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.

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.

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.

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.

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.

Assessing the Safety and Utility of Wound VAC Temporization of the Sarcoma or Benign Aggressive Tumor Bed Until Final Margins Are Achieved.

BACKGROUND: Local recurrence of microinvasive sarcoma or benign aggressive pathologies can be limb- and life-threatening. Although frozen pathology is reliable, tumor microinvasion can be subtle or missed, having an impact on surgical margins and postoperative radiation planning. The authors' service has begun to temporize the tumor bed after primary tumor excision with a wound vacuum-assisted closure (VAC) pending formal margin analysis, with coverage performed in the setting of final negative margins. METHODS: This retrospective analysis included all patients managed at a tertiary referral cancer center with VAC temporization after soft tissue sarcoma or benign aggressive tumor excision from 1 January 2000 to 1 January 2019 and at least 2 years of oncologic follow-up evaluation. The primary outcome was local recurrence. The secondary outcomes were distant recurrence, unplanned return to the operating room for wound/infectious indications, thromboembolic events, and tumor-related deaths. RESULTS: For 62 patients, VAC temporization was performed. The mean age of the patients was 62.2 ± 22.3 years (median 66.5 years; 95% confidence interval [CI] 61.7-72.5 years), and the mean age-adjusted Charlson Comorbidity Index was 5.3 ± 1.9. The most common tumor histology was myxofibrosarcoma (51.6%, 32/62). The mean volume was 124.8 ± 324.1 cm3, and 35.5% (22/62) of the cases were subfascial. Local recurrences occurred for 8.1% (5/62) of the patients. Three of these five patients had planned positive margins, and 17.7% (11/62) of the patients had an unplanned return to the operating room. No demographic or tumor factors were associated with unplanned surgery. CONCLUSIONS: The findings showed that VAC-temporized management of microinvasive sarcoma and benign aggressive pathologies yields favorable local recurrence and unplanned operating room rates suggestive of oncologic and technical safety. These findings will need validation in a future randomized controlled trial.

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.

Sclerostin Immunohistochemical Staining in Aggressive Maxillofacial Giant Cell Lesions: Initial Results and Potential Therapeutic Target.

INTRODUCTION: Maxillofacial (MF) giant cell lesions (GCLs) are benign, often locally aggressive lesions with potential for recurrence. Systemic treatments have included interferon alpha, calcitonin, bisphosphonates, and denosumab. Sclerostin (SOST) is typically thought to be a negative regulator of bone metabolism and anti-SOST agents have been used to treat osteoporosis; however, its role in central giant cell granuloma is unknown. The purpose of this study was to evaluate the expression of SOST in MF GCLs. MATERIALS AND METHODS: This was a retrospective study of patients with MF GCLs treated at a single institution between 1993 and 2008 with a minimum follow-up of 6 months. Representative tissue was used to create a tissue microarray and SOST immunohistochemical (IHC) staining and grading was performed. The primary outcomes were IHC staining of the stromal cells and giant cells. The secondary outcomes included correlation of IHC staining and patient predictor variables including clinically benign and aggressive lesions. All analyses were completed using univariate statistical tests. RESULTS: A total of 37 subjects were included (29 clinically aggressive and 8 clinically benign). Sclerostin staining was present in 30 of 37 subjects (81%). Of these, 22 (60%) had stromal cell staining and 28 (76%) had giant cell staining. The presence or absence of staining, of either cell type, was not associated with aggressiveness, presence of clinical symptoms, tumor size, previous interferon therapy, previous surgery, or the race or age of the patient. DISCUSSION: Maxillofacial GCLs have an overall high level of SOST staining; however, the role of SOST in treatment and prognosis is unknown and warrants further study.

Temporizing Wound VAC Dressing Until Final Negative Margins are Achieved Reduces Myxofibrosarcoma Local Recurrence.

BACKGROUND: The microinvasive nature of suprafascial myxofibrosarcoma reduces the accuracy of intraoperative margin assessment, and tumor bed resections after soft-tissue reconstruction are unreliable. In 2017, we began temporizing the excised tumor bed with a wound VAC, delaying soft-tissue coverage until final negative margins were achieved. We compare the oncologic/surgical outcomes of suprafascial myxofibrosarcomas managed with VAC temporization (VT) with single-stage excision/reconstruction (SS). METHODS: We retrospectively studied suprafascial myxofibrosarcomas managed from January 1, 2000 to January 1, 2019 for patients who received neoadjuvant or adjuvant radiation and had at least 2 years of oncologic follow-up at a tertiary referral cancer center. Our primary outcome was local recurrence. Comparisons were performed by using Fisher's exact test or Student's t test. A p value < 0.05 was considered significant. RESULTS: Fifty-three patients (18 VAC temporized, 35 single stage) were included. While VT patients were older (74.9 ± 10.2 vs. 63.9 ± 13.6, p = 0.003), treatment groups did not significantly differ with respect to comorbidity, tumor volume, stage and grade. VT patients had significantly fewer local recurrences (5.6% vs. 28.6% after SS, p = 0.048) and R1 resections that required an unplanned readmission for tumor bed reexcision (0% vs. 37.1% after SS, p = 0.002). VT required more total surgeries (2.8 ± 0.9 vs. 1.8 ± 0.9 for SS, p = 0.0002). Postoperative infectious and wound complications were equivalent. CONCLUSIONS: Our VAC temporization strategy had a significantly lower LR than SS treatment. While high quality multi-institutional validation is required, VT may represent a paradigm shift in the management of myxofibrosarcoma.

Identification of EWSR1-NFATC2 fusion in simple bone cysts.

AIMS: Simple bone cysts are benign intramedullary tumours primarily involving the long bones in skeletally immature individuals. Several mechanisms have been proposed for their pathogenesis. Although the diagnosis is typically straightforward, the interpretation can be problematic, because of superimposed fracture causing them to resemble aneurysmal bone cysts and other tumours. EWSR1-NFATC2 or FUS-NFATC2 fusions, which are characteristic of a subset of aggressive round cell sarcomas, have been recently detected in simple bone cysts. The aim of this study was to examine the clinicopathological and molecular features in a series of simple bone cysts. METHODS AND RESULTS: Using RNA-based next-generation sequencing and/or fluorescence in-situ hybridisation, we investigated the presence of EWSR1 or FUS rearrangements in nine simple bone cysts. The patients were five females and four males, aged 3-23 years (median, 14 years); the tumours ranged from 19 mm to 160 mm (median, 46 mm) in size, and involved the femur (n = 3), humerus (n = 2), fibula (n = 2), tibia (n = 1), and iliac wing (n =1). We identified three cases with EWSR1-NFATC2 fusion (showing identical breakpoints to those in EWSR1-NFATC2 sarcomas) and one additional case with FUS rearrangement. Unlike in EWSR1-NFATC2 sarcomas, immunohistochemical expression of NKX3.1 and NKX2.2 was absent in two simple bone cysts tested. CONCLUSIONS: More than 40% of simple bone cysts harbour genetic alterations confirming that they are neoplastic, investigation of EWSR1 and/or FUS rearrangement may help to distinguish simple bone cysts from mimics, and NFATC2 rearrangement is not pathognomonic of malignancy.

Low-dose preoperative radiation, resection, and reduced-field postoperative radiation for soft tissue sarcomas.

BACKGROUND AND OBJECTIVES: Radiotherapy (RT) enables conservative surgery for soft tissue sarcoma (STS). RT can be delivered either pre-operatively (PreRT) or postoperatively (PORT), yet in some patients, neither approach is fully satisfactory (e.g., urgent surgery or wound healing risk prevents PreRT, yet PORT alone cannot cover the entire surgical field). We hypothesized that, in such situations, low-dose PreRT (LD-PreRT) would decrease the risk of intraoperative tumor seeding and thus permit PORT to a reduced volume (covering the high-risk tumor bed but not all surgically manipulated tissues). METHODS: We identified a single-institution retrospective cohort of 78 patients treated with LD-PreRT (10-30 Gy), resection, and PORT between 1980 and 2018. RESULTS: At a median follow-up of 8.2 years, 8-year overall survival (OS) was 65.9%, disease-free survival (DFS) 50.5%, and local control (LC) 76.7%; in 45 patients with extremity/superficial trunk (E/ST) STS, 8-year LC was 80.9%. Both before and after propensity score adjustment, there were no differences in OS, DFS, or LC between this cohort and a separate cohort of 394 STS (221 E/ST-STS) patients treated with surgery and PORT alone. CONCLUSIONS: In patients for whom neither PreRT nor PORT alone is optimal, LD-PreRT may prevent intraoperative tumor seeding and enable PORT to a reduced volume while preserving oncologic outcomes.

Adjunct diagnostic strategies in improving diagnostic yields in image-guided biopsies of musculoskeletal neoplasms-A cost-effectiveness analysis.

BACKGROUND: Routine use of adjunct intraprocedural fresh frozen biopsy (FFP) or point-of-care (POC) cytology at the time of image-guided biopsy can improve diagnostic tissue yields for musculoskeletal neoplasms, but these are associated with increased costs. OBJECTIVE: This study aimed to ascertain the most cost-effective adjunctive test for image-guided biopsies of musculoskeletal neoplasms. METHODS: This expected value cost-effectiveness microsimulation compared the payoffs of cost (2020 United States dollars) and effectiveness (quality-adjusted life, in days) on each of the competing strategies. A literature review and institutional data were used to ascertain probabilities, diagnostic yields, utility values, and direct medical costs associated with each strategy. Payer and societal perspectives are presented. One- and two-way sensitivity analyses evaluated model uncertainties. RESULTS: The total cost and effectiveness for each of the strategies were $1248.98, $1414.09, $1980.53, and 80.31, 79.74, 79.69 days for the use of FFP, permanent pathology only, and POC cytology, respectively. The use of FFP dominated the competing strategies. Sensitivity analyses revealed FFP as the most cost-effective across all clinically plausible values. CONCLUSIONS: Adjunct FFP is most cost-effective in improving the diagnostic yield of image-guided biopsies for musculoskeletal neoplasms. These findings are robust to sensitivity analyses using clinically plausible probabilities.

Surface osteosarcoma: Predictors of outcomes.

BACKGROUND AND OBJECTIVES: The subtypes of surface osteosarcomas include well-differentiated, low-grade parosteal osteosarcoma (POS), intermediate-grade periosteal osteosarcoma (PerOS), high-grade surface osteosarcoma (HGSO), and high-grade, dedifferentiated POS (dPOS). We aimed to determine disease progression, defined as local recurrence and metastatic disease, and overall (OS) and disease-specific survival (DSS). We identify outcome predictive factors and report functional results. METHODS: This retrospective study evaluated patients with primary surface osteosarcoma at our hospital from 1992 to 2019. Fifty-one patients had a median follow-up of 6.1 years (range: 0.1-25.2). Histologic subtypes included 32 POS, 11 PerOS, 4 HGSO, and 3 dPOS. Bone and soft tissue margins were classified using the American Joint Committee on Cancer residual tumor classification (Rx = Not evaluable; R0 = negative margin; R1 = microscopic positive margin; and R2 = macroscopic positive margin) and the modified R classification (mRx = not evaluable; mR0 = negative margin >1 mm; mR1 = negative margin ≤1 mm; mR1-dir: Positive microscopic margin locally; mR2a: Positive macroscopic margin locally; mR2b: positive macroscopic margin distally; and mR2C: positive macroscopic margin locally and distally). Forty-one patients had functional outcomes. RESULTS: Three POS patients developed recurrence: two had R0 margins and one an intralesional resection. Five patients developed lung metastases (POS: 3, dPOS: 2). Four patients died. The only significant disease progression predictor was age. OS at 10 years was 97%. 48 patients had negative bone margins (R0 or mR0 and mR1) and 47 patients had negative soft-tissue margins (R0 or mR0 and mR1). The average MSTS score was 88.43 (range: 34.29-100). CONCLUSIONS: We advocate surgery for POS and believe R0 (mR0 and mR1 resections) or planned R1 (mR1-dir) to preserve function are acceptable. We favor chemotherapy and surgery for PerOS, though a chemotherapeutic response is highly variable. High-grade tumors are the most infrequent subtype, but HGSO and dPOS seem to portend a poorer prognosis. Good function can be obtained.

Do Cohabitants Reliably Complete Questionnaires for Patients in a Terminal Cancer Stage when Assessing Quality of Life, Pain, Depression, and Anxiety?

BACKGROUND: Patients with bone metastases often are unable to complete quality of life (QoL) questionnaires, and cohabitants (such as spouses, domestic partners, offspring older than 18 years, or other people who live with the patient) could be a reliable alternative. However, the extent of reliability in this complicated patient population remains undefined, and the influence of the cohabitant's condition on their assessment of the patient's QoL is unknown. QUESTIONS/PURPOSES: (1) Do QoL scores, measured by the 5-level EuroQol-5D (EQ-5D-5L) version and the Patient-reported Outcomes Measurement Information System (PROMIS) version 1.0 in three domains (anxiety, pain interference, and depression), reported by patients differ markedly from scores as assessed by their cohabitants? (2) Do cohabitants' PROMIS-Depression scores correlate with differences in measured QoL results? METHODS: This cross-sectional study included patients and cohabitants older than 18 years of age. Patients included those with presence of histologically confirmed bone metastases (including lymphoma and multiple myeloma), and cohabitants must have been present at the clinic visit. Patients were eligible for inclusion in the study regardless of comorbidities, prognosis, prior surgery, or current treatment. Between June 1, 2016 and March 1, 2017 and between October 1, 2017 and February 26, 2018, all 96 eligible patients were approached, of whom 49% (47) met the selection criteria and were willing to participate. The included 47 patient-cohabitant pairs independently completed the EQ-5D-5L and the eight-item PROMIS for three domains (anxiety, pain, and depression) with respect to the patients' symptoms. The cohabitants also completed the four-item PROMIS-Depression survey with respect to their own symptoms. RESULTS: There were no clinically important differences between the scores of patients and their cohabitants for all questionnaires, and the agreement between patient and cohabitant scores was moderate to strong (Spearman correlation coefficients ranging from 0.52 to 0.72 on the four questionnaires; all p values < 0.05). However, despite the good agreement in QoL scores, an increased cohabitant's depression score was correlated with an overestimation of the patient's symptom burden for the anxiety and depression domains (weak Spearman correlation coefficient of 0.33 [95% confidence interval 0.08 to 0.58]; p = 0.01 and moderate Spearman correlation coefficient of 0.52 [95% CI 0.29 to 0.74]; p < 0.01, respectively). CONCLUSION: The present findings support that cohabitants might be reliable raters of the QoL of patients with bone metastases. However, if a patient's cohabitant has depression, the cohabitant may overestimate a patient's symptoms in emotional domains such as anxiety and depression, warranting further research that includes cohabitants with and without depression to elucidate the effect of depression on the level of agreement. For now, clinicians may want to reconsider using the cohabitant's judgement if depression is suspected. CLINICAL RELEVANCE: These findings suggest that a cohabitant's impressions of a patient's quality of life are, in most instances, accurate; this is potentially helpful in situations where the patient cannot weigh in. Future studies should employ longitudinal designs to see how or whether our findings change over time and with disease progression, and how specific interventions-like different chemotherapeutic regimens or surgery-may factor in.

Orthopaedic Disaster Course: Preparing for the Worst/Best Moment in the Operating Room.

Orthopaedic surgeons perform a variety of procedures where life-threatening or limb-threatening clinical scenarios or complications are relatively rare. Because these devastating complications and disaster presentations are infrequent, the occurrence can lead to concerns regarding training and preparedness. This chapter will provide a general knowledge base of common intraoperative disasters as well as life-threatening and/or limb-threatening conditions related to the upper extremity, pelvis, and lower extremity. Fundamental clinical and surgical management strategies are explored with respect to these conditions to provide a level of preparedness to help any orthopaedic surgeon control a potentially devastating complication or emergency.

Diagnoses, treatment, and oncologic outcomes in patients with calcaneal malignances: Case series, systematic literature review, and pooled cohort analysis.

BACKGROUND AND OBJECTIVES: Malignant tumors of the calcaneus are rare but pose a treatment challenge. AIMS: (1) describe the demographics of calcaneal malignancies in a large cohort; (2) describe survival after amputation versus limb-salvage surgery for high-grade tumors. METHODS: Study group: a "pooled" cohort of patients with primary calcaneal malignancies treated at two cancer centers (1984-2015) and systematic literature review. Kaplan-Meier analyses described survival across treatment and diagnostic groups; proportional hazards modeling assessed mortality after amputation versus limb salvage. RESULTS: A total of 131 patients (11 treated at our centers and 120 patients from 53 published studies) with a median 36-month follow-up were included. Diagnoses included Ewing sarcoma (41%), osteosarcoma (30%), and chondrosarcoma (17%); 5-year survival rates were 43%, 73% (70%, high grade only), and 84% (60%, high grade only), respectively. Treatment involved amputation in 52%, limb salvage in 27%, and no surgery in 21%. There was no difference in mortality following limb salvage surgery (vs. amputation) for high-grade tumors (HR 0.38; 95% CI 0.14-1.05), after adjusting for Ewing sarcoma diagnosis (HR 5.15; 95% CI 1.55-17.14), metastatic disease at diagnosis (HR 3.88; 95% CI 1.29-11.64), and age (per-year HR 1.04; 95% CI 1.02-1.07). CONCLUSIONS: Limb salvage is oncologically-feasible for calcaneal malignancies.

Development and Internal Validation of Machine Learning Algorithms for Preoperative Survival Prediction of Extremity Metastatic Disease.

BACKGROUND: A preoperative estimation of survival is critical for deciding on the operative management of metastatic bone disease of the extremities. Several tools have been developed for this purpose, but there is room for improvement. Machine learning is an increasingly popular and flexible method of prediction model building based on a data set. It raises some skepticism, however, because of the complex structure of these models. QUESTIONS/PURPOSES: The purposes of this study were (1) to develop machine learning algorithms for 90-day and 1-year survival in patients who received surgical treatment for a bone metastasis of the extremity, and (2) to use these algorithms to identify those clinical factors (demographic, treatment related, or surgical) that are most closely associated with survival after surgery in these patients. METHODS: All 1090 patients who underwent surgical treatment for a long-bone metastasis at two institutions between 1999 and 2017 were included in this retrospective study. The median age of the patients in the cohort was 63 years (interquartile range [IQR] 54 to 72 years), 56% of patients (610 of 1090) were female, and the median BMI was 27 kg/m (IQR 23 to 30 kg/m). The most affected location was the femur (70%), followed by the humerus (22%). The most common primary tumors were breast (24%) and lung (23%). Intramedullary nailing was the most commonly performed type of surgery (58%), followed by endoprosthetic reconstruction (22%), and plate screw fixation (14%). Missing data were imputed using the missForest methods. Features were selected by random forest algorithms, and five different models were developed on the training set (80% of the data): stochastic gradient boosting, random forest, support vector machine, neural network, and penalized logistic regression. These models were chosen as a result of their classification capability in binary datasets. Model performance was assessed on both the training set and the validation set (20% of the data) by discrimination, calibration, and overall performance. RESULTS: We found no differences among the five models for discrimination, with an area under the curve ranging from 0.86 to 0.87. All models were well calibrated, with intercepts ranging from -0.03 to 0.08 and slopes ranging from 1.03 to 1.12. Brier scores ranged from 0.13 to 0.14. The stochastic gradient boosting model was chosen to be deployed as freely available web-based application and explanations on both a global and an individual level were provided. For 90-day survival, the three most important factors associated with poorer survivorship were lower albumin level, higher neutrophil-to-lymphocyte ratio, and rapid growth primary tumor. For 1-year survival, the three most important factors associated with poorer survivorship were lower albumin level, rapid growth primary tumor, and lower hemoglobin level. CONCLUSIONS: Although the final models must be externally validated, the algorithms showed good performance on internal validation. The final models have been incorporated into a freely accessible web application that can be found at https://sorg-apps.shinyapps.io/extremitymetssurvival/. Pending external validation, clinicians may use this tool to predict survival for their individual patients to help in shared treatment decision making. LEVEL OF EVIDENCE: Level III, therapeutic study.

Thirty-day Postoperative Complications After Surgery For Metastatic Long Bone Disease Are Associated With Higher Mortality at 1 Year.

BACKGROUND: The benefits of surgical treatment of a metastasis of the extremities may be offset by drawbacks such as potential postoperative complications. For this group of patients, the primary goal of surgery is to improve quality of life in a palliative setting. A better comprehension of factors associated with complications and the impact of postoperative complications on mortality may prevent negative outcomes and help surgeons in surgical decision-making. QUESTIONS/PURPOSES: (1) What is the risk of 30-day postoperative complications after surgical treatment of osseous metastatic disease of the extremities? (2) What predisposing factors are associated with a higher risk of 30-day complications? (3) Are minor and major 30-day complications associated with higher mortality at 1 year? METHODS: Between 1999 and 2016, 1090 patients with osseous metastatic disease of the long bones treated surgically at our institution were retrospectively included in the study. Surgery included intramedullary nailing (58%), endoprosthetic reconstruction (22%), plate-screw fixation (14%), dynamic hip screw fixation (2%), and combined approaches (4%). Surgery was performed if patients were deemed healthy enough to proceed to surgery and wished to undergo surgery. All data were retrieved by manually reviewing patients' records. The overall frequency of complications, which were defined using the Clavien-Dindo classification system, was calculated. We did not include Grade I complications as postoperative complications and complications were divided into minor (Grade II) and major (Grades III-V) complications. A multivariate logistic regression analysis was used to identify factors associated with 30-day postoperative complications. A Cox regression analysis was used to assess the association between postoperative complications and overall survival. RESULTS: Overall, 31% of the patients (333 of 1090) had a postoperative complication within 30 days. The following factors were independently associated with 30-day postoperative complications: rapidly growing primary tumors classified according to the modified Katagiri classification (odds ratio 1.6; 95% confidence interval, 1.1-2.2; p = 0.011), multiple bone metastases (OR 1.6; 95% CI, 1.1-2.3; p = 0.008), pathologic fracture (OR 1.5; 95% CI, 1.1-2.0; p = 0.010), lower-extremity location (OR 2.2; 95% CI, 1.6-3.2; p < 0.001), hypoalbuminemia (OR 1.7; 95% CI, 1.2-2.4; p = 0.002), hyponatremia (OR 1.5; 95% CI, 1.0-2.2; p = 0.044), and elevated white blood cell count (OR 1.6; 95% CI, 1.1-2.4; p = 0.007). Minor and major postoperative complications within 30 days after surgery were both associated with greater 1-year mortality (hazard ratio 1.6; 95% CI, 1.3-1.8; p < 0.001 and HR 3.4; 95% CI, 2.8-4.2, respectively; p < 0.001). CONCLUSION: Patients with metastatic disease in the long bones are vulnerable to postoperative adverse events. When selecting patients for surgery, surgeons should carefully assess a patient's cancer status, and several preoperative laboratory values should be part of the standard work-up before surgery. Furthermore, 30-day postoperative complications decrease survival within 1 year after surgery. Therefore, patients at a high risk of having postoperative complications are less likely to profit from surgery and should be considered for nonoperative treatment or be monitored closely after surgery. LEVEL OF EVIDENCE: Level III, therapeutic study.