Chief Resident & Enfolded Spine Fellow Northwell Health Manhasset, NY, US
Introduction: Sarcomas affecting the spine present unique therapeutic challenges, requiring carefully coordinated treatment approaches. While tumor purity and mutation load are emerging as important biomarkers in cancer therapy, their relationship and clinical significance in sarcomas, particularly those affecting the spine, remain poorly understood. Understanding these molecular characteristics could provide crucial insights for treatment selection and timing of interventions in spinal tumors.
Methods: We analyzed 7,126 sarcoma cases from the openly available Memorial Sloan Kettering 2022 cohort available through cBioPortal, including soft tissue (69.8%), bone (15.8%), and uterine (9.5%) sarcomas. Molecular characteristics were assessed using the MSK-IMPACT platform, with quality control measures excluding 368 cases due to incomplete data. We examined correlations between tumor purity, mutation load, age, and sex using non-parametric methods. Subtype-specific analyses were performed using Kruskal-Wallis tests with Bonferroni-corrected post-hoc comparisons. Microsatellite instability status was evaluated across all cases.
Results: We identified significant correlations between mutation load and tumor purity (ρ=0.320, P<.001), with marked heterogeneity across subtypes. Tumor purity varied substantially between subtypes, ranging from 20.0% in brain tumors to 78.5% in skin sarcomas. Strong age-related molecular changes were observed in brain (ρ=0.711, P=.006) and skin sarcomas (ρ=0.450, P=.006), suggesting distinct evolutionary patterns. Males demonstrated lower mutation loads compared to females (median: 1.61 vs 2.42, P<.001) and lower tumor purity (median: 53.0% vs 60.0%, P<.001). Microsatellite instability-high status was rare (0.24%) but associated with significantly higher mutation loads (median 25.84 vs 2.42, P<.001), particularly in uterine sarcomas (0.7% prevalence).
Conclusion : This comprehensive molecular analysis reveals distinct patterns across sarcoma subtypes that may inform treatment approaches for spinal tumors. The identified relationships between tumor purity, mutation load, and clinical characteristics suggest potential implications for therapeutic stratification, particularly regarding timing and selection of treatment modalities. These findings add to the foundation for molecular-guided treatment selection in sarcoma patients and highlight the importance of integrating molecular features into clinical decision-making for spinal tumor management. Future studies specifically examining these molecular patterns in primary spinal sarcomas may further refine treatment algorithms for this challenging patient population.