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桥脑儿童弥漫性中线胶质瘤分子与突变分析中的放疗后磁共振成像特征

Postradiation MR Imaging Features in Molecular and Mutational Analyses in Pontine Pediatric Diffuse Midline Gliomas.

作者信息

Rameh V, Ziaei A, Vajapeyam S, Chen N, London W B, Wright K, Poussaint T Y

机构信息

From the Department of Radiology (V.R., A.Z., S.V., T.Y.P.), Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.

Department of Pediatric Oncology (N.C., W.B.L., K.W.), Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.

出版信息

AJNR Am J Neuroradiol. 2025 Sep 25. doi: 10.3174/ajnr.A8817.

DOI:10.3174/ajnr.A8817
PMID:40280708
Abstract

BACKGROUND AND PURPOSE

We aimed to describe the postradiation imaging features in children with pontine pediatric diffuse midline glioma, and to identify associations between these changes and histone mutational status, as well as overall survival.

MATERIALS AND METHODS

Patients were recruited as part of an institutional review board-approved, multicenter clinical trial: Molecularly Determined Treatment of Diffuse Intrinsic Pontine Glioma. Subjects had baseline MR imaging that showed classic imaging criteria of pontine diffuse midline glioma and postradiation imaging at regular intervals. All patients underwent biopsy before therapy initiation and received standard radiation therapy with adjuvant bevacizumab. Patients were subsequently stratified based on methylation status and epidermal growth factor receptor expression in the biopsy specimen. Imaging analyses included postradiation T2/FLAIR and enhancing tumor volumes, as well as normalized ADC (nADC) histogram metrics (mean, median, mode, skewness, and kurtosis) at 2 and 4 months postradiation. The mutation subgroups were compared by using a Wilcoxon rank-sum test.

RESULTS

Forty-one patients met eligibility criteria, and mutational status was identified in 35. The median age was 6 years (range: 1.2-17). Seventeen of 35 (49%) had histone mutations, 10 of 35 (29%) had , and 8 of 35 (22%) were wild-type (WT). Except for enhancing volume at postradiation time point 2 (4 months postradiation; RT2), all imaging features had a statistically significant change ( < .05) from baseline to time point 1 (2 months postradiation; RT1) and RT2. Within the cohort of patients that had H3-mutant tumors ( = 27), patients with had statistically significantly higher mean nADC_FLAIR ( = .05), mode nADC_FLAIR ( = .003), median nADC_FLAIR ( = .02), and mode nADC-enhancement ( = .04) than patients with H3-3A at RT1. These nADC histogram metrics were not statistically significantly different at RT2. Moreover, we found no statistically significant difference in ADC histogram metrics postradiation, when we compared H3-mutant versus WT tumors.

CONCLUSIONS

Postradiation MR imaging features are differentially correlated with the underlying mutational status of pediatric pontine diffuse midline glioma.

摘要

背景与目的

我们旨在描述桥脑儿童弥漫性中线胶质瘤患儿放疗后的影像学特征,并确定这些变化与组蛋白突变状态以及总生存期之间的关联。

材料与方法

患者作为机构审查委员会批准的多中心临床试验“弥漫性脑桥内胶质瘤的分子决定治疗”的一部分被招募。受试者有基线磁共振成像,显示桥脑弥漫性中线胶质瘤的经典影像学标准,并定期进行放疗后成像。所有患者在开始治疗前接受活检,并接受标准放疗及辅助贝伐单抗治疗。随后根据活检标本中的甲基化状态和表皮生长因子受体表达对患者进行分层。影像学分析包括放疗后T2/液体衰减反转恢复序列(FLAIR)和强化肿瘤体积,以及放疗后2个月和4个月时的标准化表观扩散系数(nADC)直方图指标(均值、中位数、众数、偏度和峰度)。使用Wilcoxon秩和检验对突变亚组进行比较。

结果

41例患者符合入选标准,35例患者确定了突变状态。中位年龄为6岁(范围:1.2 - 17岁)。35例中的17例(49%)有组蛋白突变,35例中的10例(29%)有[此处原文缺失相关内容],35例中的8例(22%)为野生型(WT)。除放疗时间点2(放疗后4个月;RT2)的强化体积外,所有影像学特征从基线到时间点1(放疗后2个月;RT1)和RT2均有统计学显著变化(P < .05)。在有H3突变肿瘤的患者队列(n = 27)中,在RT1时,有[此处原文缺失相关内容]的患者的平均nADC_FLAIR(P = .05)、众数nADC_FLAIR(P = .003)、中位数nADC_FLAIR(P = .02)和众数nADC强化(P = .04)在统计学上显著高于有H3 - 3A的患者。这些nADC直方图指标在RT2时无统计学显著差异。此外,当我们比较H3突变肿瘤与WT肿瘤时,放疗后ADC直方图指标无统计学显著差异。

结论

放疗后磁共振成像特征与儿童桥脑弥漫性中线胶质瘤的潜在突变状态存在不同程度的相关性。

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