Central Nervous System Metastases in Lung Cancer Patients: From Prevention to Diagnosis and Treatment

Approximately 40% of lung cancer patients will develop central nervous system (CNS) metastases during the course of their disease. Most of these are brain metastases, but up to 10% will develop leptomeningeal metastases. Known risk factors for CNS metastases development are small cell lung cancer (SCLC), adenocarcinoma histology, epidermal growth factor receptor (EGFR) mutant or anaplastic lymphoma kinase (ALK) rearranged lung cancer, advanced nodal status, tumor stage and younger age. CNS metastases can have a negative impact on quality of life (QoL) and overall survival (OS). The proportion of lung cancer patients diagnosed with CNS metastases has increased over the years due to increased use of brain imaging as part of initial cancer staging, advances in imaging techniques and better systemic disease control. Post contrast gadolinium enhanced magnetic resonance imaging (gd-MRI) is preferred, however when this is contra-indicated a contrast enhanced computed tomography (CE-CT) is mentioned as an alternative option. When CNS metastases are diagnosed, local treatment options consist of radiotherapy (stereotactic or whole brain) and surgery. Local treatment can be complicated by symptomatic radiation necrosis for which no high level evidence based treatment exists. Moreover, differential diagnosis with metastasis progression is difficult. Systemic treatment options have expanded over the last years. Until recently, chemotherapy was the only treatment option with a poor penetration in the CNS. Angiogenesis inhibitors are promising in the treatment of primary CNS tumors as well as radiation necrosis but clinical trials of anti-angiogenic agents in NSCLC have largely excluded patients with CNS metastases . Furthermore, research has also focused on methods to prevent development of CNS disease, for example with prophylactic cranial irradiation. Recently, checkpoint inhibitors have become available for NSCLC patients, and tyrosine kinase inhibitors (TKIs) have improved prognosis significantly in those with a druggable driver mutation. Newer TKIs are often designed to have better CNS penetration compared to first-generation TKIs. Despite advances in treatment options CNS metastases remain a problem in lung cancer and cause morbidity and mortality.

The scope of this Research Topic will cover advances in the understanding of CNS metastases development and how to identify and screen NSCLC patients with a high risk of developing CNS metastases. Local and systemic treatment options (preventive as well as for diagnosed CNS disease) for patients with and without driver mutations will be discussed including possible complications arising from these treatments. The value of utilizing prognostic criteria such as RPA (recursive partitioning analysis) or GPA (Graded Prognostic Assessment) in selecting patients for local versus systemic therapies will be discussed. Moreover, utility of RANO brain metastases criteria in clinical trials of brain metastases will be reviewed. Furthermore, this research topic will focus on the neurocognitive and psychological impact of having CNS metastases.

The goal of this Research Topic is to provide an extensive resource of articles describing advances in CNS metastases management in lung cancer patients, from prevention to diagnosis and treatment. Studies on CNS metastases biomarkers, imaging, prevention, local treatment, systemic treatment (e.g. chemotherapy, angiogenesis inhibitors, TKIs, checkpoint inhibitors) and psychology are encouraged. The focus can be on translational as well as clinical research. We welcome the submission of original articles, perspective articles, reviews, theory, opinion, technology reports, and case reports.

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