Survival and functional outcomes of molecularly defined childhood posterior fossa ependymoma: Cure at a cost
Survival and functional outcomes of molecularly defined childhood posterior fossa ependymoma: Cure at a cost
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DOI：
10.1002/cncr.31995
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发表时间：
2019-06-01
期刊：
影响因子：
6.2
通讯作者：
Ramaswamy, Vijay
中科院分区：
文献类型：
--
作者：
Zapotocky, Michal;Beera, Kiran;Ramaswamy, Vijay
背景 后颅窝室管膜瘤 (PFE) 包括 2 组：PF A 组 (PFA) 和 PF B 组 (PFB)，其结果存在明显差异。然而，据作者所知，PFA 室管膜瘤的长期结果尚未得到充分描述。本研究的目的是确定 30 年以上 PFE 患者连续亚组队列中生存率和神经认知结果的预测因子。方法 收集了 1985 年至 2014 年在加拿大安大略省多伦多病童医院诊断为 PFE 的连续患者的人口统计、生存和神经认知数据。使用全基因组甲基化芯片和/或组蛋白 H3 K27 三甲基化 (H3K27me3) 的免疫反应性分配亚组。结果 共发现 72 例 PFE 病例，其中 89% 为 PFA。 PFB 患者中没有发现疾病复发。所有 PFA 患者的 10 年无进展生存率都很低，为 37.1%（95% 置信区间，25.9%-53.1%）。对连续 10 年时期的分析显示，随着时间的推移，无进展生存期和/或总生存期显着改善。这与观察期内总（宏观）总切除率从 35% 增加到 77% 以及前期放疗的使用从 65% 增加到 96% 有关，并在多变量模型中得到证实。使用混合线性模型，对接受局灶放疗的 PFA 患者的纵向神经心理学结果进行分析，结果表明，即使在校正脑积水、手术次数和诊断时年龄的情况下，随着时间的推移，随着时间的推移，全量程智商也会显着持续下降（-1.33 +/- 0.42 点/年；P = .0042）。结论 来自大量 PFE 患者的分子信息数据清楚地表明，随着时间的推移，生存率有所提高，这与更积极的手术和前期放疗有关。然而，据作者所知，目前的研究是第一个在分组队列中证明这种方法会随着时间的推移导致神经认知结果减少的研究。
Background Posterior fossa ependymoma (PFE) comprises 2 groups, PF group A (PFA) and PF group B (PFB), with stark differences in outcome. However, to the authors' knowledge, the long-term outcomes of PFA ependymoma have not been described fully. The objective of the current study was to identify predictors of survival and neurocognitive outcome in a large consecutive cohort of subgrouped patients with PFE over 30 years. Methods Demographic, survival, and neurocognitive data were collected from consecutive patients diagnosed with PFE from 1985 through 2014 at the Hospital for Sick Children in Toronto, Ontario, Canada. Subgroup was assigned using genome-wide methylation array and/or immunoreactivity to histone H3 K27 trimethylation (H3K27me3). Results A total of 72 PFE cases were identified, 89% of which were PFA. There were no disease recurrences noted among patients with PFB. The 10-year progression-free survival rate for all patients with PFA was poor at 37.1% (95% confidence interval, 25.9%-53.1%). Analysis of consecutive 10-year epochs revealed significant improvements in progression-free survival and/or overall survival over time. This pertains to the increase in the rate of gross (macroscopic) total resection from 35% to 77% and the use of upfront radiotherapy increasing from 65% to 96% over the observed period and confirmed in a multivariable model. Using a mixed linear model, analysis of longitudinal neuropsychological outcomes restricted to patients with PFA who were treated with focal irradiation demonstrated significant continuous declines in the full-scale intelligence quotient over time with upfront conformal radiotherapy, even when correcting for hydrocephalus, number of surgeries, and age at diagnosis (-1.33 +/- 0.42 points/year; P = .0042). Conclusions Data from a molecularly informed large cohort of patients with PFE clearly indicate improved survival over time, related to more aggressive surgery and upfront radiotherapy. However, to the best of the authors' knowledge, the current study is the first, in a subgrouped cohort, to demonstrate that this approach results in reduced neurocognitive outcomes over time.