Albany Medical College, Albany, New York, USA.
Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Pediatr Blood Cancer. 2023 Mar;70(3):e30139. doi: 10.1002/pbc.30139. Epub 2022 Dec 26.
Pediatric central nervous system (CNS) tumors are the leading cause of pediatric cancer mortality. Research addressing genomic biomarkers and clinical outcomes is needed to inform therapeutic decision-making.
We conducted a retrospective analysis of pediatric patients (age <21) diagnosed with a primary CNS tumor at four upstate New York hospitals from 2008 to 2021. Clinical and histopathologic data were identified from each patient, including genomic analysis of somatic mutations and tumor mutational burden (TMB) where available. These variables were each compared with overall survival using Cox regression analyses. Multivariable analysis was conducted to identify patient characteristics that may independently predict survival.
We identified 119 patients. Common tumor types included low-grade glioma (N = 51), high-grade glioma (N = 29), and medulloblastoma (N = 11). Common driver mutations included TP53 inactivation (N = 16), BRAF-KIAA1549 fusion (N = 16), FGFR1 amplification (N = 12), BRAF V600E mutation (N = 12), NF1 loss (N = 12), and H3F3A K28M mutation (N = 6). Median TMB was one mutation/megabase (mut/Mb, range = 0-132). Overall survival was 79.9%. Variables associated with poorer survival on univariable analysis were higher TMB (p = .002, HR 4.97), high-grade tumors (p = .009, HR 84.3), and high-grade glioma histology (p = .021, HR 3.14). Multivariable analyses further identified TMB (p = .011, HR 4.46) and high-grade histology (p = .015, HR 5.28) as independently predictive of worse survival. Tumor progression was more common in high-TMB (N = 15, 44%) than in low-TMB tumors (N = 19, 35%).
High TMB is correlated with higher rates of progression and death as compared to low-TMB tumors. These findings may help identify patients who may benefit from alternative treatments, such as immunotherapies.
小儿中枢神经系统（CNS）肿瘤是小儿癌症死亡的主要原因。需要研究基因组生物标志物和临床结果，以为治疗决策提供信息。
我们对 2008 年至 2021 年期间在纽约州北部四家医院诊断为原发性 CNS 肿瘤的小儿患者（年龄<21 岁）进行了回顾性分析。从每位患者中确定了临床和组织病理学数据，包括体细胞突变和肿瘤突变负荷（TMB）的基因组分析（如果有）。使用 Cox 回归分析比较了这些变量与总生存情况。进行多变量分析以确定可能独立预测生存的患者特征。
我们确定了 119 名患者。常见的肿瘤类型包括低级别胶质瘤（N=51）、高级别胶质瘤（N=29）和髓母细胞瘤（N=11）。常见的驱动突变包括 TP53 失活（N=16）、BRAF-KIAA1549 融合（N=16）、FGFR1 扩增（N=12）、BRAF V600E 突变（N=12）、NF1 缺失（N=12）和 H3F3A K28M 突变（N=6）。中位 TMB 为 1 个突变/兆碱基（mut/Mb，范围 0-132）。总体生存率为 79.9%。单变量分析中与较差生存率相关的变量包括较高的 TMB（p=0.002，HR 4.97）、高级别肿瘤（p=0.009，HR 84.3）和高级别胶质瘤组织学（p=0.021，HR 3.14）。多变量分析进一步确定 TMB（p=0.011，HR 4.46）和高级别组织学（p=0.015，HR 5.28）是独立预测生存率较差的因素。高 TMB 肿瘤（N=15，44%）比低 TMB 肿瘤（N=19，35%）更常见肿瘤进展。
与低 TMB 肿瘤相比，高 TMB 与更高的进展和死亡率相关。这些发现可能有助于识别可能受益于替代治疗（如免疫疗法）的患者。
