Beyond Anatomical Resectability: A Hypermetabolic and Highly Aggressive Subtype of Spinal Chordoma Associated with Cancer-Specific Progression.

Abstract

Spinal chordoma demonstrates substantial biological heterogeneity, with a subset exhibiting highly aggressive behavior. However, existing isolated prognostic factors remain insufficient for reliable preoperative risk stratification. To characterize a metabolically aggressive phenotype (MAP) of spinal chordoma associated with malignant events (MEs) and to develop a preliminary preoperative prognostic stratification score. Retrospective single-center cohort study. 36 patients with newly diagnosed spinal chordoma who underwent preoperative PET/CT examination and comprehensive clinical, radiological, and pathological evaluation were finally included. The median follow-up was 78.5 months. Primary outcomes were recurrence, metastasis, and cancer-specific death (CSD). The composite MEs endpoint comprised recurrence, metastasis, and CSD. PET/CT-derived metabolic parameters together with clinical, imaging, pathological, and laboratory variables were analyzed to identify patients at increased risk of MEs. Model performance was evaluated using time-dependent ROC curves, calibration curves, decision curve analysis, and bootstrap validation. Across analyses of the individual outcomes, higher PET/CT-derived metabolic tumor volume (MTV), total lesion glycolysis (TLG), Spinal Instability Neoplastic Score (SINS) >10, Enneking stage of IIB, elevated C-reactive protein levels, and hemorrhagic-necrotic pathology emerged as significant adverse features. In multivariable analysis, SINS score >10 (HR=4.685, P=0.026) and Enneking stage of IIB (HR=4.647, P=0.014) were significantly associated with MEs, whereas MTV >35 cm³ showed a borderline association (HR=2.242, P=0.053). The model demonstrated a C-index of 0.812 (bootstrap-corrected: 0.782), and time-dependent AUCs of 0.706, 0.899, and 0.918 at 12, 36, and 60 months. A preliminary MAP-associated MEs score was developed to stratify patients into low-, intermediate-, or high-risk groups. The MAP in spinal chordoma is characterized by a triad of elevated PET/CT-derived MTV and/or TLG, hemorrhagic-necrotic pathology, and increased inflammatory activity. MAP is associated with MEs and demonstrates concordance with clinical and radiological indicators. The MAP-associated MEs score provides a biologically interpretable framework for risk stratification and may support individualized multidisciplinary treatment planning.