ReviewA systematic review and meta-analysis on the impact of pre-operative neutrophil lymphocyte ratio on long term outcomes after curative intent resection of solid tumours
Introduction
Cancer is one of the leading causes of mortality and morbidity in both the developing and developed world [1]. Lung, breast, colorectal, gastric and pancreatic cancer are associated with the poorest prognosis; complete resection of localized disease represents the best opportunity for cure [1]. Identifying prognostic indicators of cancer progression forms a significant part of cancer research, as it allows for risk stratification and subsequent improvement in the selection of patients for potentially curative resection [2], [3]. It is well recognized that clinical outcomes are not only determined by the baseline characteristics of the tumour but also the host's response to the progressing malignancy [4]. A variety of host-related factors have been implicated as prognostic indicators of cancer related survival [5], [6]; these include weight loss, performance status and the systemic inflammatory response.
It has become increasingly evident that cancer progression is influenced by the systemic inflammatory response, first described by Virchow in 1876 by demonstrating the presence of leukocytes in neoplastic tissue [7]. Inflammation in the tumour microenvironment plays an important role in the proliferation and survival of malignant cells: it promotes angiogenesis, invasion and metastasis, through recruitment of T lymphocytes, chemokines, activated cytokines, IL6, TNF alpha, secretion of CRP, neutrophilia, subversion of the adaptive immune system, and alteration of response to hormones and chemotherapeutic agents [8], [9].
Recently, it has been demonstrated that several biomarkers and haematological indices representative of the inflammatory response, notably C-reactive protein (CRP), neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR), are associated with worse outcomes [9]. The neutrophil-lymphocyte ratio in particular has gained notable interest, with several studies over the last five years investigating its role in prognosticating long-term outcomes in patients undergoing loco-regional therapy [8], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47], [48], [49], [50], [51], [52], [53], [54], [55], [56], [57], [58], [59]. As haematological tests are routinely conducted in cancer patients, the neutrophil-lymphocyte ratio represents a simple, robust and convenient parameter of the inflammatory response. Thus, we investigated the prognostic value of NLR, in predicting long term outcomes following curative-intent surgery for solid tumours.
Section snippets
Search strategy and inclusion criteria
An online search was conducted using the US National Library of Medicine (Medline) and the Exerpta Medica database (EBASE). Search terms included (“neutrophil lymphocyte ratio” or “NLR”) and (“cancer” or “malignancy”). Fig. 1 outlines the search strategy. Limits included English language and human studies. Appropriate references cited by the retrieved studies were also identified. Selection criteria included 1) NLR as a prognostic indicator of overall, disease-free and disease specific survival
Results
A literature search through MEDLINE and EMBASE yielded 274 studies. Fig. 1 demonstrates the methodology for study selection. 49 studies comprising 14282 patients were found to meet the selection criteria for this review. There were no phase III randomised controlled trials (level one evidence), no phase II studies (level two evidence) and 49 observational studies [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30]
Discussion
It is well established and accepted that there is an intimate relationship between tumour cells, the immune system and the inflammatory response triggered [7]. This inflammatory response reflects a non-specific response to tumour hypoxia, tissue injury and necrosis [16], [64]. The complex and diverse neuroendocrinological and haemopoetic changes that occur during inflammation are thought to be responsible for both the diminishing of the immune response and the increase in tumour proliferation
Conflict of interest statement
The authors have no conflicts of interest to declare.
Authorship statement
Guarantor of the integrity of the study: Ashvin Paramanathan, Akshat Saxena and David Lawson Morris.
References (73)
- et al.
Appraisal of a model for prediction of prognosis in advanced colorectal cancer
Eur J Cancer
(1994) - et al.
Inflammation and cancer: back to Virchow?
Lancet
(2001) - et al.
Preoperative hematologic markers as independent predictors of prognosis in resected pancreatic ductal adenocarcinoma: neutrophil-lymphocyte versus platelet-lymphocyte ratio
Am J Surg
(2010) - et al.
Preoperative lymphocyte count as a prognostic factor in resected pancreatic ductal adenocarcinoma
HPB
(2007) - et al.
Comparison of the prognostic value of tumour and patient related factors in patients undergoing potentially curative resection of gastric cancer
Am J Surg
(2012) - et al.
Prognostic value of neutrophil-to-lymphocyte ratio and establishment of novel preoperative risk stratification model in bladder cancer patients treated with radical cystectomy
Urology
(2012) - et al.
Low calretinin expression and high neutrophil-to-lymphocyte ratio are poor prognostic factors in patients with malignant mesothelioma undergoing extrapleural pneumonectomy
J Thoracic Oncol
(2011) - et al.
Neutrophil to lymphocyte ratio for preoperative diagnosis of uterine sarcomas: a case-matched comparison
Eur J Surg Oncol
(2010) - et al.
Evaluation of the prognostic value of systemic inflammation and socioeconomic deprivation in patients with resectable colorectal liver metastases
Eur J Cancer
(2009) - et al.
Followup of neutrophil-to-lymphocyte ratio and recurrence of Clear cell renal cell carcinoma
J Urol
(2012)
Pretreatment neutrophil-to-lymphocyte ratio as an independent predictor of recurrence in patients with nonmetastatic renal cell carcinoma
J Urol
Ten-year experience in the management of gallbladder cancer from a single hepatobiliary and pancreatic centre with review of the literature
HPB
Neutrophil/lymphocyte ratio and its association with survival after complete resection in non-small cell lung cancer
J Thorac Cardiovasc Surg
Beta blockade during and after myocardial infarction: an overview of the randomized trials
Prog Cardiovasc Dis
A comparison of inflammation-based prognostic scores in patients with cancer. A Glasgow Inflammation Outcome Study
Eur J Cancer
Tumour T-lymphocyte subset infiltration and tumour recurrence following curative resection for colorectal cancer
Eur J Surg Oncol
CancerStats
Systemic inflammatory response predicts survival following curative resection of colorectal cancer
Br J Surg
Systemic inflammation, nutritional status and survival in patients with cancer
Curr Opin Clin Nutr Metab Care
Cancer cachexia and targeting chronic inflammation: a unified approach to cancer treatment and palliative/supportive care
J Supp Oncol
Prognostic factors in advanced cancer patients: evidence-based clinical recommendations—a study by the Steering committee of the European association for palliative care
J Clin Oncol
Comparison of the prognostic value of various preoperative inflammation-based factors in patients with stage III gastric cancer
Tumor Biol
Role of systemic inflammatory response in predicting survival in patients with primary operable cancer
Future Oncol
Usefulness of the neutrophil-to-lymphocyte ratio in predicting short- and long-term mortality in breast cancer patients
Ann Surg Oncol
Analysis of factors affecting recurrence of hepatocellular carcinoma after liver transplantation with a special focus on inflammation markers
Transplantation
Systemic inflammatory response is a predictor of outcome in patients undergoing preoperative chemoradiation for locally advanced rectal cancer
Colorectal Dis
Can neutrophil-to-lymphocyte ratio predict the survival of colorectal cancer patients who have received curative surgery electively?
Int J Colorectal Dis
Pre-treatment neutrophil to lymphocyte ratio is elevated in epithelial ovarian cancer and predicts survival after treatment
Cancer Immunol Immunother
Inflammatory markers in blood and serum tumor markers predict survival in patients with epithelial appendiceal neoplasms undergoing surgical cytoreduction and intraperitoneal chemotherapy
Ann Surg
Elevated preoperative neutrophil to lymphocyte ratio predicts risk of recurrence following curative resection for stage IIA colon cancer
Int J Colorectal Dis
Comparison of the prognostic value of tumour- and patient-related factors in patients undergoing potentially curative resection of oesophageal cancer
World J Surg
Preoperative neutrophil-to-lymphocyte ratio (NLR) is associated with reduced disease-free survival following curative resection of pancreatic adenocarcinoma
World J Surg
Preoperative neutrophil-to-lymphocyte ratio as a prognostic predictor after curative resection for hepatocellular carcinoma
World J Surg
Impact of systemic inflammation on outcome following resection for intrahepatic cholangiocarcinoma
J Surg Oncol
Elevated preoperative neutrophil to lymphocyte ratio predicts survival following hepatic resection for colorectal liver metastases
Eur J Surg Oncol
Negative Impact of neutrophil-lymphocyte ratio on outcome after liver transplantation for hepatocellular carcinoma
Ann Surg
Cited by (273)
Evaluation of the Relationship between Neutrophil-Lymphocyte Ratio and Clinical Outcomes in Geriatric Patients in the Post Anesthetic Care Unit
2024, International Journal of GerontologyAssociation of the pretreatment lung immune prognostic index with immune checkpoint inhibitor outcomes in patients with advanced hepatocellular carcinoma
2023, European Journal of Medical ResearchPreoperative CA19-9 and GGT ratio as a prognostic indicator in ampullary carcinoma
2023, BMC Gastroenterology