bims-rebome 2026-02-15 papers

MedComm (2020). 2026 Feb;7(2): e70604

Bone Metastasis: Molecular Mechanisms, Clinical Management, and Therapeutic Targets.

Jingyuan Wen, Binghua Li, Shengjia Wang, Yongzhong Yao, Zhao Huang, Decai Yu.

Bone metastasis (BoMet) is a common complication in various cancers. Approximately 20-30% of patients with cancer develop BoMet, which is most frequently associated with solid tumors, such as breast, prostate, and lung cancers. BoMet can lead to skeletal-related events such as fractures, bone pain, and hypercalcemia, negatively affecting the patient's quality of life and markedly shortening overall survival. The development of BoMet is a complex, multistep process driven by dynamic interactions between tumor cells and the bone microenvironment. The bone microenvironment provides a supportive niche for disseminated tumor cells, where intricate signaling networks and stromal interactions regulate the initiation, dormancy, reactivation, and progression of BoMet. Although current bone-targeted therapies can reduce the incidence of these complications, the clinical outcomes for patients with BoMet remain poor. Therefore, elucidating the molecular mechanisms governing these interactions is essential for identifying new therapeutic strategies. This review systematically explores the molecular drivers of BoMet progression, dynamic interactions within the metastatic niche, available preclinical models, established treatment modalities, and emerging therapeutic approaches. As fundamental research continues to advance toward clinical translation, the outlook for patients with BoMet is expected to improve significantly.

Keywords: bone metastasis; bone microenvironment; bone niche; bone‐targeting therapy; cancer–bone crosstalk

DOI: https://doi.org/10.1002/mco2.70604

Medicine (Baltimore). 2026 Feb 13. 105(7): e47573

Trends and hotspots in the studies of spinal metastasis: A bibliometric analysis from 2000 to 2023.

Luming Kong, Huapeng Guan, Jinbao Liu, Wenzhe Bai, Zelin Yue, Pengpeng Qi, Nianhu Li.

BACKGROUND: Spinal metastasis (SM) is described as a metastatic malignant bone tumor with a high mortality rate and often leads to symptoms related to spinal cord or nerve compression, such as pain and debilitating neurological dysfunction. In this study, we explored the research hotspots and trends in SM using bibliometric analysis, which provided reliable novel hints and pathways for future exploration.
METHODS: We reviewed articles and reviews on SM published in the Web of Science Core Collection between 2000 and 2023. VOSviewer and CiteSpace were used to conduct the bibliometric and knowledge map analyses.
RESULTS: A total of 2325 original articles and reviews published in 489 academic journals by 10,460 authors from 2231 affiliations in 61 countries/regions were retrieved. The United States was the largest contributor. The University of Toronto was the leader in relevant research. Arjun Sahgal was the most published author and Peter C Gerszten had the most co-citations. The Journal of Neurosurgery Spine published the most SM related articles, and Spine was the most commonly cited journal. The preeminent areas of scholarly inquiry concerning SM were centered on minimally invasive treatments, radiation therapy, and the prognosis and management of patients with SM.
CONCLUSION: SM is a common type of metastatic bone tumor, and its treatment is increasingly shifting towards minimally invasive surgery and radiation therapy, with a growing emphasis on the prognosis and management of SM as a key area for future research.

Keywords: bibliometric; hotspot; spinal metastasis; visualization

DOI: https://doi.org/10.1097/MD.0000000000047573

Clin Orthop Relat Res. 2026 Feb 11.

What Predicts a Subsequent Skeletal-related Event, and How Do Factors Associated With Mortality Differ After an Initial Versus a Subsequent Event?

Hung-Ho Yen, Paul T Ogink, Hung-Kuan Yen, Jyun-Hao Chen, Wei-Lun Huang, Ta-Chun Lin, Wei-Hsin Lin, Hsiang-Chieh Hsieh, Ming-Hsiao Hu, Olivier Q Groot.

BACKGROUND: Metastatic bone disease presents challenges from debilitating symptoms and poor prognosis. Given the extended life expectancy attributed to improved treatment modalities, such as molecular treatments, patients are at risk of experiencing subsequent skeletal-related events over a prolonged period. While previous studies have identified prognostic factors for initial skeletal-related events, it remains unclear whether these findings can be applied to patients who develop subsequent events. To address this knowledge gap and help clinicians proactively manage this growing patient population, our study aimed to identify the factors that are associated with developing subsequent skeletal-related events in patients who have already experienced bone metastasis.
QUESTIONS/PURPOSES: (1) What factors are associated with a higher risk of developing subsequent skeletal-related events with death as a competing risk? (2) How do factors associated with mortality differ between patients treated for an initial skeletal-related event and those treated for subsequent skeletal-related events?
METHODS: We conducted a retrospective study of 4159 adult patients treated for bone metastasis from January 2010 to December 2018 in Taiwan. The data were drawn from a tertiary referral center and a local hospital. Patients were included if they had a surgical procedure and/or radiotherapy for an image-confirmed skeletal-related event. We excluded patients with malignant primary bone tumors (1.7% [74 of 4159]), those whose initial treatment was at a different medical facility (2.6% [109 of 4159]), and patients with uncertain tumor histology (3.9% [162 of 4159]), resulting in a final cohort of 3814 patients. Patient identification was conducted through a comprehensive institutional medical database that longitudinally integrates diagnostic, treatment, and outcome data across departments, which substantially minimizes the risk of conventional loss to follow-up. All patients were categorized into two groups: a single skeletal-related event group (83% [3159]) and a subsequent skeletal-related event group (17% [655]). Patients who developed subsequent skeletal-related events were younger (median [IQR] age 59 years [50 to 67] versus 62 years [53 to 71]; p < 0.001), had a higher BMI (median [IQR] 25 kg/m2 [23 to 27] versus 22 kg/m2 [20 to 25]; p = 0.01), and had a higher prevalence of brain metastasis (28% [182 of 655] versus 16% [504 of 3159]; p < 0.001) and visceral metastasis (39% [258 of 655] versus 27% [864 of 3159]; p < 0.001). With respect to primary tumor characteristics, the distribution of tumor growth categories, which was defined by the median survival time of patients with malignancy, differed significantly between groups, with a higher proportion of intermediate-growth tumors observed in the subsequent skeletal-related event group (39% [256 of 655] versus 32% [1004 of 3159]). The anatomic site of the initial metastatic lesion also differed: Patients who developed subsequent skeletal-related events more frequently had extremity involvement (34% [224 of 655] versus 28% [869 of 3159]; p = 0.001) and less frequently had spinal involvement (66% [431 of 655] versus 72% [2290 of 3159]). Regarding baseline clinical status, the subsequent skeletal-related event group had fewer patients with additional Charlson comorbidities (29% [188 of 655] versus 34% [1080 of 3159]; p = 0.008) and a better Eastern Cooperative Oncology Group (ECOG) performance status, with a higher proportion of patients scoring 0 to 1 (53% [344 of 655] versus 41% [1295 of 3159]; p = 0.004). Laboratory findings further reflected that the subsequent skeletal-related event group had more favorable baseline characteristics, including higher albumin levels (median [IQR] 4.0 g/dL [3.4 to 4.3] versus 3.7 g/dL [3.2 to 4.2]; p < 0.001) and higher hemoglobin levels (12.2 g/dL [10.6 to 13.4] versus 11.3 g/dL [9.9 to 12.8]; p < 0.001). In terms of local management of the initial skeletal-related event, patients who developed subsequent skeletal-related events were more likely to have undergone surgical intervention (30% [194 of 655] versus 24% [758 of 3159]; p = 0.002) and less likely to have received radiotherapy (86% [562 of 655] versus 92% [2906 of 3159]; p < 0.001) compared with those who experienced only a single skeletal-related event. These baseline imbalances were adjusted as covariates in multivariable analyses. Missing data were imputed using the MissForest algorithm. Competing risk models and Fine and Gray subdistribution hazard models were applied to identify factors associated with developing subsequent skeletal-related events with death as a competing risk. Cox proportional hazards models were performed to compare the HRs of factors associated with mortality between the two groups.
RESULTS: After accounting for death as a competing risk, independent factors associated with an increased risk of subsequent skeletal-related events included the following: increasing age (for each year of increasing age, the hazard increased 0.7%; subdistribution HR 1.01 [95% confidence interval (CI) 1.00 to 1.01]; p < 0.001), male sex (subdistribution HR 1.10 [95% CI 1.02 to 1.19]; p = 0.01), intermediate-growth tumors (subdistribution HR 1.16 [95% CI 1.02 to 1.32]; p = 0.02), rapid-growth tumors (subdistribution HR 2.00 [95% CI 1.77 to 2.26]; p < 0.001), increase in alkaline phosphatase (for each 100-IU/L increase in alkaline phosphatase, the hazard increased 4%; subdistribution HR 1.04 [95% CI 1.03 to 1.05]; p < 0.001), and the presence of brain metastasis (subdistribution HR 1.22 [95% CI 1.11 to 1.34]; p < 0.001). Of the factors analyzed for their association with mortality in patients with skeletal-related events, 83% of the factors demonstrated a similar association in both patients with an initial skeletal-related event and those who experienced subsequent events. In the group with subsequent skeletal-related events, for each unit of increasing international normalized ratio, the hazard increased 91% (HR 1.91 [95% CI 1.33 to 2.74]; p < 0.001), indicating a stronger association with mortality. Conversely, factors such as ECOG score < 2 (HR 0.65 [95% CI 0.59 to 0.71]; the hazard decreased 35% compared with patients with an ECOG score ≥ 2; p < 0.001) and albumin levels (HR 0.75 [95% CI 0.71 to 0.79]; for each g/dL increase in albumin, the hazard decreased 25%; p < 0.001) showed a stronger correlation with mortality in the patients with an initial skeletal-related event compared with those who further developed subsequent skeletal-related events.
CONCLUSION: In patients with metastatic bone disease, the association of older age, male sex, aggressive tumors, elevated alkaline phosphatase levels, and brain metastases with a greater likelihood of subsequent skeletal-related events should guide clinical practice. For these patients, we recommend tailoring management strategies to include intensified surveillance with more frequent follow-up imaging, such as radiography and shortened bone scan intervals, to facilitate the early detection of impending fractures and allow for timely prophylactic treatment. These findings are intended to inform the design and integration of a predictive model, which we believe is a crucial area for future research.
LEVEL OF EVIDENCE: Level III, therapeutic study.

DOI: https://doi.org/10.1097/CORR.0000000000003845

Clin Oncol (R Coll Radiol). 2026 Jan 22. pii: S0936-6555(26)00029-4. [Epub ahead of print]51 104058

Risk of Symptomatic Skeletal Events After Discontinuation of Long-term Denosumab in Patients With Bone Metastases: A Retrospective Cohort Study.

H Hara, N Fukase, R Sawada, T Takemori, Y Nakamatsu, R Kuroda, T Akisue.

AIMS: The optimal duration of denosumab (Dmab) therapy for patients with bone metastases remains uncertain, particularly regarding the balance between preventing skeletal-related events and the risk of medication-related osteonecrosis of the jaw (MRONJ) after treatment discontinuation. This study evaluated the incidence and risk factors of symptomatic skeletal events (SSEs) following Dmab discontinuation.
MATERIALS AND METHODS: We retrospectively analysed 178 patients with bone metastases who discontinued Dmab after ≥6 doses and had ≥3 months of follow-up. Incidence, timing, and risk factors of SSEs were assessed using Cox regression. A landmark analysis was performed in patients treated for ≥2 years (n = 152), with SSE-free survival compared between discontinuation and continuation groups, with and without propensity score matching (PSM). Incidence rates of SSEs and MRONJ were compared between patients treated for <2 and ≥2 years.
RESULTS: SSEs occurred in 16.9% of patients, with 77% developing within one year after discontinuation, particularly within six months. Longer Dmab treatment duration was associated with reduced SSE risk (HR, 0.96; 95% CI, 0.93-0.99). The incidence of SSEs was lower in the ≥2-year group compared with the <2-year group (0.044 vs. 0.201 per person-year), whereas MRONJ incidence was higher (0.091 vs. 0.055 per person-year, P < 0.001). In the ≥2-year landmark cohort, the number of prior SSEs was the only independent predictor of subsequent SSEs. After ≥2 years, SSE-free survival was not significantly different between discontinuation and continuation groups after PSM (P = 0.074). Median overall survival from Dmab initiation was 41 months, with 1- and 2-year survival rates of 96% and 72%, respectively.
CONCLUSION: Discontinuation of Dmab after ≥2 years may be a reasonable option for selected patients with stable disease. However, decisions must balance the benefit of reduced SSE risk with the increased likelihood of MRONJ. Patients with a history or greater burden of SSEs remain at increased risk and require close monitoring.

Keywords: Bone metastases; denosumab discontinuation; medication-related osteonecrosis of the jaw; skeletal-related events; symptomatic skeletal events

DOI: https://doi.org/10.1016/j.clon.2026.104058

Global Spine J. 2026 Feb 14. 21925682261426935

Clinical Outcomes of Patients Who Underwent Palliative Surgery for Spinal Metastases With and Without a History of Radiation: A Multicenter Registry Study.

Ichiro Kawamura, Hiroyuki Tominaga, Hirofumi Shimada, Hiromi Sasaki, Noboru Taniguchi, Yuki Shiratani, Akinobu Suzuki, Hidetomi Terai, Takaki Shimizu, Kenichiro Kakutani, Yutaro Kanda, Masayuki Ishihara, Masaaki Paku, Yohei Takahashi, Toru Funayama, Kousei Miura, Eiki Shirasawa, Hirokazu Inoue, Atsushi Kimura, Takuya Iimura, Hiroshi Moridaira, Hideaki Nakajima, Shuji Watanabe, Koji Akeda, Norihiko Takegami, Kazuo Nakanishi, Hirokatsu Sawada, Koji Matsumoto, Masahiro Funaba, Hidenori Suzuki, Haruki Funao, Tsutomu Oshigiri, Takashi Hirai, Bungo Otsuki, Kazu Kobayakawa, Koji Uotani, Hiroaki Manabe, Shinji Tanishima, Ko Hashimoto, Chizuo Iwai, Daisuke Yamabe, Akihiko Hiyama, Shoji Seki, Yuta Goto, Masashi Miyazaki, Kazuyuki Watanabe, Toshio Nakamae, Takashi Kaito, Hiroaki Nakashima, Narihito Nagoshi, Satoshi Kato, Shiro Imagama, Kota Watanabe, Gen Inoue, Takeo Furuya.

Study DesignA multicenter retrospective cohort study using prospectively collected data.ObjectivesRadiotherapy (RT) is the standard treatment for spinal metastases; however, the optimal timing of RT in patients requiring surgery remains unclear. This study compared the clinical outcomes of palliative surgery according to RT timing.MethodsAmong 413 patients screened across 35 centers, 146 patients with spinal metastases limited to the spine who underwent palliative surgery were included. Patients were classified into three groups based on RT timing: preoperative RT, postoperative RT, and no RT. Short-term outcomes were compared among the three groups.ResultsOf the 146 patients (preoperative RT: n = 42; postoperative RT: n = 59; no RT: n = 45), baseline characteristics and postoperative functional outcomes were comparable between the postoperative RT and no RT groups. Preoperative opioid use was significantly more frequent in the preoperative RT group. Postoperative complications were more common in the preoperative RT group. Functional outcomes improved in all groups; however, greater improvements in pain and numbness were observed in the nonpreoperative RT group than in the preoperative RT group, with a significant difference noted in numbness improvement.ConclusionsPostoperative recovery after palliative surgery was largely comparable among the three groups. Although greater improvements in pain and numbness were observed in patients who did not receive preoperative RT, the clinical impact of preoperative RT in patients with mechanical instability remains uncertain. Postoperative wound complications were more frequent in the preoperative RT group, but these findings should be interpreted with cautiously given the limited number of events.

Keywords: clinical outcomes; complications; preoperative opioid administration; preoperative radiation therapy; spine metastasis

DOI: https://doi.org/10.1177/21925682261426935

Transl Lung Cancer Res. 2026 Jan 31. 15(1): 19

Pathophysiology and treatment of leptomeningeal metastases in lung cancer.

Toyoaki Hida.

Leptomeningeal metastases (LMs) cause neurological symptoms, including nausea, headache, radicular pain, gait disturbance, and cranial nerve palsies. Lung and breast cancer as well as melanoma are the most common primary tumors in patients with leptomeningeal metastasis. The incidence of LMs is increasing, and this may be due to the improved survival of patients following the development of novel therapies, which may be less effective within the central nervous system. Barrier mechanisms in central nervous system such as blood-brain barrier constitute the critical interfaces between the periphery and brain that actively restrict the entry of solutes and cells into the brain parenchyma and leptomeninges. However, cancer cells could metastasize into the meninges via the brain or choroid plexus, by crossing pial blood vessels, or through vascular channels which connect the bone marrow and meninges. Conventional treatments for LMs, such as chemotherapy, photon-based radiation therapy, and intrathecal chemotherapy, have limited efficacy. However, advances in the understanding of the pathophysiology of LMs and novel treatment modalities are shifting this paradigm. Recent advances in molecularly targeted therapies, antibody-drug conjugates therapies, immunotherapies, intrathecal therapies, proton craniospinal irradiation, and expected therapies such as dendritic and NK cell-engaging therapies may improve the outcomes of patients with LMs. This mini review briefly outlines the pathophysiology and current treatment options for LMs.

Keywords: Leptomeningeal metastases (LMs); blood-brain barrier (BBB); lung cancer; pathophysiology; treatment

DOI: https://doi.org/10.21037/tlcr-2025-aw-1247

Eur Radiol. 2026 Feb 09.

ESR Essentials: bone marrow MRI in oncology-practice recommendations by the European Society of Musculoskeletal Radiology.

Frédéric E Lecouvet, Lokmane Taihi, Thomas Kirchgesner, Vassiliki Pasoglou, Marin Halut, Hatice Tuba Sanal, Salvatore Gitto, Teodoro Martín-Noguerol, Violeta Vasilevska-Nikodinovska, Filip Vanhoenacker, Joan C Vilanova.

Involvement of the bone marrow by metastases from solid tumors or multiple myeloma (MM) is a critical challenge in oncologic imaging. Lesion detection and staging, as well as accurate assessment of treatment response, disease recurrence, and complications, are key to optimal patient management. This article provides recommendations for performing and interpreting bone marrow MRI in cancer patients. MRI should be the primary imaging modality for patients suspected of having skeletal bone metastases or MM, and should replace radiography, bone scintigraphy, and CT for these indications. Protocols must be tailored to the clinical context and to each specific cancer. Whole-body MRI (WB-MRI) is preferred for a comprehensive assessment, while axial skeleton MRI (AS-MRI) is a fast and reliable alternative for targeted or follow-up evaluations. We recommend standardized protocols that incorporate anatomical sequences (preferably fast spin echo T2 Dixon) and diffusion-weighted imaging (DWI). Quantitative biomarkers, e.g., apparent diffusion coefficient (ADC) and fat fraction (FF), should be implemented to improve diagnostic accuracy and evaluate treatment response. Radiologists must be familiar with the typical patterns of bone marrow replacement by cancer cells, response assessment principles, and common imaging pitfalls. Every medical imaging facility should offer optimal bone marrow MRI and implement these recommendations using available MRI systems and existing disease-oriented guidelines. This ESR Essentials illustrates when, how, and why to perform bone marrow MRI to improve diagnostic precision and oncologic care across a broad range of indications. KEY POINTS: Prefer MRI of the bone marrow over radiographs, bone scintigraphy, or CT for suspected bone metastases of solid cancers and for myeloma staging. Use MRI for diagnosis of bone involvement, disease staging, assessment of lesion response to treatment, detection of recurrence, and assessment of osseous complications. Tailor MRI protocol to cancer type following existing guidelines, targeting either the axial skeleton or the "whole body," and using a panel of sequences with fat-sensitive, fast spin echo T2 Dixon and diffusion-weighted sequences as the fundamental components.

Keywords: Bone; Bone marrow; Neoplasms; Therapeutics; Treatment outcome

DOI: https://doi.org/10.1007/s00330-025-12307-4

Orthop Surg. 2026 Feb 13.

Evaluation of the Enhanced Recovery After Surgery (ERAS) Guidance for Patients With Spinal Metastasis.

Fanjie Li, Wenlong Yu, Changchang Shen, Jinxin Luo, Zhibin Li, Qiang Gao, Chengchun Jin, Tao Li, Quan Huang, Shuqiang Wang, Peilin Chu, Mengchen Yin.

Surgery continues to remain the most effective treatment for spinal metastasis (SM). As the number of surgeries continues to grow, the need for consensus guidelines for optimal perioperative care is imperative. Enhanced recovery after surgery (ERAS) protocols were created for this purpose. The objective of this study is to review evidence-based ERAS guidelines for SM surgery. A group of multiple experienced spine surgeons was invited to participate in this study. This group identified 19 ERAS items for SM surgery. The principal literature search utilized MEDLINE, Embase, and Cochrane databases to identify contributions related to the topic published. Systematic reviews, randomized controlled trials (RCTs), and observational cohort studies which reported SM surgery related to the ERAS topics were included. The evidence was graded according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. Consensus recommendations were reached by the group after a critical appraisal of the literature. Five articles were included to develop the consensus statements for 19 ERAS items. All recommendations on ERAS protocol items are based on the best available evidence. They span topics from preoperative patient education and nutritional evaluation, intraoperative anesthetic and surgical techniques, and postoperative multimodal analgesic strategies. The level of evidence for the use of each recommendation is presented. Based on the best evidence available for each ERAS item within the multidisciplinary perioperative pathways, we presented this comprehensive consensus review for SM surgery. This ERAS elements can be implemented and practiced clinically.

Keywords: GRADE; consensus statement; enhanced recovery after surgery; recommendations; spinal metastasis

DOI: https://doi.org/10.1111/os.70251

AJNR Am J Neuroradiol. 2026 Feb 09. pii: ajnr.A9211. [Epub ahead of print]

Spinal Metastasis Reporting: Evidence Based Recommendation on behalf of the American Society of Spine Radiology Education and Standards Committee.

Rami W Eldaya, Saad Ali, Mohiuddin Hadi, Jacob W Ormsby, Sandra Abi Fadel, Mai-Lan Ho.

Structured reporting in radiology is universally endorsed by the radiology societies, including American Society of Neuroradiology/American Society of Spine Radiology (ASNR/ASSR), Structured reporting offers many advantages including: standardization of reports and simplifying reports for referring providers and researchers to extract meaningful and important information. Furthermore, templates can guide radiologists by providing a "checklist" on necessary items to include in the report which can facilitate patient care and optimize patient management.Despite the known benefits of structured reporting, currently structured reporting of spinal metastasis continues to lack. This is explained by many factors including complexity of spinal metastasis, variability of its appearance based on primaries, multiplicity of lesions/variable extent of disease, and technical differences among MRI acquisition protocols between institutions.In this white paper from the American Society of Spine Radiology Education and Standards, we aim to provide a recommended structured reporting of spinal metastasis highlighting pertinent observations that are needed in reporting metastasis, reflecting relevance of radiology report to recent advances in treatment modalities, discussing advanced and emerging imaging modalities, and finally touching briefly on follow up recommendations and challenges.

DOI: https://doi.org/10.3174/ajnr.A9211