Soft Tissue Sarcoma Subtypes Research Articles

Transcriptomic profiles of myxofibrosarcoma and undifferentiated pleomorphic sarcoma correlate with clinical and genomic features.

Myxofibrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS) are two common and aggressive subtypes of soft tissue sarcoma. The aim of this study was to assess potential transcriptomic differences between MFS and UPS tumours and to evaluate the extent to which differences in gene expression profiles were associated with genomic and clinical features. The study included 162 patients with tumours diagnosed as MFS (N = 62) or UPS (N = 100). The patients had been diagnosed and treated at two Swedish sarcoma centres during a 30-year period. For gene expression profiling and gene fusion detection all tumours were analysed using RNA-sequencing and could be compared with data on clinical outcome (N = 155), global copy number profiles (N = 145), and gene mutations (N = 128). Gene expression profiling revealed three transcriptomic clusters (TCs) without any clear separation of MFS and UPS. One TC was associated with longer metastasis-free survival. These tumours had lower tumour mutation burden (TMB), were enriched for a copy number signature representative of focal LOH and chromosomal instability on a diploid background, and were relatively immune-depleted. MFS and UPS showed extensive genomic overlap, with whole genome doubling occurring more frequently among the latter. The results support the idea that MFS and UPS tumours have largely overlapping genomic and transcriptomic features, with UPS tumours showing more aggressive behaviour and more complex genomes. Independently of the tumour type, clinically relevant subgroups were revealed by gene expression analysis, and the finding of multiple genomic subgroups strongly suggest the existence of subgroups of relevance to treatment stratification. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Case Report : Undifferentiated Synovial Sarcoma Presenting as a Large Thoracic Mass: A Rare and Challenging Diagnosis

Background: Undifferentiated synovial sarcoma (USS) is a rare and aggressive subtype of soft tissue sarcoma. Its presentation as a large thoracic mass poses significant diagnostic and therapeutic challenges.  Case Presentation: A 34-year-old male presented with a three-month history of progressive chest pain and hemoptysis. Imaging studies revealed a large, cystic thoracic mass with pleural effusion. Initial serological testing suggested hydatid cyst, but subsequent testing revealed negative Echinococcus (Hydatid) IgG antibodies.  Diagnostic and Therapeutic Interventions: Repeat fine-needle aspiration cytology (FNAC) was deferred due to revised ultrasound findings indicating a solid fibrocystic vascular lesion. Bronchial artery embolization (BAE) was performed to control life- threatening hemorrhage. Thoracotomy and en-bloc mass excision were subsequently undertaken.  Histopathological Diagnosis: Histopathological examination of the resected specimen revealed undifferentiated synovial sarcoma and spindle cell sarcoma.  Clinical Implications: This case highlights the importance of correlating imaging and serological findings, managing vascular complications, and the efficacy of BAE in controlling hemorrhage. The significance of thoracotomy and mass excision in achieving diagnostic clarity and therapeutic success is underscored.  Conclusion: Undifferentiated synovial sarcoma presenting as a large thoracic mass poses significant diagnostic and therapeutic challenges. A multidisciplinary approach, incorporating imaging, serological testing, and surgical intervention, is crucial for achieving optimal patient outcomes.

High-Throughput Transcriptomics Identifies Chemoresistance-Associated Gene Expression Signatures in Human Angiosarcoma

Angiosarcomas, clinically aggressive cancers of endothelial origin, are a rare subtype of soft-tissue sarcomas characterized by resistance to chemotherapy and dismal prognosis. In this study, we aim to identify the transcriptomic biomarkers of chemoresistance in angiosarcoma. We examined 72 cases of Asian angiosarcomas, including 35 cases treated with palliative chemotherapy, integrating information from NanoString gene expression profiling, whole transcriptome profiling (RNA-seq), immunohistochemistry, cell line assays, and clinicopathological data. In the chemoresistant cohort (defined as stable disease or progression), we observed the significant overexpression of genes, including SPP1 (log2foldchange 3.49, adj. p = 0.0112), CXCL13, CD48, and CLEC5A, accompanied by the significant enrichment of myeloid compartment and cytokine and chemokine signaling pathways, as well as neutrophils and macrophages. RNA-seq data revealed higher SPP1 expression (p = 0.0008) in tumor tissues over adjacent normal compartments. Immunohistochemistry showed a significant moderate positive correlation between SPP1 protein and gene expression (r = 0.7016; p < 0.00110), while higher SPP1 protein expression correlated with lower chemotherapeutic sensitivity in patient-derived angiosarcoma cell lines MOLAS and ISOHAS. In addition, SPP1 mRNA overexpression positively correlated with epithelioid histology (p = 0.007), higher tumor grade (p = 0.0023), non-head and neck location (p = 0.0576), and poorer overall survival outcomes (HR 1.84, 95% CI 1.07–3.18, p = 0.0288). There was no association with tumor mutational burden, tumor inflammation signature, the presence of human herpesvirus-7, ultraviolet exposure signature, and metastatic state at diagnosis. In conclusion, SPP1 overexpression may be a biomarker of chemoresistance and poor prognosis in angiosarcoma. Further investigation is needed to uncover the precise roles and underlying mechanisms of SPP1.

Rhabdomyosarcoma Presenting as an Infective Midline Nodule on the Chin in an Eight-year-old Child

Background and Aims: Rhabdomyosarcoma (RMS) is the most common subtype of soft tissue sarcoma (STS) in children. Early diagnosis is the most favourable prognostic factor and thus physicians need to include RMS in the differential diagnosis of more common diseases developing within the head and neck region. This report highlights the same while describing a case of an eight-year-old child who presented with a chin swelling which turned out to be an RMS. Methods: We present a rare case of an eight-year-old child with a midline painless mass. Results: This child had a transoral resection of the mass. He undertook further chemotherapy and was completely cured with no tumour recurrence. Conclusion: In a painless rapidly increasing mass in the head and neck area, despite rare, but RMS should be included as a differential diagnosis. This is important as early diagnosis and proper resection and treatment are paramount in the prognosis of the disease.

MEK inhibitors lead to PDGFR pathway upregulation and sensitize tumors to RAF dimer inhibitors in NF1-deficient malignant peripheral nerve sheath tumor (MPNST).

Malignant peripheral nerve sheath tumor (MPNST) is a highly aggressive subtype of soft tissue sarcoma with a high propensity to metastasize and extremely limited treatment options. Loss of the RAS-GAP NF1 leads to sustained RAF/MEK/ERK signaling in MPNST. However, single-agent MEK inhibitors (MEKi) have failed to elicit a sustained inhibition of the MAPK signaling pathway in MPNST. We employed pharmacological, biochemical, and genetic perturbations of the receptor tyrosine kinase (RTK) and MAPK signaling pathway regulators to investigate the mechanisms of MEKi resistance and evaluated combination therapeutic strategies in various preclinical MPNST models in vitro and in vivo. Here, we report that MEKi treatment resistance in MPNST involves two adaptive pathways: direct transcriptional upregulation of the receptor tyrosine kinase (RTK) PDGFRβ, and MEKi-induced increase in RAF dimer formation and activation of downstream signaling. While the pharmacological combination of MEKi with a PDGFRβ specific inhibitor was more effective than treatment with MEKi alone, the combination of MEKi and RAF-dimer inhibitors led to a robust inhibition of the MAPK pathway signaling. This combination treatment was effective in vitro and in vivo, as demonstrated by the significant increase in drug synergism and its high effectiveness in decreasing MPNST viability. Our findings suggest that the combination of MEKi and PDGFR and/or RAF dimer inhibitors can overcome MEKi resistance and may serve as a novel targeted therapeutic strategy for NF1-deficient MPNST patients, which in turn could impact future clinical investigations for this patient population.

Cellular origin and clonal evolution of human dedifferentiated liposarcoma

Dedifferentiated liposarcoma (DDLPS) is the most frequent high-grade soft tissue sarcoma subtype. It is characterized by a component of undifferentiated tumor cells coexisting with a component of well-differentiated adipocytic tumor cells. Both dedifferentiated (DD) and well-differentiated (WD) components exhibit MDM2 amplification, however their cellular origin remains elusive. Using single-cell RNA sequencing, DNA sequencing, in situ multiplex immunofluorescence and functional assays in paired WD and DD components from primary DDLPS tumors, we characterize the cellular heterogeneity of DDLPS tumor and micro-environment. We identify a population of tumor adipocyte stem cells (ASC) showing striking similarities with adipocyte stromal progenitors found in white adipose tissue. We show that tumor ASC harbor the ancestral genomic alterations of WD and DD components, suggesting that both derive from these progenitors following clonal evolution. Last, we show that DD tumor cells keep important biological properties of ASC including pluripotency and that their adipogenic properties are inhibited by a TGF-β-high immunosuppressive tumor micro-environment.

Real-world efficacy, safety data and predictive clinical parameters for treatment outcomes in advanced soft tissue sarcoma treated with combined immunotherapy and antiangiogenic therapy

BackgroundThe combination of immunotherapy and antiangiogenic therapy has shown potential in the treatment of numerous malignant tumors, but limited evidence was available for soft tissue sarcomas (STS). Therefore, the aim of the present study is to assess the efficacy and safety of immunotherapy in conjunction with antiangiogenic therapy in patients diagnosed with advanced STS (aSTS).MethodsThe study enrolled patients with aSTS from January 2014 to October 2022. Eligible participants had previously received anthracycline-based chemotherapy, presented with an anthracycline-resistant sarcoma subtype, or were ineligible for anthracycline treatment due to medical conditions. Following enrollment, these patients received a combination of immunotherapy and antiangiogenic therapy. The primary endpoints were the objective response rate (ORR) and progression-free survival (PFS), while the secondary endpoints included the disease control rate (DCR), overall survival (OS), and the incidence of adverse events.ResultsFifty-one patients were included in this cohort study. The median duration of follow-up was 15.8 months. The ORR and DCR were 17.6%, and 76.5%, respectively. The median PFS (mPFS) was 5.8 months (95% CI: 4.8–6.8) for all patients, and the median OS had not been reached as of the date cutoff. Multivariate analysis indicated that Eastern Cooperative Oncology Group performance status of 0–1 and ≤ second-line treatment were positive predictors for both PFS and OS. Patients with alveolar soft part sarcoma or clear cell sarcoma had longer mPFS (16.2 months, 95% CI: 7.8–25.6) when compared to those with other subtypes of STS (4.4 months, 95% CI: 1.4–7.5, P < 0.001). Among the observed adverse events, hypertension (23.5%), diarrhea (17.6%), and proteinuria (17.6%) were the most common, with no treatment-related deaths reported.ConclusionThe combination of immunotherapy and antiangiogenic agents showed promising efficacy and acceptable toxicity in patients with aSTS, especially those with alveolar soft part sarcoma or clear cell sarcoma.

Radiological evaluation of response in patients with locally advanced/metastatic soft tissue sarcoma treated with trabectedin.

Background: Trabectedin is an antineoplastic drug approved for patients (pts) with advanced soft tissue sarcomas (STS). Interestingly, the radiological evaluation of response during trabectedin therapy is peculiar. Methods: The aim of this single-center retrospective study is to analyze the concordance of response assessment according to RECIST compared with Choi criteria in patients with STS treated with trabectedin between 2009 and 2020 at Regina Elena National Cancer Institute in Rome. Results: We present the preliminary data collected in the last 2months (mos) on 37pts who received the diagnosis between 2015 and 2020, with a median age of 52.5years (range 32-78). The median number of trabectedin cycles administered was four (range 2-50) for a median follow up of 5.83months (range 1-60). Histological subtypes of STS were five (13.5%) leiomyosarcoma, 14 (37.8%) liposarcoma, nine (24.3%) undifferentiated pleomorphic sarcoma, three (8.1%) synovial sarcoma, and six (16.2%) other rare histological subtypes. Eight pts (21.6%) received trabectedin in the first line setting, 21 (56.8%) in the second line, and seven (18.9%) received it in subsequent lines. One pt received trabectedin as neoadjuvant therapy in a clinical trial (ISG-STS 1001). Median progression-free survival was 3.6months (CI95% 2.7-4.6); median overall survival was 34.3months (CI95% 0-75.4). The radiological responses were evaluated with both RECIST and Choi criteria; responses matched in 33pts (89.2%) but not in four (10.8%). The best responses obtained according to RECIST criteria were two (5.4%) partial response (PR), 13 (35.1%) stable disease (SD), and 22 (59.5%) progressive disease (PD). Instead, two (5.4%), 13 (35.1%), and 22 (59.5%) pts obtained PR, SD, and PD respectively, according to Choi criteria. Cohen's kappa coefficient of concordance was 0.792 (p-value <0.002). A specialized radiologist performed all imaging examinations using a dedicated workstation in the same center. Conclusion: In this first analysis, the concordance between RECIST and Choi assessments demonstrates no statistically significant difference. Responses did not match for four pts. We are expanding the analysis to all pts included in the original cohort to confirm or deny these initial results.

The single cell transcriptional landscape of fibrosarcoma.

235 Background: Fibrosarcoma (FS) is a relatively uncommon subtype of soft tissue sarcoma, which predominantly occurs in the extremities and girdles of elderly individuals. FS are famous for its high recurrence and metastasis rate. However, the current treatment regimens have shown poor efficacy in treating these progressive lesions. Therefore, a deep understanding of the tumor microenvironment characteristics of fibrosarcoma is needed to develop more effective drugs.Therefore, a deeper understanding of the tumor microenvironment characteristics of fibrosarcoma is needed for further development of therapeutic drugs. Methods: We performed single-cell transcriptome sequencing for the first time on 6 patients bearing with FS. Bulk-seq data of soft tissue sarcoma was downloaded from public database including TCGA and GEO for prognostic analysis. What' s more, a cohort of 54 FS patients was retrospectively collected for protein detection. Results: The tumor microenvironment landscape was characterized by the presence of malignant fibroblast, diverse macrophages, limited T-cell presence, and high levels of vascular infiltration. The expression of siglec15 was significantly upregulated in the malignant cells. And the prognostic significance of siglec15 was confirmed by the TCGA public database. What’s more, the high expression of siglec15 protein was negatively related to overall survival of fibrosarcoma patients from our institution. We also explored the interactions among different cell subtypes, especially the interactions between malignant cells and endothelial cells, as well as macrophages and endothelial cells, which not only promote tumor progression but also inhibit T-cell infiltration and function. Conclusions: In total, our work has uncovered the low T cell infiltration landscape of FS. The primary reason of insufficient immune infiltration may be due to the blockage of T cell extravasation caused by the interaction between endothelial cells, malignant cells and macrophages.

Collagen modification remodels the sarcoma tumor microenvironment and promotes resistance to immune checkpoint inhibition.

Molecular mechanisms underlying immune checkpoint inhibitor (ICI) response heterogeneity in solid tumors, including soft tissue sarcomas (STS), remain poorly understood. Herein, we demonstrate that the collagen-modifying enzyme, procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (Plod2), which is over-expressed in many tumors relative to normal tissues, promotes immune evasion in undifferentiated pleomorphic sarcoma (UPS), a relatively common and aggressive STS subtype. This finding is consistent with our earlier observation that Plod2 promotes tumor metastasis in UPS, and its enzymatic target, collagen type VI (ColVI), enhances CD8+ T cell dysfunction. We determined that genetic and pharmacologic inhibition of Plod2 with the pan-Plod transcriptional inhibitor minoxidil, reduces UPS growth in an immune competent syngeneic transplant system and enhances the efficacy of anti-Pd1 therapy. These findings suggest that PLOD2 is an actionable cancer target and its modulation could augment immunotherapy responses in patients with UPS, and potentially other sarcomas and carcinomas.

Real-world outcomes of metastatic clear cell sarcoma sequential chemotherapy

Clear cell sarcoma is an ultra-rare chemoresistant subtype of soft tissue sarcoma. This retrospective analysis aimed to clarify the efficacy of palliative chemotherapy in CCS by assessing response rates, progression-free survival (PFS), and overall survival (OS) at a referral center. A retrospective analysis of palliative treatment was conducted on patients with CCS treated at the sarcoma unit from 1997 to 2023. Treatment responses were assessed using RECIST criteria, and the Kaplan–Meier method was used to calculate PFS and OS. The analysis covered 23 CCS chemotherapy-treated patients with 11 (47.8%) men. The median age at the palliative treatment start was 32 years (range 18-59). The median follow-up was 8.2 months. Four patients were referred to our centre for M1 disease, and 6 received perioperative chemotherapy and progressed during follow-up. In the first line, 14 patients received anthracycline-based chemotherapy (60.9%), five were treated with ifosfamide (HD-IFO), and four received other regimens. One patient (4.3%) achieved partial response (PR), and 12 patients (52.2%) achieved stable disease (SD) as the best response. Median PFS in 1 line was 2.79 months (95% CI: 2.04–8.38), and 1.76 months (95% CI: 0.72–6.97) in the second line. The median OS from first-line palliative chemotherapy was 8.2 months (95% CI: 6.2–14), and the second-line palliative chemotherapy mOS was 4.6 months (95% CI: 3.9–NA). Perioperatively anthracycline-pretreated worsened patients’ median PFS in the M1 setting. Poor responses to conventional chemotherapy were observed in CCS, indicating a need for further clinical trials in this indication.

Safety and Preliminary Efficacy of Once-Weekly Split-Dose Selinexor in Soft Tissue Sarcoma: Results of the Phase Ib METSSAR Clinical Trial.

The approved dose of Selinexor, 60 mg twice-weekly, is associated with several clinically relevant toxicities. Preclinical studies show that a sustained-release formulation of selinexor results in a lower toxicity profile. The phase 1b METSSAR trial assessed the safety and tolerability of an alternative dosing schedule of selinexor (to mimic the sustained-release formulation) in advanced soft tissue sarcoma (STS) patients. Selinexor was administered in a split-dose schedule (40 mg, 20 mg, 20 mg in the morning, afternoon, and evening, respectively) on days 1, 8, 15, and 22 of a 28-day cycle, until unacceptable toxicity or disease progression. The primary endpoint was the rate of grade ≥ 3 treatment-related adverse events (TRAEs). Secondary objectives were EORTC QLQ-C30 quality of life (QoL) assessment, and preliminary efficacy. Twenty patients with 12 STS subtypes were enrolled and received a median of four cycles of treatment. There were no grade ≥ 3 TRAEs. Dysgeusia, nausea, fatigue, and thrombocytopenia were the most common grade ≤ 2 TRAEs. No treatments were discontinued due to TRAE, but four patients (20%) required dose reduction. Median change in global health status (GHS) score from baseline to cycle 2 (by QLQ-C30 v3.0) was - 8.33, and only 39% of patients reported a clinically meaningful decline in GHS score (≥10 points). Median symptom scale scores on treatment were increased for fatigue (+12.35), nausea/vomiting (+18.52), and anorexia (+16.67), but reduced for pain (- 3.70). The median progression-free survival (PFS) was 4.0 months (95% confidence interval 1.9-7.5). Split-dose once-weekly selinexor was reasonably well tolerated in this heterogeneous group of advanced STS patients with a better, or at least similar, clinician- and patient-reported toxicity profile compared to the standard dosing regimen. Further clinical evaluation is warranted, as better dose delivery can lead to improved antitumor efficacy.

An NCDB analysis of patient treatment trends in soft tissue angiosarcoma.

e23563 Background: Angiosarcoma is a rare subtype of soft tissue sarcoma associated with a generally poor prognosis and high mortality rate. Median survival of patients with angiosarcoma typically ranges from 15 to 24 months, with a 5-year survival of 12-33%. Angiosarcomas have a high propensity for local recurrence, metastasis, and multiple organ involvement as they originate from vascular endothelial cells. Though surgical excision currently plays a central role in the treatment of angiosarcoma, no significant study has analyzed NCDB for treatment trends in these patients. This study aims to characterize the effect of different treatment modalities on overall survival of angiosarcoma patients. Methods: The National Cancer Database (NCDB) was used to identify patients diagnosed with angiosarcoma from 2004 to 2020 using histology code 9120 as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, ANOVA, Chi-Square, Cox Proportional Hazards and Logistic Regression tests were performed, and data were analyzed using SPSS version 29. Statistical significance was set at α = 0.05. Results: 3560 patients with angiosarcoma of the soft tissue were queried. The most common primary site for a tumor was the head, neck, or face (920 patients, 31.3%). Of the initial sample, 1889 ( 53.1%) patients received surgery alone, 450 ( 12.6%) patients received adjuvant chemotherapy, 55 ( 1.54%) received adjuvant radiation, and 30 ( 0.84%) patients received adjuvant chemoradiation. Surgery alone conferred the greatest median survival; no surgery conferred the least ( 31.4 months vs. 7.2 months; p &lt; 0.001). In the crude and adjusted logistic regression models, combined chemoradiation (OR = .210; 95% CI:.100-.400) and surgery alone were associated with the lowest odds of death (OR = .271; 95% CI: .224-.329) relative to no surgical procedure of the primary site. This finding persisted once the model was adjusted for age, stage, and tumor size. Surgery alone conferred the lowest hazard ratio (HR = .352; 95% CI: .323-.384) relative to no surgery. Conclusions: In angiosarcoma patients, surgical excision at the primary site alone was associated with the greatest median survival and the lowest hazard ratio. Additionally, angiosarcoma patients who did not receive surgery had the least median survival. Surgery with adjuvant chemoradiation and surgery alone had the lowest odds of death. These findings affirm that surgical excision at the site of the primary tumor plays a key role in increasing the survival of angiosarcoma patients. Further research is necessary in characterizing treatment trends in angiosarcoma patients to supplement current standardized treatment protocols and improve the mortality of this lethal cancer.

Efficacy and safety of anthracycline combined with alkylating agent for treatment of advanced leiomyosarcoma.

e23558 Background: Leiomyosarcoma(LMS) accounts for 12-14% of all soft tissue sarcomas(STSs) and this STS subtype has high metastatic potential. We evaluated the efficacy and safety of epirubicin combined with temozolomide(EPI-TMZ) for treatment of advanced LMS. Methods: Oral TMZ(200 or 300 mg) was administered each day on days 1-5, and intravenous EPI(60 mg/m2) was administered on days 1-4, with even distribution over these 96h within a 21‐day cycle. After 8 cycles of intensive chemotherapy, monodrug maintenance therapy consisted of TMZ alone(dosing as in the primary therapy, most choices, stop taking medication after 1 year control), and two-drug maintenance therapy consisted of TMZ with thalidomide(only 3 patients). All patients-initiated EPI-TMZ treatment between January 2018 and January 2024. Results: We examined 31 patients who received EPI-TMZ. There were 25 females and 6 males, with average age 50.5 years old. All were unresectable patients derived from abdominal retroperitoneum, uterus, inferior vena cava, mesentery, small intestine, stomach, thighs, elbows, wrists, pancreas, nasal cavity, meantime with distant metastasis. Average Ki67 is above 40%. This was a first-line treatment in 16 patients, a second- or third-line in 13, and a fourth-line in 2. At the time of data cutoff (January 31, 2024), the median PFS was 12.6 months, 1 patient had cCR, 9 PR and 20 SD. The ORR was 32.3%(10/31) and DCR was 96.8%(30/31). The only patient who progressed after two cycles of medication had PMS2 deficiency, and studies have reported that it may have a primary resistance mechanism. Even the shortest disease control period is also 5 months, indicating this regime has significant clinical benefit. Some patients have undergone tumor reduction surgery to improve quality of life after achieving significant tumor relief. The current longest PFS is 42 months up to now and under continuous tumor control. Previous retrospective studies indicated the best mPFS was 9.2 months and the best ORR was 30.9%. 2023 ESMO declared prospective doxorubicin with trabectedin obtained mPFS of 12.19 months. The most common treatment-related adverse effects were leukopenia, neutropenia, thrombocytopenia, anemia, nausea, vomiting, fatigue, and oral mucositis. Two patients had severe febrile neutropenia, but there were no treatment-related deaths, survival data follow-up. Conclusions: EPI-TMZ is potentially effective for treatment of advanced LMS, and the adverse effects appear tolerable. EPI-TMZ may provide better outcomes than reported in previous studies of other treatments for advanced LMS, worth further prospective research.

Overall survival in soft tissue sarcomas (STS) in Hispanic vs non-Hispanic White patients: Single center experience.

e23526 Background: Racial, ethnic, and socioeconomic factors have been implicated in the variability of survival rates among soft tissue sarcoma (STS). These disparities are multifactorial and may reflect differences in disease biology, access to care, treatment responses, and others. In situations where different racial groups have equitable access to healthcare, healthcare disparities can decrease, and survival gaps can narrow. Differences in survival in STS in racial minorities have been poorly studied. Recognizing the potential impact of such disparities, our study thereby contributes to the ongoing discourse on healthcare equity in STS outcomes. Methods: We conducted a retrospective analysis of 30 STS patients, stratifying them into Hispanic (H) and non-Hispanic white (NHW) groups at Dignity Health Cancer Institute in Phoenix, Arizona. The Mann-Whitney U test was chosen to compare survival distributions, given the non-normal distribution of our sample. Survival analysis was performed using the Kaplan-Meier method, and the log-rank test was applied to determine statistical significance. All analyses were executed in GraphPad Prism software. Results: Our cohort comprised 13 (43%) NHW and 17 (57%) H patients. The mean ages were 57.2 years for NHW and 48.9 years for H, with a balanced gender distribution across groups. The most common subtypes of STS in NHW were liposarcoma (n = 3, 23.1%), and spindle cell carcinoma (n = 2,15.4%). Comparatively, the most common subtypes of STS in H were liposarcoma (n = 5, 29.4%) and leiomyosarcoma (n = 3, 17.6%). All patients were diagnosed with Stage 4 STS. Treatment modalities differed marginally, with NHW patients undergoing more surgical interventions, while H patients were more frequently administered chemotherapy. Median overall survival from the start of first-line therapy was 412 days for NHW and 500 days for H patients. Despite the longer median overall survival observed in Hispanics, the intergroup difference did not reach statistical significance (P = 0.68). Conclusions: The similar survival times between H and NHW STS patients at our institution may hint at an equitable provision of care across racial demographics in a relatively controlled single-center experience. However, the trend of extended survival in the Hispanic group, while not statistically confirmed, raises questions that merit further inquiry. This study serves as a preliminary exploration into racial disparities in STS, advocating for larger-scale research with more diverse patient populations. Further studies are essential to understand these findings and identify and optimize factors contributing to narrowing the survival gap in minorities, with the goal of enhancing STS prognosis for all racial groups.

Efficacy and safety of SHR-2554 in advanced epithelioid sarcoma: A phase 2 trial.

11549 Background: Epithelioid sarcoma (ES) is a rare and aggressive subtype of soft-tissue sarcoma. The loss of SMARCB1 (INI1) expression which leads to oncogenic dependence on the transcriptional repressor EZH2 has been observed in over 90% of ES. Patients (pts) with metastatic ES have a poor prognosis. We investigated the efficacy and safety of SHR-2554, an oral selective EZH2 inhibitor, in pts with refractory ES. Methods: To be eligible for inclusion, pts had to fulfill the following criteria: 8 years or older; histologically confirmed advanced or metastatic ES with loss of INI1 or upregulated mRNA level of EZH2; progressive disease after at least one line of doxorubicin-containing chemotherapy; the presence of measurable disease according to RECIST 1.1; an ECOG performance status of 0-1. Pts received SHR2554 (350 mg, bid, po) until disease progression or unacceptable toxicity. The primary endpoint was progression-free rate at 12 weeks. A Simon two-stage design was applied. If there were 3 pts remaining progression-free at 12 weeks within the first 9 pts, the cohort would expand to 17 pts and the outcome would be positive if more than 7 pts remained progression-free at 12 weeks. Results: Between Jul 2021 and Dec 2023, a total of 17 pts were enrolled and received at least 1 dose of SHR-2554. The median age was 32 years (range 8-57) and 41.2% were males. 9 (52.9%) pts had received immunotherapy targeting PD-1/L1 and 6 (35.3%) pts had received anti-angiogenesis therapy before enrollment. The median line of previous treatment was 2 (range 1-4). Loss of INI1 was confirmed in 14 (82.4%) pts. Tumor response was evaluated in 14 pts at data cutoff. 9 (64.3%) of 14 pts remained progression-free at 12 weeks. The primary endpoint was met. Based on investigator assessment, 3 (21.4%) of 14 pts achieved partial response and 8 (57.1%) pts had stable disease as best response. Adverse events (AEs) were generally mild. The most common treatment-related hematological AEs were anaemia, platelet count decreased and hyperuricaemia. Conclusions: SHR-2554 showed promising efficacy and an acceptable safety profile in pts with refractory ES, warranting further investigation. Clinical trial information: ChiCTR2100046099.

Malignant Tumor of the Sheaths and Peripheral Nerves: A Case Report

Malignant Peripheral Nerve Sheath Tumors (MPNST) are a rare anatomopathological subtype of soft tissue sarcoma. We report a case of MPNST in a patient without a history of neurofibromatosis. He presented with a progressively developing ulcerobourgennate lesion on the left buttock. Histopathological analysis of a biopsy of the mass confirmed MPNST. These are rare tumors that can occur in patients without any particular history and are difficult to manage at an advanced stage.

New targeted therapies in liposarcoma: state of art and future perspectives.

Liposarcomas (LPSs) represent the most common soft tissue sarcoma (STS) subtype, and exhibit distinct clinical molecular features according to histological subgroup. Chemotherapy (ChT), and in particular anthracycline-based schedules, still remains the standard of treatment for all LPS forms. However, given the increasing knowledge gained throughout last years about LPS molecular biology and their genomic profiling, new therapeutic alternatives with targeted drugs are now to be considered. In this review, we will highlight most promising ongoing and published clinical trials regarding targeted therapies in LPSs and provide some insights about future approaches and possible new treatment options for this rare disease. Among all the explored targets, mouse double minute 2 homolog amplification and CKD4-Rb axis inhibition seem to be the most promising target in well differentiated/dedifferentiated LPS subtype. On the other hand, myxoid LPS is known to have a particular sensitivity for trabectedin, which acts like a targeted drug due to its specific action on cellular DNA. In addition to these, multiple other strategies are now being evaluated in LPSs, including the administration of immune-checkpoint inhibitors (ICIs) and 'new-old' cytotoxic agents, such as cabazitaxel, in a continuously growing scenario. Although preliminary, results of recently published and ongoing examined clinical trials will hopefully be translated in clinical practice in the next future, leading the way to future research in this rare disease.

High-Grade Pleomorphic Sarcomas Treated with Immune Checkpoint Blockade: The MD Anderson Cancer Center Experience.

Undifferentiated pleomorphic sarcomas (UPSs) are amongst the most common subtypes of soft-tissue sarcomas. Few real-world data on the use of immune checkpoint blockade (ICB) in UPS patients and other high-grade pleomorphic STS patients are available. The purpose of our study is to describe the efficacy and toxicity of ICB in patients with advanced UPSs and other high-grade pleomorphic sarcomas treated at our institution. This is a retrospective, observational study of all patients with metastatic high-grade pleomorphic sarcomas treated with FDA-approved ICB at MD Anderson Cancer Center between 1 January 2015 and 1 January 2023. Patients included in trials for which results are not yet published were excluded. Thirty-six patients with advanced/metastatic pleomorphic sarcomas were included. The median age was 52 years. A total of 26 patients (72%) had UPSs and 10 patients (28%) had other high-grade pleomorphic sarcomas. The median follow-up time was 8.8 months. The median PFS was 2.9 months. The 3-month PFS and 6-month PFS were 46% and 32%, respectively. The median OS was 12.9 months. The 12-month OS and 24-month OS were 53% and 29%, respectively. The best response, previous RT, and type of ICB treatment were significantly and independently associated with shorter PFS (p = 0.0012, p = 0.0019 and p = 0.036, respectively). No new safety signal was identified, and the toxicity was overall manageable with no toxic deaths and only four patients (11%) stopping treatment due to toxicity. Real-world retrospective data are consistent with the published literature, with a promising 6-month PFS of 32%. Partial or stable responders to ICB treatment have significantly improved PFS compared to progressors.

Molecular Heterogeneity in Leiomyosarcoma and Implications for Personalised Medicine.

Leiomyosarcoma (LMS) is one of the more common subtypes of soft tissue sarcomas (STS), accounting for about 20% of cases. Differences in anatomical location, risk of recurrence and histomorphological variants contribute to the substantial clinical heterogeneity in survival outcomes and therapy responses observed in patients. There is therefore a need to move away from the current one-size-fits-all treatment approach towards a personalised strategy tailored for individual patients. Over the past decade, tissue profiling studies have revealed key genomic features and an additional layer of molecular heterogeneity among patients, with potential utility for optimal risk stratification and biomarker-matched therapies. Furthermore, recent studies investigating intratumour heterogeneity and tumour evolution patterns in LMS suggest some key features that may need to be taken into consideration when designing treatment strategies and clinical trials. Moving forward, national and international collaborative efforts to aggregate expertise, data, resources and tools are needed to achieve a step change in improving patient survival outcomes in this disease of unmet need.