Two Cases of Sarcoma Arising in Giant Cell Tumor of Bone Treated with Denosumab
TLDR
Review of the literature shows one case report of malignant transformation of GCT in a patient being treated with denosumab, and larger, controlled studies are needed to ascertain whether denosumsumab may play a role in malignant Transformation of giant cell tumor of bone.Abstract:
Giant cell tumor (GCT) of bone is a generally benign, but often locally aggressive, neoplasm of bone, with a propensity for recurrence. Sarcomatous transformation is rare and typically occurs with a history of recurrences and radiation treatment. Denosumab, an inhibitor of the RANK ligand involved in bone resorption in GCT, is increasingly used in treatment of recurrent or unresectable giant cell tumor of bone. We report two cases of sarcomatous transformation of GCT to osteosarcoma in patients receiving denosumab. One was a 59-year-old male with a 12-year history of GCT and multiple recurrences taking denosumab for 2.5 years. The second case was in a 56-year-old male with a seven-year history of GCT taking denosumab for six months. Review of the literature shows one case report of malignant transformation of GCT in a patient being treated with denosumab. As the use of denosumab for treatment of GCT will likely increase, larger, controlled studies are needed to ascertain whether denosumab may play a role in malignant transformation of giant cell tumor of bone.read more
Citations
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Giant Cell Tumor of Bone: Review of Current Literature, Evaluation, and Treatment Options.
TL;DR: Advances in medical management of the disease have also demonstrated promise as an effective treatment; however, its use has usually been limited to the treatment of metastatic disease, recurrent disease or when advanced local disease would require surgical treatment felt to be overly morbid.
Journal ArticleDOI
Challenges of denosumab in giant cell tumor of bone, and other giant cell-rich tumors of bone
TL;DR: For the related but heterogenous group of giant cell rich tumors of bone, like aneurysmal bone cysts and central giant cell granuloma (CGCG), denosumab is a new treatment modality under investigation and could be a promising treatment option for selected patients with advanced disease.
Journal ArticleDOI
How safe and effective is denosumab for bone giant cell tumour
TL;DR: A study showed that cell proliferation is only diminished by denosumab; the cells continue to proliferate in vitro, albeit at a slower rate, and inhibition of RANKL may increase the risk of new malignancies due to immunosuppression.
Journal ArticleDOI
Giant cell tumours of bone treated with denosumab: histological, immunohistochemical and H3F3A mutation analyses.
TL;DR: Investigation of the histopathological features and H3F3A mutation status of GCTBs treated with denosumab found a mutation in the H3 histone family member 3A gene was recently identified as a genetic signature for GCTB.
Journal ArticleDOI
Does Denosumab Change the Giant Cell Tumor Treatment Strategy? Lessons Learned From Early Experience
TL;DR: Every patient showed improvement clinically in terms of pain and halting of tumor progression within three to four doses of denosumab, and one major complication that was observed was a recurrence with malignant transformation in a patient with a proximal humeral GCT.
References
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Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study
Karim Fizazi,Michael A. Carducci,Matthew R. Smith,Ronaldo Damião,Janet E. Brown,Lawrence Karsh,Piotr Milecki,Neal D. Shore,Michael Rader,H. Wang,Qi Jiang,Sylvia Tadros,Roger Dansey,Carsten Goessl +13 more
TL;DR: Denosumab was better than zoledronic acid for prevention of skeletal-related events, and potentially represents a novel treatment option in men with bone metastases from castration-resistant prostate cancer.
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Denosumab and bone-metastasis-free survival in men with castration-resistant prostate cancer : results of a phase 3, randomised, placebo-controlled trial.
Matthew R. Smith,Fred Saad,Robert E. Coleman,Neal D. Shore,Karim Fizazi,Bertrand Tombal,Kurt Miller,Paul Sieber,Lawrence Karsh,Ronaldo Damião,Teuvo L.J. Tammela,Blair Egerdie,Hendrik Van Poppel,Joseph L. Chin,Juan Morote,Francisco Gomez-Veiga,Tomasz Borkowski,Zhishen Ye,Amy Kupic,Roger Dansey,Carsten Goessl +20 more
TL;DR: This large randomised study shows that targeting of the bone microenvironment can delay bone metastasis in men with prostate cancer and significantly increased bone-metastasis-free survival.
Journal ArticleDOI
Denosumab in patients with giant-cell tumour of bone: an open-label, phase 2 study
David Thomas,Robert M. Henshaw,Keith M. Skubitz,Sant P. Chawla,Arthur P. Staddon,Jean-Yves Blay,Martine Roudier,Judy Smith,Zhishen Ye,Winnie Sohn,Roger Dansey,Susie Jun +11 more
TL;DR: In this article, the potential therapeutic effect of denosumab, a fully human monoclonal antibody against RANKL, on tumour-cell survival and growth in patients with GCT was investigated.
Journal ArticleDOI
Safety and efficacy of denosumab for adults and skeletally mature adolescents with giant cell tumour of bone: interim analysis of an open-label, parallel-group, phase 2 study.
Sant P. Chawla,Robert M. Henshaw,Leanne L. Seeger,Edwin Choy,Jean-Yves Blay,Stefano Ferrari,Judith R. Kroep,Robert J. Grimer,Peter Reichardt,Piotr Rutkowski,Scott M. Schuetze,Keith M. Skubitz,Arthur P. Staddon,David Thomas,Yi Qian,Ira Jacobs +15 more
TL;DR: Denosumab was associated with tumour responses and reduced the need for morbid surgery in patients with GCTB and represents a new treatment option for patients with the rare giant cell tumour of bone.
Journal ArticleDOI
Denosumab Induces Tumor Reduction and Bone Formation in Patients with Giant-Cell Tumor of Bone
D Branstetter,Scott D. Nelson,J. Carlos Manivel,Jean-Yves Blay,Sant P. Chawla,David Thomas,Susie Jun,Ira Jacobs +7 more
TL;DR: Denosumab treatment of patients with GCTB significantly reduced or eliminated RANK-positive tumor giant cells and reduced the relative content of proliferative, densely cellular tumor stromal cells, replacing them with nonproliferative, differentiated, densely woven new bone.