Monitoring Denosumab Therapy of Giant Cell Tumors of Bone Using a Radiologic-Pathologic Correlation

Purpose or Learning Objective: To determine the value of computed tomography, anatomical, and dynamic contrast-enhanced magnetic resonance imaging for monitoring denosumab therapy of giant cell tumors of bone by correlating it at diagnosis and during therapy to histopathology and following up tumor characteristics during therapy.

Methods or Background: Patients with giant cell tumors of bone under denosumab therapy and monitored with computed tomography and dynamic contrast-enhanced magnetic resonance imaging were retrospectively and consecutively included (2012–2021). Imaging and (semi)quantitative imaging and histopathologic measurements were used to assess response to therapy and relapse during or after therapy. Tissue samples were analyzed using computerized segmentations for vascularization and the number of neoplastic and giant cells on histopathology. Pearson's correlation and Spearman's rank coefficient and Kruskal-Wallis tests were used to assess correlations between histopathology and radiology.

Results or Findings: Six patients (28 ± 8 years of age; five men) were included and evaluated. On computed tomography, good responders showed progressive reossification (+ 8 HU/month) and cortical remodeling (woven bone formation). Magnetic resonance imaging showed a signal intensity decrease relative to muscle on T1-weighted (− 0.01 AU/month) and on fat-saturated T2-weighted sequences (− 0.03 AU/month). Time-intensity curves evolved from a type IV curve with high first pass, high amplitude, and steep washout to a slow type II curve. An increase in time to peak (+ 100%) and a decrease in K^trans (− 71%) were observed. This is consistent with microscopic examination, showing a decrease of giant cells (− 76%), neoplastic cells (− 63%), and blood vessels (− 28%). There was a strong statistically significant inverse correlation between time to peak and microvessel density (ρ = − 0.9; P = 0.01).

Significantly, fewer neoplastic (P = 0.03) and giant cells (P = 0.04) were found with a time-intensity curve type II compared with a type IV. Two patients showed relapse after initial good response when stopping denosumab. Inverse imaging and pathologic findings were observed with a reduced ossification and cortical remodeling and reduced density on computed tomography. On magnetic resonance imaging, a progressive tumor reappearance was observed with a T1- and T2-weighted signal intensity increase. On dynamic contrast-enhanced magnetic resonance imaging, a reappearance of time-signal intensity curve type IV, a decrease in time to peak, and an increase in K^trans were observed. On histopathology, an increase in giant cells, neoplastic cells, and blood vessels was observed.

Conclusion: Computed tomography and dynamic contrast-enhanced magnetic resonance imaging show a good correlation with histopathology and allow adequate evaluation of response to denosumab therapy.

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Artikel online veröffentlicht:
02. Juni 2025