The role of the systemic inflammatory response in predicting outcomes in patients with operable cancer: Systematic review and meta-analysis.
ABSTRACT: Cancer remains a leading causes of death worldwide and an elevated systemic inflammatory response (SIR) is associated with reduced survival in patients with operable cancer. This review aims to examine the evidence for the role of systemic inflammation based prognostic scores in patients with operable cancers. A wide-ranging literature review using targeted medical subject headings for human studies in English was carried out in the MEDLINE, EMBASE, and CDSR databases until the end of 2016. The SIR has independent prognostic value, across tumour types and geographical locations. In particular neutrophil lymphocyte ratio (NLR) (n?=?158), platelet lymphocyte ratio (PLR) (n?=?68), lymphocyte monocyte ratio (LMR) (n?=?21) and Glasgow Prognostic Score/ modified Glasgow Prognostic Score (GPS/mGPS) (n?=?60) were consistently validated. On meta-analysis there was a significant relationship between elevated NLR and overall survival (OS) (p?
Project description:<h4>Objective</h4>The study aims to investigate the prognostic value of the lymphocyte-to-monocyte ratio (LMR) in patients with colorectal cancer (CRC) undergoing curative resection and to compare it to established biomarkers including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), modified Glasgow prognostic score (mGPS), and combined BRAF-mismatch repair (MMR) status.<h4>Background</h4>The prognostic significance of systemic inflammatory markers in CRC such as the NLR, PLR, and mGPS has been well defined. Commonly used genetic markers such as combined BRAF-MMR status have also been found to be prognostic. Recent evidence, although limited, suggests that the preoperative LMR may be prognostic in CRC.<h4>Methods</h4>Data from the Northern Sydney Local Health District from January 1998 to December 2012 were retrospectively collected. Of 3281 consecutive patients identified, 1623 patients who underwent curative resection were deemed eligible for inclusion. The relation between the LMR, clinicopathologic variables, and other biomarkers were analyzed in Kaplan-Meier log-rank survival analysis and then multivariate Cox regression models looking for association with overall survival (OS).<h4>Results</h4>In multivariate analysis of all patients, elevated LMR was associated with better OS (hazard ratio 0.569, 95% confidence interval: 0.478-0.677, P < 0.001) independent of age (P < 0.001), T stage (P < 0.001), N stage (P < 0.001), and grade (P = 0.049). The NLR, PLR, and combined BRAF-MMR status were not independently significant. In multivariate subgroup analysis of 389 patients with mGPS, LMR remained the only independently significant biomarker (hazard ratio 0.620, 95% confidence interval: 0.437-0.880, P = 0.007).<h4>Conclusions</h4>The LMR is an independent predictor of OS in patients with CRC undergoing curative resection and appears to be superior to pre-existing biomarkers.
Project description:Conflicting evidence exists regarding the effects of platelet/lymphocyte ratio (PLR) and lymphocyte/monocyte ratio(LMR) on the prognosis of colorectal cancer (CRC) patients. This study aimed to evaluate the roles of the PLR and LMR in predicting the prognosis of CRC patients via meta-analysis.Eligible studies were retrieved from the PubMed, Embase,andChina National Knowledge Infrastructure (CNKI) databases, supplemented by a manual search of references from retrieved articles. Pooled hazard ratios (HR) with 95% confidence intervals (95% CI) were calculated using the generic inverse variance and random-effect model to evaluate the association of PLR and LMR with prognostic variables in CRC, including overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS).Thirty-three studies containing 15,404 patients met criteria for inclusion. Pooled analysis suggested that elevated PLR was associated with poorer OS (pooled HR = 1.57, 95% CI: 1.41 - 1.75, p< 0.00001, I2=26%) and DFS (pooled HR = 1.58, 95% CI: 1.31 - 1.92, p< 0.00001, I2=66%). Conversely, high LMR correlated with more favorable OS (pooled HR = 0.59, 95% CI: 0.50 - 0.68, p< 0.00001, I2=44%), CSS (pooled HR = 0.54, 95% CI: 0.40 - 0.72, p< 0.00001, I2=11%) and DFS (pooled HR = 0.82, 95% CI: 0.71- 0.94,p=0.005, I2=29%).Elevated PLR was associated with poor prognosis, while high LMR correlated with more favorable outcomes in CRC patients. Pretreatment PLR and LMR could serve as prognostic predictors in CRC patients.
Project description:The aim of this study was to directly compare the prognostic value of cumulative scores and composite ratios in patients with operable rectal cancer. Within a single surgical unit preoperative differential blood cell results including neutrophil (N), lymphocyte (L), monocyte (M) and platelet (P) counts, as well as CRP (C) and albumin (A) levels were recorded. These results were used to construct a series of composite ratios (NLR, PLR, LMR, CAR) and cumulative scores (NLS, PLS, LMS, NPS, mGPS). The relationship between composite ratios and the cumulative scores and clinicopathological characteristics, cancer specific survival (CSS) and overall survival (OS) were examined. A total of 413 patients were included. When adjusted for TNM stage, surgical approach, time of surgery and margin involvement mGPS (p?< 0.05) was associated with CSS. In addition, most composite ratios/scores showed correlations with neoadjuvant therapy (p?<?0.001). When a direct comparison between NPS (myeloid) and mGPS (liver) was carried out they showed similar associations with both CSS and OS. Therefore, both composite ratios and cumulative scores have been shown to be prognostic in patients with operable rectal cancer.
Project description:Objective: Neutrophil lymphocyte ratio (NLR), Lymphocyte mononuclear cell ratio (LMR), and Platelet lymphocyte ratio (PLR) can be used as various prognostic factors for malignant tumors, but the value of prognosis for patients with adenocarcinoma of the esophagogastric junction (AEG) has not been determined. This study used meta-analysis to assess the value of these indicators in the evaluation of AEG prognosis. Methods: Relevant literatures on the prognostic relationship between NLR, LMR, PLR, and AEG was retrieved from PubMed, Web of Science, Embase, Cochrane Library, Cochrane Central Register of Controlled Trials, Wanfang data, and Chinese National Knowledge Infrastructure. The search time from database establishment to June 30, 2019. The language is limited to English and Chinese. Data was analyzed using Stata 15.0 software. Result: Six retrospective studies were included, five of them involved NLR and six of them involved PLR. No LMR literature that adequately satisfied the conditions was retrieved. Increased NLR was significantly associated with a significant reduction in overall survival (OS), cancer-specific survival (CSS), or disease specific survival (DSS) in patients with AEG [hazard ratio (HR) = 1.545, 95% CI: 1.096-2.179, P < 0.05]. Subgroup analysis showed that NLR had significant value in the prognosis of both Chinese and Non-Chinese patients (P = 0.009 vs. P = 0.000). NLR had significant prognostic value for ?3 and <3 groups (P = 0.022 vs. P = 0.000). NLR has a significant prognostic value for samples ?500 and <500 (P = 0.000 vs. P = 0.022). NLR and OS/CSS/DSS single factor meta-regression showed that regional NLR cut-off values and sample size may be the source of heterogeneity in AEG patients (all P < 0.05). There was no significant association between elevated PLR and OS in patients with AEG (HR = 1.117, 95% CI: 0.960-1.300, P > 0.05). PLR had no significant prognostic value for both Chinese and UK patients (P = 0.282 vs. P = 0.429). PLR had no significant prognostic value for ?150 group and <150 group (P = 0.141 and P = 0.724). No significant prognostic value was found in either the 300 group and <300 group (P = 0.282 vs. P = 0.429). Conclusion: Preoperative NLR rise was an adverse prognostic indicator of AEG. High-risk patients should be treated promptly. The results showed that PLR was not recommended as a prognostic indicator of AEG.
Project description:BACKGROUND:NLR, PLR, and LMR have been associated with pancreatic ductal adenocarcinoma (PDAC) survival. Prognostic value and optimal cutpoints were evaluated to identify underlying significance in surgical PDAC patients. METHODS:NLR, PLR, and LMR preoperative values were available for 277 PDAC patients who underwent resection between 2007 and 2015. OS, RFS, and survival probability estimates were calculated by univariate, multivariable, and Kaplan-Meier analyses. Continuous and dichotomized ratio analysis determined best-fit cutpoints and assessed ratio components to determine primary drivers. RESULTS:Elevated NLR and PLR and decreased LMR represented 14%, 50%, and 50% of the cohort, respectively. OS (P?=?.002) and RFS (P?=?.003) were significantly decreased in resected PDAC patients with NLR ?5 compared to those with NLR <?5. Optimal prognostic OS and RFS cutpoints for NLR, PLR, and LMR were 4.8, 192.6, and 1.7, respectively. Lymphocytes alone were the primary prognostic driver of NLR, demonstrating identical survival to NLR. CONCLUSIONS:NLR is a significant predictor of OS and RFS, with lymphocytes alone as its primary driver; we identified optimal cutpoints that may direct future investigation of their prognostic value. This study contributes to the growing evidence of immune system influence on outcomes in early-stage pancreatic cancer.
Project description:This study was aimed to examine the prognostic value of preoperative neutrophils, platelets, lymphocytes, monocytes and calculated ratios in patients with laryngeal squamous cell cancer (LSCC). From January 2007 to December 2011, 979 patients with LSCC were enrolled in our study. Preoperative neutrophils, platelets, lymphocytes, monocytes, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) were analyzed. Besides well-established clinicopathological prognostic factors, we evaluated the independent prognostic relevance of these hematological parameters by Cox regression models in disease-free survival (DFS) and cancer-specific survival (CSS). We found patients in the highest tertile of NLR (>2.40), PLR (>111.00) were at significantly higher risk of DFS and CSS (<i>P</i><0.05) compared with those in the lowest tertile after multivariate analysis, whereas presenting significantly higher risk in the lowest tertile of lymphocytes (<1.60×109/L) and LMR (<3.50). Additionally, the tertile category of NLR as well as PLR increased and lymphocytes as well as LMR decreased in shorter DFS and CSS by the Kaplan-Meier method and the log-rank test. In conclusion, this study indicated that preoperative lymphocytes, NLR, PLR and LMR were significantly associated with LSCC progression, DFS and CSS, and these hematological parameters could be considered independent prognostic values for patients with LSCC.
Project description:Systemic inflammation was recognized as an essential factor contributing to the development of malignancies. This study aimed to investigate the prognostic value of pre-operative lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) in patients with colorectal liver-only metastases (CLOM) undergoing hepatectomy. We retrospectively enrolled 150 consecutive patients with CLOM between 2000 and 2012. The optimal cutoff values of continuous LMR, NLR, and PLR were determined using the receiver operating characteristic curve analysis. Recurrence-free survival (RFS) and overall survival (OS) related to the LMR, NLR, and PLR were analyzed using both Kaplan-Meier and multivariate Cox regression methods. Elevated LMR (≥2.82) and lower NLR (<4.63) were significantly associated with better RFS and OS in patients with CLOM after hepatectomy, instead of lower PLR (<150.17). Multivariate Cox analysis identified elevated LMR as the only independent inflammatory factor for better RFS (hazard ratio, 0.591; 95% CI, 0.32-0.844; P=0.008) and OS (hazard ratio, 0.426; 95% CI, 0.254-0.716; P=0.001). In the subgroup analysis, elevated LMR was a significant favorable factor in both 5-year RFS and OS of patients with male gender, lymph node metastases, colon cancer, liver tumor with the largest diameter <5 cm, preoperative carcinoembryonic antigen level <200 ng/mL, negative hepatitis B virus infection, non-anatomic liver resection, postoperative chemotherapy, and non-preoperative chemotherapy. This study demonstrated that the preoperative LMR was an independent predictor of RFS and OS in patients with CLOM undergoing hepatic resection, and it appeared to be superior to the NLR and PLR.
Project description:Growing evidence has indicated that some inflammatory markers, including lymphocyte to monocyte ratio (LMR), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and prognostic nutritional index (PNI), can be used as indicators in the prognosis of colorectal cancer (CRC). However, there is controversy concerning what is the best predictor of prognosis in CRC.A cohort of 1744 CRC patients in our institution was analyzed retrospectively. Harrell's concordance index (c-index) and Bayesian information criterion (BIC) were used to determine the optimal cut-off values of inflammatory markers and compare their predictive capacity. The association of inflammatory markers with overall survival (OS) and cancer-specific survival (CSS) was analyzed using Kaplan-Meier methods with log-rank test, followed by multivariate Cox proportional hazards model.The multivariate analysis indicated that among these inflammatory markers, NLR (< 2.0 vs. ? 2.0) was the only independent prognostic factor for poor OS [hazard ratio (HR) = 0.758, 95% confidence intervals (CI) = 0.598-0.960, P = 0.021)] and CSS (HR = 0.738, 95% CI = 0.573-0.950, P = 0.018). Among these inflammatory markers, the c-index and BIC value for NLR were maximum and minimum for OS, respectively. In addition, the c-index was higher and the BIC value was smaller in TNM staging combined with NLR compared with the values obtained in TNM staging alone.NLR is a superior indicator of prognosis compared with LMR, PLR, and PNI in CRC patients, and NLR may serve as an additional indicator based on the current tumor staging system.
Project description:To examine the prognostic role of inflammatory response biomarkers in sarcomatoid renal cell carcinoma (sRCC). From January 2004 to May 2015, 103 patients with sRCC were enrolled in this study. Preoperative neutrophil to lymphocyte ratio (NLR), derived neutrophil to lymphocyte ratio (dNLR), platelet to lymphocyte ratio (PLR) and lymphocyte to monocyte ratio (LMR) were analyzed. Besides well-established clinicopathological prognostic factors, we evaluated the prognostic value of this four markers using Kaplan-Meier method and Cox regression models. Additionally, a nomogram was established to predict the prognosis of sRCC patients. Elevated NLR, dNLR and PLR were significantly associated with worse overall survival (OS), nevertheless, elevated LMR showed an adverse effect on reduced OS. Multivariate analysis revealed that NLR (HR = 4.07, 95% CI = 1.50-11.00, P = 0.006) retained as independent factor. Incorporation of the NLR into a prognostic model including T stage, M stage, tumor necrosis and percentage of sarcomatoid generated a nomogram, which accurately predicted OS for sRCC patients. Preoperative NLR may serve as a potential prognostic biomarker in patients with sRCC and may help with clinical decisions about treatment intervention in clinical practice. The proposed nomogram can be used for the prediction of OS in patients with sRCC.
Project description:Purpose: Accumulative studies suggest the Glasgow prognostic score (GPS) and modified Glasgow prognostic score (mGPS) to be potential biomarkers; however, their prognostic value remains debatable. Our meta-analysis focused on assessing the accurate prognostic value of GPS and mGPS in patients with renal cell carcinoma (RCC) in addition to their effectiveness. Methods: To investigate the relationship between mGPS/GPS and prognostic value in patients with RCC, we performed a comprehensive retrieval of relevant articles from databases such as PubMed, Embase, Web of Science, and Medline up to February 1, 2020. STATA 15.0 software was used to obtain pooled hazard ratios (HRs) and their 95% confidence intervals for survival outcome, including overall survival (OS), recurrence-free survival (RFS), progression-free survival (PFS), and cancer-specific survival (CSS). A formal meta-analysis of these outcomes was performed. Results: In total, 2,691 patients with RCC were enrolled from 15 cohort studies. Higher GPS/mGPS (GPS/mGPS of 2) indicated poorer OS, CSS, PFS, and RFS in patients with RCC. Similarly, medium GPS/mGPS (GPS/mGPS of 1) also had a significant association with poorer OS, CSS, PFS, and RFS but superior than higher GPS/mGPS in these patients. Conclusion: GPS and mGPS are effective biomarkers for predicting prognosis in patients with RCC, and higher GPS and mGPS are closely related to inferior survival outcomes. More randomized controlled trials are needed to investigate the promising value of GPS/mGPS in the future.