title: Bio-effect model applied to 131I radioimmunotherapy of refractory non-Hodgkin's lymphoma.
abstract: OBJECTIVE
  Improved data collection methods have improved absorbed dose estimation by tracking activity distributions and tumor extent at multiple time points, allowing individualized absorbed dose estimation. Treatment with tositumomab and (131)I-tositumomab anti-CD20 radioimmunotherapy (BEXXAR) yields a cold antibody antitumor response (cold protein effect) and a radiation response. Biologically effective contributions, including the cold protein effect, are included in an equivalent biological effect model that was fit to patient data.
  
  
  METHODS
  Fifty-seven tumors in 19 patients were followed using 6 single proton emission computed tomography (SPECT)/CT studies, 3 each post tracer (5 mCi) and therapy (∼100 mCi) injections with tositumomab and (131)I-tositumomab. Both injections used identical antibody mass, a flood dose of 450 mg plus 35 mg of (131)I tagged antibody. The SPECT/CT data were used to calculate absorbed dose rate distributions and tumor and whole-body time-activity curves, yielding a space-time dependent absorbed dose rate description for each tumor. Tumor volume outlines on CT were used to derive the time dependence of tumor size for tracer and therapy time points. A combination of an equivalent biological effect model and an inactivated cell clearance model was used to fit absorbed dose sensitivity and cold effect sensitivity parameters to tumor shrinkage data, from which equivalent therapy values were calculated.
  
  
  RESULTS
  Patient responses were categorized into three groups: standard radiation sensitivity with no cold effect (7 patients), standard radiation sensitivity with cold effect (11 patients), and high radiation sensitivity with cold effect (1 patient).
  
  
  CONCLUSIONS
  Fit parameters can be used to categorize patient response, implying a potential predictive capability.
authors.affiliation: Department of Radiation Oncology, University of Michigan, 519 W. William St, Argus I, Ann Arbor, MI 48103-4943, USA. roberpl@umich.edu
authors.forename: Peter L
authors.initials: PL
authors.lastname: Roberson
authors.forename: Hanan
authors.initials: H
authors.lastname: Amro
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Wilderman
authors.forename: Anca M
authors.initials: AM
authors.lastname: Avram
authors.forename: Mark S
authors.initials: MS
authors.lastname: Kaminski
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Schipper
authors.forename: Yuni K
authors.initials: YK
authors.lastname: Dewaraja
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008228:Lymphoma, Non-Hodgkin / Q000473:pathology / Q000532:radiotherapy* / Q000628:therapy; D008954:Models, Biological; D016499:Radioimmunotherapy / Q000379:methods*; D017211:Treatment Failure; D047368:Tumor Burden / Q000528:radiation effects
chemical_list: D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes; C119496:tositumomab I-131