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기사글확대 기사글축소 기사스크랩 이메일문의 프린트하기
Clinical Experiences of Giant Cell Tumors of the Spine after Treatment with Denosumab
연세대학교 의과대학 신경외과학교실 김병우 교수(김긍년, 윤도흠, 하 윤, 신동아, 이 성)
[ 2015년 01월 02일 01시 11분 ]

Objective: To describe the 4 cases of clicical and radiographic results of spinal giant cell tumors(GCTs) after treatment with the new RANKL antibody denosumab

 

Methods: The authors describe 4 patients with recurrent or unresectable spinal GCTs who received sub-cutaneous denosumab 120 mg monthly (every 4 weeks), with loading doses on days 8 and 15 of month 1. patient treatment and follow-up are ongoing. The primary endpoint is tumor response, defined as complete remission of GCTs or no radiological progression of the target lesion up to week 25. patient assessment included physical examination, ECOG performance status, blood samples, and urinary N-telo-peptide corrected by creatinine(uNTx/Cr). Spiral CT scan and MRI imaging were planned every 3 months until the end of the study. The side effects of denosumab were also reported.

 

Results: The first case was 18-year-old female patient with a recurrent unresectable spinal GCT involving C6 vertebral body and with encircling right vertebral artery and abutting left vertebral artery. Pri-mary resectable tumor of hers was treated in total removal surgery and postoperative adjuvant radiotherapy. However, she suffered tumor recurrence in 21 months. she finally underwent enbloc resection for recurrent GCT. The unresectable residual tumor was treated in monotherapy with denosumab postoperatively. The 19-month radiographic follow up demonstrated complete disappearance of the residual tumor and no recurrence.

 

The second case was 26-year-old female patient with a recurrent unresectable tumor involving T10 vertebrae and lung meatastasis. She was initially treated with enbloc resection and postoperative adjuvant radiation therapy for tumor margin. However she suffer tumor local recurrence and lung metastasis in 12 months. The wedge resection of lung and revision surgery for local recurrent tumor was performed. Within 2 months after second surgery, she suffered progression of lung metastasis. The unresectable recurrent tumor was treated in monotherapy with denosumab. Starting the denosumab in 3 months, follow-up chest CT scan showed decreased size of metastatic lung nodules and her spinal MRI also showed no evidence of local tumor recurrence.

 

The third case was 33-year-old female patient with a recurrent resectable spinal GCT involving L3/4 vertebrae, right psoas muscle and paravertebral spaces. She underwent enbloc resection surgery for primary GCT of L4 vertebrae. However, the tumor recurrence occurred in 12 months. She refused the surgery for recurrent tumor and was finally treated in mono therapy with denosumab. After 20 weeks, the painful symptom was absent and the radiographic follow-up demonstrated disappearance of the osteolytic lesion and new cortical bone formation with restoration of the bone integrity of the L4 vertebral body.

 

The fourth case was 47-year-old female patient with residual unresectable GCT of T1 vertebrae and was initially treated with enbloc resection. The residual tumor was treated in combined therapy with denosumab and radiotherapy. The first case finished the denosumab treatment schedules and maintained oral bisphosphonate only. The current image studies showed no evidence of tumor recurrence. The treatments of last 3 cases are ongoing and the assessment of tumor response is planned up to week 25. All patients suffered no major side effects of the denosumab including hypocalcemia, osteonecrosis of jaw and atypical femoral fracture.

 

Conclusion: This is the first case series of clinical and radiological response of spinal GCTs after treatment with the new RANKL antibody denosumab. Although patient number is very small and long-term follow-up studies are still necessary, denosumab promises to control the tumor recurrences and locally aggressive their behavior. Our study certainly provides the clinical evidences to establish the best therapeutic paradigm for GCTs of the spine.

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