Survival prediction in metastatic long-bone disease is essential for surgical decision-making, yet the performance of legacy prognostic models has declined in the era of immunotherapy and molecularly targeted agents. As these systemic therapies become routine, treatment patterns themselves may influence survival in ways not captured by earlier models. We, therefore, quantified preoperative systemic therapy use over the last decade and evaluated its association with postoperative overall survival in patients undergoing surgery for long-bone metastases. We conducted a retrospective cohort study of 975 consecutive adults who underwent surgery for long-bone metastases at two affiliated tertiary centers between January 2010 and June 2022. Preoperative systemic therapy was categorized into four groups: chemotherapy only, targeted therapy only, combined chemotherapy and targeted therapy, or neither. Postoperative was defined as time from surgery to death from any cause. We described temporal uptake of therapies by calendar year and assessed associations with postoperative survival using multivariable Cox regression adjusting for demographics, ECOG performance status, Katagiri primary tumor grouping, visceral/brain metastases, and laboratory variables. Adjusted survival over calendar time was summarized via marginal standardization at fixed horizons (1, 3, 12, and 24months). Use of targeted agents including checkpoint inhibitors rose markedly, from 2% in 2015 to 43% in 2022. In multivariable Cox models, preoperative chemotherapy alone was associated with worse survival versus no preoperative systemic therapy (HR 1.41, 95% CI 1.21-1.65; p<0.01), as was combined chemotherapy plus targeted therapy (HR 1.24, 95% CI 1.05-1.47; p=0.01). In contrast, targeted therapy alone before surgery was associated with better survival (HR 0.76, 95% CI 0.58-0.99; p=0.04). Adjusted survival appeared to increase modestly across calendar years, but the pre-specified joint Wald test for the calendar year spline terms was not significant (p=0.17), indicating a non-significant trend over time. This study found that preoperative systemic therapy patterns are strongly associated with post-operative survival in metastatic long-bone disease: targeted therapy alone correlates with improved survival whereas preoperative use of chemotherapy-alone or combined with targeted agents-was associated with worse survival. These findings support incorporating contemporary treatment exposure into prognostic models and suggest that model recalibration to the immunotherapy era may be warranted.

Metastases-directed radiotherapy plays an increasing role in oligometastatic prostate cancers (OMPC). Here, we investigated the role of stereotactic body radiotherapy (SBRT) for spine and non-spine bone metastases (BoM) from prostate cancer in a large real-world multicenter cohort. This multicenter cohort analysis from five tertiary cancer centers included patient data of spine and non-spine BoM irradiated between 2010 and 2024. Overall survival (OS), progression-free survival (PFS), local recurrence-free survival (LRFS), SBRT target volumes and doses, toxicity, and the role of additional systemic therapies were evaluated retrospectively. 231 patients (341 BoM) with median follow-up time of 28.3months were included. Most common localization were spine (39.3%), pelvic bone (31.7%), and ribs (17.9%). 1- and 5-year PFS for spine BoM were 93.8% (95%CI:84.2-97.6%) and 32.1% (95%CI:16.8-44.4%) and for non-spine BoM 91.7% (95%CI:85.1-95.5%) and 36.6% (95%CI:25.8-47.5%), respectively. 1- and 5-year OS for spine BoM amounted to 94.2% (95%CI:85.3-97.8%) and 69.2% (95%CI:50.2-82.2%) and for non-spine 100% and 73.3% (95%CI:59.1-83.3%). Older age (p<0.005) and additional systemic therapies (p=0.05) were associated with worse OS, older age and larger treatment volumes with worse PFS (p=0.04). Toxicities were low, with fracture rates of 0.3% (acute) and 1.2% (late). Bone SBRT for OMPC is an effective treatment with low toxicity and particularly low fracture rates for both spine and non-spine BoM with no difference in outcome based on the localization. Prospective trials will help to identify the patients benefitting most from this approach and to establish standardized SBRT concepts incorporating systemic treatments.

Ewing sarcoma (EwS) is the second most prevalent pediatric bone malignancy, characterized by its aggressive behavior and unfavorable prognosis. The tumor microenvironment (TME) of EwS is shaped by immunosuppressive components, including myeloid-derived suppressor cells, tumor-associated macrophages, and immune checkpoint molecules such as PD-1/PD-L1 and HLA-G. These elements impair anti-tumor immune responses by modulating the function of tumor-infiltrating immune cells, such as regulatory T cells (Tregs), CD8+ T cells, and natural killer cells. Chemokines, including CXCL9 and CXCL12, and cytokines, such as transforming growth factor-beta and interleukin-10, further contribute to immune suppression and promote metastatic dissemination. Recent advances in immunotherapy have highlighted the therapeutic potential of modulating immune cells and signaling pathways to enhance anti-tumor immunity. This review provides a comprehensive analysis of the complex immune landscape within the EwS TME, focusing on the mechanistic roles of key immune components and their potential as therapeutic targets. Understanding these interactions could pave the way for innovative treatment strategies to improve clinical outcomes in patients with EwS.