RT Journal Article SR Electronic T1 Safety and efficacy of holmium-166 radioembolization in hepatocellular carcinoma – the HEPAR Primary study JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP jnumed.122.263823 DO 10.2967/jnumed.122.263823 A1 Margot Thea Maria Reinders A1 Karel J. van Erpecum A1 Maarten L. J. Smits A1 Arthur Johannes Anthonius Theodorus Braat A1 Joep de Bruijne A1 Rutger C.G. Bruijnen A1 Dave Sprengers A1 Robert A. de Man A1 Erik Vegt A1 Jan N.M. IJzermans A1 Adriaan Moelker A1 Marnix Lam YR 2022 UL http://jnm.snmjournals.org/content/early/2022/05/19/jnumed.122.263823.abstract AB Hepatocellular carcinoma (HCC) is the sixth most common cancer and second in cancer-related deaths. Radioembolization using holmium-166 (166Ho)-microspheres is new in the HCC treatment landscape. Safety and efficacy of 166Ho-radioembolization was first determined in the HEPAR and HEPAR II studies, however excluding patients with 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, BCLC stage B-C, Child-Pugh (CP) score ≤B7, ECOG 0-1 without curative treatment options. Methods: Patients received 166Ho scout and therapeutic dose between Jan 2018 and Feb 2020. The primary endpoint was rate of unacceptable toxicity defined as grade 3 hyperbilirubinemia (Common Terminology Cancer Adverse Events version 4.03) in combination with low albumin and/or ascites in the absence of disease progression or treatment-related serious adverse events (SAEs). Secondary endpoints included overall toxicity, response according to RECIST 1.1 and mRECIST, survival, change in α-fetoprotein (AFP), and quality of life based on European Organization for Research and Treatment of Cancer (EORTC) C30 and HCC18 questionnaires as well as Brief Pain Inventory – Short Forms (BPI). Results: Thirty-one patients with BCLC stage B (71%) or C (29%) HCC were included, mostly multifocal disease. Median diameter of the largest tumor was 56 mm (range 15-195 mm). Treatment-related unacceptable toxicity occurred in three patients with four SAEs: two cases of spontaneous bacterial peritonitis with ascites and one case of cholecystitis with subsequent biliary fistula. Other adverse events included fatigue (71%), back pain (55%), ascites (32%), dyspnea (23%), nausea (23%), and abdominal pain (23%), mostly grade 1. Median CP score at baseline was A5 and worsened to B7 (range A5-B9) at three months follow-up, and A6 (range A5-B9) six months after treatment. At three and six months respectively, 54% and 84% of target lesions showed complete or partial response according to mRECIST. Median overall survival was 14.9 months (95% CI 10.4 months-24.9 months). No significant changes in quality of life or pain were observed. Conclusion: 166Ho-radioembolization is a treatment option with toxicity within the pre-defined limits for a selected group of patients with HCC. Response data support further evaluation.