Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 8/2017

01-08-2017 | Bone and Soft Tissue Sarcomas

Synovial Sarcoma: Advances in Diagnosis and Treatment Identification of New Biologic Targets to Improve Multimodal Therapy

Authors: Marc El Beaino, MD, MSc, Dejka M. Araujo, MD, Alexander J. Lazar, MD, PhD, Patrick P. Lin, MD

Published in: Annals of Surgical Oncology | Issue 8/2017

Login to get access

Abstract

Synovial sarcoma is a translocation-associated soft-tissue malignancy that frequently affects adolescents and young adults. It is driven by one of the fusion oncoproteins SS18-SSX1, SS18-SSX2, or rarely, SS18-SSX4. Prognosis of patients with recurrent or metastatic disease is generally poor, and newer therapeutic strategies are needed. In this review, we present recent discoveries in the pathogenesis, diagnosis, and treatment of synovial sarcoma. We discuss potential therapeutic strategies to improve clinical outcomes in this disease.
Literature
1.
Jagdis A, Rubin BP, Tubbs RR, Pacheco M, Nielsen TO. Prospective evaluation of TLE1 as a diagnostic immunohistochemical marker in synovial sarcoma. Am J Surg Pathol. 2009;33(12):1743-51.PubMedCrossRef
2.
3.
van de Rijn M, Barr FG, Xiong QB, Hedges M, Shipley J, Fisher C. Poorly differentiated synovial sarcoma: an analysis of clinical, pathologic, and molecular genetic features. Am J Surg Pathol. 1999;23(1):106-12.PubMedCrossRef
4.
Machen SK, Easley KA, Goldblum JR. Synovial sarcoma of the extremities: a clinicopathologic study of 34 cases, including semi-quantitative analysis of spindled, epithelial, and poorly differentiated areas. Am J Surg Pathol. 1999;23(3):268-75.PubMedCrossRef
5.
Guillou L, Coindre J, Gallagher G, et al. Detection of the synovial sarcoma translocation t(X;18) (SYT;SSX) in paraffin-embedded tissues using reverse transcriptase-polymerase chain reaction: a reliable and powerful diagnostic tool for pathologists. A molecular analysis of 221 mesenchymal tumors fixed in different fixatives. Hum Pathol. 2001;32(1):105-12.PubMedCrossRef
6.
Przybyl J, Sciot R, Wozniak A, et al. Metastatic potential is determined early in synovial sarcoma development and reflected by tumor molecular features. Int J Biochem Cell Biol. 2014;53:505-13.PubMedCrossRef
7.
Spurrell EL, Fisher C, Thomas JM, Judson IR. Prognostic factors in advanced synovial sarcoma: an analysis of 104 patients treated at the Royal Marsden Hospital. Ann Oncol. 2005;16(3):437-44.PubMedCrossRef
8.
9.
Storlazzi CT, Mertens F, Mandahl N, et al. A novel fusion gene, SS18L1/SSX1, in synovial sarcoma. Genes Chromosomes Cancer. 2003;37(2):195-200.PubMedCrossRef
10.
Sandberg AA, Bridge JA. Updates on the cytogenetics and molecular genetics of bone and soft-tissue tumors. Synovial sarcoma. Cancer Gen Cytogen. 2002;133(1):1-23.CrossRef
11.
Ladanyi M, Antonescu CR, Leung DH, et al. Impact of SYT-SSX fusion type on the clinical behavior of synovial sarcoma: a multi-institutional retrospective study of 243 patients. Cancer Res. 2002;62(1):135-40.PubMed
12.
13.
Guillou L, Benhattar J, Bonichon F, et al. Histologic grade, but not SYT-SSX fusion type, is an important prognostic factor in patients with synovial sarcoma: a multicenter, retrospective analysis. J Clin Oncol. 2004;22(20):4040-50.PubMedCrossRef
14.
Fernebro J, Francis P, Eden P, et al. Gene expression profiles relate to SS18/SSX fusion type in synovial sarcoma. Int J Cancer. 2006;118(5):1165-72.PubMedCrossRef
15.
Nilsson G, Skytting B, Xie Y, et al. The SYT-SSX1 variant of synovial sarcoma is associated with a high rate of tumor cell proliferation and poor clinical outcome. Cancer Res. 1999;59(13):3180-4.PubMed
16.
Dimitriadis E, Rontogianni D, Kyriazoglou A, et al. Novel SYT-SSX fusion transcript variants in synovial sarcoma. Cancer Gen Cytogen. 2009;195(1):54-8.CrossRef
17.
Brett D, Whitehouse S, Antonson P, Shipley J, Cooper C, Goodwin G. The SYT protein involved in the t(X;18) synovial sarcoma translocation is a transcriptional activator localised in nuclear bodies. Hum Mol Gen. 1997;6(9):1559-64.PubMedCrossRef
18.
Perani M, Antonson P, Hamoudi R, et al. The proto-oncoprotein SYT interacts with SYT-interacting protein/co-activator activator (SIP/CoAA), a human nuclear receptor co-activator with similarity to EWS and TLS/FUS family of proteins. J Biol Chem. 2005;280(52):42863-76.PubMedCrossRef
19.
Barco R, Hunt LB, Frump AL, et al. The synovial sarcoma SYT-SSX2 oncogene remodels the cytoskeleton through activation of the ephrin pathway. Mol Biol Cell. 2007;18(10):4003-12.PubMedPubMedCentralCrossRef
20.
Saito T, Nagai M, Ladanyi M. SYT-SSX1 and SYT-SSX2 interfere with repression of E-cadherin by snail and slug: a potential mechanism for aberrant mesenchymal to epithelial transition in human synovial sarcoma. Cancer Res. 2006;66(14):6919-27.PubMedCrossRef
21.
Kerouanton A, Jimenez I, Cellier C, et al. Synovial sarcoma in children and adolescents. J Pediatric Hematol Oncol. 2014;36(4):257-62.CrossRef
22.
Haldar M, Hancock JD, Coffin CM, Lessnick SL, Capecchi MR. A conditional mouse model of synovial sarcoma: insights into a myogenic origin. Cancer Cell. 2007;11(4):375-88.PubMedCrossRef
23.
Naka N, Takenaka S, Araki N, et al. Synovial sarcoma is a stem cell malignancy. Stem Cells. 2010;28(7):1119-31.PubMed
24.
Garcia CB, Shaffer CM, Alfaro MP, et al. Reprogramming of mesenchymal stem cells by the synovial sarcoma-associated oncogene SYT-SSX2. Oncogene. 2012;31(18):2323-34.PubMedCrossRef
25.
Middeljans E, Wan X, Jansen PW, Sharma V, Stunnenberg HG, Logie C. SS18 together with animal-specific factors defines human BAF-type SWI/SNF complexes. PloS One. 2012;7(3):e33834.PubMedPubMedCentralCrossRef
26.
Soulez M, Saurin AJ, Freemont PS, Knight JC. SSX and the synovial-sarcoma-specific chimaeric protein SYT-SSX co-localize with the human Polycomb group complex. Oncogene. 1999;18(17):2739-46.PubMedCrossRef
27.
van der Vlag J, Otte AP. Transcriptional repression mediated by the human polycomb-group protein EED involves histone deacetylation. Nature Gen. 1999;23(4):474-8.CrossRef
28.
Furuyama T, Banerjee R, Breen TR, Harte PJ. SIR2 is required for polycomb silencing and is associated with an E(Z) histone methyltransferase complex. Current Biol. 2004;14(20):1812-21.CrossRef
29.
Kadoch C, Crabtree GR. Reversible disruption of mSWI/SNF (BAF) complexes by the SS18-SSX oncogenic fusion in synovial sarcoma. Cell. 2013;153(1):71-85.PubMedPubMedCentralCrossRef
30.
Artavanis-Tsakonas S, Rand MD, Lake RJ. Notch signaling: cell fate control and signal integration in development. Science. 1999;284(5415):770-6.PubMedCrossRef
31.
Greenwald I. LIN-12/Notch signaling: lessons from worms and flies. Genes Develop. 1998;12(12):1751-62.PubMedCrossRef
32.
Radaelli S, Stacchiotti S, Casali PG, Gronchi A. Emerging therapies for adult soft-tissue sarcoma. Expert Rev Anticancer Ther. 2014;14(6):689-704.PubMedCrossRef
33.
34.
Trautmann M, Sievers E, Aretz S, et al. SS18-SSX fusion protein-induced Wnt/beta-catenin signaling is a therapeutic target in synovial sarcoma. Oncogene. Oct 16 2014;33(42):5006-16.PubMedCrossRef
35.
Linch M, Miah AB, Thway K, Judson IR, Benson C. Systemic treatment of soft-tissue sarcoma-gold standard and novel therapies. Nat Rev Clin Oncol. 2014;11(4):187-202.PubMedCrossRef
36.
Saito T, Oda Y, Kawaguchi K, et al. PTEN and other tumor suppressor gene mutations as secondary genetic alterations in synovial sarcoma. Oncology Rep. 2004;11(5):1011-5.
37.
Subramaniam MM, Calabuig-Farinas S, Pellin A, Llombart-Bosch A. Mutational analysis of E-cadherin, beta-catenin and APC genes in synovial sarcomas. Histopathology. 2010;57(3):482-6.PubMedCrossRef
38.
39.
Kelleher F, O’Donnell CP, Rafee S. WNT Signaling and synovial sarcoma. Sarcoma Res Int. 2014;1(1):5.
40.
Baird K, Davis S, Antonescu CR, et al. Gene expression profiling of human sarcomas: insights into sarcoma biology. Cancer Res. 2005;65(20):9226-35.PubMedCrossRef
41.
Nakayama R, Mitani S, Nakagawa T, et al. Gene expression profiling of synovial sarcoma: distinct signature of poorly differentiated type. Am J Surg Pathol. 2010;34(11):1599-607.PubMed
42.
Chuang HC, Hsu SC, Huang CG, Hsueh S, Ng KF, Chen TC. Reappraisal of TLE-1 immunohistochemical staining and molecular detection of SS18-SSX fusion transcripts for synovial sarcoma. Pathol Int. 2013;63(12):573-80.PubMedCrossRef
43.
Su L, Sampaio AV, Jones KB, et al. Deconstruction of the SS18-SSX fusion oncoprotein complex: insights into disease etiology and therapeutics. Cancer Cell. 2012;21(3):333-47.PubMedPubMedCentralCrossRef
44.
Jiang BH, Liu LZ. Role of mTOR in anticancer drug resistance: perspectives for improved drug treatment. Drug resistance updates: reviews and commentaries in antimicrobial and anticancer chemotherapy. 2008;11(3):63-76.CrossRef
45.
46.
Barretina J, Taylor BS, Banerji S, et al. Subtype-specific genomic alterations define new targets for soft-tissue sarcoma therapy. Nat Gen. 2010;42(8):715-21.CrossRef
47.
Teng HW, Wang HW, Chen WM, et al. Prevalence and prognostic influence of genomic changes of EGFR pathway markers in synovial sarcoma. J Surg Oncol. 2011;103(8):773-81.PubMedCrossRef
48.
Chang Q, Li Y, White MF, Fletcher JA, Xiao S. Constitutive activation of insulin receptor substrate 1 is a frequent event in human tumors: therapeutic implications. Cancer Res. 2002;62(21):6035-8.PubMed
49.
Friedrichs N, Trautmann M, Endl E, et al. Phosphatidylinositol-3’-kinase/AKT signaling is essential in synovial sarcoma. Int J Cancer. 2011;129(7):1564-75.PubMedCrossRef
50.
Bozzi F, Ferrari A, Negri T, et al. Molecular characterization of synovial sarcoma in children and adolescents: evidence of akt activation. Trans Oncol. 2008;1(2):95-101.CrossRef
51.
Setsu N, Kohashi K, Fushimi F, et al. Prognostic impact of the activation status of the Akt/mTOR pathway in synovial sarcoma. Cancer. 2013;119(19):3504-13.PubMedCrossRef
52.
Thomas DG, Giordano TJ, Sanders D, et al. Expression of receptor tyrosine kinases epidermal growth factor receptor and HER-2/neu in synovial sarcoma. Cancer. 2005;103(4):830-8.PubMedCrossRef
53.
Xie Y, Skytting B, Nilsson G, Brodin B, Larsson O. Expression of insulin-like growth factor-1 receptor in synovial sarcoma: association with an aggressive phenotype. Cancer Res. 1999;59(15):3588-91.PubMed
54.
Ho AL, Vasudeva SD, Lae M, et al. PDGF receptor alpha is an alternative mediator of rapamycin-induced Akt activation: implications for combination targeted therapy of synovial sarcoma. Cancer Res. 2012;72(17):4515-25.PubMedPubMedCentralCrossRef
55.
Michels S, Trautmann M, Sievers E, et al. SRC signaling is crucial in the growth of synovial sarcoma cells. Cancer Res. 2013;73(8):2518-28.PubMedCrossRef
56.
de Bruijn DR, Allander SV, van Dijk AH, et al. The synovial-sarcoma-associated SS18-SSX2 fusion protein induces epigenetic gene (de)regulation. Cancer Res. 2006;66(19):9474-82.PubMedCrossRef
57.
Sun Y, Gao D, Liu Y, Huang J, Lessnick S, Tanaka S. IGF2 is critical for tumorigenesis by synovial sarcoma oncoprotein SYT-SSX1. Oncogene. 2006;25(7):1042-52.PubMedCrossRef
58.
Wakamatsu T, Naka N, Sasagawa S, et al. Deflection of vascular endothelial growth factor action by SS18-SSX and composite vascular endothelial growth factor- and chemokine (C-X-C motif) receptor 4-targeted therapy in synovial sarcoma. Cancer Sci. 2014;105(9):1124-34.PubMedPubMedCentralCrossRef
59.
Nielsen TO, West RB, Linn SC, et al. Molecular characterisation of soft-tissue tumours: a gene expression study. Lancet. 2002;359(9314):1301-7.PubMedCrossRef
60.
Ishibe T, Nakayama T, Okamoto T, et al. Disruption of fibroblast growth factor signal pathway inhibits the growth of synovial sarcomas: potential application of signal inhibitors to molecular target therapy. Clin Cancer Res. 2005;11(7):2702-12.PubMedCrossRef
61.
Palmerini E, Benassi MS, Quattrini I, et al. Prognostic and predictive role of CXCR4, IGF-1R and Ezrin expression in localized synovial sarcoma: is chemotaxis important to tumor response? Orphanet J Rare Dis. 2015;10:6.PubMedPubMedCentralCrossRef
62.
Saito T. The SYT-SSX fusion protein and histological epithelial differentiation in synovial sarcoma: relationship with extracellular matrix remodeling. Int J Clin Exp Pathol. 2013;6(11):2272-9.PubMedPubMedCentral
63.
Haldar M, Randall RL, Capecchi MR. Synovial sarcoma: from genetics to genetic-based animal modeling. Clin Orthop Rel Res. 2008;466(9):2156-67.CrossRef
64.
Inagaki H, Nagasaka T, Otsuka T, Sugiura E, Nakashima N, Eimoto T. Association of SYT-SSX fusion types with proliferative activity and prognosis in synovial sarcoma. Mod Pathol. 2000;13(5):482-8.PubMedCrossRef
65.
Antonescu CR, Kawai A, Leung DH, et al. Strong association of SYT-SSX fusion type and morphologic epithelial differentiation in synovial sarcoma. Diagn Mol Pathol.2000;9(1):1-8.PubMedCrossRef
66.
Przybyl J, Sciot R, Rutkowski P, et al. Recurrent and novel SS18-SSX fusion transcripts in synovial sarcoma: description of three new cases. Tumour Biol. 2012;33(6):2245-53.PubMedPubMedCentralCrossRef
67.
Keith JL, Bilbao J, Croul S, et al. Clinical Neuropathology practice guide 6-2013: morphology and an appropriate immunohistochemical screening panel aid in the identification of synovial sarcoma by neuropathologists. Clin Neuropathol. 2013;32(6):461-70.PubMedPubMedCentralCrossRef
68.
Kohashi K, Oda Y, Yamamoto H, et al. Reduced expression of SMARCB1/INI1 protein in synovial sarcoma. Mod Pathol. 2010;23(7):981-90.PubMedCrossRef
69.
Ordonez NG, Mahfouz SM, Mackay B. Synovial sarcoma: an immunohistochemical and ultrastructural study. Hum Pathol. 1990;21(7):733-49.PubMedCrossRef
70.
Jorgensen LJ, Lyon H, Myhre-Jensen O, Nordentoft A, Sneppen O. Synovial sarcoma. An immunohistochemical study of the epithelial component. APMIS Acta Pathol Microbiol Immunol Scand. 1994;102(3):191-6.CrossRef
71.
Fisher C, Montgomery E, Healy V. Calponin and h-caldesmon expression in synovial sarcoma; the use of calponin in diagnosis. Histopathology. 2003;42(6):588-93.PubMedCrossRef
72.
Terry J, Saito T, Subramanian S, et al. TLE1 as a diagnostic immunohistochemical marker for synovial sarcoma emerging from gene expression profiling studies. Am J Surg Pathol. 2007;31(2):240-6.PubMedCrossRef
73.
Valente AL, Tull J, Zhang S. Specificity of TLE1 expression in unclassified high-grade sarcomas for the diagnosis of synovial sarcoma. Appl Immunohistochem Mol Morphol. 2013;21(5):408-13.PubMedCrossRef
74.
Foo WC, Cruise MW, Wick MR, Hornick JL. Immunohistochemical staining for TLE1 distinguishes synovial sarcoma from histologic mimics. Am J Clin Pathol. 2011;135(6):839-44.PubMedCrossRef
75.
Kosemehmetoglu K, Vrana JA, Folpe AL. TLE1 expression is not specific for synovial sarcoma: a whole section study of 163 soft-tissue and bone neoplasms. Mod Pathol. 2009;22(7):872-8.PubMedCrossRef
76.
Lai JP, Robbins PF, Raffeld M, et al. NY-ESO-1 expression in synovial sarcoma and other mesenchymal tumors: significance for NY-ESO-1-based targeted therapy and differential diagnosis. Mod Pathol. 2012;25(6):854-8.PubMedCrossRef
77.
Endo M, de Graaff MA, Ingram DR, et al. NY-ESO-1 (CTAG1B) expression in mesenchymal tumors. Mod Pathol. 2015;28(4):587-95.PubMedCrossRef
78.
Shi W, Indelicato DJ, Morris CG, Scarborough MT, Gibbs CP, Zlotecki RA. Long-term treatment outcomes for patients with synovial sarcoma: a 40-year experience at the University of Florida. Am J Clin Oncol. 2013;36(1):83-8.PubMedCrossRef
79.
Guadagnolo BA, Zagars GK, Ballo MT, et al. Long-term outcomes for synovial sarcoma treated with conservation surgery and radiotherapy. Int J Radiat Oncol Biol Phys. 2007;69(4):1173-80.PubMedCrossRef
80.
Chan JA, McMenamin ME, Fletcher CD. Synovial sarcoma in older patients: clinicopathological analysis of 32 cases with emphasis on unusual histological features. Histopathology. 2003;43(1):72-83.PubMedCrossRef
81.
Spillane AJ, A’Hern R, Judson IR, Fisher C, Thomas JM. Synovial sarcoma: a clinicopathologic, staging, and prognostic assessment. J Clin Oncol. 2000;18(22):3794-803.PubMedCrossRef
82.
Ferrari A, Gronchi A, Casanova M, et al. Synovial sarcoma: a retrospective analysis of 271 patients of all ages treated at a single institution. Cancer. 2004;101(3):627-34.PubMedCrossRef
83.
Bergh P, Meis-Kindblom JM, Gherlinzoni F, et al. Synovial sarcoma: identification of low and high risk groups. Cancer. 1999;85(12):2596-607.PubMedCrossRef
84.
ten Heuvel SE, Hoekstra HJ, Bastiaannet E, Suurmeijer AJ. The classic prognostic factors tumor stage, tumor size, and tumor grade are the strongest predictors of outcome in synovial sarcoma: no role for SSX fusion type or ezrin expression. Appl Immunohistochem Molec Morphol. 2009;17(3):189-95.CrossRef
85.
Vlenterie M, Ho VK, Kaal SE, Vlenterie R, Haas R, van der Graaf WT. Age as an independent prognostic factor for survival of localised synovial sarcoma patients. Br J Cancer. 2015;113(11):1602-6.PubMedPubMedCentralCrossRef
86.
Speth BM, Krieg AH, Kaelin A, et al. Synovial sarcoma in patients under 20 years of age: a multicenter study with a minimum follow-up of 10 years. J Child Orthop. 2011;5(5):335-42.PubMedPubMedCentralCrossRef
87.
Takenaka S, Ueda T, Naka N, et al. Prognostic implication of SYT-SSX fusion type in synovial sarcoma: a multi-institutional retrospective analysis in Japan. Oncol Rep. 2008;19(2):467-76.PubMed
88.
Golouh R, Stanta G, Bracko M, Bonin S. Correlation of MTS1/p16 and nm23 mRNA expression with survival in patients with peripheral synovial sarcoma. J Surg Oncol. 2001;76(2):83-8.PubMedCrossRef
89.
Lewis JJ, Antonescu CR, Leung DH, et al. Synovial sarcoma: a multivariate analysis of prognostic factors in 112 patients with primary localized tumors of the extremity. J Clin Oncol. 2000;18(10):2087-94.PubMedCrossRef
90.
Thway K, Fisher C. Synovial sarcoma: defining features and diagnostic evolution. Ann Diagn Pathol. 2014;18(6):369-80.PubMedCrossRef
91.
Canter RJ, Qin LX, Maki RG, Brennan MF, Ladanyi M, Singer S. A synovial sarcoma-specific preoperative nomogram supports a survival benefit to ifosfamide-based chemotherapy and improves risk stratification for patients. Clin Cancer Res. 2008;14(24):8191-7.PubMedPubMedCentralCrossRef
92.
Nagayama S, Fukukawa C, Katagiri T, et al. Therapeutic potential of antibodies against FZD 10, a cell-surface protein, for synovial sarcomas. Oncogene. 2005;24(41):6201-12.PubMedCrossRef
93.
Ishibe T, Nakayama T, Aoyama T, Nakamura T, Toguchida J. Neuronal differentiation of synovial sarcoma and its therapeutic application. Clin Ortho Res. 2008;466(9):2147-55.CrossRef
94.
Nielsen TO, Hsu FD, O’Connell JX, et al. Tissue microarray validation of epidermal growth factor receptor and SALL2 in synovial sarcoma with comparison to tumors of similar histology. Am J Pathol. 2003;163(4):1449-56.PubMedPubMedCentralCrossRef
95.
Lagarde P, Przybyl J, Brulard C, et al. Chromosome instability accounts for reverse metastatic outcomes of pediatric and adult synovial sarcomas. J Clin Oncol. 2013;31(5):608-15.PubMedCrossRef
96.
Metzger-Filho O, Catteau A, Michiels S, et al. Genomic Grade Index (GGI): feasibility in routine practice and impact on treatment decisions in early breast cancer. PloS One. 2013;8(8):e66848.PubMedPubMedCentralCrossRef
97.
Chibon F, Lagarde P, Salas S, et al. Validated prediction of clinical outcome in sarcomas and multiple types of cancer on the basis of a gene expression signature related to genome complexity. Nat Med. 2010;16(7):781-7.PubMedCrossRef
98.
El Beaino M, Araujo DM, Gopalakrishnan V, Lazar AJ, Lin PP. Prognosis of T1 synovial sarcoma depends upon surgery by oncologic surgeons. J Surg Oncol. 2016;114(4):490-4.
99.
Ryan CW, Desai J. The past, present, and future of cytotoxic chemotherapy and pathway-directed targeted agents for soft-tissue sarcoma. American Society of Clinical Oncology educational book / ASCO. American Society of Clinical Oncology meeting. 2013.
100.
Bramwell VH, Anderson D, Charette ML. Doxorubicin-based chemotherapy for the palliative treatment of adult patients with locally advanced or metastatic soft-tissue sarcoma: a meta-analysis and clinical practice guideline. Sarcoma. 2000;4(3):103-12.PubMedPubMedCentralCrossRef
101.
102.
Tascilar M, Loos WJ, Seynaeve C, Verweij J, Sleijfer S. The pharmacologic basis of ifosfamide use in adult patients with advanced soft-tissue sarcomas. Oncologist. 2007;12(11):1351-60.PubMedCrossRef
103.
Edmonson JH, Ryan LM, Falkson CI, Hicks DG, Blum RH. Phase II study of ifosfamide+doxorubicin in patients with advanced synovial sarcomas (E1793): A Trial of the Eastern Cooperative Oncology Group. Sarcoma. 2003;7(1):9-11.PubMedPubMedCentralCrossRef
104.
Siehl JM, Thiel E, Schmittel A, et al. Ifosfamide/liposomal daunorubicin is a well tolerated and active first-line chemotherapy regimen in advanced soft-tissue sarcoma: results of a phase II study. Cancer. 2005;104(3):611-7.PubMedCrossRef
105.
106.
Eilber FC, Brennan MF, Eilber FR, et al. Chemotherapy is associated with improved survival in adult patients with primary extremity synovial sarcoma. Ann Surg. 2007;246(1):105-13.PubMedPubMedCentralCrossRef
107.
Ferrari A, De Salvo GL, Dall’Igna P, et al. Salvage rates and prognostic factors after relapse in children and adolescents with initially localised synovial sarcoma. Eur J Cancer. 2012;48(18):3448-55.PubMedCrossRef
108.
Lee SH, Chang MH, Baek KK, et al. High-dose ifosfamide as second- or third-line chemotherapy in refractory bone and soft-tissue sarcoma patients. Oncology. 2011;80(3-4):257-61.PubMedCrossRef
109.
Svancarova L, Blay JY, Judson IR, et al. Gemcitabine in advanced adult soft-tissue sarcomas. A phase II study of the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer. 2002;38(4):556-9.PubMedCrossRef
110.
Okuno S, Edmonson J, Mahoney M, Buckner JC, Frytak S, Galanis E. Phase II trial of gemcitabine in advanced sarcomas. Cancer. 2002;94(12):3225-9.PubMedCrossRef
111.
Verweij J, Lee SM, Ruka W, et al. Randomized phase II study of docetaxel versus doxorubicin in first- and second-line chemotherapy for locally advanced or metastatic soft-tissue sarcomas in adults: a study of the european organization for research and treatment of cancer soft tissue and bone sarcoma group. J Clin Oncol. 2000;18(10):2081-6.PubMedCrossRef
112.
Kostler WJ, Brodowicz T, Attems Y, et al. Docetaxel as rescue medication in anthracycline- and ifosfamide-resistant locally advanced or metastatic soft-tissue sarcoma: results of a phase II trial. Ann Oncol. 2001;12(9):1281-8.PubMedCrossRef
113.
Maki RG, Wathen JK, Patel SR, et al. Randomized phase II study of gemcitabine and docetaxel compared with gemcitabine alone in patients with metastatic soft-tissue sarcomas: results of sarcoma alliance for research through collaboration study 002 [corrected]. J Clin Oncol. 2007;25(19):2755-63.PubMedCrossRef
114.
Erber R, Thurnher A, Katsen AD, et al. Combined inhibition of VEGF and PDGF signaling enforces tumor vessel regression by interfering with pericyte-mediated endothelial cell survival mechanisms. FASEB J. 2004;18(2):338-40.PubMed
115.
Timke C, Zieher H, Roth A, et al. Combination of vascular endothelial growth factor receptor/platelet-derived growth factor receptor inhibition markedly improves radiation tumor therapy. Clin Cancer Res. 2008;14(7):2210-9.PubMedCrossRef
116.
Sleijfer S, Ray-Coquard I, Papai Z, et al. Pazopanib, a multikinase angiogenesis inhibitor, in patients with relapsed or refractory advanced soft-tissue sarcoma: a phase II study from the European organisation for research and treatment of cancer-soft-tissue and bone sarcoma group (EORTC study 62043). J Clin Oncol. 2009;27(19):3126-32.PubMedCrossRef
117.
Kasper B, Sleijfer S, Litiere S, et al. Long-term responders and survivors on pazopanib for advanced soft-tissue sarcomas: subanalysis of two European Organisation for Research and Treatment of Cancer (EORTC) clinical trials 62043 and 62072. Ann Oncol. 2014;25(3):719-24.PubMedPubMedCentralCrossRef
118.
Weigel B, Malempati S, Reid JM, et al. Phase 2 trial of cixutumumab in children, adolescents, and young adults with refractory solid tumors: a report from the Children’s Oncology Group. Pediatr Blood Cancer. 2014;61(3):452-6.PubMedCrossRef
119.
Zanardi E, Maruzzo M, Montesco MC, Roma A, Rastrelli M, Basso U. Response to trabectedin in a patient with advanced synovial sarcoma with lung metastases. Anti-cancer Drugs. 2014;25(10):1227-30.PubMedPubMedCentralCrossRef
120.
Sanfilippo R, Dileo P, Blay JY, et al. Trabectedin in advanced synovial sarcomas: a multicenter retrospective study from four European institutions and the Italian Rare Cancer Network. Anti-cancer Drugs. 2015;26(6):678-81.PubMedPubMedCentral
121.
Di Giandomenico S, Frapolli R, Bello E, et al. Mode of action of trabectedin in myxoid liposarcomas. Oncogene. 2014;33(44):5201-10.PubMedCrossRef
122.
Germano G, Frapolli R, Belgiovine C, et al. Role of macrophage targeting in the antitumor activity of trabectedin. Cancer Cell. 2013;23(2):249-62.PubMedCrossRef
123.
Shiloh Y. The ATM-mediated DNA-damage response: taking shape. Trends Biochem Sci. 2006;31(7):402-10.PubMedCrossRef
124.
Bakkenist CJ, Kastan MB. DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature. 2003;421(6922):499-506.PubMedCrossRef
125.
Ito T, Ouchida M, Morimoto Y, et al. Significant growth suppression of synovial sarcomas by the histone deacetylase inhibitor FK228 in vitro and in vivo. Cancer Lett. 2005;224(2):311-9.PubMedCrossRef
126.
Watanabe R, Ui A, Kanno S, et al. SWI/SNF factors required for cellular resistance to DNA damage include ARID1A and ARID1B and show interdependent protein stability. Cancer Res. 2014;74(9):2465-75.PubMedCrossRef
127.
Barham W, Frump AL, Sherrill TP, et al. Targeting the Wnt pathway in synovial sarcoma models. Cancer Discov. 2013;3(11):1286-301.PubMedCrossRef
128.
Robbins PF, Morgan RA, Feldman SA, et al. Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1. J Clin Oncol. 2011;29(7):917-24.PubMedPubMedCentralCrossRef
129.
Gure AO, Wei IJ, Old LJ, Chen YT. The SSX gene family: characterization of 9 complete genes. Int J Cancer. 2002;101(5):448-53.PubMedCrossRef
130.
131.
Chugh R, Wathen JK, Maki RG, et al. Phase II multicenter trial of imatinib in 10 histologic subtypes of sarcoma using a bayesian hierarchical statistical model. J Clin Oncol. 2009;27(19):3148-53.PubMedCrossRef
132.
Bond M, Bernstein ML, Pappo A, et al. A phase II study of imatinib mesylate in children with refractory or relapsed solid tumors: a Children’s Oncology Group study. Pediatr Blood Cancer. 2008;50(2):254-8.PubMedCrossRef
Metadata
Title
Synovial Sarcoma: Advances in Diagnosis and Treatment Identification of New Biologic Targets to Improve Multimodal Therapy
Authors
Marc El Beaino, MD, MSc
Dejka M. Araujo, MD
Alexander J. Lazar, MD, PhD
Patrick P. Lin, MD
Publication date
01-08-2017
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 8/2017
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-017-5855-x

Other articles of this Issue 8/2017

Annals of Surgical Oncology 8/2017 Go to the issue

Hepatobiliary Tumors

Clinical Impact of Preoperative Chemotherapy on Microscopic Cancer Spread Surrounding Colorectal Liver Metastases

Gastrointestinal Oncology

Preoperative Chemoradiotherapy Versus Perioperative Chemotherapy for Patients With Resectable Esophageal or Gastroesophageal Junction Adenocarcinoma

Gastrointestinal Oncology

A Prognostic Model for Predicting Overall Survival in Patients with Peritoneal Surface Malignancy of an Appendiceal Origin Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

Hepatobiliary Tumors

Management of Neuroendocrine Tumor Liver Metastases: Long-Term Outcomes and Prognostic Factors from a Large Prospective Database

Endocrine Tumors

Increased Grade in Neuroendocrine Tumor Metastases Negatively Impacts Survival

Breast Oncology

Bilateral Mastectomy as Overtreatment for Breast Cancer in Women Age Forty Years and Younger with Unilateral Operable Invasive Breast Cancer