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Role of (Neo)adjuvant Denosumab for Giant Cell Tumor of Bone

  • Sarcoma (SH Okuno, Section Editor)
  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion statement

Denosumab is a RANK ligand inhibitor approved for the treatment of giant cell tumor of bone. While the role of denosumab in the setting of advanced and unresectable disease is well established, its role in surgically resectable disease is currently under discussion. Several prospective and retrospective series on neoadjuvant therapy in potentially resectable tumor with high morbidity surgery reported a relapse rate of 10–20% after resection and 30–40% after curettage. At the same time, less morbid surgery has obvious clinical advantages for the patient, and several studies have shown the efficacy of denosumab in downgrading of the surgical procedure. Currently, the role of neoadjuvant denosumab in operable GCTB is limited to selected cases in which a diffuse reactive bone formation and peripheral ossification can make an easier surgical procedure, for example, in tumors with a large soft tissue component. A planned resection may become less morbid when preoperative denosumab is administered. Whenever a segmental resection is thought to be indicated at diagnosis, denosumab may be considered in the neoadjuvant setting. A preoperative course of 6 months is considered safe and effective. Two case scenarios are presented and critically discussed. Because of the high recurrence rates after denosumab treatment followed by curettage, we discourage the use of denosumab when curettage is considered feasible. In this setting, a short course of preoperative denosumab (2–6 months) may be considered for highly selected cases, for example in pathological fractures. The role of adjuvant denosumab needs further investigation. Long-term disease control has been reported in case of non-surgical lesions, even after treatment interruption, but there is no consensus on ideal treatment duration and dosage for these scenarios. In all cases, multidisciplinary discussion with oncology, pathologist, radiologist, and surgeons is mandatory. Patient’s comorbidities, dental conditions, and preferences, including family planning, should always be taken into account.

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Author notes

    Authors and Affiliations

    1. Chemotherapy Unit, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy

      Emanuela Palmerini MD, PhD & Alessandra Longhi MD

    2. Orthopedic Oncology, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy

      Eric Lodewijk Staals MD, PhD & Davide Maria Donati MD

    3. Dallas Sarcoma Associates, Medical City Dallas, Dallas, USA

      Louis Baxter Jones MD

    4. Orthopaedic Surgery, UC Davis, Sacramento, USA

      R. Lor Randall MD

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    Contributions

    EP had the idea for the article, ES and LBJ performed the literature search and data analysis, and all drafted and/or critically revised the work.

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    Correspondence to Emanuela Palmerini MD, PhD.

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    Conflict of Interest

    Emanuela Palmerini has received compensation from Daiichi Sankyo, Deciphera, Lilly, and EUSA Pharma for service as a consultant and has received non-financial support from PharmaMar.

    Eric Lodewijk Staals declares that he has no conflict of interest.

    Louis Baxter Jones declares that he has no conflict of interest.

    Davide Maria Donati declares that he has no conflict of interest.

    Alessandra Longhi declares that she has no conflict of interest.

    R. Lor Randall declares that he has no conflict of interest.

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    Palmerini, E., Staals, E.L., Jones, L.B. et al. Role of (Neo)adjuvant Denosumab for Giant Cell Tumor of Bone. Curr. Treat. Options in Oncol. 21, 68 (2020). https://doi.org/10.1007/s11864-020-00766-4

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