Rationale and objectivesDenosumab is a monoclonal antibody used neo-adjuvantly in giant cell tumor of bone (GCTB) to facilitate surgery, or long term for axial tumors where surgery comes with high... Show moreRationale and objectivesDenosumab is a monoclonal antibody used neo-adjuvantly in giant cell tumor of bone (GCTB) to facilitate surgery, or long term for axial tumors where surgery comes with high morbidity. Time intervals for treatment effects to occur are unclear and monitoring tools are limited, complicating optimal drug dose titration. We assessed changes in time intensity curve (TIC) - derived perfusion features on DCE-MRI in GCTB during denosumab treatment and evaluated the duration of treatment effects on tumor perfusion.Materials and methodsPatients with GCTB who underwent dynamic contrast enhanced (DCE) MRI before (t = 0) and after 3 (t = 3), 6 (t = 6) or 12 (t = 12) months of denosumab treatment were retrospectively included in a single center. Regions of interest were placed on tumor compartments with visually most intense enhancement and TICs were created. Time-to-enhancement (TTE), wash-in rate (WIR), maximal relative enhancement (MRE), and area-under-the-curve (AUC) were calculated. Differences in perfusion features were calculated with the Wilcoxon signed-rank test.ResultsIn all 24 patients decreased perfusion on DCE-MRI after start of denosumab treatment was seen. TTE increased between t = 0 and t = 3 (p < 0.001). WIR, MRE and AUC decreased between t = 0 and t = 3 (p < 0.001, p = 0.01 and p = 0.02, respectively). No significant differences in features were found between t = 3 and t = 6 or t = 6 and t = 12. No significant perfusion differences in primary versus recurrent, or axial versus appendicular tumors, were found.ConclusionMRI perfusion significantly changed in GCTB within 3 months of denosumab treatment compared to baseline. No further significant change occurred between 3 and 6, and 6 and 12 months of treatment. These findings suggest that evaluation of treatment response and subsequent consideration of maintenance with lower doses of denosumab, may already be indicated after 3 months. In cases where long term denosumab is the preferred therapy, monitoring change in tumor characteristics on DCE-MRI may aid optimal drug dose titration, minimizing side effects. Show less
Giant cell tumor of bone (GCTB) is an intermediate, locally aggressive but rarely metastasizing tumor. Radiologically, GCTB shows typical lytic lesions. MR imaging is required to evaluate extent of... Show moreGiant cell tumor of bone (GCTB) is an intermediate, locally aggressive but rarely metastasizing tumor. Radiologically, GCTB shows typical lytic lesions. MR imaging is required to evaluate extent of GCTB for surgical planning. Preferred treatment for GCTB is extended curettage with local adjuvants, with comparable recurrence rates for different local adjuvants (27-31%). Resection can be performed when joint salvage is not feasible. Denosumab (RANKL-inhibitor) blocks and zoledronic acid (bisphosphonate) inhibits GCTB-derived osteoclast resorption. With zoledronic acid, stabilization of local and metastatic disease has been reported. Denosumab has been studied to a larger extent and seems to be effective in enabling less invasive forms of surgery. Moderate dose radiotherapy should be restricted to rare cases of unresectable or recurrent GCTB when surgery would lead to unacceptable morbidity. Tenosynovial GCT are classified into localized GCT of tendon sheath (GCTTS; nodular tenosynovitis) and diffuse-type GCT (Dt-GCT; pigmented villonodular synovitis, PVNS). Although arthroscopic synovectomy has been advocated as alternative to open synovectomy, there is a significant risk of inadequate excision. For GCT-TS, arthroscopic synovectomy may be sufficient. For Dt-GCT, open synovectomy is advised. For recurrent and extra-articular disease, moderate dose radiotherapy or systemic targeted therapy (M-CSFR-targeted tyrosine kinase inhibitors, e.g. imatinib) can be considered. Show less
Heijden, L. van der; Dijkstra, P.D.S.; Sande, M.A.J. van de; Kroep, J.R.; Nout, R.A.; Rijswijk, C.S.P. van; ... ; Gelderblom, H. 2014
