bims-rebome Biomed News
on Management of bone metastases
Issue of 2026–10–04
seven papers selected by
Alberto Selvanetti, Azienda Ospedaliera San Giovanni Addolorata
  1. Comparative Analysis of Prognostic Scoring Systems for Survival Prediction in Patients Undergoing Surgery for Spinal Metastases: A GRADE-approached Systematic Review and Meta-Analysis.
  2. [Multidisciplinary Management of Bone Metastases in Clinical Practice].
  3. When to refer for surgery in long bone metastases: A powered multivariate analysis of fracture risk and simple algorithm for referral for surgery (the metastatic fracture prediction met FRAP score).
  4. Immune checkpoint inhibition in bone metastases: lesion response heterogeneity, the osteoimmune niche, and microenvironment-directed therapy.
  5. Analysis of the heterogeneity of the immune microenvironment of bone metastases and new strategies of nanotechnology intervention.
  6. Metastatic Bone Disease Is Associated With Longitudinal Muscle Loss and Reduced Survival in Kidney Cancer.
  7. Bone metastasis in cancer: from microenvironmental remodeling to precision therapy.
  1. J Pak Med Assoc. 2026 Sep;76(Suppl 1)(9): S31
    Comparative Analysis of Prognostic Scoring Systems for Survival Prediction in Patients Undergoing Surgery for Spinal Metastases: A GRADE-approached Systematic Review and Meta-Analysis.
    Kanchan Chaudhary, Mohammad A Zaied, Abdallah Shawwa, Hamza Ahabbane, Mira Alnaser Khashman, Moath Naser.
       Objectives: Accurate estimation of survival is fundamental to guiding surgical decision-making in patients with spinal metastases. Several prognostic scoring systems have been developed, yet their relative accuracy remains uncertain. This review aimed to compare the discriminatory performance of six widely used models, Revised Tokuhashi, Tomita, Modified Bauer, Skeletal Oncology Research Group (SORG) Machine Learning, SORG Classic, and SORG Nomogram, in predicting postoperative survival.
    Method: This review adhered to the PRISMA 2020 guidelines and was prospectively registered with PROSPERO (CRD420251056914). PubMed, Scopus, and Web of Science were systematically searched to identify studies from 2014 until July/2025 and researched on 26th/January/2026, involving adults with spinal metastases treated surgically that reported time-specific AUROC or concordance index (C-index) for at least two of the aforementioned prognostic models. Data extraction and quality assessment were independently performed using the QUADS-2 tool. Random-effects meta-analyses (REML) of logit-transformed AUROCs were conducted at 3, 6, and 12 months intervals.
    RESULTS: Seventeen studies encompassing 4465 patients published between 2014 and 2025 were included. Tomita, Revised Tokuhashi, Modified Bauer scores demonstrated moderate discriminatory performance (pooled AUROC 0.60-0.69) across all time intervals, while the SORG Nomogram achieved the highest pooled performance with AUROC values of 0.72 (95% CI, 0.68-0.76) at 3 months and 0.73 (95% CI, 0.68-0.79) at 12 months while high heterogeneity (I² = 52-96%) indicated variable performance across studies.
    CONCLUSIONS: As prognostic models exhibit only moderate accuracy in survival prediction, with the SORG Nomogram performing best. Integration of such models within multidisciplinary frameworks like LMNOP may improve individualized surgical planning and optimize patient outcomes with metastatic spine disease.
    Keywords:   Spine metastases, Surgery, Survival Predication, AUROC.
    DOI:  https://doi.org/10.47391/JPMA-7ANOS-ABS-30
  2. Ned Tijdschr Geneeskd. 2026 Sep 24. pii: D8895. [Epub ahead of print]170
    [Multidisciplinary Management of Bone Metastases in Clinical Practice].
    Edwin F Dierselhuis, Paulien G Westhoff, Joris J W Ploegmakers, Jacco J de Haan.
      Bone metastases occur in approximately two-thirds of patients with advanced cancer and are associated with pain, fractures, and neurological complications. The recently revised Dutch multidisciplinary guideline on bone metastases emphasizes early diagnosis, personalized treatment, and coordinated multidisciplinary care. We present three clinical cases highlighting key aspects of management: delayed diagnosis leading to femoral destruction and loss of mobility; a missed opportunity for prophylactic fixation in a patient with limited prognosis; and curative-intent stereotactic radiotherapy for a solitary bone metastasis. These cases illustrate the importance of timely imaging, appropriate surgical and radiotherapeutic interventions, and the use of bone-strengthening agents where indicated. Patients with bone metastases are a heterogeneous group; treatment decisions should take tumor type, extent of disease, patient condition,prognosis, and the preferences of patients into account. Implementation of the guideline requires collaboration across specialties to improve outcomes and quality of life for patients with bone metastases.
  3. Surgeon. 2026 Sep 30. pii: S1479-666X(26)00059-4. [Epub ahead of print]
    When to refer for surgery in long bone metastases: A powered multivariate analysis of fracture risk and simple algorithm for referral for surgery (the metastatic fracture prediction met FRAP score).
    Samantha Downie, Calum Sreenan, Alison Stillie, Matthew Moran, Pankaj Pankaj, Cathie Sudlow, Robert U Ashford, A Hamish Rw Simpson.
       BACKGROUND: It is difficult to predict the risk of pathological fracture in patients with bone metastases. Popular scoring systems like Mirels' may overestimate need for surgery by 20%. The aim was to identify predictors of fracture at 6 months in patients with long bone metastases managed non-surgically.
    PATIENTS AND METHODS: This was an adequately powered retrospective analysis of individuals with a long bone metastasis. Patients were identified from radiology reports and excluded if they had prophylactic surgery or died within 3 months. A literature review and pilot study identified 13 variables of interest. Multivariate analysis was used to generate the metastatic fracture prediction (Met FRAP) score.
    RESULTS: From 2009 to 2021 (13 years), 2142 patients with new long bone metastases were identified. 1577 were excluded, leaving a dataset of 565 lesions in 503 patients managed non-surgically. The cohort were 45% female with a mean age of 71 years. Median follow-up in living patients was 2 years (range 1-12 years). The metastatic fracture rate at 1 year was 26%. On multivariate analysis, independent predictors of metastatic fracture included cognitive impairment, metastatic load (p < 0.001 for both), primary cancer type (p < 0.01), radiotherapy, pain requiring opiates and radiographic appearance (p < 0.05 for all). These were used to generate the Met FRAP score. Met FRAP score predicted metastatic fracture at 6 months with 82% accuracy and was more sensitive and specific than Mirels score (61% accuracy, p < 0.001).
    DISCUSSION: The Met FRAP score accurately predicts metastatic fracture at 6 months and appears to be more reliable than Mirels score.
    Keywords:  Bone metastasis; Fracture prediction; Metastatic fracture
    DOI:  https://doi.org/10.1016/j.surge.2026.09.001
  4. Front Immunol. 2026 ;17 1959101
    Immune checkpoint inhibition in bone metastases: lesion response heterogeneity, the osteoimmune niche, and microenvironment-directed therapy.
    Min Dong, Guili Zheng, Fangyuan Yu, Jiaqi Yin, Chen Zhong.
      Bone metastases are common in advanced solid tumors and are clinically important not only because they cause skeletal-related events, including bone pain, pathological fractures, and spinal cord compression, but also because they may influence responses to immune checkpoint inhibitors (ICIs). Clinical evidence has consistently associated bone metastases with poorer survival after ICI treatment. Although some studies suggest that the relative benefit of ICIs may be reduced in patients with bone metastases, most available evidence is retrospective and lacks adequate treatment-interaction testing. This apparent reduction in benefit therefore cannot be clearly distinguished from adverse baseline prognosis, greater disease burden, or confounding related to concomitant treatments. Lesion-level studies further suggest that bone and nonbone lesions may follow discordant response trajectories. Assessment of bone-lesion response is complicated by the limited measurability of bone-only lesions under RECIST 1.1 and by treatment-related sclerosis, bone flare, and mixed responses. Mechanistically, bone metastases may establish a site-specific osteoimmune niche in which abnormal bone remodeling, vascular and stromal reorganization, myeloid immunosuppression, and impaired T-cell infiltration and effector function jointly constrain local antitumor immunity. RANKL inhibition and bone-directed radiotherapy are clinically available and may have immunomodulatory effects, but current evidence does not establish that either approach consistently enhances the antitumor activity of ICIs beyond skeletal protection or local control. Most other microenvironment-directed strategies remain at the preclinical or early translational stage. Future studies should distinguish bone-lesion antitumor response from systemic disease control and skeletal clinical outcomes. Prespecified treatment-interaction analyses, longitudinal multimodal imaging, paired sampling of bone and nonbone lesions, and mechanism-embedded clinical trials will be required to determine whether specific osteoimmune niche states can guide patient selection and combination therapy.
    Keywords:  bone metastases; immune checkpoint inhibitors; lesion-level response heterogeneity; osteoimmune niche; response assessment
    DOI:  https://doi.org/10.3389/fimmu.2026.1959101
  5. Oncol Rev. 2026 ;20 1820639
    Analysis of the heterogeneity of the immune microenvironment of bone metastases and new strategies of nanotechnology intervention.
    Chenyang Wu, Xueli Qiu, Chao Wang, Jinyu Bai, Xiaozhong Zhou.
      Bone metastases constitute one of the most severe complications in patients with advanced malignancies. Conventional treatment approaches face significant limitations: surgical intervention carries a high risk of recurrence; radiotherapy and chemotherapy often cause myelosuppression; and anti-resorptive agents provide only limited control over tumor progression. Although immunotherapy has achieved remarkable success in various solid tumors in recent years, its therapeutic impact on bone metastases remains limited. This limitation is largely attributed to the distinct immunosuppressive microenvironment within bone lesions, which is marked by (1) a substantial decline in both the quantity and functional activity of effector immune cells, coupled with an abnormal accumulation of immunosuppressive cell populations, and (2) the formation of a vicious cycle of "tumor growth-bone metabolic imbalance-immune suppression," driven by complex signaling interactions among osteoblasts, osteoclasts, and tumor cells. Recently, nanomaterials have emerged as promising therapeutic platforms due to their precise targeting and delivery capacity, inherent immune-stimulatory properties, and potential to restore bone homeostasis. Nonetheless, translating nanoplatforms into clinical practice for skeletal lesions remains a formidable challenge. This review highlights how specialized organic-inorganic hybrids and biomimetic nanoplatforms have achieved the most significant microenvironment remodeling and osteolytic inhibition within intraosseous murine models. Ultimately, we provide an actionable roadmap detailing how integrating multi-omics precision profiles and temporal programmable delivery can bridge the gap between preclinical nanomedicine and clinical oncological translation.
    Keywords:  bone metastasis; immune microenvironment; immunotherapy resistance; nanotechnology; targeted delivery
    DOI:  https://doi.org/10.3389/or.2026.1820639
  6. J Cachexia Sarcopenia Muscle. 2026 Oct;17(5): e70400
    Metastatic Bone Disease Is Associated With Longitudinal Muscle Loss and Reduced Survival in Kidney Cancer.
    Jon-Luc Poirier, Samuel T Jines, Libbie M Silverman, Anuradha Valiya Kambrath, L Daniel Wurtz, Teresa A Zimmers, Christopher D Collier.
       BACKGROUND: Cachexia is a multifactorial muscle wasting syndrome and is responsible for 20%-40% of cancer-related deaths, yet no FDA-approved therapies exist. Preclinical studies suggest that metastatic bone disease may contribute to muscle wasting, but this relationship has not been evaluated in clinical populations. This study evaluated whether metastatic bone disease at diagnosis is associated with longitudinal skeletal muscle loss and whether metastatic bone disease and longitudinal skeletal muscle loss are associated with overall survival in patients with kidney cancer.
    METHODS: A total of 293 patients (66.9% male, 33.1% female, median age 60 years) were retrospectively identified with either localised kidney cancer, extraosseous metastatic disease, or osseous metastatic disease at diagnosis. Clinical and demographic variables and treatments were recorded. Body composition was quantified over time for a subset by body mass index (BMI) (N = 221) and CT analysis at the L3 vertebral level (N = 99). Longitudinal changes were analysed using linear regression, and overall survival was assessed with Kaplan-Meier and multivariable Cox proportional hazards models.
    RESULTS: Patients with osseous metastatic disease had a reduction in BMI over time compared with those with localised or extraosseous metastatic disease (median of -3.6% per year, compared with +0.7% and -2.6% respectively, p < 0.01). Skeletal muscle loss was greatest for those with osseous metastasis (-7.5% per year, compared with -0.8% and -1.2% respectively, p < 0.01). Multivariable linear regression demonstrated osseous metastasis at diagnosis was strongly associated with muscle loss (β coefficient of -20.9 [95% confidence interval (CI): -35.56 to -6.27]). In multivariable Cox regression analysis, osseous metastasis at diagnosis was associated with an increased risk of death (HR 15.8; 95% CI: 2.00 to 124.95; p < 0.01), as was longitudinal skeletal muscle loss (HR 1.02 for each 1% loss per year; 95% CI: 1.01 to 1.04; p < 0.01).
    CONCLUSIONS: This study provides the first clinical evidence that metastatic bone disease is strongly associated with skeletal muscle loss and reduced survival in kidney cancer patients. These findings extend prior preclinical observations into the clinical setting and support further investigation into the possibility that tumour-bone-muscle interactions drive systemic muscle wasting. Importantly, the observation that severe muscle loss is strongly associated with mortality in kidney cancer highlights the need to consider cachexia as a modifiable determinant of outcomes, not just a byproduct of advanced disease.
    Keywords:  bone loss; cancer cachexia; metastatic bone disease; muscle loss; renal cell carcinoma; survival
    DOI:  https://doi.org/10.1002/jcsm.70400
  7. Semin Oncol. 2026 Sep 22. pii: S0093-7754(26)00110-7. [Epub ahead of print]53(6): 152565
    Bone metastasis in cancer: from microenvironmental remodeling to precision therapy.
    Qi Feng, Xiuhai Ji, Qi Sun, Yuan Li, Caiyuan Song, Baoqing Su.
      Bone metastasis remains a major determinant of disability, treatment failure, and poor survival in solid tumors. It is no longer adequately explained as a late consequence of tumor spread or as a process driven only by osteoclast-mediated bone destruction. Current evidence supports a broader view in which bone metastasis emerges through progressive remodeling of a receptive niche, followed by selective tumor cell seeding, adaptive persistence, and eventual outgrowth under continued pressure from both local and systemic cues. In this framework, bone is not merely a target organ but an active biological system in which remodeling, hematopoiesis, immunity, and stromal signaling jointly shape metastatic fate. This perspective also helps explain why conventional management, although effective in reducing skeletal complications and relieving symptoms, rarely changes the long-term course of disease. In this review, we discuss how recent advances have redefined the biology of bone metastasis, from early niche conditioning to overt lesion progression, and examine how these insights are reshaping diagnosis and therapy. We further highlight the translational shift from lesion detection and antiresorptive treatment toward risk prediction, biological stratification, and mechanism-guided combination strategies. A more integrated understanding of tumor evolution within bone may provide the basis for earlier intervention and more durable disease control.
    Keywords:  Bone metastasis; Bone microenvironment; Pre-metastatic niche; Precision therapy; Tumor dormancy
    DOI:  https://doi.org/10.1016/j.seminoncol.2026.152565
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