Risks and benefits of combining denosumab and surgery in giant cell tumor of bone-a case series

Abstract

Background: The RANK ligand inhibitor denosumab is being investigated for treatment of giant cell tumor of bone, but the available data in the literature remains sparse and controversial. This study analyzes the results of combining denosumab with surgical treatment and highlights possible changes for the oncologic surgeon in daily practice.

Methods: A total of 91 patients were treated surgically for giant cell tumor of bone between 2010 and 2014 in an institution, whereas 25 patients of the total additionally received denosumab and were part of this study. The average age of the patients was 35 years. Eleven patients received denosumab pre- and postoperatively, whereas with 14 patients, the denosumab treatment was applied either before (7 patients) or after (7 patients) the surgery. The average preoperative therapy duration was 3.9 months and the postoperative therapy 6 months by default.

Results: Sixteen patients presented a large tumor extension necessitating a resection of the involved bone or joint. In 10 of these patients, the indication for a resection procedure was abandoned due to the preoperative denosumab treatment and a curettage was performed. In the remaining six cases, the surgical indication was not changed despite the denosumab treatment, and two of them needed a joint replacement after the tumor resection. Also with patients treated with curettage, denosumab seems to facilitate the procedure as a new peripheral bone rim around the tumor was built, though a histologic analysis reveals viable tumor cells persisting in the denosumab-induced bone formation. After an average follow-up of 23 months, one histologically proven local recurrence occurred, necessitating a second curettage. A second patient showed a lesion in the postoperative imaging highly suspicious for local relapse which remained stable under further denosumab treatment. No adverse effect of the denosumab medication was observed in this study.

Conclusions: Denosumab can be a help to the oncologic surgeon by reconstituting a peripheral rim and switching the stage from aggressive to active or latent disease. But as tumor cells remain in the new-formed bone, the surgical technique of curettage has to be changed from gentle to more aggressive to avoid higher local recurrence rates.

Keywords: Adjuvant treatment; Benign tumor; Bone; Denosumab; Giant cell tumor; Surgery.

Fig. 1

Surgical decision-making process. Schematic illustration showing the surgical decision-making process. The first line is indicating the planned surgical procedure before denosumab treatment (“intention to treat”). The second line shows the actual performed surgery after denosumab treatment (“performed surgery”)

Fig. 2

Resection after denosumab treatment. Radiographic findings of case 17 before (a) and after (b) denosumab treatment. Intraoperative presentation of the tumor (c) and implantation of an allograft prosthetic composite (d)

Fig. 3

Curettage after denosumab treatment. Intraoperative findings after curettage of the tumor in case nr. 12 (a). Introducing of several probes inside the cavity, freezing the previous applied thermoconducting and liquid gel to −100 °C, and creating an “ice ball” (b)

Fig. 4

Histologic appearance after denosumab treatment. Histologic appearance of denosumab-treated giant cell tumor of bone. The residual tumor is composed of bland spindle cells organized in short fascicles, associated with collagen matrix production. No osteoclast-like multinucleated giant cells are present