Pub Date : 2026-01-12DOI: 10.1016/j.jbo.2026.100739
Pedro Reggiani Anzuategui , Glauco José Pauka Mello , Ana Valéria Brunetti Rigolino , Lucas Emanuel Sauer Larocca , Cássio Zini , Carmen Australia Paredes Marcondes Ribas
<div><h3>Background context</h3><div>Surgical decision-making in patients with spinal metastases remains complex due to the need to balance potential surgical benefits with limited survival and common frailty. Predictive models can assist in this process, but their clinical utility is often limited by complexity and lack of validation.</div></div><div><h3>Purpose</h3><div>To externally validate a simple three-predictor frailty model for 90-day survival and complications, and to compare its performance with other commonly used tools.</div></div><div><h3>Study design/setting</h3><div>Prospective external validation study conducted at a single tertiary cancer center.</div></div><div><h3>Patient sample</h3><div>A consecutive cohort of 126 patients who underwent open posterior surgery with instrumentation for spinal metastases from solid tumors between 2018 and 2024.</div></div><div><h3>Outcome measures</h3><div>Primary outcomes were 90-day survival and the occurrence of postoperative complications. Secondary outcomes included 30-day, 180-day and overall survival. Model performance was evaluated through discrimination (AUC), risk stratification, accuracy for surgical indication and calibration.</div></div><div><h3>Methods</h3><div>The Anzuategui model (three predictors: tumor growth rate, comorbidities, and lymphocyte count) was applied preoperatively, along with four other three-predictor models (Tomita, Modified Bauer, Van der Linden, and Sioutos). Discrimination was assessed using ROC curves. Risk stratification was evaluated using predefined low-, moderate-, and high-risk categories, analyzed through Kaplan–Meier curves and complication rates. Model accuracy for surgical indication was calculated using a 90-day survival threshold as the reference. Calibration for both 90-day survival and postoperative complications was performed by comparing category-specific predicted probabilities derived from the development cohort with observed event rates in the validation cohort.</div></div><div><h3>Results</h3><div>The Anzuategui model demonstrated predictive performance for the primary outcomes comparable to the other models under evaluation. It achieved an AUC of 0.78 (95% CI: 0.70–0.85) for 90-day survival and 0.68 (95% CI: 0.59–0.76) for postoperative complications. Risk stratification showed clear separation between survival curves across the three predefined categories. Accuracy for predicting appropriate surgical indication was 70% (95% CI: 61–78), with a sensitivity of 64% and specificity of 85%. Tomita and Modified Bauer models showed comparable accuracy (75% and 74%, respectively) but lower specificity. Calibration indicated overestimation of 90-day mortality (intercept –1.75; slope 2.05) and modest miscalibration for postoperative complications (intercept –0.40; slope 0.67).</div></div><div><h3>Conclusions</h3><div>The Anzuategui model demonstrated acceptable external performance, with greater validity for predicting 90-day survival than for post
{"title":"Prospective external validation of a three-predictor frailty model for 90-day survival and complications following spinal metastasis surgery","authors":"Pedro Reggiani Anzuategui , Glauco José Pauka Mello , Ana Valéria Brunetti Rigolino , Lucas Emanuel Sauer Larocca , Cássio Zini , Carmen Australia Paredes Marcondes Ribas","doi":"10.1016/j.jbo.2026.100739","DOIUrl":"10.1016/j.jbo.2026.100739","url":null,"abstract":"<div><h3>Background context</h3><div>Surgical decision-making in patients with spinal metastases remains complex due to the need to balance potential surgical benefits with limited survival and common frailty. Predictive models can assist in this process, but their clinical utility is often limited by complexity and lack of validation.</div></div><div><h3>Purpose</h3><div>To externally validate a simple three-predictor frailty model for 90-day survival and complications, and to compare its performance with other commonly used tools.</div></div><div><h3>Study design/setting</h3><div>Prospective external validation study conducted at a single tertiary cancer center.</div></div><div><h3>Patient sample</h3><div>A consecutive cohort of 126 patients who underwent open posterior surgery with instrumentation for spinal metastases from solid tumors between 2018 and 2024.</div></div><div><h3>Outcome measures</h3><div>Primary outcomes were 90-day survival and the occurrence of postoperative complications. Secondary outcomes included 30-day, 180-day and overall survival. Model performance was evaluated through discrimination (AUC), risk stratification, accuracy for surgical indication and calibration.</div></div><div><h3>Methods</h3><div>The Anzuategui model (three predictors: tumor growth rate, comorbidities, and lymphocyte count) was applied preoperatively, along with four other three-predictor models (Tomita, Modified Bauer, Van der Linden, and Sioutos). Discrimination was assessed using ROC curves. Risk stratification was evaluated using predefined low-, moderate-, and high-risk categories, analyzed through Kaplan–Meier curves and complication rates. Model accuracy for surgical indication was calculated using a 90-day survival threshold as the reference. Calibration for both 90-day survival and postoperative complications was performed by comparing category-specific predicted probabilities derived from the development cohort with observed event rates in the validation cohort.</div></div><div><h3>Results</h3><div>The Anzuategui model demonstrated predictive performance for the primary outcomes comparable to the other models under evaluation. It achieved an AUC of 0.78 (95% CI: 0.70–0.85) for 90-day survival and 0.68 (95% CI: 0.59–0.76) for postoperative complications. Risk stratification showed clear separation between survival curves across the three predefined categories. Accuracy for predicting appropriate surgical indication was 70% (95% CI: 61–78), with a sensitivity of 64% and specificity of 85%. Tomita and Modified Bauer models showed comparable accuracy (75% and 74%, respectively) but lower specificity. Calibration indicated overestimation of 90-day mortality (intercept –1.75; slope 2.05) and modest miscalibration for postoperative complications (intercept –0.40; slope 0.67).</div></div><div><h3>Conclusions</h3><div>The Anzuategui model demonstrated acceptable external performance, with greater validity for predicting 90-day survival than for post","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"57 ","pages":"Article 100739"},"PeriodicalIF":3.5,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145982069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-04DOI: 10.1016/j.jbo.2025.100738
Cyrille B. Confavreux , Béatrice Bouvard , Nicolas Girard , Pauline Bosco-Levy , Clarisse Marchal , Maeva Nolin , Eric Lehmann , Gaelle Desameric , Manon Belhassen
Aim
To determine the use of bone-targeting agents (BTAs) in clinical practice in France and the occurrence of skeletal-related events (SREs) in cancer patients with bone metastases.
Methods
This study analysed data, recorded prospectively in a French National Health Insurance database, for patients who had a first diagnosis of bone metastases between 2009 and 2018.
Results
A total of 6,663 patients were analysed (mean age 69.7 ± 13.2 years, 53.2 % male) corresponding to 2,363 bone metastases only patients and 4,300 patients with SREs at inclusion. The most frequent primary cancers were breast (15.8 %), prostate (13.4 %), lung (12.6 %) and digestive cancer (10.6 %). Six-hundred and twenty-one patients (9.3 %) were treated with BTAs (52.7 % with denosumab). Median [IQR] time between inclusion and BTA initiation was similar with denosumab (3.3 months [1.2–7.9]) and bisphosphonates (3.3 months [1.2–8.7]). Patients with a SRE at inclusion and early BTA initiation (≤3 months) had a significative lower incidence of a second SRE at 12 months than those with late initiation (13.6 % [95 %CI: 8.1–20.4] vs. 21.6 % [14.8–29.2] respectively; p < 0.001).
Conclusion
BTAs are underused in bone metastases patients in France. There is an urgent need to optimise bone metastases management in accordance with ESMO 2020 guidelines.
{"title":"Real-life use of bone-targeting agents for bone metastases in France between 2009 and 2018: Results of the OPTIMOS study","authors":"Cyrille B. Confavreux , Béatrice Bouvard , Nicolas Girard , Pauline Bosco-Levy , Clarisse Marchal , Maeva Nolin , Eric Lehmann , Gaelle Desameric , Manon Belhassen","doi":"10.1016/j.jbo.2025.100738","DOIUrl":"10.1016/j.jbo.2025.100738","url":null,"abstract":"<div><h3>Aim</h3><div>To determine the use of bone-targeting agents (BTAs) in clinical practice in France and the occurrence of skeletal-related events (SREs) in cancer patients with bone metastases.</div></div><div><h3>Methods</h3><div>This study analysed data, recorded prospectively in a French National Health Insurance database, for patients who had a first diagnosis of bone metastases between 2009 and 2018.</div></div><div><h3>Results</h3><div>A total of 6,663 patients were analysed (mean age 69.7 ± 13.2 years, 53.2 % male) corresponding to 2,363 bone metastases only patients and 4,300 patients with SREs at inclusion. The most frequent primary cancers were breast (15.8 %), prostate (13.4 %), lung (12.6 %) and digestive cancer (10.6 %). Six-hundred and twenty-one patients (9.3 %) were treated with BTAs (52.7 % with denosumab). Median [IQR] time between inclusion and BTA initiation was similar with denosumab (3.3 months [1.2–7.9]) and bisphosphonates (3.3 months [1.2–8.7]). Patients with a SRE at inclusion and early BTA initiation (≤3 months) had a significative lower incidence of a second SRE at 12 months than those with late initiation (13.6 % [95 %CI: 8.1–20.4] vs. 21.6 % [14.8–29.2] respectively; p < 0.001).</div></div><div><h3>Conclusion</h3><div>BTAs are underused in bone metastases patients in France. There is an urgent need to optimise bone metastases management in accordance with ESMO 2020 guidelines.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"56 ","pages":"Article 100738"},"PeriodicalIF":3.5,"publicationDate":"2026-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145939112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-19DOI: 10.1016/j.jbo.2025.100737
Baiyi Liu , Dongsheng Wang , Jian Zhang , Bo Huang , Mingying Geng , Peng Liu , Yaoyao Liu
Objective
This study aimed to introduce a novel modified separation surgery combined with intraoperative radiotherapy (MSS-IORT) treatment strategy for spinal metastasis and evaluate its efficacy and safety.
Methods
A prospective study was conducted from January 2023 to June 2024. Patients with spinal metastasis exhibiting epidural spinal cord compression (ESCC) ≥ 2 grades and spinal instability neoplastic score (SINS) ≥ 7 were enrolled and underwent MSS-IORT. During the procedure, a dose of 8–10 Gy of IORT was administered to the tumor-invaded vertebrae segments during modified separation surgery. Pain intensity was assessed using the visual analog scale (VAS) preoperatively and at 1 week, 3 months, 6 months, and 12 months postoperatively. Neurological function was evaluated via the Frankel grade system, and functional status was measured using the Karnofsky performance scale (KPS) preoperatively and at 3, 6, and 12 months after surgery. Local control was evaluated based on X-ray, CT, or MRI examination. Survival time and perioperative complications were also documented.
Results
A total of 38 patients (median age: 60 years) with 46 involved vertebrae were treated with MSS-IORT. The mean operation time was 277.5 min, and the mean blood loss was 750 ml. After a mean follow-up of 174.5 days, the VAS score decreased significantly postoperatively and continued to decline over time. The KPS score increased significantly at 6 and 12 months, and the Frankel grade significantly improved at 12 months. Local control failure occurred in 3 patients, and 13 experienced adverse events without IORT.
Conclusion
The MSS-IORT strategy demonstrates both safety and efficacy, representing a promising treatment option for spine metastases, particularly in patients with ESCC grades ≥ 2 and SINS ≥ 7.
{"title":"Pilot study of separation surgery with intraoperative radiotherapy (IORT) for spine metastasis","authors":"Baiyi Liu , Dongsheng Wang , Jian Zhang , Bo Huang , Mingying Geng , Peng Liu , Yaoyao Liu","doi":"10.1016/j.jbo.2025.100737","DOIUrl":"10.1016/j.jbo.2025.100737","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to introduce a novel modified separation surgery combined with intraoperative radiotherapy (MSS-IORT) treatment strategy for spinal metastasis and evaluate its efficacy and safety.</div></div><div><h3>Methods</h3><div>A prospective study was conducted from January 2023 to June 2024. Patients with spinal metastasis exhibiting epidural spinal cord compression (ESCC) ≥ 2 grades and spinal instability neoplastic score (SINS) ≥ 7 were enrolled and underwent MSS-IORT. During the procedure, a dose of 8–10 Gy of IORT was administered to the tumor-invaded vertebrae segments during modified separation surgery. Pain intensity was assessed using the visual analog scale (VAS) preoperatively and at 1 week, 3 months, 6 months, and 12 months postoperatively. Neurological function was evaluated <em>via</em> the Frankel grade system, and functional status was measured using the Karnofsky performance scale (KPS) preoperatively and at 3, 6, and 12 months after surgery. Local control was evaluated based on X-ray, CT, or MRI examination. Survival time and perioperative complications were also documented.</div></div><div><h3>Results</h3><div>A total of 38 patients (median age: 60 years) with 46 involved vertebrae were treated with MSS-IORT. The mean operation time was 277.5 min, and the mean blood loss was 750 ml. After a mean follow-up of 174.5 days, the VAS score decreased significantly postoperatively and continued to decline over time. The KPS score increased significantly at 6 and 12 months, and the Frankel grade significantly improved at 12 months. Local control failure occurred in 3 patients, and 13 experienced adverse events without IORT.</div></div><div><h3>Conclusion</h3><div>The MSS-IORT strategy demonstrates both safety and efficacy, representing a promising treatment option for spine metastases, particularly in patients with ESCC grades ≥ 2 and SINS ≥ 7.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"56 ","pages":"Article 100737"},"PeriodicalIF":3.5,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145939114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-13DOI: 10.1016/j.jbo.2025.100736
Veli Kaan Aydin , Lubaid Saleh , Penelope Dawn Ottewell , Ingunn Holen
Doxorubicin (DOX), commonly used to treat breast cancer, is associated with cardiotoxicity and has negative effects on other organ systems, including the skeleton. DOX-induced bone damage has been demonstrated in murine models; however, results are conflicting due to the use of different doses, schedules, and rat/mouse strains. As DOX is used to limit tumour progression in models of skeletal metastasis, it is paramount to determine how the agent affects the bone microenvironment in the relevant mouse strains, to enable correct interpretation of DOX effects in tumour studies. We have therefore investigated the effects of DOX on bone structure and a range of bone and bone marrow cell populations, comparing immunocompetent and immunocompromised mice.
Groups of 7-week-old female BALB/c and BALB/c Nude mice were treated with either saline (control), 4 or 6 mg/kg DOX weekly for four weeks. Effects on bone volume and structure was determined using ex vivo µCT, a panel of bone marrow cell populations were quantified by flow cytometry and osteoblast/osteoclast numbers were assessed using bone histomorphometry.
DOX caused trabecular bone loss, with immunocompetent BALB/c mice being more sensitive to DOX than the immunocompromised BALB/c nude counterparts. The 6 mg/kg dose of DOX altered the ratio of bone marrow immune and haematopoietic cell populations in both groups, increasing the numbers of hematopoietic cells and progenitors, decreasing B cells and increasing the number of neutrophils. Bone marrow macrophage and monocyte numbers were increased following DOX treatment in BALB/c nude mice only. Our data demonstrate that DOX impacts a number of cell types in the bone microenvironment, highlighting the importance of considering treatment-induced bone effects when using DOX in models of bone metastasis.
{"title":"Doxorubicin induces bone loss and modifies multiple cell populations in vivo – Implications for modelling of bone metastasis","authors":"Veli Kaan Aydin , Lubaid Saleh , Penelope Dawn Ottewell , Ingunn Holen","doi":"10.1016/j.jbo.2025.100736","DOIUrl":"10.1016/j.jbo.2025.100736","url":null,"abstract":"<div><div>Doxorubicin (DOX), commonly used to treat breast cancer, is associated with cardiotoxicity and has negative effects on other organ systems, including the skeleton. DOX-induced bone damage has been demonstrated in murine models; however, results are conflicting due to the use of different doses, schedules, and rat/mouse strains. As DOX is used to limit tumour progression in models of skeletal metastasis, it is paramount to determine how the agent affects the bone microenvironment in the relevant mouse strains, to enable correct interpretation of DOX effects in tumour studies. We have therefore investigated the effects of DOX on bone structure and a range of bone and bone marrow cell populations, comparing immunocompetent and immunocompromised mice.</div><div>Groups of 7-week-old female BALB/c and BALB/c Nude mice were treated with either saline (control), 4 or 6 mg/kg DOX weekly for four weeks. Effects on bone volume and structure was determined using <em>ex vivo</em> µCT, a panel of bone marrow cell populations were quantified by flow cytometry and osteoblast/osteoclast numbers were assessed using bone histomorphometry.</div><div>DOX caused trabecular bone loss, with immunocompetent BALB/c mice being more sensitive to DOX than the immunocompromised BALB/c nude counterparts. The 6 mg/kg dose of DOX altered the ratio of bone marrow immune and haematopoietic cell populations in both groups, increasing the numbers of hematopoietic cells and progenitors, decreasing B cells and increasing the number of neutrophils. Bone marrow macrophage and monocyte numbers were increased following DOX treatment in BALB/c nude mice only. Our data demonstrate that DOX impacts a number of cell types in the bone microenvironment, highlighting the importance of considering treatment-induced bone effects when using DOX in models of bone metastasis.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"56 ","pages":"Article 100736"},"PeriodicalIF":3.5,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145798385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-08DOI: 10.1016/j.jbo.2025.100733
Jie Xia , Kunming Jiang , Jinyi Zhou , Lei Cao , Fan Xiao , Jingxuan Jiang
Purpose
This study aims to explore the feasibility of MRI-based habitat and peritumoral radiomics for predicting the proliferative activity of stromal cells in giant cell tumor of bone (GCTB).
Material and methods
A retrospective study was performed on 133 patients (102 in training cohort and 31 in validation cohort) diagnosed with GCTB from four centers. The tumor was meticulously segmented into three distinct habitat subregions using K-means clustering, incorporating a 1-pixel peritumoral expansion to capture the microenvironments surrounding the tumor. After feature extraction and selection, habitat, intratumoral and peritumoral models integrating three different machine learning classifiers were constructed respectively to identify GCTB patients with high and low proliferation. The performance of the models was assessed by receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA). SHAP analysis was utilized to enhance model interpretability.
Results
Among the eligible patients, 43 (32.3 %) diagnosed with high proliferative activity of stromal cells in GCTB by pathological diagnosis. Among all models tested in the validation cohort, the Logistic Regression (LR) algorithm for habitat model exhibited superior performance in the validation cohort (AUC: 0.956, 95 % CI: 0.887–1.000). The calibration curves and DCA exhibited fit for the habitat model while providing great clinical net benefit.
Conclusion
MRI-based habitat radiomics had the potential to predict the proliferative activity of stromal cells in GCTB. This model may help determine optimal treatment strategies and improve patient outcomes.
{"title":"Mri-based habitat and peritumoral radiomics for predicting the proliferative activity of stromal cells in giant cell tumor of bone","authors":"Jie Xia , Kunming Jiang , Jinyi Zhou , Lei Cao , Fan Xiao , Jingxuan Jiang","doi":"10.1016/j.jbo.2025.100733","DOIUrl":"10.1016/j.jbo.2025.100733","url":null,"abstract":"<div><h3>Purpose</h3><div>This study aims to explore the feasibility of MRI-based habitat and peritumoral radiomics for predicting the proliferative activity of stromal cells in giant cell tumor of bone (GCTB)<strong>.</strong></div></div><div><h3>Material and methods</h3><div>A retrospective study was performed on 133 patients<!--> <!-->(102 in training cohort and 31 in validation cohort) diagnosed with GCTB<!--> <!-->from four centers. The tumor was meticulously segmented into three distinct habitat subregions using K-means clustering, incorporating a 1-pixel peritumoral expansion to capture the microenvironments surrounding the tumor. After feature extraction and selection, habitat, intratumoral and peritumoral models integrating three different machine learning classifiers were constructed respectively to identify GCTB patients with high and low proliferation. The performance of the models was assessed by receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA). SHAP analysis was utilized to enhance model interpretability.</div></div><div><h3>Results</h3><div>Among the eligible patients, 43 (32.3 %) diagnosed with high proliferative activity of stromal cells in GCTB by pathological diagnosis. Among all models tested in the validation cohort, the Logistic Regression (LR) algorithm for habitat model exhibited superior performance in the validation cohort (AUC: 0.956, 95 % CI: 0.887–1.000). The calibration curves and DCA exhibited fit for the habitat model while providing great clinical net benefit.</div></div><div><h3>Conclusion</h3><div>MRI-based habitat radiomics had the potential to predict the proliferative activity of stromal cells in GCTB. This model may help determine optimal treatment strategies and improve patient outcomes.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"56 ","pages":"Article 100733"},"PeriodicalIF":3.5,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145749334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-06DOI: 10.1016/j.jbo.2025.100735
Julian P. Maier , Ida Peiss , Felix Klingler , Nikos Karvouniaris , Kilian Reising , Hagen Schmal , Georg W. Herget
Background
Pathological fractures are recognized as a potential, adverse prognostic factor in primary bone sarcomas. While some studies suggest higher recurrence rates and reduced survival, robust data specific to chondrosarcoma (CS) remain limited. This study evaluates the prognostic relevance of pathological fractures (PF) in CS patients.
Methods
A systematic review and meta-analysis were conducted according to PRISMA guidelines. Eligible studies included patients with CS of the bone, with comparative groups based on fracture status and oncological outcomes. Study design, quality, and endpoints were assessed, and pooled meta-analysis was conducted. Additionally, clinical data from an institutional cohort was analyzed retrospectively.
Results
Nine studies, with a total of 1,185 patients and 245 PF cases, met the inclusion criteria. Meta-analysis revealed that PF status was significantly associated with inferior survival at 1–5 years (pooled OR 0.40; 95 % CI 0.26–0.62; p < 0.0001). The increased risk of death was particularly evident in dedifferentiated CS (pooled HR 1.96; 95 % CI 1.46–2.63; p < 0.00001). Institutional data supported these findings, that PF was associated with worse overall survival (HR 3.90; 95 % CI 0.69–21.98; p = 0.12) and progression-free survival (HR 3.17; 95 % CI 0.58–17.36; p = 0.18), although significance was limited by sample size.
Conclusions
Pathological fractures entail a significantly adverse prognosis in chondrosarcoma, particularly in high-grade and dedifferentiated subtypes and within the first 5 years of follow-up. Our institutional data corroborates meta-analysis findings. These results underscore the importance of personalized surgical management and intensive outcome monitoring for CS patients presenting with PF.
病理性骨折被认为是原发性骨肉瘤潜在的不良预后因素。虽然一些研究表明更高的复发率和降低的生存率，但软骨肉瘤（CS）特异性的可靠数据仍然有限。本研究评估了CS患者病理性骨折（PF）与预后的相关性。方法根据PRISMA指南进行系统评价和meta分析。符合条件的研究包括骨CS患者，并根据骨折状态和肿瘤预后进行比较。对研究设计、质量和终点进行了评估，并进行了汇总荟萃分析。此外，回顾性分析了来自机构队列的临床数据。结果9项研究共纳入1185例患者和245例PF，符合纳入标准。荟萃分析显示，PF状态与1-5年的不良生存率显著相关（合并OR 0.40; 95% CI 0.26-0.62; p < 0.0001）。去分化CS的死亡风险增加尤为明显（总危险度1.96;95% CI 1.46-2.63; p < 0.00001）。机构数据支持这些发现，尽管受样本量限制，但PF与较差的总生存期（HR 3.90; 95% CI 0.69-21.98; p = 0.12）和无进展生存期（HR 3.17; 95% CI 0.58-17.36; p = 0.18）相关。结论病理性骨折对软骨肉瘤的预后有明显的不良影响，特别是在高级别和去分化亚型以及前5年的随访中。我们的机构数据证实了meta分析的结果。这些结果强调了个性化手术管理和强化预后监测对伴有PF的CS患者的重要性。
{"title":"Pathological fractures as an adverse prognostic factor in chondrosarcoma: Results of a systematic review, meta-analysis and institutional case series","authors":"Julian P. Maier , Ida Peiss , Felix Klingler , Nikos Karvouniaris , Kilian Reising , Hagen Schmal , Georg W. Herget","doi":"10.1016/j.jbo.2025.100735","DOIUrl":"10.1016/j.jbo.2025.100735","url":null,"abstract":"<div><h3>Background</h3><div>Pathological fractures are recognized as a potential, adverse prognostic factor in primary bone sarcomas. While some studies suggest higher recurrence rates and reduced survival, robust data specific to chondrosarcoma (CS) remain limited. This study evaluates the prognostic relevance of pathological fractures (PF) in CS patients.</div></div><div><h3>Methods</h3><div>A systematic review and <em>meta</em>-analysis were conducted according to PRISMA guidelines. Eligible studies included patients with CS of the bone, with comparative groups based on fracture status and oncological outcomes. Study design, quality, and endpoints were assessed, and pooled <em>meta</em>-analysis was conducted. Additionally, clinical data from an institutional cohort was analyzed retrospectively.</div></div><div><h3>Results</h3><div>Nine studies, with a total of 1,185 patients and 245 PF cases, met the inclusion criteria. Meta-analysis revealed that PF status was significantly associated with inferior survival at 1–5 years (pooled OR 0.40; 95 % CI 0.26–0.62; p < 0.0001). The increased risk of death was particularly evident in dedifferentiated CS (pooled HR 1.96; 95 % CI 1.46–2.63; p < 0.00001). Institutional data supported these findings, that PF was associated with worse overall survival (HR 3.90; 95 % CI 0.69–21.98; p = 0.12) and progression-free survival (HR 3.17; 95 % CI 0.58–17.36; p = 0.18), although significance was limited by sample size.</div></div><div><h3>Conclusions</h3><div>Pathological fractures entail a significantly adverse prognosis in chondrosarcoma, particularly in high-grade and dedifferentiated subtypes and within the first 5 years of follow-up. Our institutional data corroborates <em>meta</em>-analysis findings. These results underscore the importance of personalized surgical management and intensive outcome monitoring for CS patients presenting with PF.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"56 ","pages":"Article 100735"},"PeriodicalIF":3.5,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145698199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Giant cell tumor of bone (GCTB) is a rare, locally aggressive, intermediate-grade neoplasm. While typically benign, GCTB can exhibit atypical behavior, including indolent pulmonary metastases and malignant transformation. This study characterizes malignant and metastatic GCTB, distinguishing primary malignant GCTB (PM-GCTB), secondary malignant GCTB (SM-GCTB), and secondary osteosarcoma, and evaluates their outcomes.
Methods
A retrospectively review of 520 patients with suspected GCTB treated between 1985–2021 was performed, with malignant cases followed through 2025. Diagnosis was confirmed histologically and, where available, by H3F3A/H3F3B mutation testing. PM-GCTB was defined as a de novo high-grade sarcoma. SM-GCTB and secondary osteosarcoma were defined as malignant transformations of previously benign, histologically proven GCTB. Benign pulmonary metastases were analyzed separately. Outcomes were descriptively assessed.
Results
Twelve patients (2.4 %) had malignant GCTB: five PM-GCTB (1.0 %), five SM-GCTB (1.0 %), and two secondary osteosarcoma (0.4 %). Three patients (0.6 %) developed histologically benign pulmonary metastases with indolent behavior. Three SM-GCTB patients transformed within one year despite benign baseline pathology, indicating true rapid malignant progression rather than diagnostic error. Median latency to malignant transformation was 7.5 years for SM-GCTB and up to 35 years for secondary osteosarcoma. SM-GCTB showed the highest disease-specific mortality (80 %), compared to PM-GCTB (20 %) and secondary osteosarcoma (0 %). None malignant transformations occurred following denosumab or radiotherapy.
Conclusion
Three aggressive GCTB variants were identified: benign pulmonary metastatic GCTB, PM-GCTB, and secondary malignant transformation. SM-GCTB and osteosarcoma arise from benign GCTB but differ in morphology and prognosis. Because malignant transformation is exceptionally rare and symptomatic, a patient-centered, symptom-driven follow-up strategy is preferred over routine lifelong radiologic surveillance.
{"title":"Malignant and metastatic giant cell tumors of bone; clinical course of primary or secondary malignant and pulmonary metastatic variants","authors":"Floortje G.M. Verspoor , Gitte G.J. Krebbekx , Mylene J.C. Duivenvoorden , Vaiyapuri Sumathi , Scott Evans","doi":"10.1016/j.jbo.2025.100728","DOIUrl":"10.1016/j.jbo.2025.100728","url":null,"abstract":"<div><h3>Aims</h3><div>Giant cell tumor of bone (GCTB) is a rare, locally aggressive, intermediate-grade neoplasm. While typically benign, GCTB can exhibit atypical behavior, including indolent pulmonary metastases and malignant transformation. This study characterizes malignant and metastatic GCTB, distinguishing primary malignant GCTB (PM-GCTB), secondary malignant GCTB (SM-GCTB), and secondary osteosarcoma, and evaluates their outcomes.</div></div><div><h3>Methods</h3><div>A retrospectively review of 520 patients with suspected GCTB treated between 1985–2021 was performed, with malignant cases followed through 2025. Diagnosis was confirmed histologically and, where available, by H3F3A/H3F3B mutation testing. PM-GCTB was defined as a de novo high-grade sarcoma. SM-GCTB and secondary osteosarcoma were defined as malignant transformations of previously benign, histologically proven GCTB. Benign pulmonary metastases were analyzed separately. Outcomes were descriptively assessed.</div></div><div><h3>Results</h3><div>Twelve patients (2.4 %) had malignant GCTB: five PM-GCTB (1.0 %), five SM-GCTB (1.0 %), and two secondary osteosarcoma (0.4 %). Three patients (0.6 %) developed histologically benign pulmonary metastases with indolent behavior. Three SM-GCTB patients transformed within one year despite benign baseline pathology, indicating true rapid malignant progression rather than diagnostic error. Median latency to malignant transformation was 7.5 years for SM-GCTB and up to 35 years for secondary osteosarcoma. SM-GCTB showed the highest disease-specific mortality (80 %), compared to PM-GCTB (20 %) and secondary osteosarcoma (0 %). None malignant transformations occurred following denosumab or radiotherapy.</div></div><div><h3>Conclusion</h3><div>Three aggressive GCTB variants were identified: benign pulmonary metastatic GCTB, PM-GCTB, and secondary malignant transformation. SM-GCTB and osteosarcoma arise from benign GCTB but differ in morphology and prognosis. Because malignant transformation is exceptionally rare and symptomatic, a patient-centered, symptom-driven follow-up strategy is preferred over routine lifelong radiologic surveillance.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"55 ","pages":"Article 100728"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145614365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.jbo.2025.100731
C.H.J. Scholte , K. van Langevelde , D.M.J. Dorleijn , M. Fiocco , D. Broekhuis , P.D.S. Dijkstra , M.A.J. van de Sande , R.J.P. van der Wal
Purpose
Atypical cartilaginous tumors (ACT) are locally aggressive, cartilage-producing neoplasms, traditionally classified as chondrosarcoma grade 1. They exist within the spectrum of cartilaginous tumors, between enchondroma and high-grade chondrosarcoma. The diagnosis of ACT remains challenging, with limited consensus on optimal treatment. Despite ongoing debate, intralesional curettage is commonly performed, though the risk of pathological fractures post-treatment remains a significant complication. This study aims to investigate the impact of cortical window design on fracture risk following curettage for ACT in the distal femur.
Methods
We compared two types of cortical windows: smooth oval (low stress riser) and windows with sharp or predrilled rounded corners (high stress riser). A retrospective cohort of 153 patients treated between 2000 and 2020 was included. Fracture occurrence was recorded, and logistic regression models were used to assess the relationship between surgical technique and fracture risk. We corrected for void filling and tumour size.
Results
Our findings revealed no significant difference in fracture risk between the two types of cortical windows (OR = 1.62, 95 % CI:0.66–3.96). However, the use of cement as a void filler significantly increased fracture risk, with odds ratio (OR) approximately five times higher than those using bone chips (OR = 5.00, 95 % CI:1.81–13.88). Tumor size (cm) was also associated with fracture risk (OR 1.31, 95 % CI:1.04–1.63).
Conclusion
The study highlights the importance of choosing appropriate void filling material, with bone chips offering a lower fracture risk compared to cement. These results suggest that optimizing surgical techniques, particularly the choice of filling material, may reduce post-curettage fracture risk in ACT treatment.
{"title":"The risk of pathological fractures after intralesional curettage in Atypical Cartilaginous Tumours: A retrospective cohort study","authors":"C.H.J. Scholte , K. van Langevelde , D.M.J. Dorleijn , M. Fiocco , D. Broekhuis , P.D.S. Dijkstra , M.A.J. van de Sande , R.J.P. van der Wal","doi":"10.1016/j.jbo.2025.100731","DOIUrl":"10.1016/j.jbo.2025.100731","url":null,"abstract":"<div><h3>Purpose</h3><div>Atypical cartilaginous tumors (ACT) are locally aggressive, cartilage-producing neoplasms, traditionally classified as chondrosarcoma grade 1. They exist within the spectrum of cartilaginous tumors, between enchondroma and high-grade chondrosarcoma. The diagnosis of ACT remains challenging, with limited consensus on optimal treatment. Despite ongoing debate, intralesional curettage is commonly performed, though the risk of pathological fractures post-treatment remains a significant complication. This study aims to investigate the impact of cortical window design on fracture risk following curettage for ACT in the distal femur.</div></div><div><h3>Methods</h3><div>We compared two types of cortical windows: smooth oval (low stress riser) and windows with sharp or predrilled rounded corners (high stress riser). A retrospective cohort of 153 patients treated between 2000 and 2020 was included. Fracture occurrence was recorded, and logistic regression models were used to assess the relationship between surgical technique and fracture risk. We corrected for void filling and tumour size.</div></div><div><h3>Results</h3><div>Our findings revealed no significant difference in fracture risk between the two types of cortical windows (OR = 1.62, 95 % CI:0.66–3.96). However, the use of cement as a void filler significantly increased fracture risk, with odds ratio (OR) approximately five times higher than those using bone chips (OR = 5.00, 95 % CI:1.81–13.88). Tumor size (cm) was also associated with fracture risk (OR 1.31, 95 % CI:1.04–1.63).</div></div><div><h3>Conclusion</h3><div>The study highlights the importance of choosing appropriate void filling material, with bone chips offering a lower fracture risk compared to cement. These results suggest that optimizing surgical techniques, particularly the choice of filling material, may reduce post-curettage fracture risk in ACT treatment.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"55 ","pages":"Article 100731"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145614432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bone tumors, encompassing heterogeneous primary and metastatic lesions, are driven in their initiation, progression, and metastasis by dysregulation of the bone microenvironment (BME). Clinically manifested by localized pain, pathological fractures, and neurological deficits, these malignancies substantially threaten patient survival. Radiographic patterns (osteolytic, osteoblastic, mixed) directly reflect pathogenic BME-tumor interactions, particularly involving osteoblast-osteoclast imbalance. The BME—a specialized niche of bone-resident cells (osteocytes, osteoblasts, osteoclasts), immune cells, extracellular matrix, and bioactive factors (e.g., cytokines, growth factors)—orchestrates skeletal homeostasis physiologically, yet its dysregulation drives tumorigenesis and metastatic colonization via three interconnected axes: (1) Cellular dynamics (osteocyte senescence, immune evasion); (2) Matrix remodeling (imbalance between osteolytic and osteoblastic activity); (3) Signaling disruption (abnormal cytokine and growth factor signaling). While BME-directed therapies (e.g., receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitors, C-X-C chemokine receptor type 4(CXCR4) antagonists) show promise in disrupting tumor-supportive niches, their off-target effects on healthy bone (e.g., osteonecrosis, impaired fracture healing) pose significant clinical challenges. This review systematically synthesizes: BME composition and tumor-induced reprogramming, Mechanistic roles in metastasis and treatment resistance, Emerging targeted therapies and translational trade-offs. By positioning the BME as both a pathogenic driver and therapeutic vulnerability, we aim to inform future strategies for tissue-specific microenvironmental targeting in bone malignancies.
{"title":"The regulatory networks and mechanisms of bone microenvironment in tumorigenesis and metastasis","authors":"Guofang Huang , Tianhui Hou , Dianwen Song , Tong Meng","doi":"10.1016/j.jbo.2025.100729","DOIUrl":"10.1016/j.jbo.2025.100729","url":null,"abstract":"<div><div>Bone tumors, encompassing heterogeneous primary and metastatic lesions, are driven in their initiation, progression, and metastasis by dysregulation of the bone microenvironment (BME). Clinically manifested by localized pain, pathological fractures, and neurological deficits, these malignancies substantially threaten patient survival. Radiographic patterns (osteolytic, osteoblastic, mixed) directly reflect pathogenic BME-tumor interactions, particularly involving osteoblast-osteoclast imbalance. The BME—a specialized niche of bone-resident cells (osteocytes, osteoblasts, osteoclasts), immune cells, extracellular matrix, and bioactive factors (e.g., cytokines, growth factors)—orchestrates skeletal homeostasis physiologically, yet its dysregulation drives tumorigenesis and metastatic colonization via three interconnected axes: (1)<!--> <!-->Cellular dynamics<!--> <!-->(osteocyte senescence, immune evasion); (2)<!--> <!-->Matrix remodeling<!--> <!-->(imbalance between osteolytic and osteoblastic activity); (3)<!--> <!-->Signaling disruption<!--> <!-->(abnormal cytokine and growth factor signaling). While BME-directed therapies (e.g., receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitors, C-X-C chemokine receptor type 4(CXCR4) antagonists) show promise in disrupting tumor-supportive niches, their off-target effects on healthy bone (e.g., osteonecrosis, impaired fracture healing) pose significant clinical challenges. This review systematically synthesizes: BME composition and tumor-induced reprogramming, Mechanistic roles in metastasis and treatment resistance, Emerging targeted therapies and translational trade-offs. By positioning the BME as both a pathogenic driver and therapeutic vulnerability, we aim to inform future strategies for tissue-specific microenvironmental targeting in bone malignancies.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"55 ","pages":"Article 100729"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145614364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rotationplasty is a surgical technique primarily used in pediatric patients with malignant bone tumors around the knee. Its application in adults is rare, and outcomes are poorly defined. This study aimed to compare long-term QoL, function, and gait between patients treated with rotationplasty in childhood versus adulthood.
Methods
This cross-sectional post-hoc predefined secondary analysis included 33 patients treated between 1980–2002 (9 adults, 24 minors). Assessments included the mental and physical component score of the Short Form-36 (SF-36, MCS/ PCS), overall satisfaction, radiographs (Kellgren-Lawrence) of the pseudo-knee, contralateral ankle, and hips, Toronto Extremity Salvage Score (TESS), Musculoskeletal Tumor Society Score (MSTS), energy cost of comfortable walking during a 6-minute walk test, and 3-Dimenional gait analysis. Group comparisons were performed across all outcomes. Additionally, a systematic literature search identified published adult cases.
Results
People who underwent surgery during adulthood reported significantly higher physical QoL compared to those operated in childhood (MD 6.1, 95 % CI 0.0–12.3; p = 0.05). No significant differences were observed for the SF-36 MCS, TESS, MSTS, energy cost, sagittal-plane biomechanics, and radiographic OA prevalence. Adults exhibited a significantly shorter stride length (p < 0.01) and a longer double support phase (p = 0.01) compared to those treated in childhood. The literature review (22 studies, 51 patients) demonstrated overall favorable outcomes, though no objective gait data were reported.
Conclusion
Adults who undergo rotationplasty can achieve long-term quality of life, functional, and gait outcomes at least comparable to those operated on in childhood. These findings suggest that rotationplasty may be a viable reconstructive option in adults.
{"title":"Rotationplasty performed in adults versus minors: a comparative study of long-term quality of life, functional and biomechanical outcomes","authors":"Gitte G.J. Krebbekx , N.F.J. Waterval , M.A. Brehm , M.J.C. Duivenvoorden , I.N. Sierevelt , J.A.M. Bramer , G.M.M.J. Kerkhoffs , F.G.M. Verspoor","doi":"10.1016/j.jbo.2025.100732","DOIUrl":"10.1016/j.jbo.2025.100732","url":null,"abstract":"<div><h3>Background</h3><div>Rotationplasty is a surgical technique primarily used in pediatric patients with malignant bone tumors around the knee. Its application in adults is rare, and outcomes are poorly defined. This study aimed to compare long-term QoL, function, and gait between patients treated with rotationplasty in childhood versus adulthood.</div></div><div><h3>Methods</h3><div>This cross-sectional post-hoc predefined secondary analysis included 33 patients treated between 1980–2002 (9 adults, 24 minors). Assessments included the mental and physical component score of the Short Form-36 (SF-36, MCS/ PCS), overall satisfaction, radiographs (Kellgren-Lawrence) of the pseudo-knee, contralateral ankle, and hips, Toronto Extremity Salvage Score (TESS), Musculoskeletal Tumor Society Score (MSTS), energy cost of comfortable walking during a 6-minute walk test, and 3-Dimenional gait analysis. Group comparisons were performed across all outcomes. Additionally, a systematic literature search identified published adult cases.</div></div><div><h3>Results</h3><div>People who underwent surgery during adulthood reported significantly higher physical QoL compared to those operated in childhood (MD 6.1, 95 % CI 0.0–12.3; <em>p</em> = 0.05). No significant differences were observed for the SF-36 MCS, TESS, MSTS, energy cost, sagittal-plane biomechanics, and radiographic OA prevalence. Adults exhibited a significantly shorter stride length (p < 0.01) and a longer double support phase (p = 0.01) compared to those treated in childhood. The literature review (22 studies, 51 patients) demonstrated overall favorable outcomes, though no objective gait data were reported.</div></div><div><h3>Conclusion</h3><div>Adults who undergo rotationplasty can achieve long-term quality of life, functional, and gait outcomes at least comparable to those operated on in childhood. These findings suggest that rotationplasty may be a viable reconstructive option in adults.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"55 ","pages":"Article 100732"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145684794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：