title: Boosted selective internal radiation therapy with 90Y-loaded glass microspheres (B-SIRT) for hepatocellular carcinoma patients: a new personalized promising concept.
abstract: OBJECTIVE
  To evaluate the impact of dosimetry based on MAA SPECT/CT for the prediction of response, toxicity and survival, and for treatment planning in patients with hepatocellular carcinoma (HCC) treated with (90)Y-loaded glass microspheres (TheraSphere®).
  
  
  METHODS
  TheraSphere® was administered to 71 patients with inoperable HCC. MAA SPECT/CT quantitative analysis was used for the calculation of the tumour dose (TD), healthy injected liver dose (HILD), and total injected liver dose. Response was evaluated at 3 months using EASL criteria. Time to progression (TTP) and overall survival (OS) were evaluated using the Kaplan-Meier method. Factors potentially associated with liver toxicity were combined to construct a liver toxicity score (LTS).
  
  
  RESULTS
  The response rate was 78.8%. Median TD were 342 Gy for responding lesions and 191 Gy for nonresponding lesions (p < 0.001). With a threshold TD of 205 Gy, MAA SPECT/CT predicted response with a sensitivity of 100% and overall accuracy of 90%. Based on TD and HILD, 17 patients underwent treatment intensification resulting in a good response rate (76.4%), without increased grade III liver toxicity. The median TTP and OS were 5.5 months (2-9.5 months) and 11.5 months (2-31 months), respectively, in patients with TD <205 Gy and 13 months (10-16 months) and 23.2 months (17.5-28.5 months), respectively, in those with TD >205 Gy (p = 0.0015 and not significant). Among patients with portal vein thrombosis (PVT) (n = 33), the median TTP and OS were 4.5 months (2-7 months) and 5 months (2-8 months), respectively, in patients with TD <205 Gy and 10 months (6-15.2 months) and 21.5 months (12-28.5 months), respectively, in those with TD >205 Gy (p = 0.039 and 0.005). The median OS was 24.5 months (18-28.5 months) in PVT patients with TD >205 Gy and good PVT targeting on MAA SPECT/CT. The LTS was able to detect severe liver toxicity (n = 6) with a sensitivity of 83% and overall accuracy of 97%.
  
  
  CONCLUSIONS
  Dosimetry based on MAA SPECT/CT was able to accurately predict response and survival in patients treated with glass microspheres. This method can be used to adapt the injected activity without increasing liver toxicity, thus defining a new concept of boosted selective internal radiation therapy (B-SIRT). This new concept and LTS enable fully personalized treatment planning with glass microspheres to be achieved.
authors.affiliation: Department of Nuclear Medicine, CS 44229, Comprehensive Cancer Center, Institute Eugène Marquis, F-35042 Rennes, France. e.garin@rennes.unicancer.fr
authors.forename: E
authors.initials: E
authors.lastname: Garin
authors.forename: L
authors.initials: L
authors.lastname: Lenoir
authors.forename: J
authors.initials: J
authors.lastname: Edeline
authors.forename: S
authors.initials: S
authors.lastname: Laffont
authors.forename: H
authors.initials: H
authors.lastname: Mesbah
authors.forename: P
authors.initials: P
authors.lastname: Porée
authors.forename: L
authors.initials: L
authors.lastname: Sulpice
authors.forename: K
authors.initials: K
authors.lastname: Boudjema
authors.forename: M
authors.initials: M
authors.lastname: Mesbah
authors.forename: A
authors.initials: A
authors.lastname: Guillygomarc'h
authors.forename: E
authors.initials: E
authors.lastname: Quehen
authors.forename: M
authors.initials: M
authors.lastname: Pracht
authors.forename: J L
authors.initials: JL
authors.lastname: Raoul
authors.forename: B
authors.initials: B
authors.lastname: Clement
authors.forename: Y
authors.initials: Y
authors.lastname: Rolland
authors.forename: E
authors.initials: E
authors.lastname: Boucher
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging / Q000532:radiotherapy*; D005260:Female; D005898:Glass / Q000737:chemistry*; D006801:Humans; D008099:Liver / Q000528:radiation effects; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy*; D008297:Male; D008863:Microspheres; D008875:Middle Aged; D057285:Precision Medicine / Q000379:methods*; D011874:Radiometry; D011880:Radiotherapy Planning, Computer-Assisted; D012189:Retrospective Studies; D012449:Safety; D016019:Survival Analysis; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D015021:Yttrium Radioisotopes / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D015021:Yttrium Radioisotopes