title: Personalized dosimetry with intensification using 90Y-loaded glass microsphere radioembolization induces prolonged overall survival in hepatocellular carcinoma patients with portal vein thrombosis.
abstract: The objective of this study was to evaluate the response rate and survival of hepatocellular carcinoma portal vein thrombosis (PVT) patients treated with (90)Y-loaded glass microspheres using a personalized dosimetry and intensification concept.
  
  
  METHODS
  The microspheres were administered to 41 hepatocellular carcinoma PVT patients (main = 12; lobar/segmental = 29). (99m)Tc-macroaggregated albumin SPECT/CT quantitative analysis was used to calculate the tumor dose (TD), healthy injected liver dose (HILD), and injected liver dose (ILD). Response was evaluated at 3 mo using the criteria of the European Association for the Study of the Liver, with CT follow-up lasting until disease progression or death. Survival was assessed using the Kaplan-Meier method.
  
  
  RESULTS
  The mean injected activity was 3.1 ± 1.5 GBq, and mean ILD was 143 ± 49 Gy. When a TD threshold of 205 Gy was applied, (99m)Tc-macroaggregated albumin SPECT/CT achieved a 100% sensitivity and 90% overall accuracy (0 false-negatives; 4 false-positives) in response prediction. On the basis of TD and HILD values, 37% of patients received an intensification of the treatment (increased injected activity with the aim of achieving a TD ≥ 205 Gy and HILD < 120 Gy, applying an ILD > 150 Gy). This intensification resulted in a high response rate (85%) without increased liver toxicity of grade 3 or higher (6% vs. 12% in the patients who did not receive treatment intensification; not statistically significant). For the total 41 patients, median overall survival (OS) was 18 mo (95% confidence interval, 11-25 mo). For patients with a TD of less than 205 Gy, median OS was 4.3 mo (3.7-5 mo), versus 18.2 mo (8.5-28.7 mo) for those with a TD of 205 Gy or more (P = 0.005). Median OS was 20.9 mo for patients with a TD of 205 Gy or more and good PVT targeting (n = 36). OS was 12 mo (3 mo to ∞) for patients with main PVT, versus 21.5 mo (12-28.7 mo) for those with segmental or lobar PVT (not statistically significant). For the 5 patients with complete portal vein revascularization who underwent lobar hepatectomy, median OS was not reached yet exceeded 24.5 mo and was significantly higher than that of other patients (P = 0.0493).
  
  
  CONCLUSIONS
  Using a (99m)Tc-macroaggregated albumin SPECT/CT personalized dosimetry and intensification concept with (90)Y-loaded glass microspheres induced prolonged OS for PVT patients as compared with the standard of care (sorafenib), without increasing liver toxicity. Prospective randomized studies are therefore warranted.
authors: Department of Nuclear Medicine, Cancer Institute Eugène Marquis, Rennes, France University of Rennes 1, Rennes, France U-991, Liver Metabolism and Cancer, INSERM, Rennes, France e.garin@rennes.unicancer.fr.
authors: Etienne
authors: E
authors: Garin
authors: Department of Medical Imaging, Cancer Institute Eugène Marquis, Rennes, France.
authors: Yan
authors: Y
authors: Rolland
authors: University of Rennes 1, Rennes, France U-991, Liver Metabolism and Cancer, INSERM, Rennes, France Cancer Institute Eugène Marquis, Department of Medical Oncology, Rennes, France.
authors: Julien
authors: J
authors: Edeline
authors: Department of Nuclear Medicine, Cancer Institute Eugène Marquis, Rennes, France.
authors: Nicolas
authors: N
authors: Icard
authors: Department of Nuclear Medicine, Cancer Institute Eugène Marquis, Rennes, France University of Rennes 1, Rennes, France U-991, Liver Metabolism and Cancer, INSERM, Rennes, France.
authors: Laurence
authors: L
authors: Lenoir
authors: Department of Nuclear Medicine, Cancer Institute Eugène Marquis, Rennes, France U-991, Liver Metabolism and Cancer, INSERM, Rennes, France.
authors: Sophie
authors: S
authors: Laffont
authors: Cancer Institute Eugène Marquis, Department of Medical IT Technology, Rennes, France.
authors: Habiba
authors: H
authors: Mesbah
authors: Cancer Institute Eugène Marquis, Department of Medical IT Technology, Rennes, France.
authors: Mathias
authors: M
authors: Breton
authors: U-991, Liver Metabolism and Cancer, INSERM, Rennes, France Department of Digestive Surgery, Centre Hospitalier et Universitaire Pontchaillou, Rennes, France; and.
authors: Laurent
authors: L
authors: Sulpice
authors: University of Rennes 1, Rennes, France U-991, Liver Metabolism and Cancer, INSERM, Rennes, France Department of Digestive Surgery, Centre Hospitalier et Universitaire Pontchaillou, Rennes, France; and.
authors: Karim
authors: K
authors: Boudjema
authors: Department of Medical Imaging, Cancer Institute Eugène Marquis, Rennes, France.
authors: Tanguy
authors: T
authors: Rohou
authors: Department of Medical Oncology, Cancer Institute Paoli Calmette, Marseille, France.
authors: Jean-Luc
authors: JL
authors: Raoul
authors: U-991, Liver Metabolism and Cancer, INSERM, Rennes, France.
authors: Bruno
authors: B
authors: Clement
authors: Department of Nuclear Medicine, Cancer Institute Eugène Marquis, Rennes, France U-991, Liver Metabolism and Cancer, INSERM, Rennes, France Department of Medical Imaging, Cancer Institute Eugène Marquis, Rennes, France.
authors: Eveline
authors: E
authors: Boucher
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging* / Q000401:mortality; D004621:Embolization, Therapeutic / Q000379:methods*; D005060:Europe; D005189:False Positive Reactions; D005260:Female; D005898:Glass; D006801:Humans; D053208:Kaplan-Meier Estimate; D008099:Liver / Q000187:drug effects; D008113:Liver Neoplasms / Q000000981:diagnostic imaging* / Q000401:mortality; D008297:Male; D008863:Microspheres; D008875:Middle Aged; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives; D010671:Phenylurea Compounds / Q000008:administration & dosage; D011169:Portal Vein / Q000473:pathology*; D011874:Radiometry / Q000379:methods*; D012189:Retrospective Studies; D000077157:Sorafenib; D013927:Thrombosis / Q000628:therapy*; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D015021:Yttrium Radioisotopes / Q000494:pharmacology*
chemical_list: D010671:Phenylurea Compounds; D015021:Yttrium Radioisotopes; D009536:Niacinamide; D000077157:Sorafenib
keywords: MAA dosimetry; hepatocellular carcinoma; personalization; radioembolization