A dynamic microRNA profile that tracks a chemotherapy resistance phenotype in osteosarcoma. Implications for novel therapeutics.

Osteosarcoma is a rare primary bone tumor for which no significant therapeutic advancement has been made since the late 1980s despite ongoing efforts. Overall, the five-year survival rate remains about 65%, and is much lower in patients with tumors unresponsive to methotrexate, doxorubicin, and cisplatin therapy. Genetic studies have not revealed actionable drug targets, but our group, and others, have reported that epigenomic biomarkers, including regulatory RNAs, may be useful prognostic tools for osteosarcoma. We tested if microRNA (miRNA) transcriptional patterns mark the transition from a chemotherapy sensitive to resistant tumor phenotype. Small RNA sequencing was performed using 14 patient matched pre-chemotherapy biopsy and post-chemotherapy resection high-grade osteosarcoma frozen tumor samples. Independently, small RNA sequencing was performed using 14 patient matched biopsy and resection samples from untreated tumors. Separately, miRNA specific Illumina DASL arrays were used to assay an independent cohort of 65 pre-chemotherapy biopsy and 26 patient matched post-chemotherapy resection formalin fixed paraffin embedded (FFPE) tumor samples. mRNA specific Illumina DASL arrays were used to profile 37 pre-chemotherapy biopsy and five post-chemotherapy resection FFPE samples, all of which were also used for Illumina DASL miRNA profiling. The National Cancer Institute Therapeutically Applicable Research to Generate Effective Treatments dataset, including PCR based miRNA profiling and RNA-seq data for 86 and 93 pre-chemotherapy tumor samples, respectively, was also used. Paired differential expression testing revealed a profile of 17 miRNAs with significantly different transcriptional levels following chemotherapy. Genes targeted by the miRNAs were differentially expressed following chemotherapy, suggesting the miRNAs may regulate transcriptional networks. Finally, an in vitro pharmacogenomic screen using miRNAs and their target transcripts predicted response to a set of candidate small molecule therapeutics which potentially reverse the chemotherapy resistance phenotype and synergize with chemotherapy in otherwise treatment resistant tumors. Importantly, these novel therapeutic targets are distinct from targets identified by a similar pharmacogenomic analysis of previously published prognostic miRNA profiles from pre chemotherapy biopsy specimens.

Factors associated with skeletal-related events in patients with bone metastatic melanoma: A retrospective study of 481 patients.

OBJECTIVES: Metastatic bone disease is estimated to develop in up to 17% of patients with melanoma, compromising skeleton integrity resulting in skeletal-related events (SREs), which impair quality of life and reduce survival. The objective of the study was to investigate (1) the proportion of melanoma patients developing SREs following diagnosis of bone metastasis and (2) the predictors for SREs in this patient cohort. METHODS: Four hundred and eighty-one patients with bone metastatic melanoma from two tertiary centers in the United States from 2008 to 2018 were included. The primary outcome was 90-day and 1-year occurrence of a SRE, including pathological fractures of bones, cord compression, hypercalcemia, radiotherapy, and surgery. Fine-Gray regression analysis was performed for overall SREs and pathological fracture, with death as a competing risk. RESULTS: By 1-year, 52% (258/481) of patients experienced SREs, and 28% (137/481) had a pathological fracture. At 90-day, lytic lesions, bone pain, elevated calcium and absolute lymphocyte, and decreased albumin and hemoglobin were associated with higher SRE risk. The same factors, except for decreased hemoglobin, were shown to predict development of SREs at 1-year. CONCLUSION: The high incidence of SREs and pathological fractures warrants vigilance using the identified factors in this study and preventative measures during clinical oncological care.

Debridement, Antibiotics, and Implant Retention (DAIR) Plus Offers Similar Periprosthetic Joint Infection Treatment Success Rates to Two-Stage Revision in Oncologic Megaprosthesis.

BACKGROUND: Prosthetic joint infections (PJIs) after megaprosthesis implantation are associated with high rates of treatment failure and amputation. Our study analyzed PJI treatment success rates by surgical strategy and assessed risks of reinfection and amputation. METHODS: We retrospectively analyzed the outcomes of patients diagnosed with PJI after undergoing megaprosthesis implantation for oncologic indications. The 2011 Musculoskeletal Infection Society criteria were used to define PJI. Reinfection, reoperation, and amputation for PJI recurrence were assessed. A total of 67 patients with megaprosthesis PJIs were included. There were fourteen patients who were treated with debridement, antibiotics, and implant retention (DAIR), 31 with DAIR plus (DAIR with modular component exchange and stem retention), and 21 with two-stage revisions. Kaplan-Meier estimates were used for survival analyses and Cox proportional hazards for risk factor analyses. RESULTS: The two-year reinfection-free survival was 25% for DAIR and 60% for DAIR plus or two-stage revision (P = .049). The five-year amputation-free survival was 84% for DAIR plus or two-stage revision, and 48% for DAIR (P = .13). Reinfection-free, reoperation-free, and amputation-free survival were similar between DAIR plus and two-stage revision at the 2- and 5-year marks. Body mass index ≥30 (hazard ratio [HR] = 2.65) and chronic kidney disease (HR = 11.53) were risk factors for reinfection. Treatment with DAIR plus or two-stage revision (HR = 0.44) was a protective factor against reinfection. CONCLUSIONS: A DAIR was associated with high rates of treatment failure and higher amputation rates than DAIR plus or 2-stage surgery. A DAIR plus was not inferior to 2-stage revision clearing a PJI and might be performed in patients who cannot withstand two-stage revision surgery.

Dual Mobility for Oncological Hip Reconstruction: Significantly Reduced Dislocation Rates at 5 years.

BACKGROUND: Although dual mobility total hip arthroplasty has become increasingly common in recent years, limited remains known on dual mobility in surgical oncology. This university-based investigation compared dislocation and revision rates of DMs, conventional total hip arthroplasty (THA), and hemiarthroplasties (HAs) for oncological hip reconstruction. METHODS: An institutional tumor registry was used to identify 221 patients undergoing 45 DMs, 67 conventional THAs, and 109 HAs, performed for 17 primary hip tumors and 204 hip metastases between 2010 and 2020. The median age at surgery was 65 years, and 52% were female. The mean follow-up was 2.5 years. Kaplan-Meier survivorship curves and log-rank tests were done to compare dislocation and revision rates among all 221 patients, after a one-to-one propensity match, based on age, sex, tumor type (metastasis, primary tumor), and tumor localization (femur, acetabulum). RESULTS: The 5-year survivorship free of dislocation was 98% in DMs, 66% in conventional THAs ( P = 0.03; all P values compared with DMs), and 97% among HAs ( P = 0.48). The 5-year survivorship free of revision was 69% in DMs, 62% in conventional THAs ( P = 0.68), and 92% in HAs ( P = 0.06). After propensity matching, the 5-year survivorship free of dislocation was 42% in 45 conventional THAs ( P = 0.027; compared with all 45 DMs) and 89% in 16 matched HAs ( P = 0.19; compared with 16 DMs with femoral involvement only). The 5-year survivorship free of revision was 40% in matched conventional THAs ( P = 0.91) and 100% in matched HAs ( P = 0.19). CONCLUSIONS: DMs showed markedly lower rates of dislocation than conventional THAs, with overall revision rates remaining comparable among different designs. DMs should be considered the option of choice for oncological hip reconstruction if compared with conventional THAs. HAs are a feasible alternative when encountering femoral disease involvement only. LEVEL OF EVIDENCE: III.

Prediction of 5-year survival in soft tissue leiomyosarcoma using a machine learning model algorithm.

BACKGROUND AND OBJECTIVES: Leiomyosarcoma (LMS) is associated with one of the poorest overall survivals among soft tissue sarcomas. We sought to develop and externally validate a model for 5-year survival prediction in patients with appendicular or truncal LMS using machine learning algorithms. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used for development and internal validation of the models; external validation was assessed using our institutional database. Five machine learning algorithms were developed and then tested on our institutional database. Area under the receiver operating characteristic curve (AUC) and Brier score were used to assess model performance. RESULTS: A total of 2209 patients from the SEER database and 81 patients from our tertiary institution were included. All models had excellent calibration with AUC 0.84-0.85 and Brier score 0.15-0.16. After assessing the performance indicators according to the TRIPOD model, we found that the Elastic-Net Penalized Logistic Regression outperformed other models. The AUCs of the institutional data were 0.83 (imputed) and 0.85 (complete-case analysis) with a Brier score of 0.16. CONCLUSION: Our study successfully developed five machine learning algorithms to assess 5-year survival in patients with LMS. The Elastic-Net Penalized Logistic Regression retained performance upon external validation with an AUC of 0.85 and Brier score of 0.15.

Does the SORG Machine-learning Algorithm for Extremity Metastases Generalize to a Contemporary Cohort of Patients? Temporal Validation From 2016 to 2020.

BACKGROUND: The ability to predict survival accurately in patients with osseous metastatic disease of the extremities is vital for patient counseling and guiding surgical intervention. We, the Skeletal Oncology Research Group (SORG), previously developed a machine-learning algorithm (MLA) based on data from 1999 to 2016 to predict 90-day and 1-year survival of surgically treated patients with extremity bone metastasis. As treatment regimens for oncology patients continue to evolve, this SORG MLA-driven probability calculator requires temporal reassessment of its accuracy. QUESTION/PURPOSE: Does the SORG-MLA accurately predict 90-day and 1-year survival in patients who receive surgical treatment for a metastatic long-bone lesion in a more recent cohort of patients treated between 2016 and 2020? METHODS: Between 2017 and 2021, we identified 674 patients 18 years and older through the ICD codes for secondary malignant neoplasm of bone and bone marrow and CPT codes for completed pathologic fractures or prophylactic treatment of an impending fracture. We excluded 40% (268 of 674) of patients, including 18% (118) who did not receive surgery; 11% (72) who had metastases in places other than the long bones of the extremities; 3% (23) who received treatment other than intramedullary nailing, endoprosthetic reconstruction, or dynamic hip screw; 3% (23) who underwent revision surgery, 3% (17) in whom there was no tumor, and 2% (15) who were lost to follow-up within 1 year. Temporal validation was performed using data on 406 patients treated surgically for bony metastatic disease of the extremities from 2016 to 2020 at the same two institutions where the MLA was developed. Variables used to predict survival in the SORG algorithm included perioperative laboratory values, tumor characteristics, and general demographics. To assess the models' discrimination, we computed the c-statistic, commonly referred to as the area under the receiver operating characteristic (AUC) curve for binary classification. This value ranged from 0.5 (representing chance-level performance) to 1.0 (indicating excellent discrimination) Generally, an AUC of 0.75 is considered high enough for use in clinical practice. To evaluate the agreement between predicted and observed outcomes, a calibration plot was used, and the calibration slope and intercept were calculated. Perfect calibration would result in a slope of 1 and intercept of 0. For overall performance, the Brier score and null-model Brier score were determined. The Brier score can range from 0 (representing perfect prediction) to 1 (indicating the poorest prediction). Proper interpretation of the Brier score necessitates a comparison with the null-model Brier score, which represents the score for an algorithm that predicts a probability equal to the population prevalence of the outcome for each patient. Finally, a decision curve analysis was conducted to compare the potential net benefit of the algorithm with other decision-support methods, such as treating all or none of the patients. Overall, 90-day and 1-year mortality were lower in the temporal validation cohort than in the development cohort (90 day: 23% versus 28%; p < 0.001, and 1 year: 51% versus 59%; p<0.001). RESULTS: Overall survival of the patients in the validation cohort improved from 28% mortality at the 90-day timepoint in the cohort on which the model was trained to 23%, and 59% mortality at the 1-year timepoint to 51%. The AUC was 0.78 (95% CI 0.72 to 0.82) for 90-day survival and 0.75 (95% CI 0.70 to 0.79) for 1-year survival, indicating the model could distinguish the two outcomes reasonably. For the 90-day model, the calibration slope was 0.71 (95% CI 0.53 to 0.89), and the intercept was -0.66 (95% CI -0.94 to -0.39), suggesting the predicted risks were overly extreme, and that in general, the risk of the observed outcome was overestimated. For the 1-year model, the calibration slope was 0.73 (95% CI 0.56 to 0.91) and the intercept was -0.67 (95% CI -0.90 to -0.43). With respect to overall performance, the model's Brier scores for the 90-day and 1-year models were 0.16 and 0.22. These scores were higher than the Brier scores of internal validation of the development study (0.13 and 0.14) models, indicating the models' performance has declined over time. CONCLUSION: The SORG MLA to predict survival after surgical treatment of extremity metastatic disease showed decreased performance on temporal validation. Moreover, in patients undergoing innovative immunotherapy, the possibility of mortality risk was overestimated in varying severity. Clinicians should be aware of this overestimation and discount the prediction of the SORG MLA according to their own experience with this patient population. Generally, these results show that temporal reassessment of these MLA-driven probability calculators is of paramount importance because the predictive performance may decline over time as treatment regimens evolve. The SORG-MLA is available as a freely accessible internet application at https://sorg-apps.shinyapps.io/extremitymetssurvival/ .Level of Evidence Level III, prognostic study.

Venous Thromboembolic Event Following Soft Tissue Sarcoma Diagnosis is Associated with the Development of Pulmonary Metastasis.

BACKGROUND: This study aimed to investigate whether venous thromboembolic events (VTEs) are clinically relevant predictors of pulmonary metastatic disease in patients with soft tissue sarcomas (STSs). PATIENTS AND METHODS: In this retrospective cohort analysis, we included patients with STS surgically treated for sarcoma between January 2002 and January 2020. The primary outcome of interest was development of pulmonary metastasis after non-metastatic STS diagnosis. Tumor depth, stage, type of surgical intervention, chemotherapy, radiation therapy, body mass index, and smoking status were collected. Episodes of VTEs following STS diagnosis, including deep vein thrombosis, pulmonary embolism, and other thromboembolic events, were also obtained. Univariate analyses and multivariable logistic regression were used to identify potential predictors for pulmonary metastasis. RESULTS: We included 319 patients with mean age of 54.9 ± 16 years. Thirty-seven patients (11.6%) had VTE after STS diagnosis, and 54 (16.9%) developed pulmonary metastasis. Univariate screening revealed pulmonary metastasis, pre- and postoperative chemotherapy, smoking history, and VTE after surgery as potential predictors of pulmonary metastasis. Multivariable logistic regression revealed smoking history [odds ratio (OR) 2.0, confidence interval (CI) 1.1-3.9, P = 0.04] and VTE (OR 6.3, CI 2.9-13.6, P < 0.001) as independent risk factors for predicting pulmonary metastasis in patients with STS, after adjusting for the factors in the univariate screening as well as age, sex, stage of the tumor, and neurovascular invasion. CONCLUSIONS: Patients with VTE after STS diagnosis have an odds ratio of 6.3 for developing metastatic pulmonary disease compared with patients without venous thromboembolic events. Smoking history was also associated with future pulmonary metastases.

Prognostic Significance of Percentage and Size of Dedifferentiation in Dedifferentiated Chondrosarcoma.

Dedifferentiated chondrosarcoma is rare, aggressive, and microscopically bimorphic. How pathologic features such as the amounts of dedifferentiation affect prognosis remains unclear. We evaluated the percentages and sizes of dedifferentiation in a consecutive institutional series of dedifferentiated chondrosarcomas from 1999 to 2021. The statistical analysis included cox proportional hazard models and log-rank tests. Of the 67 patients (26 women, 41 men; age, 39 to >89 [median 61] years; 2 with Ollier disease), 58 presented de novo; 9 were identified with conventional chondrosarcomas 0.6-13.2 years (median, 5.5 years) prior. Pathologic fracture and distant metastases were noted in 27 and 7 patients at presentation. The tumors involved the femur (n = 27), pelvis (n = 22), humerus (n = 7), tibia (n = 4), scapula/ribs (n = 4), spine (n = 2), and clivus (n = 1). In the 56 resections, the tumors ranged in size from 3.5 to 46.0 cm (median, 11.5 cm) and contained 1%-99.5% (median, 70%) dedifferentiated components that ranged in size from 0.6 to 24.0 cm (median, 7.3 cm). No correlation was noted between total size and percentage of dedifferentiation. The dedifferentiated components were typically fibrosarcomatous or osteosarcomatous, whereas the associated cartilaginous components were predominantly grade 1-2, rarely enchondromas or grade 3. The entire cohort's median overall survival and progression-free survival were 11.8 and 5.4 months, respectively. In the resected cohort, although the total size was not prognostic, the percentage of dedifferentiation ≥20% and size of dedifferentiation >3.0 cm each predicted worse overall survival (9.9 vs 72.5 months; HR, 3.76; 95% CI, 1.27-11.14; P = .02; 8.7 vs 58.9 months; HR, 3.03; 95% CI, 1.21-7.57; P = .02, respectively) and progression-free survival (5.3 vs 62.1 months; HR, 3.05; 95% CI, 1.13-8.28; P = .03; 5.3 vs 56.6 months; HR, 2.50; 95% CI, 1.06-5.88; P = .04, respectively). In conclusion, both the percentages and sizes of dedifferentiation were better prognostic predictors than total tumor sizes in dedifferentiated chondrosarcomas, highlighting the utility of their pathologic evaluations.

Predictors of Symptomatic Venous Thromboembolism in Patients with Soft Tissue Sarcoma in the Lower Extremity.

Orthopedic surgery and soft-tissue sarcoma (STS) both independently increase the risk of developing symptomatic venous thromboembolic events (SVTE), but there are no established risk factors or guidelines for how to prophylactically treat patients with STS undergoing surgery. The objectives of this study were to (1) identify the prevalence of SVTE in patients undergoing STS surgery, (2) identify risk factors for SVTE, and (3) determine the risk of wound complications associated with VTE prophylaxis. This retrospective study was conducted in a tertiary level, academic hospital. A total of 642 patients were treated for soft-tissue sarcoma in the lower extremity with follow up for at least 90 days for the development of SVTE such as deep venous thrombosis and pulmonary embolism. Multivariate logistic regression was used to identify predictors for these events by controlling for patient characteristics, surgical characteristics, and treatment variables, with significance held at p < 0.05. Twenty eight patients (4.36%) were diagnosed with SVTE. Multivariate analysis found six significant predictors ordered based on standardized coefficients: pre-operative (PTT) partial thromboplastin time (p < 0.001), post-operative PTT (p = 0.010), post-op chemotherapy (p = 0.013), metastasis at diagnosis (p = 0.025), additional surgery for metastasis or local recurrence (p = 0.004), and tumor size larger than 10 cm (p < 0.001). The risk of wound complications (p = 0.04) and infection (p = 0.017) increased significantly in patients who received chemical prophylaxis. Our study identifies risk factors for patients at increased risk of developing VTE. Further prospective research is necessary to identify which protocols would be beneficial in preventing SVTE in high-risk patients with a low profile of wound complications.

What Are the Functional and Surgical Outcomes of Tibial Turnup-plasty for Salvage in Patients With Chronic Lower Extremity Infection?

BACKGROUND: Tibial turnup-plasty is a rarely performed surgical option for large bone defects of the distal or entire femur and can serve as an alternative to hip disarticulation or high above-knee amputation. It entails pedicled transport of the ipsilateral tibia with or without the proximal hindfoot for use as a vascularized autograft. It is rotated 180° in the coronal or sagittal plane to the remaining proximal femur or pelvis, augmenting the functional length of the thigh. Prior reports consist of small case series with heterogeneous surgical techniques. Patient-reported outcome measures after the procedure have not been reported, and ambulatory status after the procedure is also unknown. QUESTIONS/PURPOSES: (1) What proportion of patients underwent reoperation after tibial turnup-plasty? (2) What is the ambulatory status and what proportion of patients used a prosthesis after tibial turnup-plasty? (3) What are the Patient-Reported Outcome Measurement Information System (PROMIS) Global-10 mental and physical function scores after tibial turnup-plasty? METHODS: A retrospective analysis was performed of 11 patients who underwent tibial turnup-plasty between 2003 and 2021 by a single orthopaedic oncology division in collaboration with a reconstructive plastic surgery team. Nine patients were men, with a median age of 55 years (range 34 to 75 years). All had chronic infections after arthroplasty or oncologic reconstructions, with a median number of 13 surgeries before turnup-plasty. All were considered to have no other surgical options other than hip disarticulation or high transfemoral amputation. All patients who were offered this possibility accepted it. Data of interest included patient demographics and comorbidities, surgical history that led to limb compromise, medical and surgical perioperative complications, date of prosthesis fitting, and functional capacity at the most recent follow-up interval based on ambulatory status and PROMIS Global-10 mental and physical function scores. The statistical analysis was descriptive. RESULTS: The median number of reoperations after turnup-plasty was one (range 0 to 11). Of the six patients who underwent at least one reoperation, indications for surgery included wound infection (four patients), nonunion of the osteosynthesis site (two), heterotopic ossification (one), tumor recurrence (one), and flap hypoperfusion treated with local tissue revision (one). One patient underwent conversion to external hemipelvectomy for tumor recurrence. Ten of the 11 patients were ambulatory at the final follow-up interval with standard above-knee amputation prostheses. Two ambulated unassisted, four used a single crutch or cane, and four used two crutches or a walker. Of the nine patients for whom scores were available, the median PROMIS Global-10 physical and mental health scores were 48 (range 30 to 68) and 53 (range 41 to 68), both within the standard deviation of the population mean of 50. CONCLUSION: The tibial turnup-plasty is a complex surgical option for patients with large bone defects of the femur for whom there are no alternative surgeries capable of producing residual extremities with acceptable functional length. This should be viewed as a procedure of last resort to avoid a hip disarticulation or a high transfemoral amputation in patients who have typically undergone numerous prior operations. Although ambulation with a prosthesis within 1 year can be expected, almost all patients will require an assistive device to do so, and reoperations are frequent. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Metastatic Uterine Leiomyosarcoma With Rhabdomyosarcomatous Heterologous Differentiation.

Heterologous differentiation has only been previously reported twice in metastatic uterine leiomyosarcomas. We report herein the first case of metastatic uterine leiomyosarcoma with rhabdomyosarcomatous differentiation. A 67-yr-old woman presented with femur, abductor magnus, and lymph node metastases 9 yr after the primary diagnosis. The metastatic sites showed rhabdomyosarcomatous morphologic features, and immunohistochemical studies confirmed skeletal muscle differentiation. Molecular testing revealed the same loss-of-function TP53 mutation in the uterine leiomyosarcoma and metastatic sites supporting heterologous differentiation of the primary tumor. Our case highlights the morphologic shifts metastatic tumors may manifest and the potential diagnostic problems that may arise.

Trabecular metal augments in severe malignancy-associated acetabular bone loss.

INTRODUCTION: Acetabular reconstruction is a challenging problem in orthopaedic oncology, especially in extended defects (Paprosky Type 3A and Type 3B). In revision total hip arthroplasty (THA), 1 option is trabecular metal (TM) augments with a porous metal acetabular component. This study evaluated the use of TM augments in periacetabular malignant bone disease. METHODS: 15 patients were identified from our institutional database from 2000 to 2020 with either Paprosky Type 3A or Type 3B acetabular bone loss due to periacetabular malignancies that underwent at least 1 complex THA reconstruction with TM augments. Postoperative complications were documented, and clinical and radiographic outcomes were analysed. Radiological loosening or revision of the acetabular component were defined as endpoints. RESULTS: There were 7 primary and 8 metastatic cancer patients. 5 were Type 3A and 10 were Type 3B defects after tumour resection. The average follow-up time was 23.8 (range 1.5-47) months. 1 patient required revision for acetabular component loosening after 7 months from the initial implantation. An additional 4 patients required surgical intervention for infection, they had stable TM augments at latest follow-up. CONCLUSION: TM augments with a porous metal acetabular component may be an alternative to the traditional cemented constructs.

The impact of radiotherapy on survival after surgical resection of chordoma with minimum five-year follow-up.

BACKGROUND CONTEXT: Local control remains a vexing problem in the management of chordoma despite advances in operative techniques and radiotherapy (RT) protocols. Existing studies show satisfactory local control rates with different treatment modalities. However, those studies with minimum follow-up more than 4 years demonstrate increasing rates of local failure. Therefore, mid-term local survival rates may be inadvertently elevated by studies with less than 4 years follow-up. PURPOSE: The purpose of this study is to report the mid-term results of primary spinal chordoma treated with en bloc resection and proton-based RT with minimum 5 years of follow-up. STUDY DESIGN/SETTING: Retrospective, single-center, cohort study. PATIENT SAMPLE: Patients undergoing primary surgical excision of a spine or sacral chordoma tumor between 1990 and 2016 at a single-institution were included. Patients were included if they had a local failure at any time, or they had a minimum of 5 years of follow up with no local failure. Patients were excluded if a prior surgical excision was performed or metastases were present at the time of referral. OUTCOME MEASURES: The outcome measures were local recurrence-free interval (LRFI) and overall survival (OS). METHODS: Demographic, clinical, oncologic and surgical variables, including margin status, as well as radiation doses and schedule (neoadjuvant, adjuvant, or both) were compared using Wilcoxon rank-sum or chi-squared testing. The goal RT dose was 70 Gray (total) and patients were stratified based on completing (C70) or receiving incomplete (I70) dosing. Overall survival (OS) and local-recurrence free interval (LRFI) were calculated using the Kaplan-Meier method. FUNDING STATEMENT: No funding was obtained for this work. RESULTS: Seventy-six patients were included in the final analysis. All patients had a minimum of 5-year follow-up (median 9.3 years, range 5.1-24.7 years). There were no significant clinical differences between the C70 and I70 RT groups. OS was greater for the C70 RT group (5-year OS 82% vs. 63%, p=.001). There was similar OS for the positive margin group (5-year OS 70% vs. 61%, p=.266). LRFI was greater for the C70 RT group (5-year OS 93% vs. 78%, p=.017). There was similar LRFI for the positive margin group (5-year OS 90% versus 87%, p=.810). CONCLUSION: Chordoma outcomes trend towards diminishing LRFI rates in the literature. Here we report the results of the operative management of primary spinal chordoma with minimum five year follow-up, the addition of C70 RT to surgical excision conferred a benefit to OS and local recurrence.

Comparison of carbon fibre and titanium intramedullary nails in orthopaedic oncology.

AIMS: Due to their radiolucency and favourable mechanical properties, carbon fibre nails may be a preferable alternative to titanium nails for oncology patients. We aim to compare the surgical characteristics and short-term results of patients who underwent intramedullary fixation with either a titanium or carbon fibre nail for pathological long-bone fracture. METHODS: This single tertiary-institutional, retrospectively matched case-control study included 72 patients who underwent prophylactic or therapeutic fixation for pathological fracture of the humerus, femur, or tibia with either a titanium (control group, n = 36) or carbon fibre (case group, n = 36) intramedullary nail between 2016 to 2020. Patients were excluded if intramedullary fixation was combined with any other surgical procedure/fixation method. Outcomes included operating time, blood loss, fluoroscopic time, and complications. Fisher's exact test and Mann-Whitney U test were used for categorical and continuous outcomes, respectively. RESULTS: Patients receiving carbon nails as compared to those receiving titanium nails had higher blood loss (median 150 ml (interquartile range (IQR) 100 to 250) vs 100 ml (IQR 50 to 150); p = 0.042) and longer fluoroscopic time (median 150 seconds (IQR 114 to 182) vs 94 seconds (IQR 58 to 124); p = 0.001). Implant complications occurred in seven patients (19%) in the titanium group versus one patient (3%) in the carbon fibre group (p = 0.055). There were no notable differences between groups with regard to operating time, surgical wound infection, or survival. CONCLUSION: This pilot study demonstrates a non-inferior surgical and short-term clinical profile supporting further consideration of carbon fibre nails for pathological fracture fixation in orthopaedic oncology patients. Given enhanced accommodation of imaging methods important for oncological surveillance and radiation therapy planning, as well as high tolerances to fatigue stress, carbon fibre implants possess important oncological advantages over titanium implants that merit further prospective investigation. Level of evidence: III, Retrospective study Cite this article: Bone Jt Open 2022;3(8):648-655.

Primary and Metastatic Bone Tumors of the Patella: Literature Review and Institutional Experience.

Background: Patellar tumors are rare but certainly must be considered in the differential diagnosis in patients with knee pain. Diagnosis can be challenging as often patellar neoplasms are confused with benign conditions and their clinical presentation is usually not specific. We performed an institutional and a literature review to determine what are the most common tumors affecting the patella and what is the best management. Methods: This is a case series from our institution including all patients with benign, malignant, and metastatic patellar neoplasms. Charts were reviewed for patient demographics, clinical presentation, pathology characteristics, radiographic classification, and oncologic and functional outcomes. Results: Twenty-four patients were identified; twelve patients had benign lesions, 10 metastatic and 2 primary malignant tumors. Chondroblastoma and Giant Cell Tumor were the most common tumors. Management of benign lesions with intralesional curettage and packing with bone graft or cement demonstrated excellent results with no local recurrence. In terms of malignant tumors, the spectrum of treatment is variable; it could range from medical management alone or in combination with surgical procedures to total patellectomy with reconstruction of the extensor mechanism. Conclusion: Patellar tumors should be part of the differential in patients with chronic knee pain that does not respond to initial conservative interventions. Recurrence rate with intralesional curettage and bone grafting or cement packing is very low and therefore should be the treatment of choice for benign intraosseous neoplasms. Resection with negative margins in malignant neoplasms or bone metastasis decreases local recurrence but only in the former group there is a potential impact in survival.

Sclerostin immunohistochemical staining in surgically treated giant cell tumor of bone.

BACKGROUND: Giant cell tumor of bone (GCTB) is a destructive lesion with a high potential for recurrence. RANK-ligand targeted therapy has provided promising, yet mixed results. Sclerostin (SOST) inhibition results in a net anabolic response and is currently used in the treatment of osteoporosis. The application to GCTB is unknown. OBJECTIVES: We sought to determine if GCTB stained for SOST on immunohistochemistry and correlate its expression with predictor variables. METHODS: All patients at a single institution undergoing surgery for GCTB between 1993 and 2008 with a minimum of 6 months follow-up were included. Primary outcomes included the presence of SOST staining, secondary outcomes included the correlation of patient and tumor-specific predictor variables. RESULTS: SOST antibody staining of any cell type was present in 47 of 48 cases (97.9%). Positivity of the stromal cells was present in 39 of 48 cases (81.3%) and was associated with radiographic aggressiveness (p = 0.023), symptomatic presentation (p = 0.032), prior surgery (p = 0.005), and patient age (p = 0.034). Positivity of giant cells was present in 41 of 48 cases (85.4%) and was not significant with predictive factors. CONCLUSIONS: Sclerostin staining in GCTB is a novel finding and warrants further research to define the role of sclerostin as a prognostic factor and therapeutic target.

Tumors and Tumorlike Conditions of Which Every Orthopaedic Surgeon Should Be Aware.

All orthopaedic surgeons during the course of their career will likely encounter both benign and malignant musculoskeletal neoplasms. Given the rarity of these entities and the stress conferred by diagnosing a tumor or tumorlike condition, many orthopaedic surgeons may benefit from a review of the contemporary treatment of such patients. Whether in the outpatient clinic or following a high-energy trauma, special attention should be given to concerning signs and symptoms that will aid in the workup of children and adults with a possible tumor. A thorough and logical workup in this manner will often lead to a definitive diagnosis such as metastatic bone disease or perhaps a benign lesion. In these instances, the informed general orthopaedic surgeon or subspecialist may choose to treat the patient independently. However, if the workup is inconclusive or if the diagnosis is even questionably malignant, referral to an orthopaedic oncologist should be sought as to avoid pitfalls in diagnosis and treatment.