Percutaneous Cementation for Improvement of Pain and Function for Osteolytic Pelvic Metastasis: A Systematic Review.

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

A randomized, non-comparative phase 2 study of neoadjuvant immune-checkpoint blockade in retroperitoneal dedifferentiated liposarcoma and extremity/truncal undifferentiated pleomorphic sarcoma.

Based on the demonstrated clinical activity of immune-checkpoint blockade (ICB) in advanced dedifferentiated liposarcoma (DDLPS) and undifferentiated pleomorphic sarcoma (UPS), we conducted a randomized, non-comparative phase 2 trial ( NCT03307616 ) of neoadjuvant nivolumab or nivolumab/ipilimumab in patients with resectable retroperitoneal DDLPS (n = 17) and extremity/truncal UPS (+ concurrent nivolumab/radiation therapy; n = 10). The primary end point of pathologic response (percent hyalinization) was a median of 8.8% in DDLPS and 89% in UPS. Secondary end points were the changes in immune infiltrate, radiographic response, 12- and 24-month relapse-free survival and overall survival. Lower densities of regulatory T cells before treatment were associated with a major pathologic response (hyalinization > 30%). Tumor infiltration by B cells was increased following neoadjuvant treatment and was associated with overall survival in DDLPS. B cell infiltration was associated with higher densities of regulatory T cells before treatment, which was lost upon ICB treatment. Our data demonstrate that neoadjuvant ICB is associated with complex immune changes within the tumor microenvironment in DDLPS and UPS and that neoadjuvant ICB with concurrent radiotherapy has significant efficacy in UPS.

Comparing Fibula Flap Insetting Techniques for Pediatric Oncologic Extremity Reconstruction.

BACKGROUND: Extremity reconstruction in skeletally immature patients presents unique challenges in terms of operative technique, bone healing, and limb function. A variety of insetting techniques have been described, with no clearly superior option. The authors hypothesized that vascularized fibula flaps placed in the intramedullary space are associated with shorter union times and better functionality compared with onlay flaps. METHODS: In a cohort study, the authors retrospectively reviewed the medical records of all pediatric patients who underwent fibula flap extremity reconstruction at a single center from 2001 through 2018. Comorbidities, complications, and outcomes were analyzed. Complete fibula union was based on radiographic evidence of significant cortical bridging. RESULTS: Thirty-three patients (mean age, 13.6 years; range, 2 to 18 years) underwent pedicled ( n = 7) or free ( n = 26) fibula flap reconstructions in 12 upper extremities and 21 lower extremities. Median follow-up was 69.5 months (interquartile range, 16.3 to 114.6 months). Onlay and intramedullary fibula position compared with intercalary placement (median, 13.5 and 14.6 months versus 3.4 months; P = 0.002) were associated with longer time to complete bone union. Complications including allograft fracture ( P = 0.02) and hardware removal ( P = 0.018) were also associated with longer time to complete union and eventual conversion to megaprosthesis ( P = 0.02, P = 0.038). Thirty-two patients (97%) achieved full union and a functional reconstruction. CONCLUSIONS: Fibula flap reconstruction is safe and effective for pediatric long-bone reconstruction. Longer fibula union times were associated with onlay and intramedullary fibula placement, allograft fracture, and hardware removal. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

The Use of Photodynamic Bone Stabilization to Tamponade Bleeding in a Pathologic Humeral Shaft Fracture: A Case Report.

Introduction: Hypervascular tumors such as renal and thyroid carcinoma have a significant risk of intraoperative bleeding. To help mitigate bleeding, interventional preoperative embolization is traditionally used; however, it is success is highly variable. This is the first case report to discuss using expandable balloon implants with a minimally invasive approach to achieve fracture fixation and tamponade acute intraoperative bleeding. Case Report: A 48-year-old male with clear-cell renal cell carcinoma presented with a left humeral shaft pathologic fracture. The patient was scheduled to undergo open biopsy, curettage of tumor, and fracture fixation with an intramedullary device. Intraoperatively, during open biopsy and curettage, brisk bleeding was encountered, which ceased after inserting an intramedullary photodynamic bone stabilization implant (IlluminOss). The implant's balloon expanded to the diameter of the humerus allowing for tamponade, fracture stability, and a minimally invasive approach. Conclusion: We present a possible intraoperative option for achieving control of bleeding in pathologic long bone fractures by deploying a photodynamic stabilization device. The method described can have applications in specific patients and obviate the need for pre-operative embolization for highly vascular tumors due to the implant's ability to create tamponade within the bone.

Mdm2/p53 levels in bone marrow mesenchymal stromal cells are essential for maintaining the hematopoietic niche in response to DNA damage.

Mesenchymal stromal cells (MSCs) are a key component of the bone marrow (BM) niche, providing essential support required for the maintenance of hematopoietic stem cells. To advance our understanding of physiological functions of p53 and Mdm2 in BM-MSCs, we developed traceable conditional mouse models targeting Mdm2 and/or Trp53 in vivo. We demonstrate that Mdm2 is essential for the emergence, maintenance, and hematopoietic support of BM-MSCs. Mdm2 haploinsufficiency in BM-MSCs resulted in genotoxic stress-associated thrombocytopenia, suggesting a functional role for Mdm2 in hematopoiesis. In a syngeneic mouse model of acute myeloid leukemia (AML), Trp53 deletion in BM-MSCs improved survival, and protected BM against hematopoietic toxicity from a murine Mdm2i, DS-5272. The transcriptional changes were associated with dysregulation of glycolysis, gluconeogenesis, and Hif-1α in BM-MSCs. Our results reveal a physiologic function of Mdm2 in BM-MSC, identify a previously unknown role of p53 pathway in BM-MSC-mediated support in AML and expand our understanding of the mechanism of hematopoietic toxicity of MDM2is.

What Is the Prosthetic Survival After Resection and Intercalary Endoprosthetic Reconstruction for Diaphyseal Bone Metastases of the Humerus and Femur?

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

Mdm2/p53 levels in bone marrow mesenchymal stromal cells is essential for maintaining the hematopoietic niche in response to DNA damage.

Mesenchymal stromal cells (MSCs) are a key component of the bone marrow (BM) niche, providing essential support required for maintenance of hematopoietic stem cells. To advance our understanding of physiological functions of p53 and Mdm2 in BM-MSCs, we developed traceable conditional mouse models targeting Mdm2 and/or Trp53 in vivo . We demonstrate that Mdm2 is essential for the emergence, maintenance and hematopoietic support of BM-MSCs. Mdm2 haploinsufficiency in BM-MSCs resulted in genotoxic stress-associated thrombocytopenia, suggesting a functional role for Mdm2 in hematopoiesis. In a syngeneic mouse model of acute myeloid leukemia (AML), Trp53 deletion in BM-MSCs improved survival, and protected BM against hematopoietic toxicity from a murine Mdm2i, DS-5272. The transcriptional changes were associated with dysregulation of glycolysis, gluconeogenesis, and Hif-1α in BM-MSCs. Our results reveal a physiologic function of Mdm2 in BM-MSC, identify a previously unknown role of p53 pathway in BM-MSC-mediated support in AML and expand our understanding of the mechanism of hematopoietic toxicity of MDM2is.

Free Fibula Flap for Extremity Oncologic Defects: Factors Influencing Union and Functional Outcomes.

BACKGROUND: The goal of this study was to evaluate outcomes after vascularized bone flap (VBF) reconstruction of oncologic bony extremity defects. A secondary goal was to compare union rates based on various insetting methods, including onlay, intermedullary, and intercalary. METHODS: The authors conducted a retrospective review of consecutive patients who received an extremity reconstruction with a fibula flap after oncologic resection between 2001 and 2019. RESULTS: The authors identified a total of 60 fibular VBFs in 55 patients (67% lower extremity, 33% upper extremity). The overall union rate was 91.7% (55 of 60). For lower extremity reconstructions, the mean time to full weightbearing was 16 months (range, 4 to 44 months). Fibula VBFs were onlay in 65% of cases, intercalary in 23%, and intramedullary in 12%. Forty-three percent of patients required a reoperation as a result of a surgical complication. Immediate femur reconstruction subgroup analysis demonstrated that onlay fibula flap orientation was associated with a significantly increased risk for any complication (odds ratio, 6.3; 95% CI, 1.4 to 28.7; P = 0.03) as well as an increased risk for requiring conversion to endoprostheses because of nonunion (OR, 12.1; 90% CI, 1.03 to 143.5; P = 0.03) compared with intramedullary placement. CONCLUSIONS: The free vascularized fibula flap is a reliable option for functional reconstruction of any long bone extremity defect, but complications in these complex procedures are not uncommon. In patients with immediate femur reconstructions, intramedullary fibula placement was associated with significantly lower complication and lower metallic implant conversion rates and a trend toward a more rapid early union compared with onlay VBF. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Practice Pattern Variability in the Management of Regional Lymph Node Metastasis in Extremity and Trunk Soft Tissue Sarcoma: A Survey of the Society of Surgical Oncology and Musculoskeletal Tumor Society Membership.

BACKGROUND: Regional lymph node metastasis in extremity and trunk soft tissue sarcoma (ETSTS) is rare with no standardized management. We sought to determine management patterns for regional lymph node metastasis in ETSTS. METHODS: A survey regarding the management of ETSTS lymph node metastasis was distributed to the membership of the Musculoskeletal Tumor Society (MSTS) and the Society of Surgical Oncology (SSO) in January 2022. The survey queried the type of training (surgical oncology, orthopedic oncology), details of their practice setting, and management decisions of hypothetical ETSTS scenarios that involved potential or confirmed lymph node metastasis. RESULTS: The survey was distributed to 349 MSTS members (open rate of 63%, completion rate 21%) and 3026 SSO members (open rate of 55%, completion rate 4.7%) and was completed by 214 respondents, of whom 73 (34.1%) and 141 (65.9%) were orthopedic oncology and surgical oncology fellowship-trained, respectively. The majority of respondents practiced in an academic setting (n = 171, 79.9%) and treat >10 extremity sarcoma cases annually (n = 138, 62.2%). In scenarios with confirmed nodal disease for clear cell and epithelioid sarcoma, surgical oncologists were inclined to perform lymphadenectomy, while orthopedic oncologists were inclined to offer targeted lymph node excision with adjuvant radiation (p < 0.001). There was heterogeneity of responses regarding the management of nodal disease regardless of training background. CONCLUSION: Self-reported management of nodal disease in ETSTS was variable among respondent groups with differences and similarities based on training background. These data highlight the variability of practice for nodal disease management and the need for consensus-based guidelines.

Hypofractionated, 3-week, preoperative radiotherapy for patients with soft tissue sarcomas (HYPORT-STS): a single-centre, open-label, single-arm, phase 2 trial.

BACKGROUND: The standard preoperative radiotherapy regimen of 50 Gy delivered in 25 fractions for 5 weeks for soft tissue sarcomas results in excellent local control, with major wound complications occurring in approximately 35% of patients. We aimed to investigate the safety of a moderately hypofractionated, shorter regimen of radiotherapy, which could be more convenient for patients. METHODS: This single-centre, open-label, single-arm, phase 2 trial (HYPORT-STS) was done at a single tertiary cancer care centre (MD Anderson Cancer Center, Houston, TX, USA). We administered preoperative radiotherapy to a dose of 42·75 Gy in 15 fractions of 2·85 Gy/day for 3 weeks (five fractions per week) to adults (aged ≥18 years) with non-metastatic soft tissue sarcomas of the extremities or superficial trunk and an Eastern Cooperative Oncology Group performance status of 0-3. The primary endpoint was a major wound complication occurring within 120 days of surgery. Major wound complications were defined as those requiring a secondary operation, or operations, under general or regional anaesthesia for wound treatment; readmission to the hospital for wound care; invasive procedures for wound care; deep wound packing to an area of wound measuring at least 2 cm in length; prolonged dressing changes; repeat surgery for revision of a split thickness skin graft; or wet dressings for longer than 4 weeks. We analysed our primary outcome and safety in all patients who enrolled. We monitored safety using a Bayesian, one-arm, time-to-event stopping rule simulator comparing the rate of major wound complications at 120 days post-surgery among study participants with the historical rate of 35%. This trial is registered with ClinicalTrials.gov, NCT03819985, recruitment is complete, and follow-up continues. FINDINGS: Between Dec 18, 2018, and Jan 6, 2021, we assessed 157 patients for eligibility, of whom 120 were enrolled and received hypofractionated preoperative radiotherapy. At no time did the stopping rule computation indicate that the trial should be stopped early for lack of safety. Median postoperative follow-up was 24 months (IQR 17-30). Of 120 patients, 37 (31%, 95% CI 24-40) developed a major wound complication at a median time of 37 days (IQR 25-59) after surgery. No patient had acute radiation toxicity (during radiotherapy or within 4 weeks of the radiotherapy end date) of grade 3 or worse (Common Terminology Criteria for Adverse Events [CTCAE] version 4.0) or an on-treatment serious adverse event. Four (3%) of 115 patients had late radiation toxicity (≥6 months post-surgery) of at least grade 3 (CTCAE or Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer Late Radiation Morbidity Scoring Scheme): femur fractures (n=2), lymphoedema (n=1), and skin ulceration (n=1). There were no treatment-related deaths. INTERPRETATION: Moderately hypofractionated preoperative radiotherapy delivered to patients with soft tissue sarcomas was safe and could therefore be a more convenient alternative to conventionally fractionated radiotherapy. Patients can be counselled about these results and potentially offered this regimen, particularly if it facilitates care at a sarcoma specialty centre. Results on long-term oncological, late toxicity, and functional outcomes are awaited. FUNDING: The National Cancer Institute.

Fresh Tissue Multi-omics Profiling Reveals Immune Classification and Suggests Immunotherapy Candidates for Conventional Chondrosarcoma.

PURPOSE: There is still no standard nonsurgical regimen for conventional chondrosarcoma (CHS). We aimed to identify whether any CHSs have a favored microenvironment for immunotherapy via multidimensional evaluation of the immunologic characteristics of this tumor. EXPERIMENTAL DESIGN: We obtained 98 newly-diagnosed CHS fresh tumors from several institutions and performed comprehensive analysis of data from CyTOF, whole-exome sequencing, and flow cytometry in 22 cases. Clinical data from immunotherapy responders and nonresponders were compared to explore possible biomarkers of immunotherapy response. Mechanism studies were conducted to interpret the biomarker phenotype. RESULTS: Based on the integrated data of single-cell CyTOF and flow cytometry, the CHS immune-microenvironment phenotypes were classified into three groups: subtype I, the "granulocytic-myeloid-derived suppressor cell (G-MDSC) dominant" cluster, with high number of HLA-DR- CD14- myeloid cells; subtype II, the "immune exhausted" cluster, with high exhausted T-cell and dendritic-cell infiltration; and subtype III, the "immune desert" cluster, with few immune cells. Immune cell-rich subtypes (subtype I and II) were characterized by IDH mutation, pathologic high grade, and peritumoral edema, while subtype I cases were exclusively featured by myxoid transformation. In clinical practice involving 12 individuals who received PD-1 antibody immunotherapy, all of the 3 cases with controlled diseases were retrospectively classified as subtype II. In mechanism, IDH mutation significantly elevated chemokine levels and immune-cell infiltration in immune-inactivated tumors. CONCLUSIONS: This study is the first to provide immune characterization of CHS, representing a major step to precise immunotherapy against this malignancy. Immunotherapy is promising for the "immune exhausted" subtype of patients with CHS.

Osteofibrous dysplasia and adamantinoma: A summary of diagnostic challenges and surgical techniques.

Osteofibrous dysplasia is an indolent benign fibro-osseous tumor, while adamantinoma is a locally aggressive biphasic malignancy with epithelial and fibro-osseous components. Predominantly arising in the tibial diaphysis of children and young adults, both tumors are resistant to chemotherapy and radiation. Wide surgical resection is regarded as the mainstay of therapy for adamantinoma, and limb-salvage reconstructive procedures can achieve good functional outcomes, albeit with non-negligible rates of complications. This review discusses emerging advances in the pathogenesis, histogenesis, and diagnosis of these entities and presents advantages and limitations of the most common surgical techniques used for their management.

Bone Metastases: Mechanisms of the Metastatic Process, Imaging and Therapy.

The mechanisms by which tumors metastasize to bone are complex. Upon the successful establishment of metastatic deposits in the skeleton, detection of the disease becomes essential for therapeutic planning. The roles of CT, skeletal scintigraphy, SPECT/CT, MRI, PET/CT and PET/MRI will be reviewed. Therapeutic response criteria specifically designed to evaluate bone metastases (MD Anderson/MDA criteria) can guide image interpretation. Knowledge of therapeutic strategies such as systemic therapy with bisphosphonates or radiopharmaceuticals, radiation therapy, surgery, and percutaneous interventions such as vertebroplasty and radiofrequency ablation can help the radiologist produce reports that will provide maximum benefit to clinicians and patients.

Synovial Sarcoma of the Hand and Foot: An Institutional Review.

OBJECTIVES: Synovial sarcomas (SS) arising in distal extremities are rare and have been studied using mostly case reports and small series. We aimed to evaluate clinical presentation and survival outcomes for patients with hand or foot SS. MATERIALS AND METHODS: We conducted a retrospective review of 84 patients diagnosed with primary hand (n=20) and foot (n=64) SS between 1979 and 2019. Progression-free survival (PFS), overall survival (OS), local recurrence-free survival and metastasis-free survival were estimated using the Kaplan-Meier method and log-rank test. Cox-proportional hazards regression was used to estimate the hazard ratios. RESULTS: Of 84 patients, 63 (75%) presented with localized disease with 36 years median age at diagnosis (range: 4 to 76) and 21 (25%) with metastasis with 30 years median age at diagnosis (range: 15 to 64). Among patients presenting with localized disease, (1) 5 years-PFS, OS, local recurrence-free survival, and metastasis-free survival rates were 82%, 88%, 100%, and 86%, respectively. (2) Tumor size <3.0 cm corresponded to 95% 5 years-PFS (vs. 84% for 3.0 to 4.9 cm, 53% for ≥5.0 cm; P=0.007) and 100% 5 years-OS (vs. 77% for ≥3.0 cm; P=0.04). (3) Patients with ≥5.0 cm (vs. <3.0 cm) tumor size had 7.99 (95% confidence interval: 1.68, 37.91) times higher hazard of progression. Remarkably, patients presenting with metastasis had 50% 5 years-OS rate. Also, younger age (15 to 39 vs. 40 y and above) predicted better OS among patients presenting with localized disease (P=0.04) and with metastasis (P=0.03). CONCLUSIONS: Survival outcomes are favorable for younger patients with <3.0 cm hand or foot SS. Local control is excellent, but we observed larger tumor size to be associated with poorer outcomes. Therefore, we recommend consideration of systemic therapy for patients with ≥3.0 cm hand or foot SS.

Surgical drainage after limb salvage surgery and endoprosthetic reconstruction: is 30 mL/day critical?

BACKGROUND: Periprosthetic infection is a major cause of failure after segmental endoprosthetic reconstruction. The purpose of this study is to determine whether certain aspects of drain output affect infection risk, particularly the 30 mL/day criterion for removal. METHODS: Two hundred and ninety-five patients underwent segmental bone resection and lower limb endoprosthetic reconstruction at one institution. Data on surgical drain management and occurrence of infection were obtained from a retrospective review of patients' charts and radiographs. Univariate and multivariate Cox regression analyses were performed to identify factors associated with infection. RESULTS: Thirty-one of 295 patients (10.5%) developed infection at a median time of 13 months (range 1-108 months). Staphylococcus aureus was the most common organism and was responsible for the majority of cases developing within 1 year of surgery. Mean output at the time of drain removal was 72 mL/day. Ten of 88 patients (11.3%) with ≤ 30 mL/day drainage and 21 of 207 patients (10.1%) with > 30 mL/day drainage developed infection (p = 0.84). In multivariate analysis, independent predictive factors for infection included sarcoma diagnosis (HR 4.13, 95% CI 1.4-12.2, p = 0.01) and preoperative chemotherapy (HR 3.29, 95% CI 1.1-9.6, p = 0.03). CONCLUSION: Waiting until drain output is < 30 mL/day before drain removal is not associated with decreased risk of infection for segmental endoprostheses of the lower limb after tumor resection. Sarcoma diagnosis and preoperative chemotherapy were independent predictors of infection.

Evaluating the Soft Tissue Sarcoma Paradigm for the Local Management of Extraskeletal Ewing Sarcoma.

OBJECTIVES: We reviewed our experience treating patients with localized extraskeletal Ewing sarcoma (EES) to determine optimal local management strategies for this rare disease. METHODS: Sixty patients with localized EES treated at our institution between 1994 and 2018 were reviewed. The Kaplan-Meier method was used to estimates disease outcomes. RESULTS: The median follow-up time was 74 months (interquartile range [IQR], 17-121). Half the patients (n = 30) received combined-modality local therapy (CMT) with both surgery and radiation therapy (RT), whereas the other half received single-modality local therapy (SMT) with either surgery or RT. All patients received chemotherapy. The 5-year overall survival was 76%. Twenty-two patients (37%) developed recurrence at a median time of 15 months (IQR, 5-56 months) resulting in 3-year progression-free survival (PFS) of 65%. On univariate analysis, the use of both neoadjuvant and adjuvant chemotherapy was associated with improved 5-year PFS (71% vs. 50%, p = .04) compared with those who received one or the other. Furthermore, 11 patients (18%) developed local recurrences at a median time of 14 months (IQR, 2-19 months), resulting in a 5-year local control (LC) rate of 77%. Use of CMT was not associated with improved LC (83% vs. 72% SMT, p = .41). Also, use of CMT was the only factor associated with poorer disease-specific survival (vs. SMT; hazard ratio, 3.4; p = .047; 95% confidence interval, 1.01-11.4). CONCLUSION: For patients with EES, CMT was not associated with a decreased rate of local relapse. These data suggest that SMT alone may be sufficient for LC in select patients. A multi-institutional collaborative effort should be considered to validate these findings. IMPLICATIONS FOR PRACTICE: Extraskeletal Ewing sarcoma is a rare chemosensitive sarcoma whose clinical course more closely follows Ewing sarcoma of bone rather than that of other soft tissue sarcomas. Based on this study, combined-modality local therapy did not confer a local control advantage compared with single-modality local therapy. Therefore, single-modality local therapy is likely adequate in select patients with favorable disease features, which has the advantage of ensuring prompt administration of systemic therapy. A multi-institutional collaborative effort is warranted to determine which patients may benefit from de-escalated local therapy.

Synovial Sarcoma: A Complex Disease with Multifaceted Signaling and Epigenetic Landscapes.

PURPOSE OF REVIEW: Aside from a characteristic SS18-SSX translocation identified in almost all cases, no genetic anomalies have been reliably isolated yet to drive the pathogenesis of synovial sarcoma. In the following review, we explore the structural units of wild-type SS18 and SSX, particularly as they relate to the transcriptional alterations and cellular pathway changes imposed by SS18-SSX. RECENT FINDINGS: Native SS18 and SSX contribute recognizable domains to the SS18-SSX chimeric proteins, which inflict transcriptional and epigenetic changes through selective protein interactions involving the SWI/SNF and Polycomb chromatin remodeling complexes. Multiple oncogenic and developmental pathways become altered, collectively reprogramming the cellular origin of synovial sarcoma and promoting its malignant transformation. Synovial sarcoma is characterized by complex epigenetic and signaling landscapes. Identifying the operational pathways and concomitant genetic changes induced by SS18-SSX fusions could help develop tailored therapeutic strategies to ultimately improve disease control and patient survivorship.

A reconstructive algorithm of oncologic defects of the upper trunk and shoulder girdle: Factors predicting complexity and outcomes.

BACKGROUND: Locally advanced malignancies of the upper torso and shoulder girdle (UT-SG) necessitate extensive resection and complex reconstruction. Due to the infrequent nature of these operations, a global reconstructive algorithm has not been defined. METHODS: A retrospective review of all patients who received reconstructive surgery following malignant tumor extirpation in the UT-SG from 2008 to 2018 at the University of Texas MD Anderson Cancer Center. Factors predicting the need for flap reconstruction and risk for postoperative complications were evaluated. RESULTS: In total, 252 procedures met inclusion criteria. The most common pathology was sarcoma (76%) and 52% were primary tumors. The median defect area was 112 cm2 (range 4-1350 cm2 ). Reconstructive techniques included pedicled flaps (46%), local tissue rearrangement (38%), and free flaps (16%). On univariate analysis, the probability of needing a free flap increased 39% when the defect size increased by 100 cm2 . The strongest independent predictors of requiring a free flap were major vessel exposure (adjusted odds ratio [OR] = 4.92, 95% confidence interval [CI], 1.36-17.84, P = .015) and major peripheral nerve exposure (adjusted OR = 3.2, 95% CI, 1.1-9.2, P = .031). CONCLUSION: Despite the aggressive nature of their malignancies, patients requiring an UT-SG resection demonstrate high survival rates and therefore demand a durable reconstruction. Exposed critical structures and defect size were predictive of free tissue transfer.

Diagnostic Value of TLE1 in Synovial Sarcoma: A Systematic Review and Meta-Analysis.

BACKGROUND: Synovial sarcoma can present morphologically in multiple forms, including biphasic and monophasic subtypes. As a result, the histological diagnosis can sometimes be challenging. Transducin-Like Enhancer 1 (TLE1) is a transcriptional corepressor that normally is involved in embryogenesis and hematopoiesis but is also expressed in certain tumors. This systematic review examines the potential role of TLE1 as a diagnostic biomarker for the synovial sarcoma. Materials and Methods. A literature review and meta-analysis were conducted using the electronic databases Pubmed, the Cochrane Library, and Google Scholar. Thirteen studies met our eligibility criteria and were selected for in-depth analysis. RESULTS: The mean sensitivity and specificity of TLE1 in detecting synovial sarcoma were 94% (95% CI 91%-97%) and 81% (95% CI 72%-91%), respectively, when all studies were aggregated together. The mean positive predictive value (PPV) of TLE1 was 75% (95% CI 62%-87%), whereas the negative predictive value (NPV) was 96% (95% CI 93%-98%). CONCLUSION: TLE1 is a sensitive and specific marker for synovial sarcoma that can aid in its diagnosis. Due to its involvement in several relevant signaling pathways, TLE1 might have direct relevance to the pathophysiology of the disease.