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

Abstract

BackgroundThe 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.MethodsA 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.ResultsSixteen 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.ConclusionsDenosumab 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.

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

“…Several studies have reported the newly formed sclerotic bone and thickened cortex made it difficult to identify surgical margin and to curette. 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].…”

Measurement of bone mineral density as an efficacy marker in denosumab treatment of giant cell tumour of bone

“…Müller et al have focused on benefits and risks of D-mab treatment of GCTB 7. A total of 18 patients were treated with D-mab preoperatively.…”

Denosumab Therapy in Giant Cell Bone Tumor: Review of Literature

“…Denosumab kitle çevresinde periferik bir rim oluşturarak, intraoperatif kanamayı azaltarak ve kitlenin derecesini agresiften aktif veya latent hastalığa çevirerek cerrah için önemli bir yardım oluşturur (37). Denosumab tedavisi mikrovasküler yoğunluğu azaltarak intraoperatif kanamayı azaltır (37).…”

“…Denosumab periferik bir rim oluşturarak ve aşamayı agresiften aktif veya latent hastalığa çevirerek onkolojik cerraha yardımcı olabilir. Canlı tümör hücrelerinin kalması nedeniyle akut tedavi edilebilen bir hastalığının kronik bir hastalığa çevirebilir (37,42). Denosumab tedavisinden sonra gelişen septaların duvarında canlı hücreler kalabilir tümör hücreleri yeni oluşan kemikte kaldığından dolayı küretajın cerrahi tekniği, daha yüksek lokal nüks oranları önlemek için daha agresif olarak uygulanmalıdır (37).…”

“…Canlı tümör hücrelerinin kalması nedeniyle akut tedavi edilebilen bir hastalığının kronik bir hastalığa çevirebilir (37,42). Denosumab tedavisinden sonra gelişen septaların duvarında canlı hücreler kalabilir tümör hücreleri yeni oluşan kemikte kaldığından dolayı küretajın cerrahi tekniği, daha yüksek lokal nüks oranları önlemek için daha agresif olarak uygulanmalıdır (37). Yeniden kemikleşmiş bölgelerde kalan tümöre ulaşmak için ve lokal kontrolün artırılması için intraoperatif yüksek hızlı burr kriyoterapi ,fenol, sıvı azot kullanımı önerilmektedir (9,16,55,56).…”