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Background: Current functional assessment tools for orthopaedic oncology are long surveys that contribute to patients' survey fatigue and yet lack the ability to discern meaningful differences in a patient population that is often mobile but unable to perform strenuous activities. We sought to determine whether a shorter, novel tool based on existing, validated surveys could better capture differences in a sample of orthopaedic oncology patients., Questions/purposes: (1) Can a concise fixed-item functional tool derived from the 50 items in the Toronto Extremity Salvage Score for the lower extremity (TESS LE) and the Lower Extremity Functional Scale (LEFS) demonstrate similar responsiveness in terms of sensitivity and specificity? (2) What is the precision and accuracy of the concise tool compared with the TESS LE and LEFS?, Methods: Functional outcome data were collected and maintained in a longitudinally maintained database at a single institution. Patients were included in the study if (1) they had undergone a tumor excision or a nononcologic orthopaedic procedure (for example, arthroplasty for osteoarthritis) for a bone or soft tissue tumor affecting lower extremity function, and (2) they had completed the LEFS, TESS LE, and Patient-Reported Outcomes Measurement Information System (PROMIS) global health tool on at least two clinic visits. Between September 2014 and April 2022, we treated 14,234 patients for primary bone or soft tissue sarcoma, metastatic disease to bone, or orthopaedic sequelae of chronic cancer care. Approximately 6% (854 of 14,234) were excluded due to the need of a language translator. Approximately 2% (278 of 13,380) refused or were unable to participate. Seventy-two percent (9433 of 13,102) of the patients had an operation on a lower extremity. Of these, 4% (339 of 9433) of the patients completed the TESS LE, LEFS, and Item 3 of the PROMIS global health tool on ≥ 2 clinic visits. Of the patients in the current study, 49% (167 of 339) were women, and 27% (93 of 339) had metastatic carcinoma. Twelve percent (41 of 339) of the patients died before the end of the study period. Spearman rank-order correlation, principal component analysis (PCA), and item response theory (IRT) modeling identified 14 highly discriminating items from the TESS LE and LEFS. Multiple linear stepwise regression (MLSR) was performed with the dependent variable being the summary score of the 14 items derived from the TESS LE and LEFS and standardized to a percentage of 100. The beta coefficient from the MLSR was used to derive a weight for each of the 14 items. Evaluation of the model with 10 to 17 variables was performed to ensure that the model with the 14 items met the most criteria for fit with the PCA, the receiver operating characteristic (ROC) curve, and the IRT modeling criteria. The responsiveness (sensitivity and specificity) of the change scores in the shortened 14-item survey, the 30-item TESS LE, and the 20-item LEFS as compared with the dichotomized changes in Item 3 of the PROMIS global health tool was evaluated using ROCs. The concordance (accuracy and precision) of the 14 items derived from the LEFS and TESS LE was evaluated., Results: The responsiveness (sensitivity and specificity) of the shortened 14-item survey, the TESS LE, and the LEFS to the criterion target of the PROMIS global health tool (Item 3) was similar, with areas under the curve (AUCs) ranging from 0.62 to 0.65 for the ROC curves. The responsiveness of the 14-item survey to the TESS LE showed sensitivity of 96% and specificity of 90%, with an AUC of 0.98 (p < 0.001). The responsiveness of the 14 items to the LEFS showed sensitivity of 95% and specificity of 86%, with an AUC of 0.96. The validity of the 14 items to the TESS LE was measured by concordance, with a precision of 0.98 and an accuracy of 0.97. Concordance of the 14 items to the LEFS showed a precision of 0.98 and accuracy of 0.83., Conclusion: The concise 14 items derived from patient-reported responses in the TESS LE and LEFS outcome measures showed similar responsiveness (sensitivity and specificity) as the original TESS LE and LEFS for cancer patients after lower extremity orthopaedic surgery performed for oncologic and nononcologic indications. The concise 14 items have a similar ability to the TESS LE and LEFS to tell the clinician or patient how they are functioning compared with other patients. These 14 items are shorter than the combined 50 items of the TESS LE and LEFS while retaining the capacity to describe a broad range of lower extremity function for orthopaedic oncology patients. We have named the 14-item survey the Lower Extremity Oncology Functional Assessment Tool (LEO).Level of Evidence Level II, diagnostic study., Competing Interests: Each author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research ® editors and board members are on file with the publication and can be viewed on request., (Copyright © 2024 by the Association of Bone and Joint Surgeons.)

Introduction: In this study, we evaluate the association between sociodemographics and disease presentation, treatment, and survival for children, adolescents, and young adults with Ewing sarcoma., Methods: Case-level data were downloaded from The Surveillance, Epidemiology, and End Results database. Cases included patients ages 0-24 who were diagnosed with Ewing sarcoma between 2004 and 2020., Results: One thousand two hundred forty four patients were included in the analysis. When compared to non-Hispanic White (NHW) patients, Hispanic patients were more likely to present with tumors ≥8 cm (odds ratio (OR) = 1.71, 95% confidence interval (CI) = 1.24-2.36) and metastases (OR = 1.65, 95% CI = 1.23-2.20). Black patients were less likely to receive chemotherapy (OR = 0.25, 95% CI = 0.07-0.97). The 5-year disease-specific survival rate was 73% for NHW patients, 65% for Black patients, 67% for Asian patients and 66% for Hispanic patients. When accounting for confounding factors, Hispanic and Asian patients had higher probabilities of death due to cancer compared to NHW patients (HR = 1.41, 95% CI = 1.10-1.81; HR = 1.64, 95% CI = 1.09-2.48, respectively). Young adults and adolescents were significantly more likely to present with metastases, experience ≥1 month between diagnosis and treatment, and had lower survival., Conclusions: Significant differences in Ewing sarcoma presentation, treatment, and survival were observed across age groups and race/ethnicity. Future work should focus on expanding access to care in underserved groups. Further qualitative studies could assist in determining the exact factors that prevent patients from accessing care or examine how genetic factors that contribute to Ewing sarcoma severity differ across demographic groups., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Renal cell carcinoma (RCC) bone metastatis progression is driven by crosstalk between tumor cells and the bone microenvironment, which includes osteoblasts, osteoclasts, and osteocytes. RCC bone metastases (RCCBM) are predominantly osteolytic and resistant to antiresorptive therapy. The molecular mechanisms underlying pathologic osteolysis and disruption of bone homeostasis remain incompletely understood. We previously reported that BIGH3/TGFBI (transforming growth factor-beta-induced protein ig-h3, shortened to BIGH3 henceforth) secreted by colonizing RCC cells drives osteolysis by inhibiting osteoblast differentiation, impairing healing of osteolytic lesions, which is reversible with osteoanabolic agents. Here, we report that BIGH3 induces osteocyte apoptosis in both human RCCBM tissue specimens and in a preclinical mouse model. We also demonstrate that BIGH3 reduces Cx43 expression, blocking gap junction (GJ) function and osteocyte network communication. BIGH3-mediated GJ inhibition is blocked by the lysosomal inhibitor hydroxychloroquine (HCQ), but not osteoanabolic agents. Our results broaden the understanding of pathologic osteolysis in RCCBM and indicate that targeting the BIGH3 mechanism could be a combinational strategy for the treatment of RCCBM-induced bone disease that overcomes the limited efficacy of antiresorptives that target osteoclasts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Pelvic metastasis is a common presentation among patients presenting with skeletal metastasis. Image-guided percutaneous cementation of these lesions is becoming increasingly popular for the treatment of these lesions. The objective of this study was to conduct a systematic review that investigates clinical outcomes after percutaneous cementation for pelvic metastasis., Methods: A systematic review was registered with International Prospective Register of Systematic Reviews and performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using the PubMed, SCOPUS, and Ovid MEDLINE databases. All level I to IV clinical studies published in the English language investigating the clinical outcomes after percutaneous cementation for pelvic metastasis were included., Results: Fourteen studies with 579 patients (278 men, 301 women) and 631 metastatic pelvic lesions were included in the study. The mean follow-up range was 0.7 to 26.4 months. Percutaneous cementation alone was performed in 441 patients (76.2%). Supplemental ablative procedures were performed in 77 patients (13.3%), and supplemental internal fixation using cannulated screws was performed in 107 patients (18.5%). Twelve studies with 430 patients (74.2%) reported pain-related and/or functional outcome scores, of which all studies reported overall clinically notable improvement at short-term follow-up. All studies reported periprocedural complications. Local cement leakage was the most common complication (162/631 lesions, 25.7%) followed by transient local pain (25/579 patients, 4.3%). There were no reported cases of major complications. Seven patients (1.2%) underwent re-intervention for persistent symptoms., Conclusions: Percutaneous cementation may be an effective method for treating pain and function related to pelvic metastasis. The most common complication was cement leakage surrounding the lesion. The rates of major complications were low, and most complications appeared minor and transient. Additional prospective studies are needed to further assess the efficacy of this procedure., Level of Evidence: IV, systematic review of level I to IV therapeutic studies., (Copyright © 2024 by the American Academy of Orthopaedic Surgeons.)

Purpose: Chondrosarcomas are the most common primary bone tumor in adults. Isocitrate dehydrogenase 1 (IDH1) and IDH2 mutations are prevalent. We aimed to assess the clinico-genomic properties of IDH mutant versus IDH wild-type (WT) chondrosarcomas as well as alterations in other genes., Experimental Design: We included 93 patients with conventional and dedifferentiated chondrosarcoma for which there were available clinical next-generation sequencing data. Clinical and genomic data were extracted and compared between IDH mutant and IDH WT chondrosarcomas and between TP53 mutant and TP53 WT chondrosarcomas., Results: IDH1 and IDH2 mutations are prevalent in chondrosarcoma (50.5%), more common in chondrosarcomas arising in the extremities, associated with higher age at diagnosis, and more common in dedifferentiated chondrosarcomas compared with grades 1-3 conventional chondrosarcoma. There was no difference in survival based on IDH mutation in univariate and multivariate analyses. TP53 mutation was the next most prevalent (41.9%) and is associated with worse overall survival and metastasis-free survival in both univariate and multivariate analyses. TP53 mutation was also associated with higher risk of recurrence following curative-intent surgery and worse survival among patients that presented with de novo metastatic disease., Conclusions: IDH mutations are prevalent in chondrosarcoma though were not associated with survival outcomes in this cohort. TP53 mutations were the next most common alteration and were associated with worse outcomes., (©2023 American Association for Cancer Research.)

Background: Large metastatic lesions of the diaphysis can cause considerable pain and result in difficult surgical challenges. Resection and cemented intercalary endoprosthetic reconstruction offer one solution to the problem, but it is an extensive operation that might not be tolerated well by a debilitated patient. The risk of aseptic loosening and revision after intercalary endoprosthetic replacement has varied in previous reports, which have not examined the risk of revision in the context of patient survival., Questions/purposes: (1) In a small case series from one institution, what is the survivorship of patients after cemented intercalary endoprosthetic replacement for diaphyseal metastasis, and what is the cumulative incidence of revision for any reason? (2) What are the complications associated with cemented intercalary reconstruction? (3) What is the functional outcome after the procedure as assessed by the MSTS93 score?, Methods: We retrospectively studied 19 patients with diaphyseal long bone metastases who were treated with resection and cemented intercalary endoprosthetic reconstruction by five participating surgeons at one referral center from 2006 to 2017. There were 11 men and eight women with a median age of 59 years (range 46 to 80 years). The minimum follow-up required for this series was 12 months; however, patients who reached an endpoint (death, radiographic loosening, or implant revision) before that time were included. One of these 19 patients was lost to follow-up but was not known to have died. The median follow-up was 24 months (range 0 to 116 months). Eight of the 19 patients presented with pathologic fractures. Ten of 19 lesions involved the femur, and nine of 19 were in the humerus. The most common pathologic finding was renal cell carcinoma (in 10 of 19). Survival estimates of the patients were calculated using the Kaplan-Meier method. A competing risks estimator was used to evaluate implant survival, using death of the patient as the competing risk. We also estimated the cumulative incidence of aseptic loosening in a competing risk analysis. Radiographs were analyzed for radiolucency at the bone-cement-implant interfaces, fracture, integrity of the cement mantle, and component position stability. Complications were assessed using record review that was performed by an individual who was not involved in the initial care of the patients. Functional outcomes were assessed using the MSTS93 scoring system., Results: Patient survivorship was 68% (95% CI 50% to 93%) at 1 year, 53% (95% CI 34% to 81%) at 2 years, and 14% (95% CI 4% to 49%) at 5 years; the median patient survival time after reconstruction was 25 months (range 0 to 116 months). In the competing risk analysis, using death as the competing risk, the cumulative incidence of implant revision was 11% (95% CI 2% to 29%) at 1 year and 16% (95% CI 4% to 36%) at 5 years after surgery; however, the cumulative incidence of aseptic loosening (with death as a competing risk) was 22% (95% CI 6% to 43%) at 1 year and 33% (95% CI 13% to 55%) at 5 years after surgery. Other complications included one patient who died postoperatively of cardiac arrest, one patient with delayed wound healing, two patients with bone recurrence, and one patient who experienced local soft tissue recurrence that was excised without implant revision. Total MSTS93 scores improved from a mean of 12.6 ± 8.1 (42% ± 27%) preoperatively to 21.5 ± 5.0 (72% ± 17%) at 3 months postoperatively (p < 0.001) and 21.6 ± 8.5 (72% ± 28%) at 2 years postoperatively (p = 0.98; 3 months versus 2 years)., Conclusion: Resection of diaphyseal metastases with intercalary reconstruction can provide stability and short-term improvement in function for patients with advanced metastatic disease and extensive cortical destruction. Aseptic loosening is a concern, particularly in the humerus; however, the competing risk analysis suggests the procedure is adequate for most patients, because many in this series died of disease without undergoing revision., Level of Evidence: Level IV, therapeutic study ., Competing Interests: All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research ® editors and board members are on file with the publication and can be viewed on request., (Copyright © 2023 by the Association of Bone and Joint Surgeons.)

We present a review of several bone (osteoid)-forming tumors including enostosis, osteoid osteoma, osteoblastoma, and osteosarcoma. These entities were chosen because they are reasonably common-neither seen every day nor rare. When applicable, recent information about the lesions is included., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Type 1 internal hemipelvectomies and total sacrectomies cause significant biomechanical instability, demanding pelvic ring reconstruction for ambulation and torso support. Previously described methods include autografts, allografts, and implants, commonly with poor long-term outcomes. The authors hypothesized that the free fibula flap for spinopelvic reconstruction is safe and effective, and associated with a high bony union rate and superior functional outcomes., Methods: The authors performed a retrospective review of all patients who underwent free fibula flap surgery after internal hemipelvectomy or total sacrectomy at M. D. Anderson Cancer Center from 2003 to 2018. The primary outcome was radiographic evidence of bony union. Secondary outcomes included surgical-site occurrence and lower extremity function. Univariate and multivariate logistic regression analyses were performed., Results: Forty-seven patients were included (internal hemipelvectomy, n = 38; total sacrectomy, n = 9). The mean follow-up was 3.3 years and the most common abnormality was chondrosarcoma (30.4 percent). The nonunion rate was 9.7 percent and the surgical-site occurrence rate was 34 percent; there were no flap losses. Greater age was significantly associated with nonunion (OR, 1.1; 95 percent CI, 1 to 1.2; p = 0.003), whereas obesity was the only independent predictor of surgical-site occurrence (OR, 9.2; 95 percent CI, 1.2 to 71.3; p = 0.03). Functional metrics approached those of adult norms by 3 years postoperatively. Compared to internal hemipelvectomy patients, patients undergoing total sacrectomy had more comorbidities, a higher complication rate, and a worse functional outcome., Conclusion: The free fibula flap for spinopelvic reconstruction is safe and effective, and is associated with a high bony union rate and superior functional outcomes., Clinical Question/level of Evidence: Risk, III.

Importance: Consensus is lacking as to the optimal radiotherapy dose and fractionation schedule for treating bone metastases., Objective: To assess the relative efficacy of high-dose, single-fraction stereotactic body radiotherapy (SBRT) vs standard multifraction radiotherapy (MFRT) for alleviation of pain in patients with mostly nonspine bone metastases., Design, Setting, and Participants: This prospective, randomized, single-institution phase 2 noninferiority trial conducted at a tertiary cancer care center enrolled 160 patients with radiologically confirmed painful bone metastases from September 19, 2014, through June 19, 2018. Patients were randomly assigned in a 1:1 ratio to receive either single-fraction SBRT (12 Gy for ≥4-cm lesions or 16 Gy for <4-cm lesions) or MFRT to 30 Gy in 10 fractions., Main Outcomes and Measures: The primary end point was pain response, defined by international consensus criteria as a combination of pain score and analgesic use (daily morphine-equivalent dose). Pain failure (ie, lack of response) was defined as worsening pain score (≥2 points on a 0-to-10 scale), an increase in morphine-equivalent opioid dose of 50% or more, reirradiation, or pathologic fracture. We hypothesized that SBRT was noninferior to MFRT., Results: In this phase 2 noninferiority trial of 96 men and 64 women (mean [SD] age, 62.4 [10.4] years), 81 patients received SBRT and 79 received MFRT. Among evaluable patients who received treatment per protocol, the single-fraction group had more pain responders than the MFRT group (complete response + partial response) at 2 weeks (34 of 55 [62%] vs 19 of 52 [36%]) (P = .01), 3 months (31 of 43 [72%] vs 17 of 35 [49%]) (P = .03), and 9 months (17 of 22 [77%] vs 12 of 26 [46%]) (P = .03). No differences were found in treatment-related toxic effects or quality-of-life scores after SBRT vs MFRT; local control rates at 1 and 2 years were higher in patients receiving single-fraction SBRT., Conclusions and Relevance: Delivering high-dose, single-fraction SBRT seems to be an effective treatment option for patients with painful bone metastases. Among evaluable patients, SBRT had higher rates of pain response (complete response + partial response) than did MFRT and thus should be considered for patients expected to have relatively long survival., Trial Registration: ClinicalTrials.gov identifier: NCT02163226.

Background: Bone metastasis is common in renal cell carcinoma (RCC), and the lesions are mainly osteolytic. The mechanism of bone destruction in RCC bone metastasis is unknown., Methods: We used a direct intrafemur injection of mice with bone-derived 786-O RCC cells (Bo-786) as an in vivo model to study if inhibition of osteoblast differentiation is involved in osteolytic bone lesions in RCC bone metastasis., Results: We showed that bone-derived Bo-786 cells induced osteolytic bone lesions in the femur of mice. We examined the effect of conditioned medium of Bo-786 cells (Bo-786 CM) on both primary mouse osteoblasts and MC3T3-E1 preosteoblasts and found that Bo-786 CM inhibited osteoblast differentiation. Secretome analysis of Bo-786 CM revealed that BIGH3 (Beta ig h3 protein), also known as TGFBI (transforming growth factor beta-induced protein), is highly expressed. We generated recombinant BIGH3 and found that BIGH3 inhibited osteoblast differentiation in vitro. In addition, CM from Bo-786 BIGH3 knockdown cells (786-BIGH3 KD) reduced the inhibition of osteoblast differentiation compared to CM from vector control. Intrafemural injection of mice with 786-BIGH3 KD cells showed a reduction in osteolytic bone lesions compared to vector control. Immunohistochemical staining of 18 bone metastasis specimens from human RCC showed strong BIGH3 expression in 11/18 (61%) and moderate BIGH3 expression in 7/18 (39%) of the specimens., Conclusions: These results suggest that suppression of osteoblast differentiation by BIGH3 is one of the mechanisms that enhance osteolytic lesions in RCC bone metastasis, and raise the possibilty that treatments that increase bone formation may improve therapy outcomes., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Patients with primary bone and soft tissue sarcoma are at risk for skeletal metastases. Although uncommon, these metastases can result in impending or pathologic fractures. Intramedullary nailing traditionally has been an accepted form of palliative treatment for patients with metastatic carcinoma, but we could find no studies that report specifically on intramedullary nailing of metastatic sarcoma lesions., Questions/purposes: We asked: (1) What is the survival of patients with an impending or pathologic fracture from a sarcoma metastasis? (2) What proportion of patients treated with intramedullary nailing subsequently underwent a revision procedure or nail removal during their lifetimes?, Methods: Between 1996 and 2014, we performed 40 intramedullary nailing procedures in 34 patients with multifocal metastases from sarcomas who showed signs or symptoms of impending fracture or who presented with a pathologic fracture. All of these patients are accounted for, either through the time of death or to the present, and all are included at a mean of 13 months (range, 0.3-86 months) in this retrospective study. During the study period, we generally applied the same surgical indications for patients with nailing of metastatic sarcoma lesions as we did for patients with metastatic carcinoma; in general, we used intramedullary nailing (with or without cement) rather than resection for diaphyseal lesions with less cortical destruction and no substantial soft tissue mass or metadiaphyseal lesions that could be adequately supplemented with cementation. The goal was to use this approach when it would allow immediate weightbearing, or in patients whose medical conditions were such that a more-extensive procedure seemed unsafe. During the same period, an additional 58 patients underwent resection procedures for metastatic sarcomas to long bones because they either did not meet the above indications, had a solitary resectable metastasis, or because of surgeon preference; these patients were excluded from this study. The median age of the patients was 52 years (range, 27-81 years). Eleven patients with 11 impending or pathologic fractures were documented to have received either preoperative or postoperative radiation therapy and 29 patients received some form of chemotherapy., Results: Thirty (88%) patients died during the period of observation, at a median of 5 months (range, 0.3-80 months) after surgery. Twenty-nine patients (85%) underwent no additional surgery and retained their original intramedullary nail. One patient (3%) underwent nail removal for infection, and four patients (12%) underwent further surgical revision secondary to local progression., Conclusions: Patients with an impending or pathologic fracture from multifocal metastatic sarcoma to a long bone have a dismal prognosis, but they may gain short-term benefit from surgical fixation with the goal of reducing pain and maintaining mobility. Although we have no group for comparison, such as treating with radiotherapy alone or resection and an endoprosthesis, our findings suggest that use of intramedullary nails is helpful for providing fixation that in most instances lasts for the lifetime of patients with multifocal bone metastases from sarcomas., Level of Evidence: Level IV, therapeutic study.

Bone tumor surgery is extremely challenging, particularly when tumors are located in tightly confined anatomical areas and abutting critical organs and neurovascular structures. Tumor resection requires good cutting accuracy to ensure safety, to achieve negative margins, and to preserve critical structures when possible. The purpose of this paper was to review the literature on the surgical advances for bone tumor surgery published within the last year. The majority of literature identified focused on computer-assisted surgical approaches. There is increasing evidence that 3D navigation plays an important role in the resection of bone tumors. Reconstruction materials that encourage healing and prevent infections are also in development. Optimal care includes execution of a well-developed pre-operative plan using a multidisciplinary approach led by the orthopaedic oncologist.

An enchondroma with complex cystic changes of the proximal femur is described in a 13-year-old male. The case illustrates a unique presentation of an enchondroma and reinforces the importance of considering the presence of secondary aneurysmal bone cysts in both benign and malignant lesions of bone.