Clinical, radiological and pathological outcomes following treatment of primary giant cell tumour of bone with Denosumab

Abstract

Background: Giant cell tumour of bone (GCTOB) is a relatively uncommon, benign, but locally aggressive neoplasm. Denosumab is a fully human monoclonal antibody with inhibitory effects on receptor activator of nuclear factor kappa-B ligand that has shown early promise as a possible treatment adjuvant for GCTB. However, much is still unknown about its current indications, long-term effects, the potential risk for rapid relapse and its involvement in sarcomatous transformation. Methods: We analysed the outcomes of 154 patients with GCTOB. We assessed clinical outcomes via local recurrence free-survival, metastatic free-survival and sarcomatous transformation between those treated without Denosumab and those with neo-adjuvant Denosumab. Our radiological and pathological outcomes were assessed through independent specialist reviews. Results: Four (19.0%) patients of the neo-adjuvant group had local recurrence of disease versus 16 (12.0%) patients in the surgery alone group; this results in a 3.62 times increased likelihood of developing local recurrence (P = 0.030). The median time to local recurrence was shorter for the neo-adjuvant group (421.5 days versus 788.5 days) (P = 0.01). There was no difference between Denosumab and the surgery groups in terms of metastatic disease (P = 0.45). Two patients in our cohort with GCTOB developed sarcomatous transformation, both were treated with Denosumab. Conclusion: Our use of Denosumab tended to be for those patients who had surgically difficult tumours to halt the progression and allow easier resections. Of concern we noted a trend towards increasing recurrence rates with the potential risk for rapid relapse. Furthermore, two cases experienced sarcomatous transformation, which is a growing area of concern within the literature.

Metastatic giant cell tumour of bone: a narrative review of management options and approaches

“…26 Other cases of malignancy in GCTB after denosumab exposure have been reported. 28 Although there is no evidence to support a causal relationship between denosumab and malignancy, it is a concerning finding nonetheless and warrants further investigation to understand denosumab's carcinogenic potential.…”

“…Other safety events of interest included four (<1%) atypical femoral fractures (AFF) in cohort one, which all occurred after long‐term (> 48 months) denosumab treatment, two cases (<1%) of hypercalcaemia in cohort one after denosumab discontinuation and four cases of malignant GCTB determined to be sarcomatous transformation after denosumab exposure 26 . Other cases of malignancy in GCTB after denosumab exposure have been reported 28 . Although there is no evidence to support a causal relationship between denosumab and malignancy, it is a concerning finding nonetheless and warrants further investigation to understand denosumab's carcinogenic potential.…”

The Efficacy and Safety of Denosumab for Treating Giant Cell Tumor of Bone: A Systematic Review and Meta-Analysis

“…16,19,30 Malignant transformation was defined as secondary tumor recurrence and confirmed by postoperative pathological examination. 4,30,31 Lung metastasis was presented by computed tomography scan of the chest. 19,32 We evaluated functional outcomes based on MSTS score.…”

“…Totally, we only included a total of 11 studies in our meta-analysis. 4,10,16,19,30,31,[34][35][36][37] We summarize the paper selection in Figure 1. We describe the baseline characteristics of our studies in Table 1.…”