bims-rebome 2026-02-22 papers

J Clin Neurosci. 2026 Feb 13. pii: S0967-5868(26)00079-2. [Epub ahead of print]147 111928

The Bone Microenvironment and Therapeutic Resistance in Spinal Metastases: Mechanisms and Clinical Implications.

Laura Mittelman, Luis O Vargas, Matthew Abikenari, Samuel Latzman, John Chen, Karthik Rangavajhula, Shoaib Syed, Brandon A Santhumayor, James Duehr, Nicholas Cassimatis, John Caridi, Sheng-Fu Larry Lo, Daniel M Sciubba, Randy S D'Amico.

BACKGROUND: Spinal metastases represent a biologically distinct manifestation of systemic cancer, frequently progressing despite durable visceral response. The vertebral niche is defined by hypoxia, immune suppression, osteoclast-osteoblast coupling, and stromal signaling. These features create a therapeutic sanctuary that fosters tumor dormancy, clonal evolution, and resistance to systemic therapy.
OBJECTIVE: We aim to synthesize current knowledge of the bone niche in spinal metastases, explain how microenvironmental factors and tumor-intrinsic changes converge to drive therapeutic resistance, and provide translational implications for prognosis and treatment design.
METHODS: A narrative review of English-language studies (1990-2024) from PubMed and Scopus was conducted, examining pathophysiology, bone-tumor crosstalk, dormancy, immune evasion, and resistance genetics. Foundational pre-1990 works were included when biologically essential. When available, bone-specific outcomes (skeletal progression, skeletal-related events, spine-PFS) were prioritized.
RESULTS: Spinal metastases are driven by unique interactions between tumor cells and the bone microenvironment, including RANK/RANKL signaling, hypoxia-induced HIF activation, immune sequestration, and dormancy niches. Specific molecular alterations include EGFR and ALK mutations in NSCLC, BRCA and PI3K/AKT pathway dysregulation in prostate and breast cancers, and VHL/HIF pathway alterations in RCC. Resistance patterns such as EGFR T790M and BRCA reversion mutations emerge disproportionately in bone, reflecting site-specific selective pressure. Conventional systemic therapies achieve lower efficacy in the spine, underscoring the need for site-specific biomarkers, advanced imaging, and tailored therapeutic strategies.
CONCLUSION: The vertebral niche constitutes a treatment-resistant microenvironment where dormant tumor cells persist, immune surveillance is impaired, and resistant clones evolve. Integrating bone-microenvironment biology with molecular profiling, liquid biopsy, and advanced imaging is essential for refining prognostic models, guiding intervention timing, and designing spine-specific clinical trials. By reframing spinal metastases as a biologically and therapeutically distinct disease entity, this review establishes a framework for developing bone-directed treatment strategies and advancing precision oncology in metastatic spine care.

Keywords: Bone microenvironment; Immune evasion; Precision oncology; Spinal metastases; Therapeutic resistance; Tumor dormancy; Vertebral niche

DOI: https://doi.org/10.1016/j.jocn.2026.111928

Front Oncol. 2026 ;16 1730986

Head-to-head comparative study of [68Ga]FAPI-04 PET/CT and [18F]FDG PET/CT in assessing bone metastasis of various cancers: a systematic review and meta-analysis.

MingLiu He, Jian Tan.

Purpose: The objective of our systematic review and meta-analysis is to compare the performance of [68Ga]FAPI-04 PET/CT and [18F]FDG PET/CT in diagnosing bone metastasis of various cancer types. This analysis aims to provide an objective assessment of the diagnostic capabilities of these two imaging modalities.
Methods: We conducted a search on Embase, Web of Science, Pubmed for articles published between 2023 and 2025 that meet our criteria. This study focuses on exploring the diagnostic value of [68Ga]FAPI-04 PET/CT and [18F]FDG PET/CT in various cancer bone metastases. we used random-effects analysis to assess the diagnostic capabilities of [68Ga]FAPI-04 PET/CT and [18F]FDG PET/CT in patient-based analysis (PB) with bone metastasis and bone metastatic lesion-based analysis (LB).Heterogeneity of the data was assessed through sensitivity analysis. Furthermore, the included studies underwent quality assessment using the QUADAS-2 tool, which is a bias assessment tool utilized for diagnostic test accuracy studies.
Results: In the initial search, 235 articles were identified, and finally 10 clinical studies were included by excluding related articles. All included studies were retrospective, involved diverse cancer types, and did not contain overlapping patient cohorts from the same institution. In the patient-based analysis (PB), the detection rate of [68Ga]FAPI-04 PET/CT was determined to be 0.99 (95% CI: 0.90-1.00, I²=36.5%), whereas that of [18F]FDG PET/CT was 0.79 (95% CI: 0.54-0.79, I²=62.4%),Sensitivity analysis revealed potential sources of heterogeneity. In the lesion-based analysis (LB), the detection rate of [68Ga]FAPI-04 PET/CT was determined to be 1.00 (95% CI: 0.98-1.00, I²=91.5%), while [18F]FDG PET/CT showed a detection rate of 0.71 (95% CI: 0.61-0.80, I²=95.3%), with no significant sources of heterogeneity identified.
Conclusion: By comparing the available data, [68Ga]FAPI-04 PET/CT appears to show a higher detection rate for bone metastases in various malignancies compared with [18F]FDG PET/CT. However, this finding should be interpreted with caution, as pooled sensitivity, specificity, PPV, NPV, DOR, or HSROC analyses could not be performed due to insufficient available data.

Keywords: FAPI; FDG; PET/CT; bone metastasis; meta-analysis

DOI: https://doi.org/10.3389/fonc.2026.1730986

J Orthop. 2026 May;75 46-56

Comparative complication rates of titanium vs carbon fiber intramedullary nails in pathologic long bone fractures: A systematic review and meta-analysis.

Joseph D Giacalone, Kunal Shah, Taylor Davis, Sanjana Subramanyam, James C Wittig.

Introduction: Carbon fiber (CF) intramedullary (IM) nails have emerged as a promising alternative to titanium (TI) implants for managing pathologic long bone fractures, offering advantages such as radiolucency for improved imaging, reduced artifact during surveillance, and minimal attenuation of therapeutic radiation. Although early studies suggest comparable complication rates between CF and TI constructs, existing evidence remains limited by small sample sizes and a lack of direct, high-quality comparisons of complication profiles. This study aimed to systematically compare complication rates between CF and TI IM nails for the treatment of pathologic long-bone disease secondary to malignancy.
Methods: A systematic review and meta-analysis were conducted in accordance with the PRISMA 2020 guidelines to evaluate the complication profiles of CF versus TI IM nails in patients with impending or completed pathologic long-bone fractures secondary to malignancy. Eligible studies reported on postoperative outcomes, including revision surgery, nonunion, periprosthetic fracture, implant failure, and overall complication rates. Data were analyzed using single-proportion meta-analysis and subgroup analysis in RStudio v4.5.1.
Results: Five retrospective cohort studies comprising 361 patients (194 treated with TI nails and 167 with CF nails) met the inclusion criteria. There were no statistically significant differences between cohorts in rates of nonunion (p = 0.876), periprosthetic fracture (p = 0.834), revision surgery (p = 0.757), or total complication rates (p = 0.617). However, implant failure occurred at a higher rate in the CF group (p = 0.016), based on a limited number of events.
Conclusion: CF IM nails appear to demonstrate complication rates comparable to traditional TI implants in the fixation of pathologic long bone fractures secondary to bone tumors, although they may be associated with a higher observed risk of implant failure. Given the low to very low quality of available evidence and the relatively small pooled sample size of this review, these findings should be considered exploratory. Future large-scale, prospective randomized studies are warranted to confirm these findings and enhance their generalizability across diverse oncologic populations.

Keywords: Carbon fiber; Intramedullary nail; Meta-analysis; Metastatic bone disease; Orthopedic oncology; Pathologic fracture; Systematic review; Titanium

DOI: https://doi.org/10.1016/j.jor.2026.02.005

J Am Acad Orthop Surg. 2025 Nov 19.

Contemporary Tumor Histology Grouping for Survival Prediction of Patients With Metastatic Long-bone Disease Undergoing Surgery.

Tom M de Groot, Olivier Q Groot, Rene H Kuijten, Michelle R Shimizu, Kevin A Raskin, Erik T Newman, Job N Doornberg, Paul C Jutte, Santiago A Lozano-Calderón, Joseph H Schwab.

BACKGROUND: The prevalence of metastatic bone disease continues to rise with advances in cancer diagnostics and systemic therapy. Accurate survival prediction remains essential for surgical decision-making near the end of life. The Katagiri score is a widely used tool incorporating primary tumor histology grouped by expected growth rate. However, it was developed using 2005-2008 data from mainly non-surgical, spinal metastasis patients. As oncologic treatments evolve, tumor histology groupings require reassessment. This study investigated the impact of primary tumor histology on postoperative survival in patients with metastatic long-bone disease.
METHODS: We retrospectively included 460 patients who underwent surgery for long-bone metastases at two affiliated tertiary institutions between 2016 and 2021. The primary outcome was postoperative survival. Tumor types were classified into three survival groups-better, intermediate, and worse-by setting thresholds at the 33rd and 66th percentiles of coefficients derived from multivariable Cox proportional hazards regression.
RESULTS: Median survival was 16.5 months (interquartile ranges [IQR], 4.7 to 37.9) for better-survival tumors, 9.2 months (IQR, 2.6 to 20.6) for intermediate, and 3.9 months (IQR, 1.6 to 11.6) for worse. Survival improved significantly in tumors responsive to modern systemic therapies, particularly immunotherapy, including renal cell carcinoma, melanoma, hepatocellular carcinoma, and colorectal carcinoma. Gynecological malignancies demonstrated the poorest outcomes.
DISCUSSION: This contemporary, histology-based classification reflects modern oncologic outcomes and provides a practical prognostic tool for clinicians treating patients with extremity metastases. Incorporating this updated grouping into prediction models may enhance accuracy and clinical utility. These findings emphasize the importance of regularly auditing prognostic models to remain aligned with evolving cancer therapies and survival trends.

DOI: https://doi.org/10.5435/JAAOS-D-25-00049

Br J Neurosurg. 2026 Feb 16. 1-9

In the artificial intelligence age, is Oswestry spinal risk index still useful? an external validation of Oswestry spinal risk index applied to radiotherapy patients and its relevance.

Savithru Prakash, Megan Havard, Elizabeth Hodges, Anirudh Agrawal, Sashin Ahuja.

BACKGROUND AND STUDY AIMS: In 2013, Balain et al. proposed a scoring system, the Oswestry Spinal Risk Index (OSRI), to predict survival in patients with spinal metastases (SM) and hence aid treatment decisions. This study aims to externally validate the OSRI for patients treated exclusively with radiotherapy, and assess its relevance in emergency decision making in the age of nomograms and machine learning.
MATERIALS AND METHODS: Data from 150 patients with spinal metastases (SM) treated at our Regional Cancer Centre over a four-year period were retrospectively analysed. OSRI scores were calculated for each patient, and actual survival duration from diagnosis was determined to enable comparison with predicted survival. The cohort, selected over a decade ago, ensured complete survival data for all included patients.
RESULTS: Spearman's rank correlation demonstrated a strong positive relationship between actual and OSRI-predicted survival (r = 0.706, p < 0.001). The Mantel-Cox log-rank test revealed statistically significant differences in survival curves across OSRI risk groups (p < 0.001), with lower OSRI scores associated with longer survival. Paired sample t-tests further confirmed this correlation (one-sided p = 0.009; two-sided p = 0.017). Kaplan-Meier survival plots were similar to those of the original study.
CONCLUSIONS: This study is the first to externally validate the Oswestry Spinal Risk Index (OSRI) specifically in patients treated exclusively with radiotherapy. Unlike previous validations, which included patients managed surgically or with combined modalities, our cohort focused solely on radiotherapy. We found a strong correlation between predicted and actual survival, highlighting the OSRI's simplicity, accuracy and its practical value for rapid decision-making in emergency settings.

Keywords: Spinal metastasis; machine learning; oswestry spinal risk index; prognosis scores in spinal metastasis; spinal radiotherapy

DOI: https://doi.org/10.1080/02688697.2026.2630840