"Wait & see" is currently the standard of care of recently diagnosed desmoid tumors (DT). In case of progression or symptomatic disease, medical therapy is nowadays widely used including chemotherapy.

Cryoablation has proven to be beneficial for the treatment of large, progressive and symptomatic DT.

This randomized phase II trial aims to compare cryoablation versus medical therapy in DT patients progressing after the "wait & see" period. Moreover, a cross-over design has been anticipated to allow all patients to undergo cryoablation if necessary.

Inclusion Criteria:

• Subject (male or female) with extra-peritoneal desmoid tumor (confirmed by prior biopsy by an experienced pathologist within the RRePS network)
• 13 years of age or older
• Measurable viable tumor (according to the mRECIST criteria using MRI. The baseline MRI imaging is mandatory in the 2 months prior to treatment initiation (D0).
• Progressive disease (according to the mRECIST criteria) after the watchful waiting period or significant increase in symptoms requiring an active therapy, as advised in a multidisciplinary sarcoma tumor board
• Tumor deemed accessible for cryoablation procedure by the operator in a type I center. (In pediatric cases, a careful site tumor analysis will be performed with interventional radiologist to ensure for limited consequence of cryoablation in pediatric patients especially regarding growth plates).
• 100 % of destruction of the tumor achievable in one procedure of cryoablation with 1cm security margin according to assessment by referral center (type 1) for cryoablation
• ECOG performance status 0-2 at inclusion visit
• Biological and hematological parameters (neutrophils ≥ 1,5.109/L ; platelet count ≥ 100.109/L ; no significant hemostatic abnormalities) in the 4 weeks prior to treatment initiation (D0)
• Subject able to understand the objectives and risks of the research and to give dated and signed informed consent. For minors, the consent of the 2 parents must be obtained.
• Subject affiliated to a social health insurance plan
• For a woman of childbearing age: negative blood pregnancy test at screening/inclusion visit
• Subject agreeing to use a contraceptive method

Exclusion criteria:

• Intra-peritoneal or multifocal desmoid tumor
• Concurrent or prior use of any antitumor agent for the current desmoid tumor
• Relapse after surgery for desmoid tumor
• Any contraindication including known hypersensitivity to vinorelbine or other vinca-alkaloids, or other constituents to navelbine, to vinblastine, to methotrexate or any excipients, such as, but not limited to current or recent (within 2 weeks) severe infection, severe renal failure, severe hepatic injury, chronic respiratory failure
• Any contraindication including hypersensitivity to gadoteric acid, meglumine or any drug containing gadolinium
• Concomitant treatment with: yellow fever vaccine, prophylactic treatment with phenytoin, trimethoprim, ciprofloxacin, penicillins, probenecid, acetylsalicylic acid, NSAIDs, PPIs, acitretin, azote protoxide, St John's wort
• Any contra-indication for the procedure as stated by the interventional radiologist in terms of tumor size, proximity to neural/vascular structures or adjacent organs at risk making the procedure at unacceptable risk
• Impaired hemostasis, that may interfere with the conduct of the cryoablation
• Contraindication to any form of sedation
• Others contra-indications to MRI
• Pregnancy or breastfeeding
• Concurrent participation in other experimental studies that could affect endpoints of the present study
• Impossibility to give the subject informed information (subject in an emergency situation, patient with comprehension difficulties ...)
• Psychiatric disorders
• Incompetent subject (subject to a legal protection measure: curatorship, guardianship, future protection mandate, family habilitation)