Evaluating the Optimal Management of Inoperable Giant Cell Tumors of the Spine: A Systematic Review and Meta-Analysis

SIMPLE SUMMARY: Spine giant cell tumors (SGCTs) are intermediate malignant bone tumors, sometimes aggressive and responsible for debilitating axial pain and sensorimotor impairments. Non-surgical therapies, including denosumab, radiotherapy, and selective arterial embolization (SAE), have shown promising results in the treatment of patients with inoperable SGCTs. In this systematic review, we aimed to comprehensively analyze the current literature on denosumab, radiotherapy, and SAE for inoperable SGCTs, comparing treatment outcomes and complications using a random-effect model meta-analysis. We found that all three treatments were equally effective in providing symptom improvement and radiological tumor response, also showing low and comparable rates of treatment-related complications. Patients treated with denosumab showed lower rates of local recurrences and distant metastases. ABSTRACT: Background: Surgical resection remains the preferred treatment in spine giant cell tumors (SGCTs), but it is not always feasible. Conservative strategies have been studied for inoperable cases. We systematically reviewed the literature on inoperable SGCTs treated with denosumab, radiotherapy or selective arterial embolization (SAE). Methods: PubMed, Scopus, Web-of-Science, Ovid-EMBASE, and Cochrane were searched following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to include studies of inoperable SGCTs treated with denosumab, radiotherapy or SAE. Treatment outcomes were analyzed and compared with a random-effect model meta-analysis. Results: Among the 17 studies included, 128 patients received denosumab, 59 radiotherapy, and 43 SAE. No significant differences in baseline patient characteristics were found between the three groups. All strategies were equally effective in providing symptom improvement (p = 0.187, I(2) = 0%) and reduction in tumor volume (p = 0.738, I(2) = 56.8%). Rates of treatment-related complications were low (denosumab: 12.5%; radiotherapy: 8.5%; SAE: 18.6%) and comparable (p = 0.311, I(2) = 0%). Patients receiving denosumab had significantly lower rates of local tumor recurrence (10.9%) and distant metastases (0%) compared to patients receiving radiotherapy (30.5%; 8.5%) or SAE (35.6%; 7%) (p = 0.003, I(2) = 32%; p = 0.002, I(2) = 47%). Denosumab was also correlated with significantly higher overall survival rates at 18 months (99.2%) and 24 months (99.2%) compared to radiotherapy (91.5%; 89.6%) and SAE (92.5%; 89.4%) (p = 0.019, I(2) = 8%; p = 0.004, I(2) = 23%). Mortality was higher in patients receiving SAE (20.9%) or radiotherapy (13.6%) compared to denosumab (0.8%) (p < 0.001), but deaths mostly occurred for unrelated diseases. Conclusions: Denosumab, radiotherapy, and SAE are safe and effective for inoperable SGCTs. Clinical and radiological outcomes are mostly comparable, but denosumab may provide superior tumor control.