Developing an advanced risk stratification model for pediatric intracranial ependymoma based on the prospective trial E-HIT2000 and subsequent registries.

IF 13.4 1区医学 Q1 CLINICAL NEUROLOGY

Neuro-oncology Pub Date : 2025-09-30 DOI:10.1093/neuonc/noaf218

Katja von Hoff, Denise Obrecht-Sturm, David R Ghasemi, Janna Wenning, Martin Mynarek, Nicolas U Gerber, Martin Benesch, Björn O Juhnke, Brigitte Bison, Monika Warmuth-Metz, Beate Timmermann, Andreas Faldum, Stephan Tippelt, Gudrun Fleischhack, Michael Grotzer, Pablo Hernáiz Driever, Andreas Beilken, Martin Ebinger, Norbert Graf, Michael C Frühwald, Irene Schmid, Irene Slavc, Arend Koch, Markus Bergmann, Christian Hagel, Roland Coras, Ingmar Blümcke, Guido Reifenberger, Jörg Felsberg, Kathy Keyvani, Patrick N Harter, Marco Prinz, Ori Staszewski, Till Acker, Christine Stadelmann-Nessler, Christian Hartmann, Andreas von Deimling, Clemens Sommer, Martin Hasselblatt, Markus J Riemenschneider, Camelia-Maria Monoranu, Elisabeth Rushing, Christine Haberler, Marcel Kool, Martin Sill, Stefan M Pfister, Ulrich Schüller, Torsten Pietsch, Rolf D Kortmann, Robert Kwiecien, Hendrik Witt, Kristian W Pajtler, Stefan Rutkowski

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引用次数: 0

Abstract

Background: Current treatment strategies for pediatric intracranial ependymoma do not consider molecular heterogeneity. Here, we evaluated molecular group-specific determinants of outcome and developed an improved risk stratification model.

Methods: Patients aged 0-21 years with localized intracranial ependymoma were enrolled into the prospective clinical trial E-HIT2000. Treatment included maximum safe surgery, local radiotherapy, and chemotherapy, stratified according to age, histology and, following a major amendment, residual tumor. Clinical data were analyzed in a pooled molecularly annotated cohort with data from patients treated analogously within subsequent registries.

Results: For 291 trial patients, the 5-year PFS and OS were 62±3% and 81±2%, respectively. For the molecularly annotated pooled cohort (n = 228), 5-year PFS/OS were: EPN-PFA (n = 146): 45±4%/77±4%; EPN-PFB (n = 19): 90±7%/100%; EPN-ZFTA (n = 59): 64±7%/86±5%; EPN-YAP1 (n = 4): 50±25%/100%. Patients with EPN-PFA without molecular risk factors (1q gain, and/or subtype EPN-PFA1c/d/e,2a), with complete resection, and postoperative radiotherapy showed favorable outcomes (5-year PFS/OS 75±10%/92±7%). For patients with EPN-PFA with molecular risk factors, prognosis was poor irrespective of residual tumor status (5-year PFS/OS: 33±6%/64±6%). Among EPN-ZFTA, 11/59 tumors were classified as EPN-ZFTA with alternative fusions, associated with inferior PFS (5-year PFS/OS: 36±15%/91±9%). For EPN-ZFTA-RELA, homozygous deletions of CDKN2A were associated with unfavorable outcomes (4-year PFS/OS: 19±16%/57±18% vs. 79±7%/97±3%, p = 0.0001). Finally, we developed a novel stratification model that discriminates standard and intermediate risk patients from those at high risk (p < 0.0001 for PFS and OS).

Conclusions: These results strongly suggest the inclusion of molecular parameters into stratification, and the use of distinct treatment strategies within future ependymoma trials.

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基于前瞻性试验E-HIT2000和随后的注册表，建立儿童颅内室管膜瘤的高级风险分层模型。

背景：目前儿科颅内室管膜瘤的治疗策略没有考虑分子异质性。在这里，我们评估了分子群体特异性的结果决定因素，并开发了改进的风险分层模型。方法：将0 ~ 21岁的局限性颅内室管膜瘤患者纳入前瞻性临床试验E-HIT2000。治疗包括最大安全手术，局部放疗和化疗，根据年龄，组织学和主要修复后的残余肿瘤分层。临床数据在一个汇总的分子注释队列中进行分析，数据来自随后注册的类似治疗的患者。结果：291例患者的5年PFS和OS分别为62±3%和81±2%。对于分子注释的合并队列（n = 228）， 5年PFS/OS为：EPN-PFA (n = 146): 45±4%/77±4%；EPN-PFB (n = 19): 90±7%/100%；EPN-ZFTA (n = 59): 64±7%/86±5%；EPN-YAP1 (n = 4): 50±25%/100%。无分子危险因素（1q增益，和/或亚型EPN-PFA1c/d/e，2a）的EPN-PFA患者，完全切除和术后放疗显示出良好的结果（5年PFS/OS 75±10%/92±7%）。对于具有分子危险因素的EPN-PFA患者，无论肿瘤残留状态如何，预后均较差（5年PFS/OS: 33±6%/64±6%）。在EPN-ZFTA中，11/59的肿瘤被分类为EPN-ZFTA并伴有选择性融合，并伴有较差的PFS（5年PFS/OS: 36±15%/91±9%）。对于epn - zfa - rela， CDKN2A纯合子缺失与不良结果相关（4年PFS/OS: 19±16%/57±18% vs. 79±7%/97±3%,p = 0.0001）。最后，我们开发了一种新的分层模型，将标准和中度风险患者与高风险患者区分开来(p)。结论：这些结果强烈建议在未来的室管膜瘤试验中，将分子参数纳入分层，并使用不同的治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neuro-oncology 医学-临床神经学

CiteScore

27.20

自引率

6.30%

发文量

1434

审稿时长

3-8 weeks

期刊介绍： Neuro-Oncology, the official journal of the Society for Neuro-Oncology, has been published monthly since January 2010. Affiliated with the Japan Society for Neuro-Oncology and the European Association of Neuro-Oncology, it is a global leader in the field. The journal is committed to swiftly disseminating high-quality information across all areas of neuro-oncology. It features peer-reviewed articles, reviews, symposia on various topics, abstracts from annual meetings, and updates from neuro-oncology societies worldwide.