Birzu Cristina, French Pim, Caccese Mario, Cerretti Giulia, Idbaih Ahmed, Zagonel Vittorina, Lombardi Giuseppe
Sorbonne Université, Inserm, CNRS, UMR S 1127, Institut du Cerveau, ICM, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière-Charles Foix, Service de Neurologie 2-Mazarin, F-75013 Paris, France.
Department of Neurology, Erasmus University Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, The Netherlands.
Cancers (Basel). 2020 Dec 26;13(1):47. doi: 10.3390/cancers13010047.
Glioblastoma is the most frequent and aggressive form among malignant central nervous system primary tumors in adults. Standard treatment for newly diagnosed glioblastoma consists in maximal safe resection, if feasible, followed by radiochemotherapy and adjuvant chemotherapy with temozolomide; despite this multimodal treatment, virtually all glioblastomas relapse. Once tumors progress after first-line therapy, treatment options are limited and management of recurrent glioblastoma remains challenging. Loco-regional therapy with re-surgery or re-irradiation may be evaluated in selected cases, while traditional systemic therapy with nitrosoureas and temozolomide rechallenge showed limited efficacy. In recent years, new clinical trials using, for example, regorafenib or a combination of tyrosine kinase inhibitors and immunotherapy were performed with promising results. In particular, molecular targeted therapy could show efficacy in selected patients with specific gene mutations. Nonetheless, some molecular characteristics and genetic alterations could change during tumor progression, thus affecting the efficacy of precision medicine. We therefore reviewed the molecular and genomic landscape of recurrent glioblastoma, the strategy for clinical management and the major phase I-III clinical trials analyzing recent drugs and combination regimens in these patients.
胶质母细胞瘤是成人恶性中枢神经系统原发性肿瘤中最常见且侵袭性最强的类型。新诊断的胶质母细胞瘤的标准治疗方法包括在可行的情况下进行最大程度的安全切除，随后进行放化疗以及替莫唑胺辅助化疗；尽管采用了这种多模式治疗，但几乎所有胶质母细胞瘤都会复发。一旦肿瘤在一线治疗后进展，治疗选择有限，复发性胶质母细胞瘤的管理仍然具有挑战性。在特定病例中可评估采用再次手术或再次放疗的局部区域治疗，而使用亚硝基脲和替莫唑胺再次挑战的传统全身治疗显示疗效有限。近年来，开展了一些新的临床试验，例如使用瑞戈非尼或酪氨酸激酶抑制剂与免疫疗法的联合治疗，取得了有前景的结果。特别是，分子靶向治疗在特定基因突变的患者中可能显示出疗效。然而，一些分子特征和基因改变可能在肿瘤进展过程中发生变化，从而影响精准医学的疗效。因此，我们回顾了复发性胶质母细胞瘤的分子和基因组概况、临床管理策略以及分析这些患者近期药物和联合治疗方案的主要I - III期临床试验。
