bims-rebome Biomed News
on Rehabilitation of bone metastases
Issue of 2025–08–31
eleven papers selected by
Alberto Selvanetti, Azienda Ospedaliera San Giovanni Addolorata



  1. J Clin Med. 2025 Aug 20. pii: 5885. [Epub ahead of print]14(16):
      Background: Spinal metastases can cause significant impairment of neurological function and quality of life. Hence, personalized clinical decision-making based on prognosis and likely outcome is desirable. The effectiveness of AI in predicting complications and treatment outcomes for patients with spinal metastases is assessed. Methods: A thorough search was carried out through the PubMed, Scopus, Web of Science, Embase, and Cochrane databases up until 27 January 2025. Included were studies that used AI-based models to predict outcomes for adult patients with spinal metastases. Three reviewers independently extracted the data, and screening was conducted in accordance with PRISMA principles. AUC results were pooled using a random-effects model, and the PROBAST program was used to evaluate the study's quality. Results: Included were 47 articles totaling 25,790 patients. For training, internal validation, and external validation, the weighted average AUCs were 0.762, 0.876, and 0.810, respectively. The Skeletal Oncology Research Group machine learning algorithms (SORG-MLAs) were the ones externally validated the most, continuously producing AUCs > 0.84 for 90-day and 1-year mortality. Models based on radiomics showed promise in preoperative planning, especially for outcomes of radiation and concealed blood loss. Most research concentrated on breast, lung, and prostate malignancies, which limited its applicability to less common tumors. Conclusions: AI models have shown reasonable accuracy in predicting mortality, ambulatory status, blood loss, and surgical complications in patients with spinal metastases. Wider implementation necessitates additional validation, data standardization, and ethical and regulatory framework evaluation. Future work should concentrate on creating multimodal, hybrid models and assessing their practical applications.
    Keywords:  artificial intelligence; complications; deep learning; machine learning; spine metastasis
    DOI:  https://doi.org/10.3390/jcm14165885
  2. J Clin Med. 2025 Aug 20. pii: 5877. [Epub ahead of print]14(16):
      Background: Spinal metastasis is the third most common site for metastatic localization, following the lung and liver. Manual detection through imaging modalities such as CT, MRI, PET, and bone scintigraphy can be costly and inefficient. Preliminary artificial intelligence (AI) techniques and computer-aided detection (CAD) systems have attempted to improve lesion detection, segmentation, and treatment response in oncological imaging. The objective of this review is to evaluate the current applications of AI across multimodal imaging techniques in the diagnosis of spinal metastasis. Methods: Databases like PubMed, Scopus, Web of Science Advance, Cochrane, and Embase (Ovid) were searched using specific keywords like 'spine metastases', 'artificial intelligence', 'machine learning', 'deep learning', and 'diagnosis'. The screening of studies adhered to the PRISMA guidelines. Relevant variables were extracted from each of the included articles such as the primary tumor type, cohort size, and prediction model performance metrics: area under the receiver operating curve (AUC), accuracy, sensitivity, specificity, internal validation and external validation. A random-effects meta-analysis model was used to account for variability between the studies. Quality assessment was performed using the PROBAST tool. Results: This review included 39 studies published between 2007 and 2024, encompassing a total of 6267 patients. The three most common primary tumors were lung cancer (56.4%), breast cancer (51.3%), and prostate cancer (41.0%). Four studies reported AUC values for model training, 16 for internal validation, and five for external validation. The weighted average AUCs were 0.971 (training), 0.947 (internal validation), and 0.819 (external validation). The risk of bias was the highest in the analysis domain, with 22 studies (56%) rated high risk, primarily due to inadequate external validation and overfitting. Conclusions: AI-based approaches show promise for enhancing the detection, segmentation, and characterization of spinal metastatic lesions across multiple imaging modalities. Future research should focus on developing more generalizable models through larger and more diverse training datasets, integrating clinical and imaging data, and conducting prospective validation studies to demonstrate meaningful clinical impact.
    Keywords:  artificial intelligence (AI); convolutional neural networks (CNNs); deep learning; diagnostic imaging; machine learning; radiomics; spinal metastasis
    DOI:  https://doi.org/10.3390/jcm14165877
  3. Spine (Phila Pa 1976). 2025 Aug 25.
    AO Spine Knowledge Forum Tumor
       STUDY DESIGN: Delphi Consensus.
    OBJECTIVE: To define an optimal surgical composite outcome measure in patients with metastatic spine disease (OSCO-M) through international consensus among key opinion leaders.
    METHODS: Members of the AO Spine Knowledge Forum Tumor, an international group of dedicated spine oncology surgeons and oncologists, participated in a modified Delphi process between March 2023 and November 2024. The study was conducted in two parts. The first part aimed on identifying which outcome variables were deemed important to be included in the composite outcome. The second part focused on the definition of a successful outcome with regards to the agreed variables from Part 1. Each part consisted of a questionnaire and a consensus meeting. Consensus was achieved when a threshold of 70% agreement was reached.
    RESULTS: A total of 42 dedicated spine oncology surgeons and oncologists from North America, Latin America, Europe, and Asia participated. Over 87% of respondents agreed that composite measures reflect the multidimensional aspect of the surgical process more than an individual outcome variable. Most respondents (93%) agreed/strongly agreed that composite measures should be used to assess the quality of surgical care in spine oncology. Through consensus, the following three outcome variables were selected to define the OSCO-M: the absence of SAVES-V2 (Spinal Adverse Events Severity System, Version 2) Grade 3 adverse events or higher within 30 days of surgery, maintaining or improving ECOG (Eastern Cooperative Oncology Group) performance status at 90 days, and being ambulatory (with or without aid) at 90 days.
    CONCLUSION: This is the first study defining a composite outcome measure in oncologic surgery for spinal metastases derived from an international group of key opinion leaders in spine oncology. The OSCO-M may be useful for future research in spine tumor patients and serve as a benchmark to optimize outcomes.
    Keywords:  composite outcome; metastatic spine disease; spinal tumor; spine metastases; textbook outcome
    DOI:  https://doi.org/10.1097/BRS.0000000000005479
  4. Clin Spine Surg. 2025 Aug 22.
       STUDY DESIGN: Systematic review and meta-analysis.
    OBJECTIVE: To determine the optimal time to perform surgery in patients with malignant cord compression.
    SUMMARY OF BACKGROUND DATA: Malignant cord compression (MSC) is a frequent complication of spinal metastases, being reported in about 5%-10% of all cancer patients. The sequelae caused by spinal cord compression can be devastating, causing disability, deterioration of their quality of life, and even death. Patients with malignant cord compression frequently require surgical management to preserve neurological function.
    METHODS: This systematic review identified studies that tested different therapeutic windows for surgical decompression. The articles that met the inclusion criteria were meta-analyzed to compare the patients with early versus late decompression after the onset of neurological symptoms. The result of interest was the recovery of walking ability.
    RESULTS: Out of the 1003 abstracts reviewed, 5 studies (389 patients) met the inclusion criteria. All 5 were retrospective studies that proposed surgical intervention in the first 48 hours after the onset of neurological symptoms as the necessary therapeutic window. When comparing early versus late intervention, surgery before the first 48 hours had an odds ratio of 3.92 [95% CI: 1.51-10.18] for recovering walking ability.
    CONCLUSION: Surgery in the first 48 hours after the onset of neurological symptoms in patients with malignant cord compression is associated with a greater chance of recovery of walking ability. Since the literature is scarce, studies with more evidence are needed on this topic.
    Keywords:  cancer; decompression; metastasis; spinal compression; spine
    DOI:  https://doi.org/10.1097/BSD.0000000000001915
  5. Medicina (Kaunas). 2025 Jul 31. pii: 1390. [Epub ahead of print]61(8):
      Background and Objectives: Acute metastatic cord compression (AMSCC) and femoral impending/pathological fracture negatively impact a patient's quality of life, morbidity and survival, and are considered significant life events. This study aims to compare AMSCC and FMD as distinct yet overlapping metastatic orthopedic emergencies, addressing whether they represent sequential disease stages or distinct patient subpopulations-an analysis critical for prognosis and treatment planning. Materials and Methods: Records of all patients who underwent surgery for a femoral metastatic disease (FMD) over a decade (2004-2015) and patients who were treated for acute metastatic spinal compression (AMSCC) (2007-2017) were retrieved. There were no patients lost to follow-up. Results: The treatment cohorts were similar in terms of age, gender, tumour origin, and the number of spinal metastases. Fifty-four patients were diagnosed with AMSCC. Following treatment, the Frankel muscle grading improved by 0.5 ± 0.8 grades. Two hundred and eighteen patients underwent surgical intervention for FMD. Seventy percent of femoral metastases were located in the femoral neck and trochanteric area. Impending fractures accounted for 52% of the cohort. The FMD cohort, including impending and pathological fractures, was similar to the AMSCC cohort in terms of age and the time interval between cancer diagnosis and surgery (56.7 ± 74.2 vs. 51.6 ± 69.6, respectively, p = 0.646). The Karnofsky functional score was higher for the FMD cohort (63.3 ± 16.2) than for the AMSCC cohort (48.5 ± 19.5; p < 0.001). The mean survival time for the FMD cohort was double that of the AMSCC, at 18.4 ± 23.5 months versus 9.1 ± 13.6 months, respectively (p = 0.006). Conclusions: In conclusion, this study is novel in proposing that FMD and AMSCC are distinct clinical entities, differing in their impact on patient function and, most importantly, on patient survival.
    Keywords:  compression; cord; femoral; metastases; mortality
    DOI:  https://doi.org/10.3390/medicina61081390
  6. Eur Spine J. 2025 Aug 26.
       OBJECTIVE: To identify predictors for time to first treatment modality (TTT) in patients diagnosed with spinal metastatic disease.
    METHODS: Our radiology database was retrospectively queried to identify patients with spinal metastases (01/2017-12/2021). Demographics, setting of initial imaging (inpatient/outpatient/ED), histology, treatment modality, and TTT were collected. Several different early TTT thresholds were explored (≤ 30, ≤ 21, ≤14, and ≤ 7 days). After controlling for age, gender, diagnostic setting, pathology, type of treatment multivariable linear and logistic regressions were performed for the primary and secondary thresholds at different time-points.
    RESULTS: A total of 1009 patients with spinal metastases were included, with a median age of 65 years (IQR 15) and 529 (52.4%) males. Diagnoses occurred in the inpatient (37%), outpatient (50%), and emergency department (13%) settings. The most common primary tumors were breast (22.4%), prostate (19.5%), and non-small cell lung cancer (12.8%). Treatment modalities included surgery (14.6%), chemotherapy (54.5%), and radiation therapy (43.5%). The median time to treatment (TTT) was 13 days (SD 27, range 0-676), with no significant difference by setting (p = 0.2). In multivariable linear regression, surgery was associated with shorter TTT (p = 0.037). Logistic regression using different early-TTT thresholds identified age, surgical intervention, lymphoma, and outpatient setting as significant predictors across models. Sensitivity analyses excluding TTT outliers showed that surgery was no longer a significant predictor, while other covariates remained stable.
    CONCLUSIONS: Surgical intervention and lymphoma independently predicted earlier TTT of any modality in spinal metastases, whereas older age and outpatient diagnosis were associated with delays.
    Keywords:  Neurological Compromise; Spinal Metastases; Spinal cord compression; Spine Tumors; Time to treatment
    DOI:  https://doi.org/10.1007/s00586-025-09280-3
  7. Eur J Oncol Nurs. 2025 Jul 24. pii: S1462-3889(25)00170-X. [Epub ahead of print]78 102946
       PURPOSE: This study aimed to explore the experiences of patients with advanced cancer undergoing palliative radiotherapy for bone metastases, focusing on their physical and emotional responses and coping strategies.
    METHODS: In-depth interviews were conducted to gain a comprehensive understanding of patients' lived experiences. The interviews were recorded and transcribed verbatim, followed by inductive content analysis, in which each interview was individually coded. The resulting codes were analysed to identify overarching themes.
    RESULTS: Sixteen patients with advanced cancer (10 men and 6 women) shared their experiences with palliative radiotherapy for bone metastases. Four key themes emerged, highlighting significant physical and psychological distress as well as emotional instability regarding treatment outcomes and post-radiotherapy life. However, many patients positively drew on their inner strength and coped with their circumstances. While palliative radiotherapy is a minimally invasive intervention intended to alleviate distress, patients often face unique physical and psychological challenges associated with short-term palliative treatment.
    CONCLUSIONS: These findings highlight the need for a holistic approach to palliative radiotherapy, in which healthcare professionals not only provide treatment but also address psychological distress and support patients' coping mechanisms. Nurses play a central role in integrating person-centred care into palliative radiotherapy, working collaboratively with interdisciplinary teams to enhance the treatment experience for patients.
    Keywords:  Bone neoplasms; Neoplasm metastasis; Palliative care; Qualitative research; Radiotherapy
    DOI:  https://doi.org/10.1016/j.ejon.2025.102946
  8. Cancer Med. 2025 Aug;14(16): e71175
       BACKGROUND: The COVID-19 pandemic reintroduced single-fraction radiotherapy for symptomatic bone metastases due to its efficiency, rapid realization, and cost-effectiveness. However, pain flare can occur as a side effect that can have a significant impact on a patient's quality of life. With pain flare incidence ranging between 2% and 44%, there are no definitive conclusions about which patients are at greater risk.
    AIM: This study aims to analyze the occurrence of pain flare in relation to age, patient's performance status, primary tumor, histopathology, and bone localization of metastases.
    METHODS: Our clinical, prospective, non-randomized study included 64 patients with non-complicated, painful bone metastases who underwent palliative, pain-relieving 8 Gy single-fraction radiotherapy in a single hospital visit. Response to treatment was patient-reported via telephone interview using a visual analog scale and assessed based on the international consensus panel of radiation oncologists.
    RESULTS: In the entire group of patients, 17% developed pain flare. No statistically significant difference was observed in pain flare occurrence depending on the patient's age, performance status, the primary origin of the tumor, histopathology, or location of the metastasis (bone) that was irradiated. All but one patient had a good response to treatment after the flare.
    CONCLUSION: Pain flare can be expected in less than 20% of patients receiving 8 Gy single fraction radiotherapy for painful bone metastases. It is not proven that any of the mentioned clinical parameters influence the occurrence of pain flare. Pain flare does not interfere with response to treatment.
    Keywords:  bone metastases; pain flare; prediction; radiotherapy
    DOI:  https://doi.org/10.1002/cam4.71175
  9. J Med Biochem. 2025 Jul 04. 44(4): 731-739
       Background: This study aimed to compare the effects of Zoledronic Acid (ZA) versus Denosumab (DEN) on bone metabolism, inflammatory response, and immunoglobulins in breast cancer (BC) patients with bone metastases.
    Methods: The potential study population consisted of 163 patients with bone metastases BC admitted from May 2023 to June 2024. Through propensity score matching (PSM), 122 patients were included, with 61 patients in the ZA group (treated with ZA) and 61 patients in the DEN group (treated with DEN). Levels of tartrate-resistant acid phosphatase 5b (TRACP-5b), bone glutamyl protein (BGP), bone alkaline phosphatase (BALP), and 25-hydroxyvitamin D3 (25(OH)D3) were measured before and after treatment. Additionally, bone mineral density (BMD) of the lumbar spine (L1-L4) and hip, as well as levels of inflammatory factors and immunoglobulins, were assessed.
    Results: After PSM, baseline characteristics were balanced between the ZA and DEN groups (P > 0.05). No significant difference was observed in post-treatment BMD between the two groups (P > 0.05). However, the DEN group showed significantly lower TRACP-5b and BGP levels and notably higher BALP and 25(OH)D3 levels compared to the ZA group (P <0.05). In contrast, the ZA group exhibited lower levels of inflammatory factors and higher immunoglobulin levels than the DEN group (P < 0.05). Regarding safety, a lower incidence of adverse reactions was determined in the DEN group versus the ZA group (P < 0.05).
    Conclusions: In the treatment of BC with bone metastases, DEN demonstrated superior benefits for bone metabolism, while ZA showed better regulation of inflammatory response and immune function.
    Keywords:  bone metabolism; bone metastases; breast cancer; denosumab; zoledronic acid
    DOI:  https://doi.org/10.5937/jomb0-56984
  10. Bioengineering (Basel). 2025 Jul 23. pii: 791. [Epub ahead of print]12(8):
      Background: Spinal metastases (SMs) are associated with poor prognosis and significant morbidity. We hypothesize that artificial intelligence (AI) models can enhance the identification and clinical utility of genetic and molecular signatures associated with SMs, improving diagnostic accuracy and enabling personalized treatment strategies. Methods: A systematic review of five databases was conducted to identify studies that used AI to predict genetic alterations and SMs outcomes. Accuracy, area under the receiver operating curve (AUC), and sensitivity were used for comparison. Data analysis was performed in R. Results: Eleven studies met the inclusion criteria, covering three different primary tumor origins, comprising a total of 2211 patients with an average of 201 ± 90 patients (range: 76-359 patients) per study. EGFR, Ki-67, and HER-2 were studied in ten (90.9%), two (18.1%), and one (9.1%) study, respectively. The weighted average AUC is 0.849 (95% CI: 0.835-0.863) and 0.791 (95% CI: 0.738-0.844) for internal and external validation of the established models, respectively. Conclusions: AI, through radiomics and machine learning, shows strong potential in predicting molecular markers in SMs. Our study demonstrates that AI can predict molecular markers in SMs with high accuracy.
    Keywords:  artificial intelligence; genetic markers; molecular signatures; spinal metastasis
    DOI:  https://doi.org/10.3390/bioengineering12080791
  11. Cells. 2025 Aug 15. pii: 1263. [Epub ahead of print]14(16):
      Despite the increasing number of novel therapies to treat newly diagnosed multiple myeloma (NDMM), preventing skeletal-related events (SREs) remains a challenge. This review summarizes the mechanistic causes of myeloma bone disease, data supporting the use of bisphosphonates and RANKL inhibitors, and the optimal management of preventing SREs in NDMM patients. Both zoledronic acid (ZA) and denosumab are acceptable treatment options with comparable safety and efficacy profiles. However, in patients who are candidates for autologous stem cell transplant (ASCT), denosumab may be preferred over ZA due to a progression-free survival (PFS) benefit observed in post hoc analyses when used with proteasome inhibitor-based regimens. The optimal duration of bone-directed therapy is unclear, but it is typically given for two years. Supportive care should include dental evaluation at baseline, annually, and if symptoms appear, given the risk for jaw osteonecrosis with both ZA and denosumab. Both drugs should be held in the setting of dental work. Patients should receive adequate calcium and vitamin D supplementation. Supportive procedures such as cement augmentation, radiation, and orthopedic surgery can also help treat compression fractures, uncontrolled pain, cord compression, and pathologic fractures. We conclude with our approach for managing SREs and a review of novel therapies and targets.
    Keywords:  denosumab; multiple myeloma; skeletal-related events; zoledronic acid
    DOI:  https://doi.org/10.3390/cells14161263