Pro-inflammatory State Portends Poor Outcomes with Stereotactic Radiosurgery for Brain Metastases

Abstract

LC, poor initial MR, poor OS and poor intracranial control (p=0.01, p=0.01, p=0.02 and p=0.03, respectively). A lower percentage of lymphocytes predicted for poor LC and poor MR (p=0.01 and p=0.02), and an elevated PLR predicted for poor OS and poor LC (p=0.05 and p=0.04). Additionally, a lower pretreatment albumin concentration predicted for poor LC and OS (p=0.01 and p=0.03) . Conclusion: Pretreatment systemic inflammation is associated with poor outcomes post-SRS.Metastatic brain tumors are the most common intracranial neoplasms, with an incidence that continues to rise as a result of advances in neuroimaging and more effective systemic therapies. Population-based studies suggest that up to 45% of all patients with cancer develop brain metastases and that the majority of brain metastases originate from lung cancer, breast cancer and melanoma (1). The standard-of-care for brain metastases continues to evolve given innovations in radiation technology, surgical techniques and systemic therapies. However, among patients not requiring surgical resection, stereotactic radiosurgery (SRS) represents an effective and favored treatment modality with high rates of local control (2-4).Pre-treatment markers of systemic inflammation, including an elevated platelet-to-lymphocyte ratio (PLR), elevated neutrophil count, low lymphocyte count and low serum albumin concentration, have been found to predict responses to anti-neoplastic therapies and disease outcomes across multiple different malignancies (5-11). However, these markers and the role the systemic immune system plays in treatment outcomes in the setting of SRS for brain metastases have yet to be fully evaluated. There is a growing use of immunotherapy among patients with advanced cancer, and recent studies are suggesting improvements in outcomes with the combination of SRS and immunotherapy with checkpoint inhibition for treatment of brain metastases (12). Therefore, further exploring the role the systemic immune system plays in brain radiosurgery outcomes is now essential.Although the blood-brain barrier selectively isolates the central nervous system, circulating systemic immune cells are capable of migrating from the cerebral vessels into the brain parenchyma in response to various stimuli (13). Additionally, multiple studies have established that there is substantial cross-talk between systemic immune responses and inflammatory cells in the brain (14,15). Interestingly, pathological studies on brain metastases post-SRS have identified an inflammatory cellular response to be characteristic, suggesting an interaction between the immune system and SRS outcomes (16). We therefore sought to further evaluate the relationship between outcomes brain SRS and immune responses. We determined if pretreatment immune parameters associated with systemic inflammation would predict the initial response to SRS seen on the first post-treatment magnetic resonance imaging (MRI), and for local control, distant intracranial control and overall survival in the setting of SRS for b...

Post-treatment neutrophil-to-lymphocyte ratio predicts for overall survival in brain metastases treated with stereotactic radiosurgery

“…Two prior studies [33, 34]—have specifically investigated the association between inflammatory markers and OS in patients with BM, albeit without assessing simultaneous corticosteroid use. Shaverdian et al [33] demonstrated that pre-treatment markers, including platelet count and albumin count, were associated with OS in 70 patients with BM, but not the NLR.…”

“…Shaverdian et al [33] demonstrated that pre-treatment markers, including platelet count and albumin count, were associated with OS in 70 patients with BM, but not the NLR. Importantly, the authors did not report on systemic therapy use, an important factor in assessing OS.…”

Prognostic role of neutrophil lymphocyte ratio in patients with glioma

“…And inflammation status is closely related to the pathogenesis of glioma [ 10 ]. In this context, many inflammatory markers were proposed to predict cancer outcome, such as peripheral blood neutrophil count, lymphocyte count, neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), lymphocyte monocyte ratio (LMR) and so on [ 11 – 15 ]. Among them, NLR was the most studied parameter.…”

Impact of CyberKnife Radiosurgery on Overall Survival and Various Parameters of Patients with 1-3 versus ≥ 4 Brain Metastases

“…Mitsuya et al evaluated NLRs in pre-craniotomy patients having metastasectomies [ 15 ]. An NLR < five portended an OS of 14 months, while the OS was five months with an NLR ≥ five, Shaverdian et al showed that in pre-SRS patients being treated for brain metastases, on multivariate analysis, a higher peripheral neutrophil percentage predicted poor initial brain MRI, LC, intracranial control of metastases, and OS [ 16 ]. A lower percentage of lymphocytes predicted an initial poor MRI and LC.…”