Optimal therapy for desmoid tumors: current options and challenges for the future

Abstract

Desmoid tumors, or aggressive fibromatosis, are rare, locally infiltrative neoplasms caused by mutations that activate β-catenin. Although these tumors do not metastasize, they are difficult to manage due to variability in tumor presentation and behavior. A variety of treatment options exist, including surgery, radiotherapy, chemotherapy, hormone therapy, isolated limb perfusion, cryoablation and tyrosine kinase inhibitors. Treatment-induced morbidity and poor local control rates, combined with spontaneous stabilization of some desmoid tumors, have allowed watchful waiting to recently emerge as a front-line management option. This has emphasized the need to better understand tumor behavior in order to differentiate between tumors that may stabilize and those that may progress. Here, we review the most recent findings in desmoid tumor biology and treatment options for this enigmatic disease.

Keywords:

• desmoids
• fibromatosis
• molecular biology
• observation
• prognosis
• progression
• recurrence
• surgery
• treatment
• trials

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Desmoid tumors, or aggressive fibromatosis, are rare, locally infiltrative fibrous neoplasms arising in musculoaponeurotic tissues.

• They can arise sporadically due to mutations in the β-catenin gene (CTNNB1), or in association with hereditary familial adenomatous polyposis where the APC gene is mutated. Either type of mutation leads to increased β-catenin protein level and activity.

• The natural history of desmoid tumors is not fully understood. Some desmoid tumors spontaneously regress, while others can progress rapidly. Little is known about the prognostic factors that can differentiate between indolent and aggressive cases.

• An initial period of observation is recommended when a patient first presents with an asymptomatic tumor that is not rapidly progressing. Recent findings suggest that a subgroup of patients can completely avoid the morbidity associated with wide surgical resections.

• Since desmoid tumors do not metastasize, treatment-associated morbidity is a factor that influences disease management decisions.

• A wide variety of treatment options exists. However, lack of prospective, well-controlled trials with an extended follow-up period makes it difficult to make conclusions about the optimal therapeutic approach.

• Surgical resection with negative margins is the main intervention method. Factors associated with increased risk of recurrence after surgery are younger age, positive margins, tumor located in the extremities and a large tumor size.

• Evidence suggests that radiotherapy is only useful when surgical removal is incomplete.

• Medical treatments that target the PDGFRβ pathway (imatinib, sunitinib, pazopanib and sorafenib) have been used in inoperable or recurrent tumors with some degree of success. But strong evidence for their efficacy is lacking.

• Increased understanding of the underlying molecular biology, with an emphasis on β-catenin and its target genes, will help explain tumor behavior and identify effective treatments.