Surgical versus non-surgical approach in primary desmoid-type fibromatosis patients: A nationwide prospective cohort from the French Sarcoma Group

doi:10.1016/j.ejca.2017.06.017

European Journal of Cancer

Volume 83, September 2017, Pages 125-131

https://doi.org/10.1016/j.ejca.2017.06.017 Get rights and content

Highlights

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Primary location is a prognostic factor in desmoid tumour patients.
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Overall, the wait-and-see policy provides similar outcomes compared with surgery.
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Surgery is associated with poor outcome in ‘favourable’ locations.
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Both the wait-and-see policy and surgery similar outcomes in ‘unfavourable’ locations.

Abstract

Purpose

The outcome of desmoid-type fibromatosis (DTF) is unpredictable. Currently, a wait-and-see approach tends to replace large en bloc resection as the first therapeutic approach. Nevertheless, there are no validated factors to guide the treatment choice.

Method

We conducted a prospective study of 771 confirmed cases of DTF. We analysed event-free survival (EFS) based on the occurrence of relapse after surgery, progressive disease during the wait-and-see approach, or change in therapeutic strategy. Identification of prognostic factors was performed using classical methods (log-rank test and Cox model).

Results

Overall, the 2-year EFS was 56%; this value did not differ between patients undergoing an operation and those managed by the wait-and-see approach (53% versus 58%, p = 0.415). In univariate analysis, two prognostic factors significantly influenced the outcome: the nature of diagnostic sampling (p = 0.466) and primary location (p = 0.0001). The 2-year EFS was only 32% after open biopsy. The 2-year EFS was 66% for favourable locations (abdominal wall, intra-abdominal, breast, digestive viscera and lower limb) and 41% for unfavourable locations. Among patients with favourable locations, the 2-year EFS was similar in patients treated by both surgery (70%) and the wait-and-see approach (63%; p = 0.413). Among patients with unfavourable locations, the 2-year EFS was significantly enhanced in patients initially managed with the wait-and-see approach (52%) compared with those who underwent initial surgery (25%; p = 0.001).

Conclusion

The location of DTF is a major prognostic factor for EFS. If these findings are confirmed by independent analysis, personalised management of DTF must consider this easily obtained parameter.

Introduction

Desmoid-type fibromatosis (DTF), which is also known as aggressive fibromatosis, is a rare, locally invasive non-metastasizing but potentially multifocal mesenchymal stem cell progenitor proliferation [1]. DTF includes soft tissue masses arising at any part of the body in different varieties of conjunctive tissue, including muscle and fascia aponeurosis. The most common primary sites are the abdominal wall, limbs, girdles and mesenteric areas. DTF infiltrates surrounding structures and spreads along planes and muscle which could lead to severe pain, functional impairment and more rarely life-threatening conditions. It is typically diagnosed in young adults (peak of incidence at 35–40 years), mainly in women of reproductive age [2]. Today, the course of DTF is unpredictable given that spontaneous regression, long-lasting stable disease and disease progression could occur without reliable and validated predictive factors. At least two different clinicopathological entities are noted for DTF: sporadic DTF and DTF associated with germline APC mutations.

Large en bloc surgery is no longer regarded as the cornerstone treatment of DTF given that the rate of relapse after surgery exceeds 60% in larger series, and spontaneous regression is documented in approximately 25% of cases [3]. Therefore, there is a current shift to a more conservative approach, namely the ‘wait-and-see policy’ [4]. This approach is currently assessed by different prospective trials. It is already recommended by several authors and tends to serve as the standard of care at least in Europe [5]; this European consensus approach has currently been updated and will be published very soon. A randomised clinical trial comparing surgical versus non-surgical approaches is hardly feasible, and the best level evidence in this setting could be provided by large prospective cohorts.

In France, since 2009, two labelled networks oversee the diagnosis and management of sarcomas and desmoid tumours [2]. The pathologist network (RRePS, see website: https://rreps.sarcomabcb.org/home.htm) oversees the second pathological opinion of diagnosed or suspected cases regardless of the place where the diagnosis was performed (general hospital or private clinic). This network is also in charge of molecular diagnostic tests (e.g. exon 3 CTNNB1 mutation in cases of DTF). The clinical network NetSarc is a network of referral centres in charge of the clinical management of adult sarcoma DTF. The networks include 22 and 26 centres covering the French territory and sharing an online database. This online database is prospectively annotated and enables the description of diagnoses in real time. In parallel, the French patient advocacy group, SOS Desmoïde, has supported the implementation of both networks with yearly meetings with patients and caregivers and the updating of their website describing the role of both networks and providing the list of responsible dedicated multidisciplinary committees. In a previous study, we have described the activity of both networks regarding DTF management. In the present study, we analysed the prognostic factors and the outcome of prognostic factors regarding initial patient management (surgical versus non-surgical approach).

Section snippets

Patients

The database was previously described [2]. Briefly, RRePS (expert pathologist network) is responsible for the following parameters: (i) second opinion for every suspected or diagnosed case of sarcoma, GIST and DTF, and (ii) molecular analysis systematically performed for every tumour with a suspicion of recurrent genomic lesions, such as exon 3 CTNNB1 mutation in DTF. The second opinion and molecular biology confirmatory tests are not charged to the pathologist outside the network. The RRePS

Initial characteristics

Overall, 771 patients were eligible, including 552 women (72.6%) and 219 men (27.4%), with a median age of 39 years (range, 2–90). The number of cases per year was 67 (8.7%) in 2010, 96 (12.4%) in 2011, 142 (18.4%) in 2012, 135 (17.5%) in 2013, 129 (16.7%) in 2014, 140 (18.1%) in 2015 and 62 (8.0%) in 2016. The most common primary sites were abdominal wall (236 patients, 30.6%), chest wall (209 patients, 27.1%), intra-abdominal (138 patients, 17.9%), lower limb (90 patients, 11.6%), head and

Discussion

The present large prospective nationwide study of desmoid tumours confirmed by expert pathologists revealed the following points: (i) the wait-and-see approach is the first therapeutic strategy in approximately 50% of incident cases of DTF in France, (ii) overall 2-year EFS is approximately 56% and (iii) the outcome depends on one major prognosticator, namely primary locations of DTF. The nature of diagnostic sampling influenced EFS in univariate analysis, but this parameter was not retained by

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Conflict of interest statement

None declared.

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Original ResearchSurgical versus non-surgical approach in primary desmoid-type fibromatosis patients: A nationwide prospective cohort from the French Sarcoma Group

Highlights

Abstract

Purpose

Method

Results

Conclusion

Introduction

Section snippets

Patients

Initial characteristics

Discussion

Funding

Conflict of interest statement

Eur J Cancer

Eur J Surg Oncol

Eur J Cancer

Am J Surg

Aggressive fibromatosis (desmoid tumor) is derived from mesenchymal progenitor cells

Cancer Res

A prognostic nomogram for prediction of recurrence in desmoid fibromatosis

Ann Surg

Prognostic factors influencing progression-free survival determined from a series of sporadic desmoid tumors: a wait-and-see policy according to tumor presentation

J Clin Oncol

Original Research
Surgical versus non-surgical approach in primary desmoid-type fibromatosis patients: A nationwide prospective cohort from the French Sarcoma Group