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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.

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 Although social vulnerability has been associated with worse postoperative and oncologic outcomes in other cancer types, these effects have not been characterized in patients with soft tissue sarcoma. This study evaluated the association of social vulnerability and oncologic outcomes. Methods The authors conducted a single-institution cohort study of adult patients with primary and locally recurrent extremity or truncal soft tissue sarcoma undergoing resection between January 2016 and December 2021. The social vulnerability index (SVI) was measured on a low (SVI 1–39%, least vulnerable) to high (60–100%, most vulnerable) SVI scale. The association of SVI with overall survival (OS) and recurrence-free survival (RFS) was evaluated by Kaplan-Meier analysis and Cox proportional hazard regression. Results The study identified 577 patients. The median SVI was 44 (interquartile range [IQR], 19–67), with 195 patients categorized as high SVI and 265 patients as low SVI. The median age, tumor size, histologic subtype, grade, comorbidities, stage, follow-up time, and perioperative chemotherapy and radiation utilization were similar between the high and low SVI cohorts. The patients with high SVI had worse OS ( p = 0.07) and RFS ( p = 0.016) than the patients with low SVI. High SVI was independently associated with shorter RFS in the multivariate analysis (hazard ratio, 1.64; 95% confidence interval, 1.06–2.54) but not with OS (HR, 1.47; 95% CI 0.84–2.56). Conclusion High community-level social vulnerability appears to be independently associated with worse RFS for patients undergoing resection of extremity and truncal soft tissue sarcoma. The effect of patient and community-level social risk factors should be considered in the treatment of patients with extremity sarcoma.

Opinion statementSoft tissue sarcomas are rare cancers with an expected incidence of about 14,000 new cases in 2018, and account for less than 1% of all cancers. It includes in excess of 75 heterogeneous subtypes with varying biology, molecular aberrations, and variable response to treatment. Because of the rarity of these tumors and the many different subtypes, there is no large-scale data to guide treatment, and hence the need for a multidisciplinary individualized approach to treatment, preferably at a high-volume tertiary referral center. For localized disease, surgery with or without radiation is the preferred treatment. In metastatic disease, the longest track record is with use of anthracyclines, either alone or in combination with ifosfamide, but the median overall survival even with combination was just over a year. There have been recent advances in understanding the heterogeneity of these tumors and the need for an individualized approach. With that new knowledge, recent approvals of trabectedin, eribulin, and pazopanib have been limited to some select histologic subtypes with improved outcomes. More recently, immunotherapy has been tested in select histotypes of sarcoma with encouraging activity and has led to further evaluation in combination with immunotherapeutic agents, as well as with chemotherapy and radiation treatments. Here, in this article, we summarize the data of the currently approved therapies in metastatic soft tissue sarcoma, with the principal focus on first-line therapies. We also review the recent encouraging data with PDGFR-targeted antibody (olaratumab) with doxorubicin which showed an impressive improvement in overall survival in phase II study. Molecular characterization of sarcoma subtypes will likely improve understanding of these very diverse tumors and improve target characterization. The ongoing efforts in better understanding these rare tumors hold the key to make a difference in the outcome of these patients.

High-grade soft tissue sarcoma is rare and associated with poor prognosis. This study examines racial and ethnic variation in presentation and outcomes at a Southeastern US cancer center. Among an institutional cohort of patients seen between January 2016–December 2021, racial and ethnic differences were evaluated using chi-squared tests, Kaplan Meier curves, and Cox proportional hazards models. There were 295 patients (71 ​% Non-Hispanic White, 24 ​% Black, 3 ​% Hispanic White, 2 ​% Other). Black representation was greater than national cohorts (24 ​% vs. 12 ​%). Histological subtype varied by race/ethnicity (p ​= ​0.007). Adjusting for histology and stage, survival was worse for Black vs. White patients (HR 1.71, 95 ​% CI 1.07–2.76) and those with metastatic disease (5.47, 3.54–8.44). In non-metastatic patients, survival differences for Black vs. White patients were attenuated by receipt of multi-modal treatment (1.53, 0.82–2.88). Observed racial disparities in survival of high-grade sarcoma may be addressed by early, multidisciplinary management. •Black representation in our cohort was greater than national cohorts.•Survival was worse for Black vs. White patients and those with metastatic disease.•Survival differences for Black vs. White non-metastatic patients were attenuated by receipt of multi-modal treatment.

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.

Soft tissue sarcomas (STS) have long been a formidable challenge in oncology, partly because of their rarity and diversity, which complicates large-scale studies and slows the advent of new treatments. Traditionally anchored by anthracycline-based chemotherapy, the landscape of STS treatment hasn’t shifted dramatically in the past twenty years. However, recent strides in research are starting to paint a more hopeful picture. Leveraging advanced molecular profiling, researchers are now tailoring treatments to the unique genetic makeup of tumors, with targeted therapies showing promise. Innovations such as NTRK inhibitors for NTRK-rearranged sarcomas and gamma-secretase inhibitors for desmoid tumors are changing clinical practices. The rise of immunotherapy, including novel agents like LAG-3 inhibitors and bifunctional proteins that target both TGF-β and PD-L1, offers new avenues for treatment, particularly when combined with traditional therapies like chemotherapy. Meanwhile, the approval of epigenetic treatments for specific sarcoma subtypes heralds a new wave of strategy based on histological specificity, which could lead to more personalized and effective care. While challenges remain, the field of STS treatment is evolving, driven by a deeper understanding of the disease’s biological underpinnings and a commitment to innovative research approaches.

Regional hyperthermia is considered to enhance the antitumor effects of chemotherapy and radiotherapy. In this study, we confirmed the efficacy of concomitant radiotherapy, hyperthermia, and chemotherapy (RHC) for neoadjuvant treatment of malignant soft tissue sarcoma (STS). From 1994 to 2013, we performed RHC in 150 patients. This study was limited to 60 patients using the following exclusion criteria: salvage for recurrence or unplanned excision, trunk location, metastasis at initiation, non‐STS, and no definitive surgery. As a control group, we collected data from 11,031 patients in the Bone and Soft Tissue Tumor Registry in Japan (BSTT). We performed multivariate logistic regression analysis, and propensity scores were created for comparisons between groups. The primary outcome of this study was to compare oncologic outcomes (5‐year local control rate [LC] and overall survival rate [OS]). In the RHC group, two local recurrences (3.3%) occurred, and no patients underwent amputation. Margins of definitive surgery were not identical between groups [wide margins (60.0% vs. 85.3%), marginal margins (28.3% vs. 10.5%), and intralesional margins (7.4% vs. 4.2%), RHC and BSTT groups, respectively, P < 0.001]. After adjustment, the difference in OS was not significant between groups (HR = 1.26, P = 0.532); however, a statistically significant difference in LC was observed (HR = 4.82, P = 0.037). RHC resulted in a high LC at 5 years compared to the BSTT group, and amputation was averted in the RHC group, despite the wider margins in the BSTT group. This indicates that less invasive surgery might be achieved with effective neoadjuvant therapy. The efficacy of concomitant radiotherapy, hyperthermia, and chemotherapy (RHC) for neoadjuvant treatment of malignant soft tissue sarcoma was confirmed by comparing to the Bone and Soft Tissue Tumor Registry in Japan (BSTT). RHC resulted in a high local control at 5 years compared to the BSTT group, and the difference in overall survival was not significant between groups.