From the Guidelines
Surgery is the treatment of choice for resectable giant cell tumors of bone (GCTB), with en-bloc excision associated with lower rates of recurrence than intralesional curettage, while denosumab is indicated for unresectable or metastatic disease. The management of GCTB requires a multidisciplinary approach, taking into account the tumor location, size, and aggressiveness 1.
Treatment Options
- Intralesional curettage with adjuvant therapy is a common first-line treatment for accessible tumors, with adjuvants such as high-speed burring, cement, and cryotherapy used to reduce recurrence rates 1.
- Wide resection with reconstruction may be necessary for larger or more aggressive tumors, especially those in weight-bearing bones.
- Denosumab, a RANKL inhibitor, is used for unresectable or metastatic GCTB, and can also be used preoperatively to solidify the soft tissue component and facilitate surgical resection 1.
Denosumab Treatment
- Denosumab is given as a monthly subcutaneous injection after three loading doses at weekly intervals, with daily calcium and vitamin D supplements required to minimize the risk of hypocalcemia 1.
- Potential side effects of denosumab include osteonecrosis of the jaw and atypical fractures, which need to be monitored 1.
- The optimal schedule and duration of treatment with denosumab in metastatic or surgically unsalvageable GCTB is still undefined, and the possible long-term side effects are still largely unknown 1.
Post-Treatment Monitoring
- Post-treatment monitoring is essential, with follow-up imaging every 3-6 months initially, as GCTB have a 15-30% recurrence rate, particularly within the first two years 1.
- Long-term surveillance is necessary, as GCTB can be locally aggressive and occasionally metastasize to the lungs 1.
From the Research
Giant Cell Tumor Management
- Giant cell tumors (GCTs) are benign but locally aggressive bone neoplasms that primarily affect skeletally mature individuals, characterized by a tendency for recurrence and significant morbidity 2.
- Traditional treatment has focused on surgical resection, but the role of medical therapies, such as Denosumab, has gained prominence 2.
- Denosumab is a human monoclonal antibody that inhibits receptor activator of nuclear factor kappa B ligand (RANKL) and has been FDA-approved for unresectable GCTs since 2013 2.
Denosumab Efficacy and Safety
- Clinical studies have demonstrated that Denosumab effectively reduces tumor size and improves patient outcomes 3, 4, 2.
- Denosumab treatment is associated with high rates of clinical benefit and imaging response, without changing local recurrence rates when compared to patients treated without denosumab 3.
- Adverse events presented were mostly mild, with the exception of a malignant transformation to osteosarcoma 3.
- A systematic review with meta-analysis found no differences between articles considering the researched outcomes regardless of the therapeutic regimen adopted 3.
Denosumab in Specific Cases
- Denosumab is potentially effective treatment for patients with GCTB of the spine including the sacrum, with a clinical benefit reported in 83% of patients overall 4.
- A case report highlighted the neoadjuvant use of denosumab enabling complete surgical resection of a locally advanced GCTB, with the patient being managed with continued use of denosumab as 'maintenance' and remaining free of disease 5.
- 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 6.