ORIGINAL ARTICLE Radioembolization of hepatocarcinoma with 90 Y glass microspheres: treatment optimization using the dose-toxicity relationship C. Chiesa 1 & M. Mira 1 & S. Bhoori 2 & G. Bormolini 2 & M. Maccauro 1 & C. Spreafico 3 & T. Cascella 3 & A. Cavallo 4 & M. C. De Nile 5 & S. Mazzaglia 1 & A. Capozza 6 & G. Tagliabue 7 & A. Brusa 8 & A. Marchianò 3 & E. Seregni 1 & V. Mazzaferro 2 Received: 1 December 2019 /Accepted: 28 April 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020 Abstract Aim Transarterial radioembolization (TARE) is, by all standards, a radiation therapy. As such, according to Euratom Directive 2013/59, it should be optimized by a thorough treatment plan based on the distinct evaluation of absorbed dose to the lesions and to the non-tumoural liver (two-compartment dosimetry). Since the dosimetric prediction with 99m Tc albumin macro-aggregates (MAA) of non-tumoural liver is much more accurate than the same prediction on lesions, treatment planning should focus on non-tumoural liver rather than on lesion dosimetry. The aim of this study was to determine a safety limit through the analysis of pre-treatment dosimetry with 99m Tc-MAA single photon emission computed tomography (SPECT/CT), in order to deliver the maximum tolerable absorbed dose to non-tumoural liver. Methods Data from intermediate/advanced hepato-cellular carcinoma (HCC) patients treated with 90 Y glass microspheres were collected in this single-arm retrospective study. Injection was always lobar, even in case of bilobar disease, to avoid treating the whole liver in a single session. A three-level definition of liver decompensation (LD) was introduced, considering toxicity only in cases of liver decompensation requiring medical action (LD type C, LDC). We report LDC rates, receiver operating characteristic (ROC) analysis between LDC and NO LDC absorbed dose distributions, normal tissue complication probability (NTCP) curves and uni- and multivariate analysis of risk factors associated with toxicity. Results A 6-month timeline was defined as necessary to capture all treatment-related toxicity events. Previous transarterial chemoembolization (TACE), presence or extension of portal vein tumoural thrombosis (PVTT) and tumour pattern (nodular versus infiltrative) were not associated with tolerance to TARE. On the contrary, at the multivariate analysis, the absorbed dose averaged over the whole non-tumoural liver (including the non-injected lobe) was a prognostic indicator correlated with liver decompensation (odds ratio = 4.24). Basal bilirubin > 1.1 mg/dL was a second even more significant risk factor (odds ratio = C. Chiesa and M. Mira contributed equally to this work. The medical physicist Marta Mira was temporarily supported for the present Investigator Initiated Study with a research grant received from BTG Biocompatibles L.t.d. This article is part of the Topical Collection on Dosimetry. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00259-020-04845-4) contains supplementary material, which is available to authorized users. * C. Chiesa carlo.chiesa@istitutotumori.mi.it 1 Nuclear Medicine, Foundation IRCCS Istituto Nazionale Tumori, via G. Venezian 1, Milan, Italy 2 HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy 3 Interventional Radiology, Foundation IRCCS Istituto Nazionale Tumori, Milan, Italy 4 Medical Physics Unit, Foundation IRCCS Istituto Nazionale Tumori, Milan, Italy 5 Postgraduate Specialization School in Medical Physics, University of Milan, Milan, Italy 6 Postgraduate Specialization School in Nuclear Medicine, University of Milan, Milan, Italy 7 Tumour Registry, Foundation IRCCS Istituto Nazionale Tumori, Milan, Italy 8 Radiation Protection Unit, Foundation IRCCS Istituto Nazionale Tumori, Milan, Italy European Journal of Nuclear Medicine and Molecular Imaging https://doi.org/10.1007/s00259-020-04845-4