[Systemic treatment for management of aggressive fibromatosis in both adult and children: Level of evidence and unsolved questions] [Article in French]

We summarize here available data about systemic treatments of desmoids tumors, as well in adult patients as pediatric patients. Until 2018, the level of evidence associated with these treatments (NSAI, hormonal therapies, tyrosine kinase inhibitors, chemotherapy) was very low, based on retrospective studies or non-randomized phase 2 trials with limited number of cases. In 2018-2019, 2 large randomized trials have been published, including one large superiority phase 3 trial comparing sorafenib to placebo. This trial clearly demonstrates the clinical benefit of sorafenib over placebo (level of evidence IA). To conclude, wait-and-see policy must be the first-line approach, systemic treatment is indicated in case of disease progression. Randomized trials are feasible in this exceptional disease.

After an adapted imaging, the diagnosis of a desmoid tumor (DT) is provided by a percutaneous microbiopsy, with a molecular analysis for beta-catenin or APC gene mutation. The therapeutic strategy must be decided in a specialized multidisciplinary tumor board (MTB). Surgery is no longer the first-line treatment for a DT. Except within a surgical complication, active surveillance is offered to the majority of patients, since more than half stabilize or regress after an initial progression, whether the location is peripheral or intra-abdominal. If the localization and/or volume are likely to be functional or life-threatening, medical induction therapy is discussed in MTB, before a local treatment whose potential sequelae would be definitive. Incomplete unplanned resection, recurrence, pregnancy or desmoids occurring in a polyposis context are no longer routine surgical indications. In an emergency setting (occlusion, peritonitis), it is discussed to treat only the mechanical complication and leave the DT in place, if its resection would lead to too much digestive resection, especially in patients who have already undergone colectomy for polyposis. The best indications for surgery are patients who have parietal locations with significant and documented progression, because surgery can be easily completed at the cost of an acceptable morbidity. In localizations where surgery would cause sequelae, medical treatment or other regional loco treatments are discussed in MTB.

The aim of the present study was to investigate the clinicopathological and molecular characteristics of abdominal DT in a Chinese population and to provide clues for selecting the optimal treatment strategy for different types of abdominal desmoid tumors (DT). The clinicopathological data of 15 consecutive patients with DT was collected. A review of the patient clinicopathological characteristics revealed that FAP-associated DT exhibited a higher rate of abdominal surgery history (P=0.011), with no significant differences in any other characteristics. Sequencing revealed that mutations in the APC, CTNNB1 and MUTYH genes were common in DT, and only one patient harbored no mutations in these genes. Survival analyses revealed that patients with FAP exhibited shorter time to progress TTP (P=0.030). Log-rank test demonstrated a tendency towards shorter TTP in the cases where an R2 resection was performed (P=0.072) and a tendency towards poor prognosis in the cases of DT associated with FAP (P=0.087). In conclusion, Abdominal DTs were prone to occur in patients with FAP with a history of abdominal surgery. Mutations in the APC, CTNNB1 and MUTYH genes were detected in patients with DTs. To the best of our knowledge, this is the first study of abdominal DT occurrence in patients with MUTYH-associated FAP. The prognosis of DT associated with FAP may be worse compared with that of sporadic DT.

To explore the role of open and laparoscopic surgery in the process of desmoidogenesis we crossed Apcmin/ +C57Bl/6 mice with p53 +/- mice to generate animals that developed desmoid tumors with 100% penetrance. One hour of active airflow generates substantial damage to peritoneal mesothelial cells and their microvilli as measured at 24?h post intervention, which is significantly greater than that generated by passive airflow. Use of humidified-warm CO2 mostly protects the mesothelium that had not experienced additional mechanical (surgical) damage at 24?h. Maximal damage was evident in all treatment groups regardless of flow or use of gas. At day 10 mechanically-damaged peritoneum remains in mice but is essentially repaired in the gas-treated groups. Regarding desmoidogenesis, operating procedures did not increase the frequency of desmoid tumors but their frequency correlated with time following surgery but not age of mice. Active airflow generates more peritoneal damage than passive airflow and is reduced significantly by the use of humidified-warm CO2. Introduced peritoneal damage is largely repaired in mice by day 10 with gas. Desmoid tumor incidence is not increased substantially by surgery itself but rises over time following surgery compared to non-surgery mice.

Magnetic resonance-guided focused ultrasound (MRgFUS) utilizes high-intensity focused ultrasound to noninvasively, thermally ablate lesions within the body while sparing the intervening tissues. Magnetic resonance imaging provides treatment planning and guidance, and real-time magnetic resonance thermometry provides continuous monitoring during therapy. MRgFUS is ideally suited for the treatment of extra-abdominal desmoid fibromatosis due to its noninvasiveness, lack of ionizing radiation, low morbidity, and good safety profile. Conventional treatments for these benign tumors, including surgery, radiation, and chemotherapy, can carry significant morbidity. MRgFUS provides a safe and effective alternative treatment in this often-young and otherwise healthy patient population. While there is considerable experience with MRgFUS for treatment of uterine fibroids, painful bone lesions, and essential tremor, there are few reports in the literature of its use for treatment of benign or malignant soft tissue tumors. This article reviews the principles and biologic effects of high-intensity focused ultrasound, provides an overview of the MRgFUS treatment system and use of magnetic resonance thermometry, discusses the use of MRgFUS for the treatment of extra-abdominal desmoid tumors, and provides several case examples.