Safety and Efficacy of 166Ho Radioembolization in Hepatocellular Carcinoma: The HEPAR Primary Study.

The safety and efficacy of 166Ho radioembolization was first determined in the HEPAR and HEPAR II studies, which, however, excluded patients with hepatocellular carcinoma (HCC). The aim of this prospective clinical early phase II study was to establish the toxicity profile of 166Ho radioembolization in patients with measurable, liver-dominant HCC; Barcelona clinic liver cancer stage B or C; a Child-Pugh score of no more than B7; and an Eastern Cooperative Oncology Group performance status of 0-1 without curative treatment options. Methods: The primary endpoint was a rate of unacceptable toxicity defined as grade 3 hyperbilirubinemia (Common Terminology Cancer Adverse Events, version 4.03) in combination with a low albumin or ascites level in the absence of disease progression or treatment-related serious adverse events. Secondary endpoints included overall toxicity, response, survival, change in α-fetoprotein, and quality of life. Thirty-one patients with Barcelona clinic liver cancer stage B (71%) or C (29%) HCC were included, mostly multifocal (87%) or bilobar (55%) disease. Results: Common grade 1 or 2 clinical toxicity included fatigue (71%), back pain (55%), ascites (32%), dyspnea (23%), nausea (23%), and abdominal pain (23%), with no more than 10% grade 3-5 toxicity. Grade 3 laboratory toxicity (>10%) included an aspartate transaminase and γ-glutamyltransferase increase (16%), hyperglycemia (19%), and lymphopenia (29%). Treatment-related unacceptable toxicity occurred in 3 of 31 patients. At 3 mo, 54% of target lesions showed a complete or partial response according to modified RECIST. Median overall survival was 14.9 mo (95% CI, 10.4-24.9 mo). No significant changes in quality of life or pain were observed. Conclusion: The safety of 166Ho radioembolization was confirmed in HCC, with less than 10% unacceptable toxicity. Efficacy data support further evaluation.

Trends in incidence, diagnosis, treatment and survival of hepatocellular carcinoma in a low-incidence country: Data from the Netherlands in the period 2009-2016.

OBJECTIVE: Evaluation of the trends in incidence, diagnostics, treatment and survival of patients with hepatocellular carcinoma (HCC) in the Netherlands. METHOD: Data regarding incidence, diagnostics, primary treatment and survival of patients with HCC in the period 2009-2016 were obtained from the Netherlands Cancer Registry. Trends in incidence, diagnostics, various treatment modalities (except liver transplantation, due to inaccurate data) and regional treatment preferences were analysed. Survival was evaluated using Kaplan-Meier curves and multivariable Cox proportional hazard regression modelling. RESULTS: In the period of 2009-2016, 3838 patients were diagnosed with HCC. A distinct decrease in the percentage of patients who underwent tumour biopsy was observed (from 51% in 2009-2010 to 42% in 2015-2016). Percentage of patients who underwent cancer treatment increased markedly (from 49% in 2009-2010 to 57% in 2015-2016), mainly because of an increasing use of resection and ablation. The number of hospitals where resections were performed or sorafenib treatment prescribed decreased slightly. The number of hospitals sporadically (<1 ablation per year) performing ablations increased. There were significant differences between regions in the application of resection, ablation and transarterial chemoembolisation /radioembolisation (p < 0.05 after 'case mix'-correction). One-, 3- and 5-year survival of patients with HCC significantly improved in the studied period. Receiving cancer treatment was associated with increased survival, whereas increasing age and an advanced tumour stage were both associated with decreased survival. CONCLUSION: From 2009 to 2016, patients with hepatocellular carcinoma more often received cancer treatment and their survival improved. There were significant differences in types of treatment between various regions.

[Radiologically inserted gastrostomy]. / Radiologische plaatsing van percutane voedingssondes.

Radiologically inserted gastrostomy (RIG) is an alternative to percutaneous endoscopic gastrostomy (PEG) for patients with eating difficulties who need long-term enteral nutrition. This articles provides an overview of the technique of RIG as well as an analysis of the results of RIG at our institute over the last five years and a discussion of the literature. The number of centres in the Netherlands offering RIG is growing and therefore we want to raise awareness amongst colleagues who are not familiar with this alternative to PEG.

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.

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.

Radioembolisation in Europe: A Survey Amongst CIRSE Members.

INTRODUCTION: Radioembolisation of liver tumours demands many choices from the physician regarding planning of treatment and subsequent follow-up. METHODS: An online questionnaire was distributed amongst all members of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) to investigate the current state of radioembolisation practice. RESULTS: The survey was completed by 60 centres. The increasing number of radioembolisation procedures may reflect that radioembolisation is increasingly recognised as a valuable treatment option in European cancer guidelines. Imaging modalities play an important role in decision making. Furthermore, there seems to be a trend towards less coil-embolisation of non-target vessels. In addition, type of microsphere, model for dose calculation, complications and future developments are evaluated in this article. CONCLUSIONS: This survey provides insight into the current state of radioembolisation practice across Europe.

mTOR plays an important role in cow's milk allergy-associated behavioral and immunological deficits.

Autism spectrum disorder (ASD) is multifactorial, with both genetic as well as environmental factors working in concert to develop the autistic phenotype. Immunological disturbances in autistic individuals have been reported and a role for food allergy has been suggested in ASD. Single gene mutations in mammalian target of rapamycin (mTOR) signaling pathway are associated with the development of ASD and enhanced mTOR signaling plays a central role in directing immune responses towards allergy as well. Therefore, the mTOR pathway may be a pivotal link between the immune disturbances and behavioral deficits observed in ASD. In this study it was investigated whether the mTOR pathway plays a role in food allergy-induced behavioral and immunological deficits. Mice were orally sensitized and challenged with whey protein. Meanwhile, cow's milk allergic (CMA) mice received daily treatment of rapamycin. The validity of the CMA model was confirmed by showing increased allergic immune responses. CMA mice showed reduced social interaction and increased repetitive self-grooming behavior. Enhanced mTORC1 activity was found in the brain and ileum of CMA mice. Inhibition of mTORC1 activity by rapamycin improved the behavioral and immunological deficits of CMA mice. This effect was associated with increase of Treg associated transcription factors in the ileum of CMA mice. These findings indicate that mTOR activation may be central to both the intestinal, immunological, and psychiatric ASD-like symptoms seen in CMA mice. It remains to be investigated whether mTOR can be seen as a therapeutic target in cow's milk allergic children suffering from ASD-like symptoms.