Search Results (909)

Background and Objectives: This study aimed to describe the clinical characteristics and survival outcomes of three representative complex karyotype soft tissue sarcoma (STS) subtypes—undifferentiated sarcoma (US, primarily undifferentiated pleomorphic sarcoma (UPS)), myxofibrosarcoma (MFS), and leiomyosarcoma of soft tissue (LMS-ST)—using data from a single-institution cohort. Materials and Methods: A retrospective review of 124 patients treated at a single tertiary referral center between 2002 and 2024 was conducted. Clinicopathologic characteristics and survival outcomes were analyzed. Kaplan–Meier methods were used to estimate overall survival (OS). Cox proportional hazards regression models were applied to identify independent prognostic factors for survival, incorporating variables such as age, sex, tumor stage, and treatment modality. Results: The cohort comprised 36 cases of US, 64 of MFS, and 24 of LMS-ST. OS and survival after cohort enrollment (S-NCC) were evaluated both by subtype and across the entire cohort to assess potential differences across tumor subgroups. In both univariable and multivariable analyses, US subtypes showed poorer survival than MFS and LMS-ST. FNCLCC grade 3 emerged as a significant adverse prognostic factor for survival across all three subtypes. For FNCLCC grade 3 patients, the presence of benign prostatic hyperplasia (BPH) was significantly associated with an increased risk of death. Conclusions: Among the three subtypes, US demonstrated the most aggressive clinical course, MFS was notable for frequent local recurrence but relatively favorable survival, and LMS-ST showed intermediate outcomes. These findings highlight the clinical heterogeneity of complex karyotype STS and provide a foundation for future studies integrating molecular and multi-omics data to refine risk stratification and therapeutic strategies. Full article

Background: Low-grade fibromyxoid sarcoma (LGFMS) is a rare malignant fibroblastic tumor that often appears deceptively benign. Accurate diagnosis is challenging due to its variable morphology and low mitotic activity. This systematic review provides a comprehensive overview of LGFMS and its subtypes. Methods: A systematic search of PubMed and Embase up to September 2025 identified 273 studies, complemented by four institutional cases from Amsterdam UMC. Individual patient data were pooled to analyze clinical presentation, diagnostic approaches, treatment modalities, and outcomes. Results: In total, 773 patients were included, with a median age of 35 years and equal gender distribution. Tumors were predominantly deep-seated (80%), most commonly located in the thigh or pelvis. MUC4 positivity (96%) and FUS-CREB3L2 fusion (47%) were the most consistent diagnostic markers. Surgery was the mainstay of treatment (98%), with R0 resection achieved in 36% of cases and R1 in 15%. Adjuvant therapies, including chemotherapy and radiotherapy, were rarely used and showed limited efficacy. After a median follow-up of 3.0 years, 19% developed local recurrence and 21% developed metastases. R0 resections were associated with significantly better recurrence-free survival than R1 resection (p < 0.05). Conclusions: LGFMS exhibits indolent histology but potential for late recurrence and metastasis, warranting prolonged radiological follow-up and multicenter studies to evaluate adjuvant strategies. Full article

Background: Leiomyosarcomas are an aggressive soft-tissue sarcoma that arise from smooth muscle, have a high metastatic potential and account for 10–20% of soft-tissue sarcomas. Despite decades of research, the first-line treatment remains unresolved due to the absence of direct comparative trials, heterogeneous study designs, and trade-offs between efficacy and toxicity. This systematic review evaluates the optimal therapeutic systemic chemotherapy regimens in the first-line setting, specifically gemcitabine- and doxorubicin-based regimens, including associated toxicities. Methods: A systematic search in MEDLINE (Ovid), Embase (Ovid), and Cochrane Library (Wiley) identified studies of first-line gemcitabine- or doxorubicin-based chemotherapy for leiomyosarcoma. The review protocol was registered in PROSPERO (CRD420261280028). Of the 3092 articles screened, 11 articles were eligible for inclusion, comprising results from 1225 patients. Eligible studies were in English and included ≥10 patients with advanced/metastatic leiomyosarcoma reporting on LMS-specific outcomes and no prior systemic therapy. This qualitative systematic review synthesizes prospective and retrospective evidence without quantitative meta-analysis. Results: The review included two phase 3 trials, six phase 2 trials, one phase 1b trial, and two retrospective studies. While there was no direct comparison in this setting, doxorubicin-based combinations consistently reported higher objective response rates, progression-free survival, and overall survival. The most favorable outcomes were observed in the LMS04 trial with doxorubicin plus trabectedin followed by surgery and trabectedin maintenance, yielding a median progression-free survival of 12 months, overall survival of 33 months, and objective response rate of 36%. This regimen also had the highest grade 3–4 toxicity. Conclusions: Doxorubicin-based regimens remain the most active first-line option for leiomyosarcoma, although treatment practices remain heterogeneous. Full article

Background: The prognostic value of treatment-induced necrosis in soft STS remains uncertain. This study evaluated whether MRI-based changes in necrosis (Δ necrosis) between pre- and post-neoadjuvant chemotherapy scans correlate with pathologic necrosis and clinical outcomes. Methods: In this retrospective cohort, 27 patients with STS who received neoadjuvant chemotherapy and underwent pre- and post-treatment MRI were analyzed. Necrosis was graded categorically (<5%, 5–25%, 25–50%, 50–75%, 75–95%, and >95%), and Δ necrosis was calculated as the change in estimated necrosis between scans. Correlations between MRI-derived and pathologic necrosis were assessed using Spearman’s rank coefficient. Survival analyses (progression-free, local recurrence-free, and disease-specific overall survival) were performed using Kaplan–Meier and log-rank tests. Results: Post-treatment MRI necrosis moderately correlated with pathologic necrosis (ρ = 0.44, p = 0.028), whereas Δ necrosis showed a weaker, nonsignificant correlation (ρ = 0.24, p = 0.24). Neither MRI-based nor pathologic necrosis thresholds were associated with survival outcomes. Conclusions: MRI-based Δ necrosis did not predict pathologic necrosis or oncologic outcomes in STS, suggesting that radiologic changes in necrosis may not serve as reliable markers of therapeutic response. Future studies integrating quantitative imaging and standardized pathology protocols together with future exploration of molecular tools such as ctDNA are needed to refine treatment assessment in STS. Full article

Background: Sarcomas are rare, aggressive malignancies with limited therapeutic options in advanced stages. This is the first real-world study in the MENA region evaluating the clinical utility of Next-Generation Sequencing (NGS) in guiding sarcoma treatment and improving outcomes. Methods: We retrospectively reviewed sarcoma patients who underwent NGS at a major referral center (2021–2024), comparing clinical and molecular outcomes between those who received NGS-based treatment adjustments (NBTA) and those who did not. Results: Seventy-eight patients were included (60% male; median age 44 years). Soft tissue sarcomas accounted for 70.5% of cases (n = 55), while bone sarcomas represented 29.5% (n = 23). Prior to NGS, 64.1% of patients had received a median of one line of systemic therapy. NGS was performed late in the disease course in 73% of cases. At least one mutation was detected in 87% (median 3 mutations). Targetable alterations were identified in 33% at the time of testing, rising to 42% with updated genomic knowledge and therapeutic advances. Overall, 20.5% received NBTA. Among non-NBTA patients, 67% had no actionable targets, 17% had no detectable mutations, and 16% were ineligible due to cost, limited access, or clinical deterioration. Tumor Mutational Burden was low in 79%, intermediate in 19%, and high in 2%, and all tumors were microsatellite stable. Patients receiving NBTA had a longer median Progression-Free Survival (9 vs. 2 months; p = 0.023). Median Overall Survival was longer in the NBTA group (74 vs. 48 months), though not statistically significant (p = 0.207). Genomic alterations were subtype-specific: EWSR1 rearrangements (Ewing and Desmoplastic small round cell tumors), CDK4 and MDM2 amplifications (Liposarcoma and Osteosarcoma), TP53 and RB1 mutations (Leiomyosarcoma), CDKN2A/B deletions (Undifferentiated Pleomorphic Sarcoma and Chondrosarcoma), and SS18 rearrangements (Synovial Sarcoma). Conclusions: Genomics-guided therapy in sarcoma is feasible and impactful. Expanding timely access to molecular profiling is essential for advancing precision oncology in the MENA region. Full article

Desmoplastic small round cell tumor (DSRCT) is a rare but aggressive soft tissue sarcoma of the abdomen. With an asymptomatic course and rapid dissemination, DSRCT’s prognosis is poor at diagnosis. This study characterizes the demographic variation and genomic profile of DSRCT to guide studies into diagnosis and treatment. The AACR GENIE database was utilized to identify genetic alterations in DSRCT. Data was queried to identify disease prevalence by different demographic variables. Information was collected on frequency of somatic mutations and copy number alterations, rates of mutation co-occurrence, and mutations seen in primary and metastatic samples. ARID1A, TP53, ATM, TERT, and FGFR4 were the most frequently identified somatic mutations. Copy number alterations seen in DSRCT were commonly homozygous deletions in tumor suppressor genes. Independent of sex, WT1 mutations were most common. Non-White patients saw single occurrences of many mutations but recurrent ones in ANKRD11 and KMT2C. Co-occurrence was found between FGFR4 and EP300. Moreover, primary tumor samples had exclusive mutations in AKAP9, KDM2B, MAGED1, MKI67, PCLO, and TRAF1. Metastatic samples had exclusive mutations in FIP1L1 and NRIP1. Our data highlights mutational variation across demographic cohorts. These patterns are vital to future studies into identifying diagnostic markers or therapeutic targets. Full article

Background and Objectives: Soft tissue sarcomas account for approximately 7% of all malignant tumors in the pediatric population. Diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) measurements may provide early functional biomarkers of treatment response by reflecting changes in tumor cellularity. This study evaluated whether ADC-derived parameters can serve as quantitative biomarkers of neoadjuvant chemotherapy response in pediatric rhabdomyosarcoma. Materials and Methods: This retrospective single-center study included 14 patients aged ≤18 years with histopathologically confirmed rhabdomyosarcoma who underwent MRI before treatment and after three cycles of chemotherapy. Twenty-five patients were initially identified; eleven were excluded due to imaging artifacts or absence of baseline examination. ADC maps were generated on 1.5T and 3T scanners. Regions of interest were placed over the entire lesion and areas with the lowest ADC signal. Relative ADC (rADC) was calculated by normalizing tumor ADC to adjacent healthy muscle. Paired t-tests were used to compare pre- and post-treatment values. Results: At baseline, 13/14 patients (93%) demonstrated diffusion restriction. Mean ADC increased from 1.11 × 10⁻³ mm²/s (SD ± 0.48) at baseline to 1.63 × 10⁻³ mm²/s (SD ± 0.67) after treatment. The paired t-test for rADC yielded t = −3.089 (p = 0.0086, 95% CI: −0.79 to −0.14), indicating a statistically significant change. There was a significant difference between the ADC values of the entire lesion and the areas with the lowest signal in tumors with a heterogenic structure, t = 2.862, p = 0.013. Conclusions: ADC and rADC increased significantly after neoadjuvant chemotherapy in pediatric rhabdomyosarcoma, suggesting potential utility as early functional biomarkers of treatment response. These preliminary findings require validation in larger multicenter prospective studies with correlation to histopathological response and clinical outcomes before clinical implementation. Full article

Background: Ewing’s sarcoma (EwS) is a pediatric bone and soft tissue cancer driven by the oncogenic fusion protein EWS::FLI1. Currently, EwS lacks targeted therapies, necessitating the identification of novel regulatory mechanisms. While the role of microRNAs and long non-coding RNAs has been explored in EwS, the presence and functional significance of circular RNAs (circRNAs) in EwS is not reported. This is the first study to report the presence and role of oncogenic circRNA, circZNF609 in EwS tumor progression. Methods: Expression of circZNF609 was validated in 5 different EwS cell lines using qPCR. Cellular localization of circZNF609 was identified using circFISH. Functional assays for proliferation, migration and apoptosis were performed in wild type and circZNF609 knocked down (KD) cell lines to confirm its oncogenic role. The impact of circZNF609 on EWS::FLI1 protein levels was confirmed using western blots, immunofluorescence, and polysome fractionation. Mechanistic insights were gained utilizing bioinformatic, dual-luciferase reporter assays, rescue experiments, and microscopy to identify and validate the circRNA-miRNA-mRNA regulatory axis. Results: We report the first identification of circZNF609 in EwS, demonstrating that its expression is EWS::FLI1-dependent. Functional analysis reveals that circZNF609 promotes cell proliferation and metastasis while inhibiting apoptosis. Mechanistically, circZNF609 acts as a molecular sponge for miR-145-5p. By sequestering this miRNA, circZNF609 prevents the translational repression of EWS::FLI1, thereby sustaining oncogenic signaling. Conclusions: These findings identify circZNF609 as a novel post-transcriptional regulator of EWS::FLI1 and establish its critical role in EwS pathogenesis. Our results suggest that targeting the circZNF609/miR-145-5p/EWS::FLI1 axis may offer a promising therapeutic strategy for EwS. Full article

Background: Soft tissue tumors (STTs) represent a heterogeneous group of rare lesions that frequently mimic bone sarcomas in both clinical and radiologic appearance. Accurate differentiation between benign and malignant lesions is critical for appropriate treatment planning, yet conventional imaging often remains inconclusive. Ultrasound (US) elastography, a non-invasive method that quantifies tissue stiffness, has recently emerged as a potential adjunct to standard musculoskeletal imaging for improving diagnostic confidence and guiding biopsy. Methods: A systematic review was conducted in accordance with PRISMA guidelines. PubMed, Web of Science, and Cochrane Library were searched using the keywords “elastography”, “sonoelastography”, and “soft tissue tumor”. Twelve studies encompassing 1554 patients met the inclusion criteria, assessing the diagnostic accuracy of strain, compression, and shear wave elastography for differentiating benign from malignant STTs. Results: Elastography alone demonstrated limited specificity when used as a single diagnostic technique. However, its integration into multiparametric ultrasound approaches—combining grayscale, Doppler, and contrast-enhanced imaging—significantly improved diagnostic performance. Several studies reported sensitivities and specificities exceeding 85% when elastographic parameters were incorporated into composite diagnostic scores. Conclusions: Ultrasound elastography shows promise as a quantitative imaging biomarker for the preoperative evaluation of musculoskeletal tumors, particularly in distinguishing soft tissue from bone-related lesions. Although not a substitute for histopathological confirmation, its application within multimodal ultrasound protocols may reduce unnecessary biopsies, enhance diagnostic accuracy, and facilitate tailored management of bone and soft tissue sarcomas. Full article

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

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

Background: Reconstruction of the thigh extensor mechanism following wide excision of a soft-tissue sarcoma is difficult. The aim of this study was to describe the outcomes following complete quadriceps resection for large high-grade soft-tissue sarcomas. Methods: Ten patients with AJCC grade IIIB soft-tissue sarcomas of the anterior thigh were treated with total wide margin quadricectomy, with a mean follow-up of 4 years (range: 51–163 months) in the five surviving patients with conservative surgical procedures. The minimum follow-up period for four of these patients was 8 years. The extensor mechanism was reconstructed with local muscle transfers (eight cases) or a neurotized free flap of the contralateral vastus lateralis (two cases). Results: Four patients died, two due to non-tumor related causes and two due to metastatic disease at 50 months and 43 months. The remaining six were alive and disease-free at the final follow-up. All patients received surgical revision due to wound necrosis. Another patient required an external hemipelvectomy due to early local recurrence of the disease. Functional results of the five patients who remained alive and retained their limb were good or excellent in two cases, acceptable in one, and poor in two, according to their MSTS scores. Average knee flexion was 80° (range: 10–150°). Passive extension was complete in all cases, though no patients achieved it actively. Extensor strength was 2/5 in four patients and 4/5 in the other. Conclusion: Total quadricectomy for high-grade soft-tissue sarcomas of the anterior thigh compartment ensures wide resection margins and local disease control, although local wound complications are common, particularly in older patients. Resection appears to be technically easier if performed distally to proximally in the thigh. Local muscle transfers are more suited for low-demand patients, while neurotized free muscle flaps are mainly an option for young, motivated patients. Full article

Background/Objectives: Synovial sarcoma (SS) is a malignant soft tissue neoplasm with good outcomes in adolescents with localized tumors, but poor outcomes in older adults and in advanced or metastatic cases. Targeting cancer metabolism, such as glutamine metabolism, is a promising therapeutic strategy. In this study, we investigated glutamine dependency in SS and assessed the therapeutic potential of inhibiting the glutamine transporter ASCT2 using V9302. Methods: Immunohistochemistry (IHC) was used to evaluate ASCT2 expression in SS and liposarcoma (LPS) specimen. The effects of glutamine deprivation and V9302 were examined in a SS cell line (HS-SY-II), patient-derived SS cells (SSH1), and a normal cell line (HEK293). Cell viability, apoptosis, and protein expression were assessed using the CCK-8 assay, flow cytometry, and Western blotting, respectively. The therapeutic efficacy of V9302 was evaluated in a xenograft model using IHC. Results: ASCT2 expression was elevated in SS tumor tissues compared with adjacent normal tissues and LPS specimens. Both the HS-SY-II cell line and SSH1 cells exhibited strong glutamine dependency for proliferation. V9302 selectively reduced HS-SY-II cell viability by suppressing the AKT/mTOR signaling pathway and inducing apoptosis via caspase-3 activation, with minimal effects on control cells. In vivo, V9302 administration significantly inhibited tumor growth without inducing systemic toxicity, and IHC of the treated tumors confirmed the suppression of the mTOR pathway and induction of apoptosis. Conclusions: Our findings suggest that SS is a glutamine-dependent malignancy and validate ASCT2 as a promising therapeutic target. The ASCT2 inhibitor V9302 demonstrated therapeutic efficacy both in vitro and in vivo, supporting its potential as a therapeutic agent for SS. Full article

Synovial sarcoma (SySa) is a malignant soft tissue tumor that is characterized by an SS18::SSX fusion protein, which integrates into BAF chromatin remodeling complexes and alters global gene transcription. Despite its uniform genetic driver, SySa displays striking histomorphological and phenotypic heterogeneity, including spindle cell, glandular and poorly differentiated patterns. Prognosis is variable, with around 50% of patients developing metastases. Limited response to chemotherapy highlights the need for a better understanding of the underlying molecular mechanisms to guide alternative therapeutic strategies. Given the pivotal function of BAF complexes in SySa and their recently described impact on cellular differentiation processes, this study aims to investigate the role of SS18::SSX and specific BAF subunits in SySa differentiation. Nanostring analysis revealed that silencing of SS18::SSX and the GBAF subunit BRD9 modulates the cellular differentiation pathways. SS18::SSX and BRD9 were found to regulate epithelial–mesenchymal-transition (EMT)-associated factors of Snail and Slug on different levels, with SS18::SSX repressing E-Cadherin expression. Published single-cell RNA sequencing data were analyzed to validate our finding that BRD9 contributes to SySa EMT regulation. Our study provides novel insights into the multilayered regulation of key EMT players by SS18::SSX and BRD9 in SySa, thereby defining tumor phenotype and (potentially) prognosis. Full article

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