No abstract

Background Alveolar rhabdomyosarcoma (ARMS) is an aggressive pediatric cancer and cases with fusion PAX3–FOXO1 and PAX7–FOXO1 seem to have a poor prognosis. The aim is to evaluate whether PAX–FOXO1 alterations influence clinical outcome in childhood and adolescence population with ARMS. Procedure A population‐based study was conducted between 2011 and 2016 in patients less than 17 years with a diagnosis of ARMS. Overall survival (OS) depending on fusion status with clinical factors was analyzed. Results Out of 111 ARMS patients recorded in the French National Childhood Cancer Registry during the 2011–2016 period, 61% expressed PAX3–FOXO1, 15% expressed PAX7–FOXO1, 13% were FOXO1 fusion‐positive without PAX specification, and 7% were PAX–FOXO1 negative (n = 4 missing data). Compared to patients with PAX7–FOXO1 positive ARMS, those with PAX3–FOXO1 positive tumor were significantly older (10–17 years: 57.4% vs. 29.4%), and had more often a metastatic disease (54.4% vs. 23.5%). Poorer 5‐year OS for patients with PAX3–FOXO1 and PAX not specified FOXO1‐positive tumor were observed (44.0% [32.0–55.4] and 35.7% [13.1–59.4], respectively). After adjustment for stage at diagnosis, patients with positive tumor for PAX3–FOXO1 were 3.6‐fold more likely to die than those with positive tumor for PAX7–FOXO1. Conclusion At the population level, PAX3–FOXO1 was associated with a significant higher risk of death compared to PAX7–FOXO1‐positive and PAX–FOXO1‐negative tumors, and could explain poorer 5‐year OS observed in adolescence population diagnosed with ARMS. A continuous risk score derived from the combination of clinical parameters with PAX3–FOXO1 fusion status represents a robust approach to improving current risk‐adapted therapy for ARMS.