Clear surgical margins as a prognostic indicator for disease recurrence, with no impact on survival rates in patients with myxofibrosarcoma.

Myxofibrosarcoma presents an infiltrating growth pattern that results in a high tendency for local recurrence. Clear margin resection is challenging because of microscopic infiltration. The purpose of the present study was to analyze the overall and disease-free survival rates of patients with myxofibrosarcoma and the prognostic factors that determine both survival and disease recurrence. Among the 111 patients included in our study, the 5-year overall survival rate was 65.5%. An age of more than 65 years (hazard ratio [HR] 1.9 [95% confidence interval (CI) 1.4-5.6]; p < 0.001), a tumor size of more than 5 cm (HR 2.8 [95% CI 0.9-8.1]; p = 0.049) and the G3 tumor grade (HR 14.1 [95% CI 2.1-105.0]; p < 0.001) negatively affected overall survival. The 5-year recurrence-free survival rate was 49.4%. R1/R2-type resection (HR 2.4 [95% CI 1.0-5.6]; p = 0.048) had a detrimental effect on tumor recurrence. Clear margins had a positive impact on recurrence-free survival, but did not significantly affect overall patient survival, suggesting that other factors may play a more significant role in determining patient outcomes. A surgical margin of 2 mm was not sufficient to significantly influence the incidence of recurrence. Consequently, a wider surgical margin may be necessary to reduce the risk of myxofibrosarcoma recurrence.

Dermatofibrosarcoma Protuberans: A Study of 148 Patients.

INTRODUCTION: Dermatofibrosarcoma protuberans (DFSP) is the most common sarcoma of the skin. Although distant metastases are infrequent, DFSP is highly aggressive locally with frequent local recurrences. It has been reported that the presence within the tumour of areas histopathologically mimicking fibrosarcoma may increase the risk of recurrence. OBJECTIVE: The objective of this study was to review the clinical features of our patients with DFSP and the factors associated with recurrence of the tumour, focussing on the presence of fibrosarcomatous areas. METHODS: Retrospective study of patients with DFSP diagnosed in 1990-2021 in a tertiary university hospital. The medical records were reviewed to obtain the following data: age, sex, tumour location, diameter, evolution time, presence of fibrosarcomatous areas, development of recurrence, and follow-up. Factors possibly associated with disease-free survival were analysed with Kaplan-Meier method and multivariate Cox regression. RESULTS: 148 patients (74 women/74 men, mean age 46.28 years, SD 14.431) were included in the study. Tumours involved the head and neck in 15 cases, thorax in 31, abdomen in 16, upper back in 43, lower back in 10, upper extremities in 10, and lower extremities in 23. Fibrosarcoma-like areas were observed in 16 tumours (10.81%). In 17 patients (11.49%), recurrences were observed (13 local recurrences, 3 lung metastasis, and 1 local recurrence with lung metastasis). Fibrosarcomatous DFSP recurred more frequently than classic DFSP (50% vs. 6.82%, respectively), and its disease-free survival was significantly lower (p < 0.001). In multivariate Cox regression, the presence of fibrosarcomatous areas was the only factor influencing disease-free survival. CONCLUSIONS: It is important to identify the fibrosarcomatous variant since it recurs more frequently and has lower recurrence-free survival. Distant metastases, mainly in the lung, are also more frequent in fibrosarcomatous DFSP.

Characterization of PD-1/PD-L1 immune checkpoint expression in soft tissue sarcomas.

Inhibitors of the programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) immune checkpoint system are used for treating various malignancies. However, evidence on their use in soft tissue sarcomas (STS) is limited. This study aimed to retrospectively investigate the relationship between the expression of PD-1/PD-L1 and related antigens in STS, and their association with clinical characteristics. Immunostaining for CD4, CD8, PD-1, PD-L1, IL-2, and IFN-γ was performed using pathological specimens harvested at the time of biopsy from 10 patients with undifferentiated pleomorphic sarcoma (UPS), nine with myxofibrosarcoma (MFS), and three with malignant peripheral nerve sheath tumor (MPNST) who were treated at our hospital. Subsequently, the positive immunostaining cell rates were calculated. We also examined the correlation between each immune positive cell rate and age, tissue grade, size, and maximum standardized uptake (SUV-max) values. The 3-year event-free survival (EFS) and overall survival (OS) rates were compared between the positive and negative groups (positive rate >10%; negative <10%) for various immune stains. The positive rates were also compared between the presence and absence of events groups. There was positive staining for the immune checkpoint molecules in every STS type except for PD-1 in MPNST. CD4, CD8, and PD-1 stained lymphocytes in close proximity to the tumor in adjacent tissue sections. A positive correlation was observed between the positive cell rates of each immune component including inflammatory cytokines such as IL-2 and IFN-γ. Additionally, the clinical features positively correlated with the positive PD-1/PD-L1 expression rates. No significant differences in the 3-EFS and OS rates was observed between the PD-1/PD-L1 positive and negative groups. Our results suggest that an inducible immune checkpoint mechanism may be involved in UPS, MFS, and MPNST.

Sclerosing Epithelioid Fibrosarcoma: A Distinct Sarcoma With Aggressive Features.

Since its original description in 1995, the concept of sclerosing epithelioid fibrosarcoma (SEF) as a distinctive tumor has evolved in the literature. Subsequent studies suggested that the presence of low grade fibromyxoid sarcoma (LGFMS)-like zones, occasional FUS gene rearrangements, and immunoreactivity for MUC4 all pointed to a close inter-relationship with LGFMS; however, more recent studies showed that SEF is genetically distinct from LGFMS with predominantly EWSR1-CREB3L1 fusion and complex secondary genomic alterations. To better understand the relationship between these tumors, we studied 51 cases of SEF, the largest reported series to date, and directly compared them to a previously published series of LGFMS from the same institution. The male-to-female ratio was 1.4:1 with a median age of 45 years. Tumors occurred primarily in the lower extremity (12), intra-abdominal area/visceral organs (9) and chest wall/paraspinal region (9) with a median size of 8.2 cm. The median follow-up was 49 months in 45 patients: 12 developed local recurrences and 36 developed metastases, mainly to lung and bone. Molecular studies showed EWSR1 gene rearrangement in 13 cases, 3' deletion of EWSR1 in 6, monosomy for EWSR1 in 2; FUS gene rearrangements in 3; EWSR1-CREB3L1 fusion in 7; EWSR1-CREB3L2 fusion in 1; and YAP1-KMT2A fusion in 2. Overall survival of SEF was significantly less compared with LGFMS (P≤0.0001). These results indicate that SEF is a distinct sarcoma that behaves more aggressively than LGFMS with a shorter survival, higher metastatic rate, and greater propensity to involve deep soft tissue and bone.

The clinicoradiological features and surgical outcomes of primary intracranial fibrosarcoma: a single-institute experience with a systematic review.

Primary intracranial fibrosarcoma (PIF) was a rare tumor with a high relapse rate and dismal survival rate. This study aimed to delineate the clinical characteristics of primary intracranial fibrosarcoma (PIF) and the risk factors for outcomes. We reviewed 15 PIF patients, who underwent surgical treatment at our institution from January 2009 to December 2018. Meanwhile, 36 cases from the prior literature between November 1962 and December 2019 were also retrieved and pooled to identify the risk factors. In our cohort, while cystic component (46.7%), perilesional edema (83.3%), and vascular flow void (66.7%) were commonly observed, no patient was accurately diagnosed. The 2-year relapse-free survival (RFS) and overall survival (OS) were 12.2% and 30.2%, respectively. Based on the pooled data, tumor size (p = 0.006), Ki-67 index (p = 0.004), and radiotherapy dose (p = 0.029) were prognostic factors for RFS in univariate analysis. In the univariate analysis, tumor size (p = 0.002), NGTR (p = 0.049), and high Ki-67 index (p = 0.019) were significant predictors for OS; and further multivariate analysis (n = 18) showed that large tumor size (≥ 5 cm; HR 14.613, p = 0.022) and high Ki-67 index (≥ 30%; HR 5.879, p = 0.020) were the independent risk factors for OS. Due to the rarity and nonspecific clinicoradiological features, the correct diagnosis of PIF before surgery was challenging. The outcomes of PIF were poor, and GTR plus radiotherapy (at least 60 Gy) might benefit to the outcomes and were recommended. Future study with a large cohort was needed to verify our findings.

OSmfs: An Online Interactive Tool to Evaluate Prognostic Markers for Myxofibrosarcoma.

Myxofibrosarcoma is a complex genetic disease with poor prognosis. However, more effective biomarkers that forebode poor prognosis in Myxofibrosarcoma remain to be determined. Herein, utilizing gene expression profiling data and clinical follow-up data of Myxofibrosarcoma cases in three independent cohorts with a total of 128 Myxofibrosarcoma samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, we constructed an easy-to-use web tool, named Online consensus Survival analysis for Myxofibrosarcoma (OSmfs) to analyze the prognostic value of certain genes. Through retrieving the database, users generate a Kaplan-Meier plot with log-rank test and hazard ratio (HR) to assess prognostic-related genes or discover novel Myxofibrosarcoma prognostic biomarkers. The effectiveness and availability of OSmfs were validated using genes in ever reports predicting the prognosis of Myxofibrosarcoma patients. Furthermore, utilizing the cox analysis data and transcriptome data establishing OSmfs, seven genes were selected and considered as more potentially prognostic biomarkers through overlapping and ROC analysis. In conclusion, OSmfs is a promising web tool to evaluate the prognostic potency and reliability of genes in Myxofibrosarcoma, which may significantly contribute to the enrichment of novelly potential prognostic biomarkers and therapeutic targets for Myxofibrosarcoma.

Systemic Inflammation Is Associated with Oncological Outcome in Patients with High-Grade Myxofibrosarcoma of the Extremities: A Retrospective Analysis.

BACKGROUND: The aim of this retrospective study is to verify whether preoperative systemic inflammatory markers (serum C-reactive protein [CRP] and neutrophil-lymphocyte ratio [NLR]) can help in predicting the disease-specific survival (DSS) and local recurrence (LR) rate in adult patients affected by localized myxofibrosarcoma (MFS) of the extremities. METHODS: We reviewed 126 adult patients with primary, localized MFS of the limbs. We analyzed DSS and LR. RESULTS: Median age at the time of surgery was 68 years (range 19-92). Median CRP was 0.4 mg/dL and median NLR was 2.8. A worse DSS was found in patients who had preoperative CRP >0.5 mg/dL (p = 0.002) and in those with NLR >3.5 (p < 0.001). In multivariate analysis, tumor size and grade as well as preoperative CRP values and NLR were confirmed to be prognostic factors in terms of DSS. An increased risk of LR was found in multivariate analysis in patients with a tail sign and with high gadolinium enhancement at preoperative MRI. CONCLUSIONS: Patients with high preoperative CRP and NLR levels, as well as large and high-grade tumors, might be considered as candidates for additional, more aggressive treatment approaches or more stringent follow-up schedules.

Grading in Myxofibrosarcoma of the Extremities Can Predict Survival and Local Control.

BACKGROUND: The aim of this retrospective analysis is to understand the natural history of myxofibrosarcoma (MFS), in particular whether the prognosis can be influenced by histologic grade. METHODS: We reviewed 229 adult patients with primary MFS of the limbs. We analyzed disease-specific survival (overall survival [OS]) and local recurrence (LR). RESULTS: Median age was 70 years (range, 19-92). Sixteen (7.0%) were grade 1, 38 (16.6%) grade 2, and 175 (76.4%) grade 3. A worse OS was found in grade 3 MFS (73.1%) than in grade 2 and 1 MFS (91.9 and 100%, respectively) at 5 years (p = 0.031). Locally recurred MFS had a worse OS (p = 0.018). A better LR-free rate (100% at 5 years) was observed in grade 1 MFS; however, a similar rate was observed between grade 2 and 3 tumors (77.1 and 80.0% at 5 years, respectively, p = 0.412). CONCLUSIONS: Grade 3 MFS has the worst prognosis. Grade 1 MFS have the lowest risk of LR. These data could help identify a high-risk patient group, thus selecting a more careful follow-up for higher-risk patients. Since MFS mostly affects the elderly population, it might be useful to reserve adjuvant treatments (radiotherapy and chemotherapy) to higher-risk patients.

Recurrent Fusions Between YAP1 and KMT2A in Morphologically Distinct Neoplasms Within the Spectrum of Low-grade Fibromyxoid Sarcoma and Sclerosing Epithelioid Fibrosarcoma.

Sclerosing epithelioid fibrosarcoma (SEF) is an aggressive soft tissue sarcoma. In the majority of cases, there is overexpression of MUC4, and most cases show EWSR1-CREB3L1 gene fusions. A subset of SEF displays composite histologic features of SEF and low-grade fibromyxoid sarcoma (LGFMS). These "hybrid" tumors are more likely to harbor the FUS-CREB3L2 fusion, which is also seen in most LGFMS. We, here, characterize a series of 8 soft tissue neoplasms with morphologic features highly overlapping with LGFMS and SEF but lacking MUC4 expression and EWSR1/FUS-CREB3L gene fusions. Seven tumors showed fusions of the YAP1 and KMT2A genes, and 1 had a fusion of PRRX1 and KMT2D; all but 1 case displayed reciprocal gene fusions. At gene expression profiling, YAP1 and KMT2A/PRRX1 and KMT2D tumors were distinct from LGFMS/SEF. The patients were 4 female individuals and 4 male individuals aged 11 to 91 years. Tumors with known locations were in the lower extremity (5), trunk (2), and upper extremity (1); 3 originated in acral locations. Tumor size ranged from 2.5 to 13 cm. Proportions of SEF-like and LGFMS-like areas varied considerably among tumors. All tumors that showed infiltrative growth and mitotic figures per 10 HPFs ranged from 0 to 18. Tumor necrosis was present in 1 case. Follow-up was available for 5 patients (11 to 321 mo), 2 of whom developed local recurrences, and 1 died of metastatic disease. The clinical behavior of these soft tissue sarcomas remains to be further delineated in larger series with extended follow-up; however, our limited clinical data indicate that they are potentially aggressive.

Prognostic relevance of SMC family gene expression in human sarcoma.

OBJECTIVE: To explore the prognostic value of the expression of genes encoding structural maintenance of chromosomes (SMCs) in human sarcoma. RESULTS: We found that the levels of SMC1A, SMC2, SMC3, SMC4, SMC5 and SMC6 mRNA were all higher in most tumors compared to normal tissues, and especially in sarcoma. According to the Cancer Cell Line Encyclopedia (CCLE), SMC1A, SMC2, SMC3, SMC4, SMC5 and SMC6 are also highly expressed in sarcoma cell lines. Results of Gene Expression Profiling Interactive Analysis (GEPIA) indicated that high expression of SMC1A was significantly related to poor overall survival (OS) (p<0.05) and disease-free survival (DFS) in sarcoma (p<0.05). Additionally, strong expression of SMC2 was significantly related to poor OS in sarcoma (p<0.05). In contrast, SMC3, SMC4, SMC5, and SMC6 expression had no significant impact on OS or DFS in sarcoma. CONCLUSIONS: Expression of SMC family members is significantly different in sarcoma relative to normal tissues, and SMC1A and SMC2 may be useful as prognostic biomarkers. METHODS: We performed a detailed comparison of cancer and normal tissues regarding the expression levels of mRNA for SMC family members in various cancers including sarcoma through ONCOMINE and GEPIA (Gene Expression Profile Interactive Analysis) databases.

Low-grade fibromyxoid sarcoma: A report of the Cooperative Weichteilsarkom Studiengruppe (CWS).

BACKGROUND: Low-grade fibromyxoid sarcoma (LGFMS) is a rare soft-tissue tumor with benign histologic appearance, though fully malignant behavior is possible. METHODS: Patients with LGFMS <21 years registered in Cooperative Weichteilsarkom Studiengruppe trials until 2017 were analyzed. Firstline treatment consisted of complete surgical resection whenever possible. RESULTS: Median age of 31 patients was 10.9 years (first month to 17.1 years). Twenty-six tumors were confirmed to the tissue of origin (T1), four invaded contiguous structures (T2), one was TX. Eight were >5 cm. The best surgical result was resection with free margins (R0) in 24 and microscopic residuals (R1) in seven. Five-year event-free (EFS), 5-year local-relapse-free (LRFS), and 5-year overall-survival were 71 ± 18.6% confidence interval (CI) 95%, 76 ± 17.6% CI 95%, and 100%, respectively. Six patients suffered local relapse in a median of 1 year, one combined within 1.3 year and one metastatic relapse with lesions in the lung, back muscles, and thigh discovered in whole-body imaging 6 years after the first diagnosis. In univariate analysis, T status correlated with EFS (T1 79.6 ± 18.6%, T2 50.0 ± 49.0%, P = .038). Resection with free margins tends to be associated with better LRFS (R0 82.4 ± 18.6%, R1 53.6 ± 39.4%, P = .053). Among 24 patients with R0 resection, five (21%) suffered relapse, thereof three local, one metastatic, and one combined. Among seven patients with R1-resection, three (43%) suffered local relapse. CONCLUSION: Special caution is advisable in T2 tumors. The metastatic potential with lesions in unusual sites indicates that affected patients need to be informed. If long-term follow-up with whole-body imaging is beneficial, it may be addressed in larger intergroup analyses. Further research in disease biology is essential for optimal treatment and follow-up care.

The impact of local control in the treatment of children with advanced infantile and adult-type fibrosarcoma: Experience of the cooperative weichteilsarkom studiengruppe (CWS).

BACKGROUND AND OBJECTIVES: This study aims at examining the potential survival benefits of primary versus secondary surgery of children diagnosed with advanced infantile (iFS) and adult-type fibrosarcoma (aFS). METHODS: Treatment and outcome of 89 children with FS treated within prospective Cooperative Studiengruppe (CWS) trials (1981-2016) were analyzed retrospectively. RESULTS: Localized disease (LD) was diagnosed in 87 patients: 64/66 patients with iFS (≤2 years) and 23 with aFS (>2 ≤ 18 years). Two patients (iFS) had metastatic disease. Resection was the mainstay of therapy of patients with LD resulting in microscopically complete (R0, IRS group I) (n = 29/87, 33%), microscopically incomplete (R1, IRS group II) (n = 17/87, 20%) and macroscopically incomplete (R2, IRS group III) (n = 41/87, 47%). Advanced LD (IRS group III) was present in 32/64 (50%) patients with iFS and in 9/23 (39%) with aFS. Chemotherapy was added predominantly in patients with advanced disease and an assessable objective response to CHT was seen in 71% iFS and 75% aFS. The 5-year event-free survival (EFS) of patients with iFS and aFS was 81% (±10, 95% CI) and 70% (±19, 95% CI) (p = 0.24); the 5-year overall survival (OS) was 98% (±3, 95% CI) and 82% (±16, 95% CI) (p = 0.02). Primary resection was no prognostic factor. Secondary R0/ R1 resection in patients with advanced disease improved 5-year EFS and OS in aFS (p = 0.002 and p = 0.000) but not in infants. CONCLUSIONS: Secondary resection improves outcome in advanced aFS but not in infants. Mutilating surgery in infants should be avoided. TYPE OF STUDY AND LEVEL OF EVIDENCE: Treatment study: patients were enrolled in five prospective studies and one registry, prognosis study: retrospective study. LEVEL OF EVIDENCE: II/ III. MINI-ABSTRACT: Fibrosarcoma is a very rare malignant tumor. Little is known about differences of local treatment of advanced infantile and adult-type. Data of 89 patients registered in five prospective trials and one registry of the Cooperative Weichteilsarkom Studiengruppe (CWS) (1981-2016) were analyzed.

Pediatric head and neck fibrosarcomas: A demographical, treatment, and survival analysis and review of a rare case.

OBJECTIVE: To examine pediatric head and neck fibrosarcoma cases and review the demographics, management, and survival for these patients. METHODS: Pediatric patients in the Surveillance, Epidemiology, and End Results (SEER) database were included from 1973 to 2014 based on a diagnosis of a head and neck fibrosarcoma using ICD-O-3 head and neck primary sites and histology codes. Patients were included from birth-18 years of age. Additionally, a pediatric case of a head and neck infantile fibrosarcoma treated at the Nemours Children's hospital in Orlando, Florida is presented. RESULTS: One hundred-thirteen pediatric head and neck fibrosarcomas were identified within the SEER database over the study period. The mean age at diagnosis was 9.8 years (SD: 6.2, range: 0.0-18.0). The mean age at diagnosis for infantile fibrosarcomas was 1.7 years (SD: 3.2, range: 0.0-12.0). Fifty-one (45.1%) patients were female. A majority (N = 67, 59.3%) of patients had dermatofibrosarcoma followed by 18 (15.9%) who had infantile fibrosarcomas. Nearly all patients (N = 107, 94.7%) received surgical intervention. 27.8% of patients with an infantile fibrosarcoma received chemotherapy as a part of their care compared to 1.5% of patients with a dermatofibrosaroma (p = .004). The 5-year disease-specific survival was 97%. CONCLUSIONS: Pediatric patients with head and neck fibrosarcomas are most likely to present in Caucasian males or females during late childhood or early adolescence. Infantile fibrosarcomas present in pediatric patients at a much earlier age. Surgical management is common for pediatric head and neck fibrosarcomas. Additionally, chemotherapy may be used for infantile fibrosarcomas of the head and neck. Survival rates for pediatric patients with a head and neck fibrosarcoma are excellent.

Canine oral fibrosarcoma: Changes in prognosis over the last 30 years?

Canine oral fibrosarcoma (oFSA) is a malignant, infiltrating, mesenchymal tumour affecting the oral cavity primarily of medium to large middle aged dogs. The diagnosis often is made late in the course of the disease, due to the frequent caudal location of the tumour, and histopathology is not always sufficient to discriminate undifferentiated oFSA from other poorly differentiated malignant mesenchymal tumours occurring at the same site, especially in small biopsy samples. The literature exclusively relating to oFSA is limited and outcome data following treatment are difficult to compare. The purpose of this article is to provide an overview of the literature spanning the last 30 years, specifically with regard to different treatment modalities in their relation to prognosis of canine oFSA. Overall, the survival rate for dogs with oFSA has improved in recent years (overall survival 247-743 days, compared to 30-540days in papers published before 2000), probably due to better surgical planning. The major concern in clinical management of canine oFSA is the high local rate of recurrence (up to 57%), whereas metastasis occurs late in about 10-14% of affected dogs. Wide surgical excision is the mainstay of treatment. Initially, the tumour was considered to be radioresistant, but a combination of surgery and radiotherapy seems to be the most promising treatment modality at present. Despite a histopathological diagnosis of a low-grade tumour, an aggressive treatment approach is always warranted to cure oFSA, but the ability to control local disease still represents the major challenge.

Clinical Characteristics and efficacy of chemotherapy in sclerosing epithelioid fibrosarcoma.

BACKGROUND: Sclerosing epithelioid fibrosarcoma (SEF) is a very rare soft tissue sarcoma subtype. Clinically it is an aggressive tumour; however, to our knowledge there are no published reports regarding the efficacy of chemotherapy in SEF. Therefore, the aim of this study was to document the outcome of a series of patients with SEF treated at a single referral centre with reference to systemic therapy. METHODS: A retrospective search of a prospectively maintained database was performed to identify all patients diagnosed with SEF between 1990 and 2017. The diagnosis was confirmed in each case by a dedicated soft tissue sarcoma pathologist. We analysed those with recurrent disease and the effect of systemic chemotherapy in the metastatic setting. RESULTS: Thirteen patients were identified, median overall survival from diagnosis and metastasis were 47.3 (95% CI 25.0-131.9) and 16.3 (95% CI 5.3-20.6) months, respectively. In total, 12 (92.3%) patients developed metastatic disease of which 10 died of disease, 1 was lost to follow-up and 1 had recently commenced palliative treatment. Among the 10 patients with metastatic disease, 7 received palliative chemotherapy. Palliative chemotherapy resulted in partial response in 1 patient, stable disease in 3 patients and progressive disease in 3 patients. Median time to disease progression was 2.7 (95% CI 1.2-4.4) months. Two of 13 patients were treated with adjuvant chemotherapy, receiving 6 cycles of liposomal doxorubicin and 1 cycle of doxorubicin, respectively, with a metastasis-free survival of 28.2 and 7.1 months, respectively. CONCLUSION: SEF is an aggressive sarcoma subtype with a poor outcome and with limited responsiveness to conventional chemotherapy. Patients with this subtype should be considered for participation in clinical trials with novel agents. Further investigation into the biology of this rare disease is required to improve outcomes.

Localized Myxofibrosarcomas: Roles of Surgical Margins and Adjuvant Radiation Therapy.

PURPOSE: The objective of this study was to describe the outcome and prognostic factors for adults treated for localized myxofibrosarcoma. METHODS AND MATERIALS: We conducted a retrospective multicenter study of 425 nonmetastatic patients who underwent surgery between January 1996 and December 2015 in French National Group and were enrolled in the Conticabase. Pathologic diagnosis was systematically reviewed by expert pathologists. The endpoints were relapse-free and metastasis-free survival. Log-rank tests and Cox models have been used to identified prognostic factors. RESULTS: Median age was 66 years; 53% were males; 85% of cases occurred in limbs or superficial trunk; median size was 60 mm; 47% and 39% were grades 2 and 3, respectively; 66% had R0 resection and 34% R1 resection. Adjuvant radiation therapy was given to 65% of patients, neoadjuvant radiation therapy to 3%, neoadjuvant chemotherapy to 7%, and adjuvant chemotherapy to 13%. The median follow-up was 51 months. The 5-year local relapse-free survival was 67%; independent prognostic factors for local relapse were R1 resection (hazard ratio [HR] = 1.26; P = .001) and adjuvant radiation therapy (HR = 0.35; P = .0001) (ie, R1 resection and no adjuvant radiation therapy increase the hazard ratio). In stratified analysis, adjuvant radiation therapy was beneficial after R0 resection (P = .0020) and after R1 resection (P = .0001). The 5-year overall survival was 80%. The 5-year metastasis-free survival was 83%. Independent prognostic factors for metastatic relapse were grade 3 disease (HR = 1.975; P = .0001) and tumor size (HR = 1.006; P = .001). CONCLUSIONS: This large series of myxofibrosarcoma confirms the high rate of local relapse. Combination of R0 resection and adjuvant radiation therapy provided the best local control. In parallel with an increasing rate of R0 resection and adjuvant radiation therapy, we observed a constant improvement in both metastatic and local relapse-free survival during the study.

Integrated genetic and epigenetic analysis of myxofibrosarcoma.

Myxofibrosarcoma (MFS) is a common adult soft tissue sarcoma characterized by an infiltrative growth pattern and a high local recurrence rate. Here we report the genetic and epigenetic landscape of MFS based on the results of whole-exome sequencing (N = 41), RNA sequencing (N = 29), and methylation analysis (N = 41), using 41 MFSs as a discovery set, and subsequent targeted sequencing of 140 genes in the entire cohort of 99 MFSs and 17 MFSs' data from TCGA. Fourteen driver genes are identified, including potentially actionable therapeutic targets seen in 37% of cases. There are frequent alterations in p53 signaling (51%) and cell cycle checkpoint genes (43%). Other conceivably actionable driver genes including ATRX, JAK1, NF1, NTRK1, and novel oncogenic BRAF fusion gene are identified. Methylation patterns cluster into three subtypes associated with unique combinations of driver mutations, clinical outcomes, and immune cell compositions. Our results provide a valuable genomic resource to enable the design of precision medicine for MFS.

Outcomes following surgical excision or surgical excision combined with adjunctive, hypofractionated radiotherapy in dogs with oral squamous cell carcinoma or fibrosarcoma.

OBJECTIVE To compare outcomes of dogs treated surgically for oral, nontonsillar, squamous cell carcinomas (SCCs) and fibrosarcomas (FSAs) with outcomes of dogs treated with a combination of surgery and postoperative radiotherapy; to explore whether postoperative, hypofractionated radiotherapy improved outcomes of dogs with incomplete excisions; and to identify prognostic factors associated with outcome. DESIGN Retrospective cohort study. ANIMALS 87 client-owned dogs that had undergone maxillectomy or mandibulectomy for treatment of oral SCC or FSA between 2000 and 2009. PROCEDURES Medical records were retrospectively reviewed. Survival analysis was performed with Kaplan-Meier and Cox regression analyses to evaluate potential prognostic factors associated with patient outcome. RESULTS Median survival time (MST) for all 87 dogs was 2,049 days, but was not reached for dogs with SCC, and was only 557 days for dogs with FSA; tumor type was a significant predictor of survival time. Dogs undergoing postoperative radiotherapy after incomplete excision of oral SCCs had a significantly longer MST (2,051 days) than did dogs with incompletely excised tumors and no radiotherapy (MST, 181 days). Postoperative radiotherapy of dogs with incompletely excised FSAs did not appear to offer protective value (MST, 299 days with radiotherapy and 694 days without radiotherapy). CONCLUSIONS AND CLINICAL RELEVANCE Wide-margin surgical excision should be considered the gold-standard treatment for dogs with oral SCC or FSA. For dogs with oral SCCs without clean surgical margins, survival times may be improved by providing postoperative, hypofractionated radiotherapy.

Establishment of a spontaneously transformed cell line (JU-PI) from a myxoinflammatory fibroblastic sarcoma.

Myxoinflammatory fibroblastic sarcoma is a soft-tissue neoplasm most frequently found in the distal extremities of middle-aged adults. Most myxoinflammatory fibroblastic sarcoma are low-grade tumors with propensity for local recurrence after incomplete removal. We report a myxoinflammatory fibroblastic sarcoma which developed in the foot of a 41-year-old male and showed an exceptionally aggressive course with metastatic spread and fatal outcome within 16 months. We managed to establish a spontaneously transformed continuous cell line, called JU-PI, from a metastatic lesion. The JU-PI cells have a sub-tetraploid karyotype including the 1;10 chromosomal translocation and amplification of the proximal end of 3p; these features are considered genetic signatures of myxoinflammatory fibroblastic sarcoma. Both the primary tumor and the JU-PI cells showed nuclear expression of the TFE3 transcription factor but TFE3-activating chromosomal rearrangements were not found. To our knowledge, JU-PI is the first established myxoinflammatory fibroblastic sarcoma cell line. JU-PI cells offer a tool for investigating the molecular oncology of myxoinflammatory fibroblastic sarcoma.

Primary cardiac myxofibrosarcoma: case report, literature review and pooled analysis.

BACKGROUND: Primary cardiac myxofibrosarcoma is a very rare cardiac malignancy. The majority of publications are limited to case reports. No pooled analyses of primary cardiac myxofibrosarcoma cases are available. Little clinical features and outcome patterns are acknowledged. The purpose of this study is to identify the clinical characteristics and prognostic factors of primary cardiac myxofibrosarcoma. CASE PRESENTATION: A case report of primary cardiac myxofibrosarcoma was presented, and a review of English language literatures of primary cardiac myxofibrosarcomas were performed electronically. Demographics, clinicopathologic data, therapy and follow-up were summarized. The median survival time and the mean survival time were calculated by Kaplan-Meier method. Survival distribution and overall survival were figured by log-rank test and cox proportional hazards models. We present a case, and retrospectively analyzed additional 30 patients derived from 24 isolated articles. The cohort consisted of 18 male and 13 female patients. The age was 41.87 ± 17.89 years. Some common features were found in clinical presentations, pathologic features, treatments and outcome patterns of primary cardiac myxofibrosarcoma. There were special features in echocardiography, histological and immunohistochemical examinations, which should be considered in diagnosis of primary cardiac myxofibrosarcoma. The median survival time/mean survival time (MST) was 14/32.66 months. The median survival time/mean survival time (MST) was 14/32.66 months. Compared to the other groups, the following groups had shorter survival characteristics, including age ≥ 40 years (14/11.79 months), female (14/26.26 months), mass diameter ≥ 40 mm (14/14.64 months), high-grade (2/11.81 months), and no post-treatment (14/28.09 months). Statistical analyses revealed that primary cardiac myxofibrosarcomas were more likely to present with local recurrences and dismal metastases. Tumors ≥ 40 mm in size (P = 0.055, HR = 6.79) or with high-grade (P = 0.063, HR = 11.45) had significantly worse prognosis. CONCLUSIONS: Primary cardiac myxofibrosarcomas were more likely to present with local recurrences and dismal metastases. Echocardiography, together with histological method should be considered in ordinary diagnosis. Tumors ≥ 40 mm in size or with high-grade had significantly worse prognosis, which should be early diagnosed and treated with rational surgery.