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Introduction: Synovial sarcoma is one of the most common soft tissue sarcomas in children. Guidelines regarding the adequate extent of resection margins and the role of re-resection are lacking. We sought to evaluate the adequate resection margin and the role of re-resection in predicting outcomes in children with synovial sarcomas., Methods: A cohort of 36 patients less than 18 years of age at diagnosis who were treated for localized synovial sarcoma at three tertiary pediatric hospitals between January 2004 and December 2020 were included in this study. Patient and tumor demographics, treatment information, and margin status after surgical resection were collected from the medical record. Clinical, treatment, and surgical characteristics, as well as outcomes including hazard ratios (HRs), event-free survival (EFS), and overall survival (OS) were compared by resection margins group and re-resection status., Results: Patients in the R1 resection group were significantly more likely to relapse or die compared to patients in the R0 resection group. However, there was no significant difference in EFS (HR 0.52, p = 0.54) or OS (HR 1.56, p = 0.719) in R0 patients with less than 5 mm margins compared to R0 patients with more than 5 mm margins. Patients with R1 on initial or re-resection had significantly worse OS than patients who had R0 resection on initial or re-resection (HR = 10.12, p = 0.005)., Conclusion: This study re-affirms that R0 resection is an independent prognostic predictor of better OS/EFS in pediatric synovial sarcoma. Second, our study extends this finding to report negative margins on initial resection or re-resection is associated with better OS/EFS than positive margins on initial resection or re-resection. Lastly, we found that there is no difference in outcomes associated with re-resection or <5 mm margins for R0 patients, indicating that re-resection and <5 mm margins are acceptable if microscopic disease is removed., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Introduction: The management of spinal sarcomas is complex, given their widespread involvement and high recurrence rates. Despite consensus on the need for a multidisciplinary approach with surgery at its core, there is a lack of definitive guidelines for clinical decision-making. This study examines a case series of primary spinal sarcomas, focusing on the surgical strategies, clinical results, and survival data to inform and guide therapeutic practices., Methods: We conducted a retrospective analysis of patients who underwent surgical resection for primary spinal sarcomas between 2005 and 2022. The study focused on gathering data on patient demographics, surgical details, postoperative complications, overall hospital stay, and mortality within 90 days post-surgery., Results: The study included 14 patients with a primary diagnosis of spinal sarcoma, with an average age of 48.6 ± 12.6 years. Chondrosarcoma emerged as the most common tumor type, representing 57.1% of cases, followed by Ewing sarcoma at 35.7%, and synovial sarcoma at 7.1%. Patients with chondrosarcoma were treated with en-bloc resection, while the patient with synovial sarcoma underwent intra-lesional excision and those with Ewing sarcoma received decompression and tumor debulking. Postoperative assessments revealed significant improvements in neurological conditions. Notably, functional status as measured by the Karnofski Performance Index (KPI), improved substantially post-surgery (from 61.4 to 80.0%) The mean follow-up was 34.9 ± 9.2 months. During this time period one patient experienced fatal bleeding after en-bloc resection complications involving the vena cava. None of the patient needed further surgery., Conclusions: Our 16-year study offers vital insights into managing primary spinal sarcomas, showcasing the effectiveness of surgical intervention, particularly en-bloc resection. Despite their rarity and complexity, our multidisciplinary treatment approach yields improved outcomes and highlights the potential for refined surgical strategies to become standardized care in this challenging domain., (© 2024. The Author(s).)

Background: To better understand the importance of the New York esophageal squamous cell carcinoma 1 (NY-ESO-1) and human leukocyte antigen (HLA) subtypes in treatment decision-making, further investigation of their prevalence and prognostic impact among patients with metastatic synovial sarcoma (mSS) is needed., Patients and Methods: This was a retrospective clinico-biological cohort study of adults with mSS. Patient data were collected from the French Sarcoma Group NetSARC database and supplemented by electronic medical records. Primary tumor samples were collected and analyzed for NY-ESO-1 expression by immunohistochemistry (IHC) and HLA-A∗02 status by RNA sequencing (RNA-seq). The primary cohort included patients with available primary tumor samples; the impact of a larger sample size was explored by including patients who had either a primary or metastatic sample (termed the exploratory cohort). P values are provided for descriptive purposes., Results: In 92 patients with primary tumor samples, ∼25% (n = 23) were positive for NY-ESO-1 and HLA-A∗02 expression (dual positive). Among 106 patients with IHC data, 61% (n = 65) were NY-ESO-1 positive, and among 94 patients with RNA-seq data, 45% (n = 42) were HLA-A∗02 positive. The median overall survival (OS) for positive versus negative NY-ESO-1 status was 35.3 and 21.7 months, respectively (unadjusted P = 0.0428). We observed no difference in median OS for HLA-A∗02-positive versus -negative and dual-positive patients versus others (both unadjusted P > 0.05). Multivariate analyses of OS showed no prognostic impact for NY-ESO-1 among primary tumor samples and in the exploratory cohort. However, in the latter we observed an association between NY-ESO-1 expression and OS in the first-line (P = 0.0041) but not in the second-line setting., Conclusions: The primary tumor cohort showed no association between NY-ESO-1 expression and OS (including stratification by HLA-A∗02 subtype and treatment line) when adjusting for important prognostic factors, possibly due to small sample sizes., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Though the prognosis for pediatric patients with localised synovial sarcoma (SS) is generally good, the chances of being cured after relapse are limited. This study describes a retrospective multi-institutional series of relapsing SS patients treated at six selected European referral centers for pediatric sarcoma., Patients and Methods: The study included 41 patients <21 years with relapsing SS, treated between 2002 and 2022. The analysis included patient's characteristics at first diagnosis, first-line treatments, clinical findings at relapse, and second-line treatment modalities., Results: The first relapse occurred within 3-132 months (median 18 months) after first diagnosis and was local in 34%, metastatic in 54%, and both in 12%. Treatment at first relapse included surgery in 56% of cases, radiotherapy in 34%, and systemic therapy in 88%. In all, 36 patients received second-line medical treatment, that was chemotherapy in 32 cases (with 10 different regimens) and targeted therapy in four. No patient was included in an early-phase clinical trial as second-line therapy-line therapy. Overall response rate was 42%. Median event-free survival (EFS) was 12 months, postrelapse 5-year EFS was 15.8%. Median overall survival (OS) was 30 months, postrelapse 5-year OS was 22.2%. At the Cox's multivariable regression analysis, OS was significantly associated with time and type of relapse., Conclusion: Pediatric patients with relapsed SS have a poor prognosis and generally receive an individualized approach, due to the lack of a uniform standardized approach. New comprehensive strategies are needed to improve the knowledge on the biologic landscape of SS and develop tailored prospective clinical trials., (© 2024 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Primary sarcomas of the lung represent less than 0.5% of all primary lung tumors and comprise a heterogeneous group of malignancies including synovial sarcoma (SS). Primary pleuropulmonary SS has non-specific presentations, such as chest pain, shortness of breath and cough, and its associated imaging features resemble those of other intrathoracic malignancies. The diagnosis of these tumors needs to be confirmed by cytogenetic and molecular studies. Here, we describe two rare cases of primary pleuropulmonary SS who were admitted to our hospital. We also provide a concise review of clinical, radiological, and histopathological characteristics of pleuropulmonary SS after exploring 168 studies (415 corresponding patients) that were identified through a literature search.

Purpose: Synovial sarcoma (SS) is the second most common malignant soft tissue tumor in children. ARST0332 evaluated a risk-based treatment strategy for young patients with soft tissue sarcoma designed to limit therapy for low-risk (LR) disease and to test neoadjuvant chemoradiotherapy for unresected higher-risk disease., Methods: Newly diagnosed patients with SS age < 30 years were assigned to four treatment arms based on disease features: A (surgery only), B (55.8 Gy radiotherapy [RT]), C (ifosfamide and doxorubicin [ID] chemotherapy plus 55.8 Gy RT), and D (neoadjuvant ID and 45 Gy RT, then surgery and RT boost based on margins followed by adjuvant ID). Patients treated in Arms A and B were considered LR, arms C and D without metastases as intermediate-risk (IR), and those with metastases as high-risk (HR)., Results: Of the 146 patients with SS enrolled, 138 were eligible and evaluable: LR (46), IR (71), and HR (21). Tumors were 80% extremity, 70% > 5 cm, 70% high-grade, 62% invasive, 95% deep, and 15% metastatic. Treatment was on arm A (29.7%), B (3.6%), C (16.7%), and D (50%). There were no toxic deaths and four unexpected grade 4 adverse events. By risk group, at a median follow-up of 6.8 years, estimated 5-year event-free survival was LR 82%, IR 70%, and HR 8%, and overall survival was LR 98%, IR 89%, and HR 13%. After accounting for the features that defined risk category, none of the other patient or disease characteristics (age, sex, tumor site, tumor invasiveness, and depth) improved the risk stratification model., Conclusion: The risk-based treatment strategy used in ARST0332 produced favorable outcomes in patients with nonmetastatic SS relative to historical controls despite using RT less frequently and at lower doses. The outcome for metastatic SS remains unsatisfactory and new therapies are urgently needed., Competing Interests: R. Lor RandallHonoraria: Biomet, Daiichi Sankyo, Onkos Surgical, OncliveTravel, Accommodations, Expenses: Biomet, Daiichi Sankyo/Lilly James AndersonEmployment: MerckStock and Other Ownership Interests: Merck Sharp & DohmeTravel, Accommodations, Expenses: Merck Sharp & Dohme Andrew OstrengaHonoraria: Amgen Alberto PappoHonoraria: Bayer, RocheConsulting or Advisory Role: Merck, Loxo/Bayer, EUSA Pharma, Debbio Sheri L. SpuntResearch Funding: LOXO Oncology/Bayer AG/MedPace Inc, Bayer Healthcare Pharmaceuticals, Inc - USNo other potential conflicts of interest were reported.

Objectives: Synovial sarcomas (SS) arising in distal extremities are rare and have been studied using mostly case reports and small series. We aimed to evaluate clinical presentation and survival outcomes for patients with hand or foot SS., Materials and Methods: We conducted a retrospective review of 84 patients diagnosed with primary hand (n=20) and foot (n=64) SS between 1979 and 2019. Progression-free survival (PFS), overall survival (OS), local recurrence-free survival and metastasis-free survival were estimated using the Kaplan-Meier method and log-rank test. Cox-proportional hazards regression was used to estimate the hazard ratios., Results: Of 84 patients, 63 (75%) presented with localized disease with 36 years median age at diagnosis (range: 4 to 76) and 21 (25%) with metastasis with 30 years median age at diagnosis (range: 15 to 64). Among patients presenting with localized disease, (1) 5 years-PFS, OS, local recurrence-free survival, and metastasis-free survival rates were 82%, 88%, 100%, and 86%, respectively. (2) Tumor size <3.0 cm corresponded to 95% 5 years-PFS (vs. 84% for 3.0 to 4.9 cm, 53% for ≥5.0 cm; P=0.007) and 100% 5 years-OS (vs. 77% for ≥3.0 cm; P=0.04). (3) Patients with ≥5.0 cm (vs. <3.0 cm) tumor size had 7.99 (95% confidence interval: 1.68, 37.91) times higher hazard of progression. Remarkably, patients presenting with metastasis had 50% 5 years-OS rate. Also, younger age (15 to 39 vs. 40 y and above) predicted better OS among patients presenting with localized disease (P=0.04) and with metastasis (P=0.03)., Conclusions: Survival outcomes are favorable for younger patients with <3.0 cm hand or foot SS. Local control is excellent, but we observed larger tumor size to be associated with poorer outcomes. Therefore, we recommend consideration of systemic therapy for patients with ≥3.0 cm hand or foot SS., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Synovial sarcoma is the most common soft tissue sarcomas among childhood and adolescents, accounting for 8-10% of all soft tissue sarcoma. Synovial sarcoma is considered a relatively chemosensitive tumor compared with other soft tissue sarcomas. However, the role of perioperative chemotherapy in synovial sarcoma remains controversial. The purpose of this systematic review is to evaluate the role of perioperative chemotherapy in childhood and adolescent patients with synovial sarcoma., Methods: We evaluated studies published between 1 January 1990 and 31 December 2017. The following databases were searched: MEDLINE, Cochrane database (via PubMed) and Ichushi (in Japanese)., Results: The search yielded 216 articles in English and Japanese. After the initial screening, based on the title and abstract, 160 articles were excluded. As a second screening, we then assessed the full text of the remaining 56 articles for eligibility. Finally, 10 articles were included in the systematic review. Surgical resection with R0 margin alone was recommended because of the excellent results of two prospective studies. Meta-analysis was performed using data from two retrospective studies of 261 patients. Perioperative chemotherapy did not have a significant effect on survival and event-free survival., Conclusions: We weakly do not recommend perioperative chemotherapy in patients with non-metastatic synovial sarcoma ≤ 5 cm when R0 resection is acquired. There was no consensus concerning the role of perioperative chemotherapy in patients with synovial sarcoma > 5 cm or those with ≤5 cm who undergo R1 or R2 resection., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Primary laryngeal synovial sarcoma is an extremely rare tumor predominantly affecting young adults. There are currently no well-defined guidelines to direct investigation and management, and treatment is largely based on what is known for synovial sarcoma of the upper and lower limbs. This PROSPERO-registered study aims to review the diagnostic methods, treatment regimens, and survival outcomes for patients with synovial sarcoma of the larynx. A systematic search of databases Medline, Embase, SCOPUS, and Web of Science was undertaken in December 2017. The literature search identified 1031 potentially relevant studies, and after the deletion of duplicates and excluded papers, 98 full-text articles were screened. A total of 39 cases were reviewed from 32 studies in the data extraction. The average age at the time of laryngeal synovial sarcoma diagnosis was 32 years (range, 11-79 years). In all cases (n = 39), patients underwent wide surgical excision, with 20 patients requiring a partial or total laryngectomy. A total of 18 patients received adjuvant and 3 received neoadjuvant radiotherapy. Chemotherapy was used in 10 cases, with ifosfamide the most frequently used agent. There was considerable variability in the order and combinations of the abovementioned treatments. No clinicopathologic factors or treatment regimens were associated with improved overall survival or lower rate of recurrence. There is a paucity of literature and heterogeneity in clinical approaches to this highly aggressive sarcoma. Reporting of cases must be standardized and formal guidelines must be established to guide clinical management.

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.

Background: The impact of adjuvant chemotherapy or radiation therapy on the survival of patients with synovial sarcoma (SS), which is a rare soft-tissue sarcoma, remains controversial. Bayesian statistical approaches and propensity score matching can be employed to infer treatment effects using observational data. Thus, this study aimed to identify the individual treatment effects of adjuvant therapies on the overall survival of SS patients and recognize subgroups of patients who can benefit from specific treatments using Bayesian subgroup analyses., Methods: We analyzed data from patients with SS obtained from the surveillance, epidemiology, and end results (SEER) public database. These data were collected between 1984 and 2014. The treatment effects of chemotherapy and radiation therapy on overall survival were evaluated using propensity score matching. Subgroups that could benefit from radiation therapy or chemotherapy were identified using Bayesian subgroup analyses., Results: Based on a stratified Kaplan-Meier curve, chemotherapy exhibited a positive average causal effect on survival in patients with SS, whereas radiation therapy did not. The optimal subgroup for chemotherapy includes the following covariates: older than 20 years, male, large tumor (longest diameter > 5 cm), advanced stage (SEER 3), extremity location, and spindle cell type. The optimal subgroup for radiation therapy includes the following covariates: older than 20 years, male, large tumor (longest diameter > 5 cm), early stage (SEER 1), extremity location, and biphasic type., Conclusion: In this study, we identified high-risk patients whose variables include age (age > 20 years), gender, tumor size, tumor location, and poor prognosis without adjuvant treatment. Radiation therapy should be considered in the early stages for high-risk patients with biphasic types. Conversely, chemotherapy should be considered for late-stage high-risk SS patients with spindle cell types.

Background: Synovial sarcoma (SS) is a rare, aggressive soft tissue sarcoma with a poor prognosis after metastasis. The objective of this study was to conduct a systematic review of the clinical evidence for therapeutic options for adults with metastatic or advanced SS. Materials & methods: Relevant databases were searched with predefined keywords. Results: Thirty-nine publications reported clinical data for systemic treatment and other interventions. Data on survival outcomes varied but were generally poor (progression-free survival: 1.0-7.7 months; overall survival: 6.7-29.2 months) for adults with metastatic and advanced SS. A high frequency of neutropenia with systemic treatment and low quality of life post-progression were reported. Conclusion: Reported evidence suggests poor outcomes in adults with metastatic and advanced SS and the need for the development of new treatment modalities.

Background: This is a retrospective review of synovial sarcoma (SS) patients treated over the last 12 years in Western Australia (WA). SS is both chemo and radiotherapy sensitive. Results of trials in adjuvant chemotherapy are conflicting and there is limited support for neoadjuvant chemotherapy. The use of combined chemoradiotherapy is based on institutional preferences., Aim: We reviewed the outcomes for SS patients treated in WA over a 12 year period focusing on patients who received neoadjuvant chemoradiotherapy (NACRT)., Methods: Patient details including demographics, histopathology, treatment details, were obtained from the WA sarcoma database (2006-2018). Progression free survival (PFS) and overall survival (OS) were derived for whole cohort., Results: Twenty seven patients were identified with SS with equal gender incidence. Median age of the cohort was 36 (14-76) years. The most common primary site of disease was extremity (81.5%). 22/27 patients presented with only localized disease and 59.2% of these received neo-adjuvant treatment. Of those who received neoadjuvant treatment, 56.2% had NACRT, while 25.0% and 18.7% of patients had chemotherapy and radiotherapy respectively. Mesna, doxorubicin, ifosfamide, dacarbazine (MAID) was the most commonly used chemotherapy regimen as neoadjuvant or adjuvant treatment while ifosfamide (93.7%) was the most commonly used chemotherapy drug in any setting. There was no reported case of disease progression in group of patients who received NACRT apart from one patient who had oligometastatic disease at diagnosis. Median OS of the whole cohort was 38 months while median PFS was 24 months. Bone marrow toxicity was the most commonly reported high grade toxicity in NACRT group (55.5%) but there were no treatment related deaths., Conclusion: NACRT is not widely adopted and treatment is based on institutional preferences, however our data shows that NACRT is a feasible therapy option. NACRT should be evaluated prospectively in a randomized trial., (© 2020 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

Background: Previous studies have demonstrated an association of perioperative radiotherapy (RT) with improved survival in patients with synovial sarcoma (SS) undergoing surgery, but the mechanism for this is unknown. In this study, we sought to further analyze this association using a hospital-based data set where data on chemotherapy administration and surgical margin status are available., Methods: Using the National Cancer Database, we identified 1216 patients with SS (aged ≥18 y) from 2004-2012 undergoing surgery. Cox proportional hazards analysis was used to study the effect of clinicopathologic variables on overall survival (OS)., Results: Mean age at diagnosis was 41.5 y (range 18-90), and 71.3% of tumors were high grade; 22.9% underwent surgery alone, 59.6% received RT with surgery, 44.2% received chemotherapy with surgery, and 26.3% received trimodality therapy. Age, sex, grade, Charlson-Deyo score, and RT (hazard ratio, 0.676; 95% confidence interval, 0.519-0.880; P = 0.004) were associated with improved OS, whereas chemotherapy (hazard ratio, 1.20; 95% confidence interval, 0.899-1.60; P = 0.217) and surgical margin status were not. Trimodality therapy with surgery, RT, and chemotherapy was associated with improved OS when compared with therapy with surgery and chemotherapy alone., Conclusions: In patients with SS undergoing surgery, we observed a significant improved association of OS with the addition of RT when adjusting for comorbidity score, margin status, and receipt of chemotherapy. These data further support routine implementation of RT in the treatment of patients with SS, including those receiving aggressive multimodality and trimodality care., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Outcomes data regarding advanced synovial sarcoma (SS) and myxoid/round cell liposarcoma (MRCL) are limited, consisting primarily of retrospective series and post hoc analyses of clinical trials., Methods: In this multi-center retrospective study, data were abstracted from the medical records of 350 patients from nine sarcoma centers throughout the United States and combined into a registry. Patients with advanced/unresectable or metastatic SS (n = 249) or MRCL (n = 101) who received first-line systemic anticancer therapy and had records of tumor imaging were included. Overall survival (OS), time to next treatment, time to distant metastasis, and progression-free survival (PFS) were evaluated using the Kaplan-Meier method and Cox regression., Results: At start of first-line systemic anticancer therapy, 92.4% of patients with SS and 91.1% of patients with MRCL had metastatic lesions. However, 74.7% of patients with SS and 72.3% of patients with MRCL had ≥2 lines of systemic therapy. Median OS and median PFS from first-line therapy for SS was 24.7 months (95% CI, 20.9-29.4) and 7.5 months, respectively (95% CI, 6.4-8.4). Median OS and median PFS from start of first-line therapy for MRCL was 29.9 months (95% CI, 27-44.6) and 8.9 months (95% CI 4.5-12.0)., Conclusions: To the best of our knowledge, this is the largest retrospective study of patients with SS and MRCL. It provides an analysis of real-world clinical outcomes among patients treated at major sarcoma cancer centers and could inform treatment decisions and design of clinical trials. In general, the survival outcomes for this selected population appear more favorable than in published literature., (© 2020 The Authors and Merck Sharp & Dohme Corp. Cancer Medicine published by John Wiley & Sons Ltd.)

Limb synovial sarcoma (LSS) patients with metastasis at presentation usually have a very poor prognosis. Little is known about survival prediction and risk factors in these patients owing to the condition's rarity. Thus, this study examined the survival and prognostic variables of metastatic LSS.Clinical data for LSS patients with metastasis at presentation from 1975 to 2016 were obtained from the surveillance, epidemiology, and end results database. The Kaplan-Meier method was used to determine the survival curves. Univariate and multivariate Cox regression analysis were conducted to identify the prognostic predictors.The study enrolled 217 patients. Male predominance was observed in the metastatic LSS group. The median age at diagnosis of this population was 40 years. The subtypes were "not otherwise specified" (49.8%), spindle cell (32.7%), biphasic (17.1%), and epithelioid cell (0.5%). The 3-year overall and cancer-specific survival rates of the entire group were 27.2% and 28.3%, respectively. Tumor size <10 cm, surgery, radiotherapy, and chemotherapy were independent predictors of improved overall and cancer-specific survival in the multivariate analyses.Comprehensive treatment for LSS patients with metastasis at diagnosis is necessary and effective and can prolong survival.

Synovial sarcoma, an uncommon cancer, typically affects young adults. Survival rates range from 36% to 76%, decreasing significantly when metastases are present. Synovial sarcomas form in soft tissues, often near bones, with about 10% demonstrating ossification in the tumor. The literature is inconclusive on whether the presence of ossification portends a worse prognosis. To this end, we analyzed our genetic mouse models of synovial sarcoma to determine the extent of ossification in the tumors and its relationship with morbidity. We noted higher ossification within our metastatic mouse model of synovial sarcoma. Not only did we observe ossification within the tumors at a frequency of 7%, but an even higher frequency, 72%, of bone reactivity was detected by radiography. An enrichment of bone development genes was associated with primary tumors, even in the absence of an ossification phenotype. In spite of the ossification being intricately linked with the metastatic model, the presence of ossification was not associated with a faster or worse morbidity in the mice. Our conclusion is that both metastasis and ossification are dependent on time, but that they are independent of one another.

Background: The role of neoadjuvant chemotherapy for localized synovial sarcoma is still controversial. This study aimed to explore the influence of neoadjuvant chemotherapy combined with surgery in localized synovial sarcoma through analysis of our hospital's patient records., Patients and Methods: A total of 122 patients diagnosed with synovial sarcoma were enrolled in this study from January 1980 to December 2016 at the Cancer Institute Hospital of The Japanese Foundation for Cancer Research. The impact of neoadjuvant chemotherapy on overall survival was assessed to show how clinicopathological factors (e.g. age, tumor size, treatment, dose intensity, pathological pattern and histological grading) influenced patient prognosis., Results: Among 106 patients, 76 (71.7%) received neoadjuvant chemotherapy and 30 (28.3%) did not. The median follow-up was 39.2 (range=12-286) months. The 5-year and 10-year overall survival rates were 65.4% and 58.4% respectively. The tumor size and histological grade influenced the patient's overall survival (p<0.05). Among the patients with grade 2 tumor, tumor size did not influence prognosis. Neoadjuvant chemotherapy improved the overall survival of patients who had grade 3 tumors., Conclusion: Treatment with neoadjuvant chemotherapy proved beneficial for high-risk patients with grade 3 synovial sarcoma but was not effective for those with low-risk and grade 2 tumor. Tumor size and histological grade were important factors in patient prognosis but had no connection with pathological patterns., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objectives: The purpose of this study was to investigate the patient population and outcomes of synovial sarcoma at a single institution., Methods: A retrospective review of the medical records of 28 patients with synovial sarcoma diagnosed from 1992 to 2017 was performed. Demographics, staging, disease location, treatment, and response to treatment were reviewed., Results: Individuals with larger tumors at the time of presentation had an increased risk of death. An additional factor associated with poor prognosis in synovial sarcoma was increasing patient age. The patient population had a higher rate of nonextremity disease and lower overall survival when compared with national averages., Conclusions: Nonextremity disease and large size of tumor at presentation may have contributed to the disparity in institutional outcomes from the national averages. The advanced presentation of synovial sarcoma remains a significant challenge in improving patient survival.

Introduction: Synovial sarcoma (SS) is a tumor of unknown origin and is extremely rare in the central nervous system. Most studies on intracranial SS included only one or two cases. To better understand the disease, we review a series of primary intracranial SS., Method and Materials: 16 primary intracranial SS in Tiantan Hospital during 2008-2017 were included. The clinical characteristics, including radiological and histological examination, operative records, and prognoses were reviewed., Result: The case series included nine male and seven female patients with an average age of 23.8 years. Radiological results showed that the supratentorial region (81.25%) was the most common site of the brain involved. All patients were misdiagnosed as non-SS tumors. Gross total resection (GTR) was achieved in 12 cases (75.0%), and subtotal resection (STR) was achieved in 4 cases. All cases showed the characteristic SYT-SSX fusion gene, as detected by RT-PCR. The mean progression-free survival time (PFS) was 10.0 months and the mean overall survival time (OS) was 15.5 months. Multivariate analysis revealed that GTR and postoperative adjuvant radiotherapy were independent factors for PFS (HR = 6.143, 95% CI = 1.491-25.312; P = 0.012, HR = 6.143, 95% CI = 1.491-25.312; P = 0.012 respectively) and OS (HR = 9.000, 95% CI = 1.627-49.773; P = 0.012, HR = 0.017, 95% CI = 0.001-0.213; P = 0.002 respectively)., Conclusion: Intracranial SS were more frequently observed in the supratentorial region and in young patients without sex predilection. We recommend adjuvant radiation regardless of the extent of resection. More patients and longer follow-up periods were needed to further elucidate the biological features of intracranial SS., (Copyright © 2019. Published by Elsevier Ltd.)

Background: Cardiac synovial sarcoma (CSS) is an extremely rare malignant tumor with a severe prognosis, due to frequent relapses and metastases. To obtain useful information for treatment protocols, we analyzed survival and therapy data from the cases reported in the literature., Methods: A search of MEDLINE was performed throughout December 2018. Using key words relating to primary CSS, we collected from the literature a total of 97 cases, mainly consisting of single case reports. To identify predictors of overall survival, statistical analyses were performed on a selected cohort of 55 patients for whom relevant clinicopathological data were available, including surgery and adjuvant therapy., Results: The univariable analysis revealed that patients in their first three decades of life have better overall survival. The univariable analysis also showed that patients not receiving adjuvant chemotherapy are at increased risk of death. In the multivariable analysis, tumor resection and chemotherapy are factors significantly improving overall survival., Conclusion: The survival of patients with CSS is positively influenced by a young patient's age and greatly improved by the administration of chemotherapy, even in the absence of tumor resection., (© 2019 Wiley Periodicals, Inc.)

Background: Pericardial synovial sarcomas (PSS) are very rare tumors, with dismal prognosis and limited data. We describe the clinical features and identify prognostic factors of primary PSS., Case Report: We describe the case of a 56-year-old male patient with PSS managed by the multidisciplinary team of thoracic oncology. The therapeutic plan comprised surgery, chemotherapy, stereotactic radiosurgery and targeted therapy, with excellent results., Materials and Methods: Data from 37 cases reported in English during the past 20 years were gathered and analyzed. PSS was found to occur at a mean age of 36±17.082 (range=13-67) years. Survival analysis was performed on 20 cases with follow-up of at least 6 months., Conclusion: Only complete resection of the tumor seems to be an independent prognostic factor. To our knowledge, this is the first report on the safety and effectivity of pazopanib in PSS and may provide guidance for similar cases in the future., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Sorafenib and dacarbazine have low single-agent response rates in metastatic sarcomas. As angiogenesis inhibitors can enhance the efficacy of chemotherapy, we investigated the combination of sorafenib and dacarbazine in select sarcoma subtypes., Materials and Methods: Patients with leiomyosarcoma (LMS), synovial sarcoma (SS), or malignant peripheral nerve sheath tumors (MPNST) with up to two previous lines of therapy and adequate hepatic, renal, and marrow function received 3-week cycles of sorafenib at 400 mg oral twice daily and dacarbazine 1,000 mg/m 2 intravenously (later reduced to 850 mg/m 2 ). Patients were evaluated for response every 6 weeks. The primary objective was to determine the disease control rate (DCR) of sorafenib plus dacarbazine in the selected sarcoma subtypes., Results: The study included 37 patients (19 female); median age was 55 years (range 26-87); and histologies included LMS (22), SS (11), and MPNST (4). The DCR was 46% (17/37). Median progression-free survival was 13.4 weeks. The RECIST response rate was 14% (5/37). The Choi response rate was 51% (19/37). Median overall survival was 13.2 months. Of the first 25 patients, 15 (60%) required dacarbazine dose reductions for hematologic toxicity, with one episode of grade 5 neutropenic fever. After reducing the starting dose of dacarbazine to 850 mg/m 2 , only 3 of the final 12 (25%) patients required dose reduction., Conclusion: This phase II study met its primary endpoint with an 18-week DCR of 46%. The clinical activity of dacarbazine plus sorafenib in patients with these diagnoses is modest., Implications for Practice: Metastatic soft tissue sarcomas are a heterogeneous group of relatively rare malignancies. Most patients are treated with cytotoxic chemotherapy or targeted therapy in the form of tyrosine kinase inhibitors. Response rates are relatively low, and there is a need for better therapies. This clinical trial demonstrates that combining a cytotoxic therapy (dacarbazine) with an antiangiogenic small molecule (sorafenib) is feasible and associated with favorable disease-control rates; however, it also increases the potential for significant toxicity., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2018.)

Purpose: Factors affecting long-term outcomes of synovial sarcoma (SS) remain unknown. Here, we aimed to investigate the long-term oncological outcomes and prognostic factors in a large group of patients with surgically-treated localized SS., Patients and Methods: Between 1980 and 2011, 191 patients (94 males and 97 females) were treated at a single hospital with a minimum follow-up of 5 years for survivors. The median age was 35 years (range, 3-80 years), and the median follow-up period was 83 months (range, 3-235 months)., Results: Disease-specific survival was 76.4% and 60.4% at 5 and 10 years, respectively. Local recurrence occurred in 23 patients at a median of 33 months (range, 6-158 months), and metastasis occurred in 73 patients at a median of 20 months (range, 2-166 months). In multivariate analysis, grade 3 tumors sized ≥5 cm were significantly associated with worse survival. Ten patients (5.2%) developed metastasis more than 5 years after surgery., Conclusion: Tumor size and grade govern prognosis in surgically-treated localized SS in long-term settings. If adequately treated patients have not developed metastases for 5 years after surgery, the risk of subsequently developing metastases was lower than previously reported., (© 2019 Wiley Periodicals, Inc.)

Background and Purpose: We reviewed our experience of synovial sarcoma to identify factors predictive of local recurrence and overall survival, the impact of chemotherapy and outcomes after surgical excision alone., Materials and Methods: 81 patients were treated between 1997 and 2014 of mean age 39 years (8-78). Tumours were in the extremity in 55 (67%). 9 patients presented with metastases and 10 with unresectable disease. Mean follow-up was 3.7 years (SD 3.8). Treatment groups were palliative, surgery only, surgery and radiotherapy, or surgery with chemotherapy (with or without radiotherapy)., Results: Local recurrence-free survival (LRFS) was 73% at 5 years, and 68% at 10 and 15 years. In multivariate analysis, positive surgical margins were an independent predictor of LRFS. Overall survival (OS) was 50% at 5 years for all patients, and 62% at 5 years for those treated with curative intent. Larger tumour size and non-extremity locations were predictors of poorer OS. Patients who had chemotherapy did not have significantly better OS or LRS than others., Interpretation: These results show that where feasible, curative resection should not be delayed for chemotherapy. Treatment with surgery only can be associated with good outcomes in selected patients with smaller extremity tumours; although our series is small.

Synovial sarcomas hold a low genomic complexity, making it distinct from other types of soft-tissue sarcomas. Many studies focused on targeting the SS18-SSX fusion protein, which presents in over 90% of human synovial sarcomas. This protein acts as an oncogenic promoter in the tumorigenesis of synovial sarcomas, making it an ideal therapeutic target. However, to date there have been no effective strategies targeting SS18-SSX for the treatment of synovial sarcomas. Therefore, it is an urgent need to identify alternative therapeutic targets. More recently, CDK9, a protein involved in RNA transcription regulation, has been investigated for its role in the pathogenesis of cancer. However, the expression and function of CDK9 in synovial sarcomas remains to be elucidated. In the present study, we found that CDK9 was to be largely localized to the cell nucleus, and highly expressed in all tested human synovial sarcoma cell lines and over 90% of human sarcoma tissue microarray samples. High-CDK9 expression was associated with a poorer patient prognosis of human sarcomas. Inhibition of CDK9, with either siRNA or a CDK9 inhibitor, prevented synovial sarcoma cell growth and proliferation in a dose-dependent manner. This was also accompanied with a reduction in the phosphorylation of RNA polymerase II and an increase in the expression of anti-apoptotic proteins. Moreover, CDK9 inhibition decreased sarcoma cell spheroid formation and cell motility. Collectively, these findings highlight the importance of CDK9 in human synovial sarcoma cell growth and proliferation. Therefore, CDK9 may represent a promising target for the treatment of synovial sarcomas. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:510-521, 2019., (© 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Background: Synovial sarcoma of the foot/ankle is rare. Mutilating surgery is often discussed., Methods: Patients registered from 1981 to 2013 were analyzed. Cooperative Weichteilsarkom Studiengruppe (CWS) protocols recommend chemotherapy for all synovial sarcoma patients., Results: Thirty-two of 330 patients with localized synovial sarcoma had their tumor at the foot/ankle. Eleven of thirty-two tumors were >5 cm. Twenty were T1, 11 T2, and one TX, respectively. Eight (25%) patients underwent primary complete resection with free margins (Intergroup Rhabdomyosarcoma Study [IRS] I), 12 of 32 (38%) primary complete resection with positive margins (IRS II), and 12 of 32 (38%) had macroscopic residuals (IRS III). The best surgical result at any time was R0 in 19, R1 in 10 and R2 in one patient, and missing in two. Mutilation was documented in 14 of 32 (44%). Radiotherapy was conducted in 20 patients. All patients achieved a first complete remission. Five-year-event-free survival and overall survival rates were 80% and 86%, respectively. Four patients suffered local and four other metastatic recurrences. IRS and the best surgical result at any time did not correlate with survival. There was no prognostic difference between R0- and R1-resection., Conclusion: Survival expectancies for patients with localized synovial sarcomas of the foot/ankle compare favorably to that of those with other affected sites., Discussion: Further studies are needed to set the limits of minimally required aggressiveness of local therapies., (© 2018 Wiley Periodicals, Inc.)

The association between the immune status within the tumor microenvironment and prognosis in synovial sarcoma is not well understood. We aimed to investigate the tumor immune microenvironment and analyze its prognostic impact for patients with synovial sarcoma. A total of 36 primary patients who were treated in our institution were retrospectively evaluated. Infiltration of lymphocytes (CD4+, CD8+, and FOXP3+), CD163+ macrophages, and expression of human leukocyte antigen (HLA) class I and programmed death ligand 1 (PD-L1) were evaluated by immunohistochemistry. Moreover, we investigated PD-L1 and programmed death ligand 2 (PD-L2) mRNA expression in 19 of the 36 cases, using real-time PCR. The Kaplan-Meier method was used to estimate overall survival and progression-free survival. Infiltration of lymphocytes and macrophages varied among the patients. Furthermore, the expression of HLA class I was negative or downregulated in 11 specimens. No PD-L1 expression was observed using immunohistochemistry. Moreover, although PD-L1 mRNA expression was observed in 18 of 19 specimens, the expression level was low. A higher infiltration of CD8+ or FOXP3+ lymphocytes in patients was associated with a favorable overall survival. In addition, a higher infiltration of CD163+ macrophages indicated a significantly worse overall and progression-free survival. Infiltration of CD4+ lymphocytes, HLA class I, PD-L1, and PD-L2 expression were not associated with patient prognosis. This represents the first report investigating the tumor immune microenvironment as a prognostic factor in synovial sarcoma, indicating that CD163+ macrophages are associated with tumor progression. Our results underscore the clinical significance of the tumor immune microenvironment in synovial sarcoma., (© 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Objective: To evaluate the clinicopathological characteristics of foot and ankle soft tissue and bone tumor, and to analyze the prognosis and the related factors of malignant tumors in this site. Methods: 74 patients with soft tissue and bone tumors of foot and ankle from January 2006 to February 2017 were retrospectively analyzed. The clinicopathological characteristics, the treatment and survival status of malignant tumors were followed up, and the clinical and therapeutic factors related to prognosis were analyzed. Results: Of the 74 patients, 34 were males and 40 were females. The male to female ratio was 1∶1.18; the age ranged from 12 to 64 years and the median age was 42 years. Tumors located in forefoot of 22 cases, 22 in midfoot, 10 in hind foot, 14 in ankle joint and 6 in multiple sites. 14 cases were bone tumors, including 7 benign and 7 malignant, and 60 cases were soft tissue tumors, including 14 benign and 46 malignant. The most common malignant soft tissue tumors were synovial sarcomas (13 cases), and the most common benign soft tissue tumors were hemangiomas (4 cases). 44 cases of malignant tumors underwent surgery were followed up, of which were 7 bone and 37 soft tissue malignant tumors. Limb salvage surgeries were performed in 33 cases and amputation in 11 cases. The median follow-up time was 69.8 months, and the median survival time was 40.7 months. The 1-year, 3-year and 5-year survival rate of soft tissue malignant tumors was 88.0%, 73.0%, and 63.0%, respectively. The 1-year, 3-year and 5-year survival rate of bone malignant tumors was 86.0%, 57.0% and 57.0%, respectively. Univariate analysis showed that the prognostic factors affecting 5-year survival rate were tumor size and adjuvant therapy ( P <0.05). Patient's gender, age, tumor location, histological type and surgical procedure had no effect on overall survival( P >0.05). Multivariate analysis showed that tumor size was an independent prognostic factor ( RR =7.262, P =0.005). Conclusions: Forefoot and midfoot are more common in foot and ankle soft tissue and bone tumors. Synovial sarcoma is the most common diagnosis in malignant soft tissue tumors, and hemangioma is the most common diagnosis in benign soft tissue tumors. The prognostic factor of malignant soft tissue and bone tumors in foot and ankle is tumor size. Patients with the tumor size of 5 cm or more have a worse prognosis.

Background: Synovial sarcoma is a rare malignant soft tissue tumor, more common in adolescents and young adults and entails a poor prognosis. Several good prognostic factors have been well established such as age less than 25, size less than 5 cm and absence of a poorly differentiated component. Inflammation has a well-established role in tumor proliferation and survival. The aim of this study was to investigate the prognostic significance of the neutrophil/lymphocyte ratio (NLR) in a large cohort of synovial sarcoma patients., Methods: Retrospective study of 169 consecutive patients. We analyzed the relation of preoperative NLR on disease-free survival (DFS) and overall survival (OS) using Kaplan-Meier curves and Cox proportional models., Results: Of the 169 patients included, there were 90(53.3%) females and 79(46.7%) males. Median age was 32yo (11-73). Median survival was 34.1 and mean disease-free survival was 21.4 months. Mean tumor size was 12.5 cm (1.2-77 cm). Applying receiver operating curve analysis, we determined a cut-off value of 3.5. In univariate and multivariate analysis, increased NLR was significantly associated with poor OS. A <3.5 NLR was an independent prognostic factor in all stages (p = 0.002)., Conclusions: NLR >3.5 was found to be a reliable prognostic factor in this cohort. Given its widespread availability, we believe it's use in clinical practice and further clinical trials should be considered., (Copyright © 2018. Published by Elsevier Ltd.)

The outcome for patients with unresectable or metastatic soft tissue sarcoma remains poor with few treatment options. Synovial sarcoma is a rare type of sarcoma, predominantly affecting adolescents and young adults. Following failure of first-line anthracycline-based chemotherapy, several salvage options are available. We reviewed the safety and efficacy of gemcitabine/docetaxel chemotherapy in two tertiary oncology centres. We identified patients treated with gemcitabine/docetaxel between 2004 and 2016 in a UK and a US oncology centre using retrospective pharmacy and medical records. Treatment response, toxicity and outcome data were collected. Twenty one patients were treated with gemcitabine/docetaxel, the majority as a second- or third-line treatment for metastatic disease. The response rate was 5% with a median progression-free survival of 2 months (95% CI 1.3-3.7). Toxicities reported were as expected for this chemotherapy combination. Treatment was not discontinued due to toxicity. Gemcitabine/docetaxel chemotherapy shows little efficacy in synovial sarcoma and should not be offered to this patient group outside a clinical trial context.

Synovial sarcoma (SS), a translocation-associated sarcoma characterized by SS18-SSX1/2 fusion, presents most often in the extremities of young adults. While SS regularly occurs in the pleuropulmonary parenchyma, the mediastinum is an exceedingly rare primary site; the literature on this subject is predominantly composed of case reports and small series, mostly without molecular confirmation. Cases of mediastinal SS were selected from our institutional and consultation archives. Diagnoses were confirmed by either SS18 fluorescence in situ hybridization (n=6) or reverse transcription polymerase chain reaction for SS18-SSX1/2 (n=15). Mediastinal SSs occurred in 21 patients (15 men; mean age, 38 y; range, 21 to 75). Only 1 patient was older than 50 years. Average tumor size was 13.5 cm (range: 6.4 to 23 cm). One tumor was biphasic and the rest were monophasic, 11 of which were poorly differentiated (52%). Of 10 cases with known fusion transcripts, 6 had SS18-SSX2 and 4 had SS18-SSX1. Follow-up was known for 16 patients (mean: 18.9 mo; range: 5 to 45): 14 had local disease progression or recurrence, and 6 had metastasis. Death from disease occurred in 11 of 16 patients (69%) at 5 to 32 months, and 5 (36%) were alive with disease at last follow-up (6 to 45 mo). Mediastinal SS is a rare and aggressive malignancy most common in patients younger than 50 years. Most are monophasic and reach large size before detection. Poorly differentiated morphology is common. SS should be included in the differential diagnosis of spindle cell, biphasic and poorly differentiated mediastinal tumors. Because of the rarity of SS at this site, molecular testing is recommended to confirm the diagnosis.

Purpose of Review: To present the current state of knowledge concerning the role of conservative surgery in the treatment of synovial sarcomas of the upper aero-digestive tract (UADT)., Recent Findings: The wider experience on synovial sarcomas involving the extremities and the results of retrospective reports focused on head and neck synovial sarcomas tend to justify a conservative surgical approach when dealing with tumors involving the UADT., Summary: UADT synovial sarcomas is an extremely rare clinical entity (only around 50 cases reported in the literature, with four more herein presented from our own surgical series), with no clear guidelines concerning its treatment. Resection should be aimed to an en-bloc removal of the tumor within uninvolved surgical margins. In fit patients, a conservative surgical approach should be preferred if it does not interfere with a complete resection and reasonable functional outcomes. Adjuvant treatments (radiotherapy and/or chemotherapy) are frequently needed in view of the aggressive behavior of such tumor, but they should be balanced according to patient's characteristics and tumor risk factors (grade, size, and previous treatments).

Background: Reported rates of the incidence of lymph node metastasis in soft tissue sarcoma vary considerably. Many are based on single-institution series and small patient populations. Certain sarcoma subtypes, including synovial sarcoma, have been associated with a higher risk of lymph node involvement. Most single centers have insufficient numbers of patients to assess lymph node metastasis accurately, but larger national databases may allow a more accurate estimation., Questions/purposes: We queried a large national database and asked the following questions: (1) What proportion of patients with soft tissue sarcoma have lymph node metastasis and distant metastasis? (2) What histologic subtypes are associated with increased risk of nodal metastasis? (3) What is the impact of lymph node metastases and histologic subtype on survival? (4) Does lymph node excision improve survival of patients with soft tissue sarcoma?, Methods: The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program is a national database that covers a geographic cross-section representing approximately 28% of the US population across demographic groups. Using the SEER database, we identified 15,525 adults diagnosed with histologically confirmed soft tissue sarcoma from 2004 to 2013. Proportions of patients with lymph node or distant metastases were calculated using descriptive statistics. Overall survival was computed using the Kaplan-Meier method. Multivariate analysis was performed using Cox proportional hazard regression to calculate the association of lymph node metastasis with overall survival while controlling for patient age, sex, race, tumor size, and tumor location., Results: A total of 820 of 15,525 patients had lymph node metastasis at the time of diagnosis, yielding an overall proportion of 5.3% (95% confidence interval [CI], 4.9%-5.6%). Histologic subtypes that most frequently developed nodal metastasis were rhabdomyosarcoma, clear cell sarcoma, epithelioid sarcoma, and myxoid/round cell liposarcoma. Despite frequent reports regarding its association with lymph node metastasis, the proportion of patients with lymph node metastasis among 885 patients with synovial sarcoma (4.2%) was not different from the proportion with nodal metastasis in the overall soft tissue sarcoma population. For all soft tissue sarcomas, distant metastatic disease was present at diagnosis in 1869 (12%) patients (95% CI, 11.5%-12.6%). After controlling for relevant covariates, lymph node metastasis was associated with poorer overall survival (hazard ratio [HR], 1.34; 95% CI, 1.22-1.48; p < 0.001) as was distant metastasis (HR, 2.87; 95% CI, 2.66-3.09; p < 0.001). When comparing the subgroup of patients with positive lymph nodes, lymphadenectomy in conjunction with local excision/limb salvage was associated with the highest overall 5-year survival (HR, 0.46; 95% CI, 0.31-0.67; p < 0.001)., Conclusions: In clarifying the overall proportion of patients with soft tissue sarcoma with nodal metastases, the current study indicates that lymph node metastases occur at a higher proportion than previous studies have suggested and that synovial sarcoma is not associated with a higher risk of lymphatic spread compared with soft tissue sarcoma overall. Patients with lymph node metastases are associated with poorer survival than those without metastases. Further investigation is needed to clarify the apparent improved overall survival after lymphadenectomy in the setting of nodal metastasis from soft tissue sarcoma., Level of Evidence: Level II, prognostic study.

Background: Our previous studies reported that SHC SH2-domain binding protein 1 (SHCBP1) functions as an oncogene via promoting cell proliferations in synovial sarcoma (SS) cells. However, whether SHCBP1 has any effect on tumor metastasis remains unexplored., Methods: The expression of SHCBP1 was analyzed in 76 SS tissues and two SS cell lines by immunohistochemistry and real-time RT-PCR. The relationship between SHCBP1 expression and the clinicopathological features of SS was investigated. The role of SHCBP1 in SS cell adhesion, migration, invasion and angiogenesis was explored by adhesion, Wound healing, Transwell, and Matrigel tube formation assays. Western blotting was conducted to detect the protein expressions of TGF-β1/Smad signaling pathway and EMT-related markers. The key molecules associated with migration, invasion and EMT were evaluated by immunohistochemistry in tumor specimens., Results: In current study, we demonstrated that SHCBP1 overexpression significantly enhanced adhesion, migration, invasion and angiogenesis of SS cells. In contrast, SHCBP1 knockdown elicited the opposite effects on these phenotypes in vitro. SHCBP1 promoted tumor metastasis through inducing epithelial-mesenchymal transition (EMT) in SS cells. SHCBP1 knockdown could block the incidence of metastasis and EMT in SS cells. Furthermore, transforming growth factor-β1 (TGF-β1) induced SHCBP1 expression in a time-dependent pattern and SHCBP1 knockdown inhibited TGF-β1-induced EMT. The activation of the TGF-β1/Smad signaling pathway was involved in the oncogenic functions of SHCBP1 in SS. In addition, high expression of SHCBP1 in SS patients was associated with tumor progression and decreased survival as well as poor prognosis., Conclusions: Taken together, our results indicate that SHCBP1 may promote the metastasis of SS by inducing EMT through targeting TGF-β1/Smad signaling pathway and can be a potential molecular target for SS therapy.

Introduction: The role of adjuvant chemotherapy (AC) for synovial sarcoma (SS) is controversial. Using a large national dataset we evaluate the impact of AC on overall survival (OS) following curative-intent resection of SS., Methods: Patients with stage I-III SS 2004-2012 undergoing resection were identified in the National Cancer Data Base. Clinicopathologic factors associated with OS were identified using Cox proportional-hazard modeling, adjusting for factors associated with receipt of AC., Results: Among 544 patients, 131 received AC. Median age of the cohort was 42 years; 269 were female. AC was not associated with OS in univariate analysis in the overall cohort. After stratification by stage, AC was associated with prolonged OS in univariate analysis in stage III patients only (P = 0.028), which remained significant in multivariable analysis (P = 0.033). Other factors associated with OS in stage III patients were age >55 years, (P = 0.001), positive margins (P = 0.037), biphasic histology (P = 0.013), and adjuvant radiation (P < 0.001). The association between AC and OS remained significant after adjustment for factors predictive of receipt of AC., Conclusions: In this national cohort, AC was associated with prolonged OS for SS for stage III patients but not in lower stages. Less restricted use of this therapy may be warranted in this population., (© 2017 Wiley Periodicals, Inc.)

Background: Multimodal risk-adapted treatment is used in paediatric protocols for synovial sarcoma (SS). Retrospective analyses suggest that low-risk SS patients can be safely treated with surgery alone, but no prospective studies have confirmed the safety of this approach. This analysis pooled data from the two prospective clinical trials to assess outcomes in SS patients treated with a surgery-only approach and to identify predictors of treatment failure., Methods: Patients with localised SS enrolled on the European paediatric Soft tissue sarcoma Study Group (EpSSG) NRSTS2005 and on the Children Oncology Group (COG) ARST0332 trials, treated with surgery alone were eligible for this analysis. Patients must have undergone initial complete resection with histologically free margins, with a grade 2 tumour of any size or a grade 3 tumour ≤5 cm., Results: Sixty patients under 21 years of age were eligible for the analysis; 36 enrolled in the COG (from 2007 to 2012) and 24 in the EpSSG study (from 2005 to 2012). The 3-year event-free survival was 90% (median follow-up 5.2 years, range 1.9-9.1). All eight events were local tumour recurrence, whereas no metastatic recurrences were seen. All patients with recurrence were effectively salvaged, resulting in 100% overall survival., Conclusion: This joint prospective analysis showed that patients with adequately resected ≤5 cm SS, regardless of grade, can be safely treated with a surgery-only approach. Avoiding the use of adjuvant chemotherapy and radiotherapy in this low-risk patient population may decrease both short- and long-term morbidity and mortality., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Tumors expressing programmed death ligand 1 (PD-L1) interact with the corresponding negative-signal generating immune receptor on the surface of CD8 T cells, PD-1, thereby suppressing antitumor activity. Therapeutics blocking this interaction have shown promise in various cancers by restoring functional antitumor T-cell activity. We explored the degree of PD-L1, PD-1, and CD8 expression in a retrospective analysis of 29 clinical synovial sarcoma samples. Quantitative immunohistochemistry and multiplex immunofluorescence were used to determine relative quantification of CD8 + and PD-1 + T cells and PD-L1 expression within the intratumor area and the interface between the tumor and the surrounding nontumor tissue (i.e., invasive margin), and colocalization of these factors, respectively. PD-L1, PD-1, and CD8 cell densities in the tumor-invasive margins were significantly higher in the metastatic tumors than the primary tumors (P < 0.01), and PD-L1, PD-1, and CD8 cell densities were all significantly positively correlated with one other (P < 0.0001). PD-1 cell density in the tumor-invasive margin was significantly associated with worse progression-free survival. Multiplex immunofluorescence demonstrated coexpression of PD-1 and CD8 on lymphocytes within the invasive margin, as well as relative proximity between PD-1 + CD8 cells and PD-L1 + tumor cells. Our results provide a preclinical rationale for screening of patients with synovial sarcoma for the colocalization of CD8, PD-1, and PD-L1, which may be a marker for response to PD-1 blockade therapy. Cancer Immunol Res; 5(2); 118-26. ©2016 AACR., Competing Interests: OF POTENTIAL CONFLICTS OF INTEREST: None, (©2016 American Association for Cancer Research.)

While surgical resection (±radiotherapy) is standard treatment for localized soft tissue sarcomas (STS), chemotherapy is the mainstay for managing locally advanced and metastatic disease. Expanding knowledge of the biologies and sensitivities of STS histotypes, in conjunction with results from a growing collection of retrospective reviews and prospective randomized studies, point to the importance of treating in consideration of histological subtype. Doxorubicin ± ifosfamide continues to be standard first-line therapy for most STS subtypes. Main options for second- or later-line therapy include trabectedin, dacarbazine, gemcitabine combinations, pazopanib and, most recently, eribulin. Using illustrative case studies, treatment options are reviewed for three of the more common STS subtypes - uterine leiomyosarcoma, liposarcoma and synovial sarcoma - with a focus on use of trabectedin.

Synovial sarcoma (SS) is an aggressive soft tissue sarcoma with a poor prognosis and, thus, novel therapeutic strategies for SS are urgently required. In the present study, we investigated the functional and therapeutic relevance of hepatocyte growth factor (HGF)/c-MET signaling in SS. Both HGF and c-MET were highly expressed in Yamato-SS cells, resulting in activation of c-MET and its downstream AKT and extracellular signal-regulated kinase signaling pathways, whereas c-MET was expressed but not activated in SYO-1 or HS-SY-II cells. c-MET-activated Yamato-SS cells showed higher anchorage-independent growth ability and less sensitivity to chemotherapeutic agents than did c-MET-inactivated SYO-1 or HS-SY-II cells. INC280, a selective c-MET inhibitor, inhibited growth of Yamato-SS cells both in vitro and in vivo but not that of SYO-1 or HS-SY-II cells. INC280 induced cell cycle arrest and apoptosis, and blocked phosphorylation of c-MET and its downstream effectors in Yamato-SS cells. Co-expression of HGF and c-MET in SS clinical samples correlated with a poor prognosis in patients with SS. Taken together, activation of HGF/c-MET signaling in an autocrine fashion leads to an aggressive phenotype in SS and targeting of this signaling exerts superior antitumor effects on c-MET-activated SS. HGF/c-MET expression status is a potential biomarker for identification of SS patients with a worse prognosis who can benefit from c-MET inhibitors., (© 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: The prognosis of early stage synovial sarcomas is not well-defined since long-term follow-up is lacking in most studies. The optimal use of surgery, radiation, and chemotherapy needs to be clarified for this group., Methods: From 1994 to 2012, 63 patients were treated for localized synovial sarcoma with T1 (<5 cm) tumors. There were 27 males and 36 females. Mean follow-up was 85 months (range 13-210)., Results: At 10 years, local recurrence-free survival was 82% (95% confidence interval [CI] 67-97%), and distant recurrence-free survival was 95% (95%CI 89-100%). Two patients developed metastases after 10 years. Local recurrence was associated with lack of re-excision and treatment by non-oncologic surgeons. Microscopic residual tumor was found in 43% of re-excised specimens. Metastasis was associated with local recurrence, tumor size ≥3 cm, and treatment by non-oncologic surgeons. Radiation and chemotherapy treatment did not have a significant effect in this patient cohort., Conclusions: Early stage synovial sarcomas with T1 tumors have a relatively favorable prognosis but the potential for late relapse, and long-term follow-up beyond 10 years is recommended. Re-excision of the tumor bed and definitive treatment by trained oncologic surgeons may decrease the risk of local recurrence and metastasis. J. Surg. Oncol. 2016;114:490-494. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

To clarify the clinicopathological and biological role of hepatoma-derived growth factor (HDGF) and β-catenin in synovial sarcoma. Our results showed that histological type and HDGF/β-catenin expression were the two important independent prognostic factors for overall survival in synovial sarcoma patients. HDGF knockdown dramatically inhibited cellular proliferation, colony formation, and migration but induced G1 phase arrest and apoptosis in SW982 cells. Recombinant HDGF enhanced synovial sarcoma cell growth and partially retrieved the cell growth suppression in SW982 cells upon HDGF knockdown. HDGF knockdown dramatically suppressed β-catenin and its downstream gene expression in SW982 cells. Intriguingly, β-catenin knockdown dramatically suppressed HDGF expression in SW982 cells. A direct interaction of HDGF and β-catenin was found in SW982 cells. Three HDGF-binding elements in β-catenin promoter were found and specific for transcriptional activation of β-catenin in SW982 cells. In conclusion, our findings first indicate that the interaction of HDGF and β-catenin may play a crucial role in tumorigenesis of synovial sarcoma.

Background: Prognostic factors for localized synovial sarcoma are well defined. However, few data exist regarding patients with metastases at diagnosis. Poor outcome is described but the optimal therapeutic regimen remains unclear. Our aim was to assess the outcome, identify prognostic factors, and analyze treatment strategies., Methods: Patients <21 years with synovial sarcoma and primary distant metastases treated in the consecutive prospective European Cooperative Weichteilsarkom Studiengruppe trials 1980-2010 were analyzed., Results: Twenty-nine of 296 patients had primary metastases. Twenty-seven could be included. Median age was 16.7 years. Primaries were mainly located in the limbs (78%) and 74% were ≥10 cm. Metastases involved the lungs in all patients. Two patients presented with synchronous bone metastases. Sixty-three percent of patients achieved a first remission, whereas only 26% maintained it. Relapses were metastatic with pulmonary metastases in nearly all patients. Five-year event-free survival and overall survival (OS) rates were 26% and 30%, respectively. Prognosis was best for patients with oligometastatic lung metastases (5-year OS probability 85%). Prognosis was worse for patients with multiple bilateral lung metastases (5-year OS 13%) and even poorer for those with concurrent bone metastases. Treatment elements associated with superior survival were adequate local therapy of the primary tumor and, if feasible, for metastases, chemotherapy with an ifosfamide/doxorubicin-based regimen. The use of whole lung irradiation was not correlated with better outcomes., Conclusions: The overall prognosis of primary metastatic synovial sarcoma is poor. However, individuals with oligometastatic lung metastases had very good chance for long-term survival when treated with adequate multimodal therapy., (© 2016 Wiley Periodicals, Inc.)

Importance: Synovial cell sarcoma of the head and neck (SCSHN) is a rare tumor associated with significant morbidity and mortality. The literature regarding these tumors is limited to case series and case reports. We used data from the population-based US Surveillance, Epidemiology, and End Results (SEER) cancer registry to determine factors affecting both overall survival and disease-specific survival of patients with SCSHN., Objective: To determine the clinicopathologic and therapeutic factors determining survival in patients with SCSHN., Design, Setting, and Participants: The SEER registry was reviewed for patients with primary SCSHN from January 1, 1973, to January 1, 2011., Main Outcomes and Measures: Overall survival (OS) and disease-specific survival., Results: A total of 167 cases of SCSHN were identified. The mean (SD) age at diagnosis was 37.9 (17.3) years, and 100 (59.9%) of the patients were males. The monophasic spindle cell and biphasic variants were the most common histologic subtypes. Surgical resection and radiotherapy were performed in 150 (89.8%) and 108 (64.7%) of the cases, respectively. The median OS at 2, 5, and 10 years was 77%, 66%, and 53%, respectively. Univariate Kaplan-Meier survival analysis revealed that age, race, and tumor stage and size were associated with improved survival. Histologic subtype was not associated with significant differences in survival. Radiotherapy was associated with improved disease-specific survival (hazard ratio [HR], 0.29 [95% CI, 0.12-0.68]; P = .003), but surgical management was not associated with improved survival (HR, 0.52 [95% CI, 0.19-1.46]; P = .21). Multivariate Cox regression analysis revealed that size greater than 5 cm (adjusted HR, 3.60 [95% CI, 1.43-9.08]; P = .007) and stage at presentation (adjusted HR, 3.86 [95% CI, 2.01-7.44]; P < .001) were independent determinants of OS. In separate analysis of cohorts with tumors 5 cm or less and larger than 5 cm, stage at presentation was found to be a significant indicator of the probability of survival in both cohorts (adjusted HR, 3.10 [95% CI, 1.46-6.60]; P = .003 and 5.32 [95% CI, 1.49-18.98]; P = .01, respectively); surgical resection and radiotherapy were not associated with differential survival outcomes using this model., Conclusions and Relevance: Synovial cell sarcoma of the head and neck is rare. Independent significant determinants of survival include size (>5 cm) and stage at presentation. Histologic subtype of the tumor is not a significant indicator of the probability of survival. Surgical resection and radiotherapy were not independent determinants of survival.

Introduction: Previous studies in metastatic soft tissue sarcomas (STS) showed that synovial sarcomas tend to have better survival rates and a higher chemosensitivity than other STS subtypes. However, data are derived from relatively small subgroups and statistical significance of these observations is lacking. Larger cohorts are necessary to define and confirm the specific characteristics of this subtype., Patients and Methods: Patient data were retrieved from 15 European Organisation for Research and Treatment of Cancer advanced first-line STS trials. Patient characteristics, survival and treatment response of synovial sarcoma patients were compared to other STS patients. Univariable and multivariable analyses were performed to evaluate prognostic factors., Results: In total, 3330 advanced STS patients were retrieved, of whom 313 had a synovial sarcoma. Synovial sarcoma patients were significantly younger (median 40 versus 52 years), more often had extremity primary tumours and had a better performance status (PS 0: 50.2 versus 43.4%) compared to other STS patients. Additionally, synovial sarcoma patients had a significantly better response to chemotherapy (responders: 27.8 versus 18.8%) and better survival rates (progression free survival [PFS]: 6.3 versus 3.7 months; Overall survival [OS]: 15.0 versus 11.7 months). Age, PS, and presence of metastatic disease were defined as prognostic factors for PFS and OS in the univariable analysis. The last two factors were confirmed in the multivariable analysis for OS., Discussion: Advanced synovial sarcomas are a distinct subgroup of STS, with a better response to systemic chemotherapy and longer PFS and OS. These results should be taken into account in the design of future synovial sarcoma specific studies., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Because the efficacy and safety of pazopanib in Japanese patients with soft tissue sarcoma (STS) had not been evaluated previously in a large-scale cohort, the authors investigated the efficacy and safety of pazopanib in 156 Japanese patients with relapsed STS. This was a retrospective study based on the collection of real-life, postmarketing surveillance data., Methods: Patients received pazopanib with the objective of treating local recurrence (n = 20), metastasis (n = 104), and both (n = 32). The patient median age was 53.8 years. The primary objective of this study was to clarify the efficacy of pazopanib for patients with STS., Results: The median treatment duration was 28.7 weeks, and the average dose intensity of pazopanib was 609 mg. Adverse events occurred in 127 patients (81.4%). In addition to the main common toxicities, such as hypertension and liver disorder, pneumothorax (n = 11) and thrombocytopenia (n = 16) also were observed. The median progression-free survival for all patients was 15.4 weeks. The median progression-free survival for patients with leiomyosarcoma, synovial sarcoma, undifferentiated pleomorphic sarcoma, and liposarcoma was 18.6 weeks, 16.4 weeks, 15.3 weeks, and 8 weeks, respectively. The median survival for all patients was 11.2 months. The median survival for patients with leiomyosarcoma, synovial sarcoma, undifferentiated pleomorphic sarcoma, and liposarcoma was 20.1 months, 10.6 months, 9.5 months, and 7.3 months, respectively., Conclusions: There were apparent differences in the efficacy of pazopanib treatment among histologic types of STS. Pazopanib treatment is a new treatment option; however, adverse events like pneumothorax and thrombocytopenia, which did not occur frequently in the PALETTE study (pazopanib for metastatic soft-tissue sarcoma), should be taken into consideration. Cancer 2016;122:1408-16. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society., (© 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.)

Synovial sarcoma (SS) is a rare high-grade malignant mesenchymal tumor affecting children, adolescents, and young adults. Cytogenetically, more than 90% of SS is characterized by the t(X;18)(p11.2;q11.2), translocation resulting in two chimeric fusion genes SYT-SSX1 and SYT-SSX2, confirming histological diagnosis. Pediatric SS arises most often in soft tissues of the extremities (66% of cases), and is a localized tumor without spreading to regional lymph nodes (96% of cases) nor to metastatic sites (94% of cases). Although clinical and radiologic presentation, histologic analysis and tumor biology appear similar in pediatric and adolescent SS, outcome seems better in children than in adolescents, respectively 84% vs 60% of 5years overall survival (OS). If complete resection is the gold standard in SS, other therapeutic modalities differ between pediatric and adult populations, considering SS as an intermediate chemosensitive tumor more frequently by pediatric oncologists. Prognostic factors evaluation (tumor size, site of primary and IRS group) is necessary to establish optimal treatment strategies, with multimodal therapeutic approach in children and adolescents. Thus, recent results about the European prospective EpSSG NRSTS 05 study for children and adolescent patients with localized SS showed a 5years OS >90%. Moreover, recent somatic genetic data about SS open the debate on an appropriate strategy based and stratified on tumor genomic. Multinational prospective pediatric, adolescent and young adult study is necessary to improve optimal and appropriate approach in this rare tumor., (Copyright © 2016. Published by Elsevier Masson SAS.)

Background: We performed a retrospective nationwide study to explore age as a prognostic factor in synovial sarcoma patients., Methods: Data on 613 synovial sarcoma patients were obtained from the Netherlands Cancer Registry. The prognostic relevance of age groups (children, adolescent and young adults (AYAs), adults, and elderly) was estimated by Kaplan-Meier survival curves and multivariable Cox-proportional hazards modelling., Results: A total of 461 patients had localised disease at diagnosis. The 5-year overall survival (OS) was 89.3±4.6%, 73.0±3.8%, 54.7±3.6%, and 43.0±7.0% in children (n=54), AYAs (n=148), adults (n=204), and elderly (n=55), respectively. Treatment modalities had no significant effect on survival in the univariable analysis. Multivariable analysis identified age at diagnosis, tumour localisation, and tumour size as significant factors affecting OS. Both tumour localisation and size were equally distributed over the age groups., Conclusions: We show that outcome of synovial sarcoma patients significantly decreases with age regardless of primary tumour site, size, and treatment.