Search Results (849)

Objective: This study introduces an explainable, radiomics-based machine learning framework for the automated classification of sarcoma tumors using MRI. The approach aims to empower clinicians, reducing dependence on subjective image interpretation. Methods: A total of 186 MRI scans from 86 patients diagnosed with bone and soft tissue sarcoma were manually segmented to isolate tumor regions and corresponding healthy tissue. From these segmentations, 851 handcrafted radiomic features were extracted, including wavelet-transformed descriptors. A Random Forest classifier was trained to distinguish between tumor and healthy tissue, with hyperparameter tuning performed through nested cross-validation. To ensure transparency and interpretability, model behavior was explored through Feature Importance analysis and Local Interpretable Model-agnostic Explanations (LIME). Results: The model achieved an F1-score of 0.742, with an accuracy of 0.724 on the test set. LIME analysis revealed that texture and wavelet-based features were the most influential in driving the model’s predictions. Conclusions: By enabling accurate and interpretable classification of sarcomas in MRI, the proposed method provides a non-invasive approach to tumor classification, supporting an earlier, more personalized and precision-driven diagnosis. This study highlights the potential of explainable AI to assist in more secure clinical decision-making. Full article

Sarcomas are tumors of mesenchymal origin that are generally resistant to systemic therapies and prone to local recurrence despite current multimodal treatment approaches. Focused ultrasound (FUS) is a noninvasive therapeutic technology that may enhance standard treatment strategies for primary solid malignancies. FUS exerts its effects through diverse mechanisms, including high-intensity focused ultrasound (HIFU) thermal ablation, histotripsy, sonodynamic therapy, immunomodulation, and hyperthermia-enhanced drug delivery. In this narrative review, we summarize the mechanisms of focused ultrasound that have been investigated for the treatment of sarcomas and highlight the results of preclinical, veterinary, and clinical studies related to this area. Full article

High-grade sarcomas often lack typical morphological features and exhibit no clear differentiation, often leading to a diagnosis of undifferentiated sarcoma (US). Pleomorphic leiomyosarcoma (PLMS) is a high-grade sarcoma consisting of a typical leiomyosarcoma (LMS) component alongside dedifferentiated high-grade areas. A few decades ago, PLMS was regarded as a subtype of high-grade sarcoma previously referred to as malignant fibrous histiocytoma; it is now classified as a variant of LMS. The mechanisms underlying myogenic differentiation and their relevance to the pathological diagnosis of high-grade sarcomas remain poorly understood. To investigate the gene expression networks associated with myogenic differentiation, we employed Cap Analysis of Gene Expression (CAGE) to distinguish PLMS from other high-grade sarcoma subtypes. We analyzed 27 frozen high-grade sarcoma samples, comprising 10 PLMSs, 11 high-grade myxofibrosarcomas, 3 dedifferentiated liposarcomas, 2 USs, and 1 high-grade sarcoma not otherwise specified, using CAGE profiling. Hierarchical clustering based on differentially expressed genes identified by CAGE separated 7 of the 10 PLMSs from other high-grade sarcomas, while the remaining 3 PLMSs clustered with a single US case. CAGE analysis also revealed that the myostatin (MSTN) promoter (false discovery rate [FDR] < 0.05) was more strongly activated in the high-grade sarcoma group lacking morphological and immunohistochemical smooth muscle differentiation than in the PLMS group, whereas the alpha smooth muscle actin (ACTA2) promoter (FDR < 0.05) was more prominently activated in the PLMS group. Immunohistochemical analysis showed reduced or absent myostatin expression in PLMSs, in contrast to diffuse myostatin expression in other high-grade sarcomas. Smooth muscle actin, encoded by ACTA2, was expressed in all 10 PLMS cases but only in 11 of 17 other high-grade sarcomas. Furthermore, both conventional immunohistochemistry and double immunostaining revealed that myostatin and myogenic markers exhibited largely mutually exclusive expression patterns within these tumors. A validation study was performed using 59 soft tissue sarcoma cases, including 27 PLMSs and 16 LMSs. Loss or reduction in myostatin expression was confirmed in both LMS and PLMS, and the ratio of myostatin loss was comparable (62.5% in LMS vs. 63% in PLMS). Collectively, these findings suggest that myostatin contributes to smooth muscle differentiation in high-grade sarcomas and has potential utility as a diagnostic marker. Full article

Background/Objectives: The quality of surgical margins has been shown to be a prognostic factor in many sarcoma entities, yet its role in osteosarcoma remains controversial. While previous studies have shown that the outcome was not related to the margin width in bone, the impact of the extraosseous margin width (margin at the soft tissue invasion)—which needs to be close sometimes due to neurovascular structures—needs to be assessed. This study aims to evaluate the influence of soft tissue surgical margins on local recurrence and overall survival in patients with high-grade osteosarcoma. Methods: We conducted a retrospective, single-center study including 75 patients treated for high-grade osteosarcoma. All patients underwent standardized neoadjuvant chemotherapy followed by complete surgical resection. Patients were stratified into three groups based on the histological margin width of the extraosseous parts: group 1 (<1 mm), group 2 (1–5 mm), and group 3 (≥5 mm). Primary endpoints were local recurrence and overall survival (OS), analyzed using Kaplan–Meier estimates, log-rank tests, and Cox regression. Results: Local recurrence occurred in seven patients (9%). Although the overall comparison between the three groups was not statistically significant (p = 0.074), a subgroup analysis revealed a significantly higher recurrence rate in patients with margins < 1 mm compared to those with wider margins (p = 0.024). No significant differences in overall survival (OS) were observed between the groups (p = 0.896). Tumor location, metastatic status, and UICC stage were significant predictors for both endpoints in univariate analysis. However, none of these association were confirmed in multivariate analyses. Conclusions: Very close surgical margins (<1 mm) may increase the risk of local recurrence in high-grade osteosarcoma; however, they do not appear to affect overall survival. Full article

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

Background and Clinical Significance: Myxoid liposarcoma (MLS) is a malignant soft tissue tumor that often presents as a painless, slow-growing mass and is known for its atypical extrapulmonary metastatic pattern. Although sciatic nerve involvement is rare, when present, it usually causes neurologic symptoms. In this case, a large MLS silently expanded and completely encased the sciatic nerve without causing deficits, highlighting the importance of early imaging, multidisciplinary planning, and individualized surgical strategy in managing complex soft tissue sarcomas. Case Presentation: This case report describes a 67-year-old male with a 30 cm encapsulated myxoid liposarcoma of the posterior left thigh. The tumor had grown insidiously over one year and completely encased the sciatic nerve without causing pain, paresthesia, or motor impairment. Selective embolization was performed preoperatively to minimize blood loss. A posteromedial surgical approach allowed for en bloc resection with negative margins and preservation of sciatic nerve integrity. Histopathology confirmed a myxoid liposarcoma composed primarily of spindle-shaped tumor cells. The patient experienced no postoperative complications or neurologic deficits. At the two-year follow-up, he remains disease-free with full functional recovery. Conclusions: This case illustrates the potential for large, asymptomatic myxoid liposarcomas to encase critical neurovascular structures without infiltration. Preoperative embolization as part of a multidisciplinary plan was key to achieving safe resection and excellent functional outcomes. Full article

Background/Objectives: Ewing sarcoma (ES), a highly aggressive bone and soft tissue cancer occurring in children and young adults, is defined by the ETS fusion oncoprotein EWS::FLI1. Although event-free survival rates remain high in ES patients with localized disease, those with metastatic or relapsed disease face poor long-term survival odds. Topoisomerase 1 (TOP1) inhibitors are commonly used therapeutics in ES relapse regimens. Methods: In this work, we used a genome-wide CRISPR knockout library screen to identify the deletion of the TOP1 gene as a mechanism for resistance to topoisomerase 1 inhibitors. Using isogenic cell line models, we performed a high-throughput small-molecule screen to discover a small molecule, GNF-7, which had an IC50 that was 10-fold lower in TOP1-deficient cells when compared to the wild-type cells. Results: The characterization of GNF-7 demonstrated the molecule was highly active in the inhibition of CSK, p38α, EphA2, Lyn, and ZAK and specifically downregulated genes induced by the EWS::FLI1 fusion oncoprotein. Conclusions: Together, these results suggest that GNF-7 or small molecules with a similar kinase profile could be effective treatments for ES patients in combination with TOP1 inhibitors or for those patients who have developed resistance to TOP1 inhibitors. Full article

Background: Many risk factors for cancer therapy-related cardiovascular toxicity overlap with risk factors for atherosclerosis. According to the ESC 2022 Cardio-Oncology Guidelines, coronary computed tomography angiography and coronary artery calcium score are not recommended as part of routine risk assessment prior to oncological treatment. The aim of this study was to prospectively assess the influence of coronary artery calcium score (CAC score) on cancer therapy-related cardiac dysfunction in patients with moderate and high risk of cardiovascular toxicity, qualified for anthracycline treatment. Methods: In all patients, risk factors were collected, laboratory tests, echocardiography with global longitudinal strain (GLS) assessment and coronary artery tomography with coronary artery calcium score were performed. A total of 80 patients were included in the study, of which 77 (96.25%) were followed for an average of 11.5 months. The mean age at baseline was 60.5 years and 72 (93.51%) were women. Results: During observation, five patients (6.49%) died, including two due to heart failure and three due to cancer progression. The majority of patients (59, 76.6%) had breast cancer, 11 (14.3%) were diagnosed with sarcoma and seven (9.1%) with lymphoma. According to the HFA-ICOS risk score, 40 patients (51.9%) were classified as moderate risk (MR), and 37 patients (48.1%) as high risk (HR) for cancer therapy-related cardiovascular toxicity. A CAC score greater than 100 was calculated in 17 (22.1%) patients and greater than 400 in three (3.9%) patients. The CAC score above zero was more common in older patients and in patients classified as high risk (p < 0.001). There was also a significant association between CAC score and hypertension, hyperlipidemia, chronic kidney disease, and the level of NT-proBNP. During 12-month follow-up, mild CTRCD occurred in 38 (49.4%) patients, moderate CTRCD was diagnosed in seven (9.1%), and severe in three (3.9%) patients. In the univariable analysis, CTRCD was more common in the high-risk group (p = 0.005) and in patients with a CAC score greater than zero (p = 0.036). In multivariable analysis, the incidence of CTRCD remains higher in the CAC score > 0 group, even after adjusting for age, hypertension, and hyperlipidemia. In this study group, the CTRCD rates increased with the HFA-ICOS risk score. Conclusions: In moderate and high-risk patients, a coronary artery calcium score greater than zero was identified as a significant risk factor for the development of cancer therapy-related cardiac dysfunction during anthracycline-based treatment. Furthermore, the HFA-ICOS risk score demonstrated good correlation with the incidence of CTRCD in this study, supporting its validity as a predictive tool in patients receiving anthracycline therapy. Full article

Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are a deadly subtype of soft tissue sarcoma for which effective therapeutic options are lacking. Currently, the best treatment for MPNSTs is complete surgical resection with wide negative margins, but this is often complicated by the tumor size and location and/or the presence of metastases. Radiation or chemotherapy may be combined with surgery, but patient responses are poor. Targeted treatments, including small-molecule inhibitors of oncogenic proteins such as mitogen-activated protein kinase kinase (MEK), cyclin-dependent kinases 4 and 6 (CDK4/6), and Src-homology 2 domain-containing phosphatase 2 (SHP2), are promising therapeutics for MPNSTs, especially when combined together, but they have yet to gain approval. Immunotherapeutic approaches have been revolutionary for the treatment of some other cancers, but their utility as single agents in sarcoma is limited and not approved for MPNSTs. The immunosuppressive niche of MPNSTs is thought to confer inherent treatment resistance, particularly to immunotherapies. Remodeling an inherently “cold” tumor microenvironment into a “hot” immune milieu to bolster the anti-tumor activity of immunotherapies is of great interest throughout the cancer community. This review focuses on novel therapeutics that target dysregulated factors and pathways in MPNSTs, as well as different types of immunotherapies currently under investigation for this disease. We also consider how certain therapeutics may be combined to remodel the MPNST immune microenvironment and thereby generate a durable anti-tumor immune response to immunotherapy. Full article

Rhabdomyosarcoma (RMS), the most common pediatric soft tissue sarcoma, comprises embryonal (ERMS) and alveolar (ARMS) subtypes with distinct histopathological features, clinical outcomes, and therapeutic responses. To better characterize their molecular distinctions, we performed untargeted plasma proteomics and metabolomics profiling in children with ERMS (n = 18), ARMS (n = 17), and matched healthy controls (n = 18). Differential expression, functional enrichment (GO, KEGG, RaMP-DB), co-expression network analysis (WGCNA/WMCNA), and multi-omics integration (DIABLO, MOFA) revealed distinct molecular signatures for each subtype. ARMS displayed elevated oncogenic and stemness-associated proteins (e.g., cyclin E1, FAP, myotrophin) and metabolites involved in lipid transport, fatty acid metabolism, and polyamine biosynthesis. In contrast, ERMS was enriched in immune-related and myogenic proteins (e.g., myosin-9, SAA2, S100A11) and metabolites linked to glutamate/glycine metabolism and redox homeostasis. Pathway analyses highlighted subtype-specific activation of PI3K-Akt and Hippo signaling in ARMS and immune and coagulation pathways in ERMS. Additionally, the proteomics and metabolomics datasets showed association with clinical parameters, including disease stage, lymph node involvement, and age, demonstrating clear molecular discrimination consistent with clinical observation. Co-expression networks and integrative analyses further reinforced these distinctions, uncovering coordinated protein–metabolite modules. Our findings reveal novel, subtype-specific molecular programs in RMS and propose candidate biomarkers and pathways that may guide precision diagnostics and therapeutic targeting in pediatric sarcomas. Full article

Hepatocellular carcinoma (HCC) is a malignancy with a complex pathogenesis, course, and prognosis with increasing incidence. The most significant contributing factor to the development of HCC is the chronic process of inflammation and remodeling of the cirrhotic liver, in which the interaction between the tumor microenvironment (TME) and cancer cells plays a pivotal role. In recent years, increasing focus has been directed toward the role of platelets (PLTs) in mediating interactions between tumor cells and the TME and in the progression and spread of HCC, as well as other cancers. Due to their abundance in the bloodstream and intracellular granules rich in mediators facilitating their ability to modulate the immune system, PLTs play a significant role in carcinogenesis. In the context of HCC, the role of PLTs in the healing and regeneration processes of the liver has been recognized for some time. In recent years, there has been an increasing utilization of PLTs in prognostic models for patients with HCC. Given their role and the availability of clinical options that block PLTs’ action, clinical trials of platelet blockers in the adjunctive treatment of HCC are becoming increasingly common. However, further research, both preclinical and clinical, is necessary to fully elucidate the role of PLTs in HCC and their potential use as a therapeutic target. In this literature review, we summarize the current knowledge on PLTs in HCC and focus on their potential use in everyday clinical practice. Full article

Sarcomas are heterogeneous mesenchymal tumors, and their pharmacological treatment remains challenging due to the high toxicity and poor efficacy of current therapies. This study aimed to identify common overexpressed kinases in the four most frequent sarcoma subtypes to establish novel therapeutic targets. A bioinformatics approach using patient-derived gene expression data sets identified overexpressed kinases shared across these sarcoma types. Later, BUB1 was determined as the kinase consistently overexpressed across the osteosarcoma, liposarcoma, leiomyosarcoma, and synovial sarcoma. Moreover, the role of this kinase was further validated through molecular and functional assays, including pharmacological inhibition in cell lines derived from the four sarcoma subtypes. BUB1 inhibition reduced the phosphorylation of AKT and H2A proteins, precluded cell proliferation, and inhibited colony formation in sarcoma cells. Finally, overall survival analysis highlighted a strong correlation between high BUB1 expression and poorer survival rates in sarcoma patients. Altogether, these findings underscore the potential of BUB1 as a therapeutic target and prognostic marker in sarcomas. Targeted inhibition of BUB1 may provide a novel strategy to reduce tumor growth and improve outcomes for patients with bone and soft tissue sarcomas. Full article

Background: Undifferentiated pleomorphic sarcoma (UPS) is a rare, high-grade soft-tissue sarcoma characterized by a patternless proliferation of bizarre pleomorphic tumor cells lacking identifiable lineage differentiation. Its occurrence in the oral cavity is exceptionally uncommon and poses significant diagnostic challenges due to its morphological overlap with a wide spectrum of other malignancies. Material and Methods: We report a novel case of oral UPS in a 54-year-old woman, characterized by an exceptionally large size and a rapidly progressive clinical course. The diagnostic evaluation included clinical, radiological, histopathological, immunohistochemical, and molecular analyses conducted within a multidisciplinary framework. A comprehensive review of the literature on oral UPS was also performed. Results: The patient underwent an aggressive demolitive surgical approach due to the extent of the lesion. Molecular analysis revealed a previously unreported SPECC1L::TERT gene fusion. The literature review highlighted the rarity of oral UPS, its geographic predilection for Central and East Asia, possible associations with traumatic events, and its heterogeneous clinical and histopathological presentations. Conclusions: This case underscores the critical importance of a thorough diagnostic workup to ensure the accurate diagnosis and appropriate management of this rare and aggressive tumor. Multidisciplinary evaluation is essential, especially in anatomically complex and diagnostically challenging presentations such as oral UPS. Full article

Doxorubicin (DOX) is a highly effective chemotherapy drug used in the treatment of many cancers, including solid tumors, hematological malignancies, and soft tissue sarcomas. Despite its potent antitumor effects, DOX is known to have toxic effects in non-tumorous tissues, such as skeletal muscle. Potential mediators of DOX-induced skeletal muscle toxicity are reactive oxygen species (ROS). An overproduction of ROS can disrupt the balance between oxidants and antioxidants in a cell, leading to oxidative stress. Chronic oxidative stress has been shown to upregulate proteolysis, ultimately leading to muscle wasting. Exercise stands as a potent nonpharmacological therapy capable of attenuating muscle wasting by enhancing metabolic function and antioxidant defenses while suppressing harmful ROS production. This review focuses on the current understanding of the role of oxidative stress in DOX-induced skeletal muscle toxicity. In addition, we highlight the effects of various exercise types on oxidative stress and muscle remodeling during DOX chemotherapy. Full article

Background: Liposarcoma (LPS) is a rare malignant tumor, but it is also one of the most common adult soft-tissue sarcomas. Myxoid liposarcoma (MLPS) accounts for 30% of all LPS cases. Diagnosis during pregnancy and the puerperium is very rarely reported, and only a few cases have been reported in the thigh. Case presentation: We report the case of a 36-year-old female patient on the 11th day of the puerperium after a cesarean section. The patient presented to the gynecology ward owing to the sudden appearance of a tumor in the medial part of her right thigh. The lesion was non-painful, mobile, soft, approximately 20 cm in diameter, and protruded above the level of the rest of the thigh surface. A suspicion of hematoma was raised. The final diagnosis was high-grade MLPS. Conclusions: An MLPS diagnosis is uncommon in female patients and even rarer during pregnancy. This case represents a novel occurrence, as the first instance in which symptoms manifested during the puerperium. Proper treatment and early detection could improve disease outcomes. Full article