The clinical use of neutrophil-to-lymphocyte ratio in bladder cancer patients: a systematic review and meta-analysis

The aim of this study was to evaluate the evidence regarding the neutrophil-to-lymphocyte ratio (NLR) as a factor predictive of survival in bladder cancer patients. A search of PubMed and Embase for relevant studies between January 1, 1966 and November 10, 2016 was performed with the terms [NLR OR (neutrophil lymphocyte ratio)] AND [(bladder cancer) OR BCa OR NMIBC OR MIBC]. Inclusion required studies published in English containing bladder cancer patients and evaluating NLR as a predictive factor. Endpoints of NLR and survival data were extracted for pooled analysis. The pooled results showed that an elevated NLR was a predictor for poor overall survival (OS) [hazard ratio (HR) = 1.19, 95% confidence interval (CI) 1.07–1.31], cancer-specific survival (CSS) (HR = 1.40, 95% CI 1.17–1.69), recurrence-free survival (RFS) (HR = 1.58, 95% CI 1.24–2.03) and progression-free survival (PFS) (HR = 1.33, 95% CI 1.19–1.49) in patients with bladder cancer. Heterogeneity between studies was observed for OS, CSS and RFS, but not for PFS. Publication bias was detected for all these outcomes. Our results showed that elevated NLR might be valuable as a predictive factor of survival in bladder cancer patients.     

Preoperative neutrophil-to-lymphocyte ratio as a prognosticator in early stage pancreatic ductal adenocarcinoma

Background

The neutrophil-to-lymphocyte ratio (NLR), which reflects the cancer-induced systemic inflammation response, has been proposed as a risk factor for poor long-term prognosis in cancer. We investigated the prognostic role of the NLR and the relationship between the NLR and TNM stage in pancreatic ductal adenocarcinoma (PDAC) patients following curative resection.

Validation of Neutrophil-to-lymphocyte Ratio in a Multi-institutional Cohort of Patients With T1G3 Non–muscle-invasive Bladder Cancer

Introduction

The aim of this multicenter study was to investigate the prognostic role of neutrophil-to-lymphocyte ratio (NLR) and to validate the NLR cutoff of 3 in a large multi-institutional cohort of patients with primary T1 HG/G3 non–muscle-invasive bladder cancer (NMIBC).

Prognostic impact of perioperative lymphocyte–monocyte ratio in patients with bladder cancer undergoing radical cystectomy

Various systemic inflammatory response biomarkers are associated with oncological outcome. We evaluated the superiority of prognostic predictive accuracy between neutrophil–lymphocyte ratio (NLR) and lymphocyte–monocyte ratio (LMR), and the prognostic significance of their perioperative change in patients with bladder cancer undergoing radical cystectomy (RC). We retrospectively analyzed 302 patients who had undergone RC in four institutions. Comparison of predictive accuracy between NLR and LMR was performed using receiver operating characteristic curve analysis. Overall survival (OS) and cancer-specific survival (CSS) were assessed with the Kaplan–Meier method and Cox regression analysis. Preoperative and postoperative LMR showed higher predictive accuracy for OS than NLR did (p?=?0.034). Applying a cutoff of 3.41, change in perioperative LMR stratified patients into three groups (low, intermediate, and high risk), showing a significant difference in OS and CSS (p?<?0.001, each), and pathological outcomes. Multivariable analyses for OS and CSS showed that poor changes in LMR (high risk) were an independent prognostic factor (hazard ratio 5.70, 95 % confidence interval 3.49–9.32, p?<?0.001; hazard ratio 4.53, 95 % confidence interval 2.63–7.82, p?<?0.001; respectively). Perioperative LMR is significantly associated with survival in patients with bladder cancer after RC, and it is possibly superior to NLR as a prognostic factor.     

Prognostic value of the neutrophil-to-lymphocyte ratio for overall and disease-free survival in patients with surgically treated esophageal squamous cell carcinoma

Although increasing evidence indicates that cancers are associated with inflammation, the prognostic role of the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) in patients with esophageal squamous cell carcinoma remains controversial. We determined the prognostic roles of NLR and PLR in patients with esophageal squamous cell carcinoma who underwent surgical treatment. We retrospectively reviewed 119 patients with esophageal squamous cell carcinoma who underwent surgical resection and complete lymph node dissection from 2004 to 2012. The preoperative NLR and PLR were measured. The patients included 112 (94.1 %) males (mean age, 63.64?±?8.42 years) of whom 37 (31.1 %) were pathological stage I, 33 (27.7 %) were stage II, and 49 (41.2 %) were stage III. The median follow-up period was 28.68 months. Recurrence was reported in 48 (40.3 %) patients. Mean NLR and PLR were 2.35?±?1.39 and 140.77?±?70.47, respectively. A multivariate analysis revealed that NLR was a risk factor for disease-free survival (DFS) (hazard ratio [HR], 1.194; p?=?0.031) and overall survival (OS) (HR, 1.230; p?=?0.011), whereas PLR was not a risk factor for DFS or OS. The 3-year OS rates were 51.0 % in low-NLR (<2.97) patients and 17.4 % in high-NLR (≥2.97) patients (p?=?0.007). Akaike’s information criterion decreased when the NLR was included in the multivariate model compared to the multivariate model without NLR. A high NLR was a significant prognostic factor for OS and DFS in patients with surgically treated esophageal squamous cell carcinoma, whereas PLR showed no prognostic significance.     

Significance of blood neutrophil-to-lymphocyte ratio for prognostic stratification of patients with gastroesophageal junction adenocarcinoma in the era of the 8th edition of the American Joint Committee on Cancer (AJCC8) staging

The prognosis of patients with gastroesophageal junction (GOJ) adenocarcinoma depends mainly on the clinical staging, as described by the new AJCC8 (American Joint Committee on Cancer 8th edition). Evidence suggests that peripheral blood neutrophil-to-lymphocyte ratio (NLR) may be of prognostic significance in patients with upper gastrointestinal cancers. We examined the prognostic significance of NLR in the era of the new AJCC8 staging system. In this single-centre cohort study, retrospective data on patients with operable GOJ adenocarcinoma treated with perioperative chemotherapy were analysed. The prognostic significance of baseline NLR in combination with AJCC8 clinical staging and other patient characteristics was examined for both time-to-progression (TTP) and overall survival (OS). Of 316 patients, 245 (77.5%) underwent radical surgery. Fifty-one patients (16.2%) developed unresectable disease due to early disease progression. NLR was the only baseline factor independently associated with the development of early disease progression. AJCC8 clinical staging was significantly associated with TTP and OS. In addition, NLR ≥ 3 was predictive of poorer TTP (p = 0.001) and OS (p = 0.002), confirmed in multivariate Cox-regression analysis. NLR ≥ 3 was prognostic, especially in patients with clinical stage III for TTP (p = 0.006) and OS (p = 0.025) and in patients with clinical stage IVA for OS (p = 0.017). NLR significantly improved the prognostic classification of patients by different AJCC8 clinical stages, with a c-index improved from 0.554 to 0.592 (p < 0.001). NLR was confirmed to be an independent prognostic factor in this cohort and could be used in combination with AJCC8 clinical staging to improve the baseline prognostic stratification of patients with newly diagnosed resectable GOJ adenocarcinoma.     

Prognostic significance of preoperative inflammatory response biomarkers in patients undergoing curative thoracoscopic esophagectomy for esophageal squamous cell carcinoma

Background

Recent studies have revealed significant relationships between the lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) and survival in various cancers. The purpose of this study was to confirm whether the LMR, NLR, and PLR have prognostic values, independent of clinicopathological criteria, in patients undergoing curative resection for esophageal cancer.

Prognostic significance of the ratio of absolute neutrophil to lymphocyte counts for breast cancer patients with ER/PR-positivity and HER2-negativity in neoadjuvant setting

The aim of this study was to determine the predictive or prognostic impact of absolute neutrophil count/absolute lymphocyte count ratio (NLR) in breast cancer patients with estrogen receptor/progesterone receptor (ER/PR)-positive and human epidermal growth factor receptor 2 (HER2)-negative subtype who have received neoadjuvant chemotherapy (NAC). We performed retrospective analysis of 157 patients with primary breast cancer with ER/PR-positive and HER2-negative subtype who were treated with NAC, followed by definitive surgical resection. The median follow-up after surgery was 21 months (range, 1–108 months). On univariate analysis, high NLR (>2.25) correlated with poorer recurrence-free survival (RFS) and overall survival (OS) (P?=?0.001 and P?P?=?0.001 and P?HER2-negative subtype receiving NAC. The NLR provides additional prognostic information to choose suitable patients who might profit from further therapy.     

Pre-treatment neutrophil-to-lymphocyte ratio as predictor of adverse outcomes in patients undergoing radical cystectomy for urothelial carcinoma of the bladder

Background:

An elevated neutrophil-to-lymphocyte ratio (NLR) is associated with poor outcome in various tumours. Its prognostic utility in patients with urothelial carcinoma of the bladder (UCB) undergoing radical cystectomy (RC) is yet to be fully elucidated.

Methods:

A cohort of patients undergoing RC for UCB in a tertiary referral centre between 1992 and 2012 was analysed. Neutrophil-to-lymphocyte ratio was computed using complete blood counts performed pre-RC, or before neo-adjuvant chemotherapy where applicable. Time-dependent receiver operating characteristic curves were used to determine the optimal cutoff point for predicting recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). The predictive ability of NLR was assessed using Kaplan–Meier analyses and multivariable Cox proportional hazards models. The likelihood-ratio test was used to determine whether multivariable models were improved by including NLR.

Results:

The cohort included 424 patients followed for a median of 58.4 months. An NLR of 3 was determined as the optimal cutoff value. Patients with an NLR⩾3.0 had significantly worse survival outcomes (5y-RFS: 53% vs 64%, log-rank P=0.013; 5y-CSS: 57% vs 75%, log-rank P<0.001; 5y-OS: 43% vs 64%, log-rank P<0.001). After adjusting for disease-specific predictors, an NLR ⩾3.0 was significantly associated with worse RFS (HR=1.49; 95% CI=1.12–2.0, P=0.007), CSS (HR=1.88; 95% CI=1.39–2.54, P<0.001) and OS (average HR=1.67; 95% CI=1.17–2.39, P=0.005). The likelihood-ratio test confirmed that prognostic models were improved by including NLR.

Conclusions:

Neutrophil-to-lymphocyte ratio is an inexpensive prognostic biomarker for patients undergoing RC for UCB. It offers pre-treatment prognostic value in addition to established prognosticators and may be helpful in guiding treatment decisions.     

Postoperative,but not preoperative,inflammation-based prognostic markers are prognostic factors in stage III colorectal cancer patients

Background Recent evidence suggests that both preoperative and postoperative inflammation-based prognostic markers are useful for predicting the survival of colorectal cancer (CRC) patients. However, associations between longitudinal changes in inflammation-based prognostic markers and prognosis are controversial.Methods The subjects of this study were 568 patients with stage III CRC between 2008 and 2014. Preoperative and postoperative neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), C-reactive protein/albumin ratio (CAR) and lymphocyte-to-C-reactive protein ratio (LCR) were calculated to assess the inflammatory state of subjects. Subjects were stratified into three groups for each marker: preoperatively low inflammatory state (normal group), preoperatively high but postoperatively low inflammatory state (normalised group) and persistently high inflammatory state (elevated group). Multivariable analyses for overall survival (OS) and recurrence-free survival (RFS) were performed to adjust for well-established clinicopathologic factors.Results For all assessed markers, the normalised group had a significantly better prognosis than the elevated group and a similar prognosis as the normal group for both OS and RFS.Conclusions Postoperative, but not preoperative, inflammation-based prognostic markers more accurately predict OS and RFS in patients with stage III CRC.Subject terms: Gastrointestinal cancer, Tumour biomarkers     

Neutrophil-to-lymphocyte ratio as a prognostic biomarker for men with metastatic castration-resistant prostate cancer receiving first-line chemotherapy: data from two randomized phase III trials

The derived neutrophil-to-lymphocyte ratio (dNLR) was prognostic for survival in men with metastatic castration-resistant prostate cancer receiving first-line chemotherapy in two randomized phase III trials. A high dNLR (≥2) was associated with shorter survival irrespective of the received treatment. This readily available biomarker may serve for risk stratification in future clinical trials.BackgroundThe neutrophil-to-lymphocyte ratio (NLR), a marker of host inflammation, has been associated with poor outcome in several solid tumors. Here, we investigated associations of the derived NLR (dNLR) and duration of initial androgen deprivation therapy (ADT) with survival of men with metastatic castration-resistant prostate cancer (mCRPC) receiving first-line chemotherapy.Patients and methodsData from the multinational randomized phase III studies VENICE and TAX327 included a total of 2230 men with mCRPC randomized to receive first-line chemotherapy, and were used as training and validation sets, respectively. Associations of dNLR and duration of initial ADT with overall survival (OS) were evaluated by multivariable Cox regression analysis in the training set stratified for performance status and treatment arm. The model was then tested in the validation set. Subsequently, we investigated the treatment effect of docetaxel on OS in subgroups according to dNLR and duration of initial ADT.ResultsIn the training set, both dNLR ≥median (2) and duration of initial ADT <median (15 months) were associated with increased risk of death [hazard ratio (HR) 1.29; 95% confidence interval (CI) 1.11–1.50,P < 0.001 and HR 1.41; 95% CI 1.21–1.64,P < 0.001, respectively] after adjustment for age, alkaline phosphatase, hemoglobin, and pain at baseline. In the validation set, dNLR remained an independent prognostic factor for OS (HR 1.43; 95% CI 1.20–1.70,P < 0.001), whereas duration of initial ADT was not (HR 1.16; 95% CI 0.97–1.37,P = 0.10). In subgroup analyses of the TAX327 study, docetaxel improved OS irrespective of dNLR and duration of initial ADT.ConclusionThe dNLR was prognostic for OS in men with mCRPC receiving first-line chemotherapy in two randomized phase III trials. A high dNLR (≥2) was associated with shorter survival irrespective of the received treatment. This readily available biomarker may serve for risk stratification in future clinical trials and could be incorporated into prognostic nomograms.Clinical Trials numberNCT00519285.     

Oncologic outcomes for open and laparoscopic radical nephroureterectomy in patients with upper tract urothelial carcinoma

Background

Oncologic benefits of laparoscopic radical nephroureterectomy (LNU) are unclear. We aimed to evaluate the impact of surgical approach for radical nephroureterectomy on oncologic outcomes in patients with locally advanced upper tract urothelial carcinoma (UTUC).

Methods

Of 426 patients who underwent radical nephroureterectomy at five medical centers between February 1995 and February 2017, we retrospectively investigated oncological outcomes in 229 with locally advanced UTUC (stages cT3-4 and/or cN+). The surgical approach was classified as open nephroureterectomy (ONU) or LNU, and oncologic outcomes, including intravesical recurrence-free survival (RFS), visceral RFS, cancer-specific survival (CSS), and overall survival (OS), were compared between the groups. The inverse probability of treatment weighting (IPTW)-adjusted Cox-regression analyses was performed to evaluate the impact of LNU on the prognosis.

Results

Of the 229 patients, 48 (21%) underwent LNU. There were significant differences in patient backgrounds, including preoperative renal function, lymph-node involvement, lymphovascular invasion, and surgical margins, between the groups. Before the background adjustment, intravesical RFS, visceral RFS, CSS, and OS were significantly inferior in the ONU group than in the LNU group. However, in the IPTW-adjusted Cox-regression analysis, no significant differences were observed in intravesical RFS (hazard ratio [HR], 0.65; P = 0.476), visceral RFS (HR, 0.46; P = 0.109), CSS (HR, 0.48; P = 0.233), and OS (HR, 0.40; P = 0.147).

Conclusion

Surgical approaches were not independently associated with prognosis in patients with locally advanced UTUC.

     

Clinical significance of microsatellite instability for stage II or III colorectal cancer following adjuvant therapy with doxifluridine

Microsatellite instability (MSI) is a molecular marker that can provide valuable prognostic information for colorectal cancer (CRC). However, the predictive role of the MSI status remains less clear than its role in prognostication due to mixed results from previous studies. Therefore, this study investigated the usefulness of the MSI status as a predictive factor for stage II or III CRC patients who received adjuvant doxifluridine therapy. Among 3030 patients with CRC who underwent surgical resection between 1997 and 2006, 564 patients were diagnosed with stage II or III, and adjuvant doxifluridine therapy was administered to 394 patients (70.0%). The MSI status was assessed using the markers BAT25 and BAT26, and samples with instability at both markers were scored as exhibiting high-frequency MSI (MSI-H). Among the 564 patients, 290 patients (51.4%) had stage II, and MSI-H was found in 41 patients (7.3%). With a median follow-up duration of 35.1 months (range, 0.5–135.2), the 5-year overall survival (OS) rate and relapse-free survival (RFS) rate were 87.5 and 76.2%, respectively. MSI-H showed a favorable survival trend for OS (P = 0.098) and significant survival benefit for RFS (P = 0.037) in all patients. In a univariate analysis, the doxifluridine-treated patients with MSI-H showed improved RFS compared to those with low or stable MSI (MSI-L/S) (P = 0.036), while the MSI status was not significantly associated with OS (P = 0.107). In a multivariate analysis, MSI-H was not significantly associated with RFS (Hazard ratio = 2.467, P = 0.125). In conclusion, this study confirmed the positive prognostic role of MSI-H. However, MSI-H patients with stage II or III CRC did not seem to benefit from doxifluridine adjuvant therapy.

     

Prognostic Impact of Preoperative Albumin–Globulin Ratio on Oncologic Outcomes in Upper Tract Urothelial Carcinoma Treated With Radical Nephroureterectomy

Purpose

To identify the impact of albumin–globulin ratio (AGR) on pathologic and survival outcomes in patients with upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU).

Prognostic significance of pretreatment neutrophil-to-lymphocyte ratio in older patients with metastatic cancer

BackgroundTreatment options for older patients with malignancies remain suboptimal. An accurate prognostic stratification could inform treatment decisions, which can potentially improve patient outcomes. Here, we sought to investigate whether the neutrophil-to-lymphocyte ratio (NLR) may have prognostic significance in patients with metastatic malignant tumors, with a special focus on older individuals.MethodsWe retrospectively reviewed the clinical records of 3981 patients with histology-proven metastatic cancer who underwent radiotherapy between 2000 and 2013. The pretreatment NLR was determined within 7 days before treatment initiation. Patients aged ≥65 years were considered as older. We analyzed the prognostic significance of NLR for overall survival (OS) across all age groups.ResultsCompared with their younger counterparts, older patients showed a higher NLR (P < 0.001) and a lower OS (P < 0.001). Multivariate analysis revealed that a pretreatment NLR below the median was an independent favorable predictor of OS in both older (hazard ratio [HR]: 0.669, 95.0% CI: 0.605–0.740; P < 0.001) and younger patients (HR: 0.704; 95.0% CI: 0.648–0.765; P < 0.001). Regardless of age, patients who underwent systemic therapy showed more favorable OS, especially when NLR was low. In the older subgroup, the OS of patients with a low pretreatment NLR who did not undergo systemic therapy and of those with high pretreatment NLR who underwent systemic therapy was similar.ConclusionA low pretreatment NLR predicts a more favorable OS in older patients with metastatic cancer. The most favorable OS was observed in patients with a low pretreatment NLR who received systemic therapy.     

Pre-treatment neutrophil to lymphocyte ratio as a prognostic marker to predict chemotherapeutic response and survival outcomes in metastatic advanced gastric cancer

Background

Several studies have shown that the neutrophil to lymphocyte ratio (NLR) in peripheral blood is a prognostic factor of various cancers. However, there is limited information on the clinical and prognostic significance of NLR in patients with metastatic advanced gastric cancer (AGC). Therefore, we examined whether the NLR can be used as a prognostic marker for predicting chemotherapeutic response and survival outcomes in metastatic AGC patients who are receiving palliative chemotherapy.

Method

A total of 268 patients diagnosed with metastatic AGC were enrolled. NLR was calculated from complete blood cell count taken before the first chemotherapy treatment. Patients were divided into two groups according to the median value of NLR: a high NLR group and a low NLR group.

Result

The median follow-up period was 340 days (range 72–1796 days) and median NLR was 3.06 (range 0.18–18.16). The high NLR group (NLR >3.0) contained 138 patients and the low NLR group (NLR ≤3.0) contained 130 patients. Low NLR group patients had a significantly higher chemotherapeutic disease control rate (90.0 % vs. 80.4; P = 0.028), and longer progression-free survival (PFS) and overall survival (OS) than the high NLR group patients (186 vs. 146 days; P = 0.001; 414 vs. 280 days; P < 0.001, respectively). In multivariate analysis, NLR showed a significant association with PFS (HR 1.478; 95 % CI 1.154–1.892; P = 0.002) and OS (HR 1.569; 95 % CI 1.227–2.006; P < 0.001).

Conclusion

Pretreatment NLR is a useful prognostic marker in patients with metastatic AGC who are undergoing palliative chemotherapy.     

Colorectal obstruction is a potential prognostic factor for stage II colorectal cancer

Background

Obstructive colorectal cancer (CRC) is an emergency situation with high morbidity and mortality, but long-term outcomes of stage II/III obstructive CRC remain unclear. The aim of this study was to evaluate prognostic factors, including colorectal obstruction.

Methods

Data were retrospectively reviewed from consecutive patients with stage II/III CRC who underwent curative surgery between January 2007 and December 2011 at two Japanese institutions. We analyzed overall survival (OS) and relapse-free survival (RFS), according to various prognostic factors including colorectal obstruction.

Results

In total, 979 patients with stage II/III CRC were identified for this study. Among these 979 patients, 94 patients showed colorectal obstruction (9.6%). In both stage II and stage III CRCs, colorectal obstruction showed significantly poorer OS and RFS compared to non-obstruction (5-year OS, obstruction vs. non-obstruction, stage II: 65.9 vs. 86.5%, P?=?0.002; stage III: 55.9 vs. 73.6%, P?=?0.007) (5-year RFS, obstruction vs. non-obstruction, stage II: 59.2 vs. 77.8%, P?=?0.008; stage III 31.3 vs. 56.3%, P?=?0.001). Multivariate analysis demonstrated colorectal obstruction as a significant independent and poor prognostic factor in terms of both OS (hazard ratio (HR) 2.469; 95% CI 1.339–4.545; P?=?0.004) and RFS (HR 1.992; 95% CI 1.160–3.425; P?=?0.012) for stage II CRC, as well as pT4 stage. On multivariate analysis for stage III CRC, colorectal obstruction was a significant predictor of poor RFS (HR 1.626; 95% CI 1.070–2.469; P?=?0.023), but not poor OS.

Conclusions

Colorectal obstruction is an independent poor prognostic factor for stage II CRC. Adjuvant chemotherapy might be feasible for stage II CRC with colorectal obstruction.

     

Prognostic role of neutrophil‐to‐lymphocyte ratio in colorectal cancer: A systematic review and meta‐analysis

The prognostic role of inflammation index like neutrophil‐to‐lymphocyte ratio (NLR) in colorectal cancer (CRC) remains controversial. We conduct a meta‐analysis to determine the predictable value of NLR in the clinical outcome of CRC patients. The analysis was carried out based on the data from 16 studies (19 cohorts) to evaluate the association between NLR and overall survival (OS) and progression‐free survival (PFS) in patients with CRC. In addition, the relationship between NLR and clinicopathological parameters was assessed. Hazard ratio (HR) or odds ratio (OR) with its 95% confidence interval (CI) was used as the effect size estimate. Our analysis results indicated that elevated pretreatment NLR predicted poorer OS (HR: 1.813, 95% CI: 1.499–2.193) and PFS (HR: 2.102, 95% CI: 1.554–2.843) in patients with CRC. Increased NLR is also significantly associated with the poorer differentiation of the tumor (OR: 1.574, 95% CI: 1.226–2.022) and higher carcino‐embryonie antigen (CEA) level (OR: 1.493, 95% CI: 1.308–1.705). By these results, we conclude that NLR gains a prognostic value for patients with CRC. NLR should be monitored in CRC patients for rational stratification of the patients and adjusting the treatment strategy.     

The role of <Emphasis Type="Italic">LINE</Emphasis>-<Emphasis Type="Italic">1</Emphasis> methylation in predicting survival among colorectal cancer patients: a meta-analysis

Background

The prognostic value of long interspersed nucleotide element-1 (LINE-1) methylation in patients with colorectal cancer (CRC) remains uncertain. We have therefore performed a meta-analysis to elucidate this issue.

Methods

The PubMed and Web of Science databases were searched for studies published up to 30 June 2016 which reported on an association between LINE-1 methylation and overall survival (OS), disease-free survival (DFS), or cancer-specific survival (CSS) among CRC patients. The reference lists of the identified studies were also analyzed to identify additional eligible studies. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled using the fixed-effects or the random-effects model. Stratification analysis and meta-regression analysis were performed to detect the source of heterogeneity. Analyses of sensitivity and publication bias were also carried out.

Results

Thirteen independent studies involving 3620 CRC patients were recruited to the meta-analysis. LINE-1 hypomethylation was found to be significantly associated with shorter OS (HR 2.92, 95% CI 2.20–3.88, p < 0.001) and DFS (HR 2.18, 95% CI 1.46–3.27, p < 0.001), as well as unfavorable CSS (HR 1.96, 95% CI 1.35–2.85, p < 0.001). No heterogeneity was found among the studies evaluating the associations between LINE-1 hypomethylation and OS or DFS, with the exception being CSS. Moreover, meta-regression analysis suggested that one of the contributors to between-study heterogeneity on the association between LINE-1 methylation and CSS was statistical methodology. The subgroup analysis suggested that the association in studies using the Cox model statistical method (HR 2.76, 95% CI 1.90–4.01, p < 0.001) was stronger than that in studies using the Log-rank test (HR 1.41, 95% CI 1.07–1.87, p = 0.015).

Conclusions

The results of this meta-analysis suggest that LINE-1 methylation is significantly associated with the survival of CRC patients and that it could be a predictive factor for CRC prognosis.

     

Baseline neutrophil–lymphocyte ratio (NLR) is associated with survival and response to treatment with second-line chemotherapy for advanced prostate cancer independent of baseline steroid use

We investigated the value of the neutrophil–lymphocyte ratio (NLR) in patients with CRPC treated with chemotherapy in the phase III TROPIC trial. High NLR was associated with worse survival (OS) and reduced PSA and radiographic response. Conversion (high to low NLR) was associated with improved OS. NLR can be a useful biomarker to assess prognosis and response to treatment.BackgroundThe neutrophil–lymphocyte ratio (NLR), proposed as an indicator of cancer-related inflammation, has known prognostic value in prostate cancer. We examine its association with survival (OS) and response in patients treated with second-line chemotherapy.MethodsWe analysed patients with metastatic castration-resistant prostate cancer (mCRPC) treated in the TROPIC trial, evaluating cabazitaxel versus mitoxantrone. Cox regression models were used to investigate the association of baseline NLR (BLNLR) with OS and the significance of a change in NLR count with treatment. Logistic regression models were used to determine the association of BLNLR counts with prostate specific antigen (PSA) and RECIST responses. The optimal NLR cut-off was established based on the concordance index of different values.ResultsData from 755, 654 and 405 patients was available for OS, PSA and RECIST response analysis respectively. Median OS was 14.0 months [95% confidence interval (CI) 13.2–14.8]. Median NLR was 2.9 (IQR: 1.9–5.1). BLNLR was associated with survival (HR 1.5, 95% CI 1.1–2.1,P = 0.011) in multivariable analysis (MVA) independently of variables included in the Halabi nomogram, treatment arm and corticosteroid use. The optimal cut-off for a dichotomous NLR was selected at 3.0 based on its higher c-index related to survival. BLNLR ≥3.0 was associated with lower PSA response (40.1% versus 59.9%;P < 0.001) and RECIST response (7.7% versus 15.6%,P = 0.022) in MVA. Conversion from high (≥3) to low (<3) NLR was associated with improved survival (HR 0.66; 95% CI 0.51–0.85;P = 0.001) and higher PSA response rates (66.4% versus 33.6%;P = 0.000). Use of corticosteroids at baseline did not modify the association between NLR and survival.ConclusionsNLR is a valid prognostic biomarker in CRPC and is associated with survival, PSA and RECIST responses in patients treated with second-line chemotherapy. Changes in NLR counts with treatment may indicate benefit. NLR prognostic value is independent of prior use of corticosteroids.ClinicalTrials.govNCT00417079.