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DON'T MISS THE SIGNALS

Spotting the red flags of synovial sarcoma can make all the difference.

HEALTHCARE PROFESSIONAL

See It, Know It, Diagnose It

The Diagnosis of Synovial Sarcoma Is Challenging and Often Delayed1

Many patients may already be metastatic at diagnosis2

Synovial sarcoma is a rare type of cancer that accounts for only about 5% to 10% of soft tissue sarcomas.2

Soft tissue sarcomas are a diverse group of tumors that develop in the connective tissue of the body. The insidious onset of synovial sarcoma, along with younger age and atypical symptoms at presentation, may lead to initial misdiagnoses.3

Nearly all synovial sarcoma tumors contain a chromosomal abnormality by translocation known as T(x; 18) (P11.2; q11.2), which produces the SS18-SSX fusion protein.2,4

Synovial sarcoma is associated with local recurrence and distant metastases1

Synovial sarcoma can metastasize through the lymph nodes with clinically detectable disease found in 15% to 20% of newly diagnosed patients. Most metastatic tumors develop in the lungs (80%), although bone (9.9%) and liver (4.5%) are the next most frequent locations.5

Lungs: 80%

Bone: 9.9%

Liver: 4.5%

Synovial sarcoma tumors are associated with a 5-year survival rate ranging from 50% to 60% in adult patients. The 5-year metastatic disease-free survival rate ranges from 40% to 60% in adult patients. Nearly half of synovial sarcoma deaths occur within 5-10 years of diagnosis.1,6

Rapid Progression to Multiple Lines of Therapy

With No Consensus After 1L Treatment, Unresectable or Metastatic Patients Face a Complex Journey7,8

Locally advanced or metastatic synovial sarcoma is treated with traditional cytotoxic chemotherapies in the first-line setting8,9

Existing therapies, after first-line (1L) progression, have limited effectiveness because median time to next treatment and overall survival decrease at the start of second-line therapy and are unable to halt tumor progression.10

THERE IS AN UNMET NEED FOR BETTER TREATMENTS FOR PATIENTS WITH ADVANCED OR METASTATIC DISEASE THAT PROGRESS ON OR AFTER 1L SYSTEMIC TREATMENT8,10

The Power of the Immune System

Managing Synovial Sarcoma May Warrant Targeted Cell Immunotherapy11

The immune system is pivotal in targeting and killing tumor cells

Immunotherapies have had success in improving patient outcomes in select tumor types.11

Cell therapy, a type of immunotherapy, has shown positive correlation for patients with solid tumors because it harnesses your patients’ own immune system to effectively attack tumor cells. There are different types of cell therapy. One type is T-cell receptor (TCR) T-cell therapy.12

How the immune system can target and destroy tumor cells12,13

  • TCRs target and bind to a specific human leukocyte antigen (HLA)-peptide complex, resulting in the targeting and destruction of the relevant cell
  • The HLA-peptide complex presents peptides that are derived from intracellular target proteins

    • The HLA-peptide complexes recognized by TCRs are called T-cell epitopes. Very few T-cell epitopes have been identified and targeted in immunotherapies for cancers.14

    EFFECTIVE CELL THERAPY REQUIRES IDENTIFICATION AND TARGETING OF SPECIFIC TUMOR BIOMARKERS12

    Now Is the Time to Know

    Biomarkers May Lead the Way in Determining Appropriate Cell Therapy Options5

    Certain biomarkers are known to overexpress in certain tumor types, such as synovial sarcoma5

    The immunohistochemistry for synovial sarcoma has shown that diffuse expression of B-cell lymphoma 2 is common among patients. And in 60% of cases, synovial sarcoma tumors test positive for CD99.3

    Cancer testis antigens (CTAs), which are generally not expressed in normal tissue, have high expression in synovial sarcoma compared with most cancer types. MAGE-A4, NY-ESO-1, and PRAME are strongly expressed in most synovial sarcomas.3,15,16

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    References: 1. Bakri A, Shinagare AB, Krajewski KM, et al. Synovial sarcoma: imaging features of common and uncommon primary sites, metastatic patterns, and treatment response. Am J Roentgenol. 2012;199(2):W208-W215. 2. Aytekin MN, Öztürk R, Amer K, Yapar A. Epidemiology, incidence, and survival of synovial sarcoma subtypes: SEER database analysis. J Orthop Surg (Hong Kong). 2020;28(2):1-12. doi:10.1177/2309499020936009 3. Gazendam AM, Popovic S, Munir S, Parasu N, Wilson D, Ghert M. Synovial sarcoma: a clinical review. Curr Oncol. 2021;28(3):1909-1920. 4. Jerby-Arnon L, Neftel C, Shore ME, et al. Opposing immune and genetic mechanisms shape oncogenic programs in synovial sarcoma. Nat Med. 2021;27(2):289-300. 5. de Necochea-Campion R, Zuckerman LM, Mirshahidi HR, Khosrowpour S, Chen CS, Mirshahidi S. Metastatic biomarkers in synovial sarcoma. Biomark Res. 2017;5(4):1-8. doi:10.1186/s40364-017-0083-x 6. Stacchiotti S, Van Tine BA. Synovial sarcoma: current concepts and future perspectives. J Clin Oncol. 2018;36(2):180-187. 7. Pollack SM, Somaiah N, Araujo DM, et al. Clinical outcomes of patients with advanced synovial sarcoma or myxoid/round cell liposarcoma treated at major cancer centers in the United States. Cancer Med. 2020;9(13):4593-4602. 8. Soft Tissue Sarcoma (Version 4.2019). National Comprehensive Cancer Network. September 12, 2019. Accessed November 9, 2021. https://www.nccn.org/professionals/physician_gls/pdf/sarcoma.pdf 9. Desar IME, Fleuren EDG, van der Graaf WTA. Systemic treatment for adults with synovial sarcoma. Curr Treat Options Oncol. 2018;19(2):13. doi:10.1007/s11864-018-0525 10. Savina M, Le Cesne A, Blay JY, et al. Patterns of care and outcomes of patients with METAstatic soft tissue SARComa in a real-life setting: the METASARC observational study. BMC Med. 2017;15(1):78. doi:10.1186/s12916-017-0831-7 11. Tsimberidou AM, Van Morris K, Vo HH, et al. T-cell receptor-based therapy: an innovative therapeutic approach for solid tumors. J Hematol Oncol. 2021;14(1):102. doi:10.1186/s13045-021-01115-0 12. Grimes JM, Carvajal RD, Muranski P. Cellular therapy for the treatment of solid tumors. Transfus Apher Sci. 2021;60(1):103056. doi:10.1016/j.transci.2021.103056 13. Szeto C, Lobos CA, Nguyen AT, Gras S. TCR recognition of peptide–MHC-I: rule makers and breakers. Int J Mol Sci. 2021;22(1):68. doi:10.3390/ijms22010068 14. Wang C, Xiong C, Hsu YC, Chen L. Human leukocyte antigen (HLA) and cancer immunotherapy: HLA-dependent and -independent adoptive immunotherapies. Ann Blood. 2020;5:14. doi:10.21037/aob-20-27 15. Mitchell G, Pollack SM, Wagner MJ. Targeting cancer testis antigens in synovial sarcoma. J Immunother Cancer. 2021;9(6):e002072. doi:10.1136/jitc-2020-002072 16. Iura K, Maekawa A, Kohashi K, et al. Cancer-testis antigen expression in synovial sarcoma: NY-ESO-1, PRAME, MAGEA4, and MAGEA1. Hum Pathol. 2017;61:130-139. 17. Immunotherapy for sarcoma. Cancer Research Institute. Accessed April 22, 2022. https://www.cancerresearch.org/en-us/immunotherapy/cancer-types/sarcoma#trial