Ultra-Short Course of Neo-Adjuvant Denosumab for Nerve-Sparing Surgery for Giant Cell Tumor of Bone in Sacrum

Abstract

Study Deign. This was a retrospective study about sacral giant cell tumor of bone (GCTB).Objective. This study aimed to investigate whether ultra-short course of neo-adjuvant denosumab treatment for sacral GCTB could (1) induce radiological and histological response? (2) Facilitate nerve-sparing surgery? (3) Achieve satisfactory oncological and functional outcomes? Summary of Background Data. Previous reports on long course of neo-adjuvant denosumab treatment for GCTB showed significant tumor response and a relatively high recurrent rate after curettage. Methods. Sixty-six patients with sacral GCTB treated with neoadjuvant denosumab and nerve-sparing surgery were categorized into ultra-short course group ( 3 doses and operation within D21 since 1st dose, 41 patients) or conventional group (>3 doses or operation after D21 since 1st dose, 25 patients). The radiological and histological response, operative data, oncological and functional outcomes were compared. Results. The ultra-short course group demonstrated fewer doses of neo-adjuvant denosumab (mean: 2.1 vs. 4.8, P < 0.001) and shorter time to surgery (12.2 days vs. 72.3days, P < 0.001). Similar patterns of radiological and histological response were observed in the two groups with less fibrosis and ossification in the ultra-short course group. The operative duration (199.9 min vs. 187.8 min, P ¼ 0.364) and estimated blood loss (1552.4 mL vs. 1474.0 mL, P ¼ 0.740) were comparable. Most (94.8%) of the patients received adjuvant denosumab. After a mean follow-up of 29.4 months, three cases (8.8%) and five cases (20.8%) showed local recurrence in each group (P ¼ 0.255). The estimated recurrence-free survival (56.2 vs. 51.2 months, P ¼ 0.210) and the functional status [Motor-Urination-Defecation scores: 25.9 vs. 25.7, P ¼ 0.762] did not differ between the two groups. Conclusion. Ultra-short course of neo-adjuvant denosumab for sacral GCTB could elicit radiological and histological responses as conventional course did. The less degree of fibrosis and ossification might facilitate nerve-sparing surgery and help to achieve satisfactory local control and functional status.

Reconstruction after hemisacrectomy with a novel 3D-printed modular hemisacrum implant in sacral giant cell tumor of the bone

“…With the use of bleeding control drugs, preoperative selective arterial embolization, and intraoperative aortic balloon, nerve-preserving surgery for sacral GCTB has become feasible and the risk of recurrence is acceptable. In this study, neoadjuvant treatment with a short course of preoperative denosumab reduced tumor blood supply without increasing tumor–nerve adhesions ( Liang et al, 2022 ). Abdominal aortic balloon placement on the day of surgery can provide satisfactory bleeding control.…”

Progress on Denosumab Use in Giant Cell Tumor of Bone: Dose and Duration of Therapy

“…A retrospective study comparing preoperative ultra-short courses (≤3 doses) and conventional courses (>3 doses) of PATD for sacral GCTB suggested that the former could elicit radiological and histological responses like conventional courses. A smaller degree of fibrosis and ossification facilitates nerve-sparing surgery and contributes to achieving satisfactory local control and functional status while reducing LR risk [ 26 ]. For joint-salvage surgery, a short course of PATD (≤three doses) had similar clinical scores, histological and radiological responses, or relapse-free survival as longer courses of therapy (>three doses).…”

“…Pre-operative adjuvant therapy with denosumab (PATD) may increase the risk of LR in GCTB [ 23 , 24 , 25 ]. Conversely, a short pre-operative course of denosumab (≤3 doses) may also achieve satisfactory local control and functionality in GCTB [ 26 ]. PATD can reduce blood supply and should not be used for more than 3 months [ 27 ].…”

Case Report: Unresectable pulmonary metastases of a giant cell tumor of bone treated with denosumab: a case report and review of literature

“…In another study including 43 patients with resectable GCTB and 54 patients with unresectable GCTB, all tumors were controlled by denosumab treatment, whereas 40% of patients who discontinued denosumab showed tumor progression after a median of 8 months (12). Furthermore, it is reported that neoadjuvant treatment with denosumab can downstage the lesions by increasing the thickness of cortical bone and forming new cortical rim around the soft-tissue mass that facilitates joint salvage and decrease surgery invasiveness (1,(17)(18)(19)(20)(21)(22)(23). Although denosumab does not have direct cytotoxic effect on neoplastic stromal cells, it can inhibit pulmonary metastases.…”