Susanta K Hui1, Luke Arentsen2, Thanasak Sueblinvong3, Keenan Brown4, Pat Bolan5, Rahel G Ghebre3, Levi Downs3, Ryan Shanley6, Karen E Hansen7, Anne G Minenko8, Yutaka Takhashi9, Masashi Yagi10, Yan Zhang6, Melissa Geller3, Margaret Reynolds2, Chung K Lee2, Anne H Blaes11, Sharon Allen12, Bruno Beomonte Zobel13, Chap Le14, Jerry Froelich5, Clifford Rosen15, Douglas Yee11. 1. Department of Therapeutic Radiology, University of Minnesota, MN, USA; Masonic Cancer Center, University of Minnesota, MN, USA. Electronic address: huixx019@umn.edu. 2. Department of Therapeutic Radiology, University of Minnesota, MN, USA. 3. Department of Obstetrics and Gynecology, University of Minnesota, MN, USA. 4. Mindways Software Inc., Austin, TX, USA. 5. Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, MN, USA. 6. Biostatistics Core, Masonic Cancer Center, University of Minnesota, MN, USA. 7. Department of Medicine, Division of Rheumatology, University of Wisconsin, Madison, USA. 8. Department of Medicine, University of Minnesota, MN, USA. 9. Masonic Cancer Center, University of Minnesota, MN, USA. 10. Department of Medicine, University of Minnesota, MN, USA; Masonic Cancer Center, University of Minnesota, MN, USA. 11. Masonic Cancer Center, University of Minnesota, MN, USA; Department of Medicine, University of Minnesota, MN, USA. 12. Family Medicine and Community Health, University of Minnesota, MN, USA. 13. Campus Bio-Medico University, School of Medicine, Rome, Italy. 14. Department of Biostatistics, University of Minnesota, Minneapolis, USA. 15. Maine Medical Center Research Institute, Scarborough, ME, USA.
Abstract
PURPOSE: Cancer survivors are at an increased risk for fractures, but lack of effective and economical biomarkers limits quantitative assessments of marrow fat (MF), bone mineral density (BMD) and their relation in response to cytotoxic cancer treatment. We report dual energy CT (DECT) imaging, commonly used for cancer diagnosis, treatment and surveillance, as a novel biomarker of MF and BMD. METHODS: We validated DECT in pre-clinical and phase I clinical trials and verified with water-fat MRI (WF-MRI), quantitative CT (QCT) and dual-energy X-ray absorptiometry (DXA). Basis material composition framework was validated using water and small-chain alcohols simulating different components of bone marrow. Histologic validation was achieved by measuring percent adipocyte in the cadaver vertebrae and compared with DECT and WF-MRI. For a phase I trial, sixteen patients with gynecologic malignancies (treated with oophorectomy, radiotherapy or chemotherapy) underwent DECT, QCT, WF-MRI and DXA before and 12months after treatment. BMD and MF percent and distribution were quantified in the lumbar vertebrae and the right femoral neck. RESULTS: Measured precision (3mg/cm(3)) was sufficient to distinguish test solutions. Adiposity in cadaver bone histology was highly correlated with MF measured using DECT and WF-MRI (r=0.80 and 0.77, respectively). In the clinical trial, DECT showed high overall correlation (r=0.77, 95% CI: 0.69, 0.83) with WF-MRI. MF increased significantly after treatment (p<0.002). Chemotherapy and radiation caused greater increases in MF than oophorectomy (p<0.032). L4 BMD decreased 14% by DECT, 20% by QCT, but only 5% by DXA (p<0.002 for all). At baseline, we observed a statistically significant inverse association between MF and BMD which was dramatically attenuated after treatment. CONCLUSION: Our study demonstrated that DECT, similar to WF-MRI, can accurately measure marrow adiposity. Both imaging modalities show rapid increase in MF following cancer treatment. Our results suggest that MF and BMD cannot be used interchangeably to monitor skeletal health following cancer therapy.
PURPOSE:Cancer survivors are at an increased risk for fractures, but lack of effective and economical biomarkers limits quantitative assessments of marrow fat (MF), bone mineral density (BMD) and their relation in response to cytotoxic cancer treatment. We report dual energy CT (DECT) imaging, commonly used for cancer diagnosis, treatment and surveillance, as a novel biomarker of MF and BMD. METHODS: We validated DECT in pre-clinical and phase I clinical trials and verified with water-fat MRI (WF-MRI), quantitative CT (QCT) and dual-energy X-ray absorptiometry (DXA). Basis material composition framework was validated using water and small-chain alcohols simulating different components of bone marrow. Histologic validation was achieved by measuring percent adipocyte in the cadaver vertebrae and compared with DECT and WF-MRI. For a phase I trial, sixteen patients with gynecologic malignancies (treated with oophorectomy, radiotherapy or chemotherapy) underwent DECT, QCT, WF-MRI and DXA before and 12months after treatment. BMD and MF percent and distribution were quantified in the lumbar vertebrae and the right femoral neck. RESULTS: Measured precision (3mg/cm(3)) was sufficient to distinguish test solutions. Adiposity in cadaver bone histology was highly correlated with MF measured using DECT and WF-MRI (r=0.80 and 0.77, respectively). In the clinical trial, DECT showed high overall correlation (r=0.77, 95% CI: 0.69, 0.83) with WF-MRI. MF increased significantly after treatment (p<0.002). Chemotherapy and radiation caused greater increases in MF than oophorectomy (p<0.032). L4 BMD decreased 14% by DECT, 20% by QCT, but only 5% by DXA (p<0.002 for all). At baseline, we observed a statistically significant inverse association between MF and BMD which was dramatically attenuated after treatment. CONCLUSION: Our study demonstrated that DECT, similar to WF-MRI, can accurately measure marrow adiposity. Both imaging modalities show rapid increase in MF following cancer treatment. Our results suggest that MF and BMD cannot be used interchangeably to monitor skeletal health following cancer therapy.
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