PAX-FOXO1 fusion status drives unfavorable outcome for children with rhabdomyosarcoma: A children's oncology group report
PAX-FOXO1 fusion status drives unfavorable outcome for children with rhabdomyosarcoma: A children's oncology group report
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DOI：
10.1002/pbc.24532
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发表时间：
2013-09-01
影响因子：
3.2
通讯作者：
Hawkins, Douglas S.
中科院分区：
文献类型：
--
作者：
Skapek, Stephen X.;Anderson, James;Hawkins, Douglas S.
背景资料。横纹肌肉瘤(RMS)分为肺泡型(ARMS)和胚胎型(ERMS)，大多数ARMS表达PAX3或PAX7与FOXO1融合的两种致癌基因之一(分别为P3F和P7F)。儿童肿瘤学小组(COG)进行了一项多机构临床试验，以评估PAX-FOXO1融合状态的预后价值。方法：研究方法。研究参与者接受COG方案D9803的中等风险武器或ERMS的治疗，使用多药化疗、放射治疗和手术。对预期收集的标本进行中央诊断、病理回顾和融合基因的分子检测。5年无事件(EFS)和总生存期(OS)与组织学亚型和PAX-FOXO1状态相关。结果。在616名符合条件的D9803入选者中，434例有足够的临床、分子和病理数据，可以明确分类为ERMS、ARMS P3F+或P7F+或ARMSn(未检测到融合)。P3F+和P7F+患者的EFS(54%)比ERMS患者(77%；P<；0.001)差。ARMSn和ERMS的EFS差异无统计学意义(90%vs.77%，P=0.15)。ARM P3F+患者的OS(%)低于ARM P7F+患者(87%)、ARMSn患者(89%)和ERMS患者(82%；P=0.006)。结论。ARMSn的结果类似于ERMS，与P3F或P7F的ARM相比，ARMSn的结果优于P3F或P7F，而ARMSn是为中等风险RMS儿童设计的。这项前瞻性分析支持将PAX-FOXO1融合状态纳入风险分层和治疗分配。儿科血癌2013；60：1411-1417。(C)2013年威利期刊公司。
Background. Rhabdomyosarcoma (RMS) is divided into two major histological subtypes: alveolar (ARMS) and embryonal (ERMS), with most ARMS expressing one of two oncogenic genes fusing PAX3 or PAX7 with FOXO1 (P3F and P7F, respectively). The Children's Oncology Group (COG) carried out a multi-institutional clinical trial to evaluate the prognostic value of PAX-FOXO1 fusion status. Methods. Study participants were treated on COG protocol D9803 for intermediate risk ARMS or ERMS using multi-agent chemotherapy, radiotherapy, and surgery. Central diagnostic pathology review and molecular testing for fusion genes were carried out on prospectively collected specimens. Event-free (EFS) and overall survival (OS) at 5 years were correlated with histological subtype and PAX-FOXO1 status. Results. Of 616 eligible D9803 enrollees, 434 cases had adequate clinical, molecular, and pathology data for definitive classification as ERMS, ARMS P3F+ or P7F+, or ARMSn (without detectable fusion). EFS was worse for those with ARMS P3F+ (54%) and P7F+ (65%) than those with ERMS (77%; P < 0.001). EFS for ARMSn and ERMS were not statistically different (90% vs. 77%, P = 0.15). ARMS P3F+ had poorer OS (64%) than ARMS P7F+(87%), ARMSn (89%), and ERMS (82%; P=0.006). Conclusions. ARMSn has an outcome similar to ERMS and superior EFS compared to ARMS with either P3F or P7F, when given therapy designed for children with intermediate risk RMS. This prospective analysis supports incorporation of PAX-FOXO1 fusion status into risk stratification and treatment allocation. Pediatr Blood Cancer 2013;60:1411-1417. (C) 2013 Wiley Periodicals, Inc.