New treatments for desmoid tumors.

PURPOSE OF REVIEW: Desmoid tumor is a rare disease of intermediate malignancy characterized by a locally aggressive monoclonal, fibroblastic proliferation and accompanied by a variable and often unpredictable clinical course. The purpose of this review is to give an overview on the emerging new systemic treatment options for this intriguing disease for which no established or approved drugs are available yet. RECENT FINDINGS: Over decades, surgical resection has been the established initial treatment approach; however, more recently, a paradigm shift has been introduced towards a more conservative treatment strategy. Almost 10 years ago, The Desmoid Tumor Working Group has initiated a consensus process initially in Europe and then globally with the intention to harmonize the therapeutic strategy amongst clinicians and set up management recommendations for desmoid tumor patients. SUMMARY: This review will summarize and focus on the latest emerging impressive data on the use of gamma secretase inhibitors in this disease paving a possible future perspective in the treatment armamentarium for desmoid tumor patients.

BACKGROUND: Fibroblastic soft-tissue tumors share enzymatic anomalies that result in excessive intracellular conversion of 5-aminolevulinic acid (5-ALA) to protoporphyrin IX, a photosensitizer which induces cellular apoptosis upon exposure to visible red light at a wavelength of 635 nm. We hypothesized that red light illumination of the surgical bed remaining after resection of fibroblastic tumors will result in destruction of microscopic tumor residua and may decrease the likelihood of local tumor recurrence. METHODS: Twenty-four patients with desmoid tumors, solitary fibrous tumors (SFT), and dermatofibrosarcoma protuberans (DFSP) received oral 5-ALA prior to resection of their tumors. Following tumor resection, the exposed surgical bed was illuminated with red light at a wave length of 635 nm at a dose of 150 J/cm(2) for 33 min. RESULTS: Treatment with 5-ALA was associated with minor side effects that included nausea and transient elevation of transaminases. Local tumor recurrence was detected in 1 of the 10 patients with desmoid tumors who had not undergone any previous surgery, none in the 6 patients who had SFT and 1 of the 5 patients who had DFSP. CONCLUSIONS: 5-ALA photodynamic therapy of fibroblastic soft-tissue tumors may result in decreased likelihood of local tumor recurrence. It is associated with minimal side effects and should be considered as adjuvant to tumor resection in these cases.

OBJECTIVE: In this study, we aimed to describe the clinical features, management, and outcomes of desmoid tumors (DTs) in familial adenomatous polyposis (FAP) patients at a high-volume sarcoma center. METHODS: Consecutive patients with FAP and DTs were identified from our institutional databases (1985-2021). Patient demographics, treatment, and outcomes were described. Categorical data were compared using Fisher’s exact test, and Kaplan-Meier curves were used to estimate progression-free survival (PFS). RESULTS: Forty-five patients with 67 DTs were identified: 39 mesenteric or retroperitoneal (58.2%), 17 abdominal wall (25.4%), 4 extremity (6%), 4 breast (6%) and 3 back (4.4%). Severe DT symptoms were present in 12 patients (26.7%). Initial treatments per tumor were observation in 30 (44.8%) DTs, chemotherapy in 15 (22.4%) DTs, surgery in 10 (14.9%) DTs, and other systemic therapies in 10 (14.9%) DTs. The majority of DTs remained stable with observation or a single intervention (77.8%). Median PFS was 23.4 years (95% confidence interval 7.6-39.2). In the 12 severely symptomatic patients, four patients required more than two interventions for DT control. At a median follow-up of 6.0 years (range 0.7-35.8 years), 33 (73.3%) patients were alive with disease, 7 (15.6%) were alive without disease, and 5 (11.1%) died of other causes. No patients died of DT-related complications. CONCLUSIONS: The majority of DTs in FAP patients remained stable with observation or a single intervention. There were no DT-related deaths; however, 12 of 45 patients (26.7%) experienced significant tumor morbidity and required more interventions for disease control. Further studies on quality of life are required.

Mesenteric fibromatosis is a rare tumor that grows slowly and asymptomatically and is more frequent among men. The risk factors described in the literature may not be present in all cases. The clinical presentation is variable and depends on the localization of the tumor and the involvement of surrounding structures. Imaging studies such as abdominal computed tomography and magnetic resonance imaging are the preferred methods for the diagnosis of this tumor. However, a definitive diagnosis is made based on histopathology and immunohistochemistry results. Surgical resection remains the preferred option for the treatment of mesenteric fibromatosis. This report presents a clinical case of mesenteric fibromatosis in a male patient who presented with partial abdominal obstruction and the absence of risk factors for mesenteric fibromatosis.

PURPOSE: This study aimed to determine the risk factors for local of adult patients treated for desmoid tumors by cryoablation. MATERIAL AND METHODS: Eighty-four patients treated for non-abdominopelvic desmoid tumors by cryoablation from July 2012 to July 2020 were included in a retrospective study. The population was composed of 64 women (76.19%) and 20 men (23.81%), aged from 16 to 75 years (median = 35 ± 14.25 years). Each patient had a pre procedural gadolinium enhanced MRI and was followed up to 36 months with the same technic. Clinical features, such as tumor size and previous treatment, epidemiological features, and the technical parameters of cryoablation were studied. RESULTS: Local relapse was found for 19/84 patients (22.62%). The 12-, 24-, and 36-month progression free survival (PFS) was 89% (95%CI [79 to 94]), 74% (95%CI [60 to 83]), and 68% (95%CI [53 to 79]), respectively.In univariate analysis, significant prognostic factors associated with local recurrence were: non-abdominal wall location (p = 0.042), a debulking strategy (p = 0.0105), a risk of visceral injury (p = 0.034) or peripheral nerve injury during cryoablation (p = 0.033), previous radiation therapy (p = 0.043) and treatment before 2016 (p = 0.008).At multivariate analysis, abdominal wall tumors displayed the best outcome, whereas the neck and trunk showed a high rate of recurrence (HR 7.307 [1.396-38.261]). CONCLUSION: The local recurrence of desmoid tumors after cryoablation depends on a number of prognostic factors, in particular, a non-abdominal wall location of the tumor and previous local treatment such as surgery or radiation therapy.