ATRX and Its Prognostic Significance in Soft Tissue Sarcoma.

Purpose: Recently, the association between ATRX and a more aggressive sarcoma phenotype has been shown. We performed a retrospective study of sarcomas from an individual institution to evaluate ATRX as a prognosticator in soft tissue sarcoma. Experimental Design. 128 sarcomas were collected from a single institution and stained for ATRX. The prognostic significance of these markers was evaluated in a smaller cohort of primary soft tissue sarcomas (n = 68). Kaplan-Meier curves were created for univariate analysis, and Cox regression was utilized for multivariate analysis. Results: High expression of ATRX was found to be a positive prognostic indicator for overall survival and metastasis-free survival in our group of soft tissue sarcomas both in univariate analysis and multivariate analysis (HR: 0.38 (0.17-0.85), P=0.02 and HR: 0.49 (0.24-0.99), P=0.05, respectively). Conclusions: High expression of ATRX is a positive prognostic indicator of overall survival and metastasis-free survival in patients with STS. This is consistent with studies in osteosarcoma, which indicate possible mechanisms through which loss of ATRX leads to more aggressive phenotypes. Future prospective clinical studies are required to validate the prognostic significance of these findings.

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.

Regional anesthesia is associated with improved metastasis free survival after surgical resection of bone sarcomas.

There is increasing evidence that perioperative factors, including type of anesthesia, may be an important consideration regarding oncological disease progression. Previous studies have suggested that regional anesthesia can improve oncological outcomes by reducing the surgical stress response that occurs during tumor resection surgery and that may promote metastatic progression. The purpose of this study is to provide the first robust investigation of the impact of adding regional anesthesia to general anesthesia on oncological outcomes following sarcoma resection. One hundred patients with bone sarcoma were retrospectively analyzed in this study. After adjusting for confounding variables such as age and grade of the tumor, patients with bone sarcoma receiving regional anesthesia in addition to general anesthesia during resection had improved metastasis free survival (multivariate hazard ratio of 0.47 and p = 0.034). Future studies are needed to confer the beneficial effect of regional anesthesia, and to further investigate the potential mechanism. Clinical significance: The results from this study provide evidence that regional anesthesia may be advantageous in the setting of bone sarcoma resection surgery, reducing pain while also improving oncological outcomes and should be considered when clinically appropriate.

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.

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.

Intraoperative angiography imaging correlates with wound complications following soft tissue sarcoma resection.

For soft tissue sarcoma patients receiving preoperative radiation therapy, wound complications are common and potentially devastating. The purpose of this study was to assess the feasibility of intraoperative indocyanine green fluorescent angiography (ICGA) as a predictor of wound complications in these patients. A consecutive series of patients with soft tissue sarcoma of the extremities or pelvis who received neoadjuvant radiation and a subsequent radical resection received intraoperative ICGA with the SPY PHI device (Stryker Inc.) at the time of closure. Retrospective analysis of fluorescence signal along multiple points of the wound length was performed and quantified. The primary endpoint was wound complication, defined as delayed wound healing or wound dehiscence, within 3 months of surgery. Fourteen patients with preoperative irradiated soft tissue sarcoma were consecutively imaged. There were six patients with wound complications classified as "aseptic" in five cases. Using the ICGA, blinded surgeons correctly predicted wound complications in 75% of cases. During the inflow phase, a mean ratio of normal of 0.62 maximized the area under the curve (AUC = 0.90) for predicting wound complications with a sensitivity of 100% and specificity of 77.4%. During the peak phase, a mean ratio of normal of 0.55 maximized the AUC (0.95) for predicting wound complications with a sensitivity of 88.9% and a specificity of 100%. Intraoperative use of ICGA may help to predict wound complications in patients undergoing resection of preoperatively irradiated soft tissue sarcomas of the extremities and pelvis.

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.

Extent of tumor fibrosis/hyalinization and infarction following neoadjuvant radiation therapy is associated with improved survival in patients with soft-tissue sarcoma.

INTRODUCTION: Current standard of care for most intermediate and high-grade soft-tissue sarcomas (STS) includes limb-preserving surgical resection with either neoadjuvant radiation therapy (NRT) or adjuvant radiation therapy. To date, there have been a few studies that attempt to correlate histopathologic response to NRT with oncologic outcomes in patients with STS. METHODS: Using our institutional database, we identified 58 patients who received NRT followed by surgical resection for primary intermediate or high-grade STS and 34 patients who received surgical resection without NRT but did receive adjuvant radiation therapy or did not receive any radiation therapy. We analyzed four histologic parameters of response to therapy: residual viable tumor, fibrosis/hyalinization, necrosis, and infarction (each ratiometrically determined). Data were stratified into two binary groups. Unadjusted, 5- and 10-year overall survival, and relapsed-free survival (RFS) were calculated using the Kaplan-Meier method. RESULTS: Analysis of pathologic characteristics showed that patients treated with NRT demonstrate significantly higher tumor infarction, higher tumor fibrosis/hyalinization, and a lower percent viable tumor compared with patients not treated with NRT (p < 0.0001). Based on Kaplan-Meier curve analysis and multivariate cox proportional hazard model for OS and RFS, patients treated with NRT and showing >12.5% tumor fibrosis/hyalinization have significantly higher overall survival and recurrence-free survival at 5 and 10 years. DISCUSSION AND CONCLUSION: We have identified three histopathologic characteristics-fibrosis, hyalinization, and infarction-that may serve as predictive biomarkers of response to NRT for STS patients. Future prospective studies will be needed to confirm this association.

The Utility of Chest Imaging for Surveillance of Atypical Lipomatous Tumors.

BACKGROUND: Unlike other soft tissue sarcomas, atypical lipomatous tumors (ALTs) are thought to have a low propensity for metastasis. Despite this, a standard of care for pulmonary metastasis (PM) surveillance has not been established. This study aimed to evaluate the utility of chest imaging for PM surveillance following ALT excision. METHODS: This was a multi-institution, retrospective review of all patients with primary ALTs of the extremities or superficial torso who underwent excision between 2006 and 2018. Minimum follow-up was two years. Long-term survival was evaluated using the Kaplan-Meier method. RESULTS: 190 patients with ALT were included. Average age was 61.7 years and average follow-up was 58.6 months (24 to 180 months). MDM2 testing was positive in 88 patients (46.3%), and 102 (53.7%) did not receive MDM2 testing. 188 patients (98.9%) had marginal excision, and 127 (66.8%) had marginal or positive margins. Patients received an average of 0.9 CT scans and 1.3 chest radiographs over the surveillance period. 10-year metastasis-free survival was 100%, with no documented deaths from disease. CONCLUSIONS: This study suggests that chest imaging does not have a significant role in PM surveillance following ALT excision, but advanced local imaging and chest surveillance may be considered in cases of local recurrence or concern for dedifferentiation.

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.

Staging and Surveillance of Myxoid Liposarcoma: Follow-up Assessment and the Metastatic Pattern of 169 Patients Suggests Inadequacy of Current Practice Standards.

BACKGROUND: Unlike other sarcoma subtypes, myxoid liposarcoma (MLS) has a propensity for extra-pulmonary metastases. Computed tomography (CT) scan of the chest, abdomen, and pelvis has become an accepted practice for surveillance. However, recent literature suggests that this may be inadequate. This study aimed to assess the ability of current imaging methods to detect metastases adequately in this population. METHODS: The study identified 169 patients with MLS diagnosed between 2000 and 2016. The timing and location of metastases, the reasons leading to the MLS diagnosis, and the imaging methods were recorded. The locations of metastases were classified into the following categories: pulmonary, soft tissue, bone, retroperitoneal, intraperitoneal, solid organ, and lymph node. RESULTS: An initial diagnosis of metastasis was made at presentation with staging CT scan for 3 (10 %) of 31 patients, with a follow-up surveillance CT scan for 15 (48 %) of the patients or with subsequent imaging obtained in response to patient-reported symptoms for 13 (42 %) of the patients. The proportions of patients who had metastases in each location were as follows: soft tissue (84 %), pulmonary (68 %), intraabdominal (48 %), solid organ (48 %), bone (45 %), lymph node (32 %), and retroperitoneal (29 %). Although 14 patients had bone metastases, only 1 patient had a sclerotic/blastic presentation visualized on CT scan, and the diagnosis for the remaining 13 patients was determined by magnetic resonance imaging (MRI). CONCLUSION: Due to metastatic disease identified outside surveillance imaging for 58 % of the patients, the diversity of locations, and the significant failure of CT and bone scan to identify bone metastases, this study questioned the adequacy of CT scan for surveillance of MLS. Consideration should be given to the use of whole-body MRI for detection of metastasis in MLS.

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.

Treatment of Chondroblastoma with Denosumab: A Case Report with a Correlative Analysis of Effect on the RANK Signaling Pathway.

CASE: A 15-year-old boy with chondroblastoma of the right hemipelvis presented with significant periacetabular bone destruction. Neoadjuvant denosumab treatment facilitated initial joint preserving surgery. Unfortunately, he experienced 2 local recurrences and underwent wide surgical resection 2 years after his initial diagnosis. CONCLUSION: Inhibition of the receptor activator of NF-κB (RANK)/RANK ligand (RANK-L) pathway with denosumab has been used neoadjuvantly for the treatment of giant cell tumor of bone, but its role in the treatment of chondroblastoma is less understood. This patient's clinical response and effect on cellular RANK/RANK-L activity support the consideration of denosumab in the treatment algorithm for other osteolytic bone tumors such as chondroblastoma.

The role of Denosumab in joint preservation for patients with giant cell tumour of bone.

AIMS: Local recurrence remains a challenging and common problem following curettage and joint-sparing surgery for giant cell tumour of bone (GCTB). We previously reported a 15% local recurrence rate at a median follow-up of 30 months in 20 patients with high-risk GCTB treated with neoadjuvant Denosumab. The aim of this study was to determine if this initial favourable outcome following the use of Denosumab was maintained with longer follow-up. METHODS: Patients with GCTB of the limb considered high-risk for unsuccessful joint salvage, due to minimal periarticular and subchondral bone, large soft tissue mass, or pathological fracture, were treated with Denosumab followed by extended intralesional curettage with the goal of preserving the joint surface. Patients were followed for local recurrence, metastasis, and secondary sarcoma. RESULTS: A total of 25 patients with a mean age of 33.8 years (18 to 67) with high-risk GCTB received median six cycles of Denosumab before surgery. Tumours occurred most commonly around the knee (17/25, 68%). The median follow-up was 57 months (interquartile range (IQR) 13 to 88). The joint was salvaged in 23 patients (92%). Two required knee arthroplasty due to intra-articular fracture and arthritis. Local recurrence developed in 11 patients (44%) at a mean of 32.5 months (3 to 75) following surgery, of whom four underwent repeat curettage and joint salvage. One patient developed secondary osteosarcoma and another benign GCT lung metastases. CONCLUSION: The use of Denosumab for joint salvage was associated with a higher than expected rate of local recurrence at 44%. Neoadjuvant Denosumab for joint-sparing procedures should be considered with caution in light of these results. Cite this article: Bone Joint J 2021;103-B(1):184-191.

Sarcoma treatment in the era of molecular medicine.

Sarcomas are heterogeneous and clinically challenging soft tissue and bone cancers. Although constituting only 1% of all human malignancies, sarcomas represent the second most common type of solid tumors in children and adolescents and comprise an important group of secondary malignancies. More than 100 histological subtypes have been characterized to date, and many more are being discovered due to molecular profiling. Owing to their mostly aggressive biological behavior, relative rarity, and occurrence at virtually every anatomical site, many sarcoma subtypes are in particular difficult-to-treat categories. Current multimodal treatment concepts combine surgery, polychemotherapy (with/without local hyperthermia), irradiation, immunotherapy, and/or targeted therapeutics. Recent scientific advancements have enabled a more precise molecular characterization of sarcoma subtypes and revealed novel therapeutic targets and prognostic/predictive biomarkers. This review aims at providing a comprehensive overview of the latest advances in the molecular biology of sarcomas and their effects on clinical oncology; it is meant for a broad readership ranging from novices to experts in the field of sarcoma.