bims-rebome Biomed News
on Rehabilitation of bone metastases
Issue of 2025–07–06
eight papers selected by
Alberto Selvanetti, Azienda Ospedaliera San Giovanni Addolorata



  1. J Neurooncol. 2025 Jun 29.
       PURPOSE: Leptomeningeal disease (LMD) is a morbid complication of systemic cancer typically associated with brain metastases. However, vertebral bone metastases may also serve as a route for cerebrospinal fluid spread, though this pathway is less characterized. This study aims to determine the incidence, timing, and outcomes of LMD in patients with vertebral metastases in the absence of brain or other systemic metastases, using a large real-world database.
    METHODS: Using the TriNetX global health research network (n = 133 million), we identified 7887 adult patients with vertebral metastases from common solid tumors (lung, breast, prostate, colorectal, renal, melanoma, thyroid) who had no brain metastases or other potential sources of LMD. Patients were followed to identify development of LMD, and cohorts were compared based on metastatic pathways and clinical outcomes.
    RESULTS: Among 7887 patients with vertebral metastases, 144 (1.8%) developed LMD without prior or concurrent brain or systemic metastases, isolating the spine as the sole source. Breast cancer had the highest LMD rate (36.8%), followed by lung (20.8%), prostate (18.8%), and colorectal (11.1%). Median time from vertebral metastasis to LMD was 97.5 days (IQR 17-550), longer than the 50-day median (IQR 12-182) in patients with brain metastases before LMD (p < 0.001). Patients with vertebral metastases alone developed LMD significantly earlier than those with other prior metastases (median 97.5 vs. 250 days, IQR 100-775, p < 0.01). LMD was associated with shorter overall survival (median 170 vs. 370 days, p = 0.0006; HR 0.61, 95% CI 0.46-0.81), particularly in breast cancer (170 vs. 1001 days, p < 0.01). LMD patients were more likely to require hospice or palliative care (39.6% vs. 22.2%, p < 0.001), while non-LMD patients more often reported pain (67.1% vs. 52.4%, p = 0.0113) and emotional distress (45.8% vs. 26.4%, p = 0.007). Survival after LMD diagnosis was similarly poor regardless of metastatic pathway (p = 0.966).
    CONCLUSION: Vertebral metastases can serve as an underrecognized route of LMD spread, even in the absence of brain or other systemic metastases. LMD following vertebral disease is associated with poor prognosis and increased palliative care utilization. These findings underscore the need for heightened clinical vigilance for LMD in patients with spinal metastases.
    Keywords:  Central nervous system dissemination; Leptomeningeal metastasis; Real-world data analysis; Survival and quality-of-life outcomes; TriNetX health research network; Vertebral osseous metastases
    DOI:  https://doi.org/10.1007/s11060-025-05122-w
  2. Orthop Surg. 2025 Jun 29.
       OBJECTIVE: Intramedullary nailing is a treatment method for metastatic humerus fractures that stabilizes a large area while minimizing damage to the surrounding soft tissues. However, the results of this treatment may vary depending on certain factors. This study aimed to investigate the factors influencing functional outcomes and survival in patients with pathological humeral fractures treated using humeral nails.
    METHODS: This retrospective study included 41 patients who underwent humeral nailing for metastatic pathological humerus fractures between 2009 and 2024. Functional outcomes were compared based on factors such as gender, age, cancer type, another pathological fracture surgery, visceral metastases, cancer diagnosis prior to fracture, fracture type and location, and cement use, using VAS improvement, MSTS, KPS scores, and ROM measurement. Survival analysis was performed considering these same factors. Statistical analyses included the Mann-Whitney U test, Kruskal-Wallis test, Chi-square test, and Kaplan-Meier survival curves. Cox regression analyses were used to identify factors associated with mortality.
    RESULTS: In younger patients, better VAS improvement(p = 0.001), MSTS(p = 0.038), KPS(p = 0.028), and ROM(p = 0.045) were observed compared to those 65 and older. Cancer type and visceral metastases negatively impacted MSTS(p = 0.007, p = 0.049) and KPS(p = 0.002, p = 0.022). Actual fractures showed greater VAS improvement than impending fractures(p = 0.002), and shaft fractures had greater VAS improvement than proximal fractures(p = 0.037). Unknown cancer diagnosis prior to fracture led to better VAS improvement(p = 0.008), MSTS(p = 0.018), KPS(p = 0.023), and ROM(p = 0.006). Rapid growth tumor(p < 0.001) and visceral metastasis(p = 0.007) were independently associated with poor survival. No significant effects were seen for gender or cement use on functional outcomes and mortality.
    CONCLUSION: Although intramedullary nails are feasible implants for humeral pathological fractures, there are significant factors that affect their functional outcomes and survival. Actual fractures and shaft fractures showed better pain relief. Patients with a known cancer diagnosis prior to fracture and older patients had poor functional outcomes. Rapid cancer type and visceral metastasis negatively affect both functional outcomes and survival. Although cement use carries a risk of thrombosis, no significant changes in mortality and functional outcomes were observed with cement use.
    LEVEL OF EVIDENCE: IV.
    Keywords:  cement; humerus; metastasis; nail; pathological fracture; survival
    DOI:  https://doi.org/10.1111/os.70101
  3. Eur J Surg Oncol. 2025 Jun 28. pii: S0748-7983(25)00713-9. [Epub ahead of print] 110285
       BACKGROUND: Metastatic epidural spinal cord compression (MESCC) are the most serious debilitating morbidities of spine metastases (SpMs) causing devastating neurological damages. We still lack of reliable markers to predict neurological impairment.
    METHODS: A prospective cohort study collected 164 consecutive patients presenting with MESCC between January 2014-2021, divided in two groups: ambulatory (Frankel D-E) vs non-ambulatory (Frankel A-C). We compared the oncological and radiological characteristics of the MESCC in the 131 ambulatory patients to the 33 non-ambulatory patients.
    RESULTS: The median Overall Survival (OS) for the ambulatory group was 15.6 months (SD = 2.1) vs 5.8 months (SD = 3.8) for the non-ambulatory group, p = 0.024. Forty-seven patients (28.7 %) were operated on: 23/131 (17.5 %) in the ambulatory group and 24/33 (72.7 %) in the non-ambulatory group, p = 0.001; hundred forty-four were treated with radiotherapy (87.8 %): 119/131 (90.8 %) in the ambulatory group and 25/33 (75.8 %) in the non-ambulatory group, p = 0.033. In multivariate analysis with multiple logistic regression, thoracic MESCC [OR: 0.2, 95 % CI 0.055-0.730; p = 0.015], and a vertical epiduritis-spine junction angle (VESJA) < 150° [OR: 0.231, 95 % CI 0.075-0.717; p = 0.011] were independent risk factors for impaired neurological function whereas SINS <7 was independently associated with good prognostic [OR: 3.787, 95 % CI 1.109-12.932; p = 0.034]. VESJA showed a strong interrater reliability with excellent interrater agreement (ICC: 0.83, 95 % CI: 0.74-0.89; κ: 0.85, 95 % CI: 0.73-0.96).
    CONCLUSION: SINS <7, thoracic MESCC and VESJA showed to be independently associated with neurological prognosis. These factors could assist the neurosurgeon in their decision-making process regarding whether to perform surgery.
    Keywords:  ECOG; MESCC; Neurological impairment; Pathological; Spine metastasis; Surgery; Survival; Vertebral fracture
    DOI:  https://doi.org/10.1016/j.ejso.2025.110285
  4. Future Oncol. 2025 Jul 01. 1-11
       AIM: Denosumab and bisphosphonates are commonly used in clinical practice for lung cancer patients with bone metastasis to prevent skeletal-related events (SREs). The aim of this study was to evaluate the efficacy of these two bone-modifying agents(BMAs)in advanced lung cancer patients with bone metastasis in the era of immunotherapy.
    METHODS: Electronic medical records of advanced lung cancer patients with bone metastasis between January 2020 and March 2023 were retrospectively reviewed. Overall survival (OS), progression-free survival (PFS), and the time to the first occurrence of SRE were calculated using the Kaplan - Meier method and were compared using the log-rank test.
    RESULTS: Among the 227 included patients, denosumab significantly improved OS by 5.41 months compared with bisphosphonates (27.54 months vs. 22.13 months; hazard ratio (HR): 0.61; p  = 0.031). Denosumab also delayed the time to the first occurrence of SRE (undefined vs. 31.64 months; HR: 0.43, p = 0.005) and reduced the incidence of multiple SREs. However, the incidence of hypocalcemia at grade ≥ 3 was higher in the denosumab group than in the bisphosphonate group (8.6% vs. 3.0%).
    CONCLUSIONS: In patients with bone metastatic lung cancer, the efficacy of denosumab was significantly higher than that of bisphosphonate.
    Keywords:  Bone-modifying agents; advanced lung cancer; bisphosphonates; bone metastases; denosumab; therapeutic efficacy
    DOI:  https://doi.org/10.1080/14796694.2025.2525744
  5. J Orthop Sci. 2025 Jul 03. pii: S0949-2658(25)00190-3. [Epub ahead of print]
       BACKGROUND: Patients with clear cell renal cell carcinoma (ccRCC) have a higher incidence of bone metastasis; however, the availability of immune checkpoint inhibitors (ICIs) is expected to improve their overall survival (OS). Hence, accurate data on the prognosis and survival of patients with bone metastases are necessary to recommend appropriate treatments. Therefore, we investigated the prognosis and prognostic factors of patients with ccRCC bone metastasis in the era of ICIs.
    METHODS: This retrospective cohort study included 33 patients with ccRCC who were treated for bone metastases between 2016 and 2022. We evaluated the association between OS and clinical parameters, including serum biochemical concentrations, and blood cell count, using Kaplan-Meier curves and Cox proportional hazards models.
    RESULTS: The median OS was 28 months (95 % confidence interval (CI): 8 months - not censored), and the 1-year survival rate was 64 %. Twenty-one patients were treated with ICIs after bone metastasis diagnosis. The multivariate analysis revealed that the use of ICIs after bone metastasis diagnosis was a good prognostic factor (hazard ratio, 0.32; 95 % CI: 0.11-0.89, p = 0.029). Patients in the Katagiri score 5-7 points group using ICIs had a significantly longer survival (p = 0.012) but similar OS compared to the 2-4 points group (p = 0.34).
    CONCLUSIONS: ICI use after the diagnosis of bone metastasis may be a favorable prognostic factor in patients with bone metastases due to ccRCC. The predictive power of the current scoring system could underestimate the prognoses in patients with ccRCC and bone metastasis not treated with ICIs, highlighting the need for a better predictive scoring system in the era of ICIs.
    Keywords:  Bone metastasis; Clear cell renal cell carcinoma; Immune checkpoint inhibitor; Prognostic factors
    DOI:  https://doi.org/10.1016/j.jos.2025.06.008
  6. Circ J. 2025 Jul 02.
       BACKGROUND: Venous thromboembolism (VTE) is a serious complication following spine surgery for metastatic tumors. This study used the US Nationwide Readmissions Database to identify predictors of VTE and its associations with outcomes.
    METHODS AND RESULTS: Data between 2016 and 2020 were retrospectively reviewed. Patients aged ≥18 years undergoing non-emergency surgery for spinal metastasis were included in the analysis. Multivariable regression analysis was used to assess associations of VTE with in-hospital outcomes and 30- and 90-day readmissions, as well as demographic and clinical factors associated with VTE occurrence during the index admission. In all, 2,706 patients were included in the analysis (mean age 63.6 years; 1,435 [53%] male). Of all patients, 126 (4.7%) developed VTE during the index admission. After adjustment, VTE was significantly associated with an increased risk of in-hospital mortality (adjusted odds ratio [aOR] 5.34; 95% confidence interval [CI] 2.38-11.96) and 30-day readmission (aOR 2.06; 95% CI 1.33-3.19). Delays from admission to surgery (aOR 1.88; 95% CI 1.27-2.79) and a Charlson Comorbidity Index score ≥4 (aOR 3.11; 95% CI 1.60-6.04) were independently associated with an increased risk of VTE.
    CONCLUSIONS: In patients undergoing surgery for spinal metastasis, postoperative VTE is associated with higher in-hospital mortality and 30-day readmission risks. A Charlson Comorbidity Index score ≥4 and delayed surgery are independently associated with greater risk of VTE.
    Keywords:  In-hospital outcome; Metastatic spinal tumor surgery; Prediction; Readmission; Venous thromboembolism (VTE)
    DOI:  https://doi.org/10.1253/circj.CJ-25-0153
  7. Front Oncol. 2025 ;15 1497151
       Background: Cancer-related fatigue (CRF) is one of the most prevalent symptoms which drastically affect patient health and quality of life. This study aimed to construct and validate a nomogram to accurately predict the occurrence of cancer-related fatigue in patients with glioma.
    Methods: This cross-sectional study included 470 glioma patients from two hospitals (training cohort: n=284; validation cohort: n=186). All patients were categorized into two groups based on their Numerical Rating Scale scores of cancer-related fatigue: a no or mild fatigue group (scores 0-3) and a moderate to severe fatigue group (scores 4-10). LASSO model and multivariable logistic regression analyses were used to determine the significant risk factors contributing to the occurrence of cancer-related fatigue in glioma patients. A nomogram was constructed and its predictive accuracy and conformity was validated by ROC curves, calibration curves and decision curve analysis.
    Results: Combining LASSO algorithm and multivariable logistic regression analyses, the cancer stage (p=0.014), and the scores of Perceived Social Support Scale (PSSS) (p<0.001), physical functioning (PF) (p<0.001), bodily pain (BP) (p=0.031), general health (GH) (p<0.001), and mental health (MH) (p=0.009) were the independent risk factors for cancer-related fatigue of glioma patients. A clinically quantitative predictive model nomogram was developed based on these extracted risk factors. The concordance-index of nomogram was 0.964 (0.935-0.993). The AUC values of nomogram were 0.916 (CI: 0.879-0.953) in the training cohort and 0.885 (CI: 0.829-0.941) in the validation cohort. The calibration curves of this nomogram exhibited a notable concordance with the ideal diagonal line. The decision curve analyses illuminated that this nomogram achieved high clinical net benefit.
    Conclusion: The nomogram, incorporating the cancer stage of glioma, perceived social support, and quality of life of patients, demonstrated good accuracy and clinical practicality. It can serve as a valuable prediction and evaluation tool for anticipating the occurrence of cancer-related fatigue in patients with glioma.
    Keywords:  cancer-related fatigue; glioma; nomogram; perceived social support; quality of life
    DOI:  https://doi.org/10.3389/fonc.2025.1497151
  8. Front Oncol. 2025 ;15 1593165
       Objective: To evaluate the effects of exercise interventions on bone health and body composition in postmenopausal women with breast cancer.
    Methods: A systematic search was conducted across PubMed, EMBASE, Web of Science, CENTRAL, and CNKI databases for randomized controlled trials (RCTs) published before October 2024. Data from eligible studies were extracted and analyzed using STATA software.
    Results: Eight RCTs comprising 1099 participants were included. The results indicated no significant differences between exercise and control interventions in patients' bone mineral density (BMD) at the lumbar spine (WMD = 0.116, 95% CI [-0.357, 0.589], p = 0.631), femoral neck (WMD = -0.214, 95% CI [-0.497, 0.068], p = 0.137), or total hip (WMD = 0.299, 95% CI [-0.283, 0.882], p = 0.314). For body composition parameters, exercise interventions led to significant improvements in lean mass (WMD = 0.192, 95% CI [0.023, 0.362], p = 0.026) and marked reductions in percent body fat (WMD = -1.327, 95% CI [-2.587, -0.066], p = 0.039) compared to the control. However, no significant differences were observed in body weight (WMD = -0.024, 95% CI [-0.193, 0.146], p = 0.784) or fat mass (WMD = -0.078, 95% CI [-0.703, 0.546], p = 0.806) between the two interventions.
    Conclusion: The current evidence suggested that exercise interventions effectively improve lean mass and reduce percent body fat but have a limited impact on BMD in postmenopausal women with breast cancer. A multimodal, individualized exercise program is recommended to address the challenges of bone health and body composition in this population.
    Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024613744.
    Keywords:  body composition; bone mineral density; breast cancer; exercise intervention; meta - analysis
    DOI:  https://doi.org/10.3389/fonc.2025.1593165