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European Journal of Cancer (Oxford,... Mar 2020Desmoid tumor (DT; other synonymously used terms: Desmoid-type fibromatosis, aggressive fibromatosis) is a rare and locally aggressive monoclonal, fibroblastic... (Review)
Review
Desmoid tumor (DT; other synonymously used terms: Desmoid-type fibromatosis, aggressive fibromatosis) is a rare and locally aggressive monoclonal, fibroblastic proliferation characterised by a variable and often unpredictable clinical course. Previously surgery was the standard primary treatment modality; however, in recent years a paradigm shift towards a more conservative management has been introduced and an effort to harmonise the strategy amongst clinicians has been made. We present herein an evidence-based, joint global consensus guideline approach to the management of this disease focussing on: molecular genetics, indications for an active treatment, and available systemic therapeutic options. This paper follows a one-day consensus meeting held in Milan, Italy, in June 2018 under the auspices of the European Reference Network for rare solid adult cancers, EURACAN, the European Organisation for Research and Treatment of Cancer (EORTC) Soft Tissue and Bone Sarcoma Group (STBSG) as well as Sarcoma Patients EuroNet (SPAEN) and The Desmoid tumour Research Foundation (DTRF). The meeting brought together over 50 adult and pediatric sarcoma experts from different disciplines, patients and patient advocates from Europe, North America and Japan.
Topics: Adult; Child; Combined Modality Therapy; Consensus; Disease Management; Fibromatosis, Aggressive; Humans; Practice Guidelines as Topic
PubMed: 32004793
DOI: 10.1016/j.ejca.2019.11.013 -
Advances in Therapy Sep 2023Desmoid tumors (DT) are rare, locally aggressive, fibroblastic soft-tissue tumors that are characterized by infiltrative growth and can affect organs and adjacent... (Review)
Review
Desmoid tumors (DT) are rare, locally aggressive, fibroblastic soft-tissue tumors that are characterized by infiltrative growth and can affect organs and adjacent structures, resulting in substantial clinical burden impacting patients' health-related quality of life. Searches of PubMed, Embase, Cochrane, and key conferences were conducted in November 2021 and updated periodically through March 2023 to identify articles describing the burden of DT. Of 651 publications identified, 96 relevant ones were retained. Diagnosis of DT is challenging because of its morphologic heterogeneity and variable clinical presentation. Patients visit multiple healthcare providers, often facing delays in correct diagnosis. The low incidence of DT (estimated 3-5 cases per million person-years) limits disease awareness. Patients with DT experience a high symptom burden: up to 63% of patients experience chronic pain, which leads to sleep disturbance (73% of cases), irritability (46% of cases), and anxiety/depression (15% of cases). Frequently mentioned symptoms are pain, limited function and mobility, fatigue, muscle weakness, and swelling around the tumor. Overall, quality of life in patients with DT is lower than in healthy controls. There is no treatment approved by the US Food and Drug Administration for DT; however, treatment guidelines reference available options, such as active surveillance, surgery, systemic therapy, and locoregional therapy. Choice of active treatment may depend on tumor location, symptoms, and risk of morbidity. The substantial burden of illness of DT is related to difficulties in timely and accurate diagnosis, high symptom burden (pain and functional limitations), and decreased quality of life. There is a high unmet need for treatments that specifically target DT and improve quality of life.
Topics: Humans; Fibromatosis, Aggressive; Quality of Life; Pain
PubMed: 37436594
DOI: 10.1007/s12325-023-02592-0 -
The New England Journal of Medicine Mar 2023Desmoid tumors are rare, locally aggressive, highly recurrent soft-tissue tumors without approved treatments. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Desmoid tumors are rare, locally aggressive, highly recurrent soft-tissue tumors without approved treatments.
METHODS
We conducted a phase 3, international, double-blind, randomized, placebo-controlled trial of nirogacestat in adults with progressing desmoid tumors according to the Response Evaluation Criteria in Solid Tumors, version 1.1. Patients were assigned in a 1:1 ratio to receive the oral γ-secretase inhibitor nirogacestat (150 mg) or placebo twice daily. The primary end point was progression-free survival.
RESULTS
From May 2019 through August 2020, a total of 70 patients were assigned to receive nirogacestat and 72 to receive placebo. Nirogacestat had a significant progression-free survival benefit over placebo (hazard ratio for disease progression or death, 0.29; 95% confidence interval, 0.15 to 0.55; P<0.001); the likelihood of being event-free at 2 years was 76% with nirogacestat and 44% with placebo. Between-group differences in progression-free survival were consistent across prespecified subgroups. The percentage of patients who had an objective response was significantly higher with nirogacestat than with placebo (41% vs. 8%; P<0.001), with a median time to response of 5.6 months and 11.1 months, respectively; the percentage of patients with a complete response was 7% and 0%, respectively. Significant between-group differences in secondary patient-reported outcomes, including pain, symptom burden, physical or role functioning, and health-related quality of life, were observed (P≤0.01). Frequent adverse events with nirogacestat included diarrhea (in 84% of the patients), nausea (in 54%), fatigue (in 51%), hypophosphatemia (in 42%), and maculopapular rash (in 32%); 95% of adverse events were of grade 1 or 2. Among women of childbearing potential receiving nirogacestat, 27 of 36 (75%) had adverse events consistent with ovarian dysfunction, which resolved in 20 women (74%).
CONCLUSIONS
Nirogacestat was associated with significant benefits with respect to progression-free survival, objective response, pain, symptom burden, physical functioning, role functioning, and health-related quality of life in adults with progressing desmoid tumors. Adverse events with nirogacestat were frequent but mostly low grade. (Funded by SpringWorks Therapeutics; DeFi ClinicalTrials.gov number, NCT03785964.).
Topics: Adult; Female; Humans; Amyloid Precursor Protein Secretases; Antineoplastic Agents; Double-Blind Method; Fibromatosis, Aggressive; Gamma Secretase Inhibitors and Modulators; Progression-Free Survival; Quality of Life; Tetrahydronaphthalenes; Valine
PubMed: 36884323
DOI: 10.1056/NEJMoa2210140 -
The New England Journal of Medicine Dec 2018Desmoid tumors (also referred to as aggressive fibromatosis) are connective tissue neoplasms that can arise in any anatomical location and infiltrate the mesentery,... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Desmoid tumors (also referred to as aggressive fibromatosis) are connective tissue neoplasms that can arise in any anatomical location and infiltrate the mesentery, neurovascular structures, and visceral organs. There is no standard of care.
METHODS
In this double-blind, phase 3 trial, we randomly assigned 87 patients with progressive, symptomatic, or recurrent desmoid tumors to receive either sorafenib (400-mg tablet once daily) or matching placebo. Crossover to the sorafenib group was permitted for patients in the placebo group who had disease progression. The primary end point was investigator-assessed progression-free survival; rates of objective response and adverse events were also evaluated.
RESULTS
With a median follow-up of 27.2 months, the 2-year progression-free survival rate was 81% (95% confidence interval [CI], 69 to 96) in the sorafenib group and 36% (95% CI, 22 to 57) in the placebo group (hazard ratio for progression or death, 0.13; 95% CI, 0.05 to 0.31; P<0.001). Before crossover, the objective response rate was 33% (95% CI, 20 to 48) in the sorafenib group and 20% (95% CI, 8 to 38) in the placebo group. The median time to an objective response among patients who had a response was 9.6 months (interquartile range, 6.6 to 16.7) in the sorafenib group and 13.3 months (interquartile range, 11.2 to 31.1) in the placebo group. The objective responses are ongoing. Among patients who received sorafenib, the most frequently reported adverse events were grade 1 or 2 events of rash (73%), fatigue (67%), hypertension (55%), and diarrhea (51%).
CONCLUSIONS
Among patients with progressive, refractory, or symptomatic desmoid tumors, sorafenib significantly prolonged progression-free survival and induced durable responses. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT02066181 .).
Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Double-Blind Method; Female; Fibromatosis, Aggressive; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Progression-Free Survival; Sorafenib; Survival Rate; Young Adult
PubMed: 30575484
DOI: 10.1056/NEJMoa1805052 -
Cancer Aug 2022Desmoid tumors (DTs) are rare soft tissue mesenchymal neoplasms that may be associated with impairments, disfigurement, morbidity, and (rarely) mortality. DT disease... (Review)
Review
Desmoid tumors (DTs) are rare soft tissue mesenchymal neoplasms that may be associated with impairments, disfigurement, morbidity, and (rarely) mortality. DT disease course can be unpredictable. Most DTs are sporadic, harboring somatic mutations in the gene that encodes for β-catenin, whereas DTs occurring in patients with familial adenomatous polyposis have germline mutations in the APC gene, which encodes for a protein regulator of β-catenin. Pathology review by an expert soft tissue pathologist is critical in making a diagnosis. Magnetic resonance imaging is preferred for most anatomic locations. Surgery, once the standard of care for initial treatment of DT, is associated with a significant risk of recurrence as well as avoidable morbidity because spontaneous regressions are known to occur without treatment. Consequently, active surveillance in conjunction with pain management is now recommended for most patients. Systemic medical treatment of DT has evolved beyond the use of hormone therapy, which is no longer routinely recommended. Current options for medical management include tyrosine kinase inhibitors as well as more conventional cytotoxic chemotherapy (e.g., anthracycline-based or methotrexate-based regimens). A newer class of agents, γ-secretase inhibitors, appears promising, including in patients who fail other therapies, but confirmation in Phase 3 trials is needed. In summary, DTs present challenges to physicians in diagnosis and prognosis, as well as in determining treatment initiation, type, duration, and sequence. Accordingly, evaluation by a multidisciplinary team with expertise in DT and patient-tailored management are essential. As management strategies continue to evolve, further studies will help clarify these issues and optimize outcomes for patients.
Topics: Adenomatous Polyposis Coli; Fibromatosis, Aggressive; Humans; Prognosis; Soft Tissue Neoplasms; beta Catenin
PubMed: 35670122
DOI: 10.1002/cncr.34332 -
Annals of Oncology : Official Journal... Oct 2017Desmoid-type fibromatosis is a rare and locally aggressive monoclonal, fibroblastic proliferation characterized by a variable and often unpredictable clinical course.... (Review)
Review
An update on the management of sporadic desmoid-type fibromatosis: a European Consensus Initiative between Sarcoma PAtients EuroNet (SPAEN) and European Organization for Research and Treatment of Cancer (EORTC)/Soft Tissue and Bone Sarcoma Group (STBSG).
Desmoid-type fibromatosis is a rare and locally aggressive monoclonal, fibroblastic proliferation characterized by a variable and often unpredictable clinical course. Currently, there is no established or evidence-based treatment approach available for this disease. Therefore, in 2015 the European Desmoid Working Group published a position paper giving recommendations on the treatment of this intriguing disease. Here, we present an update of this consensus approach based on professionals' AND patients' expertise following a round table meeting bringing together sarcoma experts from the European Organization for Research and Treatment of Cancer/Soft Tissue and Bone Sarcoma Group with patients and patient advocates from Sarcoma PAtients EuroNet. In this paper, we focus on new findings regarding the prognostic value of mutational analysis in desmoid-type fibromatosis patients and new systemic treatment options.
Topics: Fibromatosis, Aggressive; Humans; Randomized Controlled Trials as Topic
PubMed: 28961825
DOI: 10.1093/annonc/mdx323 -
Surgical Oncology Clinics of North... Jul 2022The management of desmoid tumors (DT) is shifting toward conservative and patient-tailored strategies. Active surveillance is currently considered the first line of... (Review)
Review
The management of desmoid tumors (DT) is shifting toward conservative and patient-tailored strategies. Active surveillance is currently considered the first line of treatment for most DT patients, according to international guidelines. When active treatment is required, several systemic and local treatments are considered. The choice of the first-line systemic therapy and the management of recurrence still represent a therapeutic challenge, for which well-defined and shared guidelines are lacking. Such issues represent the next challenge for The Desmoid Tumor Working Group.
Topics: Fibromatosis, Aggressive; Humans
PubMed: 35715144
DOI: 10.1016/j.soc.2022.03.008 -
Current Opinion in Oncology Jul 2023Desmoid tumor is a rare disease of intermediate malignancy characterized by a locally aggressive monoclonal, fibroblastic proliferation and accompanied by a variable and... (Review)
Review
PURPOSE OF REVIEW
Desmoid tumor is a rare disease of intermediate malignancy characterized by a locally aggressive monoclonal, fibroblastic proliferation and accompanied by a variable and often unpredictable clinical course. The purpose of this review is to give an overview on the emerging new systemic treatment options for this intriguing disease for which no established or approved drugs are available yet.
RECENT FINDINGS
Over decades, surgical resection has been the established initial treatment approach; however, more recently, a paradigm shift has been introduced towards a more conservative treatment strategy. Almost 10 years ago, The Desmoid Tumor Working Group has initiated a consensus process initially in Europe and then globally with the intention to harmonize the therapeutic strategy amongst clinicians and set up management recommendations for desmoid tumor patients.
SUMMARY
This review will summarize and focus on the latest emerging impressive data on the use of gamma secretase inhibitors in this disease paving a possible future perspective in the treatment armamentarium for desmoid tumor patients.
Topics: Humans; Fibromatosis, Aggressive; Combined Modality Therapy; Consensus
PubMed: 37222208
DOI: 10.1097/CCO.0000000000000953 -
Current Treatment Options in Oncology Feb 2024Desmoid tumors are rare tumors with a tendency to infiltrate locally. The lack of a standard treatment approach makes choosing the most appropriate treatment for... (Review)
Review
Desmoid tumors are rare tumors with a tendency to infiltrate locally. The lack of a standard treatment approach makes choosing the most appropriate treatment for patients challenging. Most experts recommend watchful observation for asymptomatic patients as spontaneous regression of tumor is observed in up to 20% of patients. Upfront resection of the desmoid tumor has fallen out of favor due to high morbidity and high relapse rates associated with the tumor. Systemic therapy has evolved over several decades. Where chemotherapy, hormonal therapy, and non-steroidal anti-inflammatory drugs were used over the last several decades, tyrosine kinase inhibitors came to the forefront within the last decade. Most recently, gamma-secretase inhibitors have shown significant clinical benefit in patients with desmoid tumors, bringing forth an entirely new mechanistic approach. Several Wnt pathway inhibitors are also under development. Invasive approaches like cryoablation have also shown clinical benefit in patients with extra-abdominal desmoid tumors in recent years. The recent approval of nirogacestat has ushered in a new era of treatment for patients diagnosed with desmoid tumors. Several new molecules are expected to be approved over the coming years.
Topics: Humans; Fibromatosis, Aggressive; Retrospective Studies; Neoplasm Recurrence, Local
PubMed: 38270798
DOI: 10.1007/s11864-024-01177-5 -
Gaceta Medica de Mexico 2020A literature review on desmoid tumors was carried out, which are tumors that affect soft tissues with a locally aggressive behavior and are unable to metastasize.... (Review)
Review
A literature review on desmoid tumors was carried out, which are tumors that affect soft tissues with a locally aggressive behavior and are unable to metastasize. Sporadic cases are located on the extremities and chest wall; hereditary cases have an intra-abdominal predilection, and those associated with pregnancy occur on the abdominal wall. Imaging techniques assess disease extension. Trucut biopsy is the study of choice for diagnosis. Mutations in the CTNNB1 or APC genes cause an abnormal accumulation of b-catenin within the cell. In this review, an emphasis is made on therapeutic strategies' evolution and change, and current tools for decision making are analyzed, as well as clinical outcomes. Radiation therapy can play a therapeutic or adjuvant role. Advances in the understanding of the disease have allowed establishing better targeted treatments with lower morbidity; however, there are still unanswered questions regarding the choice of the ideal candidate for surveillance and/or early treatment. Data related to quality of life are also presented, as well as the uncertainty generated by this diagnosis for both doctor and patient.
Topics: Anti-Inflammatory Agents; Antineoplastic Agents; Biopsy; Clinical Decision-Making; Female; Fibromatosis, Aggressive; Humans; Male; Quality of Life; Radiotherapy; Uncertainty; beta Catenin
PubMed: 33372933
DOI: 10.24875/GMM.M20000440