{"entity":{"id":"alveolar-soft-part-sarcoma","kind":"cancer","name":"Alveolar soft part sarcoma","aka":["ASPS","ASPSCR1-TFE3 sarcoma"],"tldr":"Alveolar soft part sarcoma is a rare, slow-growing cancer of young adults driven by a single fusion gene, ASPSCR1-TFE3, that switches on blood vessel growth. Chemotherapy does not work, but drugs that block the tumour's blood supply shrink it, and in 2023 the immunotherapy atezolizumab became the first drug approved for it.","summary":"Alveolar soft part sarcoma is defined by the unbalanced translocation der(17)t(X;17) that fuses ASPSCR1 to the transcription factor TFE3, driving a programme of angiogenesis and metabolic genes; the same TFE3 fusion partner occurs in translocation renal cell carcinoma. The tumour is richly vascular, grows slowly in deep muscle of the limbs of young adults or in the orbit and tongue of children, and metastasises early to the lungs, bone and, unusually for a sarcoma, the brain. Because it is indolent, patients with metastases often survive many years, and the disease is followed with regular brain imaging.\n\nLocalised tumours are treated with wide resection, with radiotherapy for close margins, and isolated metastases with surgery or stereotactic radiotherapy. Conventional chemotherapy is ineffective. VEGFR-directed kinase inhibitors are active: sunitinib produced responses in Italian series, cediranib improved progression-free survival against placebo in the randomised CASPS trial, pazopanib is used in Europe, and anlotinib, approved in China for soft tissue sarcoma, showed benefit in the alveolar soft part sarcoma cohort of the APROMISS phase 3 trial.\n\nDespite a low mutational burden, the tumour responds to PD-L1 blockade: the NCI-sponsored phase 2 study of atezolizumab produced durable objective responses in a substantial minority of patients, leading to the first FDA approval for any drug in this disease in December 2023 for unresectable or metastatic alveolar soft part sarcoma in patients aged two and over. Combinations of checkpoint inhibitors with anti-angiogenic drugs, including benmelstobart plus anlotinib, are the main line of current trials.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Alveolar_soft_part_sarcoma","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Alveolar_soft_part_sarcoma"}],"tags":["subtype-page"],"related":["extremity-soft-tissue-sarcoma","synovial-sarcoma"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"sarcoma","burden":"Under one percent of soft tissue sarcomas, arising in adolescents and young adults, usually in the thigh or buttock and in children in the head and neck; it grows slowly but has often already spread to the lungs, bone or brain at diagnosis, and patients live for years with metastatic disease.","subtypes":["Alveolar soft part sarcoma of the deep soft tissue of the limbs (adolescents and young adults)","Head and neck (orbit, tongue) alveolar soft part sarcoma in children","Metastatic disease to lung, bone and brain (indolent course)"],"biomarkers":["ASPSCR1-TFE3 fusion (FISH or RNA sequencing; TFE3 immunohistochemistry)","PAS-positive, diastase-resistant crystals","Brain imaging surveillance for metastases"],"standardOfCare":[{"setting":"Localised","approach":"Wide resection with radiotherapy for close or positive margins; surveillance of lungs and brain.","refs":["limb-salvage-surgery","imrt-igrt","mri"]},{"setting":"Advanced, first line","approach":"Atezolizumab (FDA approved 2023) or a VEGFR kinase inhibitor (sunitinib, pazopanib; anlotinib in China); conventional chemotherapy is not used.","refs":["atezolizumab","checkpoint-inhibitor","sunitinib","pazopanib","anlotinib","nct03016819"]},{"setting":"Oligometastatic","approach":"Metastasectomy or stereotactic radiotherapy to lung and brain lesions in slowly progressing disease.","refs":["sbrt","limb-salvage-surgery"]}],"stateOfArt":["Atezolizumab is the first approved therapy, with durable responses despite a low mutational burden.","Anti-angiogenic kinase inhibitors remain active alternatives and partners for immunotherapy.","The slow course means long survival with metastases and a need for decades of surveillance."],"history":[{"year":1952,"title":"Christopherson, Foote and Stewart name alveolar soft part sarcoma","refs":[]},{"year":2001,"title":"ASPSCR1-TFE3 fusion identified as the defining alteration","refs":[]},{"year":2009,"title":"Sunitinib shows activity in alveolar soft part sarcoma","refs":["sunitinib"]},{"year":2019,"title":"CASPS: cediranib improves progression-free survival against placebo","refs":[]},{"year":2023,"title":"Atezolizumab approved by the FDA, the first drug for the disease","refs":["atezolizumab"]}],"pipeline":["atezolizumab","anlotinib","nct07548177","nct03016819","checkpoint-inhibitor"],"openProblems":["Why a low-mutation fusion sarcoma responds to immunotherapy is not understood.","Brain metastases are common and hard to treat.","No cure for metastatic disease despite long survival."],"parent":"sarcoma"},"route":"/cancers/alveolar-soft-part-sarcoma/","neighbours":{"cancer":[{"id":"sarcoma","kind":"cancer","name":"Sarcomas (soft tissue, bone, GIST)","route":"/cancers/sarcoma/"},{"id":"extremity-soft-tissue-sarcoma","kind":"cancer","name":"Soft tissue sarcoma of the extremity (localised and advanced)","route":"/cancers/extremity-soft-tissue-sarcoma/"},{"id":"synovial-sarcoma","kind":"cancer","name":"Synovial sarcoma","route":"/cancers/synovial-sarcoma/"}],"drug":[{"id":"anlotinib","kind":"drug","name":"Anlotinib","route":"/drugs/anlotinib/"},{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"},{"id":"pazopanib","kind":"drug","name":"Pazopanib","route":"/drugs/pazopanib/"},{"id":"sunitinib","kind":"drug","name":"Sunitinib","route":"/drugs/sunitinib/"}],"trial":[{"id":"nct07548177","kind":"trial","name":"Clinical Trials of Benmelstobart Injection Combined With Anlotinib Hydrochloride Capsules in the Treatment of Advanced or Unresectable Alveolar Soft Part Sarcoma","route":"/trials/nct07548177/"},{"id":"nct03016819","kind":"trial","name":"Phase III Trial of Anlotinib, Catequentinib in Advanced Alveolar Soft Part Sarcoma, Leiomyosarcoma, Synovial Sarcoma (APROMISS)","route":"/trials/nct03016819/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"id":"imrt-igrt","kind":"technology","name":"IMRT / IGRT (modern external beam)","route":"/technologies/imrt-igrt/"},{"id":"limb-salvage-surgery","kind":"technology","name":"Limb-salvage surgery and endoprosthetic reconstruction","route":"/technologies/limb-salvage-surgery/"},{"id":"mri","kind":"technology","name":"MRI","route":"/technologies/mri/"},{"id":"sbrt","kind":"technology","name":"SBRT / SABR (stereotactic radiotherapy)","route":"/technologies/sbrt/"}]}}