High Platelet-to-lymphocyte Ratio Research Articles

The Association between Blood Cell Counts and Thrombotic Events in Japanese Patients with Polycythemia Vera: A Retrospective Database Study

Introduction: The primary goal of therapy for polycythemia vera (PV) is the prevention of thrombotic events (TE). Several studies conducted in the United States and Europe have indicated that elevated hematocrit (HCT) and white blood cell count (WBC) are associated with an increased risk of TE in patients with PV. However, these associations have not been reported in Japanese patients with PV. In this study, we aimed to evaluate the association between blood cell counts and TE in Japanese patients with PV using a real-world database. Methods: This retrospective cohort study was performed using the RWD database (Real World Data Co., Ltd) which is a large-scale electronic medical records database collected between 1987 and 2022. Patients who met the following criteria were included: 1) PV (ICD-10, D45) initially diagnosed at ≥18 years of age (index date is the date of initial diagnosis); 2) at least one hospital visit within 180 days after the index date; 3) no history of myelofibrosis or acute myeloid leukemia before the index date; 4) ≥2 HCT measurements since the index date, and 5) no phlebotomy or hydroxyurea therapy before the index date. The outcome was the time from the index date to the first TE or to the last day of follow-up for censored cases. The primary analysis evaluated the association between HCT and TE using a univariate time-dependent Cox proportional hazards (PH) model. In the secondary analysis, WBC, platelet count (PLT), hematocrit-to-hemoglobin ratio (HHR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), basophil-to-lymphocyte ratio (BLR), phlebotomy were used as time-dependent exposures, whereas age, sex, risk factors for cardiovascular disease, and Barbui's risk stratification were used as baseline variables to evaluate their associations with TE. A multivariable-adjusted Cox PH model with each time-dependent exposure and baseline variables was also conducted. Results: Of 1,796 patients diagnosed with PV, 1,259 met the eligibility criteria. The median age (interquartile range [IQR]) of the patients was 66 (55-74) years; 63.1% were male; 23.1% had a history of TE; 71.9% were in the high-risk group according to Barbui's stratification; and 37.5% had one or more comorbidities (diabetes mellitus, hypertension, or dyslipidemia). The median (IQR) follow-up period was 1.3 (0.1-4.6) years. Of the 1259 patients, 45.0% (566) developed TE during the follow-up period and the incidence rate was 14.4 (95% confidence interval [CI], 13.2-15.6) per 100 person-years. The median HCT at the time of the first TE was 49.5% (HCT <45%: 157 [32.4%], ≥45%: 328 [ 67.6%]); the median WBC and PLT were 10.2×10 9/L and 335.0×10 9/L, respectively. In the primary analysis, the hazard ratio (HR) and 95% CI for TE in patients with HCT ≥45% compared with patients with HCT <45% was 0.96 (0.77-1.21), with no significant association. Age, history of TE and Barbui's risk stratification were associated with the risk of TE (HR [95% CI]: 1.02 [1.01-1.03], 1.25 [1.02-1.54], 1.78 [1.39-2.27], respectively). Compared with patients with WBC <10×10 9/L, patients with WBC ≥15×10 9/L and 10-≤15×10 9/L were associated with an increased TE risk (multivariable-adjusted HR [95% CI]: 2.10 [1.65-2.68] and 2.05 [1.59-2.64], respectively). Compared with patients with PLT <400×10 9/L, patients with PLT ≥1000×10 9/L, 600-<1000×10 9/L, and 400-<600×10 9/L were associated with an increased TE risk (multivariable-adjusted HR [95% CI]: 1.98 [1.35-2.89], 2.18 [1.67-2.85], and 1.59 [1.20-2.12], respectively). High HHR, NLR, PLR, BLR values and phlebotomy were associated with an increased TE risk (multivariable-adjusted HR [95% CI]: 3.93 [2.37-6.51], 1.05 [1.03-1.06], 2.33 [1.46-3.73], 4.92 [2.27-10.71] and 1.99 [1.36-2.91]). Conclusions: This is the largest and first real-world cohort study to demonstrate the association between blood cell counts and TE in Japanese patients with PV. The results did not show that maintaining an HCT <45% is associated with a reduced risk of TE in Japanese patients with PV. In contrast, the risk of TE was associated with phlebotomy, Barbui's risk stratification, and elevated WBC, PLT, HHR, PLR, and BLR. These data support the need to consider blood cell counts other than HCT in treatment strategies for Japanese patients with PV in clinical practice. Furthermore, follow-up studies are required to identify the specific levels of blood cell counts associated with an increased TE risk.

Pretreatment PLR Is Preferable to NLR and LMR as a Predictor in Locally Advanced and Metastatic Bladder Cancer.

Advanced bladder cancer (BC) is associated with an inflammatory nature and poor prognosis Inflammatory biomarkers are potential predictors in BC. We conducted a study to assess the prognostic value of the pretreatment neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) in advanced bladder cancer. A total of 226-patients with muscle-invasive BC (MIBC) were included. Overall (OS) and progression-free survival were estimated using the Kaplan-Meier method and the log-rank test was used for comparison. Univariate and multivariate Cox proportional hazard models were used to determine NLR, PLR, and LMR association with OS. Our patients' median progression-free survival and OS were 12.18 and 15.54 months, respectively. Receiver operating characteristic analysis revealed cut-off values for our chosen inflammatory markers. The patients with high NLR or PLR had inferior median OS compared to their counterparts with lower ratios for both (NLR: 22.51 vs. 9.84 months, respectively, p≤0.001; PLR: 17.68 vs. 14.08 months, respectively, p=0.08). Meanwhile, patients with low LMR had inferior median OS compared to patients with higher LMR (LMR: 20.14 months vs. 10.55 months, respectively, p<0.001). The multivariate Cox regression analysis identified a high PLR as an independent predictive factor of worse OS (hazard ratio=2.774, 95% confidence interval=1.486-5.178, p=0.001) but not NLR or LMR. PLR, C-reactive protein-to-albumin ratio, and serum LDH levels, but not NLR and LMR, may function as independent predictors in patients with advanced BC prior to systemic treatment.

Prognostic significance of platelet-to-lymphocyte ratio (PLR) in patients with breast cancer treated with neoadjuvant chemotherapy: a meta-analysis

ObjectivePlatelet-to-lymphocyte ratio (PLR), known as a key systemic inflammatory parameter, has been proved to be associated with response to neoadjuvant therapy in breast cancer (BC); however, the results remain controversial....

Prognostic Value of The Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, and Platelet Count for Platinum-Sensitive Recurrent Epithelial Ovarian Cancer.

To study the prognostic value of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and platelet count in patients with platinum-sensitive recurrent epithelial ovarian cancer (PS-ROC). This was a retrospective study on a database of platinum-sensitive recurrent epithelial ovarian cancer patients who received treatment at HRH Princess Maha Chakri Sirindhorn Medical Center (MSMC) between January 2010 and December 2020. The patients' demographic data, surgical factors, pathological factors, laboratory findings, and response to treatment were reviewed from the patients' medical records. Survival analysis was conducted using the Kaplan-Meier survival estimate and Cox regression model. In total, 56 patients were recruited in this study. The median overall survival (OS) and progression-free survival (PFS) were 33 (95%CI 23-43) and 11 (95%CI 8-16) months, respectively. Survival analysis showed a high PLR was associated with decreased OS compared with low value but no significant difference in PFS. High NLR was associated with poor OS and PFS. There was no association between the platelet count and survival outcome (OS and PFS). In the multivariable Cox regression analysis, the NLR, PLR, and platelet count were not significant prognostic factors for survival outcome. However, low hemoglobin and a decreased disease-free interval were significantly associated with poor PFS. A white blood cell count (WBC) ≥ 8,000 cells/mm3 was a poor prognostic factor for overall survival (Adjusted HR 7.64; 95%CI: 2.21-26.42; p-value = 0.001). The NLR, PLR, and platelet count were not associated with both the OS or PFS in patients with PS-ROC. However, the WBC level is an easy, readily available, and economical way to predict survival outcomes in PS-ROC patients and may help physicians to tailor therapeutic interventions in the future.

Evaluation of Neutrophil to Lymphocyte Ratio and Platelet to Lymphocyte Ratio in Covid-19 Patients Treated with Tocilizumab Due to Cytokine Storm

Background/Aims: There is a significant increase in proinflammatory cytokine levels in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients entering cytokine storm. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), also increase in inflammatory diseases. The aim was to evaluate the NLR and PLR of coronavirus disease 2019 (COVID-19) patients receiving tocilizumab (TCZ) due to cytokine storm. Materials and Methods: In this retrospective, cross-sectional study conducted in between March and December 2020, adult patients with laboratory-confirmed COVID-19 were analyzed Results; The mean age of 519 patients included in the study was 61.6 ± 17.0 years, with male predominance (64.7%). 70.7% of patients had at least one type of comorbidity and the most common comorbid conditions were chronic obstructive pulmonary disease (45.9%) and asthma (28.7%). 399 patients who were given TCZ (group 1) and 120 patients who were not given TCZ (group 2) were evaluated. Compared with group 2, group 1 had more male predominance and they were older (p&amp;lt;0.001). The mortality rate, which was found to be 48.6% in group 1, was approximately twice as high in the intensive care unit (ICU). NLR and PLR were significantly higher and lymphopenia was more prominent in group 1, especially in ICU patients than group 2 (p&amp;lt;0.001). Conclusion: High NLR, PLR and lymphopenia was more common in critically ill Covid-19 patients. Therefore, they may be used as a marker to predict poor prognosis. It can be suggested to treat these patients more aggressively in the initial period.

Prognostic value of systemic inflammation response index in hepatoblastoma patients receiving preoperative neoadjuvant chemotherapy.

Inflammation is closely associated with tumor development and patient prognosis. The objective of this study is to assess the prognostic value of the preoperative inflammatory indexes in pediatric hepatoblastoma patients who receive neoadjuvant chemotherapy. A retrospective analysis was performed on clinical and pathological data of 199 hepatoblastoma patients who underwent hepatectomy with preoperative neoadjuvant chemotherapy from January 2015 to June 2020. The receiver operating characteristic curve was used to evaluate the prognostic value of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI) in predicting OS and EFS. Patients were grouped based on optimal cutoff values of preoperative inflammatory indexes. Survival rates were calculated using the Kaplan-Meier method, and survival outcomes were compared between groups using the log-rank test. Univariate and multivariate Cox proportional hazards regression models were used to identify independent prognostic factors, and a nomogram was constructed using R software to predict the probability of OS. The receiver operating characteristic curve showed prognostic value for OS, not EFS, in preoperative inflammatory indexes. Patients were categorized into low/high groups: SII ≤ 266.70/higher, NLR ≤ 1.24/higher, PLR ≤ 85.25/higher, and SIRI ≤ 0.72/higher. High NLR, PLR, SII, and SIRI groups had significantly lower 5-year OS than their low counterparts (all p-value < 0.05). The Cox analysis identified four independent prognostic factors: SIRI (HR=2.997, 95% CI: 1.119-8.031), microvascular invasion (HR=2.556, 95% CI: 1.14-5.73), the post-treatment extent of disease (POSTTEXT) staging (IV vs. I: HR=244.204, 95% CI:11.306-5274.556), and alpha-fetoprotein (>100 ng/ml: HR=0.11, 95% CI: 0.032-0.381) for hepatoblastoma patients with neoadjuvant chemotherapy. High SIRI group had more patients with adverse NLR, SII, and POSTTEXT III (all p-value < 0.05). Independent prognostic factors led to an OS nomogram with a concordance index of 0.85 (95% CI: 0.78-0.91, p-value = 1.43e-27) and the calibration curve showed a good fit between the prediction curve and the true curve. SIRI is an independent prognostic factor of hepatoblastoma patients receiving neoadjuvant chemotherapy. The OS nomogram based on SIRI, POSTTEXT staging, MiVI, and AFP can be used to assess the prognosis of those patients.

Predictive factors for response to neoadjuvant chemotherapy: inflammatory and immune markers in triple-negative breast cancer.

Tumor-infiltrating lymphocytes (TILs) predict response to neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC) patients. However, the TIL level can be determined at a few facilities. By contrast, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are easily and objectively determined from the results of full blood counts. We conducted a retrospective study to investigate whether TILs, NLR, and PLR predict NAC efficacy and whether NLR and PLR could be surrogate markers for TILs in TNBC. Of the 266 patients diagnosed with TNBC between 2013 and 2019, 66 who underwent radical surgery after sequential administration of anthracycline and taxane as NAC were included in the study. TILs, NLR, and PLR were evaluated as predictors of pathologic complete response (pCR) using cutoff values determined from receiver operating characteristic curves. The cutoff values of TILs, NLR, and PLR were 20%, 2.6, and 180, respectively. High TIL level was associated with low NLR (P = 0.01) and low PLR (P = 0.01). High TIL level (odds ratio [OR] 4.28 [95% CI 1.40-13.1]; P = 0.01), low NLR (OR 5.51 [95% CI 1.60-18.9]; P = 0.01), and low PLR (OR 3.29 [95% CI 1.13-9.57]; P = 0.03) were associated with pCR. Low NLR predicted pCR independently (OR 6.59 [95% CI 1.45-30.0]; P = 0.01). TILs, NLR, and PLR predicted NAC efficacy against TNBC. TIL level was associated with NLR and PLR. NLR was an independent predictive factor and may be a useful surrogate marker for TILs when predicting pCR.

Early changes of platelet‑lymphocyte ratio correlate with neoadjuvant chemotherapy response and predict pathological complete response in breast cancer.

Markers with inflammatory properties, such as the ratio of neutrophils to lymphocytes and the platelet-to-lymphocyte ratio (PLR), have been documented as potential indicators for predicting pathologic complete response (pCR) following neoadjuvant chemotherapy (NACT) in cases of breast cancer. However, whether early changes of PLR (ΔPLR) during NACT can predict pCR has not been reported. A total of 257 breast cancer patients who underwent NACT were retrospectively analyzed. PLR was calculated by evaluating the complete blood cell counts prior to NACT and following two cycles of NACT. The analysis focused on the association between changes in PLR and the response to chemotherapy, as well as the association with pCR. Patients who stayed in or changed to the low PLR level subgroup after two cycles of NACT exhibited a superior response to chemotherapy, in contrast to those who stayed in or changed to the high PLR level subgroup. Of the 257 patients, 75 (29.1%) achieved a pCR after NACT. In the multivariate analysis, there was a significant association between ΔPLR and pCR, whereas pre-treatment and post-treatment PLR did not show any significant association. In multivariate analysis, patients who had a ΔPLR <0 had a notably higher rate of pCR compared with patients with a ΔPLR ≥0. It was concluded that ΔPLR, rather than pre-treatment or post-treatment PLR, is associated with pCR. This suggested that the early changes of PLR after two cycles of NACT might serve as a more accurate predictor for chemotherapy response and pCR in breast cancer.

A high platelet-to-lymphocyte ratio predicts all-cause mortality and cardiovascular mortality in maintenance hemodialysis patients

Purpose The aim of this study was to further assess whether the platelet-to-lymphocyte ratio (PLR) is independently associated with all-cause mortality and cardiovascular mortality in maintenance hemodialysis (MHD) patients. Methods From January 1, 2014, to December 31, 2014, patients undergoing regular hemodialysis in the Blood Purification Center of the General Hospital of Northern Theatre Command were retrospectively selected. A total of 303 MHD patients were enrolled in accordance with the inclusion and exclusion criteria. For each patient, the endpoint of follow-up was either death or December 31, 2021. The primary endpoints were all-cause and cardiovascular death. A receiver operating characteristic (ROC) curve was drawn to detect the predictive ability of PLR, and the optimal critical value of PLR was determined to be 107.57. Kaplan–Meier curves and Cox proportional analysis were used to assess the prognostic value of PLR. We used the same method to evaluate the correlation between the neutrophil-to-lymphocyte ratio (NLR) and the prognosis of MHD patients. Results At the end of follow-up, 128 MHD patients had progressed to all-cause death, and 73 MHD patients had progressed to cardiovascular death. In multivariate Cox regression, both the high PLR group and the high NLR group were independently associated with all-cause mortality (HR 2.608, 95% CI 1.579–4.306, p < .001 vs. HR 1.634, 95% CI 1.023–2.610, p = .04). Only high PLR expression was associated with cardiovascular mortality (HR 3.379, 95% CI 1.646–6.936, p = .001). Conclusions High PLR levels can independently predict all-cause and cardiovascular mortality in MHD patients.

The Predictive Value of the Preoperative Systemic Inflammatory Response Indices in Non–Organ-Confined Disease in Upper Urinary Tract Urothelial Carcinoma

Purpose: This study aims to evaluate the systemic inflammatory response indices (SII) for the prediction of the non–organ-confined (non-OC) disease in upper urinary tract urothelial carcinoma (UTUC) patients.Materials and Methods: From March 2010 to March 2020, patients who underwent radical nephroureterectomy (RNU) in a single tertiary center were retrospectively reviewed. Tumor location, multifocality, hydronephrosis on preoperative imaging, and preoperative SII, including C-reactive protein-to-albumin ratio (CAR), neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio (PLR) were used for analysis. Non-OC defined by locally advanced (pT3-4) or node-positive disease (pN1-2) in pathologic examination. Multivariable logistic regression was used for determining independent predictive markers of non-OC disease. Factors associated with locally advanced (pT3-4), and node-positive (pN1-2) disease were also analyzed.Results: Overall, 711 UTUC patients who underwent RNU, without neoadjuvant chemotherapy, were analyzed. The average age was 68.6±9.9 years and 507 patients were male. Non-OC disease was 36.8% (262 of 711); specifically, 35.9% (255 of 711) was locally advanced and 7.2% (51 of 771) was node-positive disease. Multivariable analysis demonstrated hydronephrosis (odds ratio [OR], 1.46; 95%confidence interval [CI], 1.06–2.01; p=0.02), high PLR (OR, 1.45; 95% CI, 1.05–2.01; p=0.03), and high CAR (OR, 2.56; 95% CI, 1.79–3.66; p&lt;0.01) were independent predictive markers non-OC disease. Hydronephrosis (p=0.01), high PLR (p=0.02), and high CAR (p&lt;0.01) were predictive markers for locally advanced disease, and multifocal tumor (p&lt;0.01) and high CAR (p&lt;0.01) were predictive markers for node-positive disease.Conclusions: CAR is a novel important factor for predicting any subtype of non-OC disease among SII. Large scale, multicenter studies should validate the clinical role of CAR.

Positive regulatory loop of platelet-derived growth factor DD-induced STAT3 activation is associated with poor prognosis in advanced urothelial carcinoma

Immune checkpoint inhibitor (ICI) therapy has been established for patients with advanced urothelial cancer (UC). The necessity of overcoming resistance to ICIs and identifying a predictive factor for the same has been highlighted, such as the assessment of combination therapy with other targeted drugs and the characterization of molecular signatures in the tumor microenvironment. Recently, we reported that low hemoglobin (Hb) levels and a high platelet-to-lymphocyte ratio (PLR) were significantly associated with overall survival in patients with UC who did not benefit from pembrolizumab treatment. In the present study, we identified a possible link between these unfavorable prognostic indicators and PDGF-DD-induced STAT3 activation in UC. Overlapping patients between the high STAT3- or phosphorylated STAT3-positive score group (as assessed by immunohistochemistry) and low Hb levels or high PLR group (as assessed by blood tests) showed significantly worse outcomes after pembrolizumab treatment. Additionally, using the bladder cancer JMSU1 cell line, we demonstrated a possible positive regulatory loop between autocrine/paracrine PDGF-DD and STAT3 signaling. Therefore, we suggest that STAT3 inhibition and PDGF-DD detection in the tumor microenvironment might represent a potential therapeutic strategy to overcome resistance to pembrolizumab. Moreover, this can help identify patients with UC who could benefit from combination treatment.

A new scoring system with simple preoperative parameters as predictors of early recurrence of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) often recurs early after radical resection, and such early recurrence (ER) is associated with a poor prognosis. Predicting ER is useful for determining the optimal treatment. One hundred fifty-three patients who underwent pancreatectomy for PDAC were divided into an ER group (n = 54) and non-ER group (n = 99). Clinicopathological factors were compared between the groups, and the predictors of ER and prognosis after PDAC resection were examined. The ER group had a higher platelet count, higher platelet-to-lymphocyte ratio (PLR), higher preoperative CA19-9 concentration, higher SPan-1 concentration, larger tumor diameter, and more lymph node metastasis. The receiver operating characteristic (ROC) curve analysis identified cut-off values for PLR, carbohydrate antigen 19-9 (CA19-9), SPan-1, and tumor diameter. In the multivariate analysis, a high PLR, high CA19-9, and tumor diameter of >3.1 cm were independent predictors of ER after resection (all p < 0.05). When the parameter exceeded the cut-off level, 1 point was given, and the total score of the three factors was defined as the ER prediction score. Next, our new ER prediction model using PLR, CA19-9 and tumor diameter (Logit(p) = 1.6 + 1.2 × high PLR + 0.7 × high CA19-9 + 0.5 × tumor diameter > 3.1cm) distinguished ER with an area under the curve of 0.763, a sensitivity of 85.2%, and a specificity of 55.6%. ER after resection of PDAC can be predicted by calculation of a score using the preoperative serum CA19-9 concentration, PLR, and tumor diameter.

Blood inflammatory biomarkers in participants with idiopathic epiretinal membrane: A retrospective case series study.

The objective was to evaluate the levels of monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in patients with idiopathic epiretinal membrane (iERM). This retrospective case series study comprised of participants with iERM and participants with cataract. The values of MLR, NLR, PLR and from participants' peripheral blood were assessed among groups. The best cutoff value of MLR, NLR, and PLR in iERM was found by performing a receiver operating characteristic curve analysis and determining the optimum cutoff value for each variable. In total, 95 participants with iERM were included in the study group, and 61 participants with senile cataract were included as controls. The lymphocyte count in the iERM group was significantly lower than the control group (1.69 ± 0.63 vs. 1.95 ± 0.53, P = .003). The monocyte count in the iERM group was significantly higher than the control group (0.39 ± 0.11 vs. 0.31 ± 0.10, P < .001). The area under the curve of MLR, NLR, and PLR in differentiating patients with IERM and controls was 0.782, 0.645, and 0.657, respectively, according to receiver operating characteristic. The best cutoff value of MLR was > 0.18, with sensitivity and specificity of 74.7% and 75.4%, respectively. The NLR was > 2.06, with a sensitivity and specificity of 50.5% and 83.6%, respectively. The PLR was > 95.89, with a sensitivity and specificity of 86.3% and 41.0%, respectively. The findings of this study suggest that systemic inflammation may be associated with iERM. IERM patients may be prone to have high MLR, NLR, and PLR values.

Prognostic Values of Systemic Inflammatory Immunological Markers in Glioblastoma: A Systematic Review and Meta-Analysis.

Neutrophils are an important part of the tumor microenvironment, which stimulates inflammatory processes through phagocytosis, degranulation, release of small DNA fragments (cell-free DNA), and presentation of antigens. Since neutrophils accumulate in peripheral blood in patients with advanced-stage cancer, a high neutrophil-to-lymphocyte ratio can be a biomarker of a poor prognosis in patients with glioblastoma. The present study aimed to explore the prognostic value of the preoperative levels of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune inflammation index (SII), systemic inflammation response index (SIRI), and cell-free DNA (cfDNA) to better predict prognostic implications in the survival rate of glioblastoma patients. The meta-analysis was carried out according to the recommendations and standards established by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Databases of PubMed, EBSCO, and Medline were systematically searched to select all the relevant studies published up to December 2022. Poorer prognoses were recorded in patients with a high NLR or PLR when compared with the patients with a low NLR or PLR (HR 1.51, 95% CI 1.24-1.83, p < 0.0001 and HR 1.34, 95% CI 1.10-1.63, p < 0.01, respectively). Similarly, a worse prognosis was reported for patients with a higher cfDNA (HR 2.35, 95% CI 1.27-4.36, p < 0.01). The SII and SIRI values were not related to glioblastoma survival (p = 0.0533 and p = 0.482, respectively). Thus, NLR, PLR, and cfDNA, unlike SII and SIRI, appeared to be useful and convenient peripheral inflammatory markers to assess the prognosis in glioblastoma.

Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as prognostic biomarkers in limited-stage small-cell lung cancer: a meta-analysis.

Background: The role of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) as prognostic markers in limited-stage small-cell lung cancer (LS-SCLC) remains controversial. Methods: Using pooled hazard ratios (HR) with 95% CIs, we assessed the correlation of pre-treatment NLR and PLR with overall survival (OS) and progression-free survival (PFS) in LS-SCLC. Publication bias was assessed by Begg's and Egger's tests. Results: Ten studies were enrolled in our meta-analysis. Pooled analyses showed that pre-treatment high NLR was significantly associated with poor OS (HR: 1.80) and PFS (HR: 1.69) in LS-SCLC patients. High pre-treatment PLR was also associated with shorter OS (HR: 1.52) and PFS (HR: 1.39) in LS-SCLC patients. Conclusion: Our meta-analysis suggests that high pre-treatment NLR or PLR may be negatively related to OS and PFS in LS-SCLC.

Systemic inflammation markers ratio in heavily pretreated NSCLC patients treated with nivolumab.

e21188 Background: Inflammatory cells have important effects on tumor development. Systemicinflammation markers can be used as prognostic factors. Numerous studiesshown that high pretreatment neutrophil-to-lymphocyte ratio (NLR) and/or platelet-to-lymphocyte ratio (PLR) levels are potential prognostic predictors for poor progression-free survival (PFS) and overall survival (OS) in NSCLC patients receiving immunotherapy. Methods: We performed a cohort study of patients with metastatic or recurrent NSCLC treated with nivolumab monotherapy in second‐line or further‐line treatment in Clinical hospital centre Zagreb. Pre-treatment NLR and PLR were calculated by division of neutrophils and platelets by lymphocytes measured in peripheral blood. Patients were categorized in two sub-groups according to their NLR and PLR values. In previous meta-analyses it was suggested that significant cut-off value of NLR is NLR &lt; 5 and ≥5 and PLR &lt; 160 and ≥160. We analysed PFS and OS. Results: Overall 105 patients diagnosed with NSCLC were treated with nivolumab. The patients were enrolled from March 2017 until October 2017 and were observed them for disease progression and death until June 1st 2020. Most of the patients were male (71; 67.6%) with median age 60.3 years (36-77). Our patients were selected on the basis of good performance status, so most of them had ECOG PS 0 and 1 (103; 98.1%). Therapy was applied mostly in the second and third line (67; 64%), but even up to seventh line (2; 1.9%). Median duration of therapy was 34.5 weeks (2-149), while median number of doses was 17 (1-69).The median PFS was 7.2 months (95% CI 4.53-9.86). Regardless of previous treatment the mOS was 16.1 months (95% CI 11.26-20.93).We observed median value of NLR 4.08 (IQR 2.44-5.84) and PLR 200 (IQR 127.49-284.72). Patients with low PLR had better overall survival compared to patients with low PLR (mOS 20.5 months vs 11.9 months; 95%CI 14.07-26.92 vs 7.35-16.44; p = 0.039). The same was not as clear in mPFS, tendency of better mPFS was toward low PLR, but it did not reach statistical difference (low PLR mPFS 9.1 months vs high PLR mPFS 6.1 months; p = 0.49).Patients with low NLR had significantly better overall survival compared to patients with high NLR (mOS low NLR 18.2 vs high NLR 10.1 months; 95%CI 13.07-23.32 vs 6.04-14.15; p = 0.014). Again, the statistical significance was not reached for progression-free survival (mPFS low NLR 8.3 months vs high NLR 5.8 months; 95%CI 4.81-11.78 vs 2.91-8.68; p = 0.214). Conclusions: Here, we demonstrated that the presence of indicators of systemic inflammation suchas high NLR and high PLR are associated with poor overall survival, but not withprogression-free survival in pre‐treated NSCLC patients who received nivolumabtreatment. The limitation of our study is the lack of a randomizedcontrol and small sample size. The main strength of our study is that it is real-worldeveryday clinical setting.

Increased Preoperative Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio Are Associated With Major Adverse Events and Mortality After Fenestrated/Branched Endovascular Aortic Repair

The objective was to investigate the role of the preoperative neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) as prognostic factors associated with 30-day mortality, major adverse cardiovascular events, acute kidney injury (AKI), and long-term mortality after fenestrated/branched repair (F/BEVAR) of aortic aneurysms with complex anatomy. A retrospective analysis of prospectively collected data of patients who underwent F/BEVAR was performed including cases with a diagnosis of thoracoabdominal aortic aneurysm types I, II, III, IV, and suprarenal and juxtarenal aortic aneurysms. The main inclusion criteria were: (1) complete blood cell count with differential collected within 30 days before surgery and (2) at least 30 days of follow-up. The main exclusion criteria were: (1) comorbid autoimmune/inflammatory diseases and (2) current use of corticosteroid/immunomodulatory drugs. AKI was defined according to the RIFLE (Risk of renal dysfunction, Injury to kidney, Failure or Loss of kidney function, and End-stage kidney disease) criteria. Receiver operating characteristic (ROC) curves were used to determine cutoff values of NLR and PLR associated with the study end points. From 410 patients treated with F/BEVAR between June 2012 and December 2022, 150 were included in the study (70% male; age: 72.7 ± 8.4 years). The mean follow-up time was 29.34 ± 21.79 months. An NLR ≥5 was associated with 30-day mortality with a specificity and sensitivity of 87.1% and 66.7%, respectively, by ROC analysis (Fig 1; area under the ROC curve [AUC] = 0.841, P = .043). The negative predictive value (NPV) was 99.2%. A PLR ≥189 was associated with major adverse cardiovascular events in the first 30-day period with a specificity and sensitivity of 78.8% and 75%, respectively (Fig 2, AUC = 0.830, P = .024), and an NPV of 99.1%. A PLR ≥151 was associated with AKI, with a sensitivity and specificity of 71.4% and 64.3%, respectively (AUC = 0.732, P = .038). The NPV was 97.8%. The groups above and below the cutoffs established by the ROC curves were similar in demographic composition, comorbidities, and extension of the aneurysm. The overall long-term mortality was 27.3% in 5 years. A higher PLR was observed among non-Caucasian patients who died (mean: 190.81 ± 78.4) when compared with the individuals who survived (P = .029). The same finding was not observed in Caucasian patients. Preoperative NLR and PLR are inexpensive and easily available tests that can serve as valuable prognostic tools in patients with complex anatomy aortic aneurysms submitted to F/BEVAR. They might contribute to identifying the higher-risk patients during the preoperative preparation and consequently could indicate which cases would need even more detailed workup before the surgical procedure in the attempt to reduce the odds of adverse events.Fig 2Receiver operating characteristic (ROC) curve for platelet-to-lymphocyte ratio (PLR) considering major adverse cardiovascular event (MACE) during the first 30-day period (P = .024).View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Prognostic value of preoperative hematological markers in patients with glioblastoma multiforme and construction of random survival forest model

ObjectiveIn recent years, an increasing number of studies have revealed that patients’ preoperative inflammatory response, coagulation function, and nutritional status are all linked to the occurrence, development, angiogenesis, and metastasis of various malignant tumors. The goal of this study is to determine the relationship between preoperative peripheral blood neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), systemic immune-inflammatory index (SII), platelet to lymphocyte ratio (PLR), and platelet to fibrinogen ratio (FPR). Prognostic nutritional index (PNI) and the prognosis of glioblastoma multiforme (GBM) patients, as well as establish a forest prediction model that includes preoperative hematological markers to predict the individual GBM patient’s 3-year survival status after treatment.MethodsThe clinical and hematological data of 281 GBM patients were analyzed retrospectively; overall survival (OS) was the primary endpoint. X-Tile software was used to determine the best cut-off values for NLR, SII, and PLR, and the survival analysis was carried out by the Kaplan–Meier method as well as univariate and multivariate COX regression. Afterward, we created a random forest model that predicts the individual GBM patient’s 3-year survival status after treatment, and the area under the curve (AUC) is used to validate the model’s effectiveness.ResultsThe best cut-off values for NLR, SII, and PLR in GBM patients’ preoperative peripheral blood were 2.12, 537.50, and 93.5 respectively. The Kaplan–Meier method revealed that preoperative GBM patients with high SII, high NLR, and high PLR had shorter overall survival, and the difference was statistically significant. In addition to clinical and pathological factors. Univariate Cox showed NLR (HR = 1.456, 95% CI: 1.286 ~ 1.649, P < 0.001) MLR (HR = 1.272, 95% CI: 1.120 ~ 1.649, P < 0.001), FPR (HR = 1.183,95% CI: 1.049 ~ 1.333, P < 0.001), SII (HR = 0.218,95% CI: 1.645 ~ 2.127, P < 0.001) is related to the prognosis and overall survival of GBM. Multivariate Cox proportional hazard regression showed that SII (HR = 1.641, 95% CI: 1.430 ~ 1.884, P < 0.001) is also related to the overall survival of patients with GBM. In the random forest prognostic model with preoperative hematologic markers, the AUC in the test set and the validation set was 0.907 and 0.900, respectively.ConclusionHigh levels of NLR, MLR, PLR, FPR, and SII before surgery are prognostic risk factors for GBM patients. A high preoperative SII level is an independent risk factor for GBM prognosis. The random forest model that includes preoperative hematological markers has the potential to predict the individual GBM patient’s 3-year survival status after treatment,and assist the clinicians for making a good clinical decision.

Platelet-to-Lymphocyte Ratio (PLR) as the Prognostic Factor for Recurrence/Residual Disease in HSIL Patients After LEEP.

The platelet-to-lymphocyte ratio (PLR) is considered correlated with cancer prognosis including cervical cancer, in addition to high-risk papillomavirus (HR-HPV) infection, of which the predictive value in prognosis of high-grade squamous intraepithelial lesions (HSILs) remains unknown. Here, the prognostic predictive value of PLR in HSIL after loop electrosurgical excision procedure (LEEP) was evaluated. This study included 335 nonpregnant participants with histopathologically confirmed HSIL and 3- and 5-year follow-ups from the Fujian Cervical Lesions Screening Cohorts (FCLSCs) between September 2016 and September 2018. PLR and other variables were evaluated to identify the factors related to the recurrence/residual cervical intraepithelial neoplasia (CIN)-free survival (RFS), namely, the time from LEEP at baseline to first detection of recurrence/residual CIN or end of follow-up, by logistic and Cox regression. In the Kaplan‒Meier analysis, HR-HPV infection (p=0.049/0.012), higher PLR (p=0.031/0.038), and gland invasion (p=0.047) had a higher risk for recurrence/residual CIN at the 3-/5-year follow-up. The univariate logistic and Cox regression analyses showed significant differences and a higher cumulative risk in patients with HR-HPV infection (OR=3.917, p=0.026; HR=3.996, p=0.020) and higher PLR (OR=2.295, p=0.041; HR=2.161, p=0.030) at the 5-year follow-up. The findings by multivariate Cox regression analysis were similar, indicating a poor prognosis for patients with HR-HPV infection (HR=3.901, p=0.023) and higher PLR (HR=2.082, p=0.038) at the 5-year follow-up. The calibration plot showed a better model fit for RFS at the 3-year follow-up. Preoperative PLR level and HR-HPV infection could be available markers for predicting recurrence/residual disease of HSIL after LEEP. Clinically, combining PLR with HR-HPV tests may provide novel evaluation method and reference for management in post-treatment patients with cervical precancerous lesions.

Abstract 3018: Demographic and social patterns of average values of inflammatorymarkers in US adults: A 2009-2016 NHANES analysis

Abstract Several studies report the negative impact of elevated Neutrophil-to-Lymphocyte ratio (NLR) and elevated Platelet-to-Lymphocyte ratio (PLR) on outcomes in many surgical and medical conditions, including cancer. In order to use these inflammatory biomarkers as prognostic factors in disease, a normal value in disease-free individuals must be identified first. This study aims to (1) establish average values of various inflammatory markers using a healthy and nationally representative U.S. adult population and (2) explore heterogeneity in average values by sociodemographic and behavioral risk factors to better specify cut-off points accordingly. The National Health and Nutrition Examination Survey (NHANES) of aggregated cross-sectional data collected from 2009 to 2016 was analyzed; data extracted included markers of systemic inflammation and demographic variables. We excluded participants who were under 20 or had a history of inflammatory diseases such as arthritis and gout. Adjusted linear regression models were used to examine the association between demographic and behavioral characteristics and neutrophil counts, platelet counts, lymphocyte counts, NLR, and PLR. The average NLR is 2.16 and the average PLR is 121.31. Non-Hispanic Black participants have significantly lower mean NLR values (1.78, 95% CI 1.74–1.83 and 2.10, 95% CI 2.04–2.16 respectively) when compared to non-Hispanic Whites (2.27, 95% CI 2.22–2.30–p&amp;lt;0.0001). Participants who reported any no smoking history had significantly lower NLR than subjects who reported any smoking history and higher PLR than current smokers. The average PLR for non-Hispanic blacks is significantly lower compared to non-Hispanic whites. Participants ages 20-29 have significantly lower mean PLR vs. participants in the age groups 30-59, 60-79, and 80 and older. Additionally, current smokers have significantly higher mean PLR compared to those who never smoke. Participants in the obese category also had higher mean PLR compared to normal weight participants. This study provides nationally representative estimates for demographic and behavioral effects on NLR, and PLR, which have been associated with several chronic disease outcomes, suggesting that different cut-off points for inflammatory markers should be set according to social factors. Citation Format: Marlene Camacho-Rivera, Zachary Ye, Raisa Haq, Rose Calixte. Demographic and social patterns of average values of inflammatorymarkers in US adults: A 2009-2016 NHANES analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3018.