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Imaging findings and value of CT and DCE-MRI in monitoring denosumab therapy of giant cell tumors of bone

Thomas Van Den Berghe (UGent) , Lore Lapeire (UGent) , Maryse Lejoly (UGent) , Wouter Huysse (UGent) , David Creytens (UGent) and Koenraad Verstraete (UGent)
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Abstract
Purpose or Learning Objective To evaluate the value of CT and (DCE-)MRI for monitoring denosumab therapy of giant cell tumor of bone (GCTB). To describe imaging findings at diagnosis and during treatment. To give an overview of good and poor response, relapse and therapeutic complications. Methods or Background Twelve patients (8 males, 4 females, mean age 33.8 years old) with GCTB (4 spine, 8 limbs) were monitored six-monthly alternately with CT and (DCE-)MRI (mean follow-up 4.8 years). Response, relapse and complications were assessed on imaging studies and (semi-)quantitative measurements. Results or Findings On CT, good responders showed progressive re-ossification of osteolysis (mean increase 12HU/month), cortical remodelling and reduction of tumor and soft tissue volume (mean decrease 0.07cm³/month). On MRI, first a reduction in contrast enhancement (mean decrease of signal intensity 55A.U./month), surrounding bone marrow oedema (mean decrease of signal intensity 8A.U./month) and volume were observed. Next, focal necrosis, fatty infiltration and progressive re-ossification of the osteolytic area appeared. On DCE-MRI, the time-intensity curve evolved from a type IV curve with high first pass, high amplitude and steep wash-out rate over an intermediate type III or V to a slow type I or II. A reduction in wash-in slope, maximum signal intensity, area under the curve and amplitude of wash-in was observed, along with an increase in arrival time and time to peak. A decrease in Ktrans, initial area under curve and amplitude A was observed, along with increased Ve and Kep (extended Tofts/Brix models). These changes are consistent with transition from highly cellular and vascularized tissue with small interstitial space to a scar-like tissue with low cellularity. Patients with poor response or relapse showed the inverse findings of good responders on CT and (DCE-)MRI. Three patients showed relapse after initial good response when denosumab was stopped for pregnancy or dental surgery. Regarding evolution in time, one patient with initial good response showed a new cortical breakthrough and new rapidly growing enhancing soft tissue mass with medullary compression and extensive bone marrow oedema. Biopsy revealed a highly cellular high-grade conventional osteosarcoma with small interstitial space. Conclusion Denosumab is effective in inoperable GCTB and in operable cases with large morbidity. CT and (DCE-)MRI allow adequate evaluation of early/late response and detection of therapy failure and malignant transformation.
Keywords
CT, MRI, denosumab, giant cell tumor of bone

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MLA
Van Den Berghe, Thomas, et al. “Imaging Findings and Value of CT and DCE-MRI in Monitoring Denosumab Therapy of Giant Cell Tumors of Bone.” SEMINARS IN MUSCULOSKELETAL RADIOLOGY, vol. 26, no. 3, 2022, pp. 361–84, doi:10.1055/s-0042-1750644.
APA
Van Den Berghe, T., Lapeire, L., Lejoly, M., Huysse, W., Creytens, D., & Verstraete, K. (2022). Imaging findings and value of CT and DCE-MRI in monitoring denosumab therapy of giant cell tumors of bone. SEMINARS IN MUSCULOSKELETAL RADIOLOGY, 26(3), 361–384. https://doi.org/10.1055/s-0042-1750644
Chicago author-date
Van Den Berghe, Thomas, Lore Lapeire, Maryse Lejoly, Wouter Huysse, David Creytens, and Koenraad Verstraete. 2022. “Imaging Findings and Value of CT and DCE-MRI in Monitoring Denosumab Therapy of Giant Cell Tumors of Bone.” In SEMINARS IN MUSCULOSKELETAL RADIOLOGY, 26:361–84. https://doi.org/10.1055/s-0042-1750644.
Chicago author-date (all authors)
Van Den Berghe, Thomas, Lore Lapeire, Maryse Lejoly, Wouter Huysse, David Creytens, and Koenraad Verstraete. 2022. “Imaging Findings and Value of CT and DCE-MRI in Monitoring Denosumab Therapy of Giant Cell Tumors of Bone.” In SEMINARS IN MUSCULOSKELETAL RADIOLOGY, 26:361–384. doi:10.1055/s-0042-1750644.
Vancouver
1.
Van Den Berghe T, Lapeire L, Lejoly M, Huysse W, Creytens D, Verstraete K. Imaging findings and value of CT and DCE-MRI in monitoring denosumab therapy of giant cell tumors of bone. In: SEMINARS IN MUSCULOSKELETAL RADIOLOGY. 2022. p. 361–84.
IEEE
[1]
T. Van Den Berghe, L. Lapeire, M. Lejoly, W. Huysse, D. Creytens, and K. Verstraete, “Imaging findings and value of CT and DCE-MRI in monitoring denosumab therapy of giant cell tumors of bone,” in SEMINARS IN MUSCULOSKELETAL RADIOLOGY, Rostock, Germany, 2022, vol. 26, no. 3, pp. 361–384.
@inproceedings{8768346,
  abstract     = {{Purpose or Learning Objective
To evaluate the value of CT and (DCE-)MRI for monitoring denosumab therapy of giant cell tumor of bone (GCTB). To describe imaging findings at diagnosis and during treatment. To give an overview of good and poor response, relapse and therapeutic complications. 

Methods or Background
Twelve patients (8 males, 4 females, mean age 33.8 years old) with GCTB (4 spine, 8 limbs) were monitored six-monthly alternately with CT and (DCE-)MRI (mean follow-up 4.8 years). Response, relapse and complications were assessed on imaging studies and (semi-)quantitative measurements.

Results or Findings
On CT, good responders showed progressive re-ossification of osteolysis (mean increase 12HU/month), cortical remodelling and reduction of tumor and soft tissue volume (mean decrease 0.07cm³/month). On MRI, first a reduction in contrast enhancement (mean decrease of signal intensity 55A.U./month), surrounding bone marrow oedema (mean decrease of signal intensity 8A.U./month) and volume were observed. Next, focal necrosis, fatty infiltration and progressive re-ossification of the osteolytic area appeared. On DCE-MRI, the time-intensity curve evolved from a type IV curve with high first pass, high amplitude and steep wash-out rate over an intermediate type III or V to a slow type I or II. A reduction in wash-in slope, maximum signal intensity, area under the curve and amplitude of wash-in was observed, along with an increase in arrival time and time to peak. A decrease in Ktrans, initial area under curve and amplitude A was observed, along with increased Ve and Kep (extended Tofts/Brix models). These changes are consistent with transition from highly cellular and vascularized tissue with small interstitial space to a scar-like tissue with low cellularity.

Patients with poor response or relapse showed the inverse findings of good responders on CT and (DCE-)MRI. Three patients showed relapse after initial good response when denosumab was stopped for pregnancy or dental surgery.
Regarding evolution in time, one patient with initial good response showed a new cortical breakthrough and new rapidly growing enhancing soft tissue mass with medullary compression and extensive bone marrow oedema. Biopsy revealed a highly cellular high-grade conventional osteosarcoma with small interstitial space. 
Conclusion
Denosumab is effective in inoperable GCTB and in operable cases with large morbidity. CT and 
(DCE-)MRI allow adequate evaluation of early/late response and detection of therapy failure and malignant transformation.}},
  author       = {{Van Den Berghe, Thomas and Lapeire, Lore and Lejoly, Maryse and Huysse, Wouter and Creytens, David and Verstraete, Koenraad}},
  booktitle    = {{SEMINARS IN MUSCULOSKELETAL RADIOLOGY}},
  issn         = {{1089-7860}},
  keywords     = {{CT,MRI,denosumab,giant cell tumor of bone}},
  language     = {{eng}},
  location     = {{Rostock, Germany}},
  number       = {{3}},
  pages        = {{361--384}},
  title        = {{Imaging findings and value of CT and DCE-MRI in monitoring denosumab therapy of giant cell tumors of bone}},
  url          = {{http://dx.doi.org/10.1055/s-0042-1750644}},
  volume       = {{26}},
  year         = {{2022}},
}

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