Purpose:

Three prospective observational studies (Italy, the Netherlands, and France) on active surveillance (AS) in patients with extra-abdominal desmoid-type fibromatosis support AS as a first-line approach. Identifying prognostic factors for the failure of AS will help determine the strategy. The aim of this study was to investigate the prognostic impact of clinical and molecular variables in a larger series.

Experimental Design:

Data available as of January 31, 2024, from the three studies, in which patients were followed for ≥3 years, were pooled. Patients ≥18 years of age, with primary sporadic desmoid-type fibromatosis, and with CTNNB1 mutations available were eligible. The primary study endpoint was treatment-free survival (TFS). Secondary endpoints included the incidence of RECIST progression, spontaneous RECIST regression, and regression post-RECIST progression.

Results:

Patients (n = 282) with a median follow-up of 53 months (IQR, 39–63) were included. The 3- and 5-year TFS rates were 67% and 66%, respectively; the 3- and 5-year crude cumulative incidences were 33% and 34% for RECIST progression, 26% and 34% for RECIST regression, and 33% and 38% for regression post-RECIST progression, respectively. In multivariable analysis, larger tumor size, mutation type, and tumor locations were associated with lower TFS. The specific mutation (S45F), larger tumor size, and extremity and trunk locations were all associated with a lower probability of spontaneous RECIST regression.

Conclusions:

This study confirms that spontaneous regression occurs in a significant proportion of patients and that two-thirds are treatment free at 5 years. Initial tumor size, CTNNB1 mutation, and location should be factored into the initial decision-making process.

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©2024 The Authors; Published by the American Association for Cancer Research
2024
American Association for Cancer Research
This open access article is distributed under the Creative Commons Attribution 4.0 International (CC BY 4.0) license.
This work is licensed under a Creative Commons Attribution 4.0 International License .
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Supplementary data

Supplementary Figure 1

Supplementary Figure 1. CONSORT diagram of included patients.

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Supplementary Figure 2

Supplementary Figure 2. Kaplan-Meier curves for treatment-free survival (A) and crude cumulative incidence curves for RECIST progression (B), RECIST regression as first event (C), regression post-RECIST progression (D), first regression (E), RECIST regression as any event (F), progression free survival (PFS) (G), on the whole series.

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Supplementary Figure 3

Supplementary Figure 3. Crude cumulative incidence curves for regression post-RECIST progression according to sex (A), initial tumour size in mm (B), tumour locations (C), CTNNB1 mutation types (D)

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Supplementary Figure 4

Supplementary Figure 4. Crude cumulative incidence curves for first regression according to sex (A), initial tumour size in mm (B), tumour locations (C), CTNNB1 mutation types (D).

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Supplementary Figure 5

Supplementary Figure 5. Crude cumulative incidence curves for RECIST regression as any event according to sex (A), initial tumour size in mm (B), tumour locations (C), CTNNB1 mutation types (D).

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Supplementary Figure 6

Supplementary Figure 6. Crude cumulative incidence curves for progression free survival as any event according to sex (A), initial tumour size in mm (B), tumour locations (C), CTNNB1 mutation types (D).

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Supplementary Figure 7

Supplementary Figure 7. Flowchart of patients who received an active treatment.

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Supplementary Table 1

Supplementary Table 1. Distribution of mutation and median size according to anatomical site.

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