Treatment algorithm for metastatic malignancies in the lower extremities

Treatment algorithm for metastatic malignancies in the lower extremities | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Treatment algorithm for metastatic malignancies in the lower extremities Kazuhiko Hashimoto, Shunji Nishimura, Tomohiko Ito, Ryosuke Kakinoki, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3875909/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background A high prevalence of proximal femoral metastases persists in cancer patients, especially regarding lower extremity fractures. This study offers a detailed analysis of the clinical characteristics in patients undergoing surgical treatment for pathological or impending fractures, enhancing treatment strategies in metastatic malignancies. Methods Thirty patients who underwent treatment for impending and pathological fractures at our hospital were included. The retrospective study covered parameters such as age, sex, fracture site, type of primary malignancy, number of metastases, pre-fracture Eastern Cooperative Oncology Group performance status (ECOG-PS) score, adjuvant therapy, treatment modality, operative time, blood loss, postoperative complications, Musculoskeletal Tumor Society (MSTS) score, outcome, and follow-up period. We compared post-treatment MSTS scores in cases of impending and pathological fractures, and between intramedullary nailing and other surgical procedures. The one-year postoperative survival rate was also calculated. Furthermore, we compared the operative time, blood loss, and survival rates of impending and pathological fractures. Results Participants had a median age of 70.5 years, with disease sites primarily in the subtrochanteric femur, trochanteric femur, femoral diaphysis, femoral neck, and other locations. Pathologies included multiple myeloma, unknown primary, lung, breast, kidney, liver, gastric, esophageal, and uterine cancers. The median ECOG-PS score pre-fracture was 2. Treatment approaches involved radiotherapy, chemotherapy, and a combination of both. Surgical interventions included intramedullary nailing (16 cases), endoprosthesis (1 case), bipolar head replacement (3 cases), and compression hip screw (3 cases), among others. A negative correlation (r = -0.63) existed between MSTS and pre-fracture ECOG-PS scores. Operative time was significantly shorter in impending than pathological fractures, with impending fractures also showing significantly lower blood loss. Conclusion Our treatment algorithm for malignant bone tumors of the lower extremity was efficient, potentially optimizing treatment strategies for such cases, and contributing to improved patient care and outcomes in oncology and orthopedic surgery. pathological fractures impending fractures malignancy bone tumor surgical treatment Figures Figure 1 Figure 2 Figure 3 Figure 4 Background Approximately 10% of patients with primary malignancies develop proximal femoral metastases [ 1 ]. Bone metastases, originating mainly from breast, kidney, thyroid, prostate, or myeloma cancers, are often soluble or mixed in nature, putting patients at a high risk of pathological fractures [ 2 ]. A previous study published an algorithm for treating long bone and pelvic metastases. The patients were categorized into four classes: one, isolated lesion with a good prognosis; two, pathological fractures; three, incisional fractures; and four, other lesions [ 3 ]. Important factors influencing the choice of treatment for long bones and the pelvis include prognosis, disease type, visceral metastases, time from the primary site, risk of pathologic fracture, sensitivity to chemotherapy, hormonal therapy, and irradiation. The role of orthopedic surgeons in evaluating patients with skeletal metastases is expected to increase over time as improved cancer treatments enhance survival [ 4 ]. Additionally, pathological fractures are 3.5 times more likely to occur in the proximal femur than in the proximal humerus [ 5 ]. Despite this, there is a lack of literature describing cases of pathological or impending fractures of the lower extremities in patients with primary and metastatic malignancies. Therefore, the aim of this study is to provide a detailed description of the clinical characteristics of patients who underwent surgical treatment for pathological or impending fractures. Methods The study included 30 patients with impending and pathological fractures treated in our department between January 2019 and November 2023. Impending and pathological fractures were diagnosed based on the Mirels’ score [ 6 ]. There were 12 cases of impending fractures and 18 of pathological fractures. The retrospective survey covered the following parameters: age, sex, fracture site, types of primary malignancy, number of metastases, pre-fracture Eastern Cooperative Oncology Group performance status score (ECOG-PS) [ 7 ], adjuvant therapy, treatment modality, operative time, blood loss, postoperative complications, Musculoskeletal Tumor Society (MSTS) score [ 8 ], outcome, and follow-up period. We also compared post-treatment MSTS scores between cases of impending and pathological fractures, as well as between cases treated with intramedullary nailing and those undergoing other surgical procedures. The postoperative one-year survival rate was calculated using the Kaplan–Meier method. Additionally, the operative time, blood loss, and survival rates between impending and pathological fractures were compared. Results The patient characteristics are summarized in Table 1 , and treatments were performed according to the algorithm depicted in Fig. 1 . The median age of the participants was 70.5 years, including 13 males and 17 females. Disease sites included the subtrochanteric region of the femur (n = 10), trochanteric region of the femur (n = 6), femoral diaphysis (n = 5), femoral neck (n = 5), bilateral trochanteric femoral region (n = 1), proximal tibia (n = 2), and distal femur (n = 1). Pathological conditions included cases of lung cancer (n = 9), breast cancer (n = 7), kidney cancer (n = 3), multiple myeloma (n = 4), liver cancer (n = 2), gastric cancer (n = 2), unknown primary cancer (n = 1), uterine cancer (n = 1), and esophageal cancer (n = 1). The number of metastases was ≤ 3 in 4 cases and > 3 in 26 cases. The median ECOG-PS before the fracture was 2 (range 0–4). Adjuvant therapy comprised radiotherapy in 2 cases, chemotherapy in 15 cases, and a combination of radiotherapy and chemotherapy in 10 cases. Surgical procedures included intramedullary nailing (n = 16), endoprosthesis (n = 1), bipolar head replacement (n = 3), compression hip screw (CHS) (n = 3), conservative treatment (n = 2), bilateral intramedullary nailing (n = 2), artificial bone stem (n = 1), combined intramedullary nail and plate fixation (n = 1), right-sided artificial head replacement (n = 1), and left-sided CHS (n = 1). Operating time was 92 ± 38.7 minutes, and blood loss was 50 ± 109.1 mL (mean ± standard deviation). MSTS score was 19.9 ± 8.81 for intramedullary nailing and 22 ± 10.92 for other surgical procedures (p = 0.23), with a negative correlation between MSTS score and pre-fracture ECOG-PS (r = -0.63; Fig. 2 ). Postoperative complications included one case of implant failure following the replacement of an intramedullary nail with an endoprosthesis. The median follow-up period was 6.5 months, with outcomes categorized as alive with disease in 19 cases and dead of disease in 11 cases. The one-year postoperative overall survival rate was 48.8% (Fig. 3 ). The operative time for patients with impending fractures was significantly shorter than that for patients with pathological fractures (83.1 ± 21.9 minutes and 113.8 ± 44.3 minutes, respectively; p = 0.015). The amount of blood loss in patients with impending fractures was significantly less than that in patients with pathological fractures (46.4 ± 35 mL and 132.68 ± 132.7 mL, respectively; p = 0.015). No significant difference was observed in the 1-year survival between patients with incisional fractures and those with pathological fractures (54.6% and 43.6%, respectively; p = 0.85) (Fig. 4 ). Table 1 Characteristics of the study population Factor Patients, n Age (mean years) 70.5 ≤ 70 15 > 70 15 Gender Male 13 Female 17 Fracture site Femoral neck 5 Femoral diaphysis 5 Intertrochanteric 6 Subtrochanteric 10 Bilateral intertrochanteric 1 Proximal tibia 2 Distal femur 1 Type of cancer Lung 9 Breast 7 Kidney 3 Multiple Myeloma 4 Liver 2 Gastric 2 Unknown 1 Esophageal 1 Uterine 1 N. metastasis Equal or less than 3 4 More than 3 26 ECOG-PS 3 2 Adjuvant therapy Radiotherapy 2 Chemotherapy 15 Chemotherapy and radiotherapy 10 None 3 Treatment modality Intramedullary nail 16 Endoprosthesis 1 Fixation with plate 1 Bipolar head arthroplasty 3 Fixation with CHS 3 Bilateral intermedullary nail 2 Conservative 2 Artificial bone stem 1 Rt. Bipolar head arthroplasty, Lt. fixation with CHS 1 Operating time (min) 0–100 17 100< 11 Blood loss 0–60 15 60< 13 MSTS score 0–10 8 11–20 7 21–30 15 Outcome AWD 19 DOD 11 Follow-up periods (months) mean 6.5 range 1–150 N, number; Rt, right side; Lt, left side; ECOG-PS, Eastern Cooperative Oncology Group (ECOG) score for performance status; CHS, compression hip screw; MSTS, Musculoskeletal Tumor Society; CDF, continuous disease-free; AWD, alive with disease; DOD, dead of disease. Discussion In this study, we investigated the treatment outcomes of pathological or impending fractures in metastatic bone tumors and presented our algorithm, revealing generally favorable results. The most frequently reported sites of pathological fractures include the femur, spine, and pelvis [ 9 ]. The preferred sites of pathological fractures in the lower extremities are the femoral neck (50%), trochanter (30%), and subtrochanter (20%) [ 10 ]. Other studies have reported 47.5% in the femoral head and neck, 27.5% in the femoral metaphyseal area, and 25% below the femoral metaphyseal area [ 11 ]. In this study, the subtrochanteric and trochanteric areas were more common than the femoral neck area. Previous studies have reported that the most common primary sites leading to pathological femoral fractures were multiple myeloma, breast, renal, colorectal, thyroid, and lung cancers [ 1 ]. Specifically, multiple myeloma, breast, lung, and kidney cancers were noted as the most common primary lesions resulting in pathological fractures of the proximal femur [ 9 , 11 ]. Notably, lung cancer was relatively common in this study, potentially reflecting the specialized treatments for lung cancer provided by our oncology department. Fractures of the lower extremities are clinically more important than those of the upper extremities because of their weight-bearing nature [ 9 ]. Recommendations for the fixation of pathological fractures vary depending on the anatomical site [ 9 ]. For femoral head and neck fractures, treatment options include hemiarthroplasty, total hip arthroplasty, endoprosthesis, or plate or nail fixation with void filler. Cephalomedullary nailing is a recommended treatment for intertrochanteric, subtrochanteric, and diaphyseal fractures. In cases of distal third femoral shaft fractures, the recommended treatments involve locking plates or retrograde intramedullary nails (with careful consideration by a musculoskeletal oncologist to avoid proximal tumor spread). For supracondylar fracture, the recommended treatment option is a distal femur periarticular plate. A locking plate or endoprosthesis is recommended for proximal tibia fixation, and intramedullary nails for tibial shafts. The advantages of tumor arthroplasty include quick stability, independence from the degree of fracture healing, and minimal risk of local progression or implant failure [ 12 ]. Its disadvantages include greater surgical invasiveness, bleeding, relative difficulty in muscle reconstruction, and higher costs [ 12 ]. Intramedullary nails have the advantages of relatively low surgical invasion, the possibility of additional radiation therapy, and the ability to support load immediately after radiation [ 12 ]. Disadvantages of intramedullary nails include the need for adequate bone stock, instability near the joint, and the risk of implant fracture [ 12 ]. Alternatively, plate fixation provides benefits such as muscle cuff preservation, strong fixation with locking screws, fixation of distal fractures, and a relatively large operative field allowing visual resection of the tumor [ 12 ]. Its drawbacks include the need for large incisions, longer surgical procedures, and lack of prophylactic fixation of the entire bone [ 12 ]. Intramedullary nails were used in this study. Our approach involves reconstructing pathological fractures of the femoral neck using either artificial head replacement or tumor arthroplasty. The choice is based on tumor spread, prognosis, invasiveness, and the patient’s rehabilitation potential, including load-bearing capacity. For pathological fractures of the femoral condyle and the subtrochanteric region, reconstruction using an intramedullary nail was performed in anticipation of postoperative radiotherapy. Impending fractures of the femoral neck or transverse condyle were treated with bipolar head arthroplasty, intramedullary nails, or CHS plates. The reconstruction method was selected based on a comprehensive evaluation of postoperative radiotherapy, fixation stability, and the amount of lesion removed. Both types of fixation demonstrated generally good functional prognosis, but poor prognosis was observed when rehabilitation did not progress as expected due to the patient's general condition. We followed a protocol and treatment that resulted in the predominant use of intramedullary nails. Previous studies have reported MSTS scores of 6.4–25.2 after implant use for pathological fractures [ 11 – 13 ]. The results of this study align, supporting the general recommendation of our surgical indications (Fig. 1 ). Complications have been reported in 9–20% of cases involving intramedullary nails [ 14 , 15 ]. The primary complications include deep infection, myocardial infarction, and stroke. Additionally, it has been reported that 20% of patients require revision surgery within 3 months [ 16 ]. In contrast, dislocation has been reported to occur in 3–22% of cases as a complication of tumor arthroplasty [ 11 , 17 ]. The risk of periprosthetic failure has also been reported [ 17 – 19 ]. In this study, implant failure occurred in one case of intramedullary nailing, which was subsequently replaced with an oncological prosthesis. Typically, patients with metastatic bone tumors are in a terminal state [ 20 , 21 ]. Regarding overall patient survival, the 1-year survival range is 42–75% [ 15 , 22 , 23 ]. Fractures have been associated with an increased mortality risk in patients with malignant bone disease [ 24 ]. Although the survival rate of patients with metastases remains low, advancements in medical treatment have led to some differences in tumor histology. In this context, “improving the survival rate of the implant relative to the patient's lifespan” is essential, and appropriate treatment options should be considered with the patient’s life expectancy in mind. Previously, patients with pathological fractures demonstrated similar morbidity and mortality rates to the non-pathological fracture cohort but exhibited higher rates of perioperative blood transfusions and unscheduled readmissions [ 25 ]. In this study, pathological fractures were associated with longer operative times and greater blood loss than incisional fractures. However, no significant difference was observed in survival rates. Therefore, treatment should be initiated prior to the occurrence of pathological fractures. Study Limitations This study had a few limitations. First, the sample size was small. However, no problems were encountered during the analyses. Second, this was a retrospective study. Third, it was not randomized, potentially introducing selection bias. The study also included a small number of primary cases. Finally, the follow-up period was relatively short. Despite these limitations, we enrolled as many patients as possible during the study period. Conclusions Treatment should be carefully selected considering the patient’s general condition, especially performance status, and aligned with the anatomical site of the pathological fracture. Abbreviations ECOG-PS Eastern Cooperative Oncology Group performance status CHS compression hip screw MSTS Musculoskeletal Tumor Society Declarations Ethics approval and Consent to participate Ethical approval for this study was obtained from the Ethics Committee of Kindai University Hospital (approval no.: 31-153) (Osaka, Japan). Written informed consent was obtained from all participants included in the current study. Consent for publication Consent for publication was obtained from all participants included in the current study. Availability of data and materials The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request. Competing Interests The authors declare no conflict of interest. Funding The authors did not receive support from any organization for the submitted work. Author’s contributions Conceptualization: K.H., S.N., T.I., and K.G.; methodology: K.H., S.N., T.I., R.K., and K.G.; software: K.H., R.K., and S.N.; validation: S.N., N.S., T.I., R.K., and K.G.; formal analysis: S.N., N.S., T.I., and K.G.; investigation: K.H., T.I., R.K., and S.N.; data curation: K.H., S.N., T.I., R.K., and K.G.; writing—original draft preparation: K.H., S.N., T.I., R.K., and K.G.; writing—review and editing: K.H., S.N., T.I., R.K., and K.G. All authors have read and agreed to the published version of the manuscript. Acknowledgments The authors would like to thank Editage (www.editage.jp) for the English language editing. References Guzik G. Oncological and functional results after surgical treatment of bone metastases at the proximal femur. BMC Surg. 2018;18:5. doi.org/10.1186/s12893-018-0336-0 . Fontanella C, Fanotto V, Rihawi K, Aprile G, Puglisi F. 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Risks and complications after arthroplasty for pathological or impending pathological fracture of the hip. J Arthroplasty. 2021;36:2049–2054.e5. doi.org/10.1016/j.arth.2021.02.004 . Epub 2021 Feb 6. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3875909","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":268104015,"identity":"db705367-137c-440b-9133-ba4722a8b5e0","order_by":0,"name":"Kazuhiko Hashimoto","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABFUlEQVRIie2QMUsDMRTH3xGwy2nXV5R+hgcH7RXEz5IQuC6HFlwcigRci7PSL3EgOEcOrsvBbRK46Sg4ORQK4lDBWB10SGs3kfzgkbwHP94/AfB4/iBkiwFxaNsLgkYAHShYT7cpHbWbAhxIrxXb6i3B+q3ZfDkaJd3oMX8wUManB7NcwesYWn2HMphwHt1QGvXqRMZg8LxTChVMCmAD5QimuZYhXYj7Ou0hLFBkWijYV8DIkZCqRuUfyt307OVTsZPgbZNiZHAVUiqyw3QPbTCRGaHYxi3mibGQkgjrJIp5ieLW2L1HBbrfUg3ny3Alu+2pbMyiuBTX1bBpnsfH0vVjP+Ffp42Ekn6lfOdkd8Xj8Xj+Ke+RaGDphtrt8AAAAABJRU5ErkJggg==","orcid":"","institution":"Kindai University Hospital","correspondingAuthor":true,"prefix":"","firstName":"Kazuhiko","middleName":"","lastName":"Hashimoto","suffix":""},{"id":268104016,"identity":"febea7d9-e39e-4131-a215-616bf3f1e5b7","order_by":1,"name":"Shunji Nishimura","email":"","orcid":"","institution":"Kindai University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Shunji","middleName":"","lastName":"Nishimura","suffix":""},{"id":268104017,"identity":"caccb20a-426b-40ee-ad4e-e06217588175","order_by":2,"name":"Tomohiko Ito","email":"","orcid":"","institution":"Kindai University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Tomohiko","middleName":"","lastName":"Ito","suffix":""},{"id":268104018,"identity":"3eef65d0-3d64-4a31-b098-640ad5097330","order_by":3,"name":"Ryosuke Kakinoki","email":"","orcid":"","institution":"Kindai University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ryosuke","middleName":"","lastName":"Kakinoki","suffix":""},{"id":268104019,"identity":"1d0e2f80-ed8e-4e73-a27a-6283a415f3ed","order_by":4,"name":"Koji Goto","email":"","orcid":"","institution":"Kindai University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Koji","middleName":"","lastName":"Goto","suffix":""}],"badges":[],"createdAt":"2024-01-18 13:29:36","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3875909/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3875909/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":49992508,"identity":"5e59af29-e306-434f-8e71-b60c17469a28","added_by":"auto","created_at":"2024-01-22 18:56:42","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":315075,"visible":true,"origin":"","legend":"\u003cp\u003eThe tree diagram shows the treatment algorithm for lower leg malignancy at our hospital. Oligo, oligo metastasis in whole body; Multiple, multiple metastasis in whole body; PS, performance status; EP, endoprosthesis; BHA, bipolar head arthroplasty; IMN, intermedullary nail; ABS, artificial bone stem\u003c/p\u003e","description":"","filename":"Figure1TIFF.png","url":"https://assets-eu.researchsquare.com/files/rs-3875909/v1/53a8578eba90e04686a93d80.png"},{"id":49991706,"identity":"1e1a36a0-fecf-4f11-964c-e6af2be99e87","added_by":"auto","created_at":"2024-01-22 18:48:42","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":74756,"visible":true,"origin":"","legend":"\u003cp\u003eGraphs showing the negative correlation between the MSTS score and ECOG-PS (r = -0.63)\u003c/p\u003e","description":"","filename":"Figure2TIFF.png","url":"https://assets-eu.researchsquare.com/files/rs-3875909/v1/dbe60587c482d20a1be65cb8.png"},{"id":49991707,"identity":"c4e3e7c0-daac-49e7-bc43-c9fa42bbca92","added_by":"auto","created_at":"2024-01-22 18:48:42","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":107998,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan–Meier curves showing the survival rate. The 1-year survival rate was 48.8%\u003c/p\u003e","description":"","filename":"Figure3TIFF.png","url":"https://assets-eu.researchsquare.com/files/rs-3875909/v1/e60bf5d9578f832e2a2c5dd2.png"},{"id":49991709,"identity":"cdb2f1fd-ab8c-4992-91fc-bbfa0387a10e","added_by":"auto","created_at":"2024-01-22 18:48:42","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":111556,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan–Meier curves for cases of impending fracture (red line) and pathological fracture (blue line). There was no significant difference in 1-year survival for patients with incisional fractures compared to those with pathological fractures (54.6% and 43.6%, respectively; p = 0.85)\u003c/p\u003e","description":"","filename":"Figure4TIFF.png","url":"https://assets-eu.researchsquare.com/files/rs-3875909/v1/81359784eb970ececffcdc10.png"},{"id":50576826,"identity":"f3f5a5e2-6a5c-4bc8-9eb5-970f558a45cf","added_by":"auto","created_at":"2024-02-02 17:52:32","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":739820,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3875909/v1/4e2d2d45-d2e5-4aa3-a3a8-64bdecfea48b.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Treatment algorithm for metastatic malignancies in the lower extremities","fulltext":[{"header":"Background","content":"\u003cp\u003eApproximately 10% of patients with primary malignancies develop proximal femoral metastases [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Bone metastases, originating mainly from breast, kidney, thyroid, prostate, or myeloma cancers, are often soluble or mixed in nature, putting patients at a high risk of pathological fractures [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. A previous study published an algorithm for treating long bone and pelvic metastases. The patients were categorized into four classes: one, isolated lesion with a good prognosis; two, pathological fractures; three, incisional fractures; and four, other lesions [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Important factors influencing the choice of treatment for long bones and the pelvis include prognosis, disease type, visceral metastases, time from the primary site, risk of pathologic fracture, sensitivity to chemotherapy, hormonal therapy, and irradiation. The role of orthopedic surgeons in evaluating patients with skeletal metastases is expected to increase over time as improved cancer treatments enhance survival [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAdditionally, pathological fractures are 3.5 times more likely to occur in the proximal femur than in the proximal humerus [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Despite this, there is a lack of literature describing cases of pathological or impending fractures of the lower extremities in patients with primary and metastatic malignancies. Therefore, the aim of this study is to provide a detailed description of the clinical characteristics of patients who underwent surgical treatment for pathological or impending fractures.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThe study included 30 patients with impending and pathological fractures treated in our department between January 2019 and November 2023. Impending and pathological fractures were diagnosed based on the Mirels\u0026rsquo; score [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. There were 12 cases of impending fractures and 18 of pathological fractures. The retrospective survey covered the following parameters: age, sex, fracture site, types of primary malignancy, number of metastases, pre-fracture Eastern Cooperative Oncology Group performance status score (ECOG-PS) [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], adjuvant therapy, treatment modality, operative time, blood loss, postoperative complications, Musculoskeletal Tumor Society (MSTS) score [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], outcome, and follow-up period. We also compared post-treatment MSTS scores between cases of impending and pathological fractures, as well as between cases treated with intramedullary nailing and those undergoing other surgical procedures. The postoperative one-year survival rate was calculated using the Kaplan\u0026ndash;Meier method. Additionally, the operative time, blood loss, and survival rates between impending and pathological fractures were compared.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThe patient characteristics are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, and treatments were performed according to the algorithm depicted in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The median age of the participants was 70.5 years, including 13 males and 17 females. Disease sites included the subtrochanteric region of the femur (n\u0026thinsp;=\u0026thinsp;10), trochanteric region of the femur (n\u0026thinsp;=\u0026thinsp;6), femoral diaphysis (n\u0026thinsp;=\u0026thinsp;5), femoral neck (n\u0026thinsp;=\u0026thinsp;5), bilateral trochanteric femoral region (n\u0026thinsp;=\u0026thinsp;1), proximal tibia (n\u0026thinsp;=\u0026thinsp;2), and distal femur (n\u0026thinsp;=\u0026thinsp;1). Pathological conditions included cases of lung cancer (n\u0026thinsp;=\u0026thinsp;9), breast cancer (n\u0026thinsp;=\u0026thinsp;7), kidney cancer (n\u0026thinsp;=\u0026thinsp;3), multiple myeloma (n\u0026thinsp;=\u0026thinsp;4), liver cancer (n\u0026thinsp;=\u0026thinsp;2), gastric cancer (n\u0026thinsp;=\u0026thinsp;2), unknown primary cancer (n\u0026thinsp;=\u0026thinsp;1), uterine cancer (n\u0026thinsp;=\u0026thinsp;1), and esophageal cancer (n\u0026thinsp;=\u0026thinsp;1). The number of metastases was \u0026le;\u0026thinsp;3 in 4 cases and \u0026gt;\u0026thinsp;3 in 26 cases. The median ECOG-PS before the fracture was 2 (range 0\u0026ndash;4). Adjuvant therapy comprised radiotherapy in 2 cases, chemotherapy in 15 cases, and a combination of radiotherapy and chemotherapy in 10 cases. Surgical procedures included intramedullary nailing (n\u0026thinsp;=\u0026thinsp;16), endoprosthesis (n\u0026thinsp;=\u0026thinsp;1), bipolar head replacement (n\u0026thinsp;=\u0026thinsp;3), compression hip screw (CHS) (n\u0026thinsp;=\u0026thinsp;3), conservative treatment (n\u0026thinsp;=\u0026thinsp;2), bilateral intramedullary nailing (n\u0026thinsp;=\u0026thinsp;2), artificial bone stem (n\u0026thinsp;=\u0026thinsp;1), combined intramedullary nail and plate fixation (n\u0026thinsp;=\u0026thinsp;1), right-sided artificial head replacement (n\u0026thinsp;=\u0026thinsp;1), and left-sided CHS (n\u0026thinsp;=\u0026thinsp;1). Operating time was 92\u0026thinsp;\u0026plusmn;\u0026thinsp;38.7 minutes, and blood loss was 50\u0026thinsp;\u0026plusmn;\u0026thinsp;109.1 mL (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation). MSTS score was 19.9\u0026thinsp;\u0026plusmn;\u0026thinsp;8.81 for intramedullary nailing and 22\u0026thinsp;\u0026plusmn;\u0026thinsp;10.92 for other surgical procedures (p\u0026thinsp;=\u0026thinsp;0.23), with a negative correlation between MSTS score and pre-fracture ECOG-PS (r = -0.63; Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Postoperative complications included one case of implant failure following the replacement of an intramedullary nail with an endoprosthesis. The median follow-up period was 6.5 months, with outcomes categorized as alive with disease in 19 cases and dead of disease in 11 cases. The one-year postoperative overall survival rate was 48.8% (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The operative time for patients with impending fractures was significantly shorter than that for patients with pathological fractures (83.1\u0026thinsp;\u0026plusmn;\u0026thinsp;21.9 minutes and 113.8\u0026thinsp;\u0026plusmn;\u0026thinsp;44.3 minutes, respectively; p\u0026thinsp;=\u0026thinsp;0.015). The amount of blood loss in patients with impending fractures was significantly less than that in patients with pathological fractures (46.4\u0026thinsp;\u0026plusmn;\u0026thinsp;35 mL and 132.68\u0026thinsp;\u0026plusmn;\u0026thinsp;132.7 mL, respectively; p\u0026thinsp;=\u0026thinsp;0.015). No significant difference was observed in the 1-year survival between patients with incisional fractures and those with pathological fractures (54.6% and 43.6%, respectively; p\u0026thinsp;=\u0026thinsp;0.85) (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of the study population\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFactor\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePatients, n\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (mean years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e70.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFracture site\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemoral neck\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemoral diaphysis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntertrochanteric\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSubtrochanteric\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBilateral intertrochanteric\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProximal tibia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDistal femur\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType of cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLung\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBreast\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKidney\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMultiple Myeloma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLiver\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGastric\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEsophageal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUterine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN. metastasis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEqual or less than 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMore than 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eECOG-PS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u0026ndash;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdjuvant therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRadiotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChemotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChemotherapy and radiotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTreatment modality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntramedullary nail\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEndoprosthesis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFixation with plate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBipolar head arthroplasty\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFixation with CHS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBilateral intermedullary nail\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eConservative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArtificial bone stem\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRt. Bipolar head arthroplasty, Lt. fixation with CHS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOperating time (min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u0026ndash;100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e100\u0026lt;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlood loss\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u0026ndash;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e60\u0026lt;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMSTS score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u0026ndash;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e11\u0026ndash;20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e21\u0026ndash;30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOutcome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAWD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDOD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFollow-up periods (months)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emean\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003erange\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u0026ndash;150\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eN, number; Rt, right side; Lt, left side; ECOG-PS, Eastern Cooperative Oncology Group (ECOG) score for performance status; CHS, compression hip screw; MSTS, Musculoskeletal Tumor Society; CDF, continuous disease-free; AWD, alive with disease; DOD, dead of disease.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, we investigated the treatment outcomes of pathological or impending fractures in metastatic bone tumors and presented our algorithm, revealing generally favorable results. The most frequently reported sites of pathological fractures include the femur, spine, and pelvis [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. The preferred sites of pathological fractures in the lower extremities are the femoral neck (50%), trochanter (30%), and subtrochanter (20%) [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Other studies have reported 47.5% in the femoral head and neck, 27.5% in the femoral metaphyseal area, and 25% below the femoral metaphyseal area [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. In this study, the subtrochanteric and trochanteric areas were more common than the femoral neck area.\u003c/p\u003e \u003cp\u003ePrevious studies have reported that the most common primary sites leading to pathological femoral fractures were multiple myeloma, breast, renal, colorectal, thyroid, and lung cancers [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Specifically, multiple myeloma, breast, lung, and kidney cancers were noted as the most common primary lesions resulting in pathological fractures of the proximal femur [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Notably, lung cancer was relatively common in this study, potentially reflecting the specialized treatments for lung cancer provided by our oncology department.\u003c/p\u003e \u003cp\u003eFractures of the lower extremities are clinically more important than those of the upper extremities because of their weight-bearing nature [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Recommendations for the fixation of pathological fractures vary depending on the anatomical site [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. For femoral head and neck fractures, treatment options include hemiarthroplasty, total hip arthroplasty, endoprosthesis, or plate or nail fixation with void filler. Cephalomedullary nailing is a recommended treatment for intertrochanteric, subtrochanteric, and diaphyseal fractures. In cases of distal third femoral shaft fractures, the recommended treatments involve locking plates or retrograde intramedullary nails (with careful consideration by a musculoskeletal oncologist to avoid proximal tumor spread). For supracondylar fracture, the recommended treatment option is a distal femur periarticular plate. A locking plate or endoprosthesis is recommended for proximal tibia fixation, and intramedullary nails for tibial shafts.\u003c/p\u003e \u003cp\u003eThe advantages of tumor arthroplasty include quick stability, independence from the degree of fracture healing, and minimal risk of local progression or implant failure [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Its disadvantages include greater surgical invasiveness, bleeding, relative difficulty in muscle reconstruction, and higher costs [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Intramedullary nails have the advantages of relatively low surgical invasion, the possibility of additional radiation therapy, and the ability to support load immediately after radiation [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Disadvantages of intramedullary nails include the need for adequate bone stock, instability near the joint, and the risk of implant fracture [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Alternatively, plate fixation provides benefits such as muscle cuff preservation, strong fixation with locking screws, fixation of distal fractures, and a relatively large operative field allowing visual resection of the tumor [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Its drawbacks include the need for large incisions, longer surgical procedures, and lack of prophylactic fixation of the entire bone [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Intramedullary nails were used in this study. Our approach involves reconstructing pathological fractures of the femoral neck using either artificial head replacement or tumor arthroplasty. The choice is based on tumor spread, prognosis, invasiveness, and the patient\u0026rsquo;s rehabilitation potential, including load-bearing capacity. For pathological fractures of the femoral condyle and the subtrochanteric region, reconstruction using an intramedullary nail was performed in anticipation of postoperative radiotherapy. Impending fractures of the femoral neck or transverse condyle were treated with bipolar head arthroplasty, intramedullary nails, or CHS plates. The reconstruction method was selected based on a comprehensive evaluation of postoperative radiotherapy, fixation stability, and the amount of lesion removed. Both types of fixation demonstrated generally good functional prognosis, but poor prognosis was observed when rehabilitation did not progress as expected due to the patient's general condition.\u003c/p\u003e \u003cp\u003e We followed a protocol and treatment that resulted in the predominant use of intramedullary nails. Previous studies have reported MSTS scores of 6.4\u0026ndash;25.2 after implant use for pathological fractures [\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The results of this study align, supporting the general recommendation of our surgical indications (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eComplications have been reported in 9\u0026ndash;20% of cases involving intramedullary nails [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The primary complications include deep infection, myocardial infarction, and stroke. Additionally, it has been reported that 20% of patients require revision surgery within 3 months [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. In contrast, dislocation has been reported to occur in 3\u0026ndash;22% of cases as a complication of tumor arthroplasty [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The risk of periprosthetic failure has also been reported [\u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. In this study, implant failure occurred in one case of intramedullary nailing, which was subsequently replaced with an oncological prosthesis.\u003c/p\u003e \u003cp\u003eTypically, patients with metastatic bone tumors are in a terminal state [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Regarding overall patient survival, the 1-year survival range is 42\u0026ndash;75% [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Fractures have been associated with an increased mortality risk in patients with malignant bone disease [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Although the survival rate of patients with metastases remains low, advancements in medical treatment have led to some differences in tumor histology. In this context, \u0026ldquo;improving the survival rate of the implant relative to the patient's lifespan\u0026rdquo; is essential, and appropriate treatment options should be considered with the patient\u0026rsquo;s life expectancy in mind.\u003c/p\u003e \u003cp\u003ePreviously, patients with pathological fractures demonstrated similar morbidity and mortality rates to the non-pathological fracture cohort but exhibited higher rates of perioperative blood transfusions and unscheduled readmissions [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. In this study, pathological fractures were associated with longer operative times and greater blood loss than incisional fractures. However, no significant difference was observed in survival rates. Therefore, treatment should be initiated prior to the occurrence of pathological fractures.\u003c/p\u003e\n\u003ch3\u003eStudy Limitations\u003c/h3\u003e\n\u003cp\u003eThis study had a few limitations. First, the sample size was small. However, no problems were encountered during the analyses. Second, this was a retrospective study. Third, it was not randomized, potentially introducing selection bias. The study also included a small number of primary cases. Finally, the follow-up period was relatively short. Despite these limitations, we enrolled as many patients as possible during the study period.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eTreatment should be carefully selected considering the patient’s general condition, especially performance status, and aligned with the anatomical site of the pathological fracture.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e \u003cstrong\u003eECOG-PS\u003c/strong\u003e \u003c/p\u003e\u003cp\u003eEastern Cooperative Oncology Group performance status\u003c/p\u003e\u003cp\u003e \u003cstrong\u003eCHS\u003c/strong\u003e \u003c/p\u003e\u003cp\u003ecompression hip screw\u003c/p\u003e\u003cp\u003e \u003cstrong\u003eMSTS\u003c/strong\u003e \u003c/p\u003e\u003cp\u003eMusculoskeletal Tumor Society\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;and Consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthical approval for this study was obtained from the Ethics Committee of Kindai University Hospital (approval no.: 31-153) (Osaka, Japan).\u0026nbsp;Written informed consent was obtained from all participants included in the current study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConsent for publication was obtained from all participants included in the current study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors did not receive support from any organization for the submitted work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor\u0026rsquo;s contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConceptualization: K.H., S.N., T.I., and K.G.; methodology: K.H., S.N., T.I., R.K., and K.G.; software: K.H., R.K., and S.N.; validation: S.N., N.S., T.I., R.K., and K.G.; formal analysis: S.N., N.S., T.I., and K.G.; investigation: K.H., T.I., R.K., and S.N.; data curation: K.H., S.N., T.I., R.K., and K.G.; writing\u0026mdash;original draft preparation: K.H., S.N., T.I., R.K., and K.G.; writing\u0026mdash;review and editing: K.H., S.N., T.I., R.K., and K.G. All authors have read and agreed to the published version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank Editage (www.editage.jp) for the English language editing.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGuzik G. Oncological and functional results after surgical treatment of bone metastases at the proximal femur. BMC Surg. 2018;18:5. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003edoi.org/10.1186/s12893-018-0336-0\u003c/span\u003e\u003cspan address=\"10.1186/s12893-018-0336-0\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFontanella C, Fanotto V, Rihawi K, Aprile G, Puglisi F. Skeletal metastases from breast cancer: pathogenesis of bone tropism and treatment strategy. 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Risks and complications after arthroplasty for pathological or impending pathological fracture of the hip. J Arthroplasty. 2021;36:2049\u0026ndash;2054.e5. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003edoi.org/10.1016/j.arth.2021.02.004\u003c/span\u003e\u003cspan address=\"10.1016/j.arth.2021.02.004\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2021 Feb 6.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"pathological fractures, impending fractures, malignancy, bone tumor, surgical treatment","lastPublishedDoi":"10.21203/rs.3.rs-3875909/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3875909/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eA high prevalence of proximal femoral metastases persists in cancer patients, especially regarding lower extremity fractures. This study offers a detailed analysis of the clinical characteristics in patients undergoing surgical treatment for pathological or impending fractures, enhancing treatment strategies in metastatic malignancies.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThirty patients who underwent treatment for impending and pathological fractures at our hospital were included. The retrospective study covered parameters such as age, sex, fracture site, type of primary malignancy, number of metastases, pre-fracture Eastern Cooperative Oncology Group performance status (ECOG-PS) score, adjuvant therapy, treatment modality, operative time, blood loss, postoperative complications, Musculoskeletal Tumor Society (MSTS) score, outcome, and follow-up period. We compared post-treatment MSTS scores in cases of impending and pathological fractures, and between intramedullary nailing and other surgical procedures. The one-year postoperative survival rate was also calculated. Furthermore, we compared the operative time, blood loss, and survival rates of impending and pathological fractures.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eParticipants had a median age of 70.5 years, with disease sites primarily in the subtrochanteric femur, trochanteric femur, femoral diaphysis, femoral neck, and other locations. Pathologies included multiple myeloma, unknown primary, lung, breast, kidney, liver, gastric, esophageal, and uterine cancers. The median ECOG-PS score pre-fracture was 2. Treatment approaches involved radiotherapy, chemotherapy, and a combination of both. Surgical interventions included intramedullary nailing (16 cases), endoprosthesis (1 case), bipolar head replacement (3 cases), and compression hip screw (3 cases), among others. A negative correlation (r = -0.63) existed between MSTS and pre-fracture ECOG-PS scores. Operative time was significantly shorter in impending than pathological fractures, with impending fractures also showing significantly lower blood loss.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003e Our treatment algorithm for malignant bone tumors of the lower extremity was efficient, potentially optimizing treatment strategies for such cases, and contributing to improved patient care and outcomes in oncology and orthopedic surgery.\u003c/p\u003e","manuscriptTitle":"Treatment algorithm for metastatic malignancies in the lower extremities","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-22 18:48:38","doi":"10.21203/rs.3.rs-3875909/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"814af0b0-9684-4e77-ad19-d9c15f0d1ab6","owner":[],"postedDate":"January 22nd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-02-02T17:44:25+00:00","versionOfRecord":[],"versionCreatedAt":"2024-01-22 18:48:38","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3875909","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3875909","identity":"rs-3875909","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}