Spagnuolo Alessia, Muto Matteo, Monaco Fabio, Colantuoni Giuseppe, Gridelli Cesare
Division of Medical Oncology, 'S. G. Moscati' Hospital, Avellino, Italy.
Division of Radiotherapy, 'S. G. Moscati' Hospital, Avellino, Italy.
Transl Lung Cancer Res. 2019 Dec;8(6):1134-1151. doi: 10.21037/tlcr.2019.12.24.
In recent years, the study of the molecular characteristics of non-small cell lung cancer (NSCLC) has highlighted a specific role of some genes that represent important therapeutic targets, including epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS-1) and v-Raf murine sarcoma viral oncogene homolog B1 (BRAF). Patients with oncogene-addicted cancer benefit more from therapy with tyrosine kinase inhibitors (TKIs) than from chemotherapy. The brain is a preferred site for tumor spread in these patients. In addition, given greater control of extracranial disease and prolonged survival, the brain is often the first site of progression. Therefore, there is great interest in therapeutic approaches that optimize the control of intracranial disease associated with systemic drugs that, by penetrating the blood-brain barrier (BBB), may improve local control. On the latter, radiotherapy provides excellent efficacy but following the results of clinical trials with new brain penetrant drugs, the question of how and especially when to perform brain radiotherapy in patients with oncogene-addicted NSCLC remains open. Prospective studies may indicate which patients are most likely to benefit from combined use or in what sequence they will undergo systemic and radiotherapy treatment. Due to the heterogeneity of patients and the introduction of new generation TKIs, a multidisciplinary assessment for the best management of therapies in NSCLC patients with molecular driver alterations and brain metastases (BM) is required.
近年来，非小细胞肺癌（NSCLC）分子特征的研究突出了某些基因的特定作用，这些基因代表重要的治疗靶点，包括表皮生长因子受体（EGFR）、间变性淋巴瘤激酶（ALK）、c-ros癌基因1（ROS-1）和v-Raf鼠肉瘤病毒癌基因同源物B1（BRAF）。致癌基因成瘾性癌症患者从酪氨酸激酶抑制剂（TKIs）治疗中获益多于化疗。脑是这些患者肿瘤扩散的首选部位。此外，鉴于颅外疾病得到更好控制且生存期延长，脑常是疾病进展的首发部位。因此，人们对优化与能穿透血脑屏障（BBB）的全身药物相关的颅内疾病控制的治疗方法非常感兴趣，这类药物可能会改善局部控制。就后者而言，放射治疗疗效极佳，但根据新型脑渗透药物的临床试验结果，对于致癌基因成瘾性NSCLC患者如何以及何时进行脑放射治疗的问题仍未解决。前瞻性研究可能会表明哪些患者最有可能从联合使用中获益，或者他们将按何种顺序接受全身治疗和放射治疗。由于患者的异质性以及新一代TKIs的引入，对于分子驱动改变和脑转移（BM）的NSCLC患者的最佳治疗管理需要进行多学科评估。
