# Experience of a Referral Center with Desmoid Tumors, Part 2: A Retrospective Analysis of 109 Cases

## TL;DR

This study analyzes 109 desmoid tumor cases to understand treatment outcomes and behavior, supporting personalized and conservative management strategies.

## Contribution

The study provides real-world insights into desmoid tumor management and outcomes from a specialized referral center.

## Key findings

- Conservative initial management and R1/2 surgical margins were linked to worse event-free survival.
- Spontaneous regression occurred in 22.2% of patients under active surveillance.
- Cryoablation showed radiological responses in most patients, while systemic therapies had notable toxicity.

## Abstract

Desmoid tumors are rare soft tissue neoplasms with unpredictable behavior. Although they do not metastasize, they can grow locally and cause pain or functional impairment. Due to the potential for spontaneous regression, therapeutic strategies have recently evolved toward more conservative and individualized approaches, prioritizing active surveillance and functional preservation whenever possible. This study presents the experience of our national sarcoma reference center, reviewing more than 100 patients treated over the past decade. We analyze demographic, clinical, radiological, and treatment-related variables to explore potential prognostic factors associated with disease evolution and therapeutic outcomes. Our findings contribute to a better understanding of desmoid tumor behavior in a real-world, multidisciplinary setting, which will help support more individualized decision-making in routine clinical practice.

Background: Desmoid tumors (DTs) are rare, locally aggressive fibroblastic neoplasms with highly heterogeneous clinical behavior. The present work constitutes the second part of a two-part project, following our previously published multidisciplinary review of the diagnostic and therapeutic landscape of DTs. It provides a comprehensive analysis of our institutional experience as a national reference center for sarcoma. We aim to describe real-world diagnostic pathways, management strategies, and clinical outcomes in a high-volume cohort. Methods: We conducted a retrospective cohort study that included patients diagnosed with DT at our center between 2014 and 2024. Demographic, clinical, molecular, treatment, and outcome data were collected. Management strategies were analyzed according to tumor location, symptoms, progression patterns, and multidisciplinary decision-making. Outcomes included response rates, event-free survival (EFS), need for active treatment, response to systemic therapy, and recurrence after local treatments. Results: A total of 109 patients were included (median age 36.8 years; 56.9% women). Somatic CTNNB1 mutations were identified in 23 of 29 tested patients, predominantly T41A, while germline alterations were found in 18 patients, mainly in APC. Initial management was conservative in 40.4% of patients and active in 59.6%, primarily through surgery. After a median follow-up of 41.5 months, 44.9% of patients experienced disease progression. Among patients managed with active surveillance, spontaneous regression occurred in 22.2%, and 58% remained treatment-free. Surgical relapse occurred in 35.8% of patients undergoing upfront resection, with major postoperative complications limited to externally operated cases. Cryoablation achieved radiological responses in most evaluable patients, while systemic therapies showed clinical activity but relevant toxicity, particularly with tyrosine kinase inhibitors. The median EFS for the whole cohort was 57 months. Conservative initial management and R1/2 surgical margins were independently associated with worse EFS. Conclusions: Our results support a personalized, multidisciplinary management strategy for DTs, prioritizing conservative approaches when appropriate and reserving active treatments for progressive or symptomatic disease. Outcomes achieved in a specialized referral center are comparable to those reported in large international retrospective series, underscoring the value of expert multidisciplinary care in optimizing DT management.