Giant Intrathoracic Desmoid Tumor – a Case Report

Desmoid tumors are soft tissue neoplasms arising from fascial and muscle-aponeurotic structure. These tumors are locally aggressive and have a high recurrence rate, even after complete resection. We present the case of a female with a giant intrathoracic desmoid tumor. She underwent complete surgical resection with no disease recurrence. Desmoid tumors’ natural history is not well defined and is often enigmatic, making these tumors difficult to manage. Currently, for intrathoracic desmoid tumors, medical treatment is the recommended approach, nevertheless, surgery can be considered in selected patients.

Purpose: To determine to the activity and safety of TGF-β inhibitor, vactosertib in combination with imatinib in patients with desmoid tumors.

Patients and methods: In this investigator-initiated, open-label, multicenter, phase Ib/II trial, patients with desmoid tumors not amendable to locoregional therapies (surgery and/or radiotherapy) or with disease progression following at least one treatment were enrolled. Participants were administered 400 mg imatinib daily in combination with vactosertib (5 days on and 2 days off, twice a day) every 28 days. In phase Ib, the vactosertib dose was set at 100 mg (level -1) and 200 mg (level 1) to determine the recommended phase II dose (RP2D). Phase II assessed the efficacy, with the primary endpoint being progression-free rate (PFR) at 16 weeks.

Results: No dose-limiting toxicities were observed during the phase Ib, therefore RP2D was defined at doses of 400 mg imatinib daily in combination with 200 mg vactosertib. Of the 27 patients evaluated, 7 (25.9%) achieved a confirmed partial response and 19 (70.4%) were stable. The PFR at 16 weeks and 1 year were 96.3% and 81.0%, respectively. The most toxicities were mild to moderate myalgia (n=10, 37%), anemia (n=10, 37%), and nausea (n=9, 33.3%). Common grade 3-4 toxicities included neutropenia (n=6, 22.2%) and anemia (n=5, 18.5%).

Conclusions: Vactosertib and imatinib combination was well-tolerated, with promising clinical activity in patients with progressive, locally advanced desmoid tumors. This is the first study investigating a novel target agent, a TGF-β inhibitor, in this rare and difficult-to-treat desmoid tumor.

Nirogacestat (OGSIVEO™) is an oral, selective, reversible, small molecule γ-secretase inhibitor developed by SpringWorks Therapeutics, Inc. γ-Secretase is a multi-subunit protease complex that cleaves multiple transmembrane protein complexes, including Notch and membrane-bound B-cell maturation antigen (BCMA). Inhibition of γ-secretase may result in growth inhibition of tumour cells overexpressing Notch, and preservation of membrane-bound BCMA may increase target density for BCMA-targeted therapy. In November 2023, nirogacestat was approved in the USA for use in adult patients with progressing desmoid tumours who require systemic treatment. This article summarizes the milestones in the development of nirogacestat leading to this first approval for the systemic treatment of desmoid tumours.

Fibromatosis is a rare locally aggressive benign tumour which arises from the musculoaponeurotic structures throughout the body. In the oral and maxillofacial region, It has been described under a variety of synonyms, including ‘extra articular desmoids’, ‘desmoids tumours’, ‘grade-1 fibrosarcomas’,’non metastasizing fibrosarcoma’and ‘aggressive fibromatosis’. The pecularity of this entity in paranasal sinuses is that it is rare in this location and are locally aggressive with higher rates of recurrence in a relatively restricted area.The purpose of this study is to present a rare case report and reviewing the literature of this entity.

Desmoid fibromatosis is also known as aggressive fibromatosis. It is a neoplastic monoclonal proliferation of fibroblasts, with an incidence of 2 to 4 per million per year. Its incidence peaks at 8 years of age and in the third/fourth decades of life. Here we discussed a patient in third decade of life who presented with unilateral nasal blockage with a picture suggestive of sinonasal polyposis on examination. On histopathology, he was diagnosed with Desmoid fibromatosis. Though a rare entity, Desmoid fibromatosis should be kept in mind as a differential diagnosis for appropriate patient management. As per our knowledge, in India this is the first documented case of desmoid fibromatosis arising from maxillary sinus.

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