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Keywords = soft tissue sarcomas (STS)

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13 pages, 938 KB  
Systematic Review
Role of Dynamic Contrast-Enhanced MRI in Detecting Post-Treatment Local Recurrence of Soft-Tissue Sarcomas: A Systematic Review and Meta-Analysis
by Arash Azhideh, Howard Chansky, Peyman Mirghaderi, Sara Haseli, Bahar Mansoori, Navid Faraji, Chankue Park, Shakiba Houshi and Majid Chalian
Diagnostics 2026, 16(1), 136; https://doi.org/10.3390/diagnostics16010136 - 1 Jan 2026
Viewed by 151
Abstract
Background: The role of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in detecting soft-tissue sarcoma (STS) local recurrence (LR) following therapeutic intervention was evaluated. Method: PubMed, Embase, and Scopus were systematically searched from January 1990 to 1 February 2024 for studies evaluating [...] Read more.
Background: The role of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in detecting soft-tissue sarcoma (STS) local recurrence (LR) following therapeutic intervention was evaluated. Method: PubMed, Embase, and Scopus were systematically searched from January 1990 to 1 February 2024 for studies evaluating DCE-MRI for LR detection in histologically confirmed STS following surgery. Two independent reviewers screened studies and extracted data, and a bivariate diagnostic test accuracy meta-analysis was performed to estimate pooled sensitivity, specificity, and the area under the summary receiver operating characteristic (SROC) curve. Results: Six studies, including 309 patients (110 with LR and 199 without LR), met the inclusion criteria. Across studies, DCE-MRI qualitative features (such as early rapid arterial enhancement and malignant time–intensity curves) and quantitative or semiquantitative parameters (such as volume transfer constants [Ktrans and Kep], initial area under the curve [iAUC], and relative plasma flow [rPF]) consistently differentiated LR from post-treatment change. When DCE-MRI parameters were added to conventional MRI, the pooled sensitivity and specificity for LR detection were 98% and 83%, respectively, with an SROC area under the curve of 0.94, indicating high overall diagnostic accuracy. Conclusions: DCE-MRI increases the accuracy of LR detection when combined with conventional MRI and offers a higher specificity and sensitivity in distinguishing LR from post-surgical changes, which support consideration of adding DCE-MRI when LR is suspected; prospective standardized studies are warranted. Full article
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15 pages, 3217 KB  
Article
Radiotherapy Combined with Immune Checkpoint Inhibitor on Murine Fibrosarcoma and a Narrative Review of Clinical Studies
by Wonwoo Kim, Hyunkyung Kim, Won Il Jang, Mi Sook Kim and Sun Hyun Bae
Curr. Issues Mol. Biol. 2026, 48(1), 20; https://doi.org/10.3390/cimb48010020 - 24 Dec 2025
Viewed by 218
Abstract
Purpose: The objective of this study was to evaluate the synergistic effect of combining an immune checkpoint inhibitor (ICI) with radiotherapy (RT) on murine fibrosarcoma and to conduct a narrative review of clinical studies on soft tissue sarcoma (STS). Materials and Methods: Forty [...] Read more.
Purpose: The objective of this study was to evaluate the synergistic effect of combining an immune checkpoint inhibitor (ICI) with radiotherapy (RT) on murine fibrosarcoma and to conduct a narrative review of clinical studies on soft tissue sarcoma (STS). Materials and Methods: Forty male C3H mice (aged 5 weeks) were injected intramuscularly with 2 × 105 FSaII cells into the right thigh and randomly assigned to four groups: (1) control; (2) RT; (3) InVivoMab™ (CD279) (mouse anti-PD-1 antibody) (ICI group); and (4) combined treatment with InVivoMab™ (CD279) and RT (combination group). On day −1, ICI was administered intraperitoneally. On day 0, RT (10 Gy, single fraction) was delivered locally to the tumors in the right hind limb. Subsequently, ICI was injected twice weekly (a total of 8 times). On day 26, all mice were euthanized, and the results were analyzed. In addition, a narrative review was conducted to identify clinical evidence. Results: On day 26, mean gross tumor volumes were 3578.13 ± 407.32 mm3 in the control group, 1995.72 ± 970.46 mm3 in the RT group, 2729.96 ± 286.47 mm3 in the ICI group, and 1007.92 ± 197.36 mm3 in the combination group. Gross tumor growth delay was most pronounced in the combination group. Moreover, the TUNEL assay demonstrated a significant increase in apoptosis in the combination group. Analysis of the underlying immune system revealed significantly higher expression of CD4+, CD8+, and IFN-γ in the combination group. The literature search identified only 12 case reports and 3 prospective studies involving patients with STS treated with the combined treatment of ICI and RT, suggesting potential synergism with acceptable toxicity. Conclusions: The current study demonstrated a synergistic effect of combining an ICI with RT in murine fibrosarcoma. There was limited data in the clinical setting. Further investigations are warranted to determine the optimal combination strategy of ICI and RT for STS. Full article
(This article belongs to the Section Molecular Medicine)
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16 pages, 638 KB  
Review
A Comprehensive Review of Margin Identification Methods in Soft Tissue Sarcoma
by Yasmin Osman, Jean-Philippe Dulude, Frédéric Leblond and Mai-Kim Gervais
Curr. Oncol. 2025, 32(12), 703; https://doi.org/10.3390/curroncol32120703 - 13 Dec 2025
Viewed by 399
Abstract
Soft tissue sarcomas (STS) are rare and heterogeneous tumors for which achieving complete tumor resection with negative surgical margins remains the cornerstone of curative treatment and a key predictor of survival. Current intraoperative resection margin status assessment techniques remain limited, as traditional intraoperative [...] Read more.
Soft tissue sarcomas (STS) are rare and heterogeneous tumors for which achieving complete tumor resection with negative surgical margins remains the cornerstone of curative treatment and a key predictor of survival. Current intraoperative resection margin status assessment techniques remain limited, as traditional intraoperative frozen section analysis is of limited accuracy for most STS histological subtypes. This comprehensive review evaluates current and emerging margin assessment techniques used intra-operatively during STS resection. A systematic search of PubMed and PubMed Central databases from 2000 to 2025 identified studies using fluorescence imaging, spectroscopy, and ultrasound-based modalities. Indocyanine green (ICG) fluorescence-guided surgery appeared to be the closest to widespread use, with the most clinical evidence showing potential to reduce positive margins. Use of acridine orange (AO) as a fluorescent dye also showed potential in decreasing local recurrences, but it remains in the experimental stage of research with little clinical data available. Raman spectroscopy has recently shown high accuracy in identifying STS from healthy tissue, but the impact of its use on patient outcomes has not been studied yet. Other techniques, such as diffuse reflectance spectroscopy (DRS), rapid evaporative ionization mass spectrometry (REIMS), optical coherence tomography (OCT), and intraoperative ultrasound (IOUS) yielded encouraging results but still require further prospective studies to validate their safety, reproducibility, and clinical utility in improving surgical precision and patient outcomes. Full article
(This article belongs to the Special Issue Sarcoma Surgeries: Oncological Outcomes and Prognostic Factors)
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17 pages, 539 KB  
Article
The Surveillance After Extremity Tumor Surgery (SAFETY) Pilot International Multi-Center Randomized Controlled Trial
by Hadia Farrukh, Patricia Schneider, Tess Hudson, Victoria Giglio, Ricardo Gehrke Becker, Samir Sabharwal, Kimmen Quan, Valerie Francescutti, Mira Goldberg, Sheila Sprague and Michelle Ghert
Curr. Oncol. 2025, 32(12), 686; https://doi.org/10.3390/curroncol32120686 - 4 Dec 2025
Viewed by 329
Abstract
Soft-tissue sarcomas (STSs) are rare malignancies predominantly found in the extremities. Surgery and radiation are standard treatments, but post-operative pulmonary surveillance, involving clinical visits and thoracic imaging, is crucial due to a high recurrence rate, most commonly to the lungs. Current pulmonary surveillance [...] Read more.
Soft-tissue sarcomas (STSs) are rare malignancies predominantly found in the extremities. Surgery and radiation are standard treatments, but post-operative pulmonary surveillance, involving clinical visits and thoracic imaging, is crucial due to a high recurrence rate, most commonly to the lungs. Current pulmonary surveillance guidelines lack robust evidence. The Surveillance AFter Extremity Tumor SurgerY (SAFETY) randomized controlled trial is designed to determine the impact of pulmonary surveillance frequency (every three versus six months) and chest imaging modality (CXR versus CT) on patient-important outcomes. The pilot phase assessed feasibility of patient enrolment, protocol adherence, and data quality, as well as aggregate outcomes at two years of follow-up. 100 patients were enrolled from 300 screened patients across 17 international sites. Minor protocol deviations were common. Follow-up, data completeness and data quality met the progression criteria of 85%. Of the 100 patients, 15 died, 21 had metastases, seven had local recurrence and 30 experienced at least one serious adverse event. This SAFETY trial study established feasibility of enrolment and data quality, and confirmed the need to emphasize protocol adherence in sarcoma care. The results of this trial are expected to provide crucial evidence to standardize STS pulmonary surveillance practices, ultimately improving patient management and expectations. Full article
(This article belongs to the Special Issue Sarcoma Surgeries: Oncological Outcomes and Prognostic Factors)
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15 pages, 2162 KB  
Article
The Immune Landscape of Canine Soft Tissue Sarcomas as a Model for Human Soft Tissue Sarcomas
by Regina Hayburn, Dongjun Chung, Arkobato Gupta, Shane Sills, Jennifer Donglan Wu, Andy Ambrus, Weiqing Jing, Juliana Ng, Pablo Penaloza-MacMaster, Aubrie Selmek, Seth M. Pollack and Shay Bracha
Cancers 2025, 17(23), 3860; https://doi.org/10.3390/cancers17233860 - 30 Nov 2025
Viewed by 706
Abstract
Background/Objectives: Soft tissue sarcomas (STS) remain a therapeutic challenge due to their limited response to radiation and conventional chemotherapies. While recent advances in immunotherapy have improved outcomes in several cancers, these strategies have been largely disappointing in STS patients. Naturally occurring STS in [...] Read more.
Background/Objectives: Soft tissue sarcomas (STS) remain a therapeutic challenge due to their limited response to radiation and conventional chemotherapies. While recent advances in immunotherapy have improved outcomes in several cancers, these strategies have been largely disappointing in STS patients. Naturally occurring STS in dogs have been suggested as a spontaneous, immunocompetent model of human STS, but further characterization of its tumor immune microenvironment is needed to validate its relevance. This study aimed to identify the shared immune-related components of canine and human STS and to determine how these factors influence the tumor biology, progression, and prognosis. Results: Data from 75 dogs with STS was analyzed. In addition, we characterized the tumor immune microenvironment using immunohistochemistry and compared gene expression between canine and human STS. Progression-free survival and time to metastasis was significantly longer in castrated males in comparison to females. In addition, dogs with appendicular tumors had better progression- and recurrence-free survival, whereas tumor recurrence following surgical excision was associated with a shorter time to metastasis. Immunohistochemistry revealed infiltration of CD204+ cells in most of the tumors examined, and disease-free intervals were shorter in dogs with tumors exhibiting FOXP3+ cell infiltration. Gene expression profiling demonstrated similarities between canine STS and human undifferentiated pleomorphic sarcomas, with MYC dysregulation emerging as a poor prognostic indicator for dogs. Conclusions: The comparative analysis between the human and canine STS microenvironment offers a valuable insight into the clinical behavior and immune landscape of canine STS, underscoring its potential as a relevant preclinical model for the translation and development of future immunotherapies. Full article
(This article belongs to the Section Tumor Microenvironment)
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19 pages, 1136 KB  
Review
Functional Assays to Guide Personalized Oncological Treatment of Patients with Soft-Tissue Sarcomas
by Sude Yarar and Panagiotis Tsagkozis
Cancers 2025, 17(21), 3452; https://doi.org/10.3390/cancers17213452 - 28 Oct 2025
Viewed by 709
Abstract
Background/Objectives: Soft tissue sarcomas (STSs) are rare tumors arising from mesenchymal tissues, comprising over 100 distinct histological subtypes with varying biological behaviors, metastatic patterns, and treatment responses Despite advances in multimodal therapy, the overall survival of patients with metastatic STS is poor, [...] Read more.
Background/Objectives: Soft tissue sarcomas (STSs) are rare tumors arising from mesenchymal tissues, comprising over 100 distinct histological subtypes with varying biological behaviors, metastatic patterns, and treatment responses Despite advances in multimodal therapy, the overall survival of patients with metastatic STS is poor, mainly due to the weak response to conventional chemotherapy based on doxorubicin and ifosfamide. Methods: This review examines the evolution from traditional one-size-fits-all treatments to personalized medicine strategies, primarily focusing on assays based on patient-derived tumor samples, and it highlights their emerging role in guiding personalized treatment decisions and improving clinical outcomes in STS. These approaches, also known as functional precision oncology, are a step closer to the clinical situation as compared to other personalized therapies that rely on the identification of targetable genomic alterations using high-throughput technologies such as whole-genome sequencing, which have thus far failed to show convincing responses in STS treatment. Results: The main functional precision oncology platforms tested in patients with STS are in vitro cell viability tests, organoid cultures, and patient-derived xenografts. Each has advantages and limitations. In this context, in vitro drug sensitivity using cell suspension or organoids has shown a strong correlation with clinical responses. Furthermore, organoids matched the original tumor histology and microenvironment to a satisfactory degree. Establishment of xenografts proved feasible in the majority of patients; the technique could also preserve the tumor architecture and displayed high physiological relevance to the clinical situation. Conclusions: Although a major clinical study directly comparing conventional chemotherapy to personalized treatment guided by functional assays is yet to be published, this approach has gained popularity given the low efficacy of personalized medicine based on genetic alterations. The results thus far show promise for a better outcome for patients with metastatic STS. Full article
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11 pages, 513 KB  
Systematic Review
The Safety of Negative-Pressure Wound Therapy in Melanoma and Sarcoma Patients: A Systematic Review
by Silvia Dal Pos, Stela Tafaj, Ilda Hoxhaj, Fortunato Cassalia, Francesco Russano, Saveria Tropea, Paolo Del Fiore and Marcodomenico Mazza
J. Clin. Med. 2025, 14(19), 7044; https://doi.org/10.3390/jcm14197044 - 5 Oct 2025
Viewed by 1068
Abstract
Background/Objectives: Negative-Pressure Wound Therapy (NPWT) is increasingly used to promote wound healing in chronic and complicated wounds, but its use in surgical oncology is still debated due to theoretical concerns about promoting local tumor recurrence. The aim of this study is to review [...] Read more.
Background/Objectives: Negative-Pressure Wound Therapy (NPWT) is increasingly used to promote wound healing in chronic and complicated wounds, but its use in surgical oncology is still debated due to theoretical concerns about promoting local tumor recurrence. The aim of this study is to review the available evidence on the oncologic safety of NPWT, specifically regarding the risk of local recurrence in patients undergoing surgery for cutaneous melanoma (CM) or soft tissue sarcoma (STS). Methods: A systematic review of the literature was conducted using the MEDLINE/PubMed, EMBASE, and Scopus databases through December 2024 (PROSPERO: CRD42024623405). Case series, retrospective cohort studies, and randomized clinical trials reporting survival data in melanoma and sarcoma patients treated with NPWT were eligible for inclusion. PRISMA guidelines were followed and quality assessment checked. Results: Seventeen studies were eligible for the analysis with a total of 285 patients, 197 affected by soft tissue sarcoma and 88 by cutaneous melanoma. The pooled proportion of local recurrence was 5% in patients treated with NPWT, regardless of the histology considered (STS and CM). When comparing NPWT to conventional wound therapy, both the pooled risk ratio (0.87; 95% CI: 0.24–3.11; Tau2 = 0.14; I2 = 8%) and odds ratio (0.83; 95% CI: 0.20–3.39; Tau2 = 0.18) indicated no statistically significant difference in the recurrence rate. Conclusions: Current evidence does not suggest an increased risk of local recurrence associated with NPWT in melanoma or sarcoma patients, and mostly, NPWT may have important advantages over standard surgical dressings. More high-power randomized controlled trials with wider follow-up periods are needed to make it possible for practitioners to use this technique without being afraid of higher risk local recurrences. Full article
(This article belongs to the Special Issue New Advances in Wound Healing and Skin Wound Treatment)
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13 pages, 451 KB  
Systematic Review
Evaluation of Treatment Modalities and Oncologic Outcomes in Hand Soft Tissue Sarcomas—A Systematic Review of the Literature
by W. Rodrigo Calmet Rocca, Rayna S. Kuthiala, Marcos R. Gonzalez and Juan Pretell-Mazzini
Cancers 2025, 17(19), 3204; https://doi.org/10.3390/cancers17193204 - 1 Oct 2025
Viewed by 1008
Abstract
Background/Objectives: Soft tissue sarcomas (STS) of the hand are rare, representing only 2% of all STS. The small size and benign appearance of these tumors often lead to unplanned excisions and diagnostic delay. This systematic review sought to characterize the clinical presentation, histology, [...] Read more.
Background/Objectives: Soft tissue sarcomas (STS) of the hand are rare, representing only 2% of all STS. The small size and benign appearance of these tumors often lead to unplanned excisions and diagnostic delay. This systematic review sought to characterize the clinical presentation, histology, treatment modalities, and oncological outcomes of hand STS. Methods: A systematic review of PubMed and Embase was conducted following PRISMA guidelines. The protocol was registered on PROSPERO. We included studies with ≥10 patients with STS that provided data on treatment options and oncologic outcomes. Data was extracted regarding demographics, tumor features, treatment modalities, and survival metrics. Results: Eighteen studies comprising 570 patients were included. Most tumors were <5 cm, and 56.8% were deep (subfascial). Epithelioid and synovial sarcomas were the most common histologies, accounting for 27% and 17% of cases, respectively. UEs were seen in 57% of cases, and 26% of patients required amputation. Positive surgical margins were reported in 16% of patients. Radiation therapy and chemotherapy were used in 40% and 17% of patients, respectively. Twelve and 15% of patients developed regional lymph node and distant metastases, respectively. Local recurrence occurred in 20% of cases. Five- and ten-year overall survival were 80% and 77%, respectively. Disease-free survival at those time points were 77% and 74%, respectively. Conclusions: Hand STSs are challenging due to their rarity, small size, and high rates of UEs. Despite favorable survival rates, local recurrence and metastases remain a concern. Early referral to specialized centers and individualized treatment strategies are essential for improving outcomes. Full article
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21 pages, 4875 KB  
Systematic Review
Reporting Matters: Severe Adverse Events in Soft Tissue Sarcoma Therapy—A 30-Year Systematic Review of Placebo- and Non-Systemic-Controlled Randomized Trials
by Rahel Aeschbacher, Bruno Fuchs, Gabriela Studer and Philip Heesen
Cancers 2025, 17(19), 3118; https://doi.org/10.3390/cancers17193118 - 25 Sep 2025
Viewed by 863
Abstract
Background: Systemic therapy for soft tissue sarcoma (STS) provides modest survival benefit but carries clinically relevant toxicity. Published trials report adverse events (AEs) of varying quality and extension. Poor toxicity reporting hampers balanced risk–benefit appraisal. Methods: A PRISMA-2020 systematic review was registered in [...] Read more.
Background: Systemic therapy for soft tissue sarcoma (STS) provides modest survival benefit but carries clinically relevant toxicity. Published trials report adverse events (AEs) of varying quality and extension. Poor toxicity reporting hampers balanced risk–benefit appraisal. Methods: A PRISMA-2020 systematic review was registered in PROSPERO CRD420251087366. PubMed, CENTRAL, and Google Scholar were searched from 16 December 2024 to 16 April 2025 for randomized controlled trials (RCTs) evaluating chemotherapy, kinase inhibitors, or immune checkpoint inhibitors in STS. AE terms were harmonized to CTCAE v5.0; event rates were normalized to patients evaluable for safety. Pooled proportions used DerSimonian–Laird random-effects models; between-group comparisons employed unpaired t-tests. Risk of bias (RoB 2) was assessed with the Cochrane RoB 2 tool. Results: Ten RCTs (1079 treated, 979 control patients; 1994–2024) met the inclusion criteria, although two lacked sufficient presentation of toxicity data and seven failed to report parallel control-arm AEs. Pooled normalized incidences for treated patients were as follows: grade ≥ 3 hematological AEs, 17% (95% CI 14–20); severe gastrointestinal AEs, 9% (8–11); and grade 4 AEs, ≤6%. Anthracycline-based and kinase-inhibitor regimens displayed comparable composite grade ≥ 3 burdens (58% vs. 84%, p = 0.64). Between-study heterogeneity was considerable for gastrointestinal and hematological events (I2 > 60%), driven by differing AE scales and denominators. Late-effect toxicities (cardiac, hepatic, neurological, and nephrological) were rarely reported, occurring in <1% of the patients. Across the three RCTs with control-arm data, experimental therapy increased common grade 3 AEs by 4–12 percentage points (p = 0.001). RoB 2 flagged serious concerns in 4/10 trials. Conclusions: Severe AEs in STS systemic therapy are moderately frequent; while the toxicity spectrum differs across drug classes (e.g., hematological for anthracyclines vs. neuropathic or fatigue-related for agents such as eribulin), the aggregate burden of severe AEs has not been lower for newer agents. Confidence in these estimates is limited by incomplete and non-standardized AE reporting. Future sarcoma trials must adopt CTCAE v5.0, specify explicit safety denominators, and publish full AE matrices to enable high-certainty risk–benefit assessment. Full article
(This article belongs to the Section Methods and Technologies Development)
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10 pages, 892 KB  
Case Report
Adult Pleomorphic Rhabdomyosarcoma: Case Report
by Beatrice Oancea and Roxana Elena Mirică
Reports 2025, 8(3), 166; https://doi.org/10.3390/reports8030166 - 1 Sep 2025
Viewed by 1893
Abstract
Background and Clinical Significance: Rhabdomyosarcoma (RMS) is a rare and aggressive malignant soft-tissue sarcoma (STS) arising from skeletal connective tissues and is most commonly seen in the pediatric population. The pleomorphic subtype is mostly seen in adults in the sixth and seventh decades [...] Read more.
Background and Clinical Significance: Rhabdomyosarcoma (RMS) is a rare and aggressive malignant soft-tissue sarcoma (STS) arising from skeletal connective tissues and is most commonly seen in the pediatric population. The pleomorphic subtype is mostly seen in adults in the sixth and seventh decades of life, representing 1% of all histological types of RMS and having a very poor prognosis. Case Presentation: This report presents the case of a 63-year-old male with a medical history of papillary thyroid cancer, who presented with an ulcer-hemorrhagic malignant tumor, namely, a poorly differentiated desmin-positive pleomorphic rhabdomyosarcoma (PRMS), with impressive dimensions located on the posterior thoracic wall. This tumor was surgically removed via a wide resection, followed by palliative chemotherapy and radiotherapy. However, the patient relapsed locally, with pulmonary, bone, and lymph node metastases. The peculiarity of this case is represented by the rapid growth, aggressive nature, and high metastatic potential of the adult RMS, as well as its poor response to treatment. Conclusions: The presented case underscores the need for early diagnosis, multidisciplinary management, and exploration of molecular profiling for therapeutic planning. Full article
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30 pages, 3010 KB  
Article
Transcriptomic-Based Classification Identifies Prognostic Subtypes and Therapeutic Strategies in Soft Tissue Sarcomas
by Miguel Esperança-Martins, Hugo Vasques, Manuel Sokolov Ravasqueira, Maria Manuel Lemos, Filipa Fonseca, Diogo Coutinho, Jorge Antonio López, Richard S. P. Huang, Sérgio Dias, Lina Gallego-Paez, Luís Costa, Nuno Abecasis, Emanuel Gonçalves and Isabel Fernandes
Cancers 2025, 17(17), 2861; https://doi.org/10.3390/cancers17172861 - 30 Aug 2025
Cited by 1 | Viewed by 2747
Abstract
Background: Soft tissue sarcomas (STSs) histopathological classification system and the clinical and molecular-based tools that are currently employed to estimate its prognosis have several limitations, impacting prognostication and treatment. Clinically driven molecular profiling studies may cover these gaps and offer alternative tools with superior [...] Read more.
Background: Soft tissue sarcomas (STSs) histopathological classification system and the clinical and molecular-based tools that are currently employed to estimate its prognosis have several limitations, impacting prognostication and treatment. Clinically driven molecular profiling studies may cover these gaps and offer alternative tools with superior prognostication capability and enhanced precision and personalized treatment approaches identification ability. Materials and Methods/Results: We performed DNA sequencing (DNA-seq) and RNA sequencing (RNA-seq) to portray the molecular profile of 102 samples of high-grade STS, comprising the three most common STS histotypes. The analysis of RNA-seq data using unsupervised machine learning models revealed previously unknown molecular patterns, identifying four transcriptomic subtypes/clusters (TCs). This TC-based classification has a clear prognostic value (in terms of overall survival (OS) and disease-free survival (DFS)), a finding that was externally validated using independent patient cohorts. The prognostic value of this TC-based classification outperforms the prognostic accuracy of clinical-based (SARCULATOR nomograms) and molecular-based (CINSARC) prognostication tools, being one of the first molecular-based classifications capable of predicting OS in STS. The analysis of DNA-seq data from the same cohort revealed numerous and, in some cases, never documented molecular targets for precision treatment across different transcriptomic subtypes. The functional and predictive value of each genomic variant was analyzed using the Molecular Tumor Board Portal. Conclusions: This newly identified TC-based classification offers a superior prognostic value when compared with current gold-standard clinical and molecular-based prognostication tools, and identifies novel molecular targets for precision treatment, representing a cutting-edge tool for predicting prognosis and guiding treatment across different stages of STS. Full article
(This article belongs to the Special Issue News and How Much to Improve in Management of Soft Tissue Sarcomas)
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13 pages, 834 KB  
Article
Rehabilitation Outcomes Following Surgical Management of Lower-Limb Soft Tissue Sarcomas: Insights from Gait Analysis
by Marco Germanotta, Francesca Falchini, Arianna Pavan, Stefania Lattanzi, Laura Cortellini, Beniamino Brunetti, Stefania Tenna, Alice Valeri, Chiara Pagnoni, Roberto Passa, Michela Angelucci, Bruno Vincenzi, Rossana Alloni, Irene Giovanna Aprile and Sergio Valeri
J. Clin. Med. 2025, 14(17), 6061; https://doi.org/10.3390/jcm14176061 - 27 Aug 2025
Viewed by 1045
Abstract
Background: Soft tissue sarcomas (STSs) are rare and heterogeneous malignancies requiring a multidisciplinary approach to diagnosis and treatment. Advances in surgical techniques, chemotherapy, and radiotherapy have improved survival rates but often result in significant functional impairments, particularly in patients undergoing limb-sparing procedures. Rehabilitation [...] Read more.
Background: Soft tissue sarcomas (STSs) are rare and heterogeneous malignancies requiring a multidisciplinary approach to diagnosis and treatment. Advances in surgical techniques, chemotherapy, and radiotherapy have improved survival rates but often result in significant functional impairments, particularly in patients undergoing limb-sparing procedures. Rehabilitation is crucial for restoring mobility and independence, with recent studies emphasizing the importance of personalized rehabilitation protocols tailored to specific surgical interventions. Quantitative assessments, such as 3D motion capture and surface electromyography, provide objective insights into gait performance and motor function, enabling more precise rehabilitation strategies to optimize recovery. Methods: This study evaluated gait performance in 21 patients with lower-limb impairment following limb-sparing surgery for STS. Patients underwent two instrumented gait assessments using marker-based 3D motion capture and surface electromyography to measure spatiotemporal gait parameters, joint kinematics, and muscle activity. Independence in the activity of daily living was assessed with the modified Barthel Index in both timepoints. Results: Following rehabilitation, patients demonstrated significant improvements in functional independence, as reflected by an increase in the modified Barthel Index (p < 0.001). Gait analysis revealed increased walking speed, stride length, cadence, and improved joint range of motion at the hip, knee, and ankle, though electromyographic analysis showed no statistically significant differences in muscle activation patterns or co-contraction indices. Conclusions: These findings underscore the importance of a rehabilitation programs personalized on gait strategies. A deeper understanding of motor adaptations based on sarcoma location and surgical approach could further refine rehabilitation protocols, ultimately enhancing patient outcomes and quality of life. Full article
(This article belongs to the Section Clinical Rehabilitation)
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17 pages, 1500 KB  
Article
Comprehensive Receptor Repertoire and Functional Analysis of Peripheral NK Cells in Soft Tissue Sarcoma Patients
by Luana Madalena Sousa, Jani-Sofia Almeida, Tânia Fortes-Andrade, Patrícia Couceiro, Joana Rodrigues, Rúben Fonseca, Manuel Santos-Rosa, Paulo Freitas-Tavares, José Manuel Casanova and Paulo Rodrigues-Santos
Cancers 2025, 17(15), 2508; https://doi.org/10.3390/cancers17152508 - 30 Jul 2025
Cited by 1 | Viewed by 997
Abstract
Background: Soft tissue sarcomas (STSs) are a rare and heterogeneous group of mesenchymal tumors with limited response to current therapies, particularly in advanced stages. STS tumors were traditionally considered “cold” tumors, characterized by limited immune infiltration and low immunogenicity. However, emerging evidence is [...] Read more.
Background: Soft tissue sarcomas (STSs) are a rare and heterogeneous group of mesenchymal tumors with limited response to current therapies, particularly in advanced stages. STS tumors were traditionally considered “cold” tumors, characterized by limited immune infiltration and low immunogenicity. However, emerging evidence is challenging this perception, highlighting a potentially critical role for the immune system in STS biology. Objective: Building on our previous findings suggesting impaired natural killer (NK) cell activity in STS patients, we aimed to perform an in-depth characterization of peripheral NK cells in STS. Methods: Peripheral blood samples from STS patients and sex- and age-matched healthy donors were analyzed to assess NK cell degranulation, IFNγ production, and receptor repertoire. Results: Functional assays revealed a notable reduction in both degranulation and IFNγ production in NK cells from STS patients. STS patients also exhibited dysregulated expression of activating and inhibitory NK cell receptors. Principal component analysis (PCA) identified CD27 and NKp44 as critical markers for distinguishing STS patients from healthy donors. Increased CD27 expression represents a shift towards a more regulatory NK cell phenotype, and we found that CD27 expression was negatively correlated with NK cell degranulation and IFNγ production. ROC curve analysis demonstrated strong potential to distinguish between the groups for both CD27 (AUC = 0.85) and NKp44 (AUC = 0.94). Conclusion: In conclusion, STS patients exhibited impaired NK cell function, altered receptor repertoire, and a shift towards a less cytotoxic and more regulatory phenotype. Full article
(This article belongs to the Section Cancer Immunology and Immunotherapy)
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8 pages, 470 KB  
Article
Preoperative Chemoradiation (Modified Eilber Protocol) Versus Preoperative/Postoperative Radiotherapy for Soft Tissue Sarcomas: A Population-Based Analysis
by Greg M. Padmore, Elizabeth C. Kurien, Michael J. Monument, Lloyd Mack, Antoine Bouchard-Fortier and on behalf of the ISARP Group
Curr. Oncol. 2025, 32(7), 374; https://doi.org/10.3390/curroncol32070374 - 26 Jun 2025
Viewed by 951
Abstract
Background: Local recurrence for high-risk extremities/trunk soft tissue sarcoma (STS) after treatment can range from 15 to 30%. The modified Eilber protocol (MEP) using low-dose intravenous chemotherapy with a reduced dosage of radiation in the preoperative setting has demonstrated excellent local control and [...] Read more.
Background: Local recurrence for high-risk extremities/trunk soft tissue sarcoma (STS) after treatment can range from 15 to 30%. The modified Eilber protocol (MEP) using low-dose intravenous chemotherapy with a reduced dosage of radiation in the preoperative setting has demonstrated excellent local control and reduced wound complications in these patients. The aim of the current study was to assess long-term local control and overall survival in patients with STS treated with the MEP versus standard preoperative or postoperative radiotherapy. Methods: Patients diagnosed with STS from 2004 to 2016 were identified using the Alberta Cancer Registry. Patients with STS treated with the MEP, preoperative or postoperative radiotherapy, were included. Patient and tumor characteristics, treatments and outcomes were abstracted from the registry and primary chart review. Characteristics were compared using one-way ANOVA for continuous variable and chi-square test and Fisher test for the categorical outcomes. Local recurrence-free survival and overall survival were analyzed using Kaplan–Meier Analysis with Log-rank test. Results: A total of 242 patients with STS were included, among which 100 (41.3%) received the MEP prior to surgery, 91 (37.6%) had preoperative radiation, and 51 (21.1%) had postoperative radiation. After a median follow up of 4.9 years, there were no significant differences in local recurrence or local recurrence-free survival between patients treated with the MEP vs. preoperative or postoperative radiotherapy (10 vs. 6.6% and 7.8%, respectively, p-value NS). There were also no significant differences between groups for recurrence-free survival and overall survival. Conclusions: This study demonstrates that the use of the MEP has non-inferior oncologic outcomes compared to standard preoperative or postoperative radiation in a population-based analysis despite reducing the overall dosage of radiation administered. The modified Eilber preoperative chemoradiation protocol may be considered as an additional option for patients with STS. Full article
(This article belongs to the Special Issue Sarcoma Surgeries: Oncological Outcomes and Prognostic Factors)
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Review
Cancer Risk Associated with Residential Proximity to Municipal Waste Incinerators: A Review of Epidemiological and Exposure Assessment Studies
by Jose L. Domingo
Green Health 2025, 1(1), 4; https://doi.org/10.3390/greenhealth1010004 - 26 May 2025
Viewed by 3143
Abstract
Municipal Solid Waste Incinerators (MSWIs) are facilities designed to burn municipal solid waste to reduce its volume and mass and generate energy. A significant concern related to MSWIs is the emission of toxic and carcinogenic pollutants, including polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs), heavy [...] Read more.
Municipal Solid Waste Incinerators (MSWIs) are facilities designed to burn municipal solid waste to reduce its volume and mass and generate energy. A significant concern related to MSWIs is the emission of toxic and carcinogenic pollutants, including polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs), heavy metals, and particulate matter. This review synthesizes global epidemiological and exposure assessment studies investigating cancer risks associated with residential proximity to MSWIs. Findings reveal a complex relationship: older incinerators with high emissions correlate with elevated risks of non-Hodgkin lymphoma (NHL), soft-tissue sarcoma (STS), and liver cancer in some studies, particularly in Europe. However, results remain inconsistent due to methodological limitations such as exposure misclassification, latency periods, and confounding factors like socioeconomic status. Modern facilities equipped with advanced pollution control technologies demonstrate reduced risks, often within regulatory thresholds. Key challenges include accurately quantifying historical exposures and disentangling MSWI-specific risks from other environmental or lifestyle factors. While advancements in dispersion modeling and biomonitoring have improved risk assessments, geographical and temporal variations in findings underscore the need for continued research. The review concludes that while historical evidence suggests potential cancer risks near older MSWIs, stricter emissions regulations and technological improvements have mitigated health impacts, although vigilance through long-term monitoring remains essential to safeguard public health. Full article
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