A Prospective Observational Study of Active Surveillance in Primary Desmoid Fibromatosis

Abstract

Purpose: To prospectively assess the behaviour of primary sporadic (not FAP associated) desmoid fibromatosis (DF) managed by active surveillance (AS). Experimental design: This is an Italian prospective, multicenter, observational study (NCT 02547831) including patients {greater than or equal to}16 years with primary sporadic DF at any site. Patients were assessed by Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1 . Primary end-point was progression-free survival (PFS) at 3 years. Treatment-free survival (TFS) was also analyzed. PFS and TFS were calculated by Kaplan-Meier plots and compared by log-rank test Cox proportional-hazard multivariable regression analyses were performed. Results: From 2013 to 2018 108 consecutive patients were included (82% female); median age was 39-yr; median size was 51 mm. CTNNB1 mutations were: T41A (50%); S45F (12%); other (19%); WT (19%). At 32.3-month median-FU, 42/108 (39%) showed RECIST progression. Spontaneous regression (SR) was initially observed in 27/108 (25%), while it followed dimensional progression in other 33/108 (31%). PFS at 36 months was 54.5% (95% CI, 44.9%-66.1%). Thirty-five/108 (32%) patients received active treatments, 18/108 (17%) after RECIST progression and 17/108 (15%) after symptomatic progression. TFS at 36 months was 65.9% (95% CI, 57.3%-75.9%). Larger tumor size and extremity location were associated to shorter TFS and a trend for S45F mutation was also observed (p=0.06), while none of the above variables was significantly associated to PFS. Conclusions: In primary DF, AS can be proposed, since disease stabilization and SR frequently occur. However extra care should be taken for patients with tumors of larger size, extremity location and S45F mutation.

Clinical results of active surveillance for extra‐abdominal desmoid‐type fibromatosis

“…The present study revealed the CTNNB1 S45F mutation as a significant poor prognostic factor for EFS using multivariate analysis. Colombo et al also reported that DF with the S45F mutation tended to have shorter treatment‐free survival ( p = 0.06) 31 . The CTNNB1 S45F mutation has been previously reported as a risk factor for recurrence after surgical treatment 5,32–34 and associated with tumor progression in patients with oral COX‐2 inhibitor treatment 17 .…”

“…Colombo et al also reported that DF with the S45F mutation tended to have shorter treatmentfree survival (p = 0.06). 31 The CTNNB1 S45F mutation has been previously reported as a risk factor for recurrence after surgical treatment 5,[32][33][34] and associated with tumor progression in patients with oral COX-2 inhibitor treatment. 17 Contrarily, drug treatment with considerable side effects, including anticancer drugs and molecular targeted drugs, has been reported to control DF with any type of CTNNB1 mutation.…”

Multimodality Imaging Assessment of Desmoid Tumors: The Great Mime in the Era of Multidisciplinary Teams

“…Most of these cancers arise as sporadic variants. Sporadic tumors are more frequently extra-abdominal [ 2 , 34 , 35 , 36 , 37 ]. Several studies show that the inherited variant can be seen in 5–16% of patients with familial adenomatosis polyposis (FAP) [ 1 , 2 , 3 ].…”

Unraveling Desmoid-Type Fibromatosis-Specific Health-Related Quality of Life: Who Is at Risk for Poor Outcomes

“…The most recent global consensus guideline recommends active surveillance (AS) as a frontline approach for asymptomatic and mildly symptomatic patients, independent of the tumour’s location or size [ 8 ]. After initial AS, the majority of DTF patients do not need active treatment, minimising overtreatment and potential treatment-related morbidity [ 7 , 9 ]. In the case of radiological or clinically significant progression or increasing symptoms, active treatment, including systemic therapies, surgical resection and local therapies, such as radiotherapy, can be considered [ 8 ].…”