Survival and failure modes of the Compress® spindle and expandable distal femur endoprosthesis among pediatric patients: A multi-institutional study.

BACKGROUND: Expandable endoprostheses can be used to equalize limb length for pediatric patients requiring reconstruction following large bony oncologic resections. Outcomes of the Compress® Compliant Pre-Stress (CPS) spindle paired with an Orthopedic Salvage System expandable distal femur endoprosthesis have not been reported. METHODS: We conducted a multi-institutional retrospective study of pediatric patients with distal femoral bone sarcomas reconstructed with the above endoprostheses. Statistical analysis utilized Kaplan-Meier survival technique and competing risk analysis. RESULTS: Thirty-six patients were included from five institutions. Spindle survivorship was 86.3% (95% confidence interval [CI], 67.7-93.5) at 10 years. Two patients had a failure of osseointegration (5.7%), both within 12 months. Twenty-two (59%) patients had 70 lengthening procedures, with mean expansions of 3.2 cm (range: 1-9) over 3.4 surgeries. The expandable mechanism failed in eight patients with a cumulative incidence of 16.1% (95% CI, 5.6-31.5) at 5 years. Twenty-nine patients sustained International Society of Limb Salvage failures requiring 63 unplanned surgeries. Periprosthetic joint infection occurred in six patients (16.7%). Limb preservation rate was 91% at 10 years. CONCLUSIONS: There is a high rate of osseointegration of the Compress® spindle among pediatric patients when coupled with an expandable implant. However, there is a high rate of expansion mechanism failure and prosthetic joint infections requiring revision surgery. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Ferumoxytol magnetic resonance imaging detects joint and pleural infiltration of bone sarcomas in pediatric and young adult patients.

BACKGROUND: The diagnosis of joint infiltration by a malignant bone tumor affects surgical management. The specificity of standard magnetic resonance imaging (MRI) for diagnosing joint infiltration is limited. During our MRI evaluations with ferumoxytol nanoparticles of pediatric and young adult patients with bone sarcomas, we observed a surprising marked T1 enhancement of joint and pleural effusions in some patients but not in others. OBJECTIVE: To evaluate if nanoparticle extravasation differed between joints and pleura with and without tumor infiltration. MATERIALS AND METHODS: We retrospectively identified 15 pediatric and young adult patients (mean age: 16±4 years) with bone sarcomas who underwent 18 MRI scans at 1 h (n=7) or 24 h (n=11) after intravenous ferumoxytol infusion. Twelve patients also received a gadolinium-enhanced MRI. We determined tumor invasion into the joint or pleural space based on histology (n=11) and imaging findings (n=4). We compared the signal-to-noise ratios (SNR) and contrast-to-noise ratios (CNR) of the joint or pleural fluid for tumors with and without invasion using a Mann-Whitney U test. RESULTS: MRI scans 24 h after intravenous ferumoxytol infusion demonstrated a positive T1 enhancement of the effusion in all joints and pleural spaces with tumor infiltration and no joint or pleural space without infiltration. Corresponding SNR (P=0.004) and CNR (P=0.004) values were significantly higher for joints and pleural spaces with tumor infiltration than without. By contrast, unenhanced MRI, gadolinium-enhanced MRI and 1-h post-contrast ferumoxytol MRI did not show any enhancement of the joint or pleural effusion, with or without tumor infiltration. CONCLUSION: This pilot study suggests that 24-h post-contrast ferumoxytol MRI scans can noninvasively differentiate between joints with and without tumor infiltration.

Distal femoral fine wire traction assisted retrograde nailing of the femur.

Here we describe the surgical technique for using distal femoral fine wire traction during retrograde femoral nailing and present case examples. This technique allows for hands-free distraction across the fracture site to restore length and alignment, while not interfering with the preparation and insertion of the retrograde femoral nail. Distal femoral fine wire traction is a useful adjunctive technique to restore length and effect an indirect reduction in femur fractures being stabilized with a retrograde nail.

Outcomes for pediatric patients with osteosarcoma treated with palliative radiotherapy.

BACKGROUND: Few studies have addressed the efficacy of palliative radiotherapy (RT) for pediatric osteosarcoma (OS), a disease generally considered to be radioresistant. We describe symptom relief, local control, and toxicity associated with palliative RT among children with OS. PROCEDURE: Patients diagnosed with OS at age 18 and under and treated with RT for palliation of symptomatic metastases or local recurrence at the primary site from 1997 to 2017 were included. We retrospectively reviewed details of RT, symptom improvement, local control, survival, and toxicity. RESULTS: Thirty-two courses of palliative RT were given to 20 patients with symptomatic metastatic and/or locally recurrent primary disease. The median equivalent dose in 2 Gy fractions (EQD2) was 40.0 Gy (range, 20.0-60.4). The median number of fractions per course was 15 (range, 5-39). Symptom improvement occurred in 24 (75%) courses of RT at a median time of 15.5 days (range, 3-43). In nine courses (37.5%), symptoms recurred after a median duration of symptom relief of 140 days (range, 1-882). Higher EQD2 correlated with longer duration of response (r = 0.39, P = 0.0003). Imaging revealed local failure in 3 of 14 courses followed with surveillance imaging studies (21.4%). The median time to progression was 12.9 months (range, 4.4-21.8). The median follow-up time following the first course of palliative RT was 17.5 months (range, 1.74-102.24), and median time to overall survival was 19.4 months. Toxicity was mild, with grade 2 toxicity occurring in one course (3.1%). CONCLUSIONS: RT is an effective method of symptom palliation for patients with recurrent or metastatic OS, with higher delivered dose correlating with longer symptom relief and with little associated toxicity.

Is MR-guided High-intensity Focused Ultrasound a Feasible Treatment Modality for Desmoid Tumors?

BACKGROUND: MR-guided high-intensity focused ultrasound is a noninvasive treatment modality that uses focused ultrasound waves to thermally ablate tumors within the human body while minimizing side effects to surrounding healthy tissues. This technology is FDA-approved for certain tumors and has potential to be a noninvasive treatment option for extremity soft tissue tumors. Development of treatment modalities that achieve tumor control, decrease morbidity, or both might be of great benefit for patients. We wanted to assess the potential use of this technology in the treatment of extremity desmoid tumors. QUESTIONS/PURPOSES: (1) Can we use MR-guided high-intensity focused ultrasound to accurately ablate a predetermined target volume within a human cadaver extremity? (2) Does MR-guided high-intensity focused ultrasound treatment stop progression and/or cause regression of extremity desmoid tumors? METHODS: Simulated tumor volumes in four human cadavers, created by using plastic markers, were ablated using a commercially available focused ultrasound system. Accuracy was determined in accordance with the International Organization of Standards location error by measuring the farthest distance between the ablated tissue and the plane corresponding to the target. Between 2012 and 2014, we treated nine patients with desmoid tumors using focused ultrasound ablation. Indications for this were tumor-related symptoms or failure of conventional treatment. Of those, five of them were available for MRI followup at 12 months or longer (mean, 18.2 months; range, 12-23 months). The radiographic and clinical outcomes of five patients who had desmoid tumors treated with focused ultrasound were prospectively recorded. Patients were assessed preoperatively with MRI and followed at routine intervals after treatment with MRI scans and clinical examination. RESULTS: The ablation accuracy for the four cadaver extremities was 5 mm, 3 mm, 8 mm, and 8 mm. Four patients' tumors became smaller after treatment and one patient has slight progression at the time of last followup. The mean decrease in tumor size determined by MRI measurements was 36% (95% confidence interval, 7%-66%). No patient has received additional adjuvant systemic or local treatment. Treatment-related adverse events included first- and second-degree skin burns occurring in four patients, which were managed successfully without further surgery. CONCLUSIONS: This preliminary investigation provides some evidence that MR-guided high-intensity focused ultrasound may be a feasible treatment for desmoid tumors. It may also be of use for other soft tissue neoplasms in situations in which there are limited traditional treatment options such as recurrent sarcomas. Further investigation is necessary to better define the indications, efficacy, role, and long-term oncologic outcomes of focused ultrasound treatment. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Sarcoma Resection With and Without Vascular Reconstruction: A Matched Case-control Study.

OBJECTIVE: To examine the impact of major vascular resection on sarcoma resection outcomes. SUMMARY BACKGROUND DATA: En bloc resection and reconstruction of involved vessels is being increasingly performed during sarcoma surgery; however, the perioperative and oncologic outcomes of this strategy are not well described. METHODS: Patients undergoing sarcoma resection with (VASC) and without (NO-VASC) vascular reconstruction were 1:2 matched on anatomic site, histology, grade, size, synchronous metastasis, and primary (vs. repeat) resection. R2 resections were excluded. Endpoints included perioperative morbidity, mortality, local recurrence, and survival. RESULTS: From 2000 to 2014, 50 sarcoma patients underwent VASC resection. These were matched with 100 NO-VASC patients having similar clinicopathologic characteristics. The rates of any complication (74% vs. 44%, P = 0.002), grade 3 or higher complication (38% vs. 18%, P = 0.024), and transfusion (66% vs. 33%, P < 0.001) were all more common in the VASC group. Thirty-day (2% vs. 0%, P = 0.30) or 90-day mortality (6% vs. 2%, P = 0.24) were not significantly higher. Local recurrence (5-year, 51% vs. 54%, P = 0.11) and overall survival after resection (5-year, 59% vs. 53%, P = 0.67) were similar between the 2 groups. Within the VASC group, overall survival was not affected by the type of vessel involved (artery vs. vein) or the presence of histology-proven vessel wall invasion. CONCLUSIONS: Vascular resection and reconstruction during sarcoma resection significantly increases perioperative morbidity and requires meticulous preoperative multidisciplinary planning. However, the oncologic outcome appears equivalent to cases without major vascular involvement. The anticipated need for vascular resection and reconstruction should not be a contraindication to sarcoma resection.

What is the use of imaging before referral to an orthopaedic oncologist? A prospective, multicenter investigation.

BACKGROUND: Patients often receive advanced imaging before referral to an orthopaedic oncologist. The few studies that have evaluated the value of these tests have been single-center studies, and there were large discrepancies in the estimated frequencies of unnecessary use of diagnostic tests. QUESTIONS/PURPOSES: (1) Is there regional variation in the use of advanced imaging before referral to an orthopaedic oncologist? (2) Are these prereferral studies helpful to the treating orthopaedic oncologist in making a diagnosis or treatment plan? (3) Are orthopaedic surgeons less likely to order unhelpful studies than other specialties? (4) Are there any tumor or patient characteristics that are associated with the ordering of an unhelpful study? METHODS: We performed an eight-center prospective analysis of patients referred for evaluation by a fellowship-trained orthopaedic oncologist. We recorded patient factors, referral details, advanced imaging performed, and presumptive diagnosis. The treating orthopaedic oncologist determined whether each study was helpful in the diagnosis or treatment of the patient based on objective and subjective criteria used in prior investigations. We analyzed the data using bivariate methods and logistic regression to determine regional variation and risk factors predictive of unhelpful advanced imaging. Of the 371 participants available for analysis, 301 (81%) were referred with an MRI, CT scan, bone scan, ultrasound, or positron emission tomography scan. RESULTS: There were no regional differences in the use of advanced imaging (range of patients presenting with advanced imaging 66%-88% across centers, p = 0.164). One hundred thirteen patients (30%) had at least one unhelpful study; non-MRI advanced imaging was more likely to be unhelpful than MRIs (88 of 129 [68%] non-MRI imaging versus 46 of 263 [17%] MRIs [p < 0.001]). Orthopaedic surgeons were no less likely than nonorthopaedic surgeons to order unhelpful studies before referral to an orthopaedic oncologist (56 of 179 [31%] of patients referred by orthopaedic surgeons versus 35 of 119 [29%] referred by primary care providers and 22 of 73 [30%] referred by nonorthopaedic specialists, p = 0.940). After controlling for potential confounding variables, benign bone lesions had an increased odds of referral with an unhelpful study (59 of 145 [41%] of benign bone tumors versus 54 of 226 [24%] of soft tissue tumors and malignant bone tumors; odds ratio, 2.80; 95% confidence interval, 1.68-4.69, p < 0.001). CONCLUSIONS: We found no evidence that the proportion of patients referred with advanced imaging varied dramatically by region. Studies other than MRI were likely to be considered unhelpful and should not be routinely ordered by referring physicians. Diligent education of orthopaedic surgeons and primary care physicians in the judicious use of advanced imaging in benign bone tumors may help mitigate unnecessary imaging. LEVEL OF EVIDENCE: Level III, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence.

Principles of musculoskeletal biopsy.

The appropriate treatment of any musculoskeletal tumor is based on a correct diagnosis. In some instances, a patient's history and imaging studies provide sufficient information to guide definitive treatment. However, in many cases, a biopsy may be necessary. A biopsy, although technically simple, must be conducted in a thoughtful manner in order to obtain an accurate tissue sample while avoiding complications. Some potential complications include inaccurate sampling, improperly placed incision that complicates future surgeries, and healthy tissue contamination that can add morbidity to the definitive surgery or preclude the chance of limb salvage. This chapter will review the considerations for planning and performing a biopsy of musculoskeletal tumors.

Antirotation pins improve stability of the compress limb salvage implant: a biomechanical study.

BACKGROUND: Limb salvage implants that rely on compliant compression osseointegration to achieve bone fixation may achieve longer survivorship rates compared with traditional cemented or press-fit stemmed implants; however, failures resulting from rotational instability have been reported. The effect of using antirotation pins on the rotational stability of the fixation has not been well studied. QUESTIONS/PURPOSES: We asked the following question: When tested in a cadaver model, does the use of antirotation pins increase the torque required to cause implant failure or rotation? METHODS: Thirty-two cadaver femurs were divided into four groups of eight femurs. We compared the torque to failure among groups containing zero, one, two, three, and four pins using a servohydraulic testing device. RESULTS: Adding antirotation pins increased the torque required to cause failure (R(2) = 0.77; p < 0.001). This increase was most notable in groups comparing zero pins with one pin (14 N-m, [95% CI, 10.9-17.1] versus 23 N-m, [95% CI 22.5-23.48]; p = 0.01) and two compared with three pins (29 N-m, [95% CI, 21.7-36.3] versus 42 N-m, [95% CI, 37.8-46.2]; p = 0.35). CONCLUSIONS: It appears that the use of antirotation pins improves rotational stability of the compliant compression endoprosthesis. Although these findings need to be verified in a clinical study, the addition of antirotation pins may improve osteointegration and we have changed our practice to use a minimum of three antirotation pins when implanting this device. CLINICAL RELEVANCE: Improvements in implant technology and surgical techniques may lead to improved clinical outcomes and patient quality of life. Addition of antirotation pins appears to improve implant stability and may decrease the need for revision surgery.

Patterns of Local Recurrence and Risk of Skin Recurrence in Soft Tissue Sarcomas After Surgical Resection.

PURPOSE: Although there is a theoretical risk of skin seeding during surgical resection of soft tissue sarcomas (STSs), current consensus guidelines recommend against routine use of bolus during radiation therapy (RT). However, the risk of skin recurrence has not been systematically assessed. We aimed to assess the patterns of local recurrence (LR) in patients with STS treated with surgery with or without RT. METHODS AND MATERIALS: We performed a retrospective analysis of adults with STSs evaluated at our institution between 2007 and 2021. For patients who developed LR, the depth was evaluated. Progression-free survival and overall survival were analyzed from time of first LR using the Kaplan-Meier method. Cumulative incidence of distant metastasis was calculated with competing risk analysis from date of LR. RESULTS: Of the 206 patients evaluated, 20 had LR (9.7%). Among patients with LR, 5 patients (25.0%) were treated with surgery alone and 15 patients (75.0%) with surgery and RT. In patients treated with RT, 46.7% had preoperative RT, 53.3% had postoperative RT, and bolus was used in 46.7%. Surgical margins were close (<1 mm) in 4 patients (20.0%) and positive in 10 patients (50.0%). LR occurred in the deep subfascial tissue in 9 patients (45%), subcutaneous tissue in 10 patients (50.0%), and skin in 1 patient (5.0%). The patient with a skin recurrence was treated with surgery alone, and the tumor involved the skin at presentation. In patients treated with RT, LR occurred within the RT field in 13 patients (86.7%). At 1 year after LR, progression-free survival was 70.3%, overall survival was 81.7%, and cumulative incidence of distant metastasis was 5.9%. CONCLUSIONS: Skin recurrences were rare after surgical resection of STSs and only occurred in a tumor that involved the skin at initial presentation. These findings support current recommendations against routine use of bolus in STSs not involving the skin at presentation.

Osteosarcoma PDX-Derived Cell Line Models for Preclinical Drug Evaluation Demonstrate Metastasis Inhibition by Dinaciclib through a Genome-Targeted Approach.

PURPOSE: Models to study metastatic disease in rare cancers are needed to advance preclinical therapeutics and to gain insight into disease biology. Osteosarcoma is a rare cancer with a complex genomic landscape in which outcomes for patients with metastatic disease are poor. As osteosarcoma genomes are highly heterogeneous, multiple models are needed to fully elucidate key aspects of disease biology and to recapitulate clinically relevant phenotypes. EXPERIMENTAL DESIGN: Matched patient samples, patient-derived xenografts (PDX), and PDX-derived cell lines were comprehensively evaluated using whole-genome sequencing and RNA sequencing. The in vivo metastatic phenotype of the PDX-derived cell lines was characterized in both an intravenous and an orthotopic murine model. As a proof-of-concept study, we tested the preclinical effectiveness of a cyclin-dependent kinase inhibitor on the growth of metastatic tumors in an orthotopic amputation model. RESULTS: PDXs and PDX-derived cell lines largely maintained the expression profiles of the patient from which they were derived despite the emergence of whole-genome duplication in a subset of cell lines. The cell lines were heterogeneous in their metastatic capacity, and heterogeneous tissue tropism was observed in both intravenous and orthotopic models. Single-agent dinaciclib was effective at dramatically reducing the metastatic burden. CONCLUSIONS: The variation in metastasis predilection sites between osteosarcoma PDX-derived cell lines demonstrates their ability to recapitulate the spectrum of the disease observed in patients. We describe here a panel of new osteosarcoma PDX-derived cell lines that we believe will be of wide use to the osteosarcoma research community.

Sarcoma microenvironment cell states and ecosystems are associated with prognosis and predict response to immunotherapy.

Characterization of the diverse malignant and stromal cell states that make up soft tissue sarcomas and their correlation with patient outcomes has proven difficult using fixed clinical specimens. Here, we employed EcoTyper, a machine-learning framework, to identify the fundamental cell states and cellular ecosystems that make up sarcomas on a large scale using bulk transcriptomes with clinical annotations. We identified and validated 23 sarcoma-specific, transcriptionally defined cell states, many of which were highly prognostic of patient outcomes across independent datasets. We discovered three conserved cellular communities or ecotypes associated with underlying genomic alterations and distinct clinical outcomes. We show that one ecotype defined by tumor-associated macrophages and epithelial-like malignant cells predicts response to immune-checkpoint inhibition but not chemotherapy and validate our findings in an independent cohort. Our results may enable identification of patients with soft tissue sarcomas who could benefit from immunotherapy and help develop new therapeutic strategies.

Development and characterization of new patient-derived xenograft (PDX) models of osteosarcoma with distinct metastatic capacities.

Models to study metastatic disease in rare cancers are needed to advance preclinical therapeutics and to gain insight into disease biology, especially for highly aggressive cancers with a propensity for metastatic spread. Osteosarcoma is a rare cancer with a complex genomic landscape in which outcomes for patients with metastatic disease are poor. As osteosarcoma genomes are highly heterogeneous, a large panel of models is needed to fully elucidate key aspects of disease biology and to recapitulate clinically-relevant phenotypes. We describe the development and characterization of osteosarcoma patient-derived xenografts (PDXs) and a panel of PDX-derived cell lines. Matched patient samples, PDXs, and PDX-derived cell lines were comprehensively evaluated using whole genome sequencing and RNA sequencing. PDXs and PDX-derived cell lines largely maintained the expression profiles of the patient from which they were derived despite the emergence of whole-genome duplication (WGD) in a subset of cell lines. These cell line models were heterogeneous in their metastatic capacity and their tissue tropism as observed in both intravenous and orthotopic models. As proof-of-concept study, we used one of these models to test the preclinical effectiveness of a CDK inhibitor on the growth of metastatic tumors in an orthotopic amputation model. Single-agent dinaciclib was effective at dramatically reducing the metastatic burden in this model.

Surgical technique: Methods for removing a Compress® compliant prestress implant.

BACKGROUND: The Compress® device uses a unique design using compressive forces to achieve bone ingrowth on the prosthesis. Because of its design, removal of this device may require special techniques to preserve host bone. DESCRIPTION OF TECHNIQUES: Techniques needed include removal of a small amount of bone to relieve compressive forces, use of a pin extractor and/or Kirschner wires for removal of transfixation pins, and creation of a cortical window in the diaphysis to gain access to bone preventing removal of the anchor plug. METHODS: We retrospectively reviewed the records of 63 patients receiving a Compress® device from 1996 to 2011 and identified 11 patients who underwent subsequent prosthesis removal. The minimum followup was 1 month (average, 20 months; range, 1-80 months). The most common reason for removal was infection (eight patients) and the most common underlying diagnosis was osteosarcoma (five patients). Three patients underwent above-knee amputation, whereas the others (eight patients) had further limb salvage procedures at the time of prosthesis removal. RESULTS: Five patients had additional unplanned surgeries after explantation. Irrigation and débridement of the surgical wound was the most common unplanned procedure followed by latissimus free flap and hip prosthesis dislocation. At the time of followup, all patients were ambulating on either salvaged extremities or prostheses. CONCLUSION: Although removal of the Compress® device presents unique challenges, we describe techniques to address those challenges.

The US Medical Licensing Examination Step 1 Scoring Change: A Survey of Orthopaedic Surgery Residency Applicants From the 2019 to 2020 Match Cycle.

INTRODUCTION: The USMLE Step 1 examination has been used as an objective measure for comparing residency applicants. Recently, the National Board of Medical Examiners and the Federation of State Medical Boards decided that the USMLE Step 1 examination will transition to a pass/fail result starting no earlier than 2022. The purpose of this study was to investigate the perspective of medical students who applied for orthopaedic surgery residency positions during the 2019 to 2020 interview cycle on the USMLE scoring change, and the potential effect this change may result in for future applicants and the residency selection process. METHODS: A 15-item anonymous web-based survey was sent to 1,090 orthopaedic surgery residency applicants from four regionally diverse residency programs. The survey elicited attitudes toward the transition of the Step 1 examination to pass/fail and perspectives this change may or may not have on the residency selection process. RESULTS: Responses were received from 356 applicants (32.7%). The majority (61.6%) disagreed with the change to pass/fail scoring, and 68.5% do not believe that the change will decrease stress levels in medical students. For interview invitations, respondents chose Step 2 clinical knowledge, letters of recommendation, and performance on away rotations as the most influential factors in the absence of a Step 1 score. CONCLUSION: Most of the students surveyed who applied for an orthopaedic surgery residency position during the most recent application cycle disagreed with the National Board of Medical Examiner/Federation of State Medical Board decision to change Step 1 to pass/fail and feel that this change may have disadvantage in certain student groups while either increasing or having no effect on medical student stress. LEVEL OF EVIDENCE: IV.

Metastatic Pattern of Truncal and Extremity Leiomyosarcoma: Retrospective Analysis of Predictors, Outcomes, and Detection.

Leiomyosarcomas (LMS) are a heterogenous group of malignant mesenchymal neoplasms with smooth muscle origin and are classified as either non-uterine (NULMS) or uterine (ULMS). Metastatic pattern, prognostic factors, and ideal staging/surveillance studies for truncal and extremity LMS have not been defined. A retrospective analysis of patients diagnosed with histopathology-confirmed truncal or extremity LMS between 2009 and 2019 was conducted. Data collected included demographics, tumor characteristics, staging, surveillance, and survival endpoints. The primary site was defined as: (1) extremity, (2) flank/Pelvis, or (3) chest wall/Spine. We identified 73 patients, 23.3% of which had metastatic LMS at primary diagnosis, while 68.5% developed metastatic disease at any point. The mean metastatic-free survival from primary diagnosis of localized LMS was 3.0 ± 2.8 years. Analysis of prognostic factors revealed that greater age (≥50 years) at initial diagnosis (OR = 3.74, p = 0.0003), higher tumor differentiation scores (OR = 12.09, p = 0.002), and higher tumor necrosis scores (OR = 3.65, p = 0.026) were significantly associated with metastases. Older patients (≥50 years, OR = 4.76, p = 0.017), patients with larger tumors (≥5 cm or ≥10 cm, OR = 2.12, p = 0.02, OR = 1.92, p = 0.029, respectively), higher differentiation scores (OR = 15.92, p = 0.013), and higher necrosis scores (OR = 4.68, p = 0.044) show worse survival outcomes. Analysis of imaging modality during initial staging and during surveillance showed greater tumor detection frequency when PET imaging was employed, compared to CT imaging (p < 0.0001). In conclusion, truncal and peripheral extremity LMS is an aggressive tumor with high metastatic potential and mortality. While there is a significant risk of metastases to lungs, extra-pulmonary tumors are relatively frequent, and broad surveillance may be warranted.

Management of Patients with Newly Diagnosed Desmoid Tumors in a First-Line Setting.

The initial management of desmoid tumors (DTs) is shifting from surgery towards active surveillance, with systemic and locally ablative treatments reserved for enlarging and/or symptomatic disease. However, it remains unclear which patients would benefit most from an initial conservative rather than interventional approach. To answer this question, we retrospectively analyzed adult and pediatric patients with DTs treated at a tertiary academic cancer center between 1992 and 2022. Outcomes measured were progression-free survival (PFS) and time to next treatment (TTNT) after first-line therapy. A total of 262 treatment-naïve patients were eligible for analysis with a median age of 36.5 years (range, 0−87 years). The 5-year PFS and the median TTNT (months) after first-line treatment were, respectively: 50.6% and 69.1 mo for surgery; 64.9% and 149.5 mo for surgery plus adjuvant radiotherapy; 57.1% and 44.7 mo for surgery plus adjuvant systemic therapy; 24.9% and 4.4 mo for chemotherapy; 26.7% and 5.3 mo for hormonal therapy; 41.3% and 29.6 mo for tyrosine kinase inhibitors (TKIs); 44.4% and 8.9 mo for cryoablation and high intensity focused ultrasound; and 43.1% and 32.7 mo for active surveillance. Age ≤ 40 years (p < 0.001), DTs involving the extremities (p < 0.001), a maximum tumor diameter > 60 mm (p = 0.04), and hormonal therapy (p = 0.03) predicted a higher risk of progression. Overall, our results suggest that active surveillance should be considered initially for patients with smaller asymptomatic DTs, while upfront TKIs, local ablation, and surgery achieve similar outcomes in those with more aggressive disease.

Local Control Outcomes Using Stereotactic Body Radiation Therapy or Surgical Resection for Metastatic Sarcoma.

PURPOSE: Traditional management of metastatic sarcoma primarily relies on systemic therapy, with surgery often used for tumor control. We analyzed the rates of recurrence, overall survival, and treatment complications in patients undergoing either surgical resection or stereotactic body radiation therapy (SBRT) for metastatic sarcoma of the bone and/or soft tissue. METHODS AND MATERIALS: The records of patients with metastatic sarcoma between 2009 and 2020 were reviewed. Local recurrence (LR) was defined as tumor growth or recurrence at the tumor site. Cumulative LR incidence was analyzed accounting for the competing risk of death, and groups were compared using the Gray test. Overall survival (OS) was assessed using the Kaplan-Meier method and log-rank test. Hazard ratios were determined using the Cox proportional hazards model. RESULTS: A total of 525 metastatic lesions in 217 patients were analyzed. The mean age of patients was 57 years (range, 4-88 years). The lung was the predominant site treated (50%), followed by intra-abdominal (13%) and soft tissue (11%). Two-year cumulative incidences of LR for surgery and SBRT were 14.8% (95% confidence interval [CI], 11.6%-18.5%) and 1.7% (95% CI, 0.1%-8.2%), respectively (P = .003). Local recurrence occurred in 72 (16.5%) of 437 tumors treated with surgery and 2 (2.3%) of 88 tumors treated with SBRT. The adjusted hazard ratio for LR of lesions treated surgically was 11.5 (P = .026) when controlling for tumor size and tumor site. Median OS was 29.8 months (95% CI, 25.6-40.9 months). There were 47 surgical complications among a total of 275 procedures (18%). Of 58 radiation treatment courses, radiation-related toxic effects were reported during the treatment of 7 lesions (12%), and none were higher than grade 2. CONCLUSIONS: We observed excellent local control among patients selected for treatment with SBRT for metastatic sarcoma, with no evidence of an increase in LR after SBRT compared with surgical management. Further investigation is necessary to better define the most appropriate local control strategies for metastatic sarcoma.

Interactions in CSF1-Driven Tenosynovial Giant Cell Tumors.

PURPOSE: A major component of cells in tenosynovial giant cell tumor (TGCT) consists of bystander macrophages responding to CSF1 that is overproduced by a small number of neoplastic cells with a chromosomal translocation involving the CSF1 gene. An autocrine loop was postulated where the neoplastic cells would be stimulated through CSF1R expressed on their surface. Here, we use single-cell RNA sequencing (scRNA-seq) to investigate cellular interactions in TGCT. EXPERIMENTAL DESIGN: A total of 18,788 single cells from three TGCT and two giant cell tumor of bone (GCTB) samples underwent scRNA-seq. The three TGCTs were additionally analyzed using long-read RNA sequencing. Immunofluorescence and IHC for a range of markers were used to validate and extend the scRNA-seq findings. RESULTS: Two recurrent neoplastic cell populations were identified in TGCT that are highly similar to nonneoplastic synoviocytes. We identified GFPT2 as a marker that highlights the neoplastic cells in TCGT. We show that the neoplastic cells themselves do not express CSF1R. We identified overlapping MAB features between the giant cells in TGCT and GCTB. CONCLUSIONS: The neoplastic cells in TGCT are highly similar to nonneoplastic synoviocytes. The lack of CSF1R on the neoplastic cells indicates they may be unaffected by current therapies. High expression of GFPT2 in the neoplastic cells is associated with activation of the YAP1/TAZ pathway. In addition, we identified expression of the platelet-derived growth factor receptor in the neoplastic cells. These findings suggest two additional pathways to target in this tumor.

Simulation-Based Mastery Learning to Teach Distal Radius Fracture Reduction.

INTRODUCTION: Distal radius fractures are common orthopedic injuries managed in emergency departments. Simulation-based mastery learning is widely recognized to improve provider competence for bedside procedures but has not been studied to teach fracture management. This study evaluated the effectiveness of a simulation-based mastery learning curriculum to teach distal radius fracture reduction to novice orthopedic surgery and emergency medicine residents. METHODS: We created a novel mastery learning checklist using the Mastery Angoff method of standard setting, paired with a new simulation model designed for this project, to teach orthopedic surgery and emergency medicine interns (N = 22) at the study site. Orthopedic surgery and emergency medicine faculty members participated in checklist development, curriculum design, and implementation. Training included just-in-time asynchronous education with a readiness assessment test, in-classroom expert demonstration, and deliberate practice with feedback. Residents completed a pretest/posttest skills examination and a presurvey/postsurvey assessing procedural confidence. RESULTS: Standard setting resulted in a 41-item checklist with minimum passing score of 37/41 items. All participants met or surpassed the minimum passing score on postexamination. Postsurvey confidence levels were significantly higher than presurvey in all aspects of the distal radius fracture procedure (P < 0.05). CONCLUSIONS: This study demonstrated that a simulation-based mastery learning curriculum improved skills and confidence performing distal radius fracture reductions for orthopedic surgery and emergency medicine interns. Future planned studies include curriculum testing across additional institutions, examination of clinical impact, and application of mastery learning for other orthopedic procedures.