Desmoid-Type Fibromatosis Tumors in Children After First-Line Failure: Clinical Aspects and Approaches for Subsequent Therapeutic Lines.

Background: Desmoid-type fibromatosis (DTF) is a rare intermediate malignancy with high local aggressiveness and recurrence in children after first-line methotrexate-vinblastine (Mtx-Vbl) regimen. The objective is to describe refractory DTF to standardize second-line therapy.

Methods: This national multicenter retrospective study included patients (<25 years) with progressive/refractory DTF after Mtx-Vbl first-line. The primary objective was to evaluate response rate (RR: complete/partial response [CR/PR]) and progression-free survival (PFS) following second-line treatments. Secondary objectives included overall burden of therapy and predictive factors for therapeutic efficacy analysis.

Results: From 2000 to 2022, 50 patients fulfilled inclusion criteria. Median age at first relapse was 15.6 years [range: 0.9-24.8]. Second-line treatments included exclusive medical treatment for 86%-majority alkaloid-based re-challenge (60%)-exclusive local therapy in 8%, both (4%) and observation (2%). RR to any medical therapy was 30% [95% CI: 16-44], specifically 35% [95% CI: 15-55] for alkaloid-based regimens with clinical benefit (CR/PR or stabilization) in 85%. The 5-year PFS was 44% [95% CI: 30-58]. Limb location was the only significant predictive factor for PFS (p < 0.01). Overall treatment load comprised a median of three lines [range: 2-8] over 27 months median duration [range: 4-90]. Local therapy was done for 50% of patients. One patient died from secondary digestive infection.

Conclusions: Refractory DTF should be considered as a chronic disease with significant treatment burden where objectives should be regularly reassessed. Even for refractory disease, local therapy might be avoided in half of cases. Authors propose a second-line treatment algorithm for pediatric refractory DTF.