Pub Date : 2025-10-04DOI: 10.1016/j.jbo.2025.100716
Jiabin Fang , Xiaojie Yang , Lingfeng Chen , Liuying Hong , Yingqiu He , Ji Huang , Jie Lin , Nengluan Xu , Hongru Li
Background
Bone is a common site of metastasis in non-small cell lung cancer (NSCLC), yet no validated prognostic model is currently available for patients presenting with bone metastases at diagnosis.
Methods
We retrospectively reviewed 1,299 NSCLC patients who underwent high-throughput sequencing between 2016 and 2023. Of these, 195 were diagnosed with bone metastases at presentation. Three machine learning algorithms were applied to identify prognostic variables. A nomogram constructed with Cox regression was used to predict overall survival (OS) and was internally validated with 1,000 bootstrap resamples.
Results
Four independent prognostic factors were identified, including age, serum calcium, monocyte-to-albumin ratio, and prognostic nutritional index. The nomogram demonstrated strong predictive performance, with areas under the curve (AUCs) of 86.53%, 78.32%, and 77.85% for 6-month, 1-year, and 2-year OS, respectively. Calibration plots showed excellent agreement between predicted and observed survival outcomes.
Conclusion
This validated nomogram provides a practical and individualized tool for predicting survival in NSCLC patients with bone metastases at diagnosis, supporting risk stratification and clinical practice.
{"title":"Development and validation of prognostic models for bone metastasis in Non-Small cell lung cancer based on Machine learning algorithms","authors":"Jiabin Fang , Xiaojie Yang , Lingfeng Chen , Liuying Hong , Yingqiu He , Ji Huang , Jie Lin , Nengluan Xu , Hongru Li","doi":"10.1016/j.jbo.2025.100716","DOIUrl":"10.1016/j.jbo.2025.100716","url":null,"abstract":"<div><h3>Background</h3><div>Bone is a common site of metastasis in non-small cell lung cancer (NSCLC), yet no validated prognostic model is currently available for patients presenting with bone metastases at diagnosis.</div></div><div><h3>Methods</h3><div>We retrospectively reviewed 1,299 NSCLC patients who underwent high-throughput sequencing between 2016 and 2023. Of these, 195 were diagnosed with bone metastases at presentation. Three machine learning algorithms were applied to identify prognostic variables. A nomogram constructed with Cox regression was used to predict overall survival (OS) and was internally validated with 1,000 bootstrap resamples.</div></div><div><h3>Results</h3><div>Four independent prognostic factors were identified, including age, serum calcium, monocyte-to-albumin ratio, and prognostic nutritional index. The nomogram demonstrated strong predictive performance, with areas under the curve (AUCs) of 86.53%, 78.32%, and 77.85% for 6-month, 1-year, and 2-year OS, respectively. Calibration plots showed excellent agreement between predicted and observed survival outcomes.</div></div><div><h3>Conclusion</h3><div>This validated nomogram provides a practical and individualized tool for predicting survival in NSCLC patients with bone metastases at diagnosis, supporting risk stratification and clinical practice.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"55 ","pages":"Article 100716"},"PeriodicalIF":3.5,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145269707","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 : 2025-09-22DOI: 10.1016/j.jbo.2025.100714
Yu Qiao , Fahu Yuan , Anna Curto-Vilalta , Rüdiger von Eisenhart-Rothe , Florian Hinterwimmer
Objective
Polyethylene terephthalate (PET) has emerged as a focal point in addressing global pollution and a critical environmental issue due to its potential health hazards. However, its role in the pathogenesis of osteosarcoma (OS) and the underlying molecular mechanisms remain largely unexplored, further highlighting the necessity of assessing its molecular toxicity.
Methods
This study integrated network toxicology, machine learning, molecular docking, and CIBERSORT-based immune infiltration analysis to systematically investigate the potential impact of PET exposure on contracting OS, elucidating its biological functions, signaling mechanisms, and immune microenvironment. Molecular docking was further applied to characterize the binding properties of PET with hub proteins, and potential therapeutic agents for OS were predicted.
Results
We identified 12 potential key targets of OS associated with PET exposure and, through machine learning models, selected six hub genes (i.e., BCAT1, CDK4, CSF1R, CXCR4, MYB, and PRTN3). Gene Ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analyses were conducted to elucidate the roles of these genes in biological processes, cellular components, molecular functions, and signaling pathways. Molecular docking results revealed that PET exhibits high specificity in binding to these hub genes, particularly by interacting with CSF1R (−8.312 kcal/mol), potentially activating the PI3K-Akt signaling pathway and modulating the OS immune microenvironment to promote tumor progression through multiple mechanisms. Furthermore, drug prediction analysis identified p-Benzoquinone and JNK-9L as potential therapeutic candidates for OS.
Conclusion
This study reveals that PET may play a critical role in OS development by regulating hub genes and signaling pathways. Molecular docking analysis demonstrates that PET can tightly bind to specific target proteins, suggesting a potential molecular mechanism underlying OS progression. These findings provide a scientific basis for further evaluating PET-related health risks and offer theoretical support for the development of future prevention and treatment strategies.
{"title":"Assessing the mechanism of osteosarcoma induced by long-term PET exposure: prediction from combined network toxicology, machine learning and molecular docking","authors":"Yu Qiao , Fahu Yuan , Anna Curto-Vilalta , Rüdiger von Eisenhart-Rothe , Florian Hinterwimmer","doi":"10.1016/j.jbo.2025.100714","DOIUrl":"10.1016/j.jbo.2025.100714","url":null,"abstract":"<div><h3>Objective</h3><div>Polyethylene terephthalate (PET) has emerged as a focal point in addressing global pollution and a critical environmental issue due to its potential health hazards. However, its role in the pathogenesis of osteosarcoma (OS) and the underlying molecular mechanisms remain largely unexplored, further highlighting the necessity of assessing its molecular toxicity.</div></div><div><h3>Methods</h3><div>This study integrated network toxicology, machine learning, molecular docking, and CIBERSORT-based immune infiltration analysis to systematically investigate the potential impact of PET exposure on contracting OS, elucidating its biological functions, signaling mechanisms, and immune microenvironment. Molecular docking was further applied to characterize the binding properties of PET with hub proteins, and potential therapeutic agents for OS were predicted.</div></div><div><h3>Results</h3><div>We identified 12 potential key targets of OS associated with PET exposure and, through machine learning models, selected six hub genes (i.e., BCAT1, CDK4, CSF1R, CXCR4, MYB, and PRTN3). Gene Ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analyses were conducted to elucidate the roles of these genes in biological processes, cellular components, molecular functions, and signaling pathways. Molecular docking results revealed that PET exhibits high specificity in binding to these hub genes, particularly by interacting with CSF1R (−8.312 kcal/mol), potentially activating the PI3K-Akt signaling pathway and modulating the OS immune microenvironment to promote tumor progression through multiple mechanisms. Furthermore, drug prediction analysis identified <em>p</em>-Benzoquinone and JNK-9L as potential therapeutic candidates for OS.</div></div><div><h3>Conclusion</h3><div>This study reveals that PET may play a critical role in OS development by regulating hub genes and signaling pathways. Molecular docking analysis demonstrates that PET can tightly bind to specific target proteins, suggesting a potential molecular mechanism underlying OS progression. These findings provide a scientific basis for further evaluating PET-related health risks and offer theoretical support for the development of future prevention and treatment strategies.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"55 ","pages":"Article 100714"},"PeriodicalIF":3.5,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145160089","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 : 2025-09-21DOI: 10.1016/j.jbo.2025.100713
Ji Yong Park , A Ram Hong , Jee Hee Yoon , Hee Kyung Kim , Ho-Cheol Kang , Seung Il Jung , Dongdeuk Kwon , Eu Chang Hwang
Introduction
Androgen deprivation therapy (ADT) for prostate cancer negatively affect areal bone mineral density (aBMD); however, its impact on volumetric BMD (vBMD) and bone geometry remains underexplored. This study aimed to evaluate changes in aBMD, vBMD, and hip structural analysis (HSA) following one year of ADT.
Materials and methods
This retrospective observational study included 41 patients with prostate cancer without bone metastasis who received ADT for one year and underwent dual-energy X-ray absorptiometry (DXA) both before and after treatment. In addition to aBMD, trabecular and cortical vBMD, integral vBMD (trabecular + cortical), cortical surface BMD (sBMD), cortical thickness, and hip structural parameters were assessed at the hip using 3D-Shaper software.
Results
The mean age and body mass index of the patients were 75.5 ± 6.8 years and 24.0 ± 3.0 kg/m2, respectively. More than half had a Gleason score of 4 or 5, and the majority had T3 disease. After one year of ADT, significant reductions in aBMD were observed at the lumbar spine (–4.5 ± 4.0 %, P < 0.001) and total hip (–3.7 ± 5.1 %, P < 0.001). 3D-DXA analysis revealed significant declines in integral vBMD (–3.8 ± 3.9 %) and trabecular vBMD (–4.9 ± 7.4 %) (both P < 0.001), while cortical vBMD showed no significant change (–1.6 ± 6.0 %, P = 0.062) at the total hip. Cortical sBMD decreased significantly by –2.7 ± 5.2 % (P < 0.001). Cortical thickness also significantly decreased at the total hip (–1.2 ± 3.2 %, P = 0.011). With respect to hip structural parameters, cross-sectional area consistently decreased, and buckling ratio increased across the femoral neck, trochanteric, and shaft regions (all P < 0.05), indicating increased femoral fragility and reduced resistance to axial and compressive forces.
Conclusions
ADT exerts a substantial detrimental effect on bone strength, resulting in reductions in aBMD, vBMD, and alteration of HSA. 3D-DXA may serve as a valuable and accessible tool for detecting structural bone changes in prostate cancer patients undergoing ADT.
{"title":"Alteration of bone architecture following androgen deprivation therapy in patients with prostate cancer using 3D-modeling from hip DXA","authors":"Ji Yong Park , A Ram Hong , Jee Hee Yoon , Hee Kyung Kim , Ho-Cheol Kang , Seung Il Jung , Dongdeuk Kwon , Eu Chang Hwang","doi":"10.1016/j.jbo.2025.100713","DOIUrl":"10.1016/j.jbo.2025.100713","url":null,"abstract":"<div><h3>Introduction</h3><div>Androgen deprivation therapy (ADT) for prostate cancer negatively affect areal bone mineral density (aBMD); however, its impact on volumetric BMD (vBMD) and bone geometry remains underexplored. This study aimed to evaluate changes in aBMD, vBMD, and hip structural analysis (HSA) following one year of ADT.</div></div><div><h3>Materials and methods</h3><div>This retrospective observational study included 41 patients with prostate cancer without bone metastasis who received ADT for one year and underwent dual-energy X-ray absorptiometry (DXA) both before and after treatment. In addition to aBMD, trabecular and cortical vBMD, integral vBMD (trabecular + cortical), cortical surface BMD (sBMD), cortical thickness, and hip structural parameters were assessed at the hip using 3D-Shaper software.</div></div><div><h3>Results</h3><div>The mean age and body mass index of the patients were 75.5 ± 6.8 years and 24.0 ± 3.0 kg/m<sup>2</sup>, respectively. More than half had a Gleason score of 4 or 5, and the majority had T3 disease. After one year of ADT, significant reductions in aBMD were observed at the lumbar spine (–4.5 ± 4.0 %, <em>P</em> < 0.001) and total hip (–3.7 ± 5.1 %, <em>P</em> < 0.001). 3D-DXA analysis revealed significant declines in integral vBMD (–3.8 ± 3.9 %) and trabecular vBMD (–4.9 ± 7.4 %) (both <em>P</em> < 0.001), while cortical vBMD showed no significant change (–1.6 ± 6.0 %, <em>P</em> = 0.062) at the total hip. Cortical sBMD decreased significantly by –2.7 ± 5.2 % (<em>P</em> < 0.001). Cortical thickness also significantly decreased at the total hip (–1.2 ± 3.2 %, <em>P</em> = 0.011). With respect to hip structural parameters, cross-sectional area consistently decreased, and buckling ratio increased across the femoral neck, trochanteric, and shaft regions (all <em>P</em> < 0.05), indicating increased femoral fragility and reduced resistance to axial and compressive forces.</div></div><div><h3>Conclusions</h3><div>ADT exerts a substantial detrimental effect on bone strength, resulting in reductions in aBMD, vBMD, and alteration of HSA. 3D-DXA may serve as a valuable and accessible tool for detecting structural bone changes in prostate cancer patients undergoing ADT.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"55 ","pages":"Article 100713"},"PeriodicalIF":3.5,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145120407","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}
Osseous invasion in extremity soft-tissue sarcomas (STS) occurs in approximately 5–11% of cases and is associated with larger tumor size, higher histologic grade, deeper location, and increased risk of metastasis. Despite its relative rarity, bone invasion is a critical prognostic factor, presenting unique diagnostic and surgical challenges.
Purpose
This review aimed to synthesize current evidence on the prevalence, diagnostic imaging, surgical management, and prognostic impact of osseous invasion in extremity STS and to offer evidence-based recommendations for clinical practice.
Methods
A comprehensive narrative review was conducted using structured searches of PubMed, Embase, and Cochrane Library, focusing on studies reporting original data on extremity STS with bone involvement. The key outcomes included diagnostic accuracy, surgical margins, functional recovery, and survival rates.
Results
Bone invasion significantly predicted poorer overall and disease-free survival, with 5-year survival rates of 27–40% compared to 60–70% in non-invasive cases. MRI remains the imaging modality of choice, although standardized radiological criteria for bone invasion are lacking. En-bloc resection provides reliable local control but carries substantial morbidity. Emerging bone-sparing techniques, such as subperiosteal and hemicortical resections, have demonstrated comparable oncologic outcomes with superior functional results in selected patients.
Conclusions
Bone invasion in extremity STS represents a high-risk tumor subset that warrants individualized multidisciplinary management. While wide resection remains the standard treatment in cases with medullary involvement, selected patients may benefit from function-preserving approaches without compromising oncologic safety. Future research should focus on standardizing the diagnostic criteria, validating conservative surgical strategies, and refining multimodal treatment protocols to optimize outcomes.
{"title":"Osseous invasion in extremity soft-tissue sarcomas: prevalence, diagnosis, and surgical management- A narrative review","authors":"Seyyed Saeed Khabiri , Khalil Kargar Shooroki , Sadegh Saberi , Hamed Naghizadeh","doi":"10.1016/j.jbo.2025.100712","DOIUrl":"10.1016/j.jbo.2025.100712","url":null,"abstract":"<div><h3>Background</h3><div>Osseous invasion in extremity soft-tissue sarcomas (STS) occurs in approximately 5–11% of cases and is associated with larger tumor size, higher histologic grade, deeper location, and increased risk of metastasis. Despite its relative rarity, bone invasion is a critical prognostic factor, presenting unique diagnostic and surgical challenges.</div></div><div><h3>Purpose</h3><div>This review aimed to synthesize current evidence on the prevalence, diagnostic imaging, surgical management, and prognostic impact of osseous invasion in extremity STS and to offer evidence-based recommendations for clinical practice.</div></div><div><h3>Methods</h3><div>A comprehensive narrative review was conducted using structured searches of PubMed, Embase, and Cochrane Library, focusing on studies reporting original data on extremity STS with bone involvement. The key outcomes included diagnostic accuracy, surgical margins, functional recovery, and survival rates.</div></div><div><h3>Results</h3><div>Bone invasion significantly predicted poorer overall and disease-free survival, with 5-year survival rates of 27–40% compared to 60–70% in non-invasive cases. MRI remains the imaging modality of choice, although standardized radiological criteria for bone invasion are lacking. En-bloc resection provides reliable local control but carries substantial morbidity. Emerging bone-sparing techniques, such as subperiosteal and hemicortical resections, have demonstrated comparable oncologic outcomes with superior functional results in selected patients.</div></div><div><h3>Conclusions</h3><div>Bone invasion in extremity STS represents a high-risk tumor subset that warrants individualized multidisciplinary management. While wide resection remains the standard treatment in cases with medullary involvement, selected patients may benefit from function-preserving approaches without compromising oncologic safety. Future research should focus on standardizing the diagnostic criteria, validating conservative surgical strategies, and refining multimodal treatment protocols to optimize outcomes.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"54 ","pages":"Article 100712"},"PeriodicalIF":3.5,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145094887","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 : 2025-09-11DOI: 10.1016/j.jbo.2025.100710
Franziska Nägler , Isabell Seiler , Sebastian Schäfer , Johannes Meents , Fabian Lohaus , Arne Grün , Olaf Wittenstein , Kenneth Klischies , Julia Remmele , Alexander Rühle , Miriam Eckl , Oliver Blanck , Judit Boda-Heggemann , Frank A. Giordano , Christos Moustakis , Nils H. Nicolay , Lena Kästner
Background and purpose
Metastases-directed radiotherapy plays an increasing role in oligometastatic prostate cancers (OMPC). Here, we investigated the role of stereotactic body radiotherapy (SBRT) for spine and non-spine bone metastases (BoM) from prostate cancer in a large real-world multicenter cohort.
Material and methods
This multicenter cohort analysis from five tertiary cancer centers included patient data of spine and non-spine BoM irradiated between 2010 and 2024. Overall survival (OS), progression-free survival (PFS), local recurrence-free survival (LRFS), SBRT target volumes and doses, toxicity, and the role of additional systemic therapies were evaluated retrospectively.
Results
231 patients (341 BoM) with median follow-up time of 28.3 months were included. Most common localization were spine (39.3 %), pelvic bone (31.7 %), and ribs (17.9 %). 1- and 5-year PFS for spine BoM were 93.8 % (95 %CI:84.2–97.6 %) and 32.1 % (95 %CI:16.8–44.4 %) and for non-spine BoM 91.7 % (95 %CI:85.1–95.5 %) and 36.6 % (95 %CI:25.8–47.5 %), respectively. 1- and 5-year OS for spine BoM amounted to 94.2 % (95 %CI:85.3–97.8 %) and 69.2 % (95 %CI:50.2–82.2 %) and for non-spine 100 % and 73.3 % (95 %CI:59.1–83.3 %). Older age (p < 0.005) and additional systemic therapies (p = 0.05) were associated with worse OS, older age and larger treatment volumes with worse PFS (p = 0.04). Toxicities were low, with fracture rates of 0.3 % (acute) and 1.2 % (late).
Conclusion
Bone SBRT for OMPC is an effective treatment with low toxicity and particularly low fracture rates for both spine and non-spine BoM with no difference in outcome based on the localization. Prospective trials will help to identify the patients benefitting most from this approach and to establish standardized SBRT concepts incorporating systemic treatments.
{"title":"Stereotactic body radiotherapy for spine and non-spine bone metastases in prostate carcinoma – a multicenter cohort analysis","authors":"Franziska Nägler , Isabell Seiler , Sebastian Schäfer , Johannes Meents , Fabian Lohaus , Arne Grün , Olaf Wittenstein , Kenneth Klischies , Julia Remmele , Alexander Rühle , Miriam Eckl , Oliver Blanck , Judit Boda-Heggemann , Frank A. Giordano , Christos Moustakis , Nils H. Nicolay , Lena Kästner","doi":"10.1016/j.jbo.2025.100710","DOIUrl":"10.1016/j.jbo.2025.100710","url":null,"abstract":"<div><h3>Background and purpose</h3><div>Metastases-directed radiotherapy plays an increasing role in oligometastatic prostate cancers (OMPC). Here, we investigated the role of stereotactic body radiotherapy (SBRT) for spine and non-spine bone metastases (BoM) from prostate cancer in a large real-world multicenter cohort.</div></div><div><h3>Material and methods</h3><div>This multicenter cohort analysis from five tertiary cancer centers included patient data of spine and non-spine BoM irradiated between 2010 and 2024. Overall survival (OS), progression-free survival (PFS), local recurrence-free survival (LRFS), SBRT target volumes and doses, toxicity, and the role of additional systemic therapies were evaluated retrospectively.</div></div><div><h3>Results</h3><div>231 patients (341 BoM) with median follow-up time of 28.3 months were included. Most common localization were spine (39.3 %), pelvic bone (31.7 %), and ribs (17.9 %). 1- and 5-year PFS for spine BoM were 93.8 % (95 %CI:84.2–97.6 %) and 32.1 % (95 %CI:16.8–44.4 %) and for non-spine BoM 91.7 % (95 %CI:85.1–95.5 %) and 36.6 % (95 %CI:25.8–47.5 %), respectively. 1- and 5-year OS for spine BoM amounted to 94.2 % (95 %CI:85.3–97.8 %) and 69.2 % (95 %CI:50.2–82.2 %) and for non-spine 100 % and 73.3 % (95 %CI:59.1–83.3 %). Older age (p < 0.005) and additional systemic therapies (p = 0.05) were associated with worse OS, older age and larger treatment volumes with worse PFS (p = 0.04). Toxicities were low, with fracture rates of 0.3 % (acute) and 1.2 % (late).</div></div><div><h3>Conclusion</h3><div>Bone SBRT for OMPC is an effective treatment with low toxicity and particularly low fracture rates for both spine and non-spine BoM with no difference in outcome based on the localization. Prospective trials will help to identify the patients benefitting most from this approach and to establish standardized SBRT concepts incorporating systemic treatments.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"54 ","pages":"Article 100710"},"PeriodicalIF":3.5,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145094886","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 : 2025-09-06DOI: 10.1016/j.jbo.2025.100711
K. Kilk , G. Kask , J. Nieminen , M.K. Laitinen
Background
Skeletal metastases related pathological fracture reconstruction methods in proximal femur range from osteosynthesis to tumor prostheses with acetabular reconstruction, depending on lesion size and location. This retrospective study, of 299 patients surgically treated for proximal femur metastases, investigates implant survival, complications, and functional outcomes of various surgical strategies for treating pathological fractures of the proximal femur.
Patients and methods
This retrospective study of 299 patients surgically treated for proximal femur metastases, investigates implant survival (Kaplan–Meier), complications, and functional outcomes of different surgical strategies. The chi-test and Mann-Witney U test were used for analysis between groups. The subdistribution Hazard Ratio (SHR) of the role of factors affecting implant survival was calculated using competing risk analysis.
Results
Reconstruction methods comprised osteosynthesis (n = 59), hemiarthroplasty (n = 72), total hip replacement (THA) (n = 43), and endoprosthetic replacement (EPR) either with or without acetabular component (n = 125). The precise location and size of the metastases was evaluated. The mean implant survival was 17 months (SD 21.2). Complications occurred in 33 patients, 20 required revision surgery. In prosthesis patients, infections and dislocations were the main complications, while mechanical failure predominated in the osteosynthesis group. Mean implant failure time was 11 months, shortest in THA and osteosynthesis. Functional outcomes in 38 patients showed a mean Oxford Hip Score (OHS) of 33, with no significant differences across methods.
Interpretation
Patient survival is a critical factor in selecting the appropriate reconstruction method for trochanteric metastatic lesions. Osteosynthesis is suitable for patients with a limited life expectancy. In cases of metastases involving the head-neck anatomical region, arthroplasty with acetabular reconstruction offers no advantage over hemiarthroplasty. With our data there was no statistical difference in functional outcome between different surgical methods.
{"title":"Metastatic bone disease in proximal femur. Outcome of surgical treatments. − Do we know what to do?","authors":"K. Kilk , G. Kask , J. Nieminen , M.K. Laitinen","doi":"10.1016/j.jbo.2025.100711","DOIUrl":"10.1016/j.jbo.2025.100711","url":null,"abstract":"<div><h3>Background</h3><div>Skeletal metastases related pathological fracture reconstruction methods in proximal femur range from osteosynthesis to tumor prostheses with acetabular reconstruction, depending on lesion size and location. This retrospective study, of 299 patients surgically treated for proximal femur metastases, investigates implant survival, complications, and functional outcomes of various surgical strategies for treating pathological fractures of the proximal femur.</div></div><div><h3>Patients and methods</h3><div>This retrospective study of 299 patients surgically treated for proximal femur metastases, investigates implant survival (Kaplan–Meier), complications, and functional outcomes of different surgical strategies. The chi-test and Mann-Witney <em>U</em> test were used for analysis between groups. The subdistribution Hazard Ratio (SHR) of the role of factors affecting implant survival was calculated using competing risk analysis.</div></div><div><h3>Results</h3><div>Reconstruction methods comprised osteosynthesis (n = 59), hemiarthroplasty (n = 72), total hip replacement (THA) (n = 43), and endoprosthetic replacement (EPR) either with or without acetabular component (n = 125). The precise location and size of the metastases was evaluated. The mean implant survival was 17 months (SD 21.2). Complications occurred in 33 patients, 20 required revision surgery. In prosthesis patients, infections and dislocations were the main complications, while mechanical failure predominated in the osteosynthesis group. Mean implant failure time was 11 months, shortest in THA and osteosynthesis. Functional outcomes in 38 patients showed a mean Oxford Hip Score (OHS) of 33, with no significant differences across methods.</div></div><div><h3>Interpretation</h3><div>Patient survival is a critical factor in selecting the appropriate reconstruction method for trochanteric metastatic lesions. Osteosynthesis is suitable for patients with a limited life expectancy. In cases of metastases involving the head-neck anatomical region, arthroplasty with acetabular reconstruction offers no advantage over hemiarthroplasty. With our data there was no statistical difference in functional outcome between different surgical methods.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"54 ","pages":"Article 100711"},"PeriodicalIF":3.5,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145026898","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 : 2025-09-02DOI: 10.1016/j.jbo.2025.100709
E.W. Dootjes , J.J. Willeumier , C.W.P.G. van der Wal , R.J.P. van der Wal , P. van der Zwaal , A. Leithner , A.A.M. van der Veldt , M. Fiocco , D.L.M. van Broekhoven , Y.M. van der Linden
Aims
For patients with long bone metastasis (LBM), we have previously developed OPTIModel. In this study, we investigated whether the OPTIModel could be improved for patients with metastatic renal cell cancer (mRCC) by including oligometastatic bone metastases (OBM) as a risk factor.
Methods
Patients with mRCC and symptomatic LBMs were included in a retrospective and prospective multicenter cohort. Bone metastases (BMs) were categorized as: solitary (SBM), limited BMs (2–4 BMs) or diffuse BMs (DBM; >4 BMs). OBM were defined as ≤ 4 BMs. Overall survival was estimated using Kaplan Meier method. Effect of risk factors on overall survival were assessed using multivariate Cox regression model. Based on these results, the OPTIModel was modified. To assess the discriminatory ability, Harrell’s C-statistic was used.
Results
178 patients were included. Overall, median overall survival was 12.1 months (95 % confidence interval (CI): 8.8–15.3). Median survival for SBM (n = 53, 29.8 %), limited BMs (n = 60, 33.7 %) and DBMs (n = 65, 36.5 %) was 19.6 months (95 %CI: 6.8–32.4), 14.8 months (95 %CI: 7.6–21.9) and 6.1 months (95 %CI: 2.7–9.5), respectively. Median survival was 16.3 months (95 %CI: 10.6–22.0) in patients with OBM (n = 113, 63.5 %), with a hazard ratio of 2.11 (95 %CI: 1.44–3.09) compared to patients with DBM. Including OBM in the OPTIModel for mRCC improved C-statistic from 0.585 (standard error (SE) = 0.027) to 0.618 (SE = 0.024).
Conclusion
Both SBM and limited BMs were associated with a longer overall survival in patients with mRCC and symptomatic LBMs. The modified OPTIModel for mRCC with inclusion of oligometastatic disease could guide decisions about local treatment of symptomatic LBMs.
{"title":"Modified OPTIModel with oligometastatic disease for the prediction of overall survival of patients with renal cell cancer and symptomatic long bone metastases","authors":"E.W. Dootjes , J.J. Willeumier , C.W.P.G. van der Wal , R.J.P. van der Wal , P. van der Zwaal , A. Leithner , A.A.M. van der Veldt , M. Fiocco , D.L.M. van Broekhoven , Y.M. van der Linden","doi":"10.1016/j.jbo.2025.100709","DOIUrl":"10.1016/j.jbo.2025.100709","url":null,"abstract":"<div><h3>Aims</h3><div>For patients with long bone metastasis (LBM), we have previously developed OPTIModel. In this study, we investigated whether the OPTIModel could be improved for patients with metastatic renal cell cancer (mRCC) by including oligometastatic bone metastases (OBM) as a risk factor.</div></div><div><h3>Methods</h3><div>Patients with mRCC and symptomatic LBMs were included in a retrospective and prospective multicenter cohort. Bone metastases (BMs) were categorized as: solitary (SBM), limited BMs (2–4 BMs) or diffuse BMs (DBM; >4 BMs). OBM were defined as ≤ 4 BMs. Overall survival was estimated using Kaplan Meier method. Effect of risk factors on overall survival were assessed using multivariate Cox regression model. Based on these results, the OPTIModel was modified. To assess the discriminatory ability, Harrell’s C-statistic was used.</div></div><div><h3>Results</h3><div>178 patients were included. Overall, median overall survival was 12.1 months (95 % confidence interval (CI): 8.8–15.3). Median survival for SBM (n = 53, 29.8 %), limited BMs (n = 60, 33.7 %) and DBMs (n = 65, 36.5 %) was 19.6 months (95 %CI: 6.8–32.4), 14.8 months (95 %CI: 7.6–21.9) and 6.1 months (95 %CI: 2.7–9.5), respectively. Median survival was 16.3 months (95 %CI: 10.6–22.0) in patients with OBM (n = 113, 63.5 %), with a hazard ratio of 2.11 (95 %CI: 1.44–3.09) compared to patients with DBM. Including OBM in the OPTIModel for mRCC improved C-statistic from 0.585 (standard error (SE) = 0.027) to 0.618 (SE = 0.024).</div></div><div><h3>Conclusion</h3><div>Both SBM and limited BMs were associated with a longer overall survival in patients with mRCC and symptomatic LBMs. The modified OPTIModel for mRCC with inclusion of oligometastatic disease could guide decisions about local treatment of symptomatic LBMs.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"55 ","pages":"Article 100709"},"PeriodicalIF":3.5,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145099382","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 : 2025-08-18DOI: 10.1016/j.jbo.2025.100708
Xia Yan , Hongyu Liu , Xueqi Bai , Jin Xu , Xiaojun Lou , Lai Wang
Purpose
To characterize causes of death in patients with bone metastases and to support data-driven approaches to survivorship planning and clinical decision-making in this population.
Methods
Using data from the SEER registry (2010–2021), we identified 186,404 patients with newly diagnosed bone metastases. Causes of death were classified as related to the cancer-specific, non-cancer, or subsequent cancer. Standardized mortality ratios (SMRs) were calculated to assess excess non-cancer mortality relative to the general population.
Results
During follow-up, 133,393 patients (71.5 %) died from the primary cancer, 11,062 (5.9 %) from non-cancer causes, and 929 (0.5 %) from other malignancies. Although cancer remained the predominant cause of death, non-cancer mortality increased over time (from 6.3 % in 2010 to 9.5 % in 2021). Cardiovascular disease, COPD, and cerebrovascular events were the most common non-cancer causes. The greatest excess mortality was observed for HIV-related infection conditions (SMR: 13.24), septicemia (10.60), suicide (6.68), and pneumonia/influenza (6.04).
Conclusion
Non-cancer mortality is an increasingly important contributor to death among patients with bone metastases, underscoring the need for targeted prevention strategies for infections, cardiovascular disease, and other avoidable causes in this vulnerable population.
{"title":"Comprehensive analysis of cancer and non-cancer mortality in patients with bone metastases: A population-based study","authors":"Xia Yan , Hongyu Liu , Xueqi Bai , Jin Xu , Xiaojun Lou , Lai Wang","doi":"10.1016/j.jbo.2025.100708","DOIUrl":"10.1016/j.jbo.2025.100708","url":null,"abstract":"<div><h3>Purpose</h3><div>To characterize causes of death in patients with bone metastases and to support data-driven approaches to survivorship planning and clinical decision-making in this population.</div></div><div><h3>Methods</h3><div>Using data from the SEER registry (2010–2021), we identified 186,404 patients with newly diagnosed bone metastases. Causes of death were classified as related to the cancer-specific, non-cancer, or subsequent cancer. Standardized mortality ratios (SMRs) were calculated to assess excess non-cancer mortality relative to the general population.</div></div><div><h3>Results</h3><div>During follow-up, 133,393 patients (71.5 %) died from the primary cancer, 11,062 (5.9 %) from non-cancer causes, and 929 (0.5 %) from other malignancies. Although cancer remained the predominant cause of death, non-cancer mortality increased over time (from 6.3 % in 2010 to 9.5 % in 2021). Cardiovascular disease, COPD, and cerebrovascular events were the most common non-cancer causes. The greatest excess mortality was observed for HIV-related infection conditions (SMR: 13.24), septicemia (10.60), suicide (6.68), and pneumonia/influenza (6.04).</div></div><div><h3>Conclusion</h3><div>Non-cancer mortality is an increasingly important contributor to death among patients with bone metastases, underscoring the need for targeted prevention strategies for infections, cardiovascular disease, and other avoidable causes in this vulnerable population.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"54 ","pages":"Article 100708"},"PeriodicalIF":3.5,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144886742","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 : 2025-08-05DOI: 10.1016/j.jbo.2025.100707
Tom M. de Groot , Lotte R. van der Linden , Angad D.S. Bedi , Andreea A. Lucaciu , Caleb C. Jang , Olivier Q. Groot , Job N. Doornberg , Paul C. Jutte , Santiago A. Lozano-Calderon , J.H. Schwab
Background
Social Determinants of Health (SDOH) are non-medical factors that influence health, which have gained recognition across medical disciplines. Their impact on survival and disease presentation of patients with metastatic bone disease (MBD) remains unexplored.
Methods
This retrospective observational study included 712 undergoing surgery for symptomatic long-bone metastases patients between 2013 and 2022. SDOH were evaluated using Cox Proportional hazards regression for post-operative survival. A multivariate logistic regression analysis was performed to identify associated factors for clinical presentation with a completed pathologic fracture.
Results
The median overall survival was 264 days (IQR 74–772). Clinical presentation with a pathologic fracture as the initial symptom of metastatic bone disease (MBD) was observed in 15 % of patients (106/712).
SDOH factors played a significant role in clinical presentation. Patients with secondary insurance coverage were substantially less likely to present with a pathologic fracture (OR 0.26, 95 % CI 0.14–0.49; p < 0.01). In a sub-analysis of the most common tumors (breast, renal, and lung cancer patients; n = 353), attending college was associated with a significantly lower likelihood of presenting with a pathologic fracture as the initial symptom of metastatic bone disease (OR 0.54, 95 % CI 0.30–0.95; p = 0.03)
Conclusion
This study suggests that unfavorable SDOH factors are associated with decreased post-operative survival and a higher likelihood of initial clinical presentation with a completed pathological fracture. Incorporating social determinants into comprehensive care strategies for individuals with MBD may guide targeted interventions and optimize patient management to improve outcomes.
健康的社会决定因素（SDOH）是影响健康的非医学因素，已获得医学学科的认可。它们对转移性骨病（MBD）患者的生存和疾病表现的影响尚不清楚。方法回顾性观察研究纳入2013年至2022年间712例接受手术治疗的有症状的长骨转移患者。采用Cox比例风险回归对SDOH进行术后生存评估。进行多因素logistic回归分析，以确定与完全病理性骨折的临床表现相关的因素。结果中位总生存期为264天（IQR 74-772）。15%的患者（106/712）以病理性骨折为转移性骨病（MBD）的初始症状。SDOH因素在临床表现中起重要作用。二级保险覆盖的患者出现病理性骨折的可能性大大降低(OR 0.26, 95% CI 0.14-0.49；p & lt;0.01)。在最常见肿瘤（乳腺癌、肾癌和肺癌患者）的亚分析中；n = 353)，上大学与以病理性骨折为转移性骨病初始症状的可能性显著降低相关(OR 0.54, 95% CI 0.30-0.95；p = 0.03)结论：SDOH不良因素与术后生存率降低有关，其首发临床表现为完全性病理性骨折的可能性较高。将社会决定因素纳入MBD患者的综合护理策略可以指导有针对性的干预措施并优化患者管理以改善结果。
{"title":"Social determinants are associated with clinical presentation of acute pathological fracture in metastatic long-bone disease","authors":"Tom M. de Groot , Lotte R. van der Linden , Angad D.S. Bedi , Andreea A. Lucaciu , Caleb C. Jang , Olivier Q. Groot , Job N. Doornberg , Paul C. Jutte , Santiago A. Lozano-Calderon , J.H. Schwab","doi":"10.1016/j.jbo.2025.100707","DOIUrl":"10.1016/j.jbo.2025.100707","url":null,"abstract":"<div><h3>Background</h3><div>Social Determinants of Health (SDOH) are non-medical factors that influence health, which have gained recognition across medical disciplines. Their impact on survival and disease presentation of patients with metastatic bone disease (MBD) remains unexplored.</div></div><div><h3>Methods</h3><div>This retrospective observational study included 712 undergoing surgery for symptomatic long-bone metastases patients between 2013 and 2022. SDOH were evaluated using Cox Proportional hazards regression for post-operative survival. A multivariate logistic regression analysis was performed to identify associated factors for clinical presentation with a completed pathologic fracture.</div></div><div><h3>Results</h3><div>The median overall survival was 264 days (IQR 74–772). Clinical presentation with a pathologic fracture as the initial symptom of metastatic bone disease (MBD) was observed in 15 % of patients (106/712).</div><div>SDOH factors played a significant role in clinical presentation. Patients with secondary insurance coverage were substantially less likely to present with a pathologic fracture (OR 0.26, 95 % CI 0.14–0.49; p < 0.01). In a sub-analysis of the most common tumors (breast, renal, and lung cancer patients; n = 353), attending college was associated with a significantly lower likelihood of presenting with a pathologic fracture as the initial symptom of metastatic bone disease (OR 0.54, 95 % CI 0.30–0.95; p = 0.03)</div></div><div><h3>Conclusion</h3><div>This study suggests that unfavorable SDOH factors are associated with decreased post-operative survival and a higher likelihood of initial clinical presentation with a completed pathological fracture. Incorporating social determinants into comprehensive care strategies for individuals with MBD may guide targeted interventions and optimize patient management to improve outcomes.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"54 ","pages":"Article 100707"},"PeriodicalIF":3.5,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144781765","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 : 2025-07-28DOI: 10.1016/j.jbo.2025.100706
Sheng-Fen Liu
Background
Osteosarcoma frequently metastasizes to the lungs. The role of surgical intervention in patients with isolated pulmonary metastases and early-stage primary tumors (T1-T2) remains unclear.
Methods
Data from the SEER database were used to identify osteosarcoma patients diagnosed with T1-T2 stage disease and isolated lung metastases. Patients were categorized based on whether they underwent surgery for the primary tumor. Propensity score matching (PSM) was applied to reduce baseline differences.
Results
Before PSM, surgery was associated with significantly improved overall survival (OS) (median OS: 19.0 vs 7.0 months, P < 0.001). After PSM, a trend toward better OS persisted (median OS: 13.0 vs 9.0 months, P = 0.253), though not statistically significant. Surgery was also associated with lower cancer-related death rates both before and after PSM.
Conclusions
Surgical resection of the primary tumor may confer a survival benefit in T1-T2 osteosarcoma patients with isolated pulmonary metastases. These findings support the continued evaluation of surgical strategies in metastatic osteosarcoma and underscore the need for prospective validation.
背景：骨肉瘤经常转移到肺部。手术干预在孤立性肺转移和早期原发性肿瘤（T1-T2）患者中的作用尚不清楚。方法采用SEER数据库中的数据，识别诊断为T1-T2期疾病和分离肺转移的骨肉瘤患者。患者根据是否接受原发肿瘤手术进行分类。倾向评分匹配（PSM）用于减少基线差异。结果在PSM之前，手术与总生存期（OS）的显著改善相关（中位OS: 19.0 vs 7.0个月，P < 0.001）。PSM后，OS改善的趋势持续存在（中位OS: 13.0 vs 9.0个月，P = 0.253），尽管没有统计学意义。手术也与PSM前后较低的癌症相关死亡率相关。结论手术切除原发肿瘤可能会提高T1-T2骨肉瘤患者的生存率。这些发现支持了转移性骨肉瘤手术策略的持续评估，并强调了前瞻性验证的必要性。
{"title":"Surgery for osteosarcoma with isolated pulmonary metastases: A SEER-based analysis","authors":"Sheng-Fen Liu","doi":"10.1016/j.jbo.2025.100706","DOIUrl":"10.1016/j.jbo.2025.100706","url":null,"abstract":"<div><h3>Background</h3><div>Osteosarcoma frequently metastasizes to the lungs. The role of surgical intervention in patients with isolated pulmonary metastases and early-stage primary tumors (T1-T2) remains unclear.</div></div><div><h3>Methods</h3><div>Data from the SEER database were used to identify osteosarcoma patients diagnosed with T1-T2 stage disease and isolated lung metastases. Patients were categorized based on whether they underwent surgery for the primary tumor. Propensity score matching (PSM) was applied to reduce baseline differences.</div></div><div><h3>Results</h3><div>Before PSM, surgery was associated with significantly improved overall survival (OS) (median OS: 19.0 vs 7.0 months, P < 0.001). After PSM, a trend toward better OS persisted (median OS: 13.0 vs 9.0 months, P = 0.253), though not statistically significant. Surgery was also associated with lower cancer-related death rates both before and after PSM.</div></div><div><h3>Conclusions</h3><div>Surgical resection of the primary tumor may confer a survival benefit in T1-T2 osteosarcoma patients with isolated pulmonary metastases. These findings support the continued evaluation of surgical strategies in metastatic osteosarcoma and underscore the need for prospective validation.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"54 ","pages":"Article 100706"},"PeriodicalIF":3.5,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145094884","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}
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