title: Volume reduction versus radiation dose for tumors in previously untreated lymphoma patients who received iodine-131 tositumomab therapy. Conjugate views compared with a hybrid method.
abstract: BACKGROUND
  A Phase II study of previously untreated patients with malignant low grade follicular lymphoma given a combination of unlabeled tositumomab and tositumomab labeled with iodine-131 has recently been completed. The responses of these patients have been characterized, and for some of them tumor dosimetry during therapy has been estimated not only by pretherapy tracer conjugate views but also by a hybrid method.
  
  
  METHODS
  Available patients were studied if they had had a pelvic or abdominal tumor evaluation by single photon emission computed tomography (SPECT) and achieved a partial response. A tumor outlined on the iodine-131 conjugate-view images was called a composite tumor. Its volume estimate came from multiple, not necessarily contiguous, regions of interest (ROI) on the pretherapy computed tomography (CT) scan. Its radiation dose was estimated from the weeklong series of pretherapy images and standard Medical Internal Radiation Dose methods. Computed tomography ROI were also grouped into smaller, contiguous volumes that defined individual tumors. Their radiation doses were estimated by the hybrid method. This method employed the activity measured for each individual tumor by a single intratherapy SPECT scan, as well as the tumor's volume, to individually normalize the composite time-activity curve as appropriate. The individual normalization factors then converted the composite radiation dose to radiation doses for individual tumors. Reduction in tumor volume was calculated for both composite and individual tumors at 12 weeks posttherapy.
  
  
  RESULTS
  For 14 composite tumors in 10 patients, the median pretherapy volume was 170 cm(3). Application of a sigmoidal curve function to the plot of volume reduction versus radiation absorbed dose resulted in degeneration of the curve into a straight line with a negative slope. There was no statistical significance in the relationship (P = 0.73). For 43 individual tumors, the median pretherapy tumor volume was 26 cm(3). The plot of volume reduction versus dose was fairly well fit by a sigmoidal curve, and the relationship approached statistical significance (P = 0.06). The representation assigned 56% of the shrinkage to the effects of unlabeled tositumomab. For the subset of individual tumors with a pretherapy volume less than 10 cm(3) from 6 patients (n = 15), the relationship was significant (P = 0.03). The sigmoidal representation assigned only 12% of the shrinkage to unlabeled tositumomab, as contrasted with 72% for tumors with pretherapy volume greater than 10 cm(3).
  
  
  CONCLUSIONS
  For patients who attained a partial response, analysis of individual tumors by a hybrid dosimetric method led to a dependence between volume reduction at 12 weeks and radiation dose that tended to be significant. The same was not true with dosimetry of composite tumors based on pretherapy conjugate views alone. It appeared that volume reductions from both unlabeled antibody and radiation dose were important in tositumomab therapy of lymphoma patients, with unlabeled antibody relatively more important for larger tumors.
authors.affiliation: University of Michigan Medical Center, Ann Arbor, Michigan 48109-0552, USA. kenkoral@umich.edu
authors.forename: Kenneth F
authors.initials: KF
authors.lastname: Koral
authors.forename: Isaac R
authors.initials: IR
authors.lastname: Francis
authors.forename: Stewart
authors.initials: S
authors.lastname: Kroll
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Zasadny
authors.forename: Mark S
authors.initials: MS
authors.lastname: Kaminski
authors.forename: Richard L
authors.initials: RL
authors.lastname: Wahl
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use*; D008228:Lymphoma, Non-Hodgkin / Q000532:radiotherapy*; D017063:Outcome Assessment, Health Care; D011829:Radiation Dosage; D011874:Radiometry
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D018796:Immunoconjugates; C119496:tositumomab I-131