Does Denosumab Change the Giant Cell Tumor Treatment Strategy? Lessons Learned From Early Experience

Abstract

Background Although giant cell tumors (GCTs) are benign, their aggressiveness and tendency to recur locally challenge the orthopaedic surgeon's ability to perform joint-preserving intralesional surgery with an acceptably low risk of local recurrence. Denosumab has emerged as a possible medical treatment of GCT because it seems to halt the progression of GCT, alleviate pain, and increase perilesional bone formation, but its exact role has been questioned, and specifically its efficacy and associated complications are not well characterized. Questions/purposes (1) Does denosumab reduce the risk of recurrence after resection or intralesional surgery? (2) What are the complications associated with the use of denosumab? Each author certifies that he or she has no commercial associations (eg, consultancies, stock ownership, equity interest, patent/ licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request. Each author certifies that his or her institution waived approval for the human protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research.

Pre-operative denosumab is associated with higher risk of local recurrence in giant cell tumor of bone: a systematic review and meta-analysis

“…Residue tumor cells may hide within the new bone and thickened cortex and may recur once denosumab is discontinued [22,24,25].Traub et al [25] described that the tumor tissue was replaced by gritty, fibrous-like tissue new bone, they suggested intra-operative fluoroscopy to guide the extent of resection. On the other hand, it is argued that the newly formed peripheral bone rim and hardened tumor tissue reduced the risk of inadvertent contamination [19]. Although we did not acquire sufficient data to conduct pooled-analysis on the outcome of denosumab combining curettage and local adjuvant, it is strongly recommended in many studies to use local adjuvant and high speed burr [3,24,26,27].Most studies included in our analysis applied various methods of local adjuvant in most patients except for one study specified that no local adjuvant was used [20].…”

“…Complications and others 6 studies [9,13,15,19,21,22] reported denosumab-related complications, in the 388 cases treated with denosumab, no osteo-necrosis of jaw or hypocalcemia was observed. 1 study [13] reported a periapical abscess and a periodontal disease during the course of denosumab administration.…”

“…Surgical choice was taken into account by comparing cases underwent curettage with denosumab and curettage alone in 4 studies [9,[16][17][18](OR: 2.13, 95% CI: 0.95 to 4.76, p=0.07, I 2 =29%)( Figure 3), though the result was not statistically significant. 7 studies [9,[15][16][17][18][19][20] reported outcome on primary lesions, which also suggest significantly higher risk of local recurrence in the denosumab group(OR: 1.91, 95% CI: 1.17 to 3.09, p=0.009, I 2 =36%)( Figure 4).…”

“…Scoccianti et al [9] conducted dental check before denosumab administration. Oral supplementary of Vitamin D and calcium is administered in 4 studies [3,9,13,19].Generally, Vitamin D was given more than 400IU/day and calcium more than 500mg/day. Administration of denosumab were similar, most studies administered denosumab once a month with 1-3 additional doses during the first month, the duration of administration prior to surgery differs for various reasons.…”

“…Ueda et al [11] used CT/MRI and 18FDG-PET/PET-CT to assess objective response of giant cell tumor of bone after denosumab treatment and found a 35%/82%/71% response rate according to RECIST/EORTC/Choi Criteria respectively, suggesting a robust radiographic response after denosumab treatment. Images of GCT of bone on X-ray reported by Agarwal et al [19] was cited in Figure 8 upon permission from editorial office.…”