PNNL

Abstract

Objectives: Myeloablative radioimmunotherapy (RIT) using 131I tositumomab (anti-CD 20) monoclonal antibodies is an effective new therapy for B-cell non-Hodgkins lymphoma (NHL). The goal of this work is to determine optimum methods to deliver maximal myeloablative radioactivity without exceeding the radiation tolerance of critical normal organs such as liver and lungs, and avoiding serious toxicity. Methods: We reviewed dosimetry records for 100 consecutive patients who underwent biodistribution and dosimetry after a test infusion of 131I- tositumomab. Serial gamma camera images were used to determine organ and tissue activities over time and to calculate radiation-absorbed doses. Volumes of critical normal organs were determined from CT scans to adjust the dose estimates for the individual patient. These dose estimates helped us determine an appropriate therapy based on projected dose to the critical normal organ receiving a maximum tolerable radiation dose. We compared our method of organ-specific dosimetry for treatment planning with the standard clinical approaches using a whole-body dose-assessment method by assessing the difference in projected amounts of radiation-absorbed doses, as well as the ratios of projected amounts, that would be prescribed for therapy by each of these two strategies. Results: The mean organ doses (mGy/MBq) estimated by both methods were (1) Whole body method: liver = 0.33 and lungs = 0.33; and (2) Organ-specific method: liver 1.52 and lungs 1.72 (p = .0001). The median difference between the radiation-absorbed dose estimates was 3.40 (range of 1.37 to 7.96) for the lungs, 3.05 (range of 1.04 to 6.20) for the liver, and –0.05 for whole body (range of –0.18 to 0.16). The median ratio (OS divided by WB method) of radiation-absorbed dose estimates was 5.12 (range of 2.33 to 10.01) for the lungs, 4.14 (range of 2.16 to 6.67) for the liver, and 0.94 (range of 0.79 to 1.22) for whole body. There was significant difference between the dose estimated by the two methods for liver and lungs (p = 0.0001) and a significant correlation for whole body dose estimates by the two methods (R = 0.97) indicating confidence in the whole body dose estimation methods. Conclusions: Dosimetry based only on whole body retention will under-estimate the organ doses in a substantial number of patients, likely because it assumes a uniform distribution and clearance without accounting for patient-specific variations in biodistribution. Myeloablative treatment based on individual organ radiation absorbed dose provides the ability to safely administer the largest possible amounts of radioactivity and deliver an optimized radiation dose to tumor within the tolerance of normal organs.