成人胶质瘤患者的主要治疗方法,神经胶质神经和神经元肿瘤由手术的组合组成,放疗和化疗。对于许多系统性癌症,有针对性的治疗是护理标准的一部分,然而,大多数这些靶标在CNS肿瘤中的预测意义仍未得到很好的研究.尽管如此,越来越多地使用先进的分子诊断来识别潜在的目标,并且已经批准了对CNS肿瘤中也存在的靶标的肿瘤不可知监管批准。这就提出了一个问题,即在患有中枢神经系统肿瘤的成年患者中,何时以及针对哪个目标进行测试是有意义的。本循证指南回顾了RAS/MAPK通路改变的靶向治疗的证据(BRAF,NF1),在生长因子受体(EGFR,ALK,FGFR,NTRK,PDGFRA,ROS1),在细胞周期信号(CDK4/6,MDM2/4,TSC1/2)和改变的基因组稳定性(错配修复,POLE,TMB高,HRD)在成人胶质瘤患者中,神经胶质神经和神经元肿瘤。目前,BRAFp.V600E改变的靶向治疗被认为是复发性胶质瘤患者标准治疗的一部分,等待监管部门批准。对于NTRK融合和高TMB的经批准的肿瘤不可知治疗,成人中枢神经系统肿瘤患者疗效的证据非常有限,和治疗应最好在前瞻性临床注册和试验中给予。对于FGFR融合或突变的中枢神经系统肿瘤的靶向治疗,临床试验正在进行中,以证实迄今为止在篮子试验中观察到的适度活动.对于所有其他审查的目标,目前缺乏对中枢神经系统肿瘤有益的证据,和测试/治疗应在现有临床试验的背景下进行。
The mainstay of treatment for adult patients with gliomas, glioneuronal and neuronal tumors consists of combinations of surgery, radiotherapy, and chemotherapy. For many systemic cancers, targeted treatments are a part of the standard of care, however, the predictive significance of most of these targets in central nervous system (CNS) tumors remains less well-studied. Despite that, there is increasing use of advanced molecular diagnostics that identify potential targets, and tumor-agnostic regulatory approvals on targets also present in CNS tumors have been granted. This raises the question of when and for which targets it is meaningful to test in adult patients with CNS tumors. This evidence-based guideline reviews the evidence available for targeted treatment for alterations in the RAS/MAPK pathway (BRAF, NF1), in growth factor receptors (EGFR, ALK, fibroblast growth factor receptor (FGFR), neurotrophic tyrosine receptor kinase (NTRK), platelet-derived growth factor receptor alpha, and ROS1), in cell cycle signaling (CDK4/6, MDM2/4, and TSC1/2) and altered genomic stability (mismatch repair, POLE, high tumor mutational burden (TMB), homologous recombination deficiency) in adult patients with gliomas, glioneuronal and neuronal tumors. At present, targeted treatment for BRAF p.V600E alterations is to be considered part of the standard of care for patients with recurrent gliomas, pending regulatory approval. For approved tumor agnostic treatments for NTRK fusions and high TMB, the evidence for efficacy in adult patients with CNS tumors is very limited, and treatment should preferably be given within prospective clinical registries and trials. For targeted treatment of CNS tumors with FGFR fusions or mutations, clinical trials are ongoing to confirm modest activity so far observed in basket trials. For all other reviewed targets, evidence of benefit in CNS tumors is currently lacking, and testing/treatment should be in the context of available clinical trials.