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Synovial sarcoma is a young person's sarcoma driven by a single fusion gene, SS18-SSX, that scrambles how genes are switched on. It is treated with surgery, radiotherapy and ifosfamide-based chemotherapy, and in 2024 it became the first solid tumour with an approved engineered T-cell receptor therapy.
Synovial sarcoma has nothing to do with the synovium; it is defined by the SS18-SSX fusion, which hijacks the BAF chromatin remodelling complex. It presents as a slow-growing deep mass near the knee, ankle or other joints in people aged 15 to 40, and is graded high by default. Treatment is wide resection with radiotherapy, and chemotherapy with ifosfamide and doxorubicin is used more readily than in other sarcomas because responses are frequent, including in the neoadjuvant setting; pazopanib and trabectedin have activity in advanced disease. Most tumours express the cancer-testis antigens MAGE-A4 and NY-ESO-1, and afamitresgene autoleucel, a MAGE-A4-directed T-cell receptor therapy, was approved in the United States in 2024 for advanced disease in HLA-A*02 patients, with letetresgene autoleucel against NY-ESO-1 following in trials.
Five to ten percent of soft-tissue sarcomas, typically in adolescents and young adults near the joints of the limbs; about half eventually metastasise, often to the lungs, and it is one of the few sarcomas where chemotherapy clearly helps.
Bone sarcomas favour the fast-growing ends of long bones (osteosarcoma) or the shaft (Ewing), soft tissue sarcomas the deep muscle compartments; spread is through the blood to the lungs, rarely via lymph nodes.
Lymph node spread is rare (except epithelioid, synovial, clear cell and rhabdomyosarcoma); sarcomas go through the blood to the lungs.
Same organ: Adamantinoma of bone, Dedifferentiated chordoma, Poorly differentiated chordoma (SMARCB1-deficient), Desmoplastic small round cell tumour, Leiomyosarcoma, Liposarcoma, Sarcomas (soft tissue, bone, GIST), Osteosarcoma, Ewing sarcoma, Rhabdomyosarcoma, Chordoma, Desmoid tumour, Tenosynovial giant cell tumour (TGCT), Epithelioid sarcoma, Vascular tumours (angiosarcoma, epithelioid haemangioendothelioma, kaposiform haemangioendothelioma), Chondrosarcoma, Angiosarcoma, Undifferentiated pleomorphic sarcoma (UPS), Myxofibrosarcoma, Alveolar soft part sarcoma, Perivascular epithelioid cell tumour (PEComa), Epithelioid haemangioendothelioma, Malignant peripheral nerve sheath tumour (MPNST), Retroperitoneal sarcoma, Soft tissue sarcoma of the extremity (localised and advanced)
Wide resection with pre- or postoperative radiotherapy; neoadjuvant or adjuvant ifosfamide-doxorubicin for large high-risk tumours.
Ifosfamide-based chemotherapy, doxorubicin; pazopanib or trabectedin later.
Afamitresgene autoleucel after chemotherapy; NY-ESO-1 TCR therapy in trials.
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Patients with advanced synovial sarcoma, a rare cancer of young adults with few effective drugs, now have an approved cell therapy that produces responses lasting about a year in a substantial minority, if their tissue type and tumour antigen match. It proves that engineered T cells can work against a solid tumour when a good target is present, which had been elusive. It is not a cure for most, requires specialised centres, and only a minority of patients are eligible.
This study opened the path to engineered T-cell receptor therapy in synovial sarcoma, leading to afamitresgene autoleucel targeting MAGE-A4 (SPEARHEAD-1) and its approval in 2024.
Three cycles of neoadjuvant anthracycline-ifosfamide is a reasonable standard for fit patients with high-risk limb or trunk sarcoma, particularly undifferentiated pleomorphic sarcoma.
Single-agent doxorubicin is the standard first-line palliative treatment for most advanced sarcomas, with doxorubicin-ifosfamide reserved for fit patients in whom tumour shrinkage matters.
SS18-SSX fusion testing confirms the diagnosis of synovial sarcoma, and the fusion's disruption of the BAF chromatin remodelling complex underlies experimental therapies such as BRD9 degraders; the tumour's MAGE-A4 and NY-ESO-1 expression enabled T-cell receptor therapy.
Query for this cancer: (TITLE:"Synovial sarcoma" OR ABSTRACT:"Synovial sarcoma" OR TITLE:"SS18-SSX sarcoma" OR ABSTRACT:"SS18-SSX sarcoma") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Synovial sarcoma, not a curated reading list.
The targets of this cancer's medicines and the ones linked to it directly.
Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes.
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Bleeding that does not stop by itself, bleeding from more than one site, or new bruising in several places or one large area.
Sudden severe abdominal pain, a hard or very tender abdomen, or abdominal pain with vomiting and fever. Boxed warning for gastrointestinal perforation on bevacizumab.
Fainting, near-fainting, or an irregular or racing heartbeat; several kinase inhibitors prolong the QT interval and the labels require ECG and electrolyte monitoring.
Cumulative dose: risk rises steeply above 400-550 mg/m² (see the anthracycline calculator).
Take on an empty stomach (1 hour before or 2 hours after food).
Alcohol: avoid (hepatotoxicity). Dexamethasone 20 mg before each dose protects the liver.
See all on the product pages:DoxorubicinIfosfamidePazopanibTrabectedin·Printable cards in the navigator
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Everything in development, the medicines held by this cancer's subtypes, the open problems and what is being done about them, the roadmaps, and what changed on this record.
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