Sarcoma最新文献

Prognosis remains poor for patients with relapsed or refractory Ewing sarcoma, with limited treatment options after first-line therapy. Oral etoposide has efficacy in the paediatric setting; however, data are limited in adults. A retrospective analysis was conducted on 33 patients with relapsed or refractory Ewing sarcoma who completed at least one cycle of oral etoposide at the Peter MacCallum Cancer Centre from 2005 to 2020. The median age at diagnosis and first relapse was 21 and 23 years, respectively. All patients had prior exposure to intravenous etoposide. Nine patients (27%) had stable disease for at least 6 months, and six patients (18%) had a partial response. The clinical benefit rate was 45%. The median PFS was 3.6 months (95% CI: 1.7-5.5), and OS was 8.5 months (95% CI: 4.1-13.0). Despite prior exposure, oral etoposide demonstrated antitumour activity and durable responses in the relapsed or refractory setting for adult patients with Ewing sarcoma.

The classification of undifferentiated pleomorphic sarcoma (UPS) has been evolving with advances in immunohistochemistry and genomic profiling over the past 20 years. There is a lack of current information on UPS incidence. Due to the lack of designated histology codes for UPS in the Surveillance, Epidemiology, and End Results (SEERs) program, we estimated UPS incidence by three different definitions based on clinical opinions using the 2000-2020 data from 22 registries of the SEER program. The incidence varied widely across the three definitions with 0.06 per 100,000 persons for the least inclusive definition and 0.67 per 100,000 persons for the most inclusive definition in 2016-2020, making it challenging to estimate the exact incidence of UPS. Regardless, all the incidences decreased between 2000 and 2020. Guidelines in UPS diagnosis and classification need to be better implemented in the US.

Desmoplastic small round blue cell tumor (DSRCT) is a highly aggressive fatal sarcoma without evidence-based therapeutic guidelines. We present here seven patients with DSRCT including immunohistochemistry combined with fluorescence in situ hybridization (FISH), next generation sequencing (NGS, n = 6) as well as OncoScan array (n = 3) analyses and show consecutive therapeutic approaches. All seven DSRCT patients presented with an extended abdominal mass; median age at diagnosis was 24.8 years. NGS analyses revealed five class 4 or 5 sequence variants. Remarkably, OncoScan and targeted analyses by FISH identified genomic gains of CCND1 in two cases. Cyclin D1 expression was present in all seven tumors as shown by immunohistochemical staining. Multimodal therapeutic concepts included systemic therapies, resection, and radiation. Six patients were treated as first-line therapy with conventional chemotherapy. All except one patient had a dismal therapy response. Subsequent therapy lines consisted of chemotherapeutic combinations followed by targeted therapies. Due to Cyclin D1 expression, the CDK4/6 inhibitor palbociclib was applied to four patients. The median therapy duration until disease progression in these patients was 4.5 months (range, 1.5-5 months). So, CCND1 genomic gain and Cyclin D1 expression are common features pointing to cell-cycle deregulation as a possible therapeutic target.

Purpose: Recently, the association between ATRX and a more aggressive sarcoma phenotype has been shown. We performed a retrospective study of sarcomas from an individual institution to evaluate ATRX as a prognosticator in soft tissue sarcoma. Experimental Design. 128 sarcomas were collected from a single institution and stained for ATRX. The prognostic significance of these markers was evaluated in a smaller cohort of primary soft tissue sarcomas (n = 68). Kaplan-Meier curves were created for univariate analysis, and Cox regression was utilized for multivariate analysis.

Results: High expression of ATRX was found to be a positive prognostic indicator for overall survival and metastasis-free survival in our group of soft tissue sarcomas both in univariate analysis and multivariate analysis (HR: 0.38 (0.17-0.85), P=0.02 and HR: 0.49 (0.24-0.99), P=0.05, respectively).

Conclusions: High expression of ATRX is a positive prognostic indicator of overall survival and metastasis-free survival in patients with STS. This is consistent with studies in osteosarcoma, which indicate possible mechanisms through which loss of ATRX leads to more aggressive phenotypes. Future prospective clinical studies are required to validate the prognostic significance of these findings.

Background: Ewing sarcoma (EwS) is a rare and highly malignant bone tumor primarily affecting children, adolescents, and young adults. The pelvis, trunk, and lower extremities are the most common sites, while EwS of the sacrum as a primary site is very rare, and only few studies focusing on this location are published. Due to the anatomical condition, local treatment is challenging in sacral malignancies. We analyzed factors that might influence the outcome of patients suffering from sacral EwS.

Methods: We retrospectively analyzed data of the GPOH EURO-E.W.I.N.G 99 trial and the EWING 2008 trial, with a cohort of 124 patients with localized or metastatic sacral EwS. The study endpoints were overall survival (OS) and event-free survival (EFS). OS and EFS were calculated using the Kaplan-Meier method, and univariate comparisons were estimated using the log-rank test. Hazard ratios (HRs) with respective 95% confidence intervals (CIs) were estimated in a multivariable Cox regression model.

Results: The presence of metastases (3y-EFS: 0.33 vs. 0.68; P < 0.001; HR = 3.4, 95% CI 1.7 to 6.6; 3y-OS: 0.48 vs. 0.85; P < 0.001; HR = 4.23, 95% CI 1.8 to 9.7), large tumor volume (≥200 ml) (3y-EFS: 0.36 vs. 0.69; P=0.02; HR = 2.1, 95% CI 1.1 to 4.0; 3y-OS: 0.42 vs. 0.73; P=0.04; HR = 2.1, 95% CI 1.03 to 4.5), and age ≥18 years (3y-EFS: 0.41 vs. 0.60; P=0.02; HR = 2.6, 95% CI 1.3 to 5.2; 3y-OS: 0.294 vs. 0.59; P=0.01; HR = 2.92, 95% CI 1.29 to 6.6) were revealed as adverse prognostic factors.

Conclusion: Young age seems to positively influence patients` survival, especially in patients with primary metastatic disease. In this context, our results support other studies, stating that older age has a negative impact on survival. Tumor volume, metastases, and the type of local therapy modality have an impact on the outcome of sacral EwS. Level of evidence: Level 2. This trial is registered with NCT00020566 and NCT00987636.

Background: Extremity soft-tissue sarcoma (ESTS) is a group of rare, heterogeneous malignancies. Previous studies have demonstrated a progressive improvement in 5-year survival rate over time, but recent trends are unknown. Therefore, this study aimed to provide an update on the clinical characteristics and 5-year survival rate of ESTS from 1999 to 2019.

Methods: This retrospective cohort study used the Surveillance, Epidemiology, and End Results (SEER) database. Overall, 5,654 patients over the age of 15 years with primary ESTS diagnosed between 1999 and 2019 were included. Data on patient demographics, clinical characteristics, and survival were extracted. Patients were grouped by year of diagnosis: 1999-2005, 2006-2012, and 2013-2019. Kaplan-Meier and Cox proportional hazards regression analyses were performed.

Results: ESTS occurred primarily in the lower extremity (76.1%) and was frequently grade III (58.3%), >5 cm in size (69.9%), and without metastasis (77.9%) at diagnosis. Furthermore, there was a significant increase in the proportion of patients over age 60 (p < 0.001) and without metastasis (p < 0.001) over the study period. The 5-year survival rate successively improved, from 47% in 1999-2005, to 61% in 2006-2012, to 78% in 2013-2019. Similarly, in multivariate analysis, the mortality rate progressively declined from a hazard ratio (HR) of 3.4 in 1999-2005 to an HR of 2.1 in 2006-2012, with the 2013-2019 group having the best overall survival (p < 0.001). Age, tumor size, grade, and metastasis were negative prognostic factors for survival; radiation and surgery were positive prognostic factors.

Conclusions: The 5-year overall survival rate for ESTS progressively improved over the 20-year study period, perhaps due to an increasing proportion of older patients diagnosed with local disease. These findings may also be related to earlier detection or more effective treatment over the study period.

Desmoplastic small round cell tumor (DSRCT) is a rare pediatric cancer caused by the EWSR1-WT1 fusion oncogene. Despite initial response to chemotherapy, DSRCT has a recurrence rate of over 80% leading to poor patient prognosis with a 5-year survival rate of only 15-25%. Owing to the rarity of DSRCT, sample scarcity is a barrier in understanding DSRCT biology and developing effective therapies. Utilizing a novel pair of primary and recurrent DSRCTs, we present the first map of DSRCT genomic breakpoints and the first comparison of gene expression alterations between primary and recurrent DSRCT. Our genomic breakpoint map includes the lone previously published DSRCT genomic breakpoint, the breakpoint from our novel primary/recurrent DSRCT pair, as well as the breakpoints of five available DSRCT cell lines and five additional DSRCTs. All mapped breakpoints were unique and most breakpoints included a 1-3 base pair microhomology suggesting microhomology-mediated end-joining as the mechanism of translocation fusion and providing novel insights into the etiology of DSRCT. Through RNA-sequencing analysis, we identified altered genes and pathways between primary and recurrent DSRCTs. Upregulated pathways in the recurrent tumor included several DNA repair and mRNA splicing-related pathways, while downregulated pathways included immune system function and focal adhesion. We further found higher expression of the EWSR1-WT1 upregulated gene set in the recurrent tumor as compared to the primary tumor and lower expression of the EWSR1-WT1 downregulated gene set, suggesting the EWSR1-WT1 fusion continues to play a prominent role in recurrent tumors. The identified pathways including upregulation of DNA repair and downregulation of immune system function may help explain DSRCT's high rate of recurrence and can be utilized to improve the understanding of DSRCT biology and identify novel therapies to both help prevent recurrence and treat recurrent tumors.

Objectives: Fibroblast activation protein alpha (FAP) is highly expressed by cancer-associated fibroblasts in multiple epithelial cancers. The aim of this study was to characterize FAP expression in sarcomas to explore its potential utility as a diagnostic and therapeutic target and prognostic biomarker in sarcomas.

Methods: Available tissue samples from patients with bone or soft tissue tumors were identified at the University of California, Los Angeles. FAP expression was evaluated via immunohistochemistry (IHC) in tumor samples (n = 63), adjacent normal tissues (n = 30), and positive controls (n = 2) using semiquantitative systems for intensity (0 = negative; 1 = weak; 2 = moderate; and 3 = strong) and density (none, <25%, 25-75%; >75%) in stromal and tumor/nonstromal cells and using a qualitative overall score (not detected, low, medium, and high). Additionally, RNA sequencing data in publicly available databases were utilized to compare FAP expression in samples (n = 10,626) from various cancer types and evaluate the association between FAP expression and overall survival (OS) in sarcoma (n = 168).

Results: The majority of tumor samples had FAP IHC intensity scores ≥2 and density scores ≥25% for stromal cells (77.7%) and tumor cells (50.7%). All desmoid fibromatosis, myxofibrosarcoma, solitary fibrous tumor, and undifferentiated pleomorphic sarcoma samples had medium or high FAP overall scores. Sarcomas were among cancer types with the highest mean FAP expression by RNA sequencing. There was no significant difference in OS in patients with sarcoma with low versus high FAP expression.

Conclusion: The majority of the sarcoma samples showed FAP expression by both stromal and tumor/nonstromal cells. Further investigation of FAP as a potential diagnostic and therapeutic target in sarcomas is warranted.