From the Guidelines
Giant cell tumor of bone should be managed by a bone sarcoma MDT, with surgery being the treatment of choice for resectable cases, and denosumab considered for unresectable cases or those with high morbidity risk. The management of giant cell tumor of bone (GCTB) involves a multidisciplinary team (MDT) approach, as emphasized in the UK guidelines for the management of bone sarcomas 1.
Diagnosis and Treatment
Key considerations in the diagnosis of GCTB include excluding brown tumors of hyperparathyroidism through serum calcium levels. Treatment options are primarily surgical, with en-bloc excision associated with lower recurrence rates than intralesional curettage, although curettage may preserve more function 1. Surgical adjuvants like high-speed burring, cement, and cryotherapy can improve local control.
Role of Denosumab
Denosumab, a fully human monoclonal antibody to RANKL, is indicated for cases where surgery is not possible or would result in unacceptable morbidity, and in patients with metastases 1. It can also be used pre-surgically to facilitate resection by solidifying the soft tissue component, thus reducing the risk of recurrence. However, curettage after denosumab treatment is associated with a higher risk of local recurrence, making complete resection the preferred approach after denosumab treatment.
Administration and Side Effects
Denosumab is administered as a monthly subcutaneous injection, following initial loading doses, and requires daily calcium and vitamin D supplementation to mitigate potential side effects 1. Significant side effects and the need for adequate contraception due to the risk of pregnancy complications are important considerations in the management of patients on denosumab.
Outcome Considerations
The choice of treatment should weigh the morbidity of the intervention against the risk of recurrence, emphasizing the importance of individualized care plans that consider the patient's quality of life, potential for morbidity, and mortality risk associated with the treatment options 1. Given the potential for recurrence and rare malignant transformation, long-term follow-up is crucial in the management of GCTB.
From the Research
Giant Cell Tumor Treatment
- Denosumab is a RANK ligand inhibitor approved for the treatment of giant cell tumor of bone, and its role in surgically resectable disease is currently under discussion 2.
- The use of neoadjuvant denosumab in operable giant cell tumor of bone (GCTB) is limited to selected cases, and a preoperative course of 6 months is considered safe and effective 2.
- Denosumab treatment has been shown to be effective in unresectable or metastatic disease, as well as in a neoadjuvant setting, with a 2-year progression-free survival rate of 81% 3.
- The risk of recurrences after curettage of GCTB following denosumab raises questions about the optimal management of such cases, and the role of adjuvant denosumab needs further investigation 2, 3.
Denosumab Efficacy and Safety
- Denosumab has been shown to be effective in treating GCTB of the spine, including the sacrum, with a clinical benefit reported in 83% of patients overall 4.
- The adverse event profile of denosumab is consistent with the full study population, with only 2 cases of grade 3 toxicity and one osteonecrosis of the jaw reported 3, 4.
- Denosumab treatment before resection of a large tumor may aid resection without tumor spillage, particularly where important structures like the neurovascular bundle are dissected away from the tumor margin 5.
Giant Cell Tumor Management
- The management of advanced giant cell tumor of bone has shifted from local treatment alone to multidisciplinary management with the consideration of use of denosumab 6.
- Denosumab has been approved by the FDA for the management of locally advanced or metastatic GCTB, and its use has led to improved outcomes for patients with this rare and locally aggressive benign tumor 6.
- The current role of systemic therapy for management of locally advanced or metastatic GCTB is to highlight the new developments in the management of this disease, and to review the current evidence for the use of denosumab in this setting 6.