From the Guidelines
Giant cell tumor of bone should be managed by a bone sarcoma multidisciplinary team, with surgery being the treatment of choice for resectable tumors, and denosumab being used for unresectable or metastatic cases, or as a preoperative treatment to reduce tumor size and facilitate surgical resection. The treatment approach depends on the size and location of the tumor, as well as the patient's overall health and potential morbidity of treatment. According to the most recent guidelines, denosumab is indicated for unresectable or metastatic giant cell tumors of bone, and its use in the preoperative setting is debated and should be individualized for complex cases 1.
Treatment Options
- Surgical intervention, including en-bloc excision or intralesional curettage with adjuvant therapy, is the primary treatment for resectable giant cell tumors of bone 1.
- Denosumab, a RANK ligand inhibitor, is used to reduce tumor size before surgery or to manage unresectable tumors, and its optimal schedule and duration of treatment are still being defined 1.
- Radiation therapy is generally avoided due to the risk of malignant transformation, but may be considered for unresectable tumors.
Denosumab Treatment
- Denosumab is given as a monthly subcutaneous injection, with loading doses on days 8 and 15 of the first month, and requires daily calcium and vitamin D supplements to prevent hypocalcemia 1.
- Potential side effects of denosumab include osteonecrosis of the jaw and atypical fractures, which need to be monitored closely 1.
- Denosumab rechallenge can be considered in patients with progressive advanced giant cell tumor of bone after the resolution of osteonecrosis of the jaw 1.
Follow-up and Recurrence
- Regular follow-up imaging is necessary for at least 5 years after treatment to monitor for recurrence, which occurs in 15-50% of cases 1.
- Pulmonary metastases occur in approximately 3% of cases, and typically follow an indolent course 1.
From the Research
Giant Cell Tumor Overview
- Giant cell tumor of bone (GCTB) is an osteolytic, locally aggressive tumor that rarely metastasizes and typically occurs in the bones 2, 3, 4, 5.
- The primary treatment for GCTB is curettage with local adjuvants, but denosumab, a RANKL inhibitor, has emerged as an effective therapeutic option in advanced cases of GCTB 2, 3, 4, 5.
Denosumab Treatment
- Denosumab treatment has been shown to be effective in reducing tumor size and improving patient outcomes in GCTB patients 2, 3, 4, 5.
- The overall 1-year progression-free survival rate was 92.8% in a study of 35 patients with locally advanced GCTB treated with denosumab 2.
- Denosumab treatment was associated with high rates of clinical benefit and imaging response, without changing local recurrence rates when compared to patients treated without denosumab 3.
Surgical Treatment and Local Adjuvants
- Standard surgical treatment of GCT includes intralesional excision or segmental resection, with curettage having a higher recurrence rate 6.
- The use of local adjuvants such as phenol, alcohol, H2O2, Argon or cement may decrease recurrence rate, but the most effective local adjuvant is still controversial 6.
- Curettage in association with cryoablation seems to reduce the recurrence rate compared to "classic" local adjuvants 6.
Controversies and Future Directions
- Some clinicians maintain concerns and reservations regarding local recurrence and malignant transformation with denosumab treatment 4.
- Ongoing questions remain, including the optimal scheduling, patient selection, use in the adjuvant setting, and long-term toxicity concerns with denosumab treatment 5.
- Denosumab represents a potentially viable advancement in the management of GCTs, particularly in cases where surgical options are limited 4.