title: Patient-specific, 3-dimensional dosimetry in non-Hodgkin's lymphoma patients treated with 131I-anti-B1 antibody: assessment of tumor dose-response.
abstract: A comprehensive, SPECT-based, patient-specific 3-dimensional (3D) dosimetry analysis has been performed using 3D-ID, a previously developed software package. The role of the total-body tumor burden, individual lesion size, tumor absorbed dose, and the spatial distribution of the absorbed dose on response and on the time course of tumor shrinkage has been examined in patients with lymphoma treated by radioimmunotherapy.
  
  
  METHODS
  Data from 15 patients participating in a phase II study of (131)I-labeled anti-B1 antibody (tositumomab) were used. Patients were administered a tracer dose of (131)I for imaging and pharmacokinetics. Dose estimates from the tracer studies were used to prescribe the therapeutic administration such that the whole-body absorbed dose did not exceed 75 cGy. All patients received a fixed mass amount of antibody for both the tracer and the therapeutic administrations. SPECT and planar imaging were performed 3-4 d after the therapeutic administration. CT or MRI scans were available on all patients. Total tumor burden was assessed by drawing contours around all lymphoma lesions identified on whole-body CT or MRI. Mean absorbed doses were estimated for selected, index lesions by conventional dosimetry and also by 3D SPECT-based dosimetry. Using a patient-specific dosimetry package, 3D-ID, dose-volume histograms were also generated to assess the spatial distribution of absorbed dose. This approach made it possible to obtain estimates of the minimum and maximum absorbed doses for individual tumors in addition to the mean.
  
  
  RESULTS
  Mean absorbed dose estimates obtained by patient-specific SPECT-based dosimetry using 3D-ID were within 2%-5% of estimates obtained by conventional dosimetry. None of the absorbed dose parameters (mean, minimum, maximum, uniformity) were found to have a significant correlation with tumor response. The total-body tumor burden did not impact on overall response or toxicity.
  
  
  CONCLUSIONS
  This analysis represents the first full reported implementation of a patient-specific 3D dosimetry package. The absence of a dose-response relationship for tumors is surprising and suggests that absorbed dose is not the sole determinant of tumor response in these patients. The absence of a correlation between the total-body tumor burden and overall response or toxicity suggests that tailoring the milligram amount of administered antibody to patient tumor burden is not likely to improve response or reduce toxicity.
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. sgourosg@mskcc.org
authors.forename: George
authors.initials: G
authors.lastname: Sgouros
authors.forename: Shannon
authors.initials: S
authors.lastname: Squeri
authors.forename: Ase M
authors.initials: AM
authors.lastname: Ballangrud
authors.forename: Katherine S
authors.initials: KS
authors.lastname: Kolbert
authors.forename: Jerrold B
authors.initials: JB
authors.lastname: Teitcher
authors.forename: Katherine S
authors.initials: KS
authors.lastname: Panageas
authors.forename: Ronald D
authors.initials: RD
authors.lastname: Finn
authors.forename: Chaitanya R
authors.initials: CR
authors.lastname: Divgi
authors.forename: Steven M
authors.initials: SM
authors.lastname: Larson
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Zelenetz
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D000970:Antineoplastic Agents; D001792:Blood Platelets / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D021621:Imaging, Three-Dimensional / Q000379:methods*; D008228:Lymphoma, Non-Hodgkin / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000532:radiotherapy*; D008297:Male; D016499:Radioimmunotherapy / Q000379:methods; D011874:Radiometry / Q000379:methods*; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods*; D012680:Sensitivity and Specificity; D015899:Tomography, Emission-Computed, Single-Photon; D016896:Treatment Outcome; D019043:Vascular Neoplasms / Q000175:diagnosis / Q000532:radiotherapy; D014915:Whole-Body Counting / Q000379:methods
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; C119496:tositumomab I-131