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

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.

Complex immune microenvironment of chordoma: a road map for future treatment

“…In order to further investigate, the immunological characteristics of chordomas and their association with clinical parameters, we used the X-tile software to determine the threshold for survival analysis, we divided the IS and TLS into high and low groups according to the cut-off point. 8 We found that higher IS and TLS were associated with poorer prognosis (p=0.0012 and p<0.001, respectively, figure 1A,B).…”

The tumor-stroma ratio in giant cell tumor of bone: associations with the immune microenvironment and responsiveness to denosumab treatment

“…Immunohistochemical staining was conducted as previously delineated [ 7 , 9 ]. In brief, 4 μm paraffin-embedded sections of 427 GCTB specimens from four institutes were deparaffinized in xylene, rehydrated using a series of graded ethanol solutions, and rinsed in distilled water.…”

“…Despite the widespread utilization of the Campanacci staging system for guiding clinical management and stratifying prognostic risk, robust predictive models remain wanting in comparison to their counterpart [ 5 ]. Although certain molecular markers have been identified as related to the survival and prognosis of GCTB, their study is restricted to the molecular level, thereby risking the dissemination of imprecise prognostic information [ 6 , 7 ]. Furthermore, the stromal cells and tumor cells within the microenvironment are intricately linked [ 8 , 9 ], and the tumor stroma is recognized to play a crucial role in tumor formation, progression, invasion, and metastasis [ 10 , 11 ].…”

Clinicopathological characteristics and prognostic factors in axial chondroblastomas: a retrospective analysis of 61 cases and comparison with extra-axial chondroblastomas

“…LRFS was defined as the duration between tumor resection and the first recurrence, while OS referred to the time from surgical resection to the patient’s death from any cause [ 12 ]. The type of surgical resection was determined based on a previously reported method [ 13 ], distinguishing between wide resection (such as gross total or en bloc resection with negative margins) and non-wide resection (including intralesional or marginal resection).…”