title: A hepatic dose-toxicity model opening the way toward individualized radioembolization planning.
abstract: The 50% normal-tissue complication probability (NTCP) after lobar irradiation of the liver results in highly variable biologic effective doses depending on the modality used: a biologic effective dose for 50% (BED50) of 115, 93, and 250 Gy for external-beam radiotherapy, resin microsphere radioembolization, and glass microsphere radioembolization, respectively. This misunderstood property has made it difficult to predict the maximal tolerable dose as a function of microsphere activity and targeted liver volume. The evolution toward more selective catheterization techniques, resulting in more variable targeted volumes, makes it urgent to solve this issue.
  
  
  METHODS
  We computed by Monte Carlo simulations the microsphere distribution in the portal triads based on microsphere transport dynamics through a synthetically grown hepatic arterial tree. Afterward, the microscale dose distribution was computed using a dose deposition kernel. We showed that the equivalent uniform dose cannot handle microscale dosimetry and fails to solve the discordance between the BED50 values. Consequently, we developed a new radiobiologic model to compute the liver NTCP from the microscale dose distribution.
  
  
  RESULTS
  The new model explains all the observed BED50 values and provides a way to compute the hepatic dose-toxicity relationship as a function of microsphere activity and targeted liver volume. The NTCP obtained is in agreement with the data reported from clinical radioembolization studies.
  
  
  CONCLUSIONS
  The results should encourage interventional radiologists to fine-tune the delivered dose to the liver as a function of the targeted volume. The present model could be used as the backbone of the treatment planning, allowing optimization of the absorbed dose to the tumors.
authors.affiliation: Nuclear Medicine, Molecular Imaging, Radiotherapy, and Oncology Unit (MIRO), IECR, Université Catholique de Louvain, Brussels, Belgium stephan.walrand@uclouvain.be.
authors.forename: Stephan
authors.initials: S
authors.lastname: Walrand
authors.affiliation: Nuclear Medicine, Molecular Imaging, Radiotherapy, and Oncology Unit (MIRO), IECR, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Michel
authors.initials: M
authors.lastname: Hesse
authors.affiliation: Nuclear Medicine, Molecular Imaging, Radiotherapy, and Oncology Unit (MIRO), IECR, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Francois
authors.initials: F
authors.lastname: Jamar
authors.affiliation: Nuclear Medicine, Molecular Imaging, Radiotherapy, and Oncology Unit (MIRO), IECR, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Renaud
authors.initials: R
authors.lastname: Lhommel
mesh_terms: D004621:Embolization, Therapeutic / Q000009:adverse effects*; D008099:Liver / Q000000981:diagnostic imaging / Q000528:radiation effects*; D008954:Models, Biological; D009010:Monte Carlo Method; D058958:Organs at Risk / Q000528:radiation effects*; D049268:Positron-Emission Tomography; D057285:Precision Medicine; D011336:Probability; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods
keywords: Monte Carlo; PET; dosimetry; normal tissue complication probability; radioembolization