Elevated preoperative neutrophil-to-lymphocyte ratio as a predictor of worse survival after resection in patients with brain metastasis

Abstract

B rain metastases occur in 10% to 40% of patients with cancer and are the most common central nervous system neoplasm in adults. 28,33 With increased surveillance, improved control of systemic cancer, and prolonged survival, the incidence of patients with brain metastases is increasing. 17 The management of brain metastases has been revolutionized in clinical oncology by 4 developments: improved brain imaging, improved management of systemic diseases, the distribution of stereotactic irradiation, and the extension of less invasive surgical techniques that enable brain metastases to be removed even from eloquent brain areas with minimal morbidity. 5Although stereotactic irradiation and pharmacotherapies contribute to the treatment outcome of patients with brain metastasis, resection is still a mainstay for large brain metastases.The indications for resection include a symptomatic mass, a mass with considerable edema requiring high-dose ABBREVIATIONS DS-GPA = diagnosis-specific graded prognostic assessment; KPS = Karnofsky Performance Status; NLR = neutrophil-to-lymphocyte ratio; OS = overall survival; RPA = recursive partitioning analysis. SUBMITTED OBJECTIVEThe median postoperative survival duration of patients with brain metastases who undergo tumor resection is 12 months. Most of these patients die of systemic metastases or the progression of primary cancer but not brain metastases. The criteria for indicating resection are still controversial. Systemic assessment is restricted, especially in patients who need emergent management for their large-size or life-threatening brain metastases. The neutrophil-tolymphocyte ratio (NLR) is reported to correlate with survival time or progression-free survival in patients with various cancers. However, NLR has not been assessed in patients with brain metastases. The impact of NLR on the survival data of patients who had undergone resection of brain metastases was retrospectively analyzed. METHODS The clinical records of patients who underwent resection of brain metastases at Shizuoka Cancer Center between May 2007 and January 2015 were retrospectively analyzed. NLR was calculated by using the data obtained from the latest examination before resection and before the administration of steroid therapy. Kaplan-Meier curves were used for the assessment of overall survival (OS). RESULTS Of the 105 patients included, 67 patients were male. The median age of the patients was 63 years (range 36-90 years). The primary cancers were lung, colon, breast, uterus, and other cancers in 48, 19, 10, 8, and 20 patients, respectively. The postresection median survival duration was 12 months (range 1-91 months) for the entire series. The optimum NLR threshold value was identified as 5. A significant difference in the median OS was found: 14 months for 82 patients with an NLR < 5 versus 5 months for 23 patients with an NLR ≥ 5 (p = 0.001). CONCLUSIONS In this study, an elevated preoperative NLR is a predictor of worse survival after resection for brain metastases. NLR is a simple, systemic m...

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.…”

“…In addition, they only included BM due to breast, melanoma or non-small cell lung cacncer (NSCLC). Mitsuya et al [34] focused on resected BM: in a cohort of 105 patients, they found that NLR < 5 was associated with improved OS. Systemic therapy use, however, was significantly higher in the cohort with NLR < 5: 55 vs. 17%.…”

The Brain Entangled: The Contribution of Neutrophil Extracellular Traps to the Diseases of the Central Nervous System

“…A number of highly significant associations were found between neutrophils and the response to therapy of brain malignancies [91,102]. Furthermore, numerous reports point to the negative prognostic value of neutrophil presence and their participation in neuroinflammation in the milieu of brain tumors [91,93,[102][103][104][105]. As noted above, current evidence only indirectly points to the participation of NETs in the biology of primary and secondary brain tumors, and we must acknowledge that this issue has not been thoroughly studied yet.…”

The Microenvironmental Landscape of Brain Tumors

“…These observations are reminiscent of what has been shown in other metastatic organs that are not subject to immune privilege (Casbon et al, 2015; Coffelt et al, 2015; Liu et al, 2016; Wculek and Malanchi, 2015), supporting the concept that in the context of a tumor, the brain may be aberrantly exposed to pathologic inflammation that influences disease progression. Moreover, from a prognostic standpoint, a high ratio of neutrophils to lymphocytes in the peripheral blood is associated with reduced survival time, including following surgical resection, for both brain metastasis and glioblastoma patients (Bambury et al, 2013; McNamara et al, 2014; Mitsuya et al, 2016). It will therefore be imperative going forward to develop a more complete understanding of how the brain microenvironment changes in response to a primary tumor outside the CNS, in an analogous manner to what has been shown for other secondary organs such as lung or liver.…”

“…DC vaccinations such as DCVax-L have shown promising results, and as a consequence are in advanced clinical trials (newly-diagnosed glioblastoma, NCT00045968, Phase III) (Prins et al, 2011). Neutrophils also hold potential for their prognostic value in patients with primary brain tumors (Bertaut et al, 2016; Fossati et al, 1999), and metastatic disease (Koh et al, 2016; Mitsuya et al, 2016; Serdarevic et al, 2016). Targeting the vasculature through anti-angiogenic strategies is also relevant in glioblastoma patients given that this tumor type is highly vascularized; however, the current evidence seems to suggest that these strategies may be optimally used in the recurrent setting in combination with additional therapies (Friedman et al, 2009; Kreisl et al, 2009), rather than as frontline monotherapy on newly diagnosed, untreated disease (Gilbert et al, 2014).…”