. Absorbed doses were estimated using the activity distribution on posttreatment 166Ho SPECT/CT. Metabolic response was assessed using the change in total-lesion glycolysis on 18F-FDG PET/CT between baseline and 3-mo follow-up. Toxicity between treatment and 3 mo was evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5, and its relationship with parenchyma-absorbed dose was assessed using linear models. The relationship between tumor-absorbed dose and patient- and tumor-level response was analyzed using linear mixed models. Using a threshold of 100% sensitivity for response, the threshold for a minimal mean tumor-absorbed dose was determined and its impact on survival was assessed. Results: Forty patients were included. The median parenchyma-absorbed dose was 37 Gy (range, 12-55 Gy). New CTCAE grade 3 or higher clinical and laboratory toxicity was present in 8 and 7 patients, respectively. For any clinical toxicity (highest grade per patient), the mean difference in parenchymal dose (Gy) per step increase in CTCAE grade category was 5.75 (95% CI, 1.18-10.32). On a patient level, metabolic response was as follows: complete response, n = 1; partial response, n = 11; stable disease, n = 17; and progressive disease, n = 8. The mean tumor-absorbed dose was 84% higher in patients with complete or partial response than in patients with progressive disease (95% CI, 20%-180%). Survival for patients with a mean tumor-absorbed dose of more than 90 Gy was significantly better than for patients with a mean tumor-absorbed dose of less than 90 Gy (hazard ratio, 0.16; 95% CI, 0.06-0.511). Conclusion: A significant dose-response relationship in CRC patients treated with 166Ho radioembolization was established, and a positive association between toxicity and parenchymal dose was found. For future patients, it is advocated to use a 166Ho scout dose to select patients and yo personalize the administered activity, targeting a mean tumor-absorbed dose of more than 90 Gy and a parenchymal dose of less than 55 Gy.

Mode of progression after radioembolization in patients with colorectal cancer liver metastases.

BACKGROUND: Radioembolization is an established treatment modality in colorectal cancer patients with liver-dominant disease in a salvage setting. Selection of patients who will benefit most is of vital importance. The aim of this study was to assess response (and mode of progression) at 3 months after radioembolization and the impact of baseline characteristics. METHODS: Three months after radioembolization with either yttrium-90 resin/glass or holmium-166, anatomic response, according to RECIST 1.1, was evaluated in 90 patients. Correlations between baseline characteristics and efficacy were evaluated. For more detailed analysis of progressive disease as a dismal clinical entity, distinction was made between intra- and extrahepatic progression, and between progression of existing metastases and new metastases. RESULTS: Forty-two patients (47%) had extrahepatic disease (up to five ≥ 1 cm lung nodules, and ≤ 2 cm lymph nodes) at baseline. No patients showed complete response, 5 (5.5%) patients had partial response, 16 (17.8%) had stable disease, and 69 (76.7%) had progressive disease. Most progressive patients (67/69; 97%) had new metastases (intra-hepatic N = 11, extrahepatic N = 32; or both N = 24). Significantly fewer patients had progressive disease in the group of patients presenting without extrahepatic metastases at baseline (63% versus 93%; p = 0.0016). Median overall survival in patients with extrahepatic disease was 6.5 months, versus 10 months in patients without extrahepatic disease at baseline (hazard ratio 1.79, 95%CI 1.24-2.57). CONCLUSIONS: Response at 3-month follow-up and survival were heavily influenced by new metastases. Patients with extrahepatic disease at baseline had a worse outcome compared to patients without.

The Efficacy of Coil Embolization to Obtain Intrahepatic Redistribution in Radioembolization: Qualitative and Quantitative Analyses.

PURPOSE: To evaluate the efficacy of coil embolization to obtain intrahepatic redistribution in patients undergoing radioembolization. MATERIALS AND METHOD: All patients treated with radioembolization at our institute were retrospectively analyzed, and all cases in which a tumor-feeding vessel was coil-embolized were selected. Two nuclear medicine physicians visually assessed the effect of redistribution. Furthermore, the redistribution of microspheres was measured by quantifying the activity distributed to the coil-embolized (dependent) segment relative to the other (non-dependent) segments and to the tumor(s) in that segment. Quantitative analysis was performed on post-treatment 90Y-PET and 166Ho-SPECT using Simplicit90Y software. Lesion response was measured according to RECIST 1.1 criteria at 3 months post-treatment. RESULTS: Out of 37 cases, 32 were suitable for quantitative analysis and 37 for qualitative analysis. In the qualitative analysis, redistribution was deemed successful in 69% of cases. The quantitative analysis showed that the median ratio of the activity to the dependent embolized segments and the non-dependent segments was 0.88 (range 0.26-2.05) and 0.80 (range 0.19-1.62) for tumors in dependent segments compared with tumors in non-dependent segments. Using a cutoff ratio of 0.7 (30% lower activity concentration in comparison with the rest of the liver), 57% of cases were successful. At 3 months post-treatment, 6% of dependent tumors had partial response, 20% progressive disease, and 74% stable disease. In non-dependent tumors, this was, respectively, 16%, 20%, and 64%. CONCLUSION: Coil embolization of hepatic arteries to induce redistribution of microspheres has a limited success rate. Qualitative assessment tends to overrate redistribution.

Quality of life in patients with liver tumors treated with holmium-166 radioembolization.

Holmium-166 radioembolization is a palliative treatment option for patients with unresectable hepatic malignancies. Its influence on quality of life has not been evaluated yet. Since quality of life is very important in the final stages of disease, the aim of this study was to evaluate the effect of holmium-166 radioembolization on quality of life. Patients with hepatic malignancies were treated with holmium-166 radioembolization in the HEPAR I and II studies. The European Organization for Research and Treatment of Cancer QLQ-C30 and LMC21 questionnaires were used to evaluate quality of life at baseline, 1 week, 6 weeks and at 6, 9 and 12 months after treatment. The course of the global health status and symptom and functioning scales were analyzed using a linear mixed model. Quality of life was studied in a total of 53 patients with a compliance of 94%. Role functioning was the most affected functioning scale. Fatigue and pain were the most affected symptom scales. Changes in almost all categories were most notable at 1 week after treatment. A higher WHO performance score at baseline decreased global health status, physical functioning, role functioning and social functioning and it increased symptoms of fatigue, dyspnea and diarrhea. Quality of life in salvage patients with liver metastases treated with holmium-166 radioembolization was not significantly affected over time, although a striking decline was seen during the first week post-treatment. A WHO performance score > 0 at baseline significantly influenced quality of life.

First Evidence for a Dose-Response Relationship in Patients Treated with 166Ho Radioembolization: A Prospective Study.

166Ho-microspheres have recently been approved for clinical use for hepatic radioembolization in the European Union. The aim of this study was to investigate the absorbed dose-response relationship and its association with overall survival for 166Ho radioembolization in patients with liver metastases. Methods: Patients treated in the HEPAR I and II studies who underwent an 18F-FDG PET/CT scan at baseline, a posttreatment 166Ho SPECT/CT scan, and another 18F-FDG PET/CT scan at the 3-mo follow-up were included for analysis. The posttreatment 166Ho-microsphere activity distributions were estimated with quantitative SPECT/CT reconstructions using a quantitative Monte Carlo-based method. The response of each tumor was based on the change in total lesion glycolysis (TLG) between baseline and follow-up and was placed into 1 of 4 categories, according to the PERCIST criteria, ranging from complete response to progressive disease. Patient-level response was grouped according to the average change in TLG per patient. The absorbed dose-response relationship was assessed using a linear mixed model to account for correlation of tumors within patients. Median overall survival was compared between patients with and without a metabolic liver response, using a log-rank test. Results: Thirty-six patients with a total of 98 tumors were included. The relation between tumor-absorbed dose and both tumor-level and patient-level response was explored. At a tumor level, a significant difference in geometric mean absorbed dose was found between complete response (232 Gy; 95% confidence interval [CI], 178-303 Gy; n = 32) and stable disease (147 Gy; 95% CI, 113-191 Gy; n = 28) (P = 0.01) and between complete response and progressive disease (117 Gy; 95% CI, 87-159 Gy; n = 21) (P = 0.0008). This constitutes a robust absorbed dose-response relationship. At a patient level, a significant difference was found between patients with complete or partial response (210 Gy; 95% CI, 161-274 Gy; n = 13) and patients with progressive disease (116 Gy; 95% CI, 81-165 Gy; n = 9) (P = 0.01). Patients were subsequently grouped according to their average change in TLG. Patients with an objective response (complete or partial) exhibited a significantly higher overall survival than nonresponding patients (stable or progressive disease) (median, 19 mo vs. 7.5 mo; log-rank, P = 0.01). Conclusion: These results confirm a significant absorbed dose-response relationship in 166Ho radioembolization. Treatment response is associated with a higher overall survival.

Holmium-166 Microsphere Radioembolization of Hepatic Malignancies.

Holmium microspheres have recently become available in the European market as the third type of microspheres for radioembolization of unresectable liver malignancies. Holmium microspheres come with a dedicated administration system, and since these microspheres contain holmium-166 (166Ho) instead of yttrium-90, unique dosing and imaging possibilities have become available as well. In addition, a scout dose of 166Ho microspheres (Conformité Européenne mark is now granted and not pending anymore) can be used instead of 99mTc-macroaggragated albumin during the preparatory angiography procedure. So far, two prospective phase I and phase II clinical studies have been performed on 166Ho radioembolization in a population of liver metastases from mixed origins. These studies showed that a mean whole-liver dose of 60 Gy is safe and induces tumor response. Ongoing trials investigate the effect of 166Ho radioembolization in patients with neuroendocrine tumor metastases, hepatocellular carcinoma, and colorectal cancer metastases. Data derived from these studies will be used to refine the dosing schedule of 60 Gy to the whole liver and determine the optimal level of activity for each patient. This paper discusses several basics and provides an overview of relevant dosing aspects, technical aspects of performing holmium radioembolization, as well as a summary of completed and ongoing clinical studies and the upcoming developments regarding these microspheres.

Hepatobiliary Imaging in Liver-directed Treatments.

Hepatobiliary scintigraphy (HBS) is an emerging tool in the assessment of hepatic function. This nuclear imaging technique can be used to calculate both global and regional liver function. It has proven to be the most reliable way of assessing the distribution of liver function, especially in patients with impaired liver function due to, for example, cirrhosis or after chemotherapy. There are two types of tracers: Technetium-99m with a type of iminodiacetic acid and Technetium-99m galactosyl human serum albumin. The main indication for HBS is the assessment of the future liver remnant function in patients scheduled to undergo hemihepatectomy; to predict the risk of posthepatectomy liver failure. Another upcoming indication is the use of HBS in patients undergoing radioembolization.

What are the odds? Prostate metastases to ureter and peritoneum.

In patients with prostate cancer, metastases mostly develop in bone, lung, liver, pleura and adrenal glands. Prostate carcinoma metastases to the ureter are very rare, and the peritoneum is an even rarer site of prostate metastases. We present two cases of ureteral metastases of prostate cancer, of which one patient also developed malignant ascites and peritoneal metastases. An overview of the literature on these metastatic sites is also provided. Both patients presented with hydronephrosis and a ureteral mass. Biopsies of the masses were taken, which showed the presence of prostate carcinoma metastases. The first patient was treated with chemotherapy but was diagnosed with progressive disease and died 3 years later. The second patient was diagnosed with pathology-confirmed peritoneal metastases 8 months later. He died 2 years after presentation with hydronephrosis.