Pierret Thomas, Giaj-Levra Niccolò, Toffart Anne-Claire, Alongi Filippo, Moro-Sibilot Denis, Gobbini Elisa
Thoracic Oncology Unit, Grenoble University Hospital, La Tronche, France.
Department of Advanced Radiation Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Sacro Cuore Don Calabria Hospital, Negrar di Valpolicella, Italy.
Front Oncol. 2022 Apr 12;12:787080. doi: 10.3389/fonc.2022.787080. eCollection 2022.
Immunotherapy has now been integrated as a treatment strategy for most patients with non-small cell lung cancer (NSCLC). However, the pivotal clinical trials that demonstrated its impressive efficacy often did not include patients with active, untreated brain metastases or leptomeningeal carcinomatosis. Nevertheless, NSCLC is the most common tumor to metastasize to the brain, and patients develop brain and meningeal involvement in approximately 40 and 10% of cases, respectively. Consequently, the appropriate care of these patients is a recurrent clinical concern. Although there are many aspects that would merit further investigation to explain the mechanism of intracranial response to immune checkpoint inhibitors (ICPs), some data suggest that they are able to cross the blood-brain barrier, resulting in local tumor microenvironment modification. This results in a similar clinical benefit in patients with stable, previously treated brain metastases compared to the general population. Despite important limitations, some real-life studies have described that the ICPs' efficacy was maintained also in less selected patients with untreated or symptomatic brain metastases. In contrast, few data are available about patients with leptomeningeal carcinomatosis. Nevertheless, neurological complications due to ICP treatment in patients with brain metastases have to be evaluated and carefully monitored. Despite the fact that limited data are available in the literature, the purpose of this review is to show that the multimodal treatment of these patients with brain metastases and/or leptomeningeal disease should be discussed during tracing of the history of the disease, participating in the local and possibly systemic control of NSCLC.
免疫疗法现已成为大多数非小细胞肺癌（NSCLC）患者的治疗策略。然而，那些证明其显著疗效的关键临床试验通常并未纳入有活动性、未经治疗的脑转移或软脑膜癌病的患者。尽管如此，NSCLC是最常见的转移至脑部的肿瘤，患者分别约有40%和10%会出现脑和脑膜受累。因此，对这些患者的恰当治疗一直是临床反复关注的问题。尽管有许多方面值得进一步研究以解释颅内对免疫检查点抑制剂（ICP）反应的机制，但一些数据表明它们能够穿过血脑屏障，从而导致局部肿瘤微环境改变。这使得与普通人群相比，患有稳定的、先前接受过治疗的脑转移患者也能获得类似的临床益处。尽管存在重要局限性，但一些真实世界研究描述，在选择较少的未经治疗或有症状的脑转移患者中，ICP的疗效也得以维持。相比之下，关于软脑膜癌病患者的数据很少。然而，必须对脑转移患者因ICP治疗引起的神经并发症进行评估并仔细监测。尽管文献中的数据有限，但本综述的目的是表明，在疾病病程追踪过程中，应讨论对这些有脑转移和/或软脑膜疾病患者的多模式治疗，以参与NSCLC的局部及可能的全身控制。
