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Current Oncology (Toronto, Ont.) May 2021Synovial sarcomas (SS) represent a unique subset of soft tissue sarcomas (STS) and account for 5-10% of all STS. Synovial sarcoma differs from other STS by the... (Review)
Review
Synovial sarcomas (SS) represent a unique subset of soft tissue sarcomas (STS) and account for 5-10% of all STS. Synovial sarcoma differs from other STS by the relatively young age at diagnosis and clinical presentation. Synovial sarcomas have unique genomic characteristics and are driven by a pathognomonic t(X;18) chromosomal translocation and subsequent formation of the SS18:SSX fusion oncogenes. Similar to other STS, diagnosis can be obtained from a combination of history, physical examination, magnetic resonance imaging, biopsy and subsequent pathology, immunohistochemistry and molecular analysis. Increasing size, age and tumor grade have been demonstrated to be negative predictive factors for both local disease recurrence and metastasis. Wide surgical excision remains the standard of care for definitive treatment with adjuvant radiation utilized for larger and deeper lesions. There remains controversy surrounding the role of chemotherapy in the treatment of SS and there appears to be survival benefit in certain populations. As the understanding of the molecular and immunologic characteristics of SS evolve, several potential systematic therapies have been proposed.
Topics: Humans; Neoplasm Recurrence, Local; Oncogene Proteins, Fusion; Sarcoma, Synovial; Soft Tissue Neoplasms; Translocation, Genetic
PubMed: 34069748
DOI: 10.3390/curroncol28030177 -
Lancet (London, England) Apr 2024Afamitresgene autoleucel (afami-cel) showed acceptable safety and promising efficacy in a phase 1 trial (NCT03132922). The aim of this study was to further evaluate the...
BACKGROUND
Afamitresgene autoleucel (afami-cel) showed acceptable safety and promising efficacy in a phase 1 trial (NCT03132922). The aim of this study was to further evaluate the efficacy of afami-cel for the treatment of patients with HLA-A*02 and MAGE-A4-expressing advanced synovial sarcoma or myxoid round cell liposarcoma.
METHODS
SPEARHEAD-1 was an open-label, non-randomised, phase 2 trial done across 23 sites in Canada, the USA, and Europe. The trial included three cohorts, of which the main investigational cohort (cohort 1) is reported here. Cohort 1 included patients with HLA-A*02, aged 16-75 years, with metastatic or unresectable synovial sarcoma or myxoid round cell liposarcoma (confirmed by cytogenetics) expressing MAGE-A4, and who had received at least one previous line of anthracycline-containing or ifosfamide-containing chemotherapy. Patients received a single intravenous dose of afami-cel (transduced dose range 1·0 × 10-10·0 × 10 T cells) after lymphodepletion. The primary endpoint was overall response rate in cohort 1, assessed by a masked independent review committee using Response Evaluation Criteria in Solid Tumours (version 1.1) in the modified intention-to-treat population (all patients who received afami-cel). Adverse events, including those of special interest (cytokine release syndrome, prolonged cytopenia, and neurotoxicity), were monitored and are reported for the modified intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT04044768; recruitment is closed and follow-up is ongoing for cohorts 1 and 2, and recruitment is open for cohort 3.
FINDINGS
Between Dec 17, 2019, and July 27, 2021, 52 patients with cytogenetically confirmed synovial sarcoma (n=44) and myxoid round cell liposarcoma (n=8) were enrolled and received afami-cel in cohort 1. Patients were heavily pre-treated (median three [IQR two to four] previous lines of systemic therapy). Median follow-up time was 32·6 months (IQR 29·4-36·1). Overall response rate was 37% (19 of 52; 95% CI 24-51) overall, 39% (17 of 44; 24-55) for patients with synovial sarcoma, and 25% (two of eight; 3-65) for patients with myxoid round cell liposarcoma. Cytokine release syndrome occurred in 37 (71%) of 52 of patients (one grade 3 event). Cytopenias were the most common grade 3 or worse adverse events (lymphopenia in 50 [96%], neutropenia 44 [85%], leukopenia 42 [81%] of 52 patients). No treatment-related deaths occurred.
INTERPRETATION
Afami-cel treatment resulted in durable responses in heavily pre-treated patients with HLA-A*02 and MAGE-A4-expressing synovial sarcoma. This study shows that T-cell receptor therapy can be used to effectively target solid tumours and provides rationale to expand this approach to other solid malignancies.
FUNDING
Adaptimmune.
Topics: Adult; Humans; Sarcoma, Synovial; Liposarcoma, Myxoid; Cytokine Release Syndrome; Ifosfamide; Thrombocytopenia; Anemia; HLA-A Antigens; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38554725
DOI: 10.1016/S0140-6736(24)00319-2 -
Medicina Clinica Feb 2022
Topics: Humans; Sarcoma, Synovial; Translocation, Genetic
PubMed: 34666901
DOI: 10.1016/j.medcli.2021.07.019 -
Archives of Pathology & Laboratory... Feb 2017Primary intraprostatic synovial sarcoma is a rare presentation of an otherwise well-studied disease, and it is one of the few primary sarcomas to occur in the prostate.... (Review)
Review
Primary intraprostatic synovial sarcoma is a rare presentation of an otherwise well-studied disease, and it is one of the few primary sarcomas to occur in the prostate. Ancillary diagnostic techniques including immunohistochemistry and molecular genetics are useful to establish a definitive diagnosis. Despite its unorthodox location, it shares histologic and molecular genetic characteristics with tumors found elsewhere in the body. Most notably, the chromosomal translocation t(X;18)(p11;q11) encodes a chimeric transcription-activating protein, SS18-SSX, which has been identified as the primary driver mutation. The SS18-SSX fusion gene provides a consistent and dependable means of establishing a definitive diagnosis via reverse transcription-polymerase chain reaction or fluorescence in situ hybridization. Recent studies have continued to provide insight into the oncogenesis of this disease. The goal of this review is to elaborate on the clinicopathologic characteristics and underline those techniques that best facilitate the diagnosis of primary intraprostatic synovial sarcoma.
Topics: Humans; Male; Oncogene Proteins, Fusion; Prostatic Neoplasms; Sarcoma, Synovial
PubMed: 28134577
DOI: 10.5858/arpa.2016-0101-RS -
Journal of Clinical Oncology : Official... Jan 2018Synovial sarcoma (SS) is a rare sarcoma driven by a translocation between SS18 and SSX 1, 2, or 4. With approximately 800 to 1,000 cases a year in the United States, it... (Review)
Review
Synovial sarcoma (SS) is a rare sarcoma driven by a translocation between SS18 and SSX 1, 2, or 4. With approximately 800 to 1,000 cases a year in the United States, it most commonly affects young adults between the ages of 15 and 30 years. The resultant tumors are either monophasic (pure sarcomas), biphasic (a combination or epithelioid and sarcomatous components), or poorly differentiated. The hybrid transcription factor SS18:SSX alters SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling and global methylation patterns that may allow for future therapeutic opportunities. In this review, we focus on the pharmacologic management of SS, both in the curative setting, where the standard approach is wide surgical excision combined with radiotherapy and/or (neo)adjuvant chemotherapy as appropriate, and in the palliative setting. In advanced disease, chemotherapy with anthracyclines and/or ifosfamide, trabectedin, or pazopanib has been demonstrated to be more active compared with other soft tissue sarcomas. In addition, a better understanding of the molecular and immunologic characteristics of SS has allowed for the identification of new potential targets and the development of novel biology-driven therapies that are all at different stages of testing. There include targeted agents, immunotherapy, and metabolic therapies. Because the impact of these strategies for improving SS outcome is still limited, current and future research is strongly needed to better understand the tumor biology, to identify predictive biomarkers, and to improve the outcomes for patients with SS.
Topics: Adolescent; Adult; Biomarkers, Tumor; Chemoradiotherapy; Humans; Oncogene Proteins, Fusion; Sarcoma, Synovial; Soft Tissue Neoplasms; Translocation, Genetic; Young Adult
PubMed: 29220290
DOI: 10.1200/JCO.2017.75.1941 -
Journal of Basic and Clinical... Mar 2023Sarcoma is defined as a tumor located in the thoracic cavity. However, sarcoma can occur on every side of the body. Synovial sarcoma is a rare soft tissue tumor... (Review)
Review
Sarcoma is defined as a tumor located in the thoracic cavity. However, sarcoma can occur on every side of the body. Synovial sarcoma is a rare soft tissue tumor originating from pluripotent with a high malignancy rate. The most common predilection of synovial sarcoma is in the joints. Primary synovial sarcoma of the lung and mediastinum are rare tumors and generally malignant. There are only a few cases have been reported. Definite diagnosis is made by histopathological, immunohistochemistry, and cytogenetic examination. The management strategy for synovial sarcoma requires multimodality treatment with surgery, chemotherapy, and radiotherapy. However, effective and relatively non-toxic therapy for primary synovial sarcoma is still developed. The five years life expectancy is higher if the patient received adjuvant radiotherapy and/or chemotherapy after surgery.
Topics: Humans; Sarcoma, Synovial; Mediastinal Neoplasms; Mediastinum; Lung; Lung Neoplasms
PubMed: 36800987
DOI: 10.1515/jbcpp-2022-0286 -
Current Treatment Options in Oncology Mar 2023Synovial sarcoma (SS) is a fusion-driven subtype of sarcoma that is a more chemo-sensitive subtype of soft tissue sarcoma. While chemotherapy options are currently... (Review)
Review
Synovial sarcoma (SS) is a fusion-driven subtype of sarcoma that is a more chemo-sensitive subtype of soft tissue sarcoma. While chemotherapy options are currently standard of care, our fundamental understanding of the biology of SS is driving new therapies. We will review the current standard of care, as well as the current therapies showing promise in a clinical trial. It is our hope that by encouraging participation in clinical trials, the fundamental therapies available for SS will change the current treatment paradigm.
Topics: Humans; Sarcoma, Synovial; Sarcoma; Soft Tissue Neoplasms
PubMed: 36867389
DOI: 10.1007/s11864-023-01056-5 -
Current Treatment Options in Oncology Oct 2021New molecular insights are being achieved in synovial sarcoma (SS) that can provide new potential diagnostic and prognostic markers as well as therapeutic targets. In... (Review)
Review
New molecular insights are being achieved in synovial sarcoma (SS) that can provide new potential diagnostic and prognostic markers as well as therapeutic targets. In particular, the advancement of research on epigenomics and gene regulation is promising. The concrete hypothesis that the pathogenesis of SS might mainly depend on the disruption of the balance of the complex interaction between epigenomic regulatory complexes and the consequences on gene expression opens interesting new perspectives. The standard of care for primary SS is wide surgical resection combined with radiation in selected cases. The role of chemotherapy is still under refinement and can be considered in patients at high risk of metastasis or in those with advanced disease. Cytotoxic chemotherapy (anthracyclines, ifosfamide, trabectedin, and pazopanib) is the treatment of choice, despite several possible side effects. Many possible drug-able targets have been identified. However, the impact of these strategies in improving SS outcome is still limited, thus making current and future research strongly needed to improve the survival of patients with SS.
Topics: Anthracyclines; Antineoplastic Agents; Chemotherapy, Adjuvant; Epigenomics; Gene Expression Regulation, Neoplastic; Genomics; Humans; Ifosfamide; Indazoles; Molecular Targeted Therapy; Pyrimidines; Radiotherapy, Adjuvant; Sarcoma, Synovial; Soft Tissue Neoplasms; Sulfonamides; Surgical Procedures, Operative; Trabectedin
PubMed: 34687366
DOI: 10.1007/s11864-021-00914-4 -
Annals of Diagnostic Pathology Dec 2014Synovial sarcoma (SS) is a malignant mesenchymal neoplasm with variable epithelial differentiation, with a propensity to occur in young adults and which can arise at... (Review)
Review
Synovial sarcoma (SS) is a malignant mesenchymal neoplasm with variable epithelial differentiation, with a propensity to occur in young adults and which can arise at almost any site. It is generally viewed and treated as a high-grade sarcoma. As one of the first sarcomas to be defined by the presence of a specific chromosomal translocation leading to the production of the SS18-SSX fusion oncogene, it is perhaps the archetypal "translocation-associated sarcoma," and its translocation remains unique to this tumor type. Synovial sarcoma has a variety of morphologic patterns, but its chief forms are the classic biphasic pattern, of glandular or solid epithelial structures with monomorphic spindle cells and the monophasic pattern, of fascicles of spindle cells with only immunohistochemical or ultrastructural evidence of epithelial differentiation. However, there is significant morphologic heterogeneity and overlap with a variety of other neoplasms, which can cause diagnostic challenge, particularly as the immunoprofile is varied, SS18-SSX is not detected in 100% of SSs, and they may occur at unusual sites. Correct diagnosis is clinically important, due to the relative chemosensitivity of SS in relation to other sarcomas, for prognostication and because of the potential for treatment with specific targeted therapies in the near future. We review SS, with emphasis on the diagnostic spectrum, recent immunohistochemical and genetic findings, and the differential diagnosis.
Topics: Biomarkers, Tumor; Cell Differentiation; Diagnosis, Differential; Epithelial Cells; Humans; Oncogene Proteins, Fusion; Sarcoma, Synovial
PubMed: 25438927
DOI: 10.1016/j.anndiagpath.2014.09.002 -
Journal of Internal Medicine Dec 2023Sarcoma subtype classification is currently mainly based upon histopathological morphology. Molecular analyses have emerged as an efficient addition to the diagnostic... (Review)
Review
Sarcoma subtype classification is currently mainly based upon histopathological morphology. Molecular analyses have emerged as an efficient addition to the diagnostic workup and sarcoma care. Knowledge about the sarcoma genome increases, and genetic events that can either support a histopathological diagnosis or suggest a differential diagnosis are identified, as well as novel therapeutic targets. In this review, we present diagnostic, therapeutic, and prognostic molecular markers that are, or might soon be, used clinically. For sarcoma diagnostics, there are specific fusions highly supportive or pathognomonic for a diagnostic entity-for instance, SYT::SSX in synovial sarcoma. Complex karyotypes also give diagnostic information-for example, supporting dedifferentiation rather than low-grade central osteosarcoma or well-differentiated liposarcoma when detected in combination with MDM2/CDK4 amplification. Molecular treatment predictive sarcoma markers are available for gastrointestinal stromal tumor (GIST) and locally aggressive benign mesenchymal tumors. The molecular prognostic markers for sarcomas in clinical practice are few. For solitary fibrous tumor, the type of NAB2::STAT6 fusion is associated with the outcome, and the KIT/PDGFRA pathogenic variant in GISTs can give prognostic information. With the exploding availability of sequencing technologies, it becomes increasingly important to understand the strengths and limitations of those methods and their context in sarcoma diagnostics. It is reasonable to believe that most sarcoma treatment centers will increase the use of massive-parallel sequencing soon. We conclude that the context in which the genetic findings are interpreted is of importance, and the interpretation of genomic findings requires considering tumor histomorphology.
Topics: Humans; Precision Medicine; Sarcoma; Sarcoma, Synovial; Soft Tissue Neoplasms; Biomarkers, Tumor; Oncogene Proteins, Fusion
PubMed: 37643281
DOI: 10.1111/joim.13717