A Nationwide Prospective Clinical Trial on Active Surveillance in Patients With Non-intraabdominal Desmoid-type Fibromatosis: The GRAFITI Trial

Abstract

Objective: To assess tumor behavior and the efficacy of active surveillance (AS) in patients with desmoid-type fibromatosis (DTF).

Summary of background data: AS is recommended as initial management for DTF patients. Prospective data regarding the results of AS are lacking.

Methods: In this multicenter prospective cohort study (NTR4714), adult patients with non-intraabdominal DTF were followed during an initial AS approach for 3 years. Tumor behavior was evaluated according to Response Evaluation Criteria in Solid Tumors. 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 tumor size at baseline was 4.1cm (interquartile range 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% confidence interval [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 tumor size (≥5 cm; hazard ratio = 2.38 [95% CI 1.15-4.90]) and S45F mutation (hazard ratio = 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 behavior of DTF will help to tailor the follow-up schedule to the individual patient.

Figure 1

Cumulative incidence of the start of an active treatment in 105 patients initially managed with active surveillance.

Figure 2

Treatment strategies during follow-up. Systemic therapy included treatment with doxorubicine, vinorelbine, or tamoxifen.

Figure 3

Spider plot of relative change of largest desmoid-type fibromatosis diameter from baseline over time for all evaluable patients (n = 104), defined as those with baseline tumor assessments and at least 1 postbaseline assessment. (A) Patients with progressive disease (PD) during follow-up (FU) (n = 42);(B) patients with stable disease (SD) during FU (n = 33);(C) patients with partial regression (PR) during FU (n = 29). Horizontal dashes lines represent ≥20% increase in tumor size compared to baseline (PD according to RECIST) and ≥30% decrease in tumor size according to baseline (PR according to RECIST). FU, follow-up. Pink, PD; Blue, SD;Green, PR;Circle, imaging measurement;Yellow triangle, NSAID use;Red diamond, loss to FU;Black square, start of active treatment.