Association between PD-L1 expression and initial brain metastasis in patients with non-small cell lung cancer and its clinical implications.

BACKGROUND: Brain metastases frequently occur in patients with non-small cell lung cancer (NSCLC) resulting in a poor prognosis. Here, we investigated the association between PD-L1 expression and brain metastasis in patients with NSCLC and its clinical significance. METHODS: A total of 270 patients diagnosed with metastatic NSCLC who underwent PD-L1 testing on their tumor tissue between January 2017 and March 2019 were retrospectively reviewed. The VENTANA PD-L1 (SP263) assay was used, and positive PD-L1 expression was defined as staining in ≥1% of tumor cells. RESULTS: Positive PD-L1 expression was observed in 181 (67.0%) patients, and 74 (27.4%) patients had brain metastasis at diagnosis. Synchronous brain metastases were more frequently observed in PD-L1-positive compared with PD-L1-negative patients (31.5% vs. 19.1%, p = 0.045). Multiple logistic regression analysis identified positive PD-L1 expression (odds ratio [OR]: 2.24, p = 0.012) as an independent factor associated with synchronous brain metastasis, along with the histological subtype of nonsquamous cell carcinoma (OR: 2.84, p = 0.003). However, the incidence of central nervous system (CNS) progression was not associated with PD-L1 positivity, with a two-year cumulative CNS progression rate of 26.3% and 28.4% in PD-L1-positive and PD-L1-negative patients, respectively (log rank p = 0.944). Furthermore, positive PD-L1 expression did not affect CNS progression or overall survival in patients with synchronous brain metastasis (long rank p = 0.513 and 0.592, respectively). CONCLUSIONS: Initial brain metastases are common in NSCLC patients with positive PD-L1 expression. Further studies are necessary to understand the relationship between early brain metastasis and cancer immunity.

Oxygen availability and spreading depolarizations provide complementary prognostic information in neuromonitoring of aneurysmal subarachnoid hemorrhage patients.

Multimodal neuromonitoring in neurocritical care increasingly includes electrocorticography to measure epileptic events and spreading depolarizations. Spreading depolarization causes spreading depression of activity (=isoelectricity) in electrically active tissue. If the depression is long-lasting, further spreading depolarizations occur in still isoelectric tissue where no activity can be suppressed. Such spreading depolarizations are termed isoelectric and are assumed to indicate energy compromise. However, experimental and clinical recordings suggest that long-lasting spreading depolarization-induced depression and isoelectric spreading depolarizations are often recorded outside of the actual ischemic zones, allowing the remote diagnosis of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. Here, we analyzed simultaneous electrocorticography and tissue partial pressure of oxygen recording in 33 aneurysmal subarachnoid hemorrhage patients. Multiple regression showed that both peak total depression duration per recording day and mean baseline tissue partial pressure of oxygen were independent predictors of outcome. Moreover, tissue partial pressure of oxygen preceding spreading depolarization was similar and differences in tissue partial pressure of oxygen responses to spreading depolarization were only subtle between isoelectric spreading depolarizations and spreading depressions. This further supports that, similar to clustering of spreading depolarizations, long spreading depolarization-induced periods of isoelectricity are useful to detect energy compromise remotely, which is valuable because the exact location of future developing pathology is unknown at the time when the neurosurgeon implants recording devices.