-
Cancer Treatment Reviews Feb 2024Desmoid tumors (DT) are rare, slow-growing, locally invasive soft tissue tumors that often pose significant therapeutic challenges. Traditional management strategies... (Review)
Review
Desmoid tumors (DT) are rare, slow-growing, locally invasive soft tissue tumors that often pose significant therapeutic challenges. Traditional management strategies including active surveillance, surgery, radiotherapy, and systemic therapy which are associated with varying recurrence rates and high morbidity. Given the challenging nature of DT and the modest outcomes associated with current treatment strategies, there has been a growing interest in the field of γ-secretase inhibitors as a result of its action on the Wnt/β-catenin signaling pathway. In this review article, we will shed the light on the pathogenesis and molecular biology of DT, discuss its symptoms and diagnosis, and provide a comprehensive review of the traditional therapeutic approaches. We will also delve into the mechanisms of action of γ-secretase inhibitors, its efficacy, and the existing preclinical and clinical data available to date on the use of these agents, as well as the potential challenges and future prospects in the treatment landscape of these tumors.
Topics: Humans; Fibromatosis, Aggressive; Amyloid Precursor Protein Secretases
PubMed: 38159438
DOI: 10.1016/j.ctrv.2023.102675 -
The Breast Journal Oct 2021Studies suggest that surgical breast augmentation with implants is a risk factor for breast desmoid tumors. The statistical strength of this correlation is unknown, as...
BACKGROUND
Studies suggest that surgical breast augmentation with implants is a risk factor for breast desmoid tumors. The statistical strength of this correlation is unknown, as evidence is limited to anecdotal reports.
METHODS
Patients with breast desmoid tumors and a history of breast implants seen at a single center between 2000 and 2021 were identified via radiology, breast, and sarcoma databases. The standardized incidence ratio (SIR) was calculated to assess the correlation between breast desmoid tumors and breast implants. The cases were pooled with published cases for analyses. Progression-free survival curves and hazard ratios were estimated using the Kaplan-Meier method and Cox proportional-hazards modeling.
RESULTS
Fourteen patients from one institution and 66 cases in the literature were identified. All patients were female, and the mean age was 38 years old (range 20-66). 63 patients (82%) underwent resection, 9 (12%) received chemotherapy, 3 (4%) received sorafenib, 11 (14%) received hormonal therapy, and 3 (4%) underwent active surveillance. After resection, the 2-year recurrence-free survival rate was 77% (95% CI 65%-89%). The recurrence risk was lower for resection with no residual tumor (R0) compared to microscopic (R1) or macroscopic (R2) residual tumor (HR: 0.15; 95% CI 0.02-0.8; p < 0.05). The SIR was 482 (95% CI 259-775) to 823 (95% CI 442-1322), suggesting a 482-823 times higher risk of developing a breast desmoid tumor after breast augmentation than the general population.
CONCLUSION
We present a nonrandom association between breast implants and desmoid tumors. Whether the tumors arise from the surgical trauma or the implant's biomaterial is unknown. When surgery is indicated, negative margins reduce the risk of recurrence.
Topics: Adult; Aged; Breast Implants; Breast Neoplasms; Female; Fibromatosis, Aggressive; Humans; Middle Aged; Neoplasm Recurrence, Local; Retrospective Studies; Young Adult
PubMed: 34453383
DOI: 10.1111/tbj.14276 -
Surgical Oncology Clinics of North... Oct 2016Desmoid-type fibromatosis is a rare nonmetastasizing neoplasm with variable behavior. Recent discoveries into the biology of this disease hold promise for identifying... (Review)
Review
Desmoid-type fibromatosis is a rare nonmetastasizing neoplasm with variable behavior. Recent discoveries into the biology of this disease hold promise for identifying prognostic and predictive features and novel therapeutic targets. Surgery has been the historical standard of care but carries considerable drawbacks in terms of high local recurrence rates and poor functional outcomes. Improved understanding of the natural history of desmoid-type fibromatosis has resulted in a paradigm shift toward nonoperative management. Effective medical treatment options include nonsteroidal antiinflammatory drugs, hormone therapy, cytotoxic chemotherapy, and targeted agents. A treatment algorithm has been proposed with the objective of optimizing treatment.
Topics: Antineoplastic Agents; Disease Management; Disease Progression; Fibromatosis, Aggressive; Humans; Prognosis; Treatment Outcome
PubMed: 27591500
DOI: 10.1016/j.soc.2016.05.010 -
International Journal of Cancer Jul 2023The aim of this study is to evaluate the prevalence, determinants and prognostic value of pain at diagnosis in patients with desmoid-type fibromatosis (DF). We selected...
The aim of this study is to evaluate the prevalence, determinants and prognostic value of pain at diagnosis in patients with desmoid-type fibromatosis (DF). We selected patients from the ALTITUDES cohort (NCT02867033), managed by surgery, active surveillance or systemic treatments, with pain assessment at diagnosis. Patients were invited to fill QLQ-C30 questionnaire and Hospital Anxiety Depression Scale. Determinants were identified using logistic models. Prognostic value on event-free survival (EFS) was evaluated using the Cox model. Overall, 382 patients were included in the current study (median age: 40.2 years; 117 men). The prevalence of pain was 36%, without significant difference according to first-line treatment (P = .18). In the multivariate analysis, pain was significantly associated with tumor size >50 mm (P = .013) and tumor site (P < .001); pain was more frequent in the neck and shoulder locations (odds ratio: 3.05 [1.27-7.29]). Pain at baseline was significantly associated with poor quality of life (P < .001), depression (P = .02), lower performance status (P = .03) and functional impairment (P = .001); we also observed a nonsignificant association with anxiety (P = .10). In the univariate analysis, baseline pain was associated with poor EFS; the 3-year EFS was 54% in patients with pain compared to 72% in those without pain. After adjustment for sex, age, size and line of treatment, pain was still associated with poor EFS (hazard ratio: 1.82 [1.23-2.68], P = .003). One third of recently diagnosed patients with DF experienced pain, especially those with larger tumors and neck/shoulder locations. Pain was associated with unfavorable EFS after adjustment for the confounders.
Topics: Adult; Humans; Male; Fibromatosis, Aggressive; Pain; Prevalence; Prognosis; Quality of Life
PubMed: 36883417
DOI: 10.1002/ijc.34493 -
Scientific Reports Jan 2018Desmoid tumors (aggressive fibromatosis) are locally invasive soft tissue tumors that lack the ability to metastasize. There are no directed therapies or standard...
Desmoid tumors (aggressive fibromatosis) are locally invasive soft tissue tumors that lack the ability to metastasize. There are no directed therapies or standard treatment plan, and chemotherapeutics, radiation, and surgery often have temporary effects. The majority of desmoid tumors are related to T41A and S45F mutations of the beta-catenin encoding gene (CTNNB1). Using broad spectrum metabolomics, differences were investigated between paired normal fibroblast and desmoid tumor cells from affected patients. There were differences identified, also, in the metabolomics profiles associated with the two beta-catenin mutations, T41A and S45F. Ongoing drug screening has identified currently available compounds which inhibited desmoid tumor cellular growth by more than 50% but did not affect normal fibroblast proliferation. Two drugs were investigated in this study, and Dasatinib and FAK Inhibitor 14 treatments resulted in unique metabolomics profiles for the normal fibroblast and desmoid tumor cells, in addition to the T41A and S45F. The biochemical pathways that differentiated the cell lines were aminoacyl-tRNA biosynthesis in mitochondria and cytoplasm and signal transduction amino acid-dependent mTORC1 activation. This study provides preliminary understanding of the metabolic differences of paired normal and desmoid tumors cells, their response to desmoid tumor therapeutics, and new pathways to target for therapy.
Topics: Cell Line, Tumor; Dasatinib; Drug Screening Assays, Antitumor; Female; Fibromatosis, Aggressive; Gene Expression Regulation, Neoplastic; Humans; Male; Metabolome; Metabolomics; Mutation; Pilot Projects; Protein Kinase Inhibitors; beta Catenin
PubMed: 29330550
DOI: 10.1038/s41598-017-18921-7 -
Bulletin Du Cancer Mar 2020About 15 % of patients with familial adenomatous polyposis "PAF" develop one or more desmoid tumors in their lifetime. These are benign mesenchymal tumors with local... (Review)
Review
About 15 % of patients with familial adenomatous polyposis "PAF" develop one or more desmoid tumors in their lifetime. These are benign mesenchymal tumors with local aggressivity but with no potential for metastases. Most of the desmoids tumors result from a sporadic genetic anomaly in the β catenin gene. When related to familial adenomatous polyposis or "PAF", this mutation is not present, and the patients must be sent in genetic counselling. The PAF is a dominant autosomic illness related to a germinal mutation in the APC gene. Sometimes, these tumors can be the first manifestation of the illness. The diagnosis in a context of PAF can be easily done by imaging, but a pathological confirmation is needed. These tumors raise a therapeutic problem because of their heterogeneity and the absence of predictive biomarkers along illness evolution. The identification of prognostic biological and clinical factors would make easier the selection of patients requiring first-line treatment, as spontaneous remissions have also been observed in patients with FAP whom which an active surveillance could also be a valid therapeutic option. The particularity of desmoids tumors associated to PAF lies in their predominantly intra-abdominal location and the risk of complication. In the last ten years, surgery has largely given way to conservative treatments such as chemotherapy and more recently to tyrosine kinase inhibitors that have shown their efficacy with a significant improvement in progression-free survival of patients.
Topics: Abdominal Neoplasms; Abdominal Wall; Adenomatous Polyposis Coli; Female; Fibromatosis, Aggressive; Gardner Syndrome; Genes, APC; Humans; Male; Patient Selection; Pregnancy; Pregnancy Complications, Neoplastic; Prognosis; Protein Kinase Inhibitors; Watchful Waiting
PubMed: 31882269
DOI: 10.1016/j.bulcan.2019.10.011 -
Expert Review of Anticancer Therapy Jun 2024APC-associated polyposis is a rare hereditary disorder characterized by the development of multiple adenomas in the digestive tract. Individuals with APC-associated... (Review)
Review
INTRODUCTION
APC-associated polyposis is a rare hereditary disorder characterized by the development of multiple adenomas in the digestive tract. Individuals with APC-associated polyposis need to be managed by specialized multidisciplinary teams in dedicated centers.
AREAS COVERED
The study aimed to review the literature on Familial adenomatous polyposis (FAP) to provide an update on diagnostic and surgical management while focusing on strategies to minimize the risk of desmoid-type fibromatosis, cancer in anorectal remnant, and postoperative complications. FAP individuals require a comprehensive approach that includes diagnosis, surveillance, preventive surgery, and addressing specific extracolonic concerns such as duodenal and desmoid tumors. Management should be personalized considering all factors: genotype, phenotype, and personal needs. Total colectomy and ileo-rectal anastomosis have been shown to yield superior QoL results when compared to Restorative Procto colectomy and ileopouch-anal anastomosis with acceptable oncological risk of developing cancer in the rectal stump if patients rigorously adhere to lifelong endoscopic surveillance. Additionally, a low-inflammatory diet may prevent adenomas and cancer by modulating systemic and tissue inflammatory indices.
EXPERT OPINION
FAP management requires a multidisciplinary and personalized approach. Integrating genetic advances, innovative surveillance techniques, and emerging therapeutic modalities will contribute to improving outcomes and quality of life for FAP individuals.
Topics: Humans; Adenomatous Polyposis Coli; Quality of Life; Colectomy; Postoperative Complications; Patient Care Team; Precision Medicine; Phenotype; Genotype; Fibromatosis, Aggressive
PubMed: 38785081
DOI: 10.1080/14737140.2024.2344649 -
Mayo Clinic Proceedings Oct 2022
Topics: Breast; Breast Neoplasms; Female; Fibromatosis, Aggressive; Gardner Syndrome; Humans
PubMed: 36202497
DOI: 10.1016/j.mayocp.2022.06.014 -
Cardiovascular and Interventional... Jan 2020Cryoablation is being more and more often used to treat desmoid tumors. We report our experience of cryoablation as a local and analgesic treatment for inoperable or...
OBJECTIVE
Cryoablation is being more and more often used to treat desmoid tumors. We report our experience of cryoablation as a local and analgesic treatment for inoperable or recurring desmoid tumors.
METHODS
This study includes 34 patients who underwent percutaneous cryoablation of 41 desmoid tumors between July 2012 and September 2016. All patients underwent pain assessment using a visual analog scale (VAS) and preoperative imaging. All cryoablation procedures were performed using the same cryoablation system. Patients received clinical and radiological follow-up at 6 months post-procedure, with pain-rating and adverse events being recorded. A long-term follow-up was achieved until 31 December 2018. Disease-free survival at 3 years was also recorded. Radiological tumor response was determined by tumor measurements using RECIST 1.1.
RESULTS
Twelve patients benefitted from curative treatment on 100% of the tumor volume, but 22 patients received debulking treatment because of the risk of neighboring structures. Two patients had a postoperative hematoma grade 2 of the CIRSE classification system for complications, and two patients had grade 4 complications involving palsy of the common fibular nerve. Disease-free survival at 3 years was 42.2%. The mean VAS pain scores were 5.7 and 2.4 at pretreatment and 6 months, respectively, showing a mean reduction of 3.3 (p < 0.001). At 6 months, all measured tumor dimensions were significantly lower than pretreatment.
CONCLUSION
Cryoablation is an effective therapeutic option for the local treatment and for the analgesic management of desmoid tumors.
Topics: Adolescent; Adult; Aged; Analgesia; Cohort Studies; Cryosurgery; Disease-Free Survival; Female; Fibromatosis, Aggressive; Follow-Up Studies; Humans; Male; Middle Aged; Pain; Retrospective Studies; Treatment Outcome; Young Adult
PubMed: 31471720
DOI: 10.1007/s00270-019-02323-5 -
Annals of Surgical Oncology Aug 2023In this study, we aimed to describe the clinical features, management, and outcomes of desmoid tumors (DTs) in familial adenomatous polyposis (FAP) patients at a...
OBJECTIVE
In this study, we aimed to describe the clinical features, management, and outcomes of desmoid tumors (DTs) in familial adenomatous polyposis (FAP) patients at a high-volume sarcoma center.
METHODS
Consecutive patients with FAP and DTs were identified from our institutional databases (1985-2021). Patient demographics, treatment, and outcomes were described. Categorical data were compared using Fisher's exact test, and Kaplan-Meier curves were used to estimate progression-free survival (PFS).
RESULTS
Forty-five patients with 67 DTs were identified: 39 mesenteric or retroperitoneal (58.2%), 17 abdominal wall (25.4%), 4 extremity (6%), 4 breast (6%) and 3 back (4.4%). Severe DT symptoms were present in 12 patients (26.7%). Initial treatments per tumor were observation in 30 (44.8%) DTs, chemotherapy in 15 (22.4%) DTs, surgery in 10 (14.9%) DTs, and other systemic therapies in 10 (14.9%) DTs. The majority of DTs remained stable with observation or a single intervention (77.8%). Median PFS was 23.4 years (95% confidence interval 7.6-39.2). In the 12 severely symptomatic patients, four patients required more than two interventions for DT control. At a median follow-up of 6.0 years (range 0.7-35.8 years), 33 (73.3%) patients were alive with disease, 7 (15.6%) were alive without disease, and 5 (11.1%) died of other causes. No patients died of DT-related complications.
CONCLUSIONS
The majority of DTs in FAP patients remained stable with observation or a single intervention. There were no DT-related deaths; however, 12 of 45 patients (26.7%) experienced significant tumor morbidity and required more interventions for disease control. Further studies on quality of life are required.
Topics: Humans; Fibromatosis, Aggressive; Quality of Life; Adenomatous Polyposis Coli; Mesentery
PubMed: 37237094
DOI: 10.1245/s10434-023-13675-1