External Beam Radiation Therapy for Palliation of Symptomatic Bone Metastases: An ASTRO Clinical Practice Guideline.

PURPOSE: This guideline provides evidence-based recommendations for palliative external beam radiation therapy (RT) in symptomatic bone metastases. METHODS: The ASTRO convened a task force to address 5 key questions regarding palliative RT in symptomatic bone metastases. Based on a systematic review by the Agency for Health Research and Quality, recommendations using predefined consensus-building methodology were established; evidence quality and recommendation strength were also assessed. RESULTS: For palliative RT for symptomatic bone metastases, RT is recommended for managing pain from bone metastases and spine metastases with or without spinal cord or cauda equina compression. Regarding other modalities with RT, for patients with spine metastases causing spinal cord or cauda equina compression, surgery and postoperative RT are conditionally recommended over RT alone. Furthermore, dexamethasone is recommended for spine metastases with spinal cord or cauda equina compression. Patients with nonspine bone metastases requiring surgery are recommended postoperative RT. Symptomatic bone metastases treated with conventional RT are recommended 800 cGy in 1 fraction (800 cGy/1 fx), 2000 cGy/5 fx, 2400 cGy/6 fx, or 3000 cGy/10 fx. Spinal cord or cauda equina compression in patients who are ineligible for surgery and receiving conventional RT are recommended 800 cGy/1 fx, 1600 cGy/2 fx, 2000 cGy/5 fx, or 3000 cGy/10 fx. Symptomatic bone metastases in selected patients with good performance status without surgery or neurologic symptoms/signs are conditionally recommended stereotactic body RT over conventional palliative RT. Spine bone metastases reirradiated with conventional RT are recommended 800 cGy/1 fx, 2000 cGy/5 fx, 2400 cGy/6 fx, or 2000 cGy/8 fx; nonspine bone metastases reirradiated with conventional RT are recommended 800 cGy/1 fx, 2000 cGy/5 fx, or 2400 cGy/6 fx. Determination of an optimal RT approach/regimen requires whole person assessment, including prognosis, previous RT dose if applicable, risks to normal tissues, quality of life, cost implications, and patient goals and values. Relatedly, for patient-centered optimization of treatment-related toxicities and quality of life, shared decision making is recommended. CONCLUSIONS: Based on published data, the ASTRO task force's recommendations inform best clinical practices on palliative RT for symptomatic bone metastases.

Intraosseous Spindle Cell Rhabdomyosarcoma with MEIS1::NCOA2 Fusion - Case Report with Substantial Clinical Follow-up and Review of the Literature.

Spindle cell/sclerosing rhabdomyosarcoma (SSRMS) is a clinicopathologically and molecularly heterogeneous disease. Gene fusions have been identified in intraosseous SSRMS, consisting predominantly of EWSR1/FUS::TFCP2 and MEIS1::NCOA2. The former often follow an aggressive clinical course; there is limited clinical follow-up available for the latter. We report here a new case of the very rare intraosseous SSRMS with MEIS1::NCOA2 gene fusion and include the detailed treatment course and 52 months of clinical follow-up. SSRMS with MEIS1::NCOA2 gene fusion appears biologically distinct from other intraosseous SSRMS, following a course characterized by local recurrence with rare reports of metastasis to date.

Opioid Use in Surgical Management in Musculoskeletal Oncology.

BACKGROUND: Opioid prescribing in the context of orthopaedic surgery has been recognized as having a critical role in the ongoing opioid epidemic. Given the negative consequences of chronic opioid use, great efforts have been made to reduce both preoperative and postoperative opioid prescribing and consumption in orthopaedic surgery. Musculoskeletal oncology patients represent a unique subset of patients, and there is a paucity of data evaluating perioperative opioid consumption and the risk for chronic use. The objective of the present study was to describe opioid consumption patterns and evaluate predictors of chronic opioid use in musculoskeletal oncology patients undergoing limb-salvage surgery and endoprosthetic reconstruction. METHODS: The present study was a secondary analysis of the recently completed PARITY (Prophylactic Antibiotic Regimens in Tumor Surgery) trial and included musculoskeletal oncology patients undergoing lower-extremity endoprosthetic reconstruction. The primary outcome was the incidence of opioid consumption over the study period. A multivariate binomial logistic regression model was created to explore predictors of chronic opioid consumption at 1 year postoperatively. RESULTS: Overall, 193 (33.6%) of 575 patients were consuming opioids preoperatively. Postoperatively, the number of patients consuming opioids was 82 (16.7%) of 492 at 3 months, 37 (8%) of 460 patients at 6 months, and 28 (6.6%) of 425 patients at 1 year. Of patients consuming opioids preoperatively, 12 (10.2%) of 118 had continued to consume opioids at 1 year postoperatively. The adjusted regression model found that only surgery for metastatic bone disease was predictive of chronic opioid use (odds ratio, 4.90; 95% confidence interval, 1.54 to 15.40; p = 0.007). Preoperative opioid consumption, older age, sex, longer surgical times, reoperation rates, and country of origin were not predictive of chronic use. CONCLUSIONS: Despite a high prevalence of preoperative opioid use, an invasive surgical procedure, and a high rate of reoperation, few patients had continued to consume opioids at 1 year postoperatively. The presence of metastases was associated with chronic opioid use. These results are a substantial departure from the existing orthopaedic literature evaluating other patient populations, and they suggest that specific prescribing guidelines are warranted for musculoskeletal oncology patients. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Pediatric and Adult Patients Have Similar Functional Improvement After Endoprosthetic Reconstruction of Lower-Extremity Tumors.

BACKGROUND: Although the treatment of lower-extremity bone tumors is similar between adult and pediatric patients, differences in outcomes are unknown. Outcomes for lower-extremity oncologic reconstruction have been challenging to study because of the low incidence and heterogeneity in disease and patient characteristics. The PARITY (Prophylactic Antibiotic Regimens in Tumor Surgery) trial is the largest prospective data set assembled to date for patients with lower-extremity bone tumors and presents an opportunity to investigate differences in outcomes between these groups. METHODS: Patient details were acquired from the prospectively collected PARITY trial database. The 1993 Musculoskeletal Tumor Society (MSTS-93) and Toronto Extremity Salvage Score (TESS) questionnaires were administered preoperatively and at 3, 6, and 12 months postoperatively. Continuous outcomes were compared between groups with use of the Student t test, and dichotomous outcomes were compared with use of the Pearson chi-square test. RESULTS: A total of 150 pediatric and 447 adult patients were included. Pediatric patients were more likely than adult patients to have a primary bone tumor (146 of 150 compared with 287 of 447, respectively; p < 0.001) and to have received adjuvant chemotherapy (140 of 149 compared with 195 of 441, respectively; p < 0.001). Reoperation rates were not significantly different between age groups (45 of 105 pediatric patients compared with 106 of 341 adult patients; p ≤ 0.13). Pediatric patients had higher mean MSTS-93 scores (64.7 compared with 53.8 among adult patients; p < 0.001) and TESS (73.4 compared with 60.4 among adult patients; p < 0.001) at baseline, which continued to 1 year postoperatively (mean MSTS-93 score, 82.0 compared with 76.8 among adult patients; p = 0.02; mean TESS, 87.7 compared with 78.6 among adult patients; p < 0.001). Despite the differences in outcomes between cohorts, pediatric and adult patients demonstrated similar improvement in MSTS-93 scores (mean difference, 17.4 and 20.0, respectively; p = 0.48) and TESS (mean difference, 14.1 and 14.7, respectively; p = 0.83) from baseline to 1 year postoperatively. CONCLUSIONS: Pediatric patients had significantly better functional outcomes than adult patients at nearly all of the included postoperative time points; however, pediatric and adult patients showed similar mean improvement in these outcomes at 1 year postoperatively. These findings may be utilized to help guide the postoperative expectations of patients undergoing oncologic reconstruction. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Does the Use of Negative Pressure Wound Therapy and Postoperative Drains Impact the Development of Surgical Site Infections?: A PARITY Trial Secondary Analysis.

BACKGROUND: Surgical site infections (SSIs) represent a major complication following oncologic reconstructions. Our objectives were (1) to assess whether the use of postoperative drains and/or negative pressure wound therapy (NPWT) were associated with SSIs following lower-extremity oncologic reconstruction and (2) to identify factors associated with the duration of postoperative drains and with the duration of NPWT. METHODS: This is a secondary analysis of the Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY) trial, a multi-institution randomized controlled trial of lower-extremity oncologic reconstructions. Data were recorded regarding the use of drains alone, NPWT alone, or both NPWT and drains, including the total duration of each postoperatively. We analyzed postoperative drain duration and associations with tourniquet use, intraoperative thromboprophylaxis or antifibrinolytic use, incision length, resection length, and total operative time, through use of a linear regression model. A Cox proportional hazards model was used to evaluate the independent predictors of SSI. RESULTS: Overall, 604 patients were included and the incidence of SSI was 15.9%. Postoperative drains alone were used in 409 patients (67.7%), NPWT alone was used in 15 patients (2.5%), and both postoperative drains and NPWT were used in 68 patients (11.3%). The median (and interquartile range [IQR]) duration of drains and of NPWT was 3 days (IQR, 2 to 5 days) and 6 days (IQR, 4 to 8 days), respectively. The use of postoperative drains alone, NPWT alone, or both drains and NPWT was not associated with SSI (p = 0.14). Increased postoperative drain duration was associated with longer operative times and no intraoperative tourniquet use, as shown on linear regression analysis (p < 0.001 and p = 0.03, respectively). A postoperative drain duration of ≥14 days (hazard ratio [HR], 3.6; 95% confidence interval [CI], 1.3 to 9.6; p = 0.01) and an operative time of ≥8 hours (HR, 4.5; 95% CI, 1.7 to 11.9; p = 0.002) were independent predictors of SSI following lower-extremity oncologic reconstruction. CONCLUSIONS: A postoperative drain duration of ≥14 days and an operative time of ≥8 hours were independent predictors of SSI following lower-extremity oncologic reconstruction. Neither the use of postoperative drains nor the use of NPWT was a predictor of SSI. Future research is required to delineate the association of the combined use of postoperative drains and NPWT with SSI. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Is the Addition of Anaerobic Coverage to Perioperative Antibiotic Prophylaxis During Soft Tissue Sarcoma Resection Associated With a Reduction in the Proportion of Wound Complications?

BACKGROUND: Wound complications are common after resection of soft tissue sarcomas, with published infection rates ranging from 10% to 35%. Multiple studies have reported on the atypical flora comprising these infections, which are often polymicrobial and contain anaerobic bacteria, and recent studies have noted the high prevalence of anaerobic bacterial infections after soft tissue sarcoma resection [ 26, 35 ]. Based on this, our institution changed clinical practice to include an antibiotic with anaerobic coverage in addition to the standard first-generation cephalosporin for prophylaxis during soft tissue sarcoma resections. The current study was undertaken to evaluate whether this change was associated with a change in major wound complications, and if the change should therefore be adopted for future patients. QUESTIONS/PURPOSES: (1) After controlling for potentially confounding variables, was the broadening of the prophylactic antibiotic spectrum to cover anaerobic bacteria associated with a lower odds of major wound complications after soft tissue sarcoma resection? (2) Was the broadening of the prophylactic antibiotic spectrum to cover anaerobic bacteria associated with a lower odds of surgical site infections with polymicrobial or anaerobic infections after soft tissue sarcoma resection? (3) What are the factors associated with major wound complications after soft tissue sarcoma resection? METHODS: We retrospectively identified 623 patients who underwent soft tissue sarcoma resection at a single center between January 2008 and January 2021 using procedural terminology codes. Of these, four (0.6%) pediatric patients were excluded, as were five (0.8%) patients with atypical lipomatous tumors and two (0.3%) patients with primary bone tumors; 5% (33 of 623) who were lost to follow-up, leaving 579 for final analysis. The prophylactic antibiotic regimen given at the resection and whether a wound complication occurred were recorded. Patients received the augmented regimen based on whether they underwent resection after the change in practice in July 2018. A total of 497 patients received a standard antibiotic regimen (usually a first-generation cephalosporin), and 82 patients received an augmented regimen with anaerobic coverage (most often metronidazole). Of the 579 patients, 53% (307) were male (53% [264 of 497] in the standard regimen and 52% [43 of 82] in the augmented regimen), and the mean age was 59 ± 17 years (59 ± 17 and 60 ±17 years in the standard and augmented groups, respectively). Wound complications were defined as any of the following within 120 days of the initial resection: formal wound debridement in the operating room, other interventions such as percutaneous drain placement, readmission for intravenous antibiotics, or deep wound packing for more than 120 days from the resection. Patients were considered to have a surgical site infection if positive cultures resulted from deep tissue cultures taken intraoperatively at the time of debridement. The proportion of patients with major wound complications was 26% (150 of 579); it was 27% (136 of 497) and 17% (14 of 82) in the standard and augmented antibiotic cohorts, respectively (p = 0.049). With the numbers we had, we could not document that the addition of antibiotics with anaerobic coverage was associated with lower odds of anaerobic (4% versus 6%; p = 0.51) or polymicrobial infections (9% versus 14%; p = 0.25). Patient, tumor, and treatment (surgical, radiotherapy, and chemotherapy) variables were collected to evaluate factors associated with overall infection and anaerobic or polymicrobial infection. Patient follow-up was 120 days to capture early wound complications. A multivariable analysis was performed for all variables found to be significant in the univariate analysis. A p value < 0.05 was used as the threshold for statistical significance for all analyses. No patients were found to have an adverse reaction to the augmented regimen, including allergic reactions or Clostridioides (formerly Clostridium) difficile infection. RESULTS: After controlling for other potentially confounding factors such as neoadjuvant radiation, tumor size and anatomic location, as well as patient BMI, anaerobic coverage was associated with smaller odds of wound complications (OR 0.36 [95% confidence interval (CI) 0.18 to 0.68]; p = 0.003). Other factors associated with major wound complications were preoperative radiation (versus no preoperative radiation) (OR 2.66 [95% CI 1.72 to 4.15]; p < 0.001), increasing tumor size (OR 1.04 [95% CI 1.00 to 1.07]; p = 0.03), patient BMI (OR 1.07 [95% CI 1.04 to 1.11]; p < 0.001), and tumor in the distal upper extremity (versus proximal upper extremity, pelvis/groin/hip, and lower extremity) (OR 0.18 [95% CI 0.04 to 0.62]; p = 0.01). CONCLUSION: The addition of anaerobic coverage to the standard prophylactic regimen during soft tissue sarcoma resection demonstrated an association with smaller odds of major wound complications and no documented adverse reactions. Treating physicians should consider these findings but note that they are preliminary, and that further work is needed to replicate them in a more controlled study design such as a prospective trial. LEVEL OF EVIDENCE: Level III, therapeutic study.

Comparison of Prophylactic Intravenous Antibiotic Regimens After Endoprosthetic Reconstruction for Lower Extremity Bone Tumors: A Randomized Clinical Trial.

IMPORTANCE: The use of perioperative, prophylactic, intravenous antibiotics is standard practice to reduce the risk of surgical site infection after oncologic resection and complex endoprosthetic reconstruction for lower extremity bone tumors. However, evidence guiding the duration of prophylactic treatment remains limited. OBJECTIVE: To assess the effect of a 5-day regimen of postoperative, prophylactic, intravenous antibiotics compared with a 1-day regimen on the rate of surgical site infections within 1 year after surgery. DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical superiority trial was performed at 48 clinical sites in 12 countries from January 1, 2013, to October 29, 2019. The trial included patients with a primary bone tumor or a soft tissue sarcoma that had invaded the femur or tibia or oligometastatic bone disease of the femur or tibia with expected survival of at least 1 year who required surgical management by excision and endoprosthetic reconstruction. A total of 611 patients were enrolled, and 7 were excluded for ineligibility. INTERVENTIONS: A 1- or 5-day regimen of postoperative prophylactic intravenous cephalosporin (cefazolin or cefuroxime) that began within 8 hours after skin closure and was administered every 8 hours thereafter. Those randomized to the 1-day regimen received identical saline doses every 8 hours for the remaining 4 days; patients, care providers, and outcomes assessors were blinded to treatment regimen. MAIN OUTCOMES AND MEASURES: The primary outcome in this superiority trial was a surgical site infection (superficial incisional, deep incisional, or organ space) classified according to the criteria established by the Centers for Disease Control and Prevention within 1 year after surgery. Secondary outcomes included antibiotic-related complications, unplanned additional operations, oncologic and functional outcomes, and mortality. RESULTS: Of the 604 patients included in the final analysis (mean [SD] age, 41.2 [21.9] years; 361 [59.8%] male; 114 [18.9%] Asian, 43 [7.1%] Black, 34 [5.6%] Hispanic, 15 [2.5%] Indigenous, 384 [63.8%] White, and 12 [2.0%] other), 293 were randomized to a 5-day regimen and 311 to a 1-day regimen. A surgical site infection occurred in 44 patients (15.0%) allocated to the 5-day regimen and in 52 patients (16.7%) allocated to the 1-day regimen (hazard ratio, 0.93; 95% CI, 0.62-1.40; P = .73). Antibiotic-related complications occurred in 15 patients (5.1%) in the 5-day regimen and in 5 patients (1.6%) allocated to the 1-day regimen (hazard ratio, 3.24; 95% CI, 1.17-8.98; P = .02). Other secondary outcomes did not differ significantly between treatment groups. CONCLUSIONS AND RELEVANCE: This randomized clinical trial did not confirm the superiority of a 5-day regimen of postoperative intravenous antibiotics over a 1-day regimen in preventing surgical site infections after surgery for lower extremity bone tumors that required an endoprosthesis. The 5-day regimen group had significantly more antibiotic-related complications. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01479283.

Willingness of patients with sarcoma to participate in cancer surveillance research: a cross-sectional patient survey.

OBJECTIVES: To determine the proportion of patients with extremity sarcoma who would be willing to participate in a clinical trial in which they would be randomised to one of four different postoperative sarcoma surveillance regimens. Additionally, we assessed patients' perspectives on the burden of cancer care, factors that influence comfort with randomisation and the importance of cancer research. DESIGN: Prospective, cross-sectional patient survey. SETTING: Outpatient sarcoma clinics in Canada, the USA and Spain between May 2017 and April 2020. Survey data were entered into a study-specific database. PARTICIPANTS: Patients with extremity sarcoma who had completed definitive treatment from seven clinics across Canada, the USA and Spain. MAIN OUTCOME MEASURES: The proportion of patients with extremity sarcoma who would be willing to participate in a randomised controlled trial (RCT) that evaluates varying postoperative cancer surveillance regimens. RESULTS: One hundred thirty complete surveys were obtained. Respondents reported a wide range of burdens related to clinical care and surveillance. The majority of patients (85.5%) responded that they would agree to participate in a cancer surveillance RCT if eligible. The most common reason to participate was that they wanted to help future patients. Those that would decline to participate most commonly reported that participating in research would be too much of a burden for them at a time when they are already feeling overwhelmed. However, most patients agreed that cancer research will help doctors better understand and treat cancer. CONCLUSIONS: These results demonstrate that most participants would be willing to participate in an RCT that evaluates varying postoperative cancer surveillance regimens. Participants' motivation for trial participation included altruistic reasons to help future patients and deterrents to trial participation included the overwhelming burden of a cancer diagnosis. These results will help inform the development of patient-centred RCT protocols in sarcoma surveillance research. LEVEL OF EVIDENCE: V.

Compressive osseointegration for endoprosthetic reconstruction.

This review summarizes the biomechanical concepts, clinical outcomes and limitations of compressive osseointegration fixation for endoprosthetic reconstruction. Compressive osseointe - gration establishes stable fixation and integration through a novel mechanism; a Belleville washer system within the spindle applies 400-800 PSI force at the boneimplant interface. Compressive osseointegration can be used whenever standard endoprosthetic reconstruction is indicated. However, its mode of fixation allows for a shorter spindle that is less limited by the length of remaining cortical bone. Most often compressive osseointegration is used in the distal femur, proximal femur, proximal tibia, and humerus but these devices have been customized for use in less traditional locations. Aseptic mechanical failure occurs earlier than with standard endoprosthetic reconstruction, most often within the first two years. Compressive osseointegration has repeatedly been proven to be non-inferior to standard endoprosthetic reconstruction in terms of aseptic mechanical failure. No demographic, device specific, oncologic variables have been found to be associated with increased risk of aseptic mechanical failure. While multiple radiographic parameters are used to assess for aseptic mechanical failure, no suitable method of evaluation exists. The underlying pathology associated with aseptic mechanical failure demonstrates avascular bone necrosis. This is in comparison to the bone hypertrophy and ingrowth at the boneprosthetic interface that seals the endosteal canal, preventing aseptic loosening.

Mirels Scores in Patients Undergoing Prophylactic Stabilization for Femoral Metastatic Bone Disease in the Veterans Administration Healthcare System.

INTRODUCTION: A retrospective review was performed for patients in the Veterans Administration Healthcare System who underwent prophylactic stabilization of the femur for metastatic disease. The goal was to evaluate indications for prophylactic stabilization through Mirels criteria. METHODS: All veterans who underwent inpatient prophylactic femoral stabilization between October 2010 and September 2015 were identified. Procedure and demographic variables were collected by using chart review. Provider notes and radiographs were reviewed to calculate Mirels scores. RESULTS: Ninety-two patients underwent confirmed prophylactic stabilization for metastatic bone disease. Lung cancer and multiple myeloma accounted for most lesions. The mean Mirels score was 10.3 (range 7 to 12). 3.2% of patients had a score of 7, and 6.5% had a score of 8. Most lesions were peritrochanteric (66%) and lytic (85%). There was more variability in size (mean 2.3), with 15% being under one third of bony width and 38% between one and two-thirds. The mean pain score was 2.5; 73% reported functional pain. Of lytic and peritrochanteric lesions (53% of all cases), 55% were less than two-thirds the cortical width and 31% lacked functional pain. CONCLUSION: This retrospective study of prophylactically stabilized metastatic lesions revealed that more than 90% of patients had Mirels scores greater than 8, suggesting a substantial risk of pathologic fracture. Over half of all stabilized lesions were peritrochanteric and lytic. These criteria alone achieve a minimum Mirels score of 8; however, one-third of these lacked functional pain. Notably, Mirels' original paper found location and type criteria to be the least predictive of impending fracture. Contrariwise, functional pain was the most accurate predictor. Multiple studies have found poor specificity of the Mirels criteria. The high scores achievable by the location and type criteria may represent an overrepresentation of their contribution to fracture risk. Reconsideration of the relative weights of each criterion warrants further examination.

Is There an Association Between Prophylactic Femur Stabilization and Survival in Patients with Metastatic Bone Disease?

BACKGROUND: The femur is the most common site of metastasis in the appendicular skeleton, and metastatic bone disease negatively influences quality of life. Orthopaedic surgeons are often faced with deciding whether to prophylactically stabilize an impending fracture, and it is unclear if prophylactic fixation increases the likelihood of survival. QUESTIONS/PURPOSES: Is prophylactic femur stabilization in patients with metastatic disease associated with different overall survival than fixation of a complete pathologic fracture? METHODS: We performed a retrospective, comparative study using the national Veterans Administration database. All patient records from September 30, 2010 to October 1, 2015 were queried. Only nonarthroplasty procedures were included. The final study sample included 950 patients (94% males); 362 (38%) received prophylactic stabilization of a femoral lesion, and 588 patients (62%) underwent fixation of a pathologic femur fracture. Mean followup duration was 2 years (range, 0-7 years). We created prophylactic stabilization and pathologic fracture fixation groups for comparison using Common Procedural Terminology and ICD-9 codes. The primary endpoint of the analysis was overall survival. Univariate survival was estimated using the Kaplan-Meier method; between-group differences were compared using the log-rank test. Covariate data were used to create a multivariate Cox proportional hazards model for survival to adjust for confounders in the two groups, including Gagne comorbidity score and cancer type. RESULTS: After adjusting for comorbidities and cancer type, we found that patients treated with prophylactic stabilization had a lower risk of death than did patients treated for pathologic femur fracture (hazard ratio = 0.75, 95% CI, 0.62-0.89; p = 0.002). CONCLUSIONS: In the national Veterans Administration database, we found greater overall survival between patients undergoing prophylactic stabilization of metastatic femoral lesions and those with fixation of complete pathologic fractures. We could not determine the cause of this association, and it is possible, if not likely, that patients treated for fracture had more aggressive disease causing the fracture than did those undergoing prophylactic stabilization. Currently, most orthopaedic surgeons who treat pathological fractures stabilize the fracture prophylactically when reasonable to do so. We may be improving survival in addition to preventing a pathological fracture; further study is needed to determine whether the association is cause-and-effect and whether additional efforts to identify and treat at-risk lesions improves patient outcomes. LEVEL OF EVIDENCE: Level III, therapeutic study.

Radiographic parameter-driven decision tree reliably predicts aseptic mechanical failure of compressive osseointegration fixation.

Background and purpose - Compressive osseointegration fixation is an alternative to intramedullary fixation for endoprosthetic reconstruction. Mechanical failure of compressive osseointegration presents differently on radiographs than stemmed implants, therefore we aimed to develop a reliable radiographic method to determine stable integration.Patients and methods - 8 reviewers evaluated 11 radiographic parameters from 29 patients twice, 2 months apart. Interclass correlation coefficients (ICCs) were used to assess test-retest and inter-rater reliability. We constructed a fast and frugal decision tree using radiographic parameters with substantial test-retest agreement, and then tested using radiographs from a new cohort of 49 patients. The model's predictions were compared with clinical outcomes and a confusion matrix was generated.Results - 6 of 8 reviewers had non-significant intra-rater ICCs for ≥ one parameter; all inter-rater ICCs were highly reliable (p < 0.001). Change in length between the top of the spindle sleeve and bottom of the anchor plug (ICC 0.98), bone cortex hypertrophy (ICC 0.86), and bone pin hypertrophy (ICC 0.81) were used to create the decision tree. The sensitivity and specificity of the training cohort were 100% (95% CI 52-100) and 87% (CI 74-94) respectively. The decision tree demonstrated 100% (CI 40-100) sensitivity and 89% (CI 75-96) specificity with the test cohort.Interpretation - A stable spindle length and at least 3 cortices with bone hypertrophy at the implant interface predicts stable osseointegration; failure is predicted in the absence of bone hypertrophy at the implant interface if the pin sites show hypertrophy. Thus, our decision tree can guide clinicians as they follow patients with compressive osseo-integration implants.

Oncology Patients Are High Cost Outliers in Total Joint Replacement Bundled Payment Systems.

BACKGROUND: In 2016, the Centers for Medicare and Medicaid Services began its first mandatory bundled payment program, the Comprehensive Care for Joint Replacement (CJR) model, which covers a 90-day episode of care. This study determined whether oncology patients enrolled in the CJR bundle incur higher hospital costs than patients with osteoarthritis (OA). METHODS: A retrospective review of all patients enrolled in the CJR bundled payments system from April 1, 2016 to June 31, 2018 at a single academic medical center was conducted. To determine whether tumor patients had higher total episode costs, this group was compared to patients diagnosed with OA using a 2-tailed t-test. To adjust for moderators of total hospital costs, we used generalized linear regression with a log-link, including multiple variables abstracted from chart review. RESULTS: Three hundred fourteen patients met inclusion criteria (12 primary or metastatic tumors, 302 OA). Fifty-eight percent of tumor patients were over the target price vs 16% of OA patients. The mean tumor patient had $40,862 for total internal hospital costs compared to $16,356 in the OA group (P < .001). Length of stay was greater in the tumor group (6.75 vs 2.0 days, P < .001). A greater percentage of tumor patients were discharged to a skilled nursing facility (67% vs 27%, P = .006) with significantly higher skilled nursing facility episode costs ($18,852 vs $7731, P = .04). With adjustment for fracture status, tumor patients were 5.36 times more likely to exceed the CJR target price than OA patients (risk ratio 5.36, confidence interval 3.44-8.35, P < .001) and 50 times more likely to be outliers over the regional threshold than OA patients (risk ratio 50.33, confidence interval 16.33-155.19, P < .001). CONCLUSION: Oncology patients enrolled in the CJR bundled payment model incur significantly higher costs and have higher cost variability than patients with OA. We recommend that oncology patients be excluded from the CJR bundle.

Reliability and Validity of the Vancouver Classification in Periprosthetic Fractures Around Cementless Femoral Stems.

BACKGROUND: The Vancouver classification of periprosthetic femur fractures divides B1 and B2 subtypes based on the stability of the femoral stem. However, this classification was described and validated with cemented femoral stems. We sought to assess reliability and validity of the Vancouver classification in patients with cementless femoral stems. METHODS: This is a blinded radiographic study which included patients treated for Vancouver B cementless periprosthetic femur fractures between February 2007 and December 2017. Adult reconstruction-trained and trauma fellowship-trained orthopedic surgeons graded all preoperative radiographs using the Vancouver classification on 3 separate occasions. Interobserver and intraobserver reliability was assessed via the Fleiss' kappa statistic. Validity was assessed via accuracy between radiographic and intraoperative assessments. The Landis and Koch criteria were used to interpret the kappa values. RESULTS: Fifty-three patients with Vancouver B fractures (B1, 8; B2, 45) around a cementless femoral stem were included in the study. Five reconstruction-trained and 5 trauma-trained orthopedic surgeons graded all radiographs. The interobserver reliability kappa value was 0.45 (moderate agreement), with all raters agreeing on only 43% of radiographs. Validity analysis showed demonstrated 79% agreement. Overall, 20% (range, 14%-24%) of unstable B2 fractures were misread as B1 fractures. Intraobserver reliability was 0.71 between readings. CONCLUSION: The reliability of the Vancouver classification for cementless total hip arthroplasty is lower than previously described in cemented femoral stems. Radiographic assessment alone may be inadequate for determination of stability of cementless stems in periprosthetic femur fractures. LEVEL OF EVIDENCE: Level III therapeutic study: retrospective comparative study.

Identification of infectious species after resection of soft-tissue sarcomas.

BACKGROUND: Pathogenic species in deep tissue infections after soft-tissue sarcoma (STS) resection is largely unstudied, particularly the role of anaerobic bacteria, risks factors for those pathogens, and the time course of infection presentation. METHODS: Retrospective analysis of 64 patients requiring operative debridement for deep tissue infection after STS resection was undertaken to identify infectious species and study risk factors for anaerobic infections. Kaplan-Meier methods examined the time course of infection presentation. RESULTS: STS subtypes were most commonly pleomorphic STS, myxofibrosarcoma, and undifferentiated STS. Staphylococcus aureus was the most common organism isolated (56%). Twenty (31%) infections were positive for ≥1 anaerobic organism. Twelve gram-positive and 10 gram-negative aerobic organisms were isolated. Most (90%) anaerobic-containing infections were polymicrobial, vs 52% of purely aerobic infections. No significant risk factors for anaerobic infections were identified. Median time from tumor resection until debridement was significantly greater for anaerobic infections (54.5 days) than for purely aerobic infections (29.5 days; P = 0.004), a difference so pronounced that using "presentation after 53 days" as a proxy for the presence of anaerobic pathogens had an accuracy of 81%. CONCLUSIONS: Because polymicrobial and anaerobic bacterial infections are common, we strongly support antibiotic use with anaerobic coverage at debridement, particularly for infections presenting later.

Epirubicin and Ifosfamide with Preoperative Radiation for High-Risk Soft Tissue Sarcomas.

BACKGROUND: The optimal treatment of high-risk soft tissue sarcomas (STS) of the extremities remains controversial. We report follow-up from a phase II study of dose-intense chemotherapy with preoperative hypofractionated radiation in this population supplemented with subsequent data from an extensive institutional experience using this regimen. METHODS: Patients with localized, intermediate- or high-grade STS of the extremity or body wall measuring > 5 cm were treated with epirubicin 30 mg/m2/day and ifosfamide 2.5 g/m2/day on days 1-4 every 21 days for 3 preoperative and 3 postoperative cycles. During cycle 2 of preoperative therapy, epirubicin was omitted, and a total of 28 Gy of radiation (8 fractions) was delivered. Twenty-five patients were treated on the phase II study (2002-2005). Fifty-one additional patients were identified from a retrospective chart review (2005-2014). RESULTS: The 5-year rates for overall survival, distant disease-free survival, and freedom from local regional failure were 70.4% (95% CI 59.2-83.7%), 55.9% (95% CI 44.5-70.2%), and 87.2% (95% CI 77.9-96.5%) respectively. Thirty-eight percent of tumors (29/76) demonstrated ≥ 90% pathologic response. Wound complications occurred in 32% (24/76) of patients. DISCUSSION: Treatment with preoperative radiation and pre- and post-operative epirubicin and ifosfamide was associated with favorable clinical outcomes. Survival and recurrence rates were comparable to those reported with other preoperative chemotherapy regimens in high-risk extremity sarcomas. Use of trimodality therapy should be considered for appropriate high-risk STS patients.

What Factors Are Associated With Failure of Compressive Osseointegration Fixation?

BACKGROUND: Compressive osseointegration is as an alternative to traditional intramedullary fixation. Two- to 10-year survivorship and modes of failure have been reported; however, as a result of relatively small numbers, these studies are limited in their ability to identify risk factors for failure. QUESTIONS/PURPOSES: (1) What is survivorship free from aseptic mechanical and survivorship free from overall failure of compressive osseointegration fixation? (2) What patient factors (age, sex, body mass index [BMI], anatomic location of reconstruction, indication for reconstruction, radiation, chemotherapy) are associated with increased risk of failure? METHODS: Between 2006 and 2014, surgeons at one center treated 116 patients with 137 Compress® implants for lower extremity oncologic reconstructions, revision arthroplasty, and fracture nonunion or malunion. One hundred sixteen implants were available for review with a minimum of 2-year followup (mean, 4 years; range, 2-9 years). Kaplan-Meier survival plots were produced to examine survivorship and Cox regression modeling was used to generate hazard ratios (HRs) for potential risk factors for failure. Patient factors (age, sex, BMI, anatomic location of reconstruction, indication for reconstruction, radiation, chemotherapy) were obtained from chart review and an institutional database. RESULTS: Survivorship free from aseptic mechanical failure was 95% (95% confidence interval [CI], 91%-99%) at 18 months and 93% (95% CI, 86%-99%) at 4 years. Survivorship free from overall failure was 82% (95% CI, 75%-89%) at 18 months and 75% (95% CI, 66%-84%) at 4 years. Risk of overall failure was increased with reconstruction of the proximal tibia (HR, 4.42; 95% CI 0.98-19.9) and distal femur (HR, 1.74; 95% CI, 0.50-6.09) compared to the proximal femur (HR, 1; referent; p = 0.049). Risk of aseptic mechanical failure was increased with reconstruction of the proximal tibia (HR, 1; referent) and distal femur (HR, 0.37; 95% CI, 0.08-1.77) compared with the proximal femur (HR, 0, p = 0.048). Radiation was associated with increased risk of overall failure (HR, 3.85; 95% CI, 1.84-8.02; p < 0.003), but not aseptic mechanical failure. Age, sex, BMI, chemotherapy, and surgical indication were not associated with increased risk of aseptic or overall failure. CONCLUSIONS: This study questions the use of age as a contraindication for the use of this technology and suggests this technology may be considered in proximal femoral reconstruction and for patients with indications other than primary oncologic reconstructions. Future research should establish long-term survivorship data to compare this approach with conventional intramedullary stems and to evaluate the potential benefits of preventing stress shielding and preserving bone stock in revision situations. LEVEL OF EVIDENCE: Level III, therapeutic study.

Evaluation of Soft Tissue Sarcoma Response to Preoperative Chemoradiotherapy Using Dynamic Contrast-Enhanced Magnetic Resonance Imaging.

This study aims to assess the utility of quantitative dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) parameters in comparison with imaging tumor size for early prediction and evaluation of soft tissue sarcoma response to preoperative chemoradiotherapy. In total, 20 patients with intermediate- to high-grade soft tissue sarcomas received either a phase I trial regimen of sorafenib + chemoradiotherapy (n = 8) or chemoradiotherapy only (n = 12), and underwent DCE-MRI at baseline, after 2 weeks of treatment with sorafenib or after the first chemotherapy cycle, and after therapy completion. MRI tumor size in the longest diameter (LD) was measured according to the RECIST (Response Evaluation Criteria In Solid Tumors) guidelines. Pharmacokinetic analyses of DCE-MRI data were performed using the Shutter-Speed model. After only 2 weeks of treatment with sorafenib or after 1 chemotherapy cycle, Ktrans (rate constant for plasma/interstitium contrast agent transfer) and its percent change were good early predictors of optimal versus suboptimal pathological response with univariate logistic regression C statistics values of 0.90 and 0.80, respectively, whereas RECIST LD percent change was only a fair predictor (C = 0.72). Post-therapy Ktrans, ve (extravascular and extracellular volume fraction), and kep (intravasation rate constant), not RECIST LD, were excellent (C > 0.90) markers of therapy response. Several DCE-MRI parameters before, during, and after therapy showed significant (P < .05) correlations with percent necrosis of resected tumor specimens. In conclusion, absolute values and percent changes of quantitative DCE-MRI parameters provide better early prediction and evaluation of the pathological response of soft tissue sarcoma to preoperative chemoradiotherapy than the conventional measurement of imaging tumor size change.

Phase I trial of preoperative chemoradiation plus sorafenib for high-risk extremity soft tissue sarcomas with dynamic contrast-enhanced MRI correlates.

PURPOSE: We conducted a phase I trial of the addition of sorafenib to a chemoradiotherapy regimen in patients with high-risk (intermediate/high grade, >5 cm) extremity soft tissue sarcoma undergoing limb salvage surgery. We conducted a correlative study of quantitative dynamic contrast-enhanced MRI (DCE-MRI) to assess response to treatment. EXPERIMENTAL DESIGN: Patients were treated at increasing dose levels of sorafenib (200 mg daily, 400 mg daily, 400 mg twice daily) initiated 14 days before three preoperative and three postoperative cycles of epirubicin/ifosfamide. Radiation (28 Gy) was administered during cycle 2 with epirubicin omitted. The primary objective was to determine the maximum tolerated dose (MTD) of sorafenib. DCE-MRI was conducted at baseline, after 2 weeks of sorafenib, and before surgery. The imaging data were subjected to quantitative pharmacokinetic analyses. RESULTS: Eighteen subjects were enrolled, of which 16 were evaluable. The MTD of sorafenib was 400 mg daily. Common grade 3-4 adverse events included neutropenia (94%), hypophosphatemia (75%), anemia (69%), thrombocytopenia (50%), and neutropenic fever/infection (50%). Of note, 38% developed wound complications requiring surgical intervention. The rate of ≥95% histopathologic tumor necrosis was 44%. Changes in DCE-MRI biomarker ΔK(trans) after 2 weeks of sorafenib correlated with histologic response (R(2) = 0.67, P = 0.012) at surgery. CONCLUSION: The addition of sorafenib to preoperative chemoradiotherapy is feasible and warrants further investigation in a larger trial. DCE-MRI detected changes in tumor perfusion after 2 weeks of sorafenib and may be a minimally invasive tool for rapid assessment of drug effect in soft tissue sarcoma.