Key References

Kurtz JE et al., 2021. CRYODESMO-O1: A prospective, open phase II study of cryoablation in desmoid tumour patients progressing after medical treatment. European Journal of Cancer.◦ This multicenter French phase II trial (NCT02476305) of 50 patients with non-abdominopelvic desmoid tumors progressing after at least two lines of medical therapy met its primary endpoint with an 86% non-progression rate at 12 months and median PFS not reached at 31 months of follow-up. Cryoablation was safe (22% grade 3–4 events, no grade 5) and produced durable improvements in Brief Pain Inventory and EQ5D-3L scores, establishing the first prospective evidence for cryoablation as a tissue-sparing local therapy in progressive, heavily pretreated extra-abdominal disease.Gounder M et al., 2023. Nirogacestat, a γ-Secretase Inhibitor for Desmoid Tumors. New England Journal of Medicine.◦ The phase III DeFi trial (NCT03785964) randomized 142 adults with progressing desmoid tumors to oral nirogacestat 150 mg twice daily or placebo and demonstrated a 71% reduction in the risk of progression or death (HR 0.29; 95% CI 0.15–0.55; P<0.001), with objective response rates of 41% vs. 8% and significant improvements across all patient-reported outcomes. Despite frequent but mostly low-grade toxicities (diarrhea 84%, ovarian dysfunction in 75% of women of childbearing potential), this trial provided the first high-level randomized evidence supporting a targeted systemic therapy and led to the first FDA-approved treatment for desmoid tumors.Huang K et al., 2023. Efficacy and safety of different thermal ablative therapies for desmoid-type fibromatosis: a systematic review and meta-analysis. Quantitative Imaging in Medicine and Surgery.◦ This meta-analysis of 23 studies and 568 patients with 694 desmoid tumors treated by cryoablation, HIFU, or microwave ablation reported pooled rates of 90% symptom relief, 88% local control, 76% non-perfused volume, and only 3% major complications. Although HIFU showed numerically higher local control (99%) than cryoablation (80%) or microwave ablation (78%) (P=0.01), this difference likely reflects selection bias toward superficial tumors with adequate acoustic windows rather than intrinsic modality superiority, as HIFU cohorts systematically exclude deep, bone-adjacent, or gas-shielded lesions that are routinely treated with cryoablation. By quantitatively aggregating fragmented retrospective data across modalities and imaging guidance, this analysis supports the integration of image-guided thermal ablation into multidisciplinary management of progressive or symptomatic desmoid disease and helps reconcile divergent NCCN, ESMO, and Desmoid Tumor Working Group recommendations.