title: Estimating functional liver reserve following hepatic irradiation: adaptive normal tissue response models.
abstract: OBJECTIVE
  To estimate the limit of functional liver reserve for safe application of hepatic irradiation using changes in indocyanine green, an established assay of liver function.
  
  
  METHODS
  From 2005 to 2011, 60 patients undergoing hepatic irradiation were enrolled in a prospective study assessing the plasma retention fraction of indocyanine green at 15-min (ICG-R15) prior to, during (at 60% of planned dose), and after radiotherapy (RT). The limit of functional liver reserve was estimated from the damage fraction of functional liver (DFL) post-RT [1-(ICG-R15pre-RT/ICG-R15post-RT)] where no toxicity was observed using a beta distribution function.
  
  
  RESULTS
  Of 48 evaluable patients, 3 (6%) developed RILD, all within 2.5 months of completing RT. The mean ICG-R15 for non-RILD patients pre-RT, during-RT and 1-month post-RT was 20.3%(SE 2.6), 22.0%(3.0), and 27.5%(2.8), and for RILD patients was 6.3%(4.3), 10.8%(2.7), and 47.6%(8.8). RILD was observed at post-RT damage fractions of ≥78%. Both DFL assessed by during-RT ICG and MLD predicted for DFL post-RT (p<0.0001). Limiting the post-RT DFL to 50%, predicted a 99% probability of a true complication rate <15%.
  
  
  CONCLUSIONS
  The DFL as assessed by changes in ICG during treatment serves as an early indicator of a patient's tolerance to hepatic irradiation.
authors.affiliation: Department of Radiation Oncology, University of Michigan Health System, Ann Arbor, United States; Veterans Affairs Medical Center, Ann Arbor, United States. Electronic address: stenmark@umich.edu.
authors.forename: Matthew H
authors.initials: MH
authors.lastname: Stenmark
authors.affiliation: Department of Radiation Oncology, University of Michigan Health System, Ann Arbor, United States; Department of Radiology, University of Michigan Health System, Ann Arbor, United States; Department of Biomedical Engineering, University of Michigan Health System, Ann Arbor, United States.
authors.forename: Yue
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Radiation Oncology, University of Michigan Health System, Ann Arbor, United States.
authors.forename: Hesheng
authors.initials: H
authors.lastname: Wang
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, United States.
authors.forename: Andrew
authors.initials: A
authors.lastname: Jackson
authors.affiliation: University of Pennsylvania, Philadelphia, United States.
authors.forename: Edgar
authors.initials: E
authors.lastname: Ben-Josef
authors.affiliation: Department of Radiation Oncology, University of Michigan Health System, Ann Arbor, United States.
authors.forename: Randall K
authors.initials: RK
authors.lastname: Ten Haken
authors.affiliation: Department of Radiation Oncology, University of Michigan Health System, Ann Arbor, United States.
authors.forename: Theodore S
authors.initials: TS
authors.lastname: Lawrence
authors.affiliation: Department of Radiation Oncology, University of Michigan Health System, Ann Arbor, United States.
authors.forename: Mary
authors.initials: M
authors.lastname: Feng
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000503:physiopathology* / Q000532:radiotherapy*; D004396:Coloring Agents / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007208:Indocyanine Green / Q000493:pharmacokinetics; D008099:Liver / Q000378:metabolism / Q000503:physiopathology* / Q000528:radiation effects; D008111:Liver Function Tests; D008113:Liver Neoplasms / Q000378:metabolism / Q000503:physiopathology* / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011832:Radiation Injuries / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods; D020266:Radiotherapy, Conformal
chemical_list: D004396:Coloring Agents; D007208:Indocyanine Green
keywords: Adaptive radiotherapy; Indocyanine green; Liver; Radiotherapy