AF is a rare non-metastasizing connective tissue tumor (< 300 cases/year in France), associated with high risk of local relapse, functional impairment and pain. AF is most frequently (about 85%) sporadic and then associated with a somatic mutation of the CTNNB1 gene. In about 15% of cases, AF is associated with heredity condition, as complication of familial adenomatous polyposis FAP (with germinal mutation of APC gene). The natural course of AF is unpredictable. As the consequence the decision making for starting curative intent treatment is difficult. Therapeutic options are: wait-and-see policy, surgery (sometimes mutilating), radiotherapy or systemic treatment (non-steroidal anti-inflammatory drugs, hormonal therapy, chemotherapy, sorafenib). Regarding these uncertainties, physicians can hardly answer to patient questions.
ALTITUDES is a national multicenter cohort of 600 patients who will be included in 39 centers (NCT02867033). The primary outcome is number of cases diagnosed in reference centers. Secondary outcomes are rate of cases related to FAP, rate of cases associated with CTNNB1 mutations, description of natural history, description of management, impact in terms of Anxiety and Depression, in QoL. Main eligibility criteria are a diagnosis later than 01/01/2016, with central pathological review. A translational part is attached to this cohort. On the one hand, the purpose is detection of FA specific CTNNB1 mutations using a targeted strategy Digital-droplet PCR (ddPCR) on cell-free DNA (cfDNA) extracted from blood samples and to correlate total plasmatic cfDNA concentration with natural history. On the other hand, We hypothesize that APC and CTNNB1 mutations are mutually exclusive and that patients with a CTNNB1 mutation do not have an increased risk of developing polyposis and/or colon cancer and therefore should not benefit from screening colonoscopy. In this study, colonoscopy is mandatory and a search for somatic mutations of CTNNB1 and APC. Since opening of enrolment (03/2016), 360 patients were included. Along these patients, 316 were included in the translational part. End of recruitment is planned 03/2022.
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All authors have declared no conflicts of interest.