Longitudinal Study Of Fat Composition Changes In Bone Marrow During Chemotherapy And Radiation Therapy For Pelvic Malignancies

To assess the magnitude, rate, and pattern of change in bone marrow fat fraction in patients receiving pelvic (chemo)radiation therapy, and to determine associations between peripheral blood cell counts and the change in fat fraction. This prospective, longitudinal, IRB-approved study was conducted in 19 patients who received either highly myelotoxic (IMRT plus either cisplatin, 5FU/MMC or cisplatin/5FU/cetuximab) or less myelotoxic treatment (capacitabine-IMRT or no concurrent chemotherapy). Patients underwent concurrent MR imaging and venipuncture at baseline, mid-treatment, and post-treatment visits. We performed linear mixed effects modeling of the mean proton density fat fraction (PDFF(%)) as a function of linear-time, treatment, and vertebral column region (L4-S2 vs T10-L3 vs C3-T9). Spearman rank correlations were performed by blood cell counts versus the difference in PDFF(%) pre- and post-treatment. In the highly myelotoxic group, we observed significant changes in PDFF(%) per visit within L4-S2 (16.1, 95% CI: 13.0,19.2) and within T10-L3 (3.98, 95% CI: 0.88,7.08) relative to the reference C3-T9. In the less myelotoxic group, we observed significant changes in PDFF (%) per visit within L4-S2 (10.7, 95% CI: 6.55,14.9) relative to the reference C3-T9. The difference between treatment groups in the rate of change of PDFF(%) per visit within L4-S2 was 5.39 (95% CI: 0.20,10.58). Rank correlations of the inverse log difference in WBC versus the difference in PDFF(%) overall and within T10-S2 ranged from 0.69-0.78 (p<0.05). Rank correlations of the inverse log difference in ANC versus the difference in PDFF(%) overall and within L4-S2 ranged from 0.79-0.81 (p<0.05). MRI fat quantification is sensitive to marrow composition changes that result from (chemo)radiation therapy. These changes are associated with peripheral blood cell counts. This study supports a rationale for bone marrow sparing treatment planning to reduce the risk of hematologic toxicity.