Desmoid Tumors-Biology-Driven Management and Treatment Selection

Desmoid tumors (DTs) are rare fibroblastic neoplasms driven by altered Wnt signaling pathways, through activating mutations in β-catenin (CTNNB1) or loss of repressive APC. DTs are considered as intermediate neoplasms that can be locally aggressive, with potential for significant medical complications that can threaten life and limb, as well as impact on patient function, quality of life, and emotional well-being. Historically, DTs were treated with similar paradigms as soft tissue sarcomas, with complete surgical resection the priority despite frequent postoperative recurrences, or use of radiation or cytotoxic chemotherapies for refractory/recurrent cases. Today, improved understanding of DT biology and natural history, along with the development of molecularly targeted therapies, has greatly changed the recommended approach to DT management. In this review, we highlight the role of active surveillance for initial management of most DTs, recognizing the potential for tumor stability or spontaneous regression. In the case of highly symptomatic or progressive tumors, we review the spectrum of treatment options, including surgery for select cases, systemic therapies such as novel gamma secretase inhibitors and tyrosine kinase inhibitors, and emerging local treatment options including cryoablation and high-intensity focused ultrasound. Through a multidisciplinary approach and careful assessment of the individual patient's DT biology and symptomatic impacts, the optimal treatment strategy can be selected to minimize unnecessary morbidity and toxicity and to improve outcomes and quality of life for this unique patient population.