Evolving strategies for management of desmoid tumor

Abstract

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.

Keywords: active surveillance; antineoplastic agents; desmoid tumor; fibromatosis, aggressive; radiotherapy; tyrosine kinase inhibitors; γ-secretase inhibitors.

FIGURE 1

(A) T1‐weighted and (B) T2‐weighted, fat‐suppressed magnetic resonance images in the coronal plain of a 28‐year‐old woman with a large desmoid tumor (DT) in the shoulder region (straight arrows). The curved arrow indicates a nodular protrusion that raises concern for pleural invasion. (C) Axial, contrast‐enhanced computed tomography image from a 27‐year‐old woman with a nonresectable, solitary intra‐abdominal DT not associated with familial adenomatous polyposis. An arrow indicates a large, well defined mass adherent to the small bowel and mesenteric vessels. (D) Transverse ultrasound of a sporadic right paraspinal musculature extra‐abdominal DT in a 26‐year‐old woman. Linear fascial extension (tail sign) is indicated by the arrow. A and B reprinted from: Shinagare AB, Ramaiya NH, Jagannathan JP, et al. A to Z of desmoid tumors. AJR Am J Roentgenol. 2011;197(6):W1008–W1014, with permission from the American Roentgen Ray Society. Copyright©2011, American Roentgen Ray Society. C and D reprinted from: Braschi‐Amirfarzan M, Keraliya AR, Krajewski KM, et al. Role of imaging in management of desmoid‐type fibromatosis: a primer for radiologists. Radiographics. 2016;36(3):767–782, with permission from The Radiological Society of North America. Copyright©2016, The Radiological Society of North America.

FIGURE 2

(A) Macroscopic view of the cut surface of an extra‐abdominal desmoid tumor. (B) Abdominal desmoid tumor showing typical infiltrative growth pattern of skeletal muscle (hematoxylin and eosin staining, original magnification ×200). A and B reprinted from: Leithner A, Gapp M, Radl R, et al. Immunohistochemical analysis of desmoid tumours. J Clin Pathol. 2005;58(11)1152–1156, with permission from BMJ Publishing Group. Permission conveyed through Copyright Clearance Center, Inc.

FIGURE 3

Schema for the management of patients with desmoid tumor recommended by the Desmoid Tumor Working Group. ILP, isolated limb perfusion; MTx, medical treatment; RTx, radiotherapy; Sx, surgery; Sx*, surgery is an option if morbidity is limited. Reprinted from: Desmoid Tumor Working Group. The management of desmoid tumours: a joint global consensus‐based guideline approach for adult and paediatric patients. Eur J Cancer. 2020;127:96–107, with permission from Elsevier Science & Technology Journals. Permission conveyed through Copyright Clearance Center, Inc.

FIGURE 4

Kaplan–Meier plot of duration of progression‐free survival in patients with advanced and refractory desmoid tumors in the sorafenib and placebo arms of a clinical trial (ClinicalTrials.gov identifier NCT02066181). NE indicates not estimable. Reprinted from: Gounder MM, Mahoney MR, Van Tine BA, et al. Sorafenib for advanced and refractory desmoid tumors. N Engl J Med. 2018;379 (25):2417–2428, with permission from Massachusetts Medical Society. Copyright©2018 Massachusetts Medical Society.