A Nationwide Prospective Clinical Trial on Active Surveillance in Patients with Non-Intra-Abdominal Desmoid-Type Fibromatosis: The GRAFITI Trial

OBJECTIVE: To assess tumour behaviour and the efficacy of active surveillance (AS) in patients with desmoid-type fibromatosis (DTF).

SUMMARY BACKGROUND DATA: AS is recommended as initial management for DTF patients. Prospective data regarding the results of AS are lacking.

METHODS: In this multicentre prospective cohort study (NTR4714), adult patients with non-intra-abdominal DTF were followed during an initial AS approach for 3 years. Tumour behaviour was evaluated according to RECIST. Cumulative incidence of the start of an active treatment and progression-free survival (PFS) were calculated using the Kaplan-Meier method. Factors predictive for start of active treatment were assessed by Cox regression analyses.

RESULTS: A total of 105 patients started with AS. Median tumour size at baseline was 4.1 cm (IQR 3.0-6.6). Fifty-seven patients had a T41A CTNNB1 mutation; 14 patients a S45F CTNNB1 mutation. At 3 years, cumulative incidence of the start of active treatment was 30% (95% CI 21-39) and PFS was 58% (95% CI 49-69). Median time to start active treatment and PFS were not reached at a median follow-up of 33.7 months. During AS, 32% of patients had stable disease, 28% regressed and 40% demonstrated initial progression. Larger tumour size (≥5 cm; hazard ratio (HR) = 2.38 [95% CI 1.15-4.90]) and S45F mutation (HR = 6.24 [95% CI 1.92-20.30]) were associated with the start of active treatment.

CONCLUSIONS: The majority DTF patients undergoing AS do not need an active treatment and experience stable or regressive disease, even after initial progression. Knowledge about the natural behaviour of DTF will help to tailor the follow-up schedule to the individual patient.