Raze Thomas, Lapouble Eve, Lacour Brigitte, Guissou Sandra, Defachelles Anne-Sophie, Gaspar Nathalie, Delattre Olivier, Pierron Gaelle, Desandes Emmanuel
Registre National des cancers de l'Enfant, Registre National des Tumeurs Solides de l'Enfant, CHRU Nancy, Vandœuvre-lès-Nancy, France.
Département de génétique, Unité de Génétique Somatique, Institut Curie, Paris, France.
Pediatr Blood Cancer. 2023 Apr;70(4):e30228. doi: 10.1002/pbc.30228. Epub 2023 Jan 31.
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.
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.
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.
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.
肺泡横纹肌肉瘤（ARMS）是一种侵袭性儿童癌症，伴有PAX3-FOXO1和PAX7-FOXO1融合的病例预后似乎较差。目的是评估PAX-FOXO1改变是否会影响儿童和青少年ARMS患者的临床结局。
2011年至2016年期间对年龄小于17岁、诊断为ARMS的患者进行了一项基于人群的研究。分析了取决于融合状态及临床因素的总生存期（OS）。
在2011-2016年期间法国国家儿童癌症登记处记录的111例ARMS患者中，61%表达PAX3-FOXO1，15%表达PAX7-FOXO1，13%为未明确PAX的FOXO1融合阳性，7%为PAX-FOXO1阴性（4例数据缺失）。与PAX7-FOXO1阳性ARMS患者相比，PAX3-FOXO1阳性肿瘤患者年龄显著更大（10-17岁：57.4%对29.4%），且更常发生转移性疾病（54.4%对23.5%）。观察到PAX3-FOXO1和未明确PAX的FOXO1阳性肿瘤患者的5年总生存期较差（分别为44.0%[32.0-55.4]和35.7%[13.1-59.4]）。在调整诊断分期后，PAX3-FOXO1阳性肿瘤患者死亡的可能性是PAX7-FOXO1阳性肿瘤患者的3.6倍。
在人群水平上，与PAX7-FOXO1阳性和PAX-FOXO1阴性肿瘤相比，PAX3-FOXO1与显著更高的死亡风险相关，并且可以解释在诊断为ARMS的青少年人群中观察到的较差的5年总生存期。源自临床参数与PAX3-FOXO1融合状态相结合的连续风险评分是一种改进当前ARMS风险适应性治疗的可靠方法。
