Managing Central Nervous System Spread of Lung Cancer: The State of the Art

Abstract

Brain metastases (BrM) are common in both non–small-cell lung cancer and small-cell lung cancer. Substantial progress in BrM management has occurred in the past decade related to advances in both radiation and medical oncology. Recent and ongoing radiation trials have focused on increasing the candidacy for focal therapy of BrM with stereotactic radiosurgery; reducing the toxicity and improving patient selection for whole brain radiotherapy; and, in small-cell lung cancer, evaluating brain magnetic resonance imaging surveillance without prophylactic cranial irradiation, hippocampal avoidance in prophylactic cranial irradiation and whole brain radiotherapy, and the role of upfront stereotactic radiosurgery for BrM. In medical oncology, the development of multiple tyrosine kinase inhibitors with encouraging CNS activity and emerging data on the CNS activity of immune checkpoint inhibitors in some patients have opened the door to novel systemic and multidisciplinary treatment strategies for the management of BrM. Future research will focus on more robust characterizations of the CNS activity of targeted therapy and immunotherapies, as well as optimal integration and patient selection for multidisciplinary strategies involving CNS-active drugs, radiation therapy, and CNS surveillance.

Assessing the Relationship Between Liver Metastases and the Survival of Patients With Non-Small Cell Lung Cancer After Immune Checkpoint Inhibitors Treatment: A Systematic Review and Meta-Analysis

“…All PFS and OS analyses were presented using HR and its 95% confidence interval. Heterogeneity analysis was performed using the I 2 test, with I 2 ≤ 50% representing low heterogeneity, and a fixed-effects model method was used for meta-analysis. I 2 > 50% represented significant heterogeneity, and the random effects model method was used for analysis.…”

Emerging Systemic Treatment Perspectives on Brain Metastases: Moving Toward a Better Outlook for Patients

“…Most of the existing data establishing the CNS activity of TKI in oncogenic addicted NSCLC is derived from trials not designed to robustly generate such data, as baseline screening for brain metastases was not always mandated and stratification often did not occur. 115,117 With the firstgeneration EGFR inhibitors such as erlotinib, gefitinib, and icotinib, CNS relapses occurred frequently due to pharmacologic failure as blood-brain barrier penetration of these TKIs is poor. Data for second-generation EGFR-TKIs is scarce and lacking for dacomitinib but suggests a higher intracranial activity compared with first-generation EGFR-TKIs.…”

Re-Whole Brain Radiotherapy May Be One of the Treatment Choices for Symptomatic Brain Metastases Patients

“…Moreover, there is increasing evidence that molecular targeted therapies or immunotherapy can treat BM [ 44 ]. Multiple clinical trials demonstrated that the central nervous system objective response rates are > 50% when using newer generation tyrosine kinase inhibitors, and treatment strategies involving upfront central nervous system active tyrosine kinase inhibitors alone with close magnetic resonance imaging surveillance may be considered for some patients with asymptomatic BM [ 45 ]. Therefore, unsympathetic patients who are adaptable to systemic therapy may be suitable for systemic therapy before re-WBRT is considered.…”