Pellerino Alessia, Franchino Federica, Soffietti Riccardo, Rudà Roberta
Department of Neuro-Oncology, University and City of Health and Science Hospital, Turin, Italy -
Department of Neuro-Oncology, University and City of Health and Science Hospital, Turin, Italy.
Q J Nucl Med Mol Imaging. 2018 Sep;62(3):225-238. doi: 10.23736/S1824-4785.18.03096-0. Epub 2018 Apr 26.
High-grade gliomas (HGGs) are the most common primary tumors of the central nervous system, which include anaplastic gliomas (grade III) and glioblastomas (GBM, grade IV). Surgery is the mainstay of treatment in HGGs in order to achieve a histological and molecular characterization, as well as relieve neurological symptoms and improve seizure control. Combinations of some molecular factors, such as IDH 1-2 mutations, 1p/19q codeletion and MGMT methylation status, allow to classify different subtypes of gliomas and identify patients with different outcome. The SOC in HGGs consists in a combination of radiotherapy and chemotherapy with alkylating agents. Despite this therapeutic approach, tumor recurrence occurs in HGGs, and new surgical debulking, reirradiation or second-line chemotherapy are needed. Considering the poor results in terms of survival, several clinical trials have explored the efficacy and tolerability of antiangiogenic agents, targeted therapies against epidermal growth factor receptor (EGFR) and different immunotherapeutic approaches in recurrent and newly-diagnosed GBM, including immune checkpoint inhibitors (ICIs), and cell- or peptide-based vaccination with unsatisfactory results in term of disease control. In this review we describe the major updates in molecular biology of HGGs according to 2016 WHO Classification, the current management in newly-diagnosed and recurrent GBM and grade III gliomas, and the results of the most relevant clinical trials on targeted agents and immunotherapy.
高级别胶质瘤（HGGs）是中枢神经系统最常见的原发性肿瘤，包括间变性胶质瘤（三级）和胶质母细胞瘤（GBM，四级）。手术是HGGs治疗的主要手段，目的是实现组织学和分子特征分析，以及缓解神经症状和改善癫痫控制。一些分子因素的组合，如异柠檬酸脱氢酶1-2（IDH 1-2）突变、1p/19q共缺失和O6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）甲基化状态，有助于对不同亚型的胶质瘤进行分类，并识别预后不同的患者。HGGs的标准治疗方案（SOC）包括放疗和使用烷化剂的化疗。尽管采用了这种治疗方法，HGGs仍会出现肿瘤复发，需要进行新的手术减瘤、再次放疗或二线化疗。考虑到生存结果不佳，多项临床试验探索了抗血管生成药物、针对表皮生长因子受体（EGFR）的靶向治疗以及在复发性和新诊断的GBM中不同免疫治疗方法的疗效和耐受性，包括免疫检查点抑制剂（ICIs）以及基于细胞或肽的疫苗接种，但在疾病控制方面结果不尽人意。在本综述中，我们根据2016年世界卫生组织（WHO）分类描述了HGGs分子生物学的主要更新、新诊断和复发性GBM及三级胶质瘤的当前治疗方法，以及关于靶向药物和免疫治疗的最相关临床试验结果。
