Molecular Characterization and Treatment Approaches for Pediatric H3 K27-Altered Diffuse Midline Glioma: Integrated Systematic Review of Individual Clinical Trial Participant Data.
Molecular Characterization and Treatment Approaches for Pediatric H3 K27-Altered Diffuse Midline Glioma: Integrated Systematic Review of Individual Clinical Trial Participant Data.
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小儿H3 K27的分子表征和治疗方法进行了弥漫性中线胶质瘤：单个临床试验参与者数据的综合系统综述。
作者：
弥漫性中线胶质瘤，H3 k27改变是主要影响儿童人群的中枢神经系统肿瘤。目前，没有治疗方法，有几个已完成和正在进行的临床试验探索许多不同的治疗选择。在本系统综述中，我们利用来自已发表临床试验的个体参与者数据来评估治疗方案、分子组成和临床特征对总生存期的影响。这些发现旨在为未来的干预措施提供指导，同时表明有必要继续评估临床试验的结果，因为它们在更大范围内可用。弥漫性中线胶质瘤（DMG）， H3 k27改变是高度侵袭性的，无法治愈的中枢神经系统（CNS）肿瘤。目前标准的姑息治疗是放射治疗，大多数儿童在诊断后不到一年就死于这种疾病。在过去的十年中，我们在分子水平上对这些异质性肿瘤的理解取得了重大进展。因此，大多数较新的临床试验提供了更有针对性的方法，从肿瘤活检中获得信息。在本系统综述中，我们使用了过去五年中发表的符合纳入和排除标准的七个近期临床试验的个体参与者数据来分析影响总生存期（OS）的因素。我们发现最突出的遗传改变H3.3 （H3F3A）和TP53与较差的OS相关，而ACVR具有保护作用。此外，再照射是唯一具有统计学意义的治疗方式，显示出任何生存益处。我们的研究结果强调了DMG、H3 k27改变的一些重要特征及其对OS的影响，以及继续回顾临床试验数据以改进这些致命肿瘤治疗方法的重要性。
Diffuse midline glioma, H3 K27-altered are central nervous system tumors that primarily affect the pediatric population. Currently, there are no curative therapies, with several completed and on-going clinical trials exploring many different therapeutic options. In this systematic review, we utilized individual participant data from published clinical trials to assess the effect of treatment options, molecular makeup and clinical characteristics on overall survival. These findings are intended to provide guidance for future interventions along with indicate the need to continue to assess results from clinical trials as they become available at a larger scale. Diffuse midline glioma (DMG), H3 K27-altered are highly aggressive, incurable central nervous system (CNS) tumors. The current standard palliative treatment is radiotherapy, with most children succumbing to the disease in less than one year from the time of diagnosis. Over the past decade, there have been significant advancements in our understanding of these heterogeneous tumors at the molecular level. As a result, most of the newer clinical trials offered utilize more targeted approaches with information derived from the tumor biopsy. In this systematic review, we used individual participant data from seven recent clinical trials published over the past five years that met our inclusion and exclusion criteria to analyze factors that influence overall survival (OS). We found that the most prominent genetic alterations H3.3 (H3F3A) and TP53 were associated with worse OS and that ACVR had a protective effect. In addition, re-irradiation was the only statistically significant treatment modality that showed any survival benefit. Our findings highlight some important characteristics of DMG, H3 K27-altered and their effects on OS along with the importance of continuing to review clinical trial data to improve our therapies for these fatal tumors.
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