Cell-cycle phase progression analysis identifies three unique phenotypes in soft tissue sarcoma.

PURPOSE: Loddo et al. (Br J Cancer 100:959-70, 2009) established the prognostic significance of cell cycle markers and "Cell-Cycle Phenotypes" in breast carcinoma. This study aims to 1) identify prognostic cell-cycle markers in sarcoma, and 2) assess the prognostic potential of specific cell-cycle phenotypes in sarcoma. METHODS: Tissue samples from 128 soft tissue sarcomas were stained for four cell cycle-specific markers: Mcm2, Geminin, Plk1, and H3S10ph. Only primary soft tissue tumors (liposarcoma, leiomyosarcoma, synovial sarcoma, and undifferentiated pleomorphic sarcoma) were included in the analysis. Any tumor coming from a recurrent or metastatic lesion were excluded from the analysis. Three cell-cycle phenotypes (I, II, III) were derived from marker expression patterns. Prognostic significance was evaluated in a subset of primary soft tissue sarcomas using Cox regression for survival analysis. RESULTS: Compared to phenotype I, the phenotype III tumors had a decreased 5-year overall survival (HR 6.81 [2.36-19.61]; p = < 0.001), 5-year disease-free survival (HR 1.07 (1.02-1.18); p = 0.004), and 5-year metastasis-free survival (HR 4.34 [1.58-11.93]; p = 0.004). High expression of Plk1 was associated with decreased 5-year overall survival (HR: 4.04 CI [1.21-6.67; p = 0.02) and 5-year metastasis-free survival (HR: 2.91 CI [1.15-7.37]; p = 0.03). Geminin was also found to have a decreased 5-year overall survival (HR:2.84 CI [1.21-6.67]; p = 0.02). No statistical difference in prognostication were noted between phenotypes and the AJCC system. CONCLUSIONS: We identified three unique sarcoma cell cycle phenotypes that have prognostic significance. This performs similarly to the AJCC staging system.

Case of a CIC::DUX4 fusion gene in a vascular neoplasm extends the spectrum of CIC-rearranged sarcomas.

CIC-rearranged sarcomas comprise a group of exceptionally aggressive round-cell sarcomas. These tumors most commonly demonstrate CIC::DUX4 fusion and show similar histopathology to Ewing sarcomas, though lesions mimicking vascular neoplasms have recently been described. Here, we describe a case of a patient with CIC::DUX4 fusion sarcoma identified using RNA-based molecular testing who was initially diagnosed with an endothelial neoplasm. The tumor showed extensive vasoformative growth, complete WT1 negativity, and global positive staining for ERG, CD31, and DUX4 by immunohistochemistry. Methylation testing of the tumor clustered more closely with angiosarcomas than with CIC-rearranged sarcomas. Our findings suggest that CIC::DUX4 fused neoplasms may demonstrate a more diverse phenotypic range than previously appreciated and offer evidence that both molecular and immunohistochemical studies are needed for accurate diagnosis.

Exploring versatile applications of a vacuum-assisted bone harvester in orthopedic surgery.

BACKGROUND: Orthopedic procedures often require removing bone or pathological tissue, with traditional methods involving instruments like curettes and rongeurs. However, these methods can be time-consuming and lead to increased blood loss. To mitigate these side effects, vacuum-assisted tools have been developed to aid in tissue removal. These devices enable surgeons to suction tissue without discarding it, potentially improving outcomes in conditions such as osteomyelitis or tumor removal while enabling collection of the material for downstream applications. Despite limited research, vacuum-assisted devices show promise beyond bone marrow harvesting. This study assesses infection and clearance rates, estimated blood loss, and total procedure time associated with the use of vacuum-assisted tissue removal, with a goal to understand if these devices can be used for tissue removal across a variety of pathologic conditions. METHODS: A retrospective cohort study was conducted on patients undergoing orthopedic procedures with the Avitus® Bone Harvester repurposed from its original design from December 1, 2021, to July 1, 2023. Procedures were categorized into oncology, and debridement for infection cases. Infection cases were further categorized into those secondary to trauma and those involving primary infections (osteomyelitis and periprosthetic joint infection). Clinical variables, including demographics, intraoperative details, complications, and follow-up, were reviewed. Statistical analysis included descriptive statistics computed with R Studio. RESULTS: The study included 44 patients, with debridement for infection cases being the most common (primary infection: 45.5%; infection secondary to trauma: 18.1%), followed by oncology cases (36.4%). In all oncology cases, a definitive diagnosis was established using the device, and no post-operative infections were reported. The infection clearance rate was 85.0% for primary infection cases and 50.0% for cases of infection following trauma. Across the entire cohort, the average blood loss was 314.52 mL (sd: 486.74), and the average total procedure time was 160.93 min (sd: 91.07). The overall reoperation rate was 47.7%, with an unplanned reoperation rate of 11.4%. CONCLUSION: The vacuum-assisted bone harvester was effectively utilized in a wide range of debridement and curettage procedures across diverse orthopedic surgeries. In oncology cases, the device enabled effective tissue removal with comparable recurrence rates, demonstrating its potential to minimize contamination while preserving tissue for accurate diagnoses. Additionally, a high rate of osteomyelitis eradication was observed in debridement for primary infection cases (85%). Despite the relatively high reoperation rate of 47.7%, it is crucial to interpret this figure within the context of the varied reasons for reoperation. Many of these reoperations were planned as part of a staged approach to treatment or were unrelated to the device's performance. It is crucial to acknowledge that isolating the device's contribution to these results can be difficult. The utilization of the device should be guided by considerations of cost-effectiveness and patient-specific risk factors.

Tumor necrosis is an underappreciated histopathologic factor in the grading of chondrosarcoma.

BACKGROUND: Cartilaginous neoplasms can be challenging to grade; there is a need to create an evidence-based rubric for grading. The goal of this study was to identify histopathologic features of chondrosarcoma that were associated with 5-year survival and to compare these to traditional patient, tumor and treatment variables. METHODS: This was a retrospective review of all patients undergoing surgical resection of a primary chondrosarcoma with at least 2 years of follow up. All specimens were independently reviewed by two pathologists and histopathologic features scored. Univariate and multivariate analyses were performed utilizing Kaplan Meier and proportional hazards methods to identify variables associated with 5-year disease specific survival (DSS) and disease free survival (DFS). RESULTS: We identified 51 patients with an average follow up of 49 months eligible for inclusion. 30% of tumors were low grade, 45% were intermediate grade, and 25% were high grade. In a univariate analysis considering histopathologic factors, higher tumor mitotic rate (HR 8.9, p < 0.001), tumor dedifferentiation (HR 7.3, p < 0.001), increased tumor cellularity (HR 5.8, p = 0.001), increased tumor atypia (HR 5.8, p = 0.001), LVI (HR 4.7, p = 0.04) and higher tumor necrosis (HR 3.7, p = 0.02) were all associated with worse 5-year DSS. In a multivariate analysis controlling for potentially confounding variables, higher tumor necrosis was significantly associated with disease specific survival survival (HR 3.58, p = 0.035); none of the factors were associated with DFS. CONCLUSIONS: This study provides an evidence-based means for considering histopathologic markers and their association with prognosis in chondrosarcoma. Our findings suggest that necrosis and LVI warrant further study.

Giant cell tumor of bone in the pediatric population: a retrospective study highlighting cases of metaphyseal only location and increased local recurrence rates in skeletally immature patients.

OBJECTIVE: To describe the presentation of giant cell tumors (GCT) of the bone in the pediatric population to (1) improve the differential diagnosis of pediatric bone tumors and (2) identify the origin of GCT. Understanding the origin of bone tumors assists in establishing appropriate diagnoses and recommending treatment options. This is particularly important in children, where evaluating the need for invasive procedures is balanced with the desire to avoid overtreatment. GCT have historically been considered epiphyseal lesions with potential metaphyseal extension. Therefore, GCT may be inappropriately excluded from the differential diagnosis of metaphyseal lesions in the skeletally immature. MATERIALS AND METHODS: We identified 14 patients from 1981 to 2021 at a single institution who had histologic confirmation of GCT and were less than 18 years old at diagnosis. Patient characteristics, tumor location, surgical treatment, and local recurrence rates were collected. RESULTS AND CONCLUSIONS: Ten (71%) patients were female. Eleven (78.6%) were epiphysiometaphyseal (1 epiphyseal, 4 metaphyseal, 6 epiphysiometaphyseal). Five patients had an open adjacent physis, of which three (60%) had tumors confined solely to the metaphysis. Of the five patients with open physis, four (80%) developed local recurrence while only one patient (11%) with a closed physis had local recurrence (p value = 0.0023). Our results illustrate that for the skeletally immature, GCT can (and in our results more commonly did) occur in the metaphyseal location. These findings suggest that GCT should be included in the differential diagnosis of primary metaphyseal-only lesions in the skeletally immature.

Antibiotic Prophylaxis for Megaprosthetic Reconstructions: Drug and Dosing May Matter More than Duration.

In orthopedic oncology, the implant of a megaprosthetic device is standard of care after large-scale tumor resection involving segmental removal of bone. Infection remains the leading cause of implant failure, often resulting in major morbidity. Perioperative antibiotic practices for megaprosthetic reconstructions are not standardized and are based on guidelines for conventional joint arthroplasties. This study aims to evaluate the efficacy of current prophylactic strategies for megaprosthetic reconstructions. We conducted a retrospective review of megaprosthetic reconstructions performed at Duke University from 2001 to 2021. Logistic regression with GEE was used to assess whether a prolonged course of postoperative antibiotics is associated with infection risk. We assessed the microbial profile and corresponding susceptibilities of megaprosthetic infections through record review. Additionally, we designed a pharmacokinetic subgroup analysis using liquid chromatography-tandem mass spectrometry to quantify antibiotic concentrations in surgical tissue. Wilcoxon rank-sum tests were used to correlate tissue concentrations with infection risk. Out of 184 cases, 23 (12.5%) developed infection within 1 year. Extended postoperative antibiotics were not significantly associated with infection risk (P = 0.23). Among 18 culture-positive cases, 4 (22.2%) were caused by cefazolin-susceptible organisms. Median bone and muscle concentrations of cefazolin among cases that developed postoperative infection (0.065 ng/mL and 0.2 ng/mL, respectively) were significantly lower than those of cases that did not (0.42 ng/mL and 1.95 ng/mL, P < 0.01 and P = 0.03). This study is the first to comprehensively assess aspects of perioperative prophylaxis for megaprosthetic reconstructions. Extending postoperative antibiotics did not reduce infection risk. We detected a high frequency of cefazolin nonsusceptible organisms among postoperative infections. Additionally, intraoperative antibiotic tissue concentrations may be predictive of later infection. Future studies ought to examine optimal drug choices and dosing strategies.

Identifying Modifiable and Non-modifiable Risk Factors of Readmission and Short-Term Mortality in Chondrosarcoma: A National Cancer Database Study.

BACKGROUND: Limited data are available to inform the risk of readmission and short-term mortality in musculoskeletal oncology. The goal of this study was to identify factors independently associated with 30-day readmission and 90-day mortality following surgical resection of chondrosarcoma. METHODS: We retrospectively reviewed 6653 patients following surgical resection of primary chondrosarcoma in the National Cancer Database (2004-2017). Both demographic and clinicopathologic variables were assessed for correlation with readmission and short-term mortality utilizing univariate and multivariate logistic regression modeling. RESULTS: Of 220 readmissions (3.26%), risk factors independently associated with an increased risk of unplanned 30-day readmission included Charlson-Deyo Comorbidity Index (CDCC) (odds ratio [OR] 1.31; p = 0.027), increasing American Joint Committee on Cancer (AJCC) stage (OR 1.31; p = 0.004), undergoing major amputation (OR 2.38; p = 0.001), and axial skeletal location (OR 1.51; p = 0.028). A total of 137 patients died within 90 days of surgery (2.25%). Risk factors associated with increased mortality included the CDCC (OR 1.60; p = 0.001), increasing age (OR 1.06; p < 0.001), having Medicaid insurance status (OR 3.453; p = 0.005), living in a zip code with a higher educational attainment (OR 1.59; p = 0.003), increasing AJCC stage (OR 2.32; p < 0.001), longer postoperative length of stay (OR 1.015; p = 0.033), and positive surgical margins (OR 2.75; p = 0.001). Although a majority of the cohort did not receive radiation therapy (88.8%), receiving radiotherapy (OR 0.132; p = 0.010) was associated with a decreased risk of short-term mortality. CONCLUSIONS: Several tumor, treatment, and patient factors can help inform the risk of readmission and short-term mortality in patients with surgically treated chondrosarcoma.

Juxtametallic Bipolar Bone Radiofrequency Ablation: Thermal Monitoring in an Ex-Vivo Model with Specimen MRI and Histopathologic Correlation.

PURPOSE: To measure the ablation zone temperature and nontarget tissue temperature during radiofrequency (RF) ablation in bone containing metal instrumentation versus no metal instrumentation (control group). MATERIALS AND METHODS: Ex vivo experiments were performed on 15 swine vertebrae (control, n = 5; titanium screw, n = 5; stainless steel screw, n = 5). Screws and RF ablation probe were inserted identically under fluoroscopy. During RF ablation (3 W, 5 minutes), temperature was measured 10 mm from RF ablation centerpoint and in muscle contacting the screw. Magnetic resonance (MR) imaging, gross pathologic, and histopathologic analyses were performed on 1 specimen from each group. RESULTS: Ablation zone temperatures at 2.5 and 5 minutes increased by 12.2 °C ± 2.6 °C and 21.5 °C ± 2.1 °C (control); 11.0 °C ± 4.1 °C and 20.0 °C ± 2.9 °C (juxta-titanium screw), and 10.0 °C ± 3.4 °C and 17.2 °C ± 3.5 °C (juxta-stainless steel) screw; differences among groups did not reach significance by analysis of variance (P = .87). Mixed-effects linear regression revealed a statistically significant increase in temperature over time in all 3 groups (4.2 °C/min ± 0.4 °C/min, P < .001). Compared with the control, there was no significant difference in the temperature change over time for titanium (-0.3 °C/min ± 0.5 °C/min, P = .53) or steel groups (-0.4 °C/min ± 0.5 °C/min, P = .38). The mean screw temperature at the final time point did not show a statistically significant change compared with baseline in either the titanium group (-1.2 °C ± 2.3 °C, P = .50) or steel group (2.6 °C ± 2.9 °C, P = .11). MR imaging and pathologic analyses revealed homogeneous ablation without sparing of the peri-hardware zones. CONCLUSIONS: Adjacent metallic instrumentation did not affect the rate of or absolute increase in temperature in the ablation zone, did not create peri-metallic ablation inhomogeneities, and did not result in significant nontarget heating of muscle tissue in contact with the metal instrumentation.

Investigating readmission rates for patients undergoing oncologic resection and endoprosthetic reconstruction for primary sarcomas and tumors involving bone.

BACKGROUND: Little is known about the drivers of readmission in patients undergoing Orthopaedic oncologic resection. The goal of this study was to identify factors independently associated with 90-day readmission for patients undergoing oncologic resection and subsequent prosthetic reconstruction for primary tumors involving bone. METHODS: This was a retrospective comparative cohort study of patients treated from 2008 to 2019 who underwent endoprosthetic reconstruction for a primary bone tumor or soft tissue tumor involving bone, as well as those who underwent a revision endoprosthetic reconstruction if the primary endoprosthetic reconstruction was performed for an oncologic resection. The primary outcome measure was unplanned 90-day readmission. RESULTS: A total of 149 patients were identified who underwent 191 surgeries were for a primary bone or soft tissue tumor. The 90-day readmission rate was 28.3%. Female gender, depression, higher tumor grade, vascular reconstruction, longer procedure duration, longer length of stay (LOS), multiple surgeries during an admission and disposition to a Skilled Nursing Facility were associated with readmission (p < 0.05). In a multivariate analysis, female sex, higher tumor grade and longer procedure duration were independently associated with risk of readmission (p < 0.05). CONCLUSIONS: Readmission rates are high following endoprosthetic reconstruction for Orthopaedic oncologic resections. Further work is necessary to help minimize unplanned readmissions.

Why Do Patients Undergoing Extremity Prosthetic Reconstruction for Metastatic Disease Get Readmitted?

BACKGROUND: Orthopedic oncology patients are particularly susceptible to increased readmission rates and poor surgical outcomes, yet little is known about readmission rates. The goal of this study is to identify factors independently associated with 90-day readmission for patients undergoing oncologic resection and subsequent prosthetic reconstruction for metastatic disease of the hip and knee. METHODS: This is a retrospective comparative cohort study of all patients treated from 2013 to 2019 at a single tertiary care referral institution who underwent endoprosthetic reconstruction by an orthopedic oncologist for metastatic disease of the extremities. The primary outcome measure was unplanned 90-day readmission. RESULTS: We identified 112 patients undergoing 127 endoprosthetic reconstruction surgeries. Metastatic disease was most commonly from renal (26.8%), lung (23.6%), and breast (13.4%) cancer. The most common type of skeletal reconstruction performed was simple arthroplasty (54%). There were 43 readmissions overall (33.9%). When controlling for confounding factors, body mass index >40, insurance status, peripheral vascular disease, and longer hospital length of stay were independently associated with risk of readmission (P ≤ .05). CONCLUSION: Readmission rates for endoprosthetic reconstructions for metastatic disease are high. Although predicting readmission remains challenging, risk stratification presents a viable option for helping minimize unplanned readmissions. LEVEL OF EVIDENCE: III.

Identifying Modifiable and Non-modifiable Risk Factors of Readmission and Short-Term Mortality in Osteosarcoma: A National Cancer Database Study.

BACKGROUND: There are limited data to inform risk of readmission and short-term mortality in musculoskeletal oncology. The goal of this study was to identify factors independently associated with 30-day readmission and 90-day mortality following surgical resection of osteosarcoma. METHODS: We retrospectively reviewed patients (n = 5293) following surgical resection of primary osteosarcoma in the National Cancer Database (2004-2015). Univariate and multivariate methods were used to correlate variables with readmission and short-term mortality. RESULTS: Of 210 readmissions (3.97%), risk factors independently associated with unplanned 30-day readmission included comorbidity burden (odds ratio [OR] 2.4, p = 0.042), Medicare insurance (OR 1.9, p = 0.021), and axial skeleton location (OR 1.5, p = 0.029). A total of 91 patients died within 90 days of their surgery (1.84%). Risk factors independently associated with mortality included age (hazard ratio 1.1, p < 0.001), increasing comorbidity burden (OR 6.6, p = 0.001), higher grade (OR 1.7, p = 0.007), increasing tumor size (OR 2.2, p = 0.03), metastatic disease at presentation (OR 8.5, p < 0.001), and amputation (OR 2.0, p = 0.04). Chemotherapy was associated with a decreased risk of short-term mortality (p < 0.001). CONCLUSIONS: Several trends were clear: insurance status, tumor location and comorbidity burden were independently associated with readmission rates, while age, amputation, grade, tumor size, metastatic disease, and comorbidity burden were independently associated with short-term mortality.

Reverse total shoulder arthroplasty for oncologic reconstruction of the proximal humerus: a systematic review.

BACKGROUND: In recent years, there has been growing interest in the use of reverse total shoulder arthroplasty (rTSA) for reconstruction of the proximal humerus after oncologic resection. However, the indications and outcomes of oncologic rTSA remain unclear. METHODS: We conducted a systematic review to identify studies that reported outcomes of patients who underwent rTSA for oncologic reconstruction of the proximal humerus. Extracted data included demographic characteristics, indications, operative techniques, outcomes, and complications. Weighted means were calculated according to sample size. RESULTS: Twelve studies were included, containing 194 patients who underwent rTSA for oncologic reconstruction of the proximal humerus. The mean patient age was 48 years, and 52% of patients were male. Primary malignancies were present in 55% of patients; metastatic disease, 30%; and benign tumors, 9%. The mean humeral resection length was 12 cm. The mean postoperative Musculoskeletal Tumor Society score was 78%; Constant score, 60; and Toronto Extremity Salvage Score, 77%. The mean complication rate was 28%, with shoulder instability accounting for 63% of complications. Revisions were performed in 16% of patients, and the mean implant survival rate was 89% at a mean follow-up across studies of 53 months. CONCLUSIONS: Although the existing literature is of poor study quality, with a high level of heterogeneity and risk of bias, rTSA appears to be a suitable option in appropriately selected patients undergoing oncologic resection and reconstruction of the proximal humerus. The most common complication is instability. Higher-quality evidence is needed to help guide decision making on appropriate implant utilization for patients undergoing oncologic resection of the proximal humerus.

Limb salvage versus amputation in patients with osteosarcoma of the extremities: an update in the modern era using the National Cancer Database.

BACKGROUND: Historically, amputation was the primary surgical treatment for osteosarcoma of the extremities; however, with advancements in surgical techniques and chemotherapies limb salvage has replaced amputation as the dominant treatment paradigm. This study assessed the type of surgical resection chosen for osteosarcoma patients in the twenty-first century. METHODS: Utilizing the largest registry of primary osteosarcoma, the National Cancer Database (NCDB), we retrospectively analyzed patients with high grade osteosarcoma of the extremities from 2004 through 2015. Differences between patients undergoing amputation and patients undergoing limb salvage are described. Unadjusted five-year overall survival between patients who received limb salvage and amputation was assessed utilizing Kaplan Meier curves. A multivariate Cox proportional hazard model and propensity matched analysis was used to determine the variables independently correlated with survival. RESULTS: From a total of 2442 patients, 1855 underwent limb salvage and 587 underwent amputation. Patients undergoing amputation were more likely to be older, male, uninsured, and live in zip codes associated with lower income. Patients undergoing amputation were also more likely to have larger tumors, more comorbid conditions, and metastatic disease at presentation. After controlling for confounders, limb salvage was associated with a significant survival benefit over amputation (HR: 0.70; p < 0.001). Although this may well reflect underlying biases impacting choice of treatment, this survival benefit remained significant after propensity matched analysis of all significantly different independent variables (HR: 0.71; p < 0.01). CONCLUSION: Among patients in the NCDB, amputation for osteosarcoma is associated with advanced age, advanced stage, larger tumors, greater comorbidities, and lower income. Limb salvage is associated with a significant survival benefit, even when controlling for significant confounding variables and differences between cohorts.

Defining a textbook surgical outcome for patients undergoing surgical resection of intermediate and high-grade soft tissue sarcomas of the extremities.

BACKGROUND: Quality measures for the surgical management soft tissue sarcoma of the extremity are limited. The purpose of this study was to define a textbook surgical outcome (TO) for soft tissue sarcoma of the extremities (STS-E) and to examine its associations with hospital volume and overall survival. METHODS: All patients in the National Cancer Database undergoing resection of primary STS-E between 2004 and 2015 were identified. The primary outcome was a TO, defined as: hospital length of stay (LOS) <75th percentile, survival >90 days from the date of surgery, no readmission within 30 days of discharge, and negative surgical margins (R0 resection). RESULTS: Overall, 7658 patients met criteria for inclusion; a TO was achieved in 4291 (56%) patients. Of patients who did not achieve TOs, 51.9% (n = 1748) had an extended LOS, and 47.3% (n = 1591) did not have negative margins. Older age, more medical comorbidities, and non-white or black race were independently associated with not receiving a TO (P = .034). With respect to tumor and treatment characteristics, larger tumor size, lower extremity location and higher grade were independently associated with not receiving a TO (P < .001). Hospital volume was not associated with a TO. TOs conferred a significant survival benefit (hazrds ratio = 0.71 [0.65-0.78], P < .001). A TO was associated with a 27.5% longer survival time (P < .001). CONCLUSIONS: This study defined a TO in intermediate and high-grade STS-E and demonstrated that this outcome measure is associated with overall survival. Facility volume was not associated with a TO.

Soft Tissue Sarcoma of the Extremities: What Is the Value of Treating at High-volume Centers?

BACKGROUND: For many cancer types, survival is improved when patients receive management at treatment centers that encounter high numbers of patients annually. This correlation may be more important with less common malignancies such as sarcoma. Existing evidence, however, is limited and inconclusive as to whether facility volume may be associated with survival in soft tissue sarcoma. QUESTIONS/PURPOSES: The purpose of this study was to examine the association between facility volume and overall survival in patients with soft tissue sarcoma of the extremities. In investigating this aim, we sought to (1) examine differences in the treatment characteristics of high- and low-volume facilities; (2) estimate the 5-year survival by facility volume; and (3) examine the association between facility volume and of traveling a further distance to a high-volume center and overall survival when controlling for confounding factors. METHODS: The largest sarcoma patient registry to date is contained within the National Cancer Database (NCDB) and captures > 70% of new cancer diagnoses annually. We retrospectively analyzed 25,406 patients with soft tissue sarcoma of the extremities in the NCDB from 1998 through 2012. Patients were stratified based on per-year facility sarcoma volume and we used univariate comparisons and multivariate proportional hazards analyses to correlate survival measures with facility volume and various other patient-, tumor-, and treatment-related factors. First, we evaluated long-term survival for all variables using the Kaplan-Meier method with statistical comparisons based on the log-rank test. Multiple patient, tumor, and treatment characteristics were compared between the two facility-volume groups and then included them in the multivariate proportional hazards model. Of the 25,406 patients analyzed, 3310 were treated at high-volume centers (≥ 20 patients annually) and 22,096 were treated at low-volume centers. Patient demographics were generally not different between both patient cohorts, although patients treated at high-volume centers were more likely to have larger and higher grade tumors (64% versus 56% size ≥ 5 cm, 28% versus 14% undifferentiated grade, p < 0.001). RESULTS: When controlling for patient, tumor, and treatment characteristics in a multivariate proportional hazards analysis, patients treated at high-volume facilities had an overall lower risk of mortality than those treated at low-volume centers (hazard ratio, 0.81 [0.75-0.88], p < 0.001). Patients treated at high-volume centers were also less likely to have positive margins (odds ratio [OR], 0.59 [0.52-0.68], p < 0.001) and in patients who received radiation, those treated at high-volume centers were more likely to have radiation before surgery (40.5% versus 21.7%, p < 0.001); there was no difference in the type of surgery performed (resection versus amputation) (OR, 1.01 [0.84-1.23], p = 0.883). CONCLUSIONS: With the largest patient cohort to date, this database review suggests that certain patients with soft tissue sarcoma of the extremities, particularly those with large high-grade tumors, may benefit from treatment at high-volume centers. Further investigation is necessary to help improve the referral of appropriate patients to high-volume sarcoma centers and to increase the treatment capacity of and access to such centers. LEVEL OF EVIDENCE: Level III, therapeutic study.

Microsurgery in musculoskeletal oncology.

Sarcomas are rare mesenchymal bone and soft tissue tumors of the musculoskeletal system. In the past, the primary treatment modality was amputation of the involved limb and the 5-year survival was very low for high-grade tumors. During the last three decades, limb salvage has become the rule rather than the exception and the use of neoadjuvant and adjuvant therapies (radiation and chemotherapy) has dramatically increased disease-free survival. Reconstruction of large bone and soft tissue defects, though, still remains a significant challenge in sarcoma patients. In particular, vascularized tissue transfer has proved extremely helpful in dealing with complex bone and soft tissue or functional defects that are frequently encountered as a result of the tumor or as a complication of surgery and adjuvant therapies. The principles, indications and results of microsurgical reconstruction differ from trauma patients and are directly related not only to the underlying disease process, but also to the local and systemic therapeutic modalities applied to the individual patient. Although plastic reconstruction in the oncological patients is not free of complications, usually these complications are manageable and do not jeopardize oncological outcome. The overall treatment strategy should be tailored to the patient's and sarcoma profile.

Race is an independent predictor of survival in patients with soft tissue sarcoma of the extremities.

BACKGROUND: In the United States, race and socioeconomic status are well known predictors of adverse outcomes in several different cancers. Existing evidence suggests that race and socioeconomic status may impact survival in soft tissue sarcoma (STS). We investigated the National Cancer Database (NCDB), which contains several socioeconomic and medical variables and contains the largest sarcoma patient registry to date. Our goal was to determine the impact of race, ethnicity and socioeconomic status on patient survival in patients with soft tissue sarcoma of the extremities (STS-E). METHODS: We retrospectively analyzed 14,067 STS-E patients in the NCDB from 1998 through 2012. Patients were stratified based on race, ethnicity and socioeconomic status. Univariate and multivariate analyses were used to correlate specific outcomes and survival measures with these factors. Then, long-term survival between groups was evaluated using the Kaplan-Meier (KM) method with comparisons based on the log-rank test. Multiple variables were analyzed between two groups. RESULTS: Of the 14,067 patients analyzed, 84.9% were white, 11% were black and 4.1% were Asian. Black patients were significantly more likely (7.18% vs 5.65% vs 4.47%) than white or Asian patients to receive amputation (p = 0.027). Black patients were also less likely to have either an above-median education level or an above-median income level (p < 0.001). In addition, black patients were more likely to be uninsured (p < 0.001) and more likely to have a higher Charleson Comorbidity Score than white or Asian patients. Tumors were larger in size upon presentation in black patients than in white or Asian patients (p < 0.001). Black patients had significantly poorer overall survival than did white or Asian patients (p < 0.001) with a KM 5-year survival of 61.4% vs 66.9% and 69.9% respectively, and a 24% higher independent likelihood of dying in a multivariate analysis. CONCLUSION: This large database review reveals concerning trends in black patients with STS-E. These include larger tumors, poorer resources, a greater likelihood of amputation, and poorer survival than white and Asian patients. Future studies are warranted to help ensure adequate access to effective treatment for all patients.

The Role of Reconstructive Surgery After Skeletal and Soft Tissue Sarcoma Resection.

BACKGROUND: Skeletal and soft tissue reconstruction after sarcoma resection remains challenging. The use of advanced reconstructive techniques has been shown to improve function and increase rates of limb salvage. This study aims to analyze the utilization of plastic surgery within a multidisciplinary team approach after sarcoma resection at Duke University Medical Center from 2001 to 2014. METHODS: Medical records were reviewed to determine procedure type, postoperative complications, and tumor recurrence. Observations were stratified by oncologic diagnosis, anatomic location, and procedure type. Patients were excluded if final pathology was not indicative of sarcoma, if resection or reconstruction was not performed at our institution, if resection preceded reconstruction by greater than 60 days, or if no follow-up was recorded within 3 months. RESULTS: Of the 747 patients who met the inclusion criteria, 116 underwent reconstructive surgery. Tumor location was associated with a need for surgical reconstruction. Patients with upper (P = 0.0073) or lower (P = 0.0265) extremity tumors had a higher occurrence of plastic surgery involvement. Patients with a history of operative interventions had a higher likelihood of reconstructive surgery after oncologic resection (odds ratio, 1.649; P = 0.019). Neoadjuvant radiotherapy was associated with an increased likelihood of reconstructive plastic surgery after sarcoma resection (odds ratio, 2.131; P = 0.0004). CONCLUSIONS: Understanding the factors that necessitate reconstructive plastic surgery after sarcoma resection can enhance coordination of care within a multidisciplinary sarcoma center and leading to improved patient outcomes, including rates of limb salvage, as well as functionality and esthetic results.

Beyond Mirels: Factors Influencing Surgical Outcome of Metastasis to the Extremities in the Modern Era.

Mirels scoring system for determining prophylactic stabilization need of skeletal metastases includes a limited number of variables and does not differentiate between procedure types. This study sought to identify additional variables associated with surgical failure, radiographic disease progression, and patient survival. A retrospective review was performed of patients from January 2004 to 2014 who underwent surgical treatment of skeletal metastases of the extremities, were >18 years of age, and had adequate radiographic surveillance. Eighty-nine metastatic bone lesions in 77 patients were included. Mirels score >8 (p = .015) and tumor origin (p = .008) were associated with surgical failure, which was 16.8%. Male gender (p < .001) and use of bone cement (p = .019) were associated with radiographic progression, 43.8% overall. Antiresorptive medications usage (p = .02) was associated with survival. The study concluded that tumor origin may be highly important when considering surgical treatment for metastatic bone disease and antiresorptive medications should be used postoperatively, given an association with survival. (Journal of Surgical Orthopaedic Advances 27(3):178-186, 2018).