Radiological findings of denosumab treatment for giant cell tumours of bone

Abstract

Giant cell tumours of bone (GCTB) are benign giant cell-rich tumours typically occurring in the epi-metaphysis of skeletally mature patients. Despite their benign classification, GCTB may be locally aggressive with local recurrence as a challenging issue. Denosumab is a human monoclonal antibody that inhibits osteolysis via the RANK-RANK ligand pathway. There is currently no consensus on optimal treatment duration or imaging modality for monitoring patients on denosumab therapy. This review illustrates the radiological findings of GCTB on denosumab treatment seen on plain radiographs, CT, MRI, PET-CT and DEXA, with reference to the current literature. Recognizing imaging features indicative of a positive response to denosumab is important for therapeutic decision-making. Imaging findings with respect to duration of denosumab treatment, tumour upregulation during treatment, tumour recurrence and malignant transformation are discussed. The development of a sclerotic neocortex and varying degrees of matrix osteosclerosis are seen on plain radiographs. Reconstitution of subarticular bone and articular surface irregularity are optimally evaluated on CT which can also quantify tumour density. MRI demonstrates heterogeneous low signal matrix and is useful to assess decrease in size of cystic and/or soft tissue components of GCTB. A fatsuppressed fluid-sensitive MR sequence is important to detect tumour reactivation. Reduction in 18 F-FDG-PET avidity represents an early sensitive sign of response to denosumab treatment. Regardless of imaging modality, close follow-up in a specialist centre and careful evaluation of nonresponders is necessary as local recurrence after cessation of denosumab treatment and malignant transformation of GCTB have been described.

New Target for Precision Medicine Treatment of Giant-Cell Tumor of Bone: Sunitinib Is Effective in the Treatment of Neoplastic Stromal Cells with Activated PDGFRβ Signaling

“…The mechanism of recurrence is based on persistent neoplastic stromal cells, which do not respond to denosumab treatment [ 14 , 15 ] and likely maintain their proliferative ability. The termination of treatment could lead to overexpression of RANKL and RANK by neoplastic stromal cells and osteoclast-like giant cells, respectively [ 32 ]. For this reason, we focused on cell signaling in tumor tissue and in tumor-derived cell lines to identify druggable targets in the neoplastic component of GCTB tissue.…”

Therapy-Related Imaging Findings in Patients with Sarcoma

“…Decrease of osteolysis and increase of bone mass is seen on radiographs and CT from 2 weeks onward if the tumor responds well to this treatment. 35 Heterogeneity on fluidsensitive sequences, thickening of cortical bone, and increased bone mass are seen on MRI from 7 weeks onward; simultaneously, a marked decrease in 18F-FDG uptake is seen in patients who respond well. Transformation to sarcoma (or initial misdiagnosis) has been described and should be suspected when the opposite is seen, that is, progressive destruction of bone and increased mass, also with soft tissue Therapy-Related Imaging Findings in Patients with Sarcoma Bloem et al 683 extension.…”

“…Transformation to sarcoma (or initial misdiagnosis) has been described and should be suspected when the opposite is seen, that is, progressive destruction of bone and increased mass, also with soft tissue Therapy-Related Imaging Findings in Patients with Sarcoma Bloem et al 683 extension. 35,36 However, loss of bone mass and osteolysis may also reflect tumor upregulation or recurrence. 35,37,38 Bisphosphonates inhibit the function of osteoclasts and are used to reduce loss of bone mass in osteoporosis, painful bone metastases, and giant cell tumors.…”

“…35,36 However, loss of bone mass and osteolysis may also reflect tumor upregulation or recurrence. 35,37,38 Bisphosphonates inhibit the function of osteoclasts and are used to reduce loss of bone mass in osteoporosis, painful bone metastases, and giant cell tumors. Long-term use of these and other drugs, including denosumab, are known to cause AVN of the mandible and external auditory canal and may cause atypical fractures, in particular transversely oriented subtrochanteric femoral fractures.…”

State of the Art and New Concepts in Giant Cell Tumor of Bone: Imaging Features and Tumor Characteristics

“…The rationale of these findings is based on the inhibition of osteoclastic activity, which determines the reduction of the necrotic-inflammatory component (markedly hyperintense) and promotes tumor ossification or tumor replacement by intermixed bone tissue and fibroblast-like spindle cells, which are typically hypointense [101,104]. Changes in the intensity of post-contrast enhancement on T1-weighted images or in the mean ADC value of the solid part of the tumor did not prove to be statistically related to a positive treatment response [104]. MRI is another valuable method in the assessment of GCTB after denosumab administration.…”