Tumor Growth Rate in Spinal Giant Cell Tumors of Bone and Association With the Immune Microenvironment and Denosumab Treatment Responsiveness: A Multicenter Study

Neurosurgery. 2023 Mar 1;92(3):524-537. doi: 10.1227/neu.0000000000002237. Epub 2022 Nov 21.

Abstract

Background: Currently, little is known about the prognostic value of tumor growth rate (TGR) in spinal giant cell tumors of bone (GCTB).

Objective: To investigate the correlation of TGR with clinicopathological features, immune microenvironment, prognosis, and response to denosumab treatment of spinal GCTB.

Methods: A total of 128 patients with spinal GCTB treated at 5 centers from 2011 to 2021 were included. TGR was assessed by 2 independent neuroradiologists using at least 2 preoperative thin-section magnetic resonance imaging scans at a minimum interval of 2 months. Immunohistochemistry was used to assess tumor-infiltrating lymphocyte subtypes for CD3, CD4, CD8, CD20, PD-1, PD-L1, and Foxp3. Then, these parameters were analyzed for their associations with patient outcomes (progression-free survival and overall survival), clinicopathological features, and denosumab treatment responsiveness.

Results: High TGR predicted both poor progression-free survival and overall survival (both P < .001). In addition, TGR was associated with postoperative neurological dysfunction ( P < .001), Enneking staging ( P = .016), denosumab treatment responsiveness ( P = .035), and the number of CD3 + ( P < .001), PD-1 + ( P = .009), PD-L1 + ( P < .001), and FoxP3 + tumor-infiltrating lymphocyte ( P = .02). Importantly, TGR outperformed the traditional Enneking, Campanacci, and American Joint Committee on Cancer staging systems in predicting the clinical outcomes of spinal GCTB.

Conclusion: These data support the use of TGR as a reliable predictive tool for clinically relevant outcomes and response to denosumab therapy of spinal GCTB, which may be helpful in guiding prognostic risk stratification and therapeutic optimization of patients.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • B7-H1 Antigen
  • Bone Density Conservation Agents* / therapeutic use
  • Bone Neoplasms* / drug therapy
  • Denosumab / therapeutic use
  • Forkhead Transcription Factors / therapeutic use
  • Giant Cell Tumor of Bone* / diagnostic imaging
  • Giant Cell Tumor of Bone* / drug therapy
  • Giant Cell Tumor of Bone* / pathology
  • Humans
  • Programmed Cell Death 1 Receptor
  • Tumor Microenvironment

Substances

  • Denosumab
  • B7-H1 Antigen
  • Bone Density Conservation Agents
  • Programmed Cell Death 1 Receptor
  • Forkhead Transcription Factors