Desmoid tumour
Desmoid tumours are locally aggressive growths of fibroblast-like cells 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 now standard, and for those that progress the first drug built for the disease, the gamma-secretase inhibitor nirogacestat, shrinks tumours and relieves pain.
Overview
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.
When 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.
Gamma-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.
State of the art today
- 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.
Where it starts and where it drains
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.
- Metaphysis, near the growth plate (osteosarcoma)
- Shaft (Ewing sarcoma)
- Deep soft tissue compartmentSporadic (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)
- Skeletal muscle (rhabdomyosarcoma)
- Neurovascular bundle (limb salvage decision)
Lymph node spread is rare (except epithelioid, synovial, clear cell and rhabdomyosarcoma); sarcomas go through the blood to the lungs.
Same organ: Sarcomas (soft tissue, bone, GIST), Osteosarcoma, Ewing sarcoma, Rhabdomyosarcoma, Chordoma, Tenosynovial giant cell tumour (TGCT), Epithelioid sarcoma, Vascular tumours (angiosarcoma, epithelioid haemangioendothelioma, kaposiform haemangioendothelioma)
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.
- AI in radiologyEstablished
- cfDNA fragmentomicsEstablished
- Colorectal cancer screening (colonoscopy, FIT, stool DNA, blood)Standard of care
- DNA methylation profilingEstablished
- HCC surveillance in cirrhosis (ultrasound + AFP)Standard of care
- High-risk pancreatic surveillance (CAPS / PRECEDE)Established
- A 28-day national pathway for people with a positive multi-cancer blood test
- A breath test to rule out cancer in people with vague symptoms
- A cancer blood test for older people arriving at A&E with unexplained symptoms
- A legislated, publicly reported 28-day standard from urgent referral to diagnosis
- A live national dashboard of stage at diagnosis as the scorecard for early detection
- A single 'cancer check at 60' appointment bundling all screening tests
Background: Alpha-fetoprotein (AFP), Barrett's oesophagus, CA 19-9, Early detection, Faecal immunochemical test (FIT). Also on OnCo: Symptoms and red flags · Early detection roadmap.
Where the cases are
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
Active surveillance with MRI at 1 to 2 months, then every 3 to 6 months; treat only on progression or symptoms.
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.
Reserved for selected abdominal wall tumours or complications (bowel obstruction, fistula); margins do not reliably predict recurrence.
Subtypes & biomarkers
top- 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)
- 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)
Target prevalence in this cancer
- 1832MacFarlane describes abdominal wall tumours later called desmoid
Named from the Greek for band-like.
- 1997CTNNB1 and APC mutations link desmoid to the WNT pathway
Tejpar and colleagues.
- 2011Prospective observation cohorts published
French Sarcoma Group and others show frequent spontaneous stabilisation, seeding the surveillance-first approach.
- 2018Sorafenib beats placebo (Alliance A091105)
Gounder and colleagues, NEJM.
- 2020Desmoid Tumor Working Group consensus
Active surveillance as initial management for most patients (Eur J Cancer).
- 2023Nirogacestat approved
DeFi phase 3 (NEJM 2023); FDA approval 27 November 2023, the first for desmoid tumours.
Open problems, and what is being done about each
Ovarian toxicity of gamma-secretase inhibitors in young women: dose interruption and intermittent schedules are being explored.
and how the field plans to fix it →What is being done about thisSide effects and quality of lifeAvailable now- Cardio-oncologyEstablished
- Exercise & lifestyle oncologyEstablished
- Geriatric assessmentEstablished
- IMRT / IGRT (modern external beam)Standard of care
- Oncology nutrition assessment and medical nutrition therapyEstablished
- Proton therapyEstablished
In trialsIdeas and roadmaps- A cheap old tablet to restore appetite
- A coordinated FLASH radiotherapy evidence programme with shared dose-rate standards
- A dedicated programme for cachexia and treatment toxicity research
- A dietitian in every gastrointestinal and head and neck tumour board
- A funded programme of organ-preservation trials to avoid radical surgery
- A lifelong late-effects registry linked to every treatment for adult survivors
Background: CTCAE toxicity grading (grade 3-4 adverse events), De-escalation, escalation and response-adapted therapy, Immune-related adverse events (irAEs), Quality of life, Toxicity grade. Also on OnCo: Side effects, symptom first · Immune-related side effects · Toxicity compare · Survivorship planner.
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.
Trials
topRecruiting now (live from ClinicalTrials.gov)
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Landmark trials in OnCo
Expert centres
topCentres linked to this cancer in OnCo
No institutions are linked to this cancer yet. The general institution ranking is the place to start.
Questions to ask
topQuestions to ask your oncologist about Desmoid tumour
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Why: Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example CTNNB1 mutation type, Germline APC testing when intra-abdominal or multifocal, Nuclear beta-catenin immunostaining, MRI T2 signal, Symptom and pain scores), and what were the results?Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Why: Recognised subtypes for this cancer include Sporadicdesmoid, FAP-associateddesmoid, often intra-abdominal, Abdominal wall desmoid.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Newly diagnosed, asymptomatic or minimally symptomatic
- For my situation (newly diagnosed, asymptomatic or minimally symptomatic), which of the standard options do you recommend and why?Why: Guideline options include: Active surveillance with MRI at 1 to 2 months, then every 3 to 6 months; treat only on progression or symptoms.
Progressive or symptomatic disease
- For my situation (progressive or symptomatic disease), which of the standard options do you recommend and why?Why: Guideline options include: 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.
- Am I a candidate for Nirogacestat, Sorafenib, Methotrexate, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of DeFi apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Surgery
- For my situation (surgery), which of the standard options do you recommend and why?Why: Guideline options include: Reserved for selected abdominal wall tumours or complications (bowel obstruction, fistula); margins do not reliably predict recurrence.
Any stage
- Are there clinical trials I could join, for example of Nirogacestat, Intermittent or stop-and-restart nirogacestat in desmoid tumours, DeFi?Why: Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Why: Supportive care improves quality of life and helps patients complete treatment.
- I read that “Ovarian toxicity of gamma-secretase inhibitors in young women: dose interruption and intermittent schedules are being explored”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “Optimal treatment duration and whether responses persist after stopping nirogacestat”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
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topQuery for this cancer: (TITLE:"Desmoid tumour" OR ABSTRACT:"Desmoid tumour" OR TITLE:"Aggressive fibromatosis" OR ABSTRACT:"Aggressive fibromatosis" OR TITLE:"Desmoid-type fibromatosis" OR ABSTRACT:"Desmoid-type fibromatosis") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Desmoid tumour, not a curated reading list.
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