{"entity":{"id":"desmoid-tumour","kind":"cancer","name":"Desmoid tumour","aka":["Aggressive fibromatosis","Desmoid-type fibromatosis"],"tldr":"Desmoid tumours are locally aggressive growths of fibroblast-like cells, classed with soft-tissue sarcomas, driven by WNT mutations, that never spread to distant organs but can invade nerves, bowel and muscle. Many stop growing or shrink on their own, so watching first is standard; if they progress, the gamma-secretase inhibitor nirogacestat, approved in 2023, shrinks tumours and relieves pain.","summary":"Desmoid tumours are monoclonal fibroblastic proliferations driven by WNT pathway activation: about 85 percent carry somatic CTNNB1 (beta-catenin) mutations (T41A, S45F, S45P) and most of the rest arise in familial adenomatous polyposis through germline APC loss. They do not metastasise but infiltrate locally in the abdominal wall, mesentery, limbs and trunk, and their course is unpredictable: a substantial fraction stabilise or regress spontaneously, which is why the Desmoid Tumor Working Group consensus (2020) recommends active surveillance as the initial approach for most patients, with treatment reserved for progression or symptoms.\n\nWhen treatment is needed the order has inverted over two decades: surgery, once first line, is now used selectively because recurrence after resection is common (S45F mutations and extra-abdominal sites recur most). Medical options are sorafenib (Alliance A091105, NEJM 2018: longer progression-free survival than placebo), nirogacestat (DeFi, NEJM 2023: fewer progressions than placebo with improvements in pain, symptom burden and physical function; FDA approval November 2023, the first drug approved for desmoid tumours), low-dose methotrexate-vinblastine or vinorelbine, and anthracycline chemotherapy for rapidly progressive disease. Cryoablation and high-intensity focused ultrasound offer local control for extra-abdominal tumours.\n\nGamma-secretase inhibitors block NOTCH cleavage, and their class toxicity is ovarian dysfunction in women of reproductive age, often reversible; a second agent, AL102, has completed the RINGSIDE phase 3. Open questions are how long to treat, whether intermittent dosing preserves benefit, and how to sequence surveillance, ablation and drugs.","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Aggressive_fibromatosis","links":[{"label":"NCI PDQ: soft tissue sarcoma","url":"https://www.cancer.gov/types/soft-tissue-sarcoma"},{"label":"Desmoid Tumor Working Group consensus (Eur J Cancer 2020)","url":"https://doi.org/10.1016/j.ejca.2020.06.022"},{"label":"DeFi trial (NEJM 2023)","url":"https://doi.org/10.1056/NEJMoa2210140"},{"label":"FDA approval of nirogacestat","url":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-nirogacestat-desmoid-tumors"}],"tags":["nci-coverage","rare","sarcoma"],"related":["tenosynovial-giant-cell-tumour","dermatofibrosarcoma-protuberans","inflammatory-myofibroblastic-tumour","gist"],"cancers":[],"sections":[],"technologies":["active-surveillance","mri","cytotoxic-chemotherapy","kinase-inhibitors"],"targets":[],"drugs":["nirogacestat","sorafenib","methotrexate","doxorubicin"],"companies":["springworks","bayer","elpiscience-suzhou-biopharma"],"institutions":[],"pathways":["wnt","notch"],"terms":["rare-cancers"],"trials":["defi","nct04871282"],"people":[],"bottlenecks":["b-rare-cancers","b-toxicity-qol"],"keyPapers":["paper-timbergen-eur-j-cancer","paper-gounder-n-engl-j-med"],"journals":["european-journal-of-cancer"],"dependsOn":[],"notes":[],"group":"sarcoma","burden":"Roughly 2 to 5 new cases per million people per year, most often in young adults; more common in women and in people with familial adenomatous polyposis.","subtypes":["Sporadic (CTNNB1-mutant) desmoid","FAP-associated (APC-mutant) desmoid, often intra-abdominal","Abdominal wall desmoid (often post-partum)","Extra-abdominal desmoid (limb, trunk, head and neck)"],"biomarkers":["CTNNB1 mutation type (S45F associated with higher recurrence)","Germline APC testing when intra-abdominal or multifocal","Nuclear beta-catenin immunostaining","MRI T2 signal (hypointense tumours are more likely to be stable or regressing)","Symptom and pain scores (treatment triggers)"],"standardOfCare":[{"setting":"Newly diagnosed, asymptomatic or minimally symptomatic","approach":"Active surveillance with MRI at 1 to 2 months, then every 3 to 6 months; treat only on progression or symptoms.","refs":["active-surveillance","mri"],"guideline":{"nccn":"Category 2A (observation)","version":"Desmoid Tumor Working Group consensus (Eur J Cancer 2020); NCCN Soft Tissue Sarcoma","url":"https://doi.org/10.1016/j.ejca.2020.06.022"}},{"setting":"Progressive or symptomatic disease","approach":"Nirogacestat (DeFi) or sorafenib (Alliance A091105); alternatives include methotrexate-vinblastine, vinorelbine, anthracycline-based chemotherapy for rapidly progressive disease, and cryoablation for accessible extra-abdominal tumours.","refs":["nirogacestat","sorafenib","defi","methotrexate"],"guideline":{"nccn":"Category 1 (nirogacestat), Category 2A (sorafenib)","version":"NCCN Soft Tissue Sarcoma"}},{"setting":"Surgery","approach":"Reserved for selected abdominal wall tumours or complications (bowel obstruction, fistula); margins do not reliably predict recurrence.","refs":["limb-salvage-surgery"]}],"stateOfArt":["Watching first is now the standard: prospective surveillance cohorts showed spontaneous stabilisation or regression in a large minority, avoiding surgical morbidity for many.","Nirogacestat is the first drug approved specifically for desmoid tumours and the first gamma-secretase inhibitor approved for any cancer, converting a WNT-driven disease into a NOTCH-targeted indication.","Sorafenib gave the first randomised evidence that a systemic drug controls the disease, and remains an option where nirogacestat is unavailable.","Local ablation (cryoablation, HIFU) offers organ-sparing control for extra-abdominal tumours and is being compared with drugs in trials."],"history":[{"year":1832,"title":"MacFarlane describes abdominal wall tumours later called desmoid","note":"Named from the Greek for band-like.","refs":[]},{"year":1997,"title":"CTNNB1 and APC mutations link desmoid to the WNT pathway","note":"Tejpar and colleagues.","refs":[]},{"year":2011,"title":"Prospective observation cohorts published","note":"French Sarcoma Group and others show frequent spontaneous stabilisation, seeding the surveillance-first approach.","refs":[]},{"year":2018,"title":"Sorafenib beats placebo (Alliance A091105)","note":"Gounder and colleagues, NEJM.","refs":["sorafenib"]},{"year":2020,"title":"Desmoid Tumor Working Group consensus","note":"Active surveillance as initial management for most patients (Eur J Cancer).","refs":["active-surveillance"]},{"year":2023,"title":"Nirogacestat approved","note":"DeFi phase 3 (NEJM 2023); FDA approval 27 November 2023, the first for desmoid tumours.","refs":["nirogacestat","defi"]}],"pipeline":["nirogacestat","idea-desmoid-intermittent-dosing","defi","varegacestat"],"openProblems":["Ovarian toxicity of gamma-secretase inhibitors in young women: dose interruption and intermittent schedules are being explored.","Optimal treatment duration and whether responses persist after stopping nirogacestat.","Predicting which tumours will regress spontaneously (MRI signal and mutation type are candidate markers).","Head-to-head comparison of cryoablation versus systemic therapy for extra-abdominal disease."],"parent":"sarcoma"},"route":"/cancers/desmoid-tumour/","neighbours":{"cancer":[{"id":"dermatofibrosarcoma-protuberans","kind":"cancer","name":"Dermatofibrosarcoma protuberans","route":"/cancers/dermatofibrosarcoma-protuberans/"},{"id":"gist","kind":"cancer","name":"Gastrointestinal stromal tumour (GIST)","route":"/cancers/gist/"},{"id":"inflammatory-myofibroblastic-tumour","kind":"cancer","name":"Inflammatory myofibroblastic tumour (IMT)","route":"/cancers/inflammatory-myofibroblastic-tumour/"},{"id":"malignant-peripheral-nerve-sheath-tumour","kind":"cancer","name":"Malignant peripheral nerve sheath tumour (MPNST)","route":"/cancers/malignant-peripheral-nerve-sheath-tumour/"},{"id":"sarcoma","kind":"cancer","name":"Sarcomas (soft tissue, bone, GIST)","route":"/cancers/sarcoma/"},{"id":"tenosynovial-giant-cell-tumour","kind":"cancer","name":"Tenosynovial giant cell tumour (TGCT)","route":"/cancers/tenosynovial-giant-cell-tumour/"}],"technology":[{"id":"active-surveillance","kind":"technology","name":"Active surveillance","route":"/technologies/active-surveillance/"},{"id":"cryoablation-systems","kind":"technology","name":"Cryoablation systems","route":"/technologies/cryoablation-systems/"},{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"},{"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":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"drug":[{"id":"doxorubicin","kind":"drug","name":"Doxorubicin","route":"/drugs/doxorubicin/"},{"id":"methotrexate","kind":"drug","name":"Methotrexate","route":"/drugs/methotrexate/"},{"id":"nirogacestat","kind":"drug","name":"Nirogacestat","route":"/drugs/nirogacestat/"},{"id":"sorafenib","kind":"drug","name":"Sorafenib","route":"/drugs/sorafenib/"},{"id":"varegacestat","kind":"drug","name":"Varegacestat","route":"/drugs/varegacestat/"}],"company":[{"id":"bayer","kind":"company","name":"Bayer","route":"/companies/bayer/"},{"id":"elpiscience-suzhou-biopharma","kind":"company","name":"Elpiscience (Suzhou) Biopharma","route":"/companies/elpiscience-suzhou-biopharma/"},{"id":"immunome","kind":"company","name":"Immunome","route":"/companies/immunome/"},{"id":"merck-kgaa","kind":"company","name":"Merck KGaA (EMD Serono)","route":"/companies/merck-kgaa/"},{"id":"springworks","kind":"company","name":"SpringWorks Therapeutics (Merck KGaA)","route":"/companies/springworks/"}],"pathway":[{"id":"notch","kind":"pathway","name":"Notch signalling","route":"/pathways/notch/"},{"id":"wnt","kind":"pathway","name":"Wnt / β-catenin","route":"/pathways/wnt/"}],"term":[{"id":"rare-cancers","kind":"term","name":"Rare cancers","route":"/terms/rare-cancers/"}],"trial":[{"id":"nct07541430","kind":"trial","name":"A Study in Adults With Desmoid Tumors","route":"/trials/nct07541430/"},{"id":"nct04871282","kind":"trial","name":"A Study of AL102 in Patients With Progressing Desmoid Tumors","route":"/trials/nct04871282/"},{"id":"nct07170644","kind":"trial","name":"A Study of Nirogacestat in Japanese Adults With Desmoid Tumors/Aggressive Fibromatosis (DT/AF)","route":"/trials/nct07170644/"},{"id":"defi","kind":"trial","name":"DeFi","route":"/trials/defi/"}],"bottleneck":[{"id":"b-rare-cancers","kind":"bottleneck","name":"Rare and paediatric cancers without markets","route":"/bottlenecks/b-rare-cancers/"},{"id":"b-toxicity-qol","kind":"bottleneck","name":"Toxicity and quality of life are undervalued","route":"/bottlenecks/b-toxicity-qol/"}],"paper":[{"id":"paper-timbergen-eur-j-cancer","kind":"paper","name":"Active surveillance in desmoid-type fibromatosis: A systematic literature review","route":"/key-papers/paper-timbergen-eur-j-cancer/"},{"id":"paper-gounder-n-engl-j-med","kind":"paper","name":"Nirogacestat, a γ-Secretase Inhibitor for Desmoid Tumors","route":"/key-papers/paper-gounder-n-engl-j-med/"}],"journal":[{"id":"european-journal-of-cancer","kind":"journal","name":"European Journal of Cancer","route":"/journals/european-journal-of-cancer/"}],"idea":[{"id":"idea-desmoid-intermittent-dosing","kind":"idea","name":"Intermittent or stop-and-restart nirogacestat in desmoid tumours","route":"/ideas/idea-desmoid-intermittent-dosing/"}],"target":[{"id":"aph1a","kind":"target","name":"APH1A","route":"/targets/aph1a/"},{"id":"aph1b","kind":"target","name":"APH1B","route":"/targets/aph1b/"},{"id":"gamma-secretase","kind":"target","name":"Gamma-secretase (PSEN1)","route":"/targets/gamma-secretase/"},{"id":"ncstn","kind":"target","name":"NCSTN","route":"/targets/ncstn/"},{"id":"psen2","kind":"target","name":"PSEN2","route":"/targets/psen2/"},{"id":"psenen","kind":"target","name":"PSENEN","route":"/targets/psenen/"}]}}