RARE DISEASE
Desmoid tumor
Desmoid tumor
Desmoid tumor
Synonyms: Aggressive fibromatosis, Desmoid type fibromatosis
Synonyms: Aggressive fibromatosis, Desmoid type fibromatosis
Synonyms: Aggressive fibromatosis, Desmoid type fibromatosis
Drug discovery
7
drugs
With orphan designations
Overview
Desmoid tumors, also known as aggressive fibromatosis, are rare, non-metastatic fibroblastic neoplasms characterized by unpredictable growth and local invasiveness into surrounding tissues. With an annual incidence of 2–5 cases per million, they primarily affect adults aged 20–40 and show a 2:1 female predominance. Management prioritizes preserving function and quality of life due to their chronic, often debilitating nature.
Therapies
Active surveillance: First-line approach for asymptomatic/stable tumors [1][6][18].
Surgery: Reserved for low-morbidity cases (e.g., abdominal wall tumors) [1][11].
Medical therapy: TKIs (sorafenib, pazopanib), methotrexate/vinblastine, and gamma secretase inhibitors (nirogacestat FDA-approved in 2023) [1][13][16].
Categories: rare neoplastic diseases
Research Papers
1,228 drug discovery papers about Desmoid tumor, with 1 first-in-class and 7 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,228 drug discovery papers about Desmoid tumor, with 1 first-in-class and 7 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-09-30 | Evolution of treatment strategies and surgical outcomes in desmoid tumors: A retrospective cohort study.
Desmoid tumors (DT) are rare fibroblastic neoplasms characterized by local aggressiveness, absence of metastatic potential, and heterogeneous clinical behavior. During the last decade, management has shifted from routine upfront surgery toward active surveillance and selective systemic therapy. We evaluated temporal changes in management and surgical outcomes within a multicenter real-world cohort. We retrospectively reviewed consecutive patients with histologically confirmed DT managed between January 2015 and January 2026 across four tertiary hospitals in Madrid, Spain. Treatment-era analyses compared 2015-2019 with 2020-2026. Local recurrence-free survival (RFS) after surgery was estimated using the Kaplan-Meier method. Eighty-two patients were included. Initial management was available for 79 patients: surgery in 48, active surveillance in 17, and systemic therapy in 14. Among 77 patients with an assignable treatment era, upfront surgery decreased from 24/30 (80.0%) in 2015-2019 to 24/47 (51.1%) in 2020-2026 (Fisher p = 0.015), while active surveillance and systemic therapy increased. Fifty-three patients underwent surgery during follow-up. Local recurrence occurred in 11/51 patients with evaluable postoperative follow-up. R1 resection was associated with a higher unadjusted risk of local recurrence than R0 resection (40.0% vs 3.8%; conditional OR 15.84, exact 95% CI 1.92-751.38; Fisher p = 0.002). Contemporary recommendations have been progressively incorporated into routine practice, with reduced reliance on upfront surgery. Surgery remains important in selected patients. The observed association between R1 margins and local recurrence is unadjusted and should be interpreted cautiously given the limited number of events and potential residual confounding.
2026-09-29 | Familial adenomatous polyposis-associated desmoid disease: comprehensive review.
Familial adenomatous polyposis (FAP)-associated desmoid disease is a rare but important manifestation of FAP and remains a major cause of morbidity and mortality. In contrast to sporadic desmoids, which most commonly occur in the abdominal wall or extra-abdominal sites, approximately 70% of FAP-associated desmoids arise intra-abdominally, usually within the small bowel mesentery. These lesions can cause bowel and ureteric obstruction, sepsis, intestinal failure, and death. This review summarizes current evidence regarding the pathogenesis, risk factors, diagnosis, surveillance, and management of FAP-associated desmoid disease, and identifies key evidence gaps. A literature search was performed in accordance with PRISMA methodology using Medline, Embase, PROSPERO, Cochrane, Campbell, and Joanna Briggs Institute databases. Original research studies, reviews, and guidelines relating to desmoid disease, FAP-associated desmoid disease, and FAP published up to August 2025 were eligible. Data were extracted and synthesized narratively by topic. Aberrant Wnt/β-catenin signalling resulting from a germline APC pathogenic variant and a somatic second hit underpin the development of FAP-associated desmoid disease. Established risk factors include a distal APC pathogenic variant, positive family history, and previous abdominal surgery. Diagnosis in patients with established FAP is usually clinicoradiological, and routine biopsy is generally unnecessary, except in select circumstances. Active surveillance is now recommended as first-line management for most patients because many lesions remain stable or regress spontaneously. Surgery is primarily reserved for complications, particularly in small bowel mesenteric disease, owing to substantial operative morbidity and a lack of demonstrated survival benefit from complete resection. Systemic therapy is indicated for progressive or symptomatic disease. Tyrosine kinase inhibitors and the γ-secretase inhibitor nirogacestat have demonstrated efficacy in randomized trials, although patients with FAP-associated disease comprise only a small proportion of enrolled patients. Evidence supporting the use of non-steroidal anti-inflammatory drugs and anti-oestrogens remains limited. Important evidence gaps remain regarding optimal imaging strategies, predictors of aggressive disease, clinically meaningful trial endpoints, and FAP-specific treatment algorithms. Dedicated studies in genetically defined FAP cohorts are required to improve risk stratification and management.
2026-09-21 | Defining absolute postoperative desmoid risk in familial adenomatous polyposis according to APC genotype and family history: retrospective cohort study.
Desmoid disease is a major cause of morbidity and mortality in familial adenomatous polyposis (FAP), particularly after prophylactic colorectal surgery. Although APC genotype and family history are recognized risk factors, previous sizeable studies report relative rather than absolute risks. This study aimed to quantify absolute postoperative desmoid risk in FAP patients undergoing risk-reducing colectomy, stratified by APC genotype, and to assess the modifying effect of family history. This retrospective observational study used records from a prospectively maintained registry. Patients with an APC pathogenic variant (PV) 3' of codon 1399 were classified as high risk, and those with an APC PV 5' of (or at) codon 1399 were classified as low risk. Patients who had not undergone prophylactic colectomy, with < 5 years of postoperative follow-up, or those with a desmoid diagnosed before or at the time of surgery were excluded. Clinical records were reviewed for details of surgery, desmoid diagnosis, and family history. A positive family history was defined as a first-degree relative with genetically confirmed FAP and a diagnosis of desmoid disease (clinical and/or radiological). Among 48 high-risk patients, 30 (63%) developed desmoid, with no significant difference between colectomy and proctocolectomy (54% versus 70%, respectively; χ2 = 1.42; P = 0.233). Family history was present in 35 of the 48 patients (73%) and increased desmoid risk relative to no family history (80% versus 15%, respectively; P < 0.01). Among the 1213 low-risk patients, 154 (12.7%) developed desmoids, with no significant effect of surgical procedure (13.9% versus 12.1% for proctocolectomy and total/partial colectomy, respectively; χ² = 0.77; P = 0.380). Family history increased desmoid risk relative to no family history (30% versus 10%, respectively; P < 0.01). A family history of desmoid disease appears to be an important determinant of postoperative desmoid risk in FAP. Although APC PV 3' of codon 1399 does confer a high overall risk, this is largely confined to individuals with first-degree relatives with desmoid. In the absence of a family history, postoperative desmoid risk appeared relatively low regardless of genotype. This supports a more individualized approach to perioperative counselling and surgical decision-making in patients with FAP. In addition, these data highlight that patients with both a 3' APC PV and a positive family history are a particularly high-risk subgroup who may represent an appropriate target population for future chemoprevention trials.
2026-09-19 | Efficacy of celecoxib and methotrexate-vinblastine regimen in desmoid-type fibromatosis: A retrospective cohort study.
Desmoid tumors are classified as borderline malignancies and are characterized by a high rate of local recurrence despite the absence of distant metastasis. Low-dose methotrexate combined with vinblastine, known as the methotrexate and vinblastine (MV) regimen, has been reported as an effective treatment for desmoid-type fibromatosis (DF). At our institution, we adopt a treatment strategy beginning with celecoxib as the first-line therapy, escalating to the MV regimen only in cases showing disease progression. This study evaluates treatment outcomes based on this protocol. At our institution, 10 patients diagnosed with DF between 2003 and 2025 received surgical resection and/or pharmacotherapy. The standard approach involved initiating treatment with oral celecoxib; if no clinical improvement was observed, therapy was escalated to the MV regimen. Treatment response was assessed using Response Evaluation Criteria in Solid Tumors 1.1 criteria. Of the 10 cases, 1 achieved complete response, 5 showed partial response, 2 maintained stable disease, and 2 exhibited progressive disease, yielding a response rate of 60%. Among patients treated with the MV regimen, extended dosing intervals did not lead to tumor progression, and sustained suppression was observed in several cases. No grade 3 or 4 adverse events were reported. Celecoxib and the MV regimen appear to be effective and well-tolerated options for DF. Given its low toxicity and favorable tolerability, celecoxib should be considered the first-line treatment, especially since tumor control was achieved in half of the cases. Although tumor progression occurred in the remaining cases, disease control was subsequently achieved by introducing the MV regimen. These findings support recent trends favoring nonsurgical management and suggest that the celecoxib followed by the MV regimen strategy should be considered a primary therapeutic approach.
2026-07-29 | Deni Study: Real-World Data on the Use of Nirogacestat in Patients With Desmoid Tumors in the French Sarcoma Group.
The DeFi trial revealed a significant improvement in progression-free survival (PFS) with nirogacestat in patients with desmoid tumors. The DeNi study reports outcomes of patients treated with nirogacestat through the French compassionate use program. DeNi is a retrospective, real-world study. Outcomes included objective response, pain improvement, 1-year PFS, and toxicity. Between February and June 2024, 55 patients with desmoid tumors were included (37 women). Data were updated until November 2025. The median age was 38.6 years (range: 18.0-66.7). The median number of previous therapies was 2, including local therapies. The median follow-up was 21.4 months [95% CI: 19.5; 25.6]. The estimated median duration of nirogacestat treatment was 16 months. Partial response and stable disease were observed in 33 (60%) and 17 patients (31%), respectively. The 1-year PFS rate was 76.2%, and 77.0% of patients remained without treatment change at 1 year, including patients with dose reductions. Of the 49 patients with baseline pain, 38 (78%) experienced pain improvement under nirogacestat; 35 (71%) reduced or discontinued analgesics. The most frequent side effects (all grades) were diarrhea (53%), fatigue (47%), and rash (29%). Thirteen patients (24%) required dose reduction: 11 for digestive adverse events (85%), 1 for mucositis, and 1 for fatigue with hypertension. The DeNi study confirms the clinical benefits of nirogacestat in patients with desmoid tumors, with improvements in pain and tumor shrinkage observed in 60% of patients and PFS consistent with that reported in the phase III DeFi trial.
cell therapies
2026-06-22 | Intestinal transplantation for tumors.
Transplantation of the intestine is a vital component in the treatment of many intrabdominal tumors. This is a comprehensive review of current practice and outcome of intestinal transplantation for tumors. Most commonly described for the intrabdominal desmoid tumor, excellent survival outcomes can be attained, particularly for the more aggressive desmoid tumors associated with familial adenomatous polyposis syndrome and early referral is critical in order to avoid diffuse tumor spread which would necessitate a more complex multivisceral transplant. Currently, consensus within the intestinal transplant community lists invasive intrabdominal desmoid tumor as a primary indication for intestinal transplantation. Rare tumors such as metastatic neuroendocrine tumors confined to the abdomen, and pseudomyxoma peritonei have been associated with acceptable survival and recurrence outcomes with intestinal transplantation in carefully selected patients who would otherwise have a dismal prognosis. In addition, intestinal transplantation is an option for patients with a history of abdominal malignancy who have been rendered with intestinal failure due to surgical complications from resection of a primary tumor. Intestinal transplantation is a therapeutic option with excellent results in selected patients with intrabdominal desmoid tumors, neuroendocrine tumors and pseudomyxoma peritonei. Careful patient selection, technical expertise, and posttransplant oncologic surveillance is critical for successful long-term outcomes.
2024-06-24 | The Role of Colon in Isolated Intestinal Transplantation: Description of 4 Cases.
Intra-abdominal desmoid tumors are a rare and complex clinical problem. These tumors are locally invasive, and surgical ablation represents the mainstay of treatment. When localized at the root of the mesentery, their resection may require extensive excision of the intestine resulting in intestinal failure and life-long total parenteral nutrition. Intestinal transplantation, either autotransplantation or allotransplantation, has been used as a viable option to treat this group of patients. Herein, we describe a series of 4 patients with unresectable intra-abdominal desmoid tumor who underwent cadaveric isolated intestinal and ascending colon transplantation.
2024-01-24 | Treatment of Complex Desmoid Tumors in Familial Adenomatous Polyposis Syndrome by Intestinal Transplantation.
Desmoid tumors are fibroblastic lesions which often have an unpredictable and variable clinical course. In the context of familial adenomatous polyposis (FAP), these frequently occur intra-abdominally, especially in the small-bowel mesentery resulting in sepsis, fistulation, and invasion of the abdominal wall and retroperitoneum. In selected cases where other modalities have failed, the most radical option is to perform a total enterectomy and intestinal transplantation (ITx). In this study, we present our center's experience of ITx for desmoid in patients with FAP. We performed a retrospective review of our prospectively collected database between 2007 and 2022. All patients undergoing ITx for FAP-related desmoid were included. Between October 2007 and September 2023, 144 ITx were performed on 130 patients at our center. Of these, 15 patients (9%) were for desmoid associated with FAP (7 modified multivisceral transplants, 6 isolated ITx, and 2 liver-containing grafts). The median follow-up was 57 mo (8-119); 5-y patient survival was 82%, all with functioning grafts without local desmoid recurrence. These patients presented us with several complex surgical issues, such as loss of abdominal domain, retroperitoneal/abdominal wall involvement, ileoanal pouch-related issues, and the need for foregut resection because of adenomatous disease. ITx is a viable treatment in selected patients with FAP and extensive desmoid disease. The decision to refer for ITx can be challenging, particularly the timing and sequence of treatment (simultaneous versus sequential exenteration). Delays can result in additional disease burden, such as secondary liver disease or invasion of adjacent structures.
2023-09-04 | Sporadic Desmoid Tumor Mimicking Myofascial Pain Syndrome in a Chiropractic Clinic
Chiropractors are primary healthcare providers who diagnose and manage various health conditions, including rare cases like desmoid tumors. Desmoid tumors are locally aggressive soft-tissue tumors originating from fibroblasts. This report presents the case of a 30-year-old woman who initially sought chiropractic care for persistent neck pain that was later discovered to be a symptom of a sporadic desmoid tumor. The patient presented with severe right upper neck pain, which was diagnosed as myofascial pain syndrome and yielded no significant improvement after various treatments. Physical examination by a chiropractor revealed a soft-tissue mass in the right upper trapezius and rhomboid region. In addition, magnetic resonance imaging revealed an intramuscular lesion measuring 8 × 4 cm in the right rhomboids, and subsequent biopsy confirmed the diagnosis of a sporadic desmoid tumor. The patient underwent successful surgical excision of the tumor. Postoperatively, the chiropractor initiated a comprehensive 12-week rehabilitation program that significantly improved the patient's range of motion and muscular strength and alleviated pain. The remarkable aspect of this case was the location of the tumor in the right rhomboid muscle, a less common site for desmoid tumors. This case underscores the crucial role of chiropractors as primary healthcare providers in the early detection of oncological cases and management of post-surgical rehabilitation.
2023-04-25 | CD142 Identifies Neoplastic Desmoid Tumor Cells, Uncovering Interactions Between Neoplastic and Stromal Cells That Drive Proliferation
The interaction between neoplastic and stromal cells within a tumor mass plays an important role in cancer biology. However, it is challenging to distinguish between tumor and stromal cells in mesenchymal tumors because lineage-specific cell surface markers typically used in other cancers do not distinguish between the different cell subpopulations. Desmoid tumors consist of mesenchymal fibroblast-like cells driven by mutations stabilizing beta-catenin. Here we aimed to identify surface markers that can distinguish mutant cells from stromal cells to study tumor–stroma interactions. We analyzed colonies derived from single cells from human desmoid tumors using a high-throughput surface antigen screen, to characterize the mutant and nonmutant cells. We found that CD142 is highly expressed by the mutant cell populations and correlates with beta-catenin activity. CD142-based cell sorting isolated the mutant population from heterogeneous samples, including one where no mutation was previously detected by traditional Sanger sequencing. We then studied the secretome of mutant and nonmutant fibroblastic cells. PTX3 is one stroma-derived secreted factor that increases mutant cell proliferation via STAT6 activation. These data demonstrate a sensitive method to quantify and distinguish neoplastic from stromal cells in mesenchymal tumors. It identifies proteins secreted by nonmutant cells that regulate mutant cell proliferation that could be therapeutically. Significance: Distinguishing between neoplastic (tumor) and non-neoplastic (stromal) cells within mesenchymal tumors is particularly challenging, because lineage-specific cell surface markers typically used in other cancers do not differentiate between the different cell subpopulations. Here, we developed a strategy combining clonal expansion with surface proteome profiling to identify markers for quantifying and isolating mutant and nonmutant cell subpopulations in desmoid tumors, and to study their interactions via soluble factors.
gene therapies
2025-07-25 | Single-Cell Transcription Reveals the Fibroblast Heterogeneity and Neural Cells' Significance in Desmoid Fibromatosis.
Desmoid fibromatosis (DF) is a refractory tumor with a high recurrence rate, resulting in severe organ's deformity, morbidity, and mortality. The cellular characteristics of DF remain elusive. Herein, we performed single-cell RNA sequencing (scRNA-seq) to reveal the cell landscape of DF. To uncover the exclusive characteristics of DF, we compared the transcriptional profile of DF with that of keloid fibroblast (KF) and normal fibroblast (NF) in the public data (GSE163973). When compared with KF and NF, mesenchymal fibroblasts were significantly expanded in DF. The mesenchymal fibroblasts were further divided into two subtypes according to the differentiation states, among which LAMP5+ SULF1+ fibroblasts may account for the hard property of DF by promoting tumor ossification. ADAM12 and CREB3L1 were identified as the specific marker and transcription factor for DF, respectively. Both the quiescent and proliferative COL11A1+ neural cells exerted dominant roles in the maintenance of the profibrotic microenvironment in DF through modulating extracellular matrix. This study revealed the heterogeneity of fibroblasts in DF for the first time. The novel gene markers and transcription factor identified in DF and the significance of neural cells in the tumor microenvironment may point to new directions for the targeted therapy of DF in the future.
2024-05-14 | Desmoid-type Fibromatosis of the Breast. A Literature Review Based on 2 Case Reports
Abstract The goal of this review is twofold; to highlight the difficulties in identifying, diagnosing, and treating desmoid-type fibromatosis (DF) of the breast and to discuss the current understanding of the key genetic mutations in the disease process that lead to specific treatment regimens. Currently, there are three groups of DF as classified by the World Health Organization (WHO): abdominal wall, extra-abdominal, and intrabdominal. They all present unique diagnostic challenges; however, the gold standard for diagnosis remains histopathologic confirmation even with the increased availability and sensitivity of imaging modalities. Given the importance of genetic alteration in this disease, the following three genes will be discussed: Catenin Beta 1, Rad51, and Poly Adenosine Diphosphate Ribose Polymerase-1. There is mounting evidence that these could potentially be targets for therapy in addition to surgery alone. Historically, diagnosis and treatment of DF of the breast have been difficult, which leads to a need for an interdisciplinary team approach composed of surgeons, pathologists, radiologists, oncologists, and internists which leads to the best overall care for patients with this pathology.
2012-12-19 | Children's Oncology Group's 2013 blueprint for research: Soft tissue sarcomas
Abstract In the US, approximately 850–900 children are diagnosed each year with soft tissue sarcomas (STS). Key findings from recent Children's Oncology Group (COG) clinical trials include safe reduction in therapy for low risk rhabdomyosarcoma (RMS), validation of FOXO1 fusion as a prognostic factor, a modest improvement in outcome for high‐risk RMS, and a biologically designed non‐cytotoxic therapy for pediatric desmoid tumor. Planned Phase 2 trials include targeted agents for VEGF/PDGF, mTOR, and IGF‐1R for children with RMS and VEGF for children with non‐RMS STS (NRSTS). For RMS, COG Phase 3 trials potentially will explore VEGF/mTOR inhibition or chemotherapy interval compression. For NRSTS, a COG Phase 3 trial will explore VEGF inhibition. Pediatr Blood Cancer 2013; 60: 1001–1008. © 2012 Wiley Periodicals, Inc.
2008-11-28 | The management of desmoids in patients with familial adenomatous polyposis (FAP)
Desmoids are rare in the general population but occurs in between 10 to 20% of patients with familial adenomatous polyposis (FAP). This risk is about 852 times the risk for the population at large. Desmoids are benign neoplasms that are capable of infiltrating locally with a high risk of recurrence (25-65%) even after extirpating surgery. Desmoids in FAP may occur extra-abdominally, or within the abdominal wall or most commonly intra-abdominally within the mesentery or retroperitoneal Desmoids are a major problem in patients with FAP. Mortality from desmoids is high in such patients and ranges from 18 to 31%, compared to peri-ampullary carcinomas at about 22% and cancer in the retained rectum at only about 8%. Simple drug treatment with tamoxifen or NSAIDS like sulindac should be used as first line treatment as it carries a response in 30-50% of patients. Surgery should be reserved for extra-abdominal tumours alone and only when needed. Surgery for intra-abdominal desmoids should really only be attempted for intestinal obstruction or ureteric obstruction. Dacarbazine-Doxorubicin chemotherapy may have dramatic response in some cases. Genetic transfer may unlock this disease in future and may give patients with FAP and severe desmoids hope for the future.
2008-09-30 | Therapeutic Potential of Replication-Selective Oncolytic Adenoviruses on Cells from Familial and Sporadic Desmoid Tumors
Abstract Purpose: Constitutive activation of the Wnt signaling pathway is a hallmark of many cancers and has been associated with familial and sporadic desmoid tumors. The aim of the present study is to assess the therapeutic potential of oncolytic adenoviruses selectively replicating in cells in which the Wnt signaling pathway is active on primary cells from desmoid tumors. Experimental Design: Primary cells extracted from familial (n = 3) or sporadic (n = 3) desmoid tumors were cultured short term. Cancer cell survival and viral replication were measured in vitro upon infection with two different oncolytic adenoviruses targeting a constitutive activation of the Wnt signaling pathway. Adenoviral infectivity was also assessed. Results: Although cells extracted from one sporadic desmoid tumor responded very well to the oncolytic action of the adenoviruses (<20% of viable cells upon infection at a multiplicity of infection of 10), cells from two tumor samples were totally resistant to the viral action. Cells from the remaining samples showed intermediate sensitivity to the oncolytic viruses. These effects were correlated to the level of infectivity of the cells. Finally, in responder cells, evidences of viral replication was observed. Conclusions: Our experimental data suggest that the response of desmoid tumor cells to oncolytic adenovirus is neither correlated to the type of mutation activating the Wnt signaling pathway nor to the familial or sporadic nature of the tumor. In addition, they highlight the variability of infectivity of individual tumors and predict a great variability in the response to oncolytic adenoviruses.
antibodies
2026-06-25 | Profiling of desmoid tumors reveals frequent mutations in chromatin-remodeling genes and identifies an Immune-myogenic subtype.
Desmoid tumors (DTs) are locally aggressive soft tissue neoplasms with variable clinical behavior and limited therapeutic biomarkers. While CTNNB1 and APC mutations are known, the broader genomic, transcriptomic, and epigenetic features remain incompletely understood. We performed integrated genomic, transcriptomic, and DNA methylation profiling on 76 DTs, including post-treatment samples. Targeted gene panel sequencing, RNA-seq, and EPIC methylation arrays were conducted. Molecular subtypes were validated in external cohorts, and immunotherapy response was predicted using immune deconvolution and TIDE analysis. Beyond canonical CTNNB1/APC mutations, we discovered frequent mutations in chromatin-remodeling genes, notably KMT2C (18%), found in over 50% of samples, including in wild-type tumors. Unsupervised transcriptomic analysis revealed two robust molecular subtypes: immune-myogenic and mesenchymal-like. The immune-myogenic subtype exhibited high expression of myogenic markers, immune checkpoint genes (PDCD1, CD274, CTLA4), tertiary lymphoid structure signatures, and global enhancer hypomethylation linked to interferon and myogenesis pathways. It showed increased infiltration of T, B, and NK cells, higher vascularization, and elevated stemness and epithelial-mesenchymal transition plasticity. TIDE analysis predicted significantly higher ICI responsiveness in the immune-myogenic subtype (58% vs. 26%, p = 0.008), confirmed in an external cohort (69% vs. 10%, p < 0.001). Transcriptomic profiles were stable across intra-tumoral regions, supporting subtype robustness. This study expands the genomic understanding of DTs by uncovering frequent epigenetic regulator mutations and identifying an immune-myogenic subtype with immunogenic and plastic features. These findings support immunotherapeutic strategies in selected DT patients and emphasize the importance of integrated molecular profiling.
2025-05-28 | Efficacy and molecular predictors of radiotherapy combined with bevacizumab on desmoid tumor (aggressive fibromatosis).
e23535 Background: Desmoid tumors are rare, highly recurrent soft-tissue tumors with limited responses to non-surgical therapies. Radiotherapy combined with bevacizumab, a VEGF inhibitor, has shown potential synergy in improving tumor response. This study evaluated the efficacy and safety of radiotherapy combined with bevacizumab and explored potential molecular predictors of response. Methods: From a cohort of 160 patients with desmoid tumors treated at Sichuan Cancer Hospital between June 2013 and September 2023, eight patients who underwent radiotherapy combined with bevacizumab were retrospectively analyzed. Clinical outcomes, including tumor response according to RECIST 1.1 and time to treatment failure (TTF), were assessed alongside health-related quality of life (QoL) using the EORTC QLQ-C30 questionnaire. Tumor specimens were analyzed for β-catenin and VEGF expression, microvessel density (MVD) via immunohistochemistry, and genetic mutations, including CTNNB1, using next-generation sequencing (NGS). Results: The study included eight patients (ages 18–69, median 30) with equal male-to-female distribution and tumors located in the chest wall, head and neck, or intrathoracic regions. Patients received radiotherapy (median dose: 51 Gy, range: 45–65.5 Gy) with concurrent or sequential bevacizumab (2–5 cycles, 200–345 mg per cycle). All exhibited nuclear β-catenin positivity, with seven harboring CTNNB1 mutations. VEGF expression was present in five patients, and MVD ranged from 7 to 29 (median: 15). Clinical responses included complete response (CR) in three patients (37.5%) and partial response (PR) in four (50%), and all patients remained progression-free with a mean TTF of 53.25 months (range: 10–134 months). Favorable QoL scores (mean: 90.6 ± 12.1) were observed. No correlation was observed between clinical response and CTNNB1 mutations, VEGF expression, or MVD. However, ATR gene alterations, involved in DNA repair, were exclusively identified in patients with CR. Functional enrichment analysis indicated that mutations were predominantly associated with pathways regulating DNA repair, angiogenesis, and endothelial cell differentiation. Conclusions: Radiotherapy combined with bevacizumab demonstrated significant efficacy and safety in desmoid tumors, with sustained tumor control and good QoL. ATR gene alterations may serve as potential predictors of response, warranting further prospective studies to elucidate their role.
2025-03-01 | 88P Head, neck and shoulder desmoid-type fibromatosis: characteristics and outcome of these ultra-rare locations
Results: Cohort1 (253 patients) included undifferentiated pleomorphic sarcoma (UPS), myxofibrosarcoma (MFS), synovial sarcoma (SS), leiomyosarcoma (LMS), dedifferentiated liposarcoma (DDLPS) and malignant peripheral nerve sheath tumor (MPNST).12 % (31/253) exhibited amp of NECTIN4.The UPS group comprised 50 cases with 11 (22%) with amp.For MFS amp was observed in 5 out of 25 cases (20%).For 100 LMS cases, 5 (5%) had the amp.Among 59 DDLPS samples, 8 presented the amp (13%).Only 1 case in the SS group, out of 10 cases analyzed, exhibited amp.No amp was observed in the MPNST group (9 cases).Cohort 2 consisted of 2,922 samples across 38 cancers.The STS collection consisted of 34 cases, including 19 cases of DDLPS, with 16% (3/19) showing amp, and 15 cases of LMS, with an amp rate of 7%.Conclusions: Our findings underscore the need for further investigation of Nectin-4 in STS, including immunohistochemical analysis and clinical trials with ADCs such as Enfortumab-vedotin, emphasizing the potential of cutting-edge therapies to improve outcomes in sarcomas.
2025-03-01 | 118P Can CD 47 be a targeted treatment in desmoid tumors?
younger age groups having lower hazard ratios.Furthermore, the results showed that Black patients have a higher risk of death, with a hazard ratio of 1.314.Conclusions: There is no significant difference in the survival rates between males and females receiving neoadjuvant therapy, These results highlight the importance of focusing on individual patient characteristics rather than gender alone when devising treatment plans Studies on the role of genetic and molecular markers in predicting patient response to therapy are needed.
2024-09-30 | Phase II basket trial of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART) SWOG S1609: the desmoid tumors.
Dual inhibition using anti-programmed death-1 (PD-1) and anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) checkpoint inhibitors has proven effective in many cancers. However, its efficacy in rare solid cancers remains unclear. Desmoid tumors are ultrarare soft-tissue tumors, traditionally treated with surgery. This study reviews the first results of using ipilimumab and nivolumab in the desmoid tumor cohort of the SWOG S1609 Dual Anti-CTLA-4 & Anti-PD-1 blockade in Rare Tumors (DART) trial. DART is a prospective/open-label/multicenter (1,016 US sites)/multicohort phase II trial of ipilimumab (1 mg/kg intravenously every 6 weeks) plus nivolumab (240 mg intravenously every 2 weeks) that opened at 1,016 US sites. The primary endpoint included overall response rate (ORR) defined as confirmed complete (CR) and partial responses (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1. Secondary endpoints include progression-free survival (PFS), overall survival (OS), clinical benefit rate (CBR; stable disease (SD) ≥6 months plus CR and PR) and toxicity. Sixteen evaluable patients (median age: 37) with desmoid tumors and a median of 1.5 prior therapies (with no prior exposure to immunotherapy) were analyzed. The tumors varied in location (eight abdomen, three lower limb, two upper limb, two pelvis, and one neck). ORR was 18.8% (3/16; 3 confirmed PR): 40% regression (PFS 30+ months), 83% regression (PFS 16 months) and 71% regression (PFS 8.4 months). Seven additional patients (43.8%) had prolonged SD over 6 months (PFS: 16.5, 22.4+, 22.6, 30.1, 38.2+, 48.3+ and 60.7+ months). Overall CBR was 62.5% (10/16). Median PFS was 19.4 months, with 6-month PFS of 73% and 1-year PFS of 67%. All patients were alive at 1 year; median OS was not assessable, as 13 patients were alive at analysis. Common adverse events included fatigue, nausea and hypothyroidism, with 50% experiencing grade 3-4 events. There were no grade 5 events. Treatment with ipilimumab and nivolumab in desmoid tumors yielded an ORR of 18.8% and a CBR of 62.5% with durable responses seen. This is the first prospective study exploring the efficacy of this combination in this rare disease. Ongoing studies aim to identify markers for response and resistance. Expanded trials are necessary. NCT02834013.
other
2022-09-28 | Fibromatosis mimicking relapse of a neuroendocrine tumor at 68Ga-DOTATOC positron-emission tomography/computed tomography.
Mesenteric fibromatosis (desmoid tumor) is a locally aggressive fibroblastic lesion, characterized by a high recurrence rate that makes treatment challenging. Currently, there is no evidence-based treatment approach. We report the case of a female patient with a history of neuroendocrine tumor, who underwent 68Ga-DOTATOC positron-emission tomography/computed tomography (PET/CT), showing increased focal abdominal uptake suggestive of disease relapse. Histological examination revealed typical findings of fibromatosis. These findings indicate the expression of staining for somatostatin receptors (SSTRs) on fibromatosis cell surface and suggest to include fibromatosis among the potential causes of false-positive results at 68Ga PET/CT. Moreover, SSTRs expressed in desmoid tumors could be further investigated as a therapeutic target.
2003-03-01 | Peptide receptor radiotherapy: a new option for the management of aggressive fibromatosis on behalf of the Italian Sarcoma Group
The management of aggressive fibromatosis (AF) is problematic, and few options are available to patients unsuitable for surgery and resistant to external-beam radiation therapy (EBRT). We report on two patients with fast-growing recurrences of AF resistant to EBRT who obtained protracted clinical benefits with (90)Y-DOTATOC. (90)Y-DOTATOC should be further investigated in this setting.
small molecules
2026-09-30 | Evolution of treatment strategies and surgical outcomes in desmoid tumors: A retrospective cohort study.
Desmoid tumors (DT) are rare fibroblastic neoplasms characterized by local aggressiveness, absence of metastatic potential, and heterogeneous clinical behavior. During the last decade, management has shifted from routine upfront surgery toward active surveillance and selective systemic therapy. We evaluated temporal changes in management and surgical outcomes within a multicenter real-world cohort. We retrospectively reviewed consecutive patients with histologically confirmed DT managed between January 2015 and January 2026 across four tertiary hospitals in Madrid, Spain. Treatment-era analyses compared 2015-2019 with 2020-2026. Local recurrence-free survival (RFS) after surgery was estimated using the Kaplan-Meier method. Eighty-two patients were included. Initial management was available for 79 patients: surgery in 48, active surveillance in 17, and systemic therapy in 14. Among 77 patients with an assignable treatment era, upfront surgery decreased from 24/30 (80.0%) in 2015-2019 to 24/47 (51.1%) in 2020-2026 (Fisher p = 0.015), while active surveillance and systemic therapy increased. Fifty-three patients underwent surgery during follow-up. Local recurrence occurred in 11/51 patients with evaluable postoperative follow-up. R1 resection was associated with a higher unadjusted risk of local recurrence than R0 resection (40.0% vs 3.8%; conditional OR 15.84, exact 95% CI 1.92-751.38; Fisher p = 0.002). Contemporary recommendations have been progressively incorporated into routine practice, with reduced reliance on upfront surgery. Surgery remains important in selected patients. The observed association between R1 margins and local recurrence is unadjusted and should be interpreted cautiously given the limited number of events and potential residual confounding.
2026-09-29 | Familial adenomatous polyposis-associated desmoid disease: comprehensive review.
Familial adenomatous polyposis (FAP)-associated desmoid disease is a rare but important manifestation of FAP and remains a major cause of morbidity and mortality. In contrast to sporadic desmoids, which most commonly occur in the abdominal wall or extra-abdominal sites, approximately 70% of FAP-associated desmoids arise intra-abdominally, usually within the small bowel mesentery. These lesions can cause bowel and ureteric obstruction, sepsis, intestinal failure, and death. This review summarizes current evidence regarding the pathogenesis, risk factors, diagnosis, surveillance, and management of FAP-associated desmoid disease, and identifies key evidence gaps. A literature search was performed in accordance with PRISMA methodology using Medline, Embase, PROSPERO, Cochrane, Campbell, and Joanna Briggs Institute databases. Original research studies, reviews, and guidelines relating to desmoid disease, FAP-associated desmoid disease, and FAP published up to August 2025 were eligible. Data were extracted and synthesized narratively by topic. Aberrant Wnt/β-catenin signalling resulting from a germline APC pathogenic variant and a somatic second hit underpin the development of FAP-associated desmoid disease. Established risk factors include a distal APC pathogenic variant, positive family history, and previous abdominal surgery. Diagnosis in patients with established FAP is usually clinicoradiological, and routine biopsy is generally unnecessary, except in select circumstances. Active surveillance is now recommended as first-line management for most patients because many lesions remain stable or regress spontaneously. Surgery is primarily reserved for complications, particularly in small bowel mesenteric disease, owing to substantial operative morbidity and a lack of demonstrated survival benefit from complete resection. Systemic therapy is indicated for progressive or symptomatic disease. Tyrosine kinase inhibitors and the γ-secretase inhibitor nirogacestat have demonstrated efficacy in randomized trials, although patients with FAP-associated disease comprise only a small proportion of enrolled patients. Evidence supporting the use of non-steroidal anti-inflammatory drugs and anti-oestrogens remains limited. Important evidence gaps remain regarding optimal imaging strategies, predictors of aggressive disease, clinically meaningful trial endpoints, and FAP-specific treatment algorithms. Dedicated studies in genetically defined FAP cohorts are required to improve risk stratification and management.
2026-09-21 | Defining absolute postoperative desmoid risk in familial adenomatous polyposis according to APC genotype and family history: retrospective cohort study.
Desmoid disease is a major cause of morbidity and mortality in familial adenomatous polyposis (FAP), particularly after prophylactic colorectal surgery. Although APC genotype and family history are recognized risk factors, previous sizeable studies report relative rather than absolute risks. This study aimed to quantify absolute postoperative desmoid risk in FAP patients undergoing risk-reducing colectomy, stratified by APC genotype, and to assess the modifying effect of family history. This retrospective observational study used records from a prospectively maintained registry. Patients with an APC pathogenic variant (PV) 3' of codon 1399 were classified as high risk, and those with an APC PV 5' of (or at) codon 1399 were classified as low risk. Patients who had not undergone prophylactic colectomy, with < 5 years of postoperative follow-up, or those with a desmoid diagnosed before or at the time of surgery were excluded. Clinical records were reviewed for details of surgery, desmoid diagnosis, and family history. A positive family history was defined as a first-degree relative with genetically confirmed FAP and a diagnosis of desmoid disease (clinical and/or radiological). Among 48 high-risk patients, 30 (63%) developed desmoid, with no significant difference between colectomy and proctocolectomy (54% versus 70%, respectively; χ2 = 1.42; P = 0.233). Family history was present in 35 of the 48 patients (73%) and increased desmoid risk relative to no family history (80% versus 15%, respectively; P < 0.01). Among the 1213 low-risk patients, 154 (12.7%) developed desmoids, with no significant effect of surgical procedure (13.9% versus 12.1% for proctocolectomy and total/partial colectomy, respectively; χ² = 0.77; P = 0.380). Family history increased desmoid risk relative to no family history (30% versus 10%, respectively; P < 0.01). A family history of desmoid disease appears to be an important determinant of postoperative desmoid risk in FAP. Although APC PV 3' of codon 1399 does confer a high overall risk, this is largely confined to individuals with first-degree relatives with desmoid. In the absence of a family history, postoperative desmoid risk appeared relatively low regardless of genotype. This supports a more individualized approach to perioperative counselling and surgical decision-making in patients with FAP. In addition, these data highlight that patients with both a 3' APC PV and a positive family history are a particularly high-risk subgroup who may represent an appropriate target population for future chemoprevention trials.
2026-09-19 | Efficacy of celecoxib and methotrexate-vinblastine regimen in desmoid-type fibromatosis: A retrospective cohort study.
Desmoid tumors are classified as borderline malignancies and are characterized by a high rate of local recurrence despite the absence of distant metastasis. Low-dose methotrexate combined with vinblastine, known as the methotrexate and vinblastine (MV) regimen, has been reported as an effective treatment for desmoid-type fibromatosis (DF). At our institution, we adopt a treatment strategy beginning with celecoxib as the first-line therapy, escalating to the MV regimen only in cases showing disease progression. This study evaluates treatment outcomes based on this protocol. At our institution, 10 patients diagnosed with DF between 2003 and 2025 received surgical resection and/or pharmacotherapy. The standard approach involved initiating treatment with oral celecoxib; if no clinical improvement was observed, therapy was escalated to the MV regimen. Treatment response was assessed using Response Evaluation Criteria in Solid Tumors 1.1 criteria. Of the 10 cases, 1 achieved complete response, 5 showed partial response, 2 maintained stable disease, and 2 exhibited progressive disease, yielding a response rate of 60%. Among patients treated with the MV regimen, extended dosing intervals did not lead to tumor progression, and sustained suppression was observed in several cases. No grade 3 or 4 adverse events were reported. Celecoxib and the MV regimen appear to be effective and well-tolerated options for DF. Given its low toxicity and favorable tolerability, celecoxib should be considered the first-line treatment, especially since tumor control was achieved in half of the cases. Although tumor progression occurred in the remaining cases, disease control was subsequently achieved by introducing the MV regimen. These findings support recent trends favoring nonsurgical management and suggest that the celecoxib followed by the MV regimen strategy should be considered a primary therapeutic approach.
2026-07-29 | Deni Study: Real-World Data on the Use of Nirogacestat in Patients With Desmoid Tumors in the French Sarcoma Group.
The DeFi trial revealed a significant improvement in progression-free survival (PFS) with nirogacestat in patients with desmoid tumors. The DeNi study reports outcomes of patients treated with nirogacestat through the French compassionate use program. DeNi is a retrospective, real-world study. Outcomes included objective response, pain improvement, 1-year PFS, and toxicity. Between February and June 2024, 55 patients with desmoid tumors were included (37 women). Data were updated until November 2025. The median age was 38.6 years (range: 18.0-66.7). The median number of previous therapies was 2, including local therapies. The median follow-up was 21.4 months [95% CI: 19.5; 25.6]. The estimated median duration of nirogacestat treatment was 16 months. Partial response and stable disease were observed in 33 (60%) and 17 patients (31%), respectively. The 1-year PFS rate was 76.2%, and 77.0% of patients remained without treatment change at 1 year, including patients with dose reductions. Of the 49 patients with baseline pain, 38 (78%) experienced pain improvement under nirogacestat; 35 (71%) reduced or discontinued analgesics. The most frequent side effects (all grades) were diarrhea (53%), fatigue (47%), and rash (29%). Thirteen patients (24%) required dose reduction: 11 for digestive adverse events (85%), 1 for mucositis, and 1 for fatigue with hypertension. The DeNi study confirms the clinical benefits of nirogacestat in patients with desmoid tumors, with improvements in pain and tumor shrinkage observed in 60% of patients and PFS consistent with that reported in the phase III DeFi trial.
cell therapies
2026-06-22 | Intestinal transplantation for tumors.
Transplantation of the intestine is a vital component in the treatment of many intrabdominal tumors. This is a comprehensive review of current practice and outcome of intestinal transplantation for tumors. Most commonly described for the intrabdominal desmoid tumor, excellent survival outcomes can be attained, particularly for the more aggressive desmoid tumors associated with familial adenomatous polyposis syndrome and early referral is critical in order to avoid diffuse tumor spread which would necessitate a more complex multivisceral transplant. Currently, consensus within the intestinal transplant community lists invasive intrabdominal desmoid tumor as a primary indication for intestinal transplantation. Rare tumors such as metastatic neuroendocrine tumors confined to the abdomen, and pseudomyxoma peritonei have been associated with acceptable survival and recurrence outcomes with intestinal transplantation in carefully selected patients who would otherwise have a dismal prognosis. In addition, intestinal transplantation is an option for patients with a history of abdominal malignancy who have been rendered with intestinal failure due to surgical complications from resection of a primary tumor. Intestinal transplantation is a therapeutic option with excellent results in selected patients with intrabdominal desmoid tumors, neuroendocrine tumors and pseudomyxoma peritonei. Careful patient selection, technical expertise, and posttransplant oncologic surveillance is critical for successful long-term outcomes.
2024-06-24 | The Role of Colon in Isolated Intestinal Transplantation: Description of 4 Cases.
Intra-abdominal desmoid tumors are a rare and complex clinical problem. These tumors are locally invasive, and surgical ablation represents the mainstay of treatment. When localized at the root of the mesentery, their resection may require extensive excision of the intestine resulting in intestinal failure and life-long total parenteral nutrition. Intestinal transplantation, either autotransplantation or allotransplantation, has been used as a viable option to treat this group of patients. Herein, we describe a series of 4 patients with unresectable intra-abdominal desmoid tumor who underwent cadaveric isolated intestinal and ascending colon transplantation.
2024-01-24 | Treatment of Complex Desmoid Tumors in Familial Adenomatous Polyposis Syndrome by Intestinal Transplantation.
Desmoid tumors are fibroblastic lesions which often have an unpredictable and variable clinical course. In the context of familial adenomatous polyposis (FAP), these frequently occur intra-abdominally, especially in the small-bowel mesentery resulting in sepsis, fistulation, and invasion of the abdominal wall and retroperitoneum. In selected cases where other modalities have failed, the most radical option is to perform a total enterectomy and intestinal transplantation (ITx). In this study, we present our center's experience of ITx for desmoid in patients with FAP. We performed a retrospective review of our prospectively collected database between 2007 and 2022. All patients undergoing ITx for FAP-related desmoid were included. Between October 2007 and September 2023, 144 ITx were performed on 130 patients at our center. Of these, 15 patients (9%) were for desmoid associated with FAP (7 modified multivisceral transplants, 6 isolated ITx, and 2 liver-containing grafts). The median follow-up was 57 mo (8-119); 5-y patient survival was 82%, all with functioning grafts without local desmoid recurrence. These patients presented us with several complex surgical issues, such as loss of abdominal domain, retroperitoneal/abdominal wall involvement, ileoanal pouch-related issues, and the need for foregut resection because of adenomatous disease. ITx is a viable treatment in selected patients with FAP and extensive desmoid disease. The decision to refer for ITx can be challenging, particularly the timing and sequence of treatment (simultaneous versus sequential exenteration). Delays can result in additional disease burden, such as secondary liver disease or invasion of adjacent structures.
2023-09-04 | Sporadic Desmoid Tumor Mimicking Myofascial Pain Syndrome in a Chiropractic Clinic
Chiropractors are primary healthcare providers who diagnose and manage various health conditions, including rare cases like desmoid tumors. Desmoid tumors are locally aggressive soft-tissue tumors originating from fibroblasts. This report presents the case of a 30-year-old woman who initially sought chiropractic care for persistent neck pain that was later discovered to be a symptom of a sporadic desmoid tumor. The patient presented with severe right upper neck pain, which was diagnosed as myofascial pain syndrome and yielded no significant improvement after various treatments. Physical examination by a chiropractor revealed a soft-tissue mass in the right upper trapezius and rhomboid region. In addition, magnetic resonance imaging revealed an intramuscular lesion measuring 8 × 4 cm in the right rhomboids, and subsequent biopsy confirmed the diagnosis of a sporadic desmoid tumor. The patient underwent successful surgical excision of the tumor. Postoperatively, the chiropractor initiated a comprehensive 12-week rehabilitation program that significantly improved the patient's range of motion and muscular strength and alleviated pain. The remarkable aspect of this case was the location of the tumor in the right rhomboid muscle, a less common site for desmoid tumors. This case underscores the crucial role of chiropractors as primary healthcare providers in the early detection of oncological cases and management of post-surgical rehabilitation.
2023-04-25 | CD142 Identifies Neoplastic Desmoid Tumor Cells, Uncovering Interactions Between Neoplastic and Stromal Cells That Drive Proliferation
The interaction between neoplastic and stromal cells within a tumor mass plays an important role in cancer biology. However, it is challenging to distinguish between tumor and stromal cells in mesenchymal tumors because lineage-specific cell surface markers typically used in other cancers do not distinguish between the different cell subpopulations. Desmoid tumors consist of mesenchymal fibroblast-like cells driven by mutations stabilizing beta-catenin. Here we aimed to identify surface markers that can distinguish mutant cells from stromal cells to study tumor–stroma interactions. We analyzed colonies derived from single cells from human desmoid tumors using a high-throughput surface antigen screen, to characterize the mutant and nonmutant cells. We found that CD142 is highly expressed by the mutant cell populations and correlates with beta-catenin activity. CD142-based cell sorting isolated the mutant population from heterogeneous samples, including one where no mutation was previously detected by traditional Sanger sequencing. We then studied the secretome of mutant and nonmutant fibroblastic cells. PTX3 is one stroma-derived secreted factor that increases mutant cell proliferation via STAT6 activation. These data demonstrate a sensitive method to quantify and distinguish neoplastic from stromal cells in mesenchymal tumors. It identifies proteins secreted by nonmutant cells that regulate mutant cell proliferation that could be therapeutically. Significance: Distinguishing between neoplastic (tumor) and non-neoplastic (stromal) cells within mesenchymal tumors is particularly challenging, because lineage-specific cell surface markers typically used in other cancers do not differentiate between the different cell subpopulations. Here, we developed a strategy combining clonal expansion with surface proteome profiling to identify markers for quantifying and isolating mutant and nonmutant cell subpopulations in desmoid tumors, and to study their interactions via soluble factors.
gene therapies
2025-07-25 | Single-Cell Transcription Reveals the Fibroblast Heterogeneity and Neural Cells' Significance in Desmoid Fibromatosis.
Desmoid fibromatosis (DF) is a refractory tumor with a high recurrence rate, resulting in severe organ's deformity, morbidity, and mortality. The cellular characteristics of DF remain elusive. Herein, we performed single-cell RNA sequencing (scRNA-seq) to reveal the cell landscape of DF. To uncover the exclusive characteristics of DF, we compared the transcriptional profile of DF with that of keloid fibroblast (KF) and normal fibroblast (NF) in the public data (GSE163973). When compared with KF and NF, mesenchymal fibroblasts were significantly expanded in DF. The mesenchymal fibroblasts were further divided into two subtypes according to the differentiation states, among which LAMP5+ SULF1+ fibroblasts may account for the hard property of DF by promoting tumor ossification. ADAM12 and CREB3L1 were identified as the specific marker and transcription factor for DF, respectively. Both the quiescent and proliferative COL11A1+ neural cells exerted dominant roles in the maintenance of the profibrotic microenvironment in DF through modulating extracellular matrix. This study revealed the heterogeneity of fibroblasts in DF for the first time. The novel gene markers and transcription factor identified in DF and the significance of neural cells in the tumor microenvironment may point to new directions for the targeted therapy of DF in the future.
2024-05-14 | Desmoid-type Fibromatosis of the Breast. A Literature Review Based on 2 Case Reports
Abstract The goal of this review is twofold; to highlight the difficulties in identifying, diagnosing, and treating desmoid-type fibromatosis (DF) of the breast and to discuss the current understanding of the key genetic mutations in the disease process that lead to specific treatment regimens. Currently, there are three groups of DF as classified by the World Health Organization (WHO): abdominal wall, extra-abdominal, and intrabdominal. They all present unique diagnostic challenges; however, the gold standard for diagnosis remains histopathologic confirmation even with the increased availability and sensitivity of imaging modalities. Given the importance of genetic alteration in this disease, the following three genes will be discussed: Catenin Beta 1, Rad51, and Poly Adenosine Diphosphate Ribose Polymerase-1. There is mounting evidence that these could potentially be targets for therapy in addition to surgery alone. Historically, diagnosis and treatment of DF of the breast have been difficult, which leads to a need for an interdisciplinary team approach composed of surgeons, pathologists, radiologists, oncologists, and internists which leads to the best overall care for patients with this pathology.
2012-12-19 | Children's Oncology Group's 2013 blueprint for research: Soft tissue sarcomas
Abstract In the US, approximately 850–900 children are diagnosed each year with soft tissue sarcomas (STS). Key findings from recent Children's Oncology Group (COG) clinical trials include safe reduction in therapy for low risk rhabdomyosarcoma (RMS), validation of FOXO1 fusion as a prognostic factor, a modest improvement in outcome for high‐risk RMS, and a biologically designed non‐cytotoxic therapy for pediatric desmoid tumor. Planned Phase 2 trials include targeted agents for VEGF/PDGF, mTOR, and IGF‐1R for children with RMS and VEGF for children with non‐RMS STS (NRSTS). For RMS, COG Phase 3 trials potentially will explore VEGF/mTOR inhibition or chemotherapy interval compression. For NRSTS, a COG Phase 3 trial will explore VEGF inhibition. Pediatr Blood Cancer 2013; 60: 1001–1008. © 2012 Wiley Periodicals, Inc.
2008-11-28 | The management of desmoids in patients with familial adenomatous polyposis (FAP)
Desmoids are rare in the general population but occurs in between 10 to 20% of patients with familial adenomatous polyposis (FAP). This risk is about 852 times the risk for the population at large. Desmoids are benign neoplasms that are capable of infiltrating locally with a high risk of recurrence (25-65%) even after extirpating surgery. Desmoids in FAP may occur extra-abdominally, or within the abdominal wall or most commonly intra-abdominally within the mesentery or retroperitoneal Desmoids are a major problem in patients with FAP. Mortality from desmoids is high in such patients and ranges from 18 to 31%, compared to peri-ampullary carcinomas at about 22% and cancer in the retained rectum at only about 8%. Simple drug treatment with tamoxifen or NSAIDS like sulindac should be used as first line treatment as it carries a response in 30-50% of patients. Surgery should be reserved for extra-abdominal tumours alone and only when needed. Surgery for intra-abdominal desmoids should really only be attempted for intestinal obstruction or ureteric obstruction. Dacarbazine-Doxorubicin chemotherapy may have dramatic response in some cases. Genetic transfer may unlock this disease in future and may give patients with FAP and severe desmoids hope for the future.
2008-09-30 | Therapeutic Potential of Replication-Selective Oncolytic Adenoviruses on Cells from Familial and Sporadic Desmoid Tumors
Abstract Purpose: Constitutive activation of the Wnt signaling pathway is a hallmark of many cancers and has been associated with familial and sporadic desmoid tumors. The aim of the present study is to assess the therapeutic potential of oncolytic adenoviruses selectively replicating in cells in which the Wnt signaling pathway is active on primary cells from desmoid tumors. Experimental Design: Primary cells extracted from familial (n = 3) or sporadic (n = 3) desmoid tumors were cultured short term. Cancer cell survival and viral replication were measured in vitro upon infection with two different oncolytic adenoviruses targeting a constitutive activation of the Wnt signaling pathway. Adenoviral infectivity was also assessed. Results: Although cells extracted from one sporadic desmoid tumor responded very well to the oncolytic action of the adenoviruses (<20% of viable cells upon infection at a multiplicity of infection of 10), cells from two tumor samples were totally resistant to the viral action. Cells from the remaining samples showed intermediate sensitivity to the oncolytic viruses. These effects were correlated to the level of infectivity of the cells. Finally, in responder cells, evidences of viral replication was observed. Conclusions: Our experimental data suggest that the response of desmoid tumor cells to oncolytic adenovirus is neither correlated to the type of mutation activating the Wnt signaling pathway nor to the familial or sporadic nature of the tumor. In addition, they highlight the variability of infectivity of individual tumors and predict a great variability in the response to oncolytic adenoviruses.
antibodies
2026-06-25 | Profiling of desmoid tumors reveals frequent mutations in chromatin-remodeling genes and identifies an Immune-myogenic subtype.
Desmoid tumors (DTs) are locally aggressive soft tissue neoplasms with variable clinical behavior and limited therapeutic biomarkers. While CTNNB1 and APC mutations are known, the broader genomic, transcriptomic, and epigenetic features remain incompletely understood. We performed integrated genomic, transcriptomic, and DNA methylation profiling on 76 DTs, including post-treatment samples. Targeted gene panel sequencing, RNA-seq, and EPIC methylation arrays were conducted. Molecular subtypes were validated in external cohorts, and immunotherapy response was predicted using immune deconvolution and TIDE analysis. Beyond canonical CTNNB1/APC mutations, we discovered frequent mutations in chromatin-remodeling genes, notably KMT2C (18%), found in over 50% of samples, including in wild-type tumors. Unsupervised transcriptomic analysis revealed two robust molecular subtypes: immune-myogenic and mesenchymal-like. The immune-myogenic subtype exhibited high expression of myogenic markers, immune checkpoint genes (PDCD1, CD274, CTLA4), tertiary lymphoid structure signatures, and global enhancer hypomethylation linked to interferon and myogenesis pathways. It showed increased infiltration of T, B, and NK cells, higher vascularization, and elevated stemness and epithelial-mesenchymal transition plasticity. TIDE analysis predicted significantly higher ICI responsiveness in the immune-myogenic subtype (58% vs. 26%, p = 0.008), confirmed in an external cohort (69% vs. 10%, p < 0.001). Transcriptomic profiles were stable across intra-tumoral regions, supporting subtype robustness. This study expands the genomic understanding of DTs by uncovering frequent epigenetic regulator mutations and identifying an immune-myogenic subtype with immunogenic and plastic features. These findings support immunotherapeutic strategies in selected DT patients and emphasize the importance of integrated molecular profiling.
2025-05-28 | Efficacy and molecular predictors of radiotherapy combined with bevacizumab on desmoid tumor (aggressive fibromatosis).
e23535 Background: Desmoid tumors are rare, highly recurrent soft-tissue tumors with limited responses to non-surgical therapies. Radiotherapy combined with bevacizumab, a VEGF inhibitor, has shown potential synergy in improving tumor response. This study evaluated the efficacy and safety of radiotherapy combined with bevacizumab and explored potential molecular predictors of response. Methods: From a cohort of 160 patients with desmoid tumors treated at Sichuan Cancer Hospital between June 2013 and September 2023, eight patients who underwent radiotherapy combined with bevacizumab were retrospectively analyzed. Clinical outcomes, including tumor response according to RECIST 1.1 and time to treatment failure (TTF), were assessed alongside health-related quality of life (QoL) using the EORTC QLQ-C30 questionnaire. Tumor specimens were analyzed for β-catenin and VEGF expression, microvessel density (MVD) via immunohistochemistry, and genetic mutations, including CTNNB1, using next-generation sequencing (NGS). Results: The study included eight patients (ages 18–69, median 30) with equal male-to-female distribution and tumors located in the chest wall, head and neck, or intrathoracic regions. Patients received radiotherapy (median dose: 51 Gy, range: 45–65.5 Gy) with concurrent or sequential bevacizumab (2–5 cycles, 200–345 mg per cycle). All exhibited nuclear β-catenin positivity, with seven harboring CTNNB1 mutations. VEGF expression was present in five patients, and MVD ranged from 7 to 29 (median: 15). Clinical responses included complete response (CR) in three patients (37.5%) and partial response (PR) in four (50%), and all patients remained progression-free with a mean TTF of 53.25 months (range: 10–134 months). Favorable QoL scores (mean: 90.6 ± 12.1) were observed. No correlation was observed between clinical response and CTNNB1 mutations, VEGF expression, or MVD. However, ATR gene alterations, involved in DNA repair, were exclusively identified in patients with CR. Functional enrichment analysis indicated that mutations were predominantly associated with pathways regulating DNA repair, angiogenesis, and endothelial cell differentiation. Conclusions: Radiotherapy combined with bevacizumab demonstrated significant efficacy and safety in desmoid tumors, with sustained tumor control and good QoL. ATR gene alterations may serve as potential predictors of response, warranting further prospective studies to elucidate their role.
2025-03-01 | 88P Head, neck and shoulder desmoid-type fibromatosis: characteristics and outcome of these ultra-rare locations
Results: Cohort1 (253 patients) included undifferentiated pleomorphic sarcoma (UPS), myxofibrosarcoma (MFS), synovial sarcoma (SS), leiomyosarcoma (LMS), dedifferentiated liposarcoma (DDLPS) and malignant peripheral nerve sheath tumor (MPNST).12 % (31/253) exhibited amp of NECTIN4.The UPS group comprised 50 cases with 11 (22%) with amp.For MFS amp was observed in 5 out of 25 cases (20%).For 100 LMS cases, 5 (5%) had the amp.Among 59 DDLPS samples, 8 presented the amp (13%).Only 1 case in the SS group, out of 10 cases analyzed, exhibited amp.No amp was observed in the MPNST group (9 cases).Cohort 2 consisted of 2,922 samples across 38 cancers.The STS collection consisted of 34 cases, including 19 cases of DDLPS, with 16% (3/19) showing amp, and 15 cases of LMS, with an amp rate of 7%.Conclusions: Our findings underscore the need for further investigation of Nectin-4 in STS, including immunohistochemical analysis and clinical trials with ADCs such as Enfortumab-vedotin, emphasizing the potential of cutting-edge therapies to improve outcomes in sarcomas.
2025-03-01 | 118P Can CD 47 be a targeted treatment in desmoid tumors?
younger age groups having lower hazard ratios.Furthermore, the results showed that Black patients have a higher risk of death, with a hazard ratio of 1.314.Conclusions: There is no significant difference in the survival rates between males and females receiving neoadjuvant therapy, These results highlight the importance of focusing on individual patient characteristics rather than gender alone when devising treatment plans Studies on the role of genetic and molecular markers in predicting patient response to therapy are needed.
2024-09-30 | Phase II basket trial of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART) SWOG S1609: the desmoid tumors.
Dual inhibition using anti-programmed death-1 (PD-1) and anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) checkpoint inhibitors has proven effective in many cancers. However, its efficacy in rare solid cancers remains unclear. Desmoid tumors are ultrarare soft-tissue tumors, traditionally treated with surgery. This study reviews the first results of using ipilimumab and nivolumab in the desmoid tumor cohort of the SWOG S1609 Dual Anti-CTLA-4 & Anti-PD-1 blockade in Rare Tumors (DART) trial. DART is a prospective/open-label/multicenter (1,016 US sites)/multicohort phase II trial of ipilimumab (1 mg/kg intravenously every 6 weeks) plus nivolumab (240 mg intravenously every 2 weeks) that opened at 1,016 US sites. The primary endpoint included overall response rate (ORR) defined as confirmed complete (CR) and partial responses (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1. Secondary endpoints include progression-free survival (PFS), overall survival (OS), clinical benefit rate (CBR; stable disease (SD) ≥6 months plus CR and PR) and toxicity. Sixteen evaluable patients (median age: 37) with desmoid tumors and a median of 1.5 prior therapies (with no prior exposure to immunotherapy) were analyzed. The tumors varied in location (eight abdomen, three lower limb, two upper limb, two pelvis, and one neck). ORR was 18.8% (3/16; 3 confirmed PR): 40% regression (PFS 30+ months), 83% regression (PFS 16 months) and 71% regression (PFS 8.4 months). Seven additional patients (43.8%) had prolonged SD over 6 months (PFS: 16.5, 22.4+, 22.6, 30.1, 38.2+, 48.3+ and 60.7+ months). Overall CBR was 62.5% (10/16). Median PFS was 19.4 months, with 6-month PFS of 73% and 1-year PFS of 67%. All patients were alive at 1 year; median OS was not assessable, as 13 patients were alive at analysis. Common adverse events included fatigue, nausea and hypothyroidism, with 50% experiencing grade 3-4 events. There were no grade 5 events. Treatment with ipilimumab and nivolumab in desmoid tumors yielded an ORR of 18.8% and a CBR of 62.5% with durable responses seen. This is the first prospective study exploring the efficacy of this combination in this rare disease. Ongoing studies aim to identify markers for response and resistance. Expanded trials are necessary. NCT02834013.
other
2022-09-28 | Fibromatosis mimicking relapse of a neuroendocrine tumor at 68Ga-DOTATOC positron-emission tomography/computed tomography.
Mesenteric fibromatosis (desmoid tumor) is a locally aggressive fibroblastic lesion, characterized by a high recurrence rate that makes treatment challenging. Currently, there is no evidence-based treatment approach. We report the case of a female patient with a history of neuroendocrine tumor, who underwent 68Ga-DOTATOC positron-emission tomography/computed tomography (PET/CT), showing increased focal abdominal uptake suggestive of disease relapse. Histological examination revealed typical findings of fibromatosis. These findings indicate the expression of staining for somatostatin receptors (SSTRs) on fibromatosis cell surface and suggest to include fibromatosis among the potential causes of false-positive results at 68Ga PET/CT. Moreover, SSTRs expressed in desmoid tumors could be further investigated as a therapeutic target.
2003-03-01 | Peptide receptor radiotherapy: a new option for the management of aggressive fibromatosis on behalf of the Italian Sarcoma Group
The management of aggressive fibromatosis (AF) is problematic, and few options are available to patients unsuitable for surgery and resistant to external-beam radiation therapy (EBRT). We report on two patients with fast-growing recurrences of AF resistant to EBRT who obtained protracted clinical benefits with (90)Y-DOTATOC. (90)Y-DOTATOC should be further investigated in this setting.
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Drug Discovery Landscape
7 orphan drug designations for Desmoid tumor, including 1 approved therapy.
7 orphan drug designations for Desmoid tumor, including 1 approved therapy.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
bi-functional antibody fusion protein targeting both cluster of differentiation 39 (CD39) and transforming growth factor beta (TGF-beta) | antibodies | FDA | Elpiscience (Suzhou) Biopharma, Ltd. | |
2,2'-((1''S,2R,2'S,5'S,8'S,10''E,12'Z,18''S,21''S,27''S,30''S,33''S,42''S,45''S,48''S)-1-acetyl-42''-(((S)-1-amino-1-oxopropan-2-yl)carbamoyl)-45''-(benzo[b]thiophen-3-ylmethyl)-30''-benzyl-21''-(3-carboxybenzyl)-24'',24'',27''-trimethyl-5'-neopentyl-3',5'',6',16',16'',19'',22'',25'',28'',31'',39'',44'',47'',50'',52''-pentadecaoxo-48''-(thiophen-3-ylmethyl)-6''-oxa-1',4',4'',7',17'',20'',23'',26'',29'',32'',38'',43'',46'',49'',51''-pentadecaazadispiro[pyrrolidine-2,15'-cyclohexadecane-8',15''-tricyclo[31.17.2.11,4]tripentacontane]-10'',12'-dien-2',18''-diyl)diacetic acid | small molecules | FDA | Parabilis Medicines, Inc. | |
varegacestat | small molecules | FDA | Immunome, Inc. | |
sorafenib | small molecules | FDA | Bayer HealthCare Pharmaceuticals, Inc. | |
nirogacestat [Ogsiveo] | small molecules | FDA | Approved | SpringWorks Therapeutics, Inc. |
tegavivint | small molecules | FDA | Beta Cat Pharmaceuticals | |
Toremifene | small molecules | FDA | Orion Corporation |
“Terminated” – programs with discontinued clinical trials, or with no updates reported for 5 years after completion or 12 years after the last trial started.
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