Active surveillance in primary desmoid tumor (DT): A prospective observational study.

Abstract

11570 Background: In recent years evidence of long term stabilization and spontaneous regression of primary sporadic DT resulted in a paradigm shift towards more conservative approaches. We present herein the results of an observational study aimed at prospectively assess the behavior of primary sporadic DT initially managed by active surveillance and its relation to CTNNB1 mutational status. Methods: This is an Italian prospective, multicenter, observational study (NCT 02547831) to evaluate primary sporadic DT behavior in patients (pts) >16 years with primary naive or incompletely resected and measurable disease, at any site, with CTNNB1 mutational status available. Pts were assessed by contrast enhanced MRI or CT scan at baseline, at 3, 6, 9, 12 months, then every 6 months until the third year. Tumor changes were assessed by RECIST. In case of dimensional or symptomatic progression active treatment could be proposed on an individualized basis CTNNB1 mutational status was obtained in all patients by Sanger and deep sequencing was performed in wild-type cases. Primary end-point was progression-free survival (PFS) at 3 yrs. Treatment-free survival (TFS) was also analyzed. PFS and TFS were calculated using survival analysis methods, including Kaplan-Meier plots, log-rank test for survival curves comparison, and Cox proportional-hazard multivariable regression (age, size, anatomic site and CTNNB1 mutational status). Results: From April 2013 to February 2018 108 pts were included (82% female, 18% male); median age was 39 (interquartile range, IQR 34-48) and median size 50 mm (IQR, 40-80 mm). Tumor location was: 4/108 (4%) = head&neck, 25/108 (23%) = trunk, 59/108 (55%) = abdominal wall, 3/108 (3%) = intra-abdominal, 17/108 (16%) = extremities. CTNNB1 mutations were as follow: T41A 54/108 (50%), S45F 13/108 (12%), WT 20/108 (19%), other mutations 21/108 (19%). At a m-FU of 32.3 months, the 3-year PFS was 54.5% (95% CI, 44.9%-66.1%). 42/108 (39%) pts showed a RECIST progression, with equal distribution among the different anatomic sites. None of the variables analyzed were associated to PFS. Spontaneous regression was initially observed in 27/108 (25%) patients, while it followed dimensional progression in another 33/108 (30%). 35/108 (32%) pts received active treatment, 18/42 (43%) after RECIST progression and 17/66 (26%) after symptomatic progressions. TFS at 36 months was 65.9% (95% CI, 57.3%-75.9%). S45F mutation, larger tumor size and extremity location were associated to a shorter TFS. No dimensional or symptomatic progression were observed after 36 months of FU. Conclusions: Active surveillance was marked by spontaneous regressions in 60/108 (55%) pts. An active treatment was needed in 32%. If no events occur after 3 yrs of FU, more relaxed FU schedules can be considered given the low risk of subsequent progression. Attention should be paid to patients with DT located to the extremity and/or carrying a S45F mutation. Clinical trial information: NCT 02547831.