Curative Potential of Neoadjuvant Denosumab in the Treatment of Giant Cell Spinal Tumor? A Case Study

BGCT/SGCT and Treatment Options

Giant cell bone tumors (BGCT - bone giant cell tumors) represent about 5% of all bone neoplasms, occurring particularly in women in their 3rd and 4th decades of life. These tumors are mostly benign but can exhibit locally aggressive growth and significant morbidity. They carry a low, albeit not negligible, metastatic potential, most commonly to the lungs, associated with an overall mortality rate of 15%.

Giant cell spinal tumor (SGCT - spine giant cell tumor) is diagnosed in 1.4–9% of cases. It is characterized by a high rate of unresectability and a high risk of pathological fractures, especially when located in the mobile part of the spine. The most common symptom is axial pain.

Surgery can have a curative effect if complete resection is achieved. In the absence of adequate resection, primary tumors recur in 55% of cases. Extremely mutilating procedures such as vertebrectomy significantly reduce the recurrence rate but have high morbidity compared to intralesional resections such as curettage.

At the cellular level, BGCTs are characterized by multinucleated giant cells of the osteoclast type, expressing the receptor activator of nuclear factor kappa B (RANK). These cells are surrounded by various mononuclear stromal cells expressing RANK ligand (RANKL), which plays a crucial role in the activation of osteoclasts. The monoclonal antibody denosumab, as a specific RANKL inhibitor, prevents their pairing, thereby reducing the bone destruction induced by BGCT.

Case Description

An 18-year-old woman was admitted to the orthopedic clinic of a university hospital in Porto, having experienced left-sided paravertebral dorsal pain for 4 months. The non-radiating pain persisted despite oral analgesics. MRI examination identified an osteolytic mass in the area of the 9th vertebra. Histopathological analysis, showing typical giant multinucleated cells surrounded by mononuclear cells with eosinophilic cytoplasm, confirmed the diagnosis of SGCT.

Following the initiation of neoadjuvant treatment with denosumab, the dorsal pain subsided within 1 month. After 9 months of treatment, a stabilization spondylosurgical procedure was performed, during which vertebral body samples were taken by curettage for histological analysis. The result was surprisingly negative. Control CT scans revealed better defined and stabilized bone mass. Post-surgery, denosumab treatment continued for another 3 months.

Three years since the start of denosumab treatment and two years post-surgery, there has been no recurrence of localized dorsal pain. The patient occasionally experiences mild postural discomfort, which can be managed with oral paracetamol.

Denosumab has demonstrated extreme efficacy as a neoadjuvant. In addition to reducing symptoms, it stabilized the bone mass and allowed for a less invasive surgical procedure. The surprisingly negative histopathological result revealed its potential curative function. Furthermore, it opened the question of whether concurrent surgery was theoretically unnecessary.

Conclusion

In recent years, denosumab has gained an increasingly significant, albeit still limited, role in the treatment of BGCT and SGCT. Its administration significantly reduces the number of morbid surgical procedures for unresectable bone masses. The absence of tumor cells in this patient’s samples suggests the potential to expand its neoadjuvant role to a curative one. However, further studies with a larger number of patients are needed to confirm this.

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Source: Xará-Leite F., Coutinho L., Fleming C. et al. Can denosumab cure giant cell tumors of the spine? A case report and literature review. Eur J Orthop Surg Traumatol 2020; 30 (1): 19–23, doi: 10.1007/s00590-019-02554-9.