Efficacy and molecular predictors of radiotherapy combined with bevacizumab on desmoid tumor (aggressive fibromatosis).

Abstract

e23535 Background: Desmoid tumors are rare, highly recurrent soft-tissue tumors with limited responses to non-surgical therapies. Radiotherapy combined with bevacizumab, a VEGF inhibitor, has shown potential synergy in improving tumor response. This study evaluated the efficacy and safety of radiotherapy combined with bevacizumab and explored potential molecular predictors of response. Methods: From a cohort of 160 patients with desmoid tumors treated at Sichuan Cancer Hospital between June 2013 and September 2023, eight patients who underwent radiotherapy combined with bevacizumab were retrospectively analyzed. Clinical outcomes, including tumor response according to RECIST 1.1 and time to treatment failure (TTF), were assessed alongside health-related quality of life (QoL) using the EORTC QLQ-C30 questionnaire. Tumor specimens were analyzed for β-catenin and VEGF expression, microvessel density (MVD) via immunohistochemistry, and genetic mutations, including CTNNB1, using next-generation sequencing (NGS). Results: The study included eight patients (ages 18–69, median 30) with equal male-to-female distribution and tumors located in the chest wall, head and neck, or intrathoracic regions. Patients received radiotherapy (median dose: 51 Gy, range: 45–65.5 Gy) with concurrent or sequential bevacizumab (2–5 cycles, 200–345 mg per cycle). All exhibited nuclear β-catenin positivity, with seven harboring CTNNB1 mutations. VEGF expression was present in five patients, and MVD ranged from 7 to 29 (median: 15). Clinical responses included complete response (CR) in three patients (37.5%) and partial response (PR) in four (50%), and all patients remained progression-free with a mean TTF of 53.25 months (range: 10–134 months). Favorable QoL scores (mean: 90.6 ± 12.1) were observed. No correlation was observed between clinical response and CTNNB1 mutations, VEGF expression, or MVD. However, ATR gene alterations, involved in DNA repair, were exclusively identified in patients with CR. Functional enrichment analysis indicated that mutations were predominantly associated with pathways regulating DNA repair, angiogenesis, and endothelial cell differentiation. Conclusions: Radiotherapy combined with bevacizumab demonstrated significant efficacy and safety in desmoid tumors, with sustained tumor control and good QoL. ATR gene alterations may serve as potential predictors of response, warranting further prospective studies to elucidate their role.