Image-based patient-specific absorbed dose to active marrow during radioimmunotherapy

Objectives To compare blood- and imaging-based red marrow absorbed dose (D_RM) estimates and to evaluate their relationship to hematoxicity in non-Hodgkin lymphoma patients treated with I-131 tositumomab.

Methods Multiple SPECT/CT and blood activity measurements were carried out in 22 patients following tracer and therapy administrations. Imaging (lumbar) based dosimetry was performed using the DPM Monte Carlo program, which was adapted (Phys. Med. Biol. 2013;58:4717-31) for estimating dose rates to active marrow using electron absorption fractions generated with the general purpose EGS5 code for varying bone volume fractions (BVF) and cellularity fractions (CF). Patient specific CFs and voxel-level BVFs were determined from iliac crest biopsy and CT-derived density maps. Relationships were evaluated between hematoxicity and D_RM as well as between hematoxicity and non-dosimetric factors such as baseline counts, disease involvement in marrow, treatment history and plasma FLT3-L cytokine levels.

Results The red marrow to blood activity concentration ratio (RMBLR) increased with time since administration (median 0.57 on day0, 0.84 on day2 and 1.09 on day8). The imaging based estimate of D_RM (median 163 cGy, range 140 to 244) was significantly higher than the blood-based estimate (median 97 cGy, range 76 - 111). There was a high correlation between tracer predicted and therapy delivered D_RM with both calculations. In univariate analyses, the blood-based D_RM was not predictive of any of the toxicity measures. However, the imaging-based D_RM correlated significantly with the % of baseline counts at nadir for both platelets (r=-0.509;p=0.016) and ANC (r=-0.468;p=0.028). In ordinal logistic regression the imaging based estimate of D_RM was predictive of toxicity grade for both platelets (p=0.010) and ANC (p=0.029). The only other covariate that was consistently predictive of toxicity was marrow involvement.

Conclusions The imaging based patient specific D_RM was a better predictor of toxicity than the blood based estimate.

Research Support NIH NIBIB R01 EB001994