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Soft-tissue sarcomas (STS) are rare tumors that account for 1% of all adult malignancies, with over 100 different histologic subtypes occurring predominately in the trunk, extremity, and retroperitoneum. This low incidence is further complicated by their variable presentation, behavior, and long-term outcomes, which emphasize the importance of centralized care in specialized centers with a multidisciplinary team approach. In the last decade, there has been an effort to improve the quality of care for patients with STS based on anatomic site and histology, and multiple ongo-ing clinical trials are focusing on tailoring therapy to histologic subtype. This report summarizes the latest evidence guiding the histiotype-specific management of ex-tremity/truncal and retroperitoneal STS with regard to surgery, radiation, and chem-otherapy.

Bone and soft tissue sarcomas are a diagnostic challenge due to their histological complexity, variety, and mutational heterogeneity. This has led to continued refinements in classification and diagnostic criteria, presented and soon to be updated by the WHO. This commentary features articles published in this journal and elsewhere that have ultilised pan‐sarcoma datasets and artificial intelligence‐based classifiers. A notable entry is the DKFZ Sarcoma Classifier, which is based on methylation profiles and available for use via a commercial platform. This work has created hope that one day a comprehensive sarcoma classifier will be available, though it is also a reminder of the many challenges apparent in studying rare cancer types.

Aims Our aim was to evaluate the activity, toxicity, and feasibility of electrochemotherapy (ECT) in patients with soft-tissue sarcomas (STS). Methods A two-stage phase II trial was conducted between October 2006 and March 2012. Patients ( N  = 34) with locally advanced or metastatic STS, unsuitable for standard oncological treatments and with maximum 3-cm deep tumors, received an intravenous bolus of bleomycin (15,000 IU/m 2 ), followed by tumor electroporation according to the European Standard Operating Procedures of ECT. Outcome measures included local response according to response evaluation criteria in solid tumors (RECIST), toxicity and tumor control. Feasibility measures included the accuracy of electrode placement and the intensity of electric current flowing in tumor tissue. Results Median tumor size was 4.0 cm (range 2–12). Objective response, assessed on 71 target lesions, was 92.2 % (complete 32.3, 95 % CI 28–64). A total of 15 patients received up to four cycles due to incomplete response, but re-treatment did not significantly improve outcome ( p  = 0.205). After a median follow-up of 19.3 months, 2-year local control rate was 72.5 %. Median time to local failure ( N  = 11 patients) was 5.1 months. Tumor response ( p  = 0.041) and control ( p  = 0.047) correlated with histological grading. Relevant toxicity consisted of G3 skin ulceration and soft tissue necrosis (35 and 23 % of patients, respectively), although this was manageable on an outpatient basis. The accuracy of electrode placement was 47.1 %, and the adequacy of electroporative current 85.3 %. Conclusions ECT may represent an active and safe treatment to achieve local control in advanced STS patients with symptomatic disease. Future research challenges include the improvement of electrode placement and voltage delivery together with the containment of soft tissue toxicity.

Objectives To evaluate the performance of a deep learning radiomic nomogram (DLRN) model at predicting tumor relapse in patients with soft tissue sarcomas (STS) who underwent surgical resection. Methods In total, 282 patients who underwent MRI and resection for STS at three independent centers were retrospectively enrolled. In addition, 113 of the 282 patients received additional contrast-enhanced MRI scans. We separated the participants into a development cohort and an external test cohort. The development cohort consisted of patients from one center and the external test cohort consisted of patients from two other centers. Two MRI-based DLRNs for prediction of tumor relapse after resection of STS were established. We universally tested the DLRNs and compared them with other prediction models constructed by using widespread adopted predictors (i.e., staging systems and Ki67) instead of radiomics features. Results The DLRN1 model incorporated plain MRI-based radiomics signature into the clinical data, and the DLRN2 model integrated radiomics signature extracted from plain and contrast-enhanced MRI with the clinical predictors. Across both study sets, the two MRI-based DLRNs had relatively better prognostic capability ( C index ≥ 0.721 and median AUC ≥ 0.746; p < 0.05 compared with most other models and predictors) and less opportunity for prediction error (integrated Brier score ≤ 0.159). The decision curve analysis indicates that the DLRNs have greater benefits than staging systems, Ki67, and other models. We selected appropriate cutoff values for the DLRNs to divide STS recurrence into three risk strata (low, medium, and high) and calculated those groups’ cumulative risk rates. Conclusion The DLRNs were shown to be a reliable and externally validated tool for predicting STS recurrence by comparing with other prediction models. Key Points • The prediction of a high recurrence rate of STS before emergence of local recurrence can help to determine whether more active treatment should be implemented. • Two MRI-based DLRNs for prediction of tumor relapse were shown to be a reliable and externally validated tool for predicting STS recurrence. • We used the DLRNs to divide STS recurrence into three risk strata (low, medium, and high) to facilitate more targeted postoperative management in the clinic.

PurposeThe aim of this study was to evaluate the role of preoperative and postoperative external beam radiation therapy (EBRT) in the treatment of resectable soft tissue sarcomas (STSs) of different tumor locations.MethodsA systematic literature search was performed to identify studies investigating the effects of EBRT (versus no EBRT) on local recurrence (LR) and overall survival (OS) or comparing different EBRT sequences. Random effects meta-analyses were calculated and presented as cumulative odds ratios (ORs).ResultsSixteen studies (n = 3958 patients) comparing EBRT versus no EBRT, including one randomized controlled trial (RCT) in extremity sarcoma, were analyzed. EBRT appeared to reduce LR in both retroperitoneal tumors (OR 0.47, p < 0.0001) and other locations (OR 0.49, p = 0.001). OS was improved by EBRT in retroperitoneal STSs (OR 0.37, p < 0.0001) but not in other tumor locations. Eleven studies (n = 2140), including one RCT, compared preoperative and postoperative radiotherapy. LR was less frequent following preoperative EBRT in retroperitoneal STSs (OR 0.03, p = 0.02), as well as in other tumor locations (OR 0.67, p = 0.01), while wound complications in extremity sarcoma were more frequent following preoperative EBRT (OR 2.92, p < 0.0001). Several studies included in this meta-analysis bear a high risk of bias and no RCT has been published for retroperitoneal STS.ConclusionsThis meta-analysis supports the use of EBRT for local tumor control in patients with resectable STSs. Based on a small number of non-randomized studies, a positive effect on OS may exist in the subgroup of retroperitoneal STSs.

Background Unplanned excisions (UE) of soft tissue sarcomas (STS) carry a high risk for local recurrence (LR) due to marginal/intralesional resections. However, there are reports about improved prognosis for UE patients who have re-resection compared with patients who undergo planned surgery. The present multicentre study was designed to define characteristics of UE patients and to investigate the impact of UE on subsequent therapy and patient outcomes. Methods A total of 728 STS patients (376 males, 352 females; mean age: 58 years) who underwent definite surgery at one of three tumour centres were retrospectively included. Time-to-event analyses were calculated with log-rank and Gray’s tests, excluding patients with primary metastasis ( n  = 59). A propensity-score (PS) of being in the UE group was estimated, based on differences at baseline between the UE group and non-UE group. An inverse-probability-of-UE weight (IPUEW) was generated and time-to-event analyses calculated after IPUEW weighting. Results Before referral, 38.6% of patients ( n  = 281) had undergone UE. Unplanned excision patients were younger ( p  = 0.036), rather male ( p  = 0.05), and had smaller ( p  < 0.005), superficially located tumours ( p  < 0.005). Plastic reconstructions ( p  < 0.005) and adjuvant radiotherapy ( p  = 0.041) more often were needed at re-resection. In univariable analysis, re-resected patients had improved overall survival (OS; p  = 0.027) and lower risk of distant metastasis (DM; p  = 0.002) than primarily resected patients, whereas risk of LR was similar ( p  = 0.359). After weighting for the IPUEW, however, differences in terms of OS ( p  = 0.459) and risk of DM ( p  = 0.405) disappeared. Conclusions The present study does not support prior findings of improved outcome for UE patients. Unplanned excisions have a major impact on subsequent therapy, yet they do not seem to affect negatively the long-term oncology outcome.

Introduction Optimal management of soft tissue sarcoma (STS) remains a challenge. A nationwide survey assessed the quality of STS care in the Netherlands, thereby aiming to identify potentialities for improvement through more centralized disease management. Methods From the Netherlands Cancer Registry (NCR), data were obtained on 3317 adult STS patients (excluding gastrointestinal stromal tumor, GIST) diagnosed in 2006–2011. Logistic regression models were employed to compare outcomes on selected clinical indicators reflecting prevailing STS guidelines between high-volume (≥10 resections annually) and low-volume (<10 resections) hospitals, between academic and general hospitals, and between sarcoma research centers and other hospitals, adjusted for case mix. Analyses were performed on imputed datasets ( m  = 50), generated through multiple imputations by chained equations. Results Overall, 89% of patients underwent surgical resection. Resection status remained unknown in 24% (excluding those with metastasized disease), and grade was not documented for one-third of tumors. Microscopic residual disease was detected in 20% with an increased risk for older patients, larger and deeply located tumors, and those located in the (retro)peritoneum or upper extremity. Almost half of patients with an R1 resection received adjuvant radiotherapy. Following adjustment for case mix factors, patients treated in high-volume hospitals less often had macroscopic residual disease (R2 resection; adjusted odds ratio: 0.54). A strongly skewed distribution of surgical volumes was observed. Conclusions These survey results indicate a potential for improving Dutch STS care. More centralized sarcoma management should improve definitive pathology reporting on tumor characteristics, adherence to treatment guidelines and overall disease outcome.

Opinion Statement Soft tissue sarcomas (STS) are a rare and heterogeneous group of cancers. Treatment options have changed little in the past thirty years, and the role of neoadjuvant chemotherapy is controversial. Accurate risk stratification is crucial in STS in order to facilitate clinical discussions around peri-operative treatment. Current risk stratification tools used in clinic, such as Sarculator, use clinicopathological characteristics and may be specific to anatomical site or to histology. More recently, risk stratification tools have been developed using molecular or immunological data. Combining Sarculator with other risk stratification tools may identify novel patient groups with differential clinical outcomes. There are several considerations when translating risk stratification tools into widespread clinical use, including establishing clinical utility, health economic value, being applicable to existing clinical pathways, having strong real-world performance, and being supported by investment into infrastructure. Future work may include incorporation of novel modalities and data integration techniques.

BackgroundEstablished practice for the management of soft tissue sarcoma (STS) of the extremity and trunk wall combines perioperative radiotherapy (RT) with limb-preserving surgery.ObjectiveThe aim of this study was to explore whether high-quality surgery at high-volume centers may offer equivalent local control in selected cases, when RT needs to be avoided.MethodsAll consecutive adult cases of primary, high-risk STSs treated in a high-volume reference center over a 12-year timeframe were included, and, on retrospective analysis, were divided into two groups. Group A received RT with surgery, and Group B received surgery alone. The primary endpoint was local recurrence-free survival (LRFS).ResultsOverall, 390 patients were included (318 in Group A and 72 in Group B), with a median follow-up of 53 months. The main reasons for avoiding RT were patient choice and technical considerations (vascular bypass or flap reconstruction). No difference in R0 resection was seen between the groups (79% vs. 70%; p = 0.18), but Group A had more G3 tumors (80.5% vs. 68%; p = 0.021). No difference in 5-year LRFS was evident (84% vs. 81%; p = 0.16).ConclusionsLRFS did not differ between patients with high-risk STSs receiving perioperative RT and those treated with surgery alone. The study was retrospective and omission of RT was largely uncontrolled with inherent bias. Nonetheless, data suggest that in experienced centers, the omission of RT did not diminish local disease outcome. Future studies on a selective approach to RT administration are awaited.

Background Neoadjuvant radiotherapy (RT) is increasingly advocated for the management of soft tissue sarcoma (STS). Therefore, this study sought to characterize the impact of neoadjuvant RT on rates of R0 resection and overall survival (OS) in extremity STS patients undergoing surgery. Methods From January 2003 to December 2012, the study identified patients with a diagnosis of extremity STS from the National Cancer Database. After exclusion of patients younger than 18 years, not treated by surgery, who had metastases at diagnosis, intraoperative RT, and missing or unknown data, 27,969 patients were identified. Logistic regression and Cox-proportional hazard analysis were used to compare rates of R0 resection among preoperative, postoperative, and no-RT cohorts and to determine predictors of R0 resection and OS. Results The mean age of the patients was 59.5 ± 17.1 years, and 45.9% were female. The median tumor size was 10.5 cm. The data showed that 51% of the patients did not receive RT, 11.8% received preoperative RT, and 37.2% received postoperative RT. The rates of R0 resection were 90.1% for the preoperative RT cohort, 74.9% for the postoperative RT cohort, and 79.9% for the no-RT cohort ( P  < 0.001). The independent predictors for achievement of R0 resection included academic facility type (odds ratio [OR] 1.36; 95% confidence interval [CI] 1.20–1.55), histologic subtype, tumor size (OR 0.99; 95% CI 0.99–0.99), Charlson score (OR 0.92; 95% CI 0.84–0.99), and preoperative RT (OR 1.83; 95% CI 1.61–2.07). Both R0 resection and RT (pre- or post-operative) were associated with increased OS. Conclusions Preoperative RT independently predicts higher rates of R0 resection for patients with extremity STS undergoing surgical resection. Negative surgical margins and pre- or postoperative RT are associated with improved OS.