Distribution of leukemia on skeletal wide bone marrow physiological space and functional marrow irradiation based on FLT-PET and dual energy CT

Objectives: Total marrow irradiation (TMI) is a sophisticated technique to achieve dose escalation while reducing dose to normal tissues compared to total body irradiation. Although TMI focuses radiation to the entire skeleton with the simplified assumption that hematologic disease is distributed homogeneously in the bone marrow, preclinical studies indicated the role of local bone marrow environment and survival of leukemia cells or leukemia resistance leading to treatment relapse. The purpose of this study was to identify disease locations and distribution in bone marrow compositions based on a novel hybrid 3-deoxy-3[(18)F]-fluorothymidine (FLT) PET-dual energy (DE) CT imaging. And functional marrow irradiation was simulated instead of standard TMI.

Methods: A control subject (full recovery patient received total body irradiation 13.2 Gy, imaged at day 100 post-transplant), and a AML patient (female, 80% blast measured by marrow aspirate) were scanned FLT PET and DECT. The leukemia niche was defined by thresholding of SUV. The red marrow and yellow marrow was segmented from DECT based on a basis material decomposition method. The overlap between leukemia niche and marrow compositions was evaluated by Dice similarity coefficient (DSC). Also, treatment planning was simulated to target irradiation differentially at a higher dose (18 Gy) to leukemia niche and a lower dose (12 Gy) to the rest of the skeleton.

Results: The maximum DSC value between red marrow regions and FLT hot regions was 0.497 with the SUV threshold > 4.0. Visually, leukemia heterogeneously distributed throughout the skeletal system with the majority in the red marrow region, the presence of leukemia in yellow marrow and close proximity to bone and active remodeling space was also observed. The primary target volume for irradiation was reduced to 26% with FLT-based TMI compared with the conventional TMI.

Conclusion: A hybrid system of functional-anatomical-physiological imaging offers the possibility of identifying spatial distribution of leukemia on site specific skeletal compositions. This method will facilitate investigating the potential association of skeletal macro-environment and leukemia heterogeneity and relapse in future clinical studies. Research Support: