# Which Clinical Factors Are Associated with the Post-Denosumab Size Reduction of Giant Cell Tumors? The Korean Society of Spinal Tumor (KSST) Multicenter Study 2023-02

## TL;DR

This study identifies clinical factors that predict tumor shrinkage in giant cell tumors of bone after denosumab treatment, helping guide personalized treatment strategies.

## Contribution

The study identifies specific clinical predictors of post-denosumab tumor shrinkage in giant cell tumors of bone.

## Key findings

- Campanacci grade III is a significant predictor of tumor shrinkage in various patient groups.
- Aneurysmal bone cyst-like changes are associated with tumor size reduction in primary lesions.
- Baseline tumor size of ≥7 cm predicts shrinkage in spinopelvic lesions.

## Abstract

Denosumab is known to reduce the size of giant cell tumor of bone (GCTB) under some conditions, which is a therapeutic effect distinct from downstaging. However, the clinical predictive factors associated with such a response remain uncertain. This study aimed to identify predictors of post-denosumab tumor shrinkage in various clinical GCTB settings. Campanacci grade III was a significant predictor of shrinkage in the overall cohort, and in patients with extremity or primary lesions. Aneurysmal bone cyst-like change was associated with size reduction in the overall cohort and in patients with primary tumors. Additionally, a large baseline tumor size predicted shrinkage in all patients and those with spinopelvic GCTBs. Recognizing these factors may help clinicians better anticipate response to denosumab and guide treatment strategies tailored to individual patients.

Background/Objectives: Denosumab has been considered effective for downstaging giant cell tumor of bone (GCTB), implying that it lowers the Campanacci grade rather than reducing tumor size. Preoperative tumor shrinkage holds therapeutic value by decreasing surgical complications. While previous studies have observed lesion shrinkage in some patients, no study has identified the types of patients likely to show treatment response. Thus, we sought to identify the clinical factors associated with post-denosumab GCTB size reduction. Methods: The data for 45 GCTB patients (29 females [64%], 16 males [36%], median age 32 years [range: 17–65]) who received denosumab were analyzed. Lesions were in the extremities (n = 25, 56%) or spinopelvic region (n = 20, 44%). Ten (22%) were recurrent. Lesion size reduction was assessed using two criteria: a ≥5% and a ≥5 mm decrease in the longest diameter. Univariate analyses were conducted for all variables, and those found to be significant were subjected to multivariate analyses. In addition, multicollinearity was evaluated. Subgroup analyses were performed based on lesion location and recurrence status. Results: Campanacci grade III predicted proportional shrinkage (≥5%) in all patients (OR 4.819, 95% CI 1.121–20.714) and in extremity (OR 11.171, 95% CI 1.023–122.014) and primary lesions (OR 5.781, 95% CI 1.181–28.297), and aneurysmal bone cyst (ABC)-like change was associated with absolute shrinkage (≥5 mm) in all patients (OR 8.734, 95% CI 1.159–65.845) and primary lesions (OR 11.936, 95% CI 1.074–132.69). The longest tumor diameter of ≥7 cm predicted absolute shrinkage in all patients (OR 12.380, 95% CI 1.038–147.694) and for spinopelvic lesions (OR 20, 95% CI 1.676–238.63). Conclusions: ABC-like change, Campanacci grade III, and the longest tumor diameter might predict post-denosumab GCTB shrinkage in all patients, though shrinkage varies with lesion location and recurrence status. These factors could help clinicians tailor treatment strategies in different settings. Further research is needed to explore how clinical factors pharmacologically influence denosumab-induced GCTB shrinkage.