Baoqing Li

Brain metastases are a significant complication of non-small-cell lung cancer (NSCLC), contributing to high morbidity and mortality rates. The introduction of immune checkpoint inhibitors (ICIs) has opened new therapeutic avenues for patients with NSCLC, including those with brain metastases. However, the distinct microenvironment of the brain presents unique challenges to the effectiveness of these treatments. This review examines the mechanisms by which ICIs impact brain metastases from NSCLC, with particular focus on immune cell trafficking across the blood–brain barrier (BBB), tumor microenvironment modulation, and transcriptomic evolution of brain-tropic tumor clones. Unlike prior reviews, we integrate emerging data from single-cell and spatial transcriptomic studies, BBB disruption mechanisms, and the tumor-supportive role of brain-resident glia. We also critically evaluate key clinical trials and real-world evidence, highlighting differences in ICI efficacy across patient subgroups and therapeutic contexts. Additionally, we address the evolving role of surgical resection, stereotactic radiosurgery, and cerebrospinal-fluid-based biomarkers in optimizing ICI-based treatment strategies. This synthesis provides a comprehensive, mechanistic, and clinically relevant framework for improving outcomes in patients with NSCLC brain metastases treated with immunotherapy.

BACKGROUND: Diffuse‐type gastric cancer is observed in approximately one‐third of gastric cancers, yet the optimal treatment remains controversial. In the recently published Intergroup 0116 trial, a subgroup analysis demonstrated a lack of a long‐term survival benefit for adjuvant chemoradiation therapy among patients with diffuse‐type gastric cancer.METHODS: The Surveillance, Epidemiology, and End Results registry database was queried for patients who were newly diagnosed with diffuse‐type gastric cancer between 2002 and 2005 and underwent surgical resection with or without adjuvant radiotherapy (RT). Overall survival (OS) was analyzed by the Kaplan‐Meier method. Cox proportional hazards models were used to investigate the association between adjuvant RT and OS, with and without adjusting for other factors. In addition, propensity score methods were used to control for the possible effects of measured confounders.RESULTS: A total of 1889 cases of surgically resected diffuse‐type gastric cancer were included in the analysis; of these cases, 782 patients received adjuvant RT and 1107 did not receive RT. The median survival time was 30 months in the group treated with adjuvant RT versus 18 months in the group that did not receive RT with matched propensity scores (P<.001). The Cox model confirmed the improvement in OS in patients who received adjuvant RT (hazard ratio, 0.75; 95% confidence interval, 0.65‐0.82 [P<.001]).CONCLUSIONS: The current population‐based observational study suggested a potential survival benefit for adjuvant RT among patients with diffuse‐type gastric cancer. The standard treatment will likely remain controversial until evidence becomes available from phase 3 randomized trials exclusively for patients with diffuse‐type gastric cancer. Cancer 2014;120:3562–3568. © 2014 American Cancer Society.