Malignant giant cell tumor of bone: A case series in the denosumab era.

Abstract

e23510 Background: Giant cell tumor of bone (GCTB) is a locally recurrent, rarely metastasizing tumor. However, GCTB can undergo malignant transformation. Malignancy in GCTB (mGCTB) may be primary (adjacent to a non-malignant GCTB, at first diagnosis) or secondary (after a GCTB recurrence). Incidence of mGCTB is unknown and diagnosis and treatment are challenging. Methods: This is a retrospective series from a prospective institutional musculoskeletal oncology database. From 1956 to 2023, 1314 GCTB patients were diagnosed. All the diagnoses were reviewed by expert pathologists. Treatments and outcome were described. Results: Overall, 31 (2%) mGCTB out of 1314 GCTB patients were diagnosed. The majority of them, 90% (28/31), were secondary mGTCB, with a median time to malignancy of 80 months (3-387); in 18% (5/28) cases secondary mGCTB occurred after radiotherapy. Denosumab was administered prior malignant transformation in 18% (5/28) of the patients, for a median of 44 months (1-150). Median age was 46 years (21-77); M/F 18/13; 24/31 (77%) had local disease, 7/31 (23%) presented with metastases (in 5 cases combined with local disease). Median size was 8.8 cm (3.5-22 cm). mGCTB most commonly occurred in the femur (11/31, 35%), tibia (7/31, 23%), and pelvis (6/31, 19%). Histologically the malignant tumors were classified as osteosarcoma in 22/31 (71%), undifferentiated spindle cell sarcoma in 6/31 (19%), and undifferentiated pleomorphic sarcoma in 3 patients. Treatments (n = 30): Local treatment was surgery in 23 patients (77%) (a resection in 12/23, an amputation/disarticulation in 10/23 and pneumonectomy in 1), carbon therapy in 1, proton 1 and none in 5 cases. Adequate surgical margins were reported in 20/23 (87%) of the cases. Systemic treatment was employed in 19 patients (63%): doxorubicin (A) in 87%, ifosfamide in 73%, cisplatin (C) in 60%, methotrexate (M) in 37.5%, and denosumab in 1 patient. Most of the patients (15/23, 65%) with localized mGCTB received chemotherapy as adjuvant or neoadjuvant treatment (3/15 preoperatively), 4/7 (60%) metastatic patients in 1 st line. Objective responses in 6 patients with measurable disease were a PR in 1/3 patients undergoing MAP and in 1/1 patient undergoing denosumab. With a median follow up of 122 months (IQR:67-186), the 5 and 10-year overall survival were 53.2% (95% CI, 33.1-69.8) and 48.8% (95% CI, 28.9-66.0), respectively; progression-free survival was 54% (95% CI, 30.0-73.4). Conclusions: Incidence of mGCTB is about 2% among GCTB and transformation might occur after more than 6 years. The prognosis is poor despite local only relapse after a previous GCTB and aggressive treatments. Accurate diagnosis is critical to avoid delayed treatment. A re-biopsy after GCTB recurrence should be always considered to rule out secondary malignant transformation, especially for large, rapidly growing lesions or pulmonary metastases. Response to denosumab of a histologically confirmed mGCTB is here described.