Malignant central nervous system (CNS) cancers include a group of heterogeneous dis-eases characterized by a relative resistance to treatments and distinguished as either primary tumors arising in the CNS or secondary tumors that spread from other organs into the brain. Despite therapeutic efforts, they often cause significant mortality and morbidity across all ages. Radiotherapy (RT) remains the main treatment for brain cancers, improving associated symptoms, improving tumor control, and inducing a cure in some. However, the ultimate goal of cancer treatment, to improve a patient’s survival, remains elusive for many CNS cancers, especially primary tumors. Over the years, there have thus been many preclinical studies and clinical trials designed to identify and overcome mechanisms of resistance to improve outcomes after RT and other therapies. For example, immunotherapy delivered concurrent with RT, especially hypo-fractionated stereotactic RT, is synergistic and has revolutionized the clinical management and outcome of some brain tumors, in particular brain metastases (secondary brain tumors). However, its impact on gliomas, the most common primary malignant CNS tumors, remains limited. In this review, we provide an overview of radioresistance mechanisms, the emerging strategies to overcome radioresistance, the role of the tumor microenviroment (TME), and the selection of the most significant results of radiation–immuno–oncological investigations. We also identify novel therapeutic opportunities in primary and secondary brain tumors with the purpose of elucidating current knowledge and stimulating further research to improve tumor control and patients’ survival.
恶性中枢神经系统（CNS）肿瘤是一组异质性疾病，其特征为对治疗具有相对抵抗性，可分为原发于中枢神经系统的肿瘤和从其他器官扩散至脑部的继发性肿瘤。尽管进行了多种治疗尝试，这类肿瘤仍常导致各年龄段患者出现显著的死亡率和发病率。放射治疗（RT）目前仍是脑癌的主要治疗手段，能够改善相关症状、提高肿瘤控制率，并在部分病例中实现治愈。然而，对于许多中枢神经系统肿瘤（尤其是原发性肿瘤）而言，提高患者生存率的癌症治疗根本目标仍难以实现。多年来，已有大量临床前研究和临床试验致力于识别并克服肿瘤的耐药机制，以提升放疗及其他疗法的疗效。例如，与放疗（尤其是大分割立体定向放疗）同步进行的免疫治疗具有协同作用，彻底改变了部分脑肿瘤（特别是脑转移瘤）的临床管理和治疗效果。然而，该疗法对胶质瘤（最常见的原发性恶性中枢神经系统肿瘤）的疗效仍有限。本文综述了放疗抵抗机制、克服放疗抵抗的新兴策略、肿瘤微环境（TME）的作用，并筛选了放射-免疫-肿瘤学研究中最具意义的成果。同时，我们针对原发性和继发性脑肿瘤提出了新的治疗机遇，旨在阐明当前认知并推动进一步研究，以提升肿瘤控制率和患者生存率。
Biological Insights and Radiation–Immuno–Oncology Developments in Primary and Secondary Brain Tumors
肿瘤(癌症)患者之家