Emanuela Palmerini1, Leanne L Seeger2, Marco Gambarotti3, Alberto Righi3, Peter Reichardt4, Susan Bukata2, Jean-Yves Blay5, Tian Dai6, Danielle Jandial6, Piero Picci7. 1. Chemotherapy Unit, IRCCS Istituto Ortopedico Rizzoli, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Bologna University, 40136, Bologna, Italy. emanuela.palmerini3@unibo.it. 2. David Geffen School of Medicine, UCLA Health System, 200 UCLA Medical Plaza Suite 165-57, Los Angeles, CA, 90095, USA. 3. Department of Pathology, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy. 4. Department of Interdisciplinary Oncology, Sarcoma Center Berlin-Brandenburg; HELIOS Klinikum Berlin-Buch, Schwanebecker Chaussee 50, 13125, Berlin, Germany. 5. Department of Medical Oncology, Leon Berard Center, 28, rue Laennec 2 69373 Lyon Cedex 08, Lyon, France. 6. Global Development (Oncology), Amgen Inc., One Amgen Center Drive, MS 38-2-B, Thousand Oaks, CA, 91320-1799, USA. 7. Chemotherapy Unit, IRCCS Istituto Ortopedico Rizzoli, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Bologna University, 40136, Bologna, Italy.
Abstract
BACKGROUND:Giant cell tumor of bone (GCTB) is a rare osteoclastogenic stromal tumor. GCTB can rarely undergo malignant transformation. This post hoc analysis evaluated and classified malignancies in patients with GCTB who receiveddenosumab. METHODS: This analysis was conducted on patients with pathologically confirmed GCTB and measurable active disease treated withdenosumab 120 mg subcutaneously once every 4 weeks, with loading doses on study days 8 and 15, as part of a phase 2, open-label, multicenter study. We identified potential cases of malignancy related to GCTB through an independent multidisciplinary review or medical history, associated imaging or histopathologic reports, and disease course. The findings were summarized and no statistical analysis was performed. RESULTS:Twenty of five hundred twenty-six patients (3.8%) who received at least one dose of denosumab were misdiagnosed with GCTB that was later discovered to be malignancies: five primary malignant GCTB, five secondary malignant GCTB, four sarcomatous transformations, and six patients with other malignancies (giant cell-rich osteosarcoma, undifferentiated pleomorphic sarcoma, spindle cell sarcoma, osteogenic sarcoma, phosphaturic mesenchymal tumor of mixed connective tissue type, and fibrosarcoma/malignant fibrous histiocytoma). Many malignancies were present before denosumab was initiated (8 definitive cases, 7 likely cases), excluding potential involvement of denosumab in these cases. Signs associated with potential misdiagnoses of GCTB included poor mineralization with denosumab treatment, rapid relapse in pain, or a failure of the typical dramatic improvement in pain normally observed with denosumab. CONCLUSIONS: Although rare, GCTB can undergo malignant transformation, and rates in this study were consistent with previous reports. Signs of poor mineralization or lack of response to denosumab treatment may warrant close monitoring. TRIAL REGISTRATION: clinicaltrials.gov , ( NCT00680992 ). Registered May 20, 2008.
RCT Entities:
BACKGROUND: Giant cell tumor of bone (GCTB) is a rare osteoclastogenic stromal tumor. GCTB can rarely undergo malignant transformation. This post hoc analysis evaluated and classified malignancies in patients with GCTB who received denosumab. METHODS: This analysis was conducted on patients with pathologically confirmed GCTB and measurable active disease treated with denosumab 120 mg subcutaneously once every 4 weeks, with loading doses on study days 8 and 15, as part of a phase 2, open-label, multicenter study. We identified potential cases of malignancy related to GCTB through an independent multidisciplinary review or medical history, associated imaging or histopathologic reports, and disease course. The findings were summarized and no statistical analysis was performed. RESULTS: Twenty of five hundred twenty-six patients (3.8%) who received at least one dose of denosumab were misdiagnosed with GCTB that was later discovered to be malignancies: five primary malignant GCTB, five secondary malignant GCTB, four sarcomatous transformations, and six patients with other malignancies (giant cell-rich osteosarcoma, undifferentiated pleomorphic sarcoma, spindle cell sarcoma, osteogenic sarcoma, phosphaturic mesenchymal tumor of mixed connective tissue type, and fibrosarcoma/malignant fibrous histiocytoma). Many malignancies were present before denosumab was initiated (8 definitive cases, 7 likely cases), excluding potential involvement of denosumab in these cases. Signs associated with potential misdiagnoses of GCTB included poor mineralization with denosumab treatment, rapid relapse in pain, or a failure of the typical dramatic improvement in pain normally observed with denosumab. CONCLUSIONS: Although rare, GCTB can undergo malignant transformation, and rates in this study were consistent with previous reports. Signs of poor mineralization or lack of response to denosumab treatment may warrant close monitoring. TRIAL REGISTRATION: clinicaltrials.gov , ( NCT00680992 ). Registered May 20, 2008.
Entities:
Keywords:
Bone neoplasms; Denosumab; Giant cell tumor of bone; RANK ligand
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