bims-rebome Biomed News
on Management of bone metastases
Issue of 2026–09–27
seven papers selected by
Alberto Selvanetti, Azienda Ospedaliera San Giovanni Addolorata



  1. J Neurosurg Spine. 2026 Sep 25. 1-10
       OBJECTIVE: Stereotactic body radiotherapy (SBRT) has emerged as a highly effective, noninvasive treatment for spinal bone metastases (SBMs). However, long-term outcomes of primary SBRT and the comparative prognostic performance of commonly used decision-making tools remain incompletely defined. This study evaluated long-term local control (LC) and systematically compared the predictive value of the Epidural Spinal Cord Compression (ESCC) grade, Spine Instability Neoplastic Score (SINS), and revised Tokuhashi score (rTS).
    METHODS: The authors retrospectively analyzed 330 patients with 537 SBMs treated with primary CyberKnife SBRT between 2012 and 2023. SBMs with surgical indications under the NOMS (neurological, oncological, mechanical, and systemic) framework, defined as high-grade epidural compression (ESCC grade 2 or 3) and/or spinal instability (SINS > 12), were excluded. LC was defined as absence of radiographic tumor regrowth ≥ 6 months post-SBRT. Cox proportional hazards models identified independent predictors of local progression (LP). Prognostic discrimination of the ESCC grade, SINS, rTS, and a novel integrated multivariable model was evaluated using receiver operating characteristic (ROC) analysis.
    RESULTS: The 1- and 2-year LC rates were 86.2% and 75.9%, respectively, with a median time to LP of 12 months. Independent predictors of LP included radioresistant histology, epidural compression, pain, osteolytic destruction, single-fraction equivalent dose < 20 Gy, and repeat SBRT. Even minimal epidural compression was strongly associated with inferior LC (adjusted hazard ratio [aHR] 2.01, p < 0.001). SBMs with SINS 7-12 also demonstrated significantly worse LC compared with SINS < 7 (aHR 1.78, p = 0.002). The prognostic contribution of rTS was largely driven by performance status alone. ROC analysis showed that the integrated model consistently outperformed the ESCC grade, SINS, and rTS at 1, 3, and 5 years (area under the curve 0.72-0.75 vs 0.59-0.65, all p < 0.05). Acute adverse events occurred in 33.9% of treated SBMs, predominantly pain flare (14.2%). Vertebral fractures developed in 17.0%, 24.2% of which were associated with LP.
    CONCLUSIONS: Primary SBRT for SBMs provided durable LC with acceptable toxicity. Although the ESCC grade, SINS, and rTS offered moderate prognostic utility, an integrated multivariable model incorporating tumor, anatomical, and clinical factors demonstrated superior predictive accuracy. Comprehensive risk stratification may refine patient selection and optimize SBRT strategies.
    Keywords:  local control; oncology; pain management; prognostic factors; spinal bone metastases; stereotactic body radiation therapy; tumor
    DOI:  https://doi.org/10.3171/2026.4.SPINE25212
  2. Curr Oncol. 2026 Sep 02. pii: 528. [Epub ahead of print]33(9):
      Purpose: Although machine learning-based prediction of overall survival (OS) in palliative radiotherapy for bone metastases has been investigated, explainable deep learning (DL) models remain underexplored. This study aimed to develop and validate an explainable DL model to predict OS in this setting, and to examine whether this flexible model provides predictive value beyond a standard Cox model based on routinely collected baseline variables. Methods and Materials: We analyzed all 472 eligible patients who received palliative radiotherapy for bone metastases between January 2013 and August 2024; patients alive with less than one year of follow-up were retained as right-censored observations. The primary endpoint was OS over a fixed 1-year horizon. A DeepSurv model using 14 baseline predictors, including the planned prescribed dose (biologically effective dose, BED10), was developed with repeated 5-fold cross-validation (K = 5, R = 10) and compared with standard and ridge-penalized Cox models fitted on identical splits. Performance was assessed by the time-dependent concordance index (C-index), integrated Brier score (IBS), time-dependent area under the curve (AUC) at 90, 180, and 365 days, and a calibration analysis at one year; 95% confidence intervals (CI) were obtained by patient-level bootstrapping of the pooled out-of-fold predictions. Shapley Additive Explanations (SHAP) and SurvLIME were computed on the held-out test sets. Results: Within one year, 242 patients (51.3%) died; median OS was 225 days (95% CI: 189-287). The DeepSurv model achieved a pooled time-dependent C-index of 0.779 (95% CI: 0.751-0.807), an IBS of 0.135 (95% CI: 0.122-0.149), and AUCs of 0.892 (0.857-0.925), 0.862 (0.822-0.895), and 0.856 (0.814-0.895) at 90, 180, and 365 days, with an observed/expected ratio of 0.94 and a calibration slope of 1.02; discrimination was comparable to the Cox model (C-index 0.763, 95% CI: 0.737-0.789). SHAP identified poor performance status as the dominant predictor (mean |SHAP| 0.178), followed by male sex (0.067), high-risk primary tumor type (0.063), multiple bone metastases (0.047), and planned dose (0.033), the latter being the only leading feature associated with lower predicted mortality; SurvLIME gave consistent results. In multivariable Cox analysis, performance status (hazard ratio [HR] 2.21 per standard deviation [SD], p < 0.001) and planned dose (HR 0.71 per SD, p < 0.001) were independently associated with OS. Conclusions: The explainable DL model predicted OS after palliative radiotherapy for bone metastases with discrimination and calibration comparable to those of a well-specified Cox model, and its feature attributions agreed with the Cox coefficients, suggesting that the prognostic information in these baseline variables is essentially additive and can therefore be delivered at the bedside as a simple score, without dedicated AI infrastructure and without loss of predictive performance. The combined use of SHAP and SurvLIME verified that the model relies on established clinical factors, most prominently performance status, and provides patient-level explanations. Pending external validation, such prediction may support individualized decisions on treatment goals and radiation schedules.
    Keywords:  bone neoplasms; deep learning; prognosis; radiation dosage; radiotherapy
    DOI:  https://doi.org/10.3390/curroncol33090528
  3. Front Oncol. 2026 ;16 1901644
       Objective: To investigate the association between surgical timing and neurological recovery and survival in patients with complete or incomplete paralysis due to metastatic spinal cord compression, and to develop a nomogram for predicting marked neurological recovery.
    Methods: A total of 302 patients who underwent surgical decompression for spinal metastasis-induced paralysis between 2019 and 2023 were retrospectively analyzed. Patients were divided into four groups based on the time from paralysis onset to surgery: <24h, 24-72h, 72h-1w, and >1w. The primary outcome was marked neurological recovery (improvement to AIS D/E). Survival outcomes were also assessed. Multivariable Firth penalized logistic regression and Cox proportional hazards regression were performed. A nomogram was constructed and validated using bootstrap resampling (C-index, calibration curve, ROC curve, and decision curve analysis).
    Results: Earlier surgery was strongly associated with better neurological recovery. Compared with the <24h group, the odds ratios for marked recovery were 0.69 (24-72h, p=0.361), 0.34 (72h-1w, p=0.019), and 0.17 (>1w, p<0.001). Delayed surgery was associated with significantly increased mortality risk: hazard ratios were 1.87 (72h-1w, p=0.026) and 4.44 (>1w, p<0.001). Preoperative AIS grade C (OR=6.86, p<0.001), higher ESCC grade (grade 2 vs. 1C: OR=0.14; grade 3 vs. 1C: OR=0.28), and flaccid muscle tone (OR=0.23, p<0.001) were independent predictors of recovery. The nomogram showed excellent discrimination with a bootstrap-corrected C-index of 0.873 and an AUC of 0.888 (95% CI: 0.852-0.925). Decision curve analysis confirmed its clinical utility.
    Conclusion: Early surgery (within 1 week, ideally <24h) was associated with better neurological recovery and longer survival in patients with spinal metastasis-induced paralysis. However, given the retrospective design and the absence of key oncological covariates-including performance status, systemic disease burden, and visceral metastases-the survival association should be interpreted with caution and does not imply causality. Preoperative AIS grade C was associated with better recovery, while higher ESCC grade (grade 2 vs. 1C: OR=0.14; grade 3 vs. 1C: OR=0.28) was associated with lower odds of recovery, indicating that patients with less severe cord compression (ESCC grade 1C) had better outcomes. Flaccid muscle tone predicted poorer outcomes. The proposed nomogram provides a preliminary tool for individualized prediction of marked neurological recovery, pending external validation.
    Keywords:  epidural spinal cord compression; neurological recovery; nomogram; paralysis; spinal metastasis; surgical timing
    DOI:  https://doi.org/10.3389/fonc.2026.1901644
  4. J Mech Behav Biomed Mater. 2026 Sep 18. pii: S1751-6161(26)00302-4. [Epub ahead of print]184 107633
      Bone metastases, remarkably common in the vertebral bodies of advanced cancer patients, are associated with an increased risk of vertebral fracture. To assess vertebral strength, subject-specific biomechanical models have been proposed based on quantitative computed tomography. Such models have been evaluated on a single dedicated dataset often acquired by the same team. The goal of this paper is to compare different biomechanical models with four experimental datasets to strengthen their validation. Finite element models developed by three groups at the University of Bern, University of Lyon, and "Institut de Biomécanique Humaine Georges Charpak" of Paris, were used to simulate the strength of four different experiments that included 1) intact non-metastatic vertebrae with endplates embedded in endcaps during experimental tests, vertebrae with simulated defects representing osteolytic bone metastasis foci with endplates removed, and metastatic vertebrae from cancer donors with the endplates removed. The simulation results show the determination coefficient to range between 0.28 and 0.96 with a slope of the correlation between experimental and numerical failure strengths from 0.32 to 1.69. The bias (difference between experimental and numerical failure strengths) varied from -3749 and + 1368 N, corresponding to -48.6% to +77%. The experimental removal of the endplates influenced FE model predictions. This study illustrates the need for extensive validation of models before their potential use in clinical practice. To encourage such validation, the experimental datasets were made available in open data.
    Keywords:  Constitutive laws; Failure criteria; Subject-specific finite element model; Vertebral body; With and without endplates
    DOI:  https://doi.org/10.1016/j.jmbbm.2026.107633
  5. Clin Spine Surg. 2026 Sep 21.
       STUDY DESIGN: Narrative review.
    OBJECTIVE: To provide an overview of outcomes, cost-effectiveness, local control, survivorship, and prognostic decision-making in cervical spine oncology.
    SUMMARY OF BACKGROUND DATA: Cervical spine oncology includes both metastatic and primary tumors, each with distinct treatment goals and oncologic considerations. Cervical spine tumors can impair quality of life through pain, neurological deficits, and mechanical instability.
    METHODS: This review synthesizes current literature on neurological and functional outcomes, health-related quality of life (HRQOL), cost-effectiveness, local control, survivorship, and prognostic decision-making in cervical spine oncology.
    RESULTS: Prospective multicenter studies demonstrate significant improvements in pain, neurological function, and HRQOL after surgery for metastatic cervical spine disease. Separation surgery followed by stereotactic body radiotherapy (SBRT) achieves high rates of local control in appropriately selected patients. Cost-effectiveness is greatest among patients with acute neurological compromise and favorable survival prognoses. We additionally review prognostic classification systems, machine-learning algorithms, and outcomes in primary cervical spine tumors including cervical chordoma.
    CONCLUSIONS: Cervical spine oncology requires individualized multidisciplinary treatment. Prospective outcomes data, validated patient-reported outcome instruments, modern radiation strategies, and prognostic algorithms support contemporary decision-making in patients with cervical spine tumors.
    Keywords:  cervical spine oncology; outcomes; patient-reported outcomes; quality of life; value
    DOI:  https://doi.org/10.1097/BSD.0000000000002167
  6. Oncol Res. 2026 ;34(10): 14
      Breast cancer (BC) has become the most commonly diagnosed malignant tumor among women worldwide, with approximately 70% of patients with advanced BC developing bone metastases. These metastases trigger bone destruction and skeletal-related events (SREs) and significantly reduce patient survival. In recent years, research into the mechanisms underlying BC bone metastasis has advanced rapidly. Molecular biological and genomic studies have revealed that BC bone metastasis is co-regulated by multiple signaling pathways through crosstalk between BC cells and the bone microenvironment. This review analyzes the research progress of signaling pathways involved in BC bone metastasis and systematically elaborates four core cascades: Wingless-related integration site (Wnt)/β-catenin, transforming growth factor-β (TGF-β), RANK/receptor activator of nuclear factor-κB ligand (RANKL)/osteoclastogenesis inhibitory factor (OPG), and phosphatidylinositol 3-Kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR). It explains how each pathway mediates epithelial-mesenchymal transition (EMT), excessive Osteoclast (OC) activation, maintenance of cancer stem cell stemness, and the formation of an immunosuppressive microenvironment. The positive feedback loops and reciprocal crosstalk between these pathways are also summarized, which together fuel the vicious cycle of osteolytic bone metastasis. This paper further consolidates therapeutic strategies targeting the aforementioned signaling pathways and outlines cutting-edge therapeutic approaches and emerging research hotspots. Nevertheless, critical obstacles including complex pathway compensation, drug resistance, and dysregulated bone immunity remain major bottlenecks hindering clinical translation. Future research will leverage single-cell sequencing and multi-omics technologies to identify pivotal molecular targets and develop potent combinatorial therapies. Such advances will facilitate the implementation of precise, individualized treatment for BC bone metastasis and ultimately improve the quality of life and long-term clinical outcomes of patients with advanced bone-metastatic disease.
    Keywords:  Breast cancer (BC); bone metastasis; bone microenvironment; signaling pathway; targeted therapy
    DOI:  https://doi.org/10.32604/or.2026.079898
  7. J Bone Oncol. 2026 Dec;61 100802
       Background: Vertebral augmentation techniques, including vertebroplasty and kyphoplasty, are widely used to relieve pain and restore spinal stability in patients with metastatic vertebral lesions. Despite their widespread use, the full spectrum and clinical significance of procedure-related complications remain incompletely characterised. This systematic review aims to summarise and characterise all reported complications associated with vertebral augmentation for metastatic thoracolumbar disease.
    Methods: A comprehensive search of PubMed/MEDLINE, Scopus, and Web of Science databases was performed. Studies reporting complications associated with vertebral augmentation procedures for metastatic thoracolumbar spinal fractures were included. Randomised controlled trials, observational studies, case series, and case reports were eligible. Due to substantial heterogeneity across studies, a descriptive synthesis was performed.
    Results: A total of 76 studies were included, comprising 3234 patients and at least 5737 vertebral levels treated. The overall weighted complication rate was 25.5%, while the weighted rate of symptomatic complications was 3.41%. Cement leakage was the most frequently reported complication, with a weighted mean incidence of 20.7%, although the majority were asymptomatic. Other complications included postprocedural pain (1.77%), pulmonary cement embolism (1.08%), and adjacent level fractures (0.79%). Studies using CT imaging reported significantly higher cement leakage rates (28.6% vs 11.9%, p = 0.004). Case reports described rare but potentially severe complications, including needle-tract tumour seeding, tumour extrusion, and cement migration to cardiac structures.
    Conclusions: This review presents a comprehensive and detailed description of all complications of vertebral augmentation for treatment of metastatic spine disease and reinforce its safety. Differences in imaging protocols and reporting standards contribute to variability in reported complication rates. Further prospective studies with standardised complication reporting are needed.
    Keywords:  Kyphoplasty; Neoplasm metastasis; Postoperative complications; Spinal fractures; Vertebroplasty
    DOI:  https://doi.org/10.1016/j.jbo.2026.100802