Therapeutic Impact of Cytoreductive Surgery and Irradiation of Posterior Fossa Ependymoma in the Molecular Era: A Retrospective Multicohort Analysis
Therapeutic Impact of Cytoreductive Surgery and Irradiation of Posterior Fossa Ependymoma in the Molecular Era: A Retrospective Multicohort Analysis
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DOI：
10.1200/jco.2015.65.7825
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发表时间：
2016-07-20
影响因子：
45.3
通讯作者：
Taylor, Michael D.
中科院分区：
文献类型：
--
作者：
Ramaswamy, Vijay;Hielscher, Thomas;Taylor, Michael D.
目的后颅窝室管膜瘤由两种不同的分子变异体EPN_PFA和EPN_PFB组成，具有不同的生物学和自然历史。在考虑了分子亚型后，细胞减灭术和放射治疗对后颅窝室管膜瘤的治疗价值尚不清楚。方法采用全基因组甲基化阵列对4个独立的、不重叠的后颅窝室管膜瘤回顾队列(n=820)进行分析。风险分层模型的设计基于已知的临床和新描述的分子生物标记物，通过多变量COX比例风险分析确定。结果即使考虑年龄或治疗方案，分子亚组仍是一个强大的独立预后预测因子。未完全切除的EPN_PFA室管膜瘤预后很差，在所有四个队列中，5年无进展生存率从26.1%到56.8%不等。虽然一线(辅助)放疗明显有利于完全切除的EPN_PFA，但相当大比例的EPN_PFB患者可以通过单独手术治愈，而复发的EPN_PFB患者通常可以通过延迟外照射获得成功。结论后颅窝室管膜瘤最有效的生物标志物是分子亚群，与其他人口统计学或治疗变量无关。然而，EPN_PFA和EPN_PFB仍然受益于切除范围的扩大，尤其是次全切除的EPN_PFA，即使辅以放射治疗，生存率也特别低。接受大体全切除的EPN_PFB患者的复发风险较低，应该考虑纳入一项随机临床试验，单独观察，并为复发患者保留放射治疗。
PurposePosterior fossa ependymoma comprises two distinct molecular variants termed EPN_PFA and EPN_PFB that have a distinct biology and natural history. The therapeutic value of cytoreductive surgery and radiation therapy for posterior fossa ependymoma after accounting for molecular subgroup is not known.MethodsFour independent nonoverlapping retrospective cohorts of posterior fossa ependymomas (n = 820) were profiled using genome-wide methylation arrays. Risk stratification models were designed based on known clinical and newly described molecular biomarkers identified by multivariable Cox proportional hazards analyses.ResultsMolecular subgroup is a powerful independent predictor of outcome even when accounting for age or treatment regimen. Incompletely resected EPN_PFA ependymomas have a dismal prognosis, with a 5-year progression-free survival ranging from 26.1% to 56.8% across all four cohorts. Although first-line (adjuvant) radiation is clearly beneficial for completely resected EPN_PFA, a substantial proportion of patients with EPN_PFB can be cured with surgery alone, and patients with relapsed EPN_PFB can often be treated successfully with delayed external-beam irradiation.ConclusionThe most impactful biomarker for posterior fossa ependymoma is molecular subgroup affiliation, independent of other demographic or treatment variables. However, both EPN_PFA and EPN_PFB still benefit from increased extent of resection, with the survival rates being particularly poor for subtotally resected EPN_PFA, even with adjuvant radiation therapy. Patients with EPN_PFB who undergo gross total resection are at lower risk for relapse and should be considered for inclusion in a randomized clinical trial of observation alone with radiation reserved for those who experience recurrence.