Baseline Neutrophil-lymphocyte Ratio Research Articles

Relationship Between the Neutrophil to Lymphocyte Ratio, Stromal Tumor-infiltrating Lymphocytes, and the Prognosis and Response to Neoadjuvant Chemotherapy in Triple-negative Breast Cancer

IntroductionNeutrophil to lymphocyte ratio (NLR) and stromal tumor-infiltrating lymphocytes (sTILs) are correlated with triple-negative breast cancer (TNBC) patient prognosis. However, there has been insufficient research regarding the relationship between systemic and local inflammatory states in patients with TNBC, and their effects on neoadjuvant chemotherapy (NAC) efficacy. MethodsThe clinical data of 395 patients with TNBC admitted from January 2010 to December 2018 were collected. The Pearson χ2 test was used to analyze correlations between clinical basic pathological features, NLR, sTILs, and pathological complete response (pCR). Kaplan-Meier and Cox analyses were performed to address which clinical parameters were prognostic factors of disease-free survival (DFS). ResultsThere was no correlation between NLR1 (baseline NLR) and sTILs (P > .05) in these patients with TNBC. Patients with TNBC with lower NLR3 (baseline NLR of patients receiving NAC) or higher sTILs scores had better pCR rates, but this failed to reach statistical significance (P > .05). Cox analysis showed that NLR1 and sTILs were independent prognostic indicators of DFS outcome in patients with TNBC (P < .01). ConclusionIn patients with TNBC, low NLR1 and high sTILs are associated with prolonged DFS. However, the link between systemic and local inflammation markers needs further exploration.

The predictive role of neutrophil-to-lymphocyte ratio in the outcomes of patients with sarcomatoid carcinoma of oral cavity.

The aim of the present study was to evaluate the prognostic value of the inflammatory response biomarkers and their impact on survival outcomes in the patients with sarcomatoid carcinoma (SC) of oral cavity, a rare variant of squamous cell carcinoma (SqC). Seventeen patients diagnosed with SC of oral cavity without metastases treated between Jan 2017 to June 2020 were identified and included in the present study. Pre- and post-operative inflammatory biomarkers and other prognostic markers were evaluated and their impact on disease-free survival (DFS) and overall survival (OS) was studied. Seventeen patients (16 males and one female) were included in the present study with a median age of 42years (IQR: 26-76years). With the median follow-up of 15months, nine of 17 patients had developed recurrence and were succumbed to either locoregional recurrence or distant progression. One-year Kaplan-Meier estimates of DFS and OS were 57% and 58.3% respectively. On univariate analysis, baseline NLR, PLR, and pathological bone/skin involvement were identified to be significant prognostic factors affecting the patient's DFS and OS. On multi-variate analysis, baseline NLR > 3 and pathological bone or skin involvement by tumour were emerged as some independent significant predictors. For the first time, the predictive role of inflammatory markers is studied and proven significant affecting patients' survival outcomes. Hence, these inflammatory biomarkers may be considered for routine clinical use as reliable and low-cost prognostic markers to tailor the management of SC of oral cavity.

The clinical potential of circulating immune cell counts in primary gastric lymphoma

High neutrophil-lymphocyte ratio (NLR) is linked to poor overall survival (OS) in gastrointestinal tract cancers. This study explores the clinical value of NLR, in addition to absolute lymphocyte count (ALC) and other hematologic parameters in association with distant metastases and OS in primary gastric lymphoma (PGL) patients. Clinical data of 139 PGL patients who received treatment at King Hussein Cancer Center (KHCC), Amman-Jordan were retrospectively evaluated. Using data from complete blood count (CBC) tests, the following hematologic parameters: absolute neutrophil count (ANC), ALC, absolute eosinophil count (AEC), absolute monocyte count (AMC), NLR, platelet-lymphocyte ratio (PLR), and monocyte-lymphocyte ratio (MLR) were assessed in association with the following clinical outcomes: presence or absence of baseline distant metastases and OS. We conducted univariate and multivariate analyses assessing the various hematologic parameters in association with distant metastases. Univariate and multivariate analyses indicated that patients with an elevated NLR (>3.14) displayed more baseline distant metastases compared to patients with a low NLR (≤3.14), (P value: 0.02 and 0.018, respectively). High baseline ALC (>1,819/µL) was associated with lower baseline distant metastases (P value: 0.04). In the OS analysis, high baseline ANC (>5,100/µL), NLR (>2.75), and PLR (>0.16) were associated with poor OS, (P value: 0.027, 0.016, and 0.011 respectively). High NLR and ALC were associated with baseline distant metastases. High baseline ANC, NLR, and PLR were associated with poor OS. Hematologic parameters might be potentially helpful in assessing and correlating NLR with the response success to treatment in PGL.

Systemic Immune-inflammation Index (SII) Predicts Pathological Complete Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer.

To determine the relationship between inflammatory markers and pathological complete response (pCR) in patients with locally advanced rectal cancer (LARC), who received neoadjuvant chemoradiotherapy (NACRT). Descriptive study. Department of Medical Oncology, Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital, Ankara, Turkey from January 2014 to June 2020. Patients older than 18 years of age, who underwent NACRT with a diagnosis of LARC, and who had no disease or drug-use that could affect inflammatory parameters, were included in the study. Inflammatory indices (neutrophil-to-lymphocyte ratio-NLR, platelet-to-lymphocyte ratio-PLR, lymphocyte monocyte ratio-LMR, systemic immune-inflammation index-SII, prognostic nutritional index-PNI) and changes in these indices, were calculated from blood samples taken before NACRT and before surgery. The relationship between pCR and calculated inflammatory indices was evaluated by comparing patients with and without pCR. Out of the 932 patients, who received NACRT with a diagnosis of LARC, 188 were eligible for the study. Median values of baseline SII for pCR and non-pCR groups were 729.3 (595.4-894.8) and 869.9(567.2-1145.2, p=0.049). Baseline NLR and PLR levels were lower in the pCR group than the non-pCR group in univariate analysis with a tendency to statistical significance. In the logistic regression analysis, which included NLR, PLR, and SII, only SII <748 was found to be an independent predictive factor of pCR (OR: 0.471, 95% CI; 0.224-0.991, p=0.047). Baseline SII might be an independent predictive factor for pCR in patients receiving NACRT with a diagnosis of LARC. Key Words: Locally advanced rectal cancer, Neoadjuvant chemoradiotherapy, Pathological complete response, Inflammatory index, Systemic immune-inflammation index, SII, NLR, PLR, LMR, PNI.

Systemic Immune-Inflammation Index and Changes of Neutrophil-Lymphocyte Ratio as Prognostic Biomarkers for Patients With Pancreatic Cancer Treated With Immune Checkpoint Blockade.

The efficacy of current treatment regimens for pancreatic cancer (PC) remains unsatisfactory. In recent years, immune checkpoint blockade (ICB) therapy has shown promising anti-tumor outcomes in many malignancies, including PC. Inexpensive and readily available biomarkers which predict therapeutic responses and prognosis are in critical need. Systemic immune-inflammation index (SII) and neutrophil-lymphocyte ratio (NLR) are emerging predictors for prognosis of various tumors. We aim to investigate the prognostic significance of baseline SII, NLR, and their changes in PC patients treated with ICB. Our retrospective analysis included PC patients treated with ICB therapy in the Chinese PLA General Hospital. All demographic, biological, and clinical data were extracted from medical records. Relative changes of SII after two doses of ICB were defined as ΔSII% and calculated as (SIIafter 2 doses-SIIbaseline)/SIIbaseline, and so was the case for ΔNLR%. Overall survival (OS) and progression-free survival (PFS) were compared using Kaplan-Meier curves. The prognostic significance of baseline SII, NLR, and their changes was assessed in univariate and multivariate analyses using the Cox proportional hazard regression model. In total, 122 patients with PC treated with ICB were included in the present analysis. Elevated baseline SII (HR=3.28; 95% CI:1.98–5.27; P=0.03) and ΔNLR% (HR=2.21; 95% CI:1.03–4.74; P=0.04) were significantly correlated with an increased risk of death. For PC patients receiving ICB combined with chemotherapies or radiotherapies as the first-line treatment, increased baseline SII was a negative predictor for both OS (HR=8.06; 95% CI:1.71–37.86; P=0.01) and PFS (HR=2.84; 95%CI:1.37–10.38; P=0.04). Our study reveals the prognostic value of baseline SII and NLR changes in PC patients receiving ICB therapy. The clinical utility of these prognostic biomarkers needs to be further studied in prospective studies.

C-reactive protein and neutrophil-lymphocyte ratio are prognostic in metastatic clear-cell renal cell carcinoma patients treated with nivolumab

ObjectiveTo evaluate the impact of markers of systemic inflammation such as C-reactive protein (CRP) and neutrophil-lymphocyte ratio (NLR) on outcomes of metastatic clear-cell renal cell carcinoma (m-ccRCC) patients treated with nivolumab. Patients and methodsWe retrospectively evaluated m-ccRCC patients treated with nivolumab and collected known prognostic factors and survival data. We used Kaplan-Meier survival analysis and cox proportional hazards regression analysis to study prognostic factors for overall survival (OS) and progression-free survival (PFS) since start of nivolumab. Harrell's C-index was used to evaluate the models. ResultsWe included 113 patients. Median OS and PFS after initiation of nivolumab was 15 (interquartile range 7–28) and 4 months (interquartile range 3–11), respectively.Elevated baseline CRP was associated with worse OS (HR per 25 mg/l 1.35, 95% CI 1.16–1.52, P < 0.001) and PFS (HR per 25 mg/l 1.19, 95% CI 1.08–1.35, P = 0.001), independent from the international metastatic renal cell carcinoma database consortium (IMDC) prognostic criteria, increasing the model's C-index from 0.72 to 0.77 for OS and 0.59 to 0.62 for PFS.Elevated NLR was associated with worse OS (HR 1.10, 95% CI 1.04–1.17, P = 0.002) and PFS (HR 1.06, 95% CI 1.01–1.11, P = 0.03) independent from the other IMDC prognostic criteria. The model's C-index decreased from 0.72 to 0.70 for OS and increased from 0.59 to 0.60 for PFS. ConclusionsElevated baseline CRP and NLR predict worse OS and PFS on nivolumab in m-ccRCC patients. Including baseline CRP in the IMDC prognostic model improves its discriminatory power to predict OS and PFS since start of nivolumab.

BLOOD-BASED PROGNOSTIC BIOMARKERS IN CROHN’S PATIENTS TREATED WITH BIOLOGICS: A NEW PROMISING TOOL TO PREDICT ENDOSCOPIC OUTCOMES

Abstract Background and aims There is a growing need for biomarkers of inflammation to monitor and predict therapeutic outcome in Crohn’s disease (CD) patients. We aimed to evaluate whether the level of circulating blood cells, expressed as ratios (NLR, neutrophil-to-lymphocyte ratio; PLR, platelet-to-lymphocyte ratio; ELR, eosinophil-to-lymphocyte ratio and ENLR, eosinophil*neutrophil-to-lymphocyte ratio), could be used as early prognostic biomarker of endoscopic response (ER) in patients starting biological therapy with infliximab, adalimumab, vedolizumab and ustekinumab. Association with steroid-free clinical remission at week 54 and endoscopic disease activity at baseline, as well as other variables related with ER were also evaluated as secondary outcomes. Methods Consecutive patients with CD who started biological therapy between June 2016 and July 2019 in two Italian tertiary centers were enrolled. We used multivariate analysis to evaluate whether NLR, PLR, ELR and ENLR at baseline and after 12 weeks of treatment could predict ER (SES-CD ≤ 2 or SES-CD ≤ 2 and Rutgeerts score i0-i1) after 54 weeks of treatment. Receiver operating characteristic (ROC) curves were generated to identify the area under the curve (AUC) and find the best cut-off values of NLR, PLR, ELR and ENLR for the prediction of ER. To enhance the diagnostic performance, these ratios were combined with baseline Harvey Bradshaw Index (HBI) in a prognostic model. Results 107 patients were included. Patients who achieved ER had significantly lower baseline NLR (p = 0.025), ELR (p = 0.013) and ENLR (p = 0.021) compared with those without ER; similar results were confirmed after 12 weeks of treatment for ELR (p = 0.006) and ENLR (p = 0.026). AUC was 0.64 (p = 0.003), 0.67 (p = 0.006) and 0.65 (p=0.014) for NLR, ELR and ENLR, respectively. The best cut-offs values were included in the HBI-based prognostic model: 81.8% of patients with HBI ≥ 5 and higher ratios did not achieve ER, while all patients with HBI &amp;lt; 5 and lower ratios reached ER. Interestingly, ENLR was found to be linearly associated with SES-CD at baseline (p= 0.035). Conclusions To the best of our knowledge, this is the first study assessing NLR, ELR and ENLR as predictive markers of therapeutic response in CD patients. Low levels of these ratios can predict endoscopic response and could be used in clinical practice for a better management of CD patients needing biological therapy. Further prospective studies are needed to confirm these results in larger cohorts.

The role of systemic inflammatory factors in gastroenteropancreatic neuroendocrine tumors (GEP-NETs) treated with peptide receptor radionuclide therapy (PRRT).

371 Background: Inflammation plays a key role in the pathophysiology of many diseases, including cancer. Systemic inflammatory factors have been validated as indicators of ongoing systemic inflammation that could be predictive markers of poor prognosis for oncological outcomes. However, it is unknown the prognostic impact of systemic inflammation markers in patients with GEP-NETs treated with PRRT. Methods: We conducted an observational, retrospective, multicentric study of 40 patients with GEP-NET treated with PRRT belonging to GGNET (Galician Research Group on Neuroendocrine Tumors) network at Nuclear Medicine Department of Santiago de Compostela University Hospital (Spain). The systemic inflammatory markers were calculated as follows: NLR = neutrophil count/lymphocyte count, PLR = platelet count/lymphocyte count, MLR= monocyte count/lymphocyte count, ALB= albumin levels and dNLR = neutrophil count/ (leucocytes count – neutrophils count). For the calculation of the different ratios, baseline analysis and after the second dose were used. The cut-off values were determined as the median of each values, correlating them with progression-free survival (PFS). Results: Data from 40 patients (pts) treated between 2016 and 2020 were recorded. Median age was 63.5 years (range 41-85) and 55% were male. Baseline ECOG PS 0/1/2 was 15 (37.5%)/16 (40%)/9 (22.5%). Tumor location was intestinal 26 pts (65%), pancreas 11 pts (27.5%) and unknown origin 3 pts (7.5%). 15 pts (37.5%) were functioning. Tumor grade G1/G2/G3 were 17 pts (42.5%)/ 20 pts (50%)/ 3 pts (7.5%), and Ki 67 &lt;2/3-20/&gt;20%/unknown were 11 pts (27.5%)/ 21 pts (52.5%)/ 3 pts (7.5%)/ 5 pts (12.5%), respectively. The most frequent site of metastasis was liver 32 pts (80%), lymph nodes 19 pts (47.5%), peritoneum 11 pts (27.5%) and bone 10 pts (25%). Surgery: 22 pts (55%) primary tumor surgery and 8 pts (20%) metastasectomy. Previous systemic treatments included somatostatin analogs (SSA) 40 pts (100%), everolimus 26 pts (65%) and sunitnib 11 pts (27.5%), others 7 pts (17.5%). The baseline cutoff-values for NLR was 2.61, for PLR 110.14, for MLR 0.31, for ALB 4.2. and for dNLR 1.71. The cutoff-values after the 2nd dose for NLR was 2.3, for PLR 2.15, for MLR 0.3, for ALB 4.2 and for dNLR 1.48. With a median follow up of 21 months, 14 pts (35%) had died. Median PFS was 27.2 m (95% CI 16.0-38.4m) and OS was not reached (NR). Pts with baseline higher NLR (&gt;2.61 vs. &lt;2.61) had a significantly lower PFS: 15.8 m vs. NR (HR 0.181; 95% CI 0.051-0.638, p=0.03), which was also true for pts with elevated dNLR (&gt;1.71 vs. &lt;1.71): PFS 15.8 m vs. NR (HR 0.174; 0.049-0.614, p=0.03). Baseline PLR, ALB, MLR and NLR, PLR, ALB, dNLR and MLR values after the 2nd dose was not statistically significant for PFS. Conclusions: We have identified that baseline NLR and dNRL are significant predictive factors in patients with GEP-NETs treated with PRRT.

The neutrophil-lymphocyte ratio and incident atherosclerotic events: analyses from five contemporary randomized trials.

The neutrophil-lymphocyte ratio (NLR) is a readily available inflammatory biomarker that may associate with atherosclerosis and predict cardiovascular (CV) events. The aims of this study are to determine whether the NLR predicts incident major adverse cardiovascular events (MACE) and is modified by anti-inflammatory therapy. Baseline and on-treatment NLRs were calculated from complete blood counts among 60087 participants randomized in the CANTOS, JUPITER, SPIRE-1, SPIRE-2, and CIRT trials to receive placebo or canakinumab, rosuvastatin, bococizumab, or methotrexate, respectively, and followed up for MACE. All analyses were performed first in CANTOS, and then externally validated in the other four trials. For the five trials, hazard ratios for major CV events and mortality comparing NLR quartiles were computed using Cox proportional hazards models, and the effect of each randomized intervention on the NLR was evaluated in comparison to placebo. The NLR modestly correlated with interleukin-6, C-reactive protein, and fibrinogen levels but minimally with lipids. In all five randomized trials, baseline NLR predicted incident CV events and death; the per-quartile increase in risk of MACE was 20% in CANTOS [95% confidence interval (CI) 14-25%, P < 0.0001], 31% in SPIRE-1 (95% CI 14-49%, P = 0.00007), 27% in SPIRE-2 (95% CI 12-43%, P = 0.0002), 9% in CIRT (95% CI 0.2-20%, P = 0.045), and 11% in JUPITER (95% CI 1-22%, P = 0.03). While lipid-lowering agents had no significant impact on the NLR, anti-inflammatory therapy with canakinumab lowered the NLR (P < 0.0001). The NLR, an easily obtained inflammatory biomarker, independently predicts CV risk and all-cause mortality, and is reduced by interleukin-1β blockade with canakinumab.

Prognostic Value of Baseline White Blood Cell Count and Neutrophil–Lymphocyte Ratio in Carcinoma Cervix

Aims: To evaluate the impact of baseline white blood cell (WBC) count and neutrophil–lymphocyte ratio (NLR) in carcinoma cervix patients treated with definitive chemoradiotherapy. Settings and Design: Retrospective cohort study, original research article in Department of Radiation Oncology, Basavatarakam Indo American Cancer hospital. Materials and Methods: Patients of squamous cell carcinoma cervix treated with radical chemoradiotherapy from January 2017 to August 2017 were included in the analysis. All patients had baseline blood counts, local imaging, and metastatic workup at diagnosis. Patients received external beam radiotherapy to a total dose of 50 Gy in 25 fractions along with weekly cisplatin (40 mg/m2) and brachytherapy (21 Gy in 3 fractions). Baseline WBC counts and baseline NLR were correlated with outcomes using chi square test and receiver operating characteristic curves. Statistical analysis used: The patients were divided into two groups based on high-baseline WBC count and normal-baseline WBC count. Baseline WBC counts and baseline NLR were correlated with patterns of recurrence using chi square test. The sensitivity and specificity of prognostic factors for recurrence were computed using ROC curves. Results: The NLR cut-off value of 3.47 had high sensitivity and specificity for predicting recurrence in these patients. Majority of the recurrences in patients having high WBC count and high NLR were distant recurrences. Conclusions: A high-baseline WBC count and high NLR resulted in higher rates of recurrence and inferior survival in carcinoma cervix patients in our study. These biomarkers can be used as predictors of outcomes in carcinoma cervix.

Circulating tumor cells and neutrophil-lymphocyte ratio are predictive markers for metastatic colorectal cancer patients

BackgroundMore accurate predictive factors for colorectal cancer (CRC) are urgently needed. This study aimed to assess the potential prognostic roles of circulating tumor cells (CTCs), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) in CRC patients.MethodsBetween 2014 and 2017, 118 CRC patients newly diagnosed at the Affiliated Zhongshan Hospital of Dalian University were retrospectively analyzed, including 72 (61%) patients that underwent radical resection (resectable CRC) and 46 (39%) advanced patients with metastatic CRC (mCRC). The CellSearch System was used to detect CTCs, and Spearman’s correlation analyses tested the correlations between CTC counts and both NLR and PLR. Statistical analyses were performed using the Kaplan-Meier method, log-rank tests, and Cox proportional hazards models.ResultsOf the resectable cohort, 24% were positive for CTCs. Of the advanced cohort, 49% were positive for CTCs. The presence of CTCs was associated with advanced age (≥63 years old; P=0.037), a high PLR value (P=0.008), and a high NLR value (P=0.034). Additionally, baseline NLR [hazard ratio (HR) =0.423; 95% confidence intervals (CI), 0.223–0.803; P=0.008], PLR (HR =0.513; 95% CI, 0.276–0.954; P=0.035), and CTC counts (HR =2.155; 95% CI, 1.152–4.032; P=0.016) were significantly associated with progression-free survival (PFS) in a univariate analysis of mCRC patients that received chemotherapy. Multivariate analysis further showed that NLR (P=0.044) and CTCs (P=0.047) were independent prognostic factors for mCRC patients.ConclusionsThis study provided evidence that NLR and CTC counts could serve as robust prognostic factors for patients with mCRC.

Prognostic significance of the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio for advanced non-small cell lung cancer patients with high PD-L1 tumor expression receiving pembrolizumab.

BackgroundWe investigated the association of peripheral blood inflammatory markers with overall survival (OS) in pembrolizumab treated advanced non-small cell lung cancer (aNSCLC) patients with programmed death ligand 1 (PD-L1) expression ≥50%. Clinical risk factors for development of immune-related adverse events (irAE) were also explored.MethodsaNSCLC patients with high PD-L1 expression receiving pembrolizumab monotherapy outside of clinical trials were identified retrospectively. All patients were treated at one of six British Columbia Cancer clinics between August 2017 and June 2019. Patients were dichotomized using baseline neutrophil-to-lymphocyte ratio (NLR, </≥6.4) and platelet-to-lymphocyte ratio (PLR, </≥441.8). Factors associated with OS were assessed with Cox proportional hazard models. Logistic regression models were utilized in landmark analysis of risk factors for irAE.ResultsAmong 220 patients, median age was 70.0 years, 55.0% were female, 40.5% had baseline Eastern Cooperative Oncology Group performance status (ECOG PS) 2/3, and 95.5% received frontline pembrolizumab. Median OS for the cohort was 11.8 months (95% CI: 8.7–15.4). On multivariable analysis, baseline NLR ≥6.4 [hazard ratio (HR): 2.31, 95% confidence interval (CI): 1.46–3.64, P<0.001], baseline PLR ≥441.8 (HR: 2.03, 95% CI 1.22–3.37, P=0.006), and pre-treatment ECOG PS 2/3 (HR: 2.19, 95% CI: 1.48–3.26, P<0.001) were associated with worse OS. The incidence of any grade irAE and irAE grade ≥3 were 40.5% and 12.3%, respectively. ECOG PS 2/3 (vs. 0/1) patients were at 3.76-fold higher risk of developing an irAE by the 8-month landmark (P=0.002).ConclusionsHigh NLR and PLR were associated with shorter OS in a cohort of patients receiving largely frontline pembrolizumab for aNSCLC in routine practice. ECOG PS 2/3 was associated with higher risk of developing an irAE. Given that NLR and PLR values are easily obtainable, prospective studies are warranted to confirm their prognostic significance in this patient population and explore a predictive utility.

Translational relevance of baseline peripheral blood biomarkers to assess the efficacy of anti-programmed cell death 1 use in solid malignancies.

This study is an overall clinical analysis of anti-programmed cell death 1 (PD1) antibodies used in a single institution, emphasizing the role of baseline peripheral blood markers as a prognostic or predictor biomarker of immunotherapy. Sixty-one patients were retrospectively analyzed from hospital medical records. The endpoint of this study was death from any cause and the survival time was calculated from the date of start of immunotherapy to the date of death. Descriptive and survival statistics was performed using SPSS version 23. Cutoff values for baseline biomarkers (neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], neutrophil-to-eosinophil ratio [NER], and lymphocyte-to-monocyte ratio [LMR]) were obtained using cutp function of Evaluate Cutpoints software (R survMisc package). Pearson and Pearman correlation coefficients were used to examine the relationship of peripheral blood biomarkers. Nighty-eight percent of the study population had Stage IV disease and total median overall survival postanti-PD1 therapy was 10.7 months. Patients receiving more than 5 doses of anti-PD1 therapy (12.6 m vs. 4.4 m, P < 0.001) and used in front lines (18.9 m vs. 10.7 m vs. 10.1 m vs. 2.8 m in first line, second line, third line, and >3 lines, respectively, P = 0.049) were found to have an impact in overall survival. Pembrolizumab showed a better survival compared to nivolumab (17.4 m vs. 8.2 m, P = 0.049) in our study. Among baseline biomarkers assessed, NLR (cutoff - 2.81, P = 0.003) and LMR (cutoff - 5.76, P = 0.017) has shown a statistically significant relationship with immunotherapy response. NER (cutoff - 24.32, P = 0.051) and PLR (cutoff - 190.8, P = 0.072) were also found to exhibit a strong relationship with anti-PD1 therapy response. NLR exhibits a statistically significant positive correlation with PLR (r = 0.917 P < 0.001) and NER (r = 0.400 P = 0.014). Real-life data analysis of anti-PD1 use for solid cancers highlights that baseline NLR, PLR, NER, and LMR have a significant role as immunotherapy biomarkers. However, larger studies are required to further prove the specificity and sensitivity.

Is there Any Relationship Between Long-Term Mortality of Acute Pulmonary Embolism and Complete Blood Count Analysis?

Purpose:Acute pulmonary embolism (PE) is a challenging disease as the third most common cause of cardiovascular death. Despite various scoring systems and blood parameters, more simple and practical predictors are being investigated. The objective of this study is to investigate the relationship between hospital and long-term mortality and complete blood count parameters, neutrophil-to-lymphocyte ratio (PLR) and platelet-to-lymphocyte ratio (PLR) in patients with acute PE. Patients and Methods:The present study is a retrospective observational study. Between June 2016 and June 2018, patients hospitalised in our chest diseases clinic with evident PE were included. Demographics, baseline complete blood count, D-dimer (mg/L) and C-reaktif protein (mg/L) values were recorded. In-hospital mortality and long-term mortality were investigated and predictors of mortality were analyzed. Results:Of all the 74 pateints, 36 (49%) were male and the mean age was 65±18 (20-89). Embolus was localised in main pulmonary artery in 51%, right heart dysfunction were noted in 8 (10%) patients. Baseline NLR was significantly higher in patients who died in hospital (9.8±7.1 vs. 5.3±4.8, respectively) (P=0.037). Additionally NLR was found as a predictor of long-term mortality (P=.,047). The other predictors for long-term mortality were male gender (P=0.002), advanced age (P=0.023) and lower hemoglobin (P=0.013) values. Conclusion:Acute PE may lead mortality and require close follow-up of patients. Higher NLR values relate both in-hospital and long-term mortality and may be used as a cheap, simple and useful prognostic predictor in patients with PE.

Peripheral blood cell ratios as prognostic factors in canine diffuse large B-cell lymphoma treated with CHOP protocol.

Diffuse large B-cell lymphoma (DLBCL) is the most common haematopoietic tumour in dogs and recognized as clinical model for its human counterpart. Recently, neutrophil-to-lymphocyte (NLR) and lymphocyte-to-monocyte (LMR) ratios have been shown to predict time-to-progression (TTP) and lymphoma-specific survival (LSS) in dogs with DLBCL treated with CHOP-based chemotherapy. We retrospectively evaluated in 59 dogs diagnosed with DLBCL the prognostic value of haematological parameters and derived ratios: NLR, LMR, platelet-to-lymphocyte (PLR) and platelet-to-neutrophil (PNR) ratios for TTP, LSS and associated secondary end-points (time-to-progression-rate [TTPR] and lymphoma-specific survival-rate [LSSR]) as rates at 180 and 365 days. PNR is an independent prognostic marker (p ≤ .001) for TTPR/180 and 365 days, dogs with a PNR above 0.032 were more likely to progress before 180 days (sensitivity 46.5%, specificity 87.5%, p=.004). On univariate analysis, NLR showed a prognostic significance for LSSR/180 (p=.006) and LSSR/365 (p=.009). A baseline NLR value below 7.45 was positively associated with survival at 180 days (sensitivity 52%, specificity 85.3%, p=.025). The presence of substage b, was associated with early progression and decreased survival at 180 days (p=.031). Anaemia significantly reduced LSSR at 365 days (p=.028). This is the first study evaluating PLR and PNR in canine DLBCL and demonstrates that PNR could be a predictor of early lymphoma progression. Since peripheral blood cell composition can be affected by several non-oncological causes, the development of larger multicenter studies with homogeneous inclusion criteria could help to better determine the true predictive values of blood cell ratios in dogs' DLBCL treated with CHOP chemotherapy.

Baseline neutrophil-lymphocyte ratio is associated with survival for infant living donor liver transplantation for biliary atresia.

Living donor liver transplantation (LDLT) in infants for congenital biliary atresia (BA) poses various challenges nowadays. We aim to investigate independent preoperative risk factors for LDLT in infants. We retrospectively analyzed medical records of infant patients who underwent LDLT surgery for BA from 1 July 2014 to 31 December 2016. Cox regression was used to explore risk factors. The Kaplan-Meier method was used to calculate the recipient and graft survival, and subgroup analysis was then applied according to the risk factors. Independent t test or Mann-Whitney U test was applied for comparison of certain factors between survival patients and death. A total of 345 infant LDLT for BA were included in the analysis. In the multivariate Cox-regression model, 3 factors were determined as independent risk factors for recipient and graft survival, there were neutrophil-lymphocyte ratio (NLR), pediatric end-stage liver disease (PELD), and recipient age. The HR (95% CI) of baseline NLR for recipient and graft survival were 1.25 (1.12-1.38) and 1.25 (1.13-1.39), with all P<.0001. Kaplan-Meier curves for NLR using different cut-offs (1.5; 1, 2) suggested that higher baseline NLR was significantly associated with recipient and graft survival. The subgroup analysis indicated that for infants with elevated NLR, the recipient survival was significantly lower when their age >6months or PELD >20. Our results indicate that infants with higher baseline NLR value may have lower survival rate 3years after transplantation. Further investigations about broaden the application of pre- and post-transplant NLR to guide nutrition intervention and immunosuppression therapy are necessary.

Abstract 13352: Decreased Absolute Lymphocyte Count and Increased Neutrophil Lymphocyte Ratio With Immune Checkpoint Inhibitors-associated Myocarditis

Introduction: Myocarditis due to immune checkpoint inhibitor (ICI) therapy is a potentially fatal immune-related adverse event (irAE). Hypothesis: Limited data have suggested an association between baseline and on-treatment absolute lymphocyte count (ALC) and neutrophil lymphocyte ratio (NLR) and the development of other irAEs; there are no data characterizing the role of ALC and NLR in ICI-associated myocarditis. Methods: This was a case control study of 55 patients with ICI myocarditis and 55 controls without any post-ICI irAEs. We leveraged clinical testing where patients underwent routine serial blood counts before and with each ICI cycle to compare the baseline and change in ALC and NLR between cases and controls. The association between the change in these parameters with clinical variables and major adverse cardiac events (MACE) was also tested. Results: In those who developed myocarditis, there was a decrease in ALC from baseline (1.6 K/μL, IQR 1.1-1.9) to admission (1.1 K/μL, IQR 0.7-1.3, p&lt;0.001, Panel A). Similarly, among those who developed myocarditis, there was an increase in NLR from baseline (3.5, IQR 2.3-5.4) to admission (6.6, IQR 4.5-14.1, p&lt;0.001, Panel B). There was no change in patients treated with an ICI who did not develop myocarditis. Among those who developed myocarditis, a greater decrease in ALC or increase in NLR was associated with a higher heart rate and a lower blood pressure at admission. In follow-up, there were 20 events; larger decreases in ALC or increases in NLR were associated with MACE (Panel C and D). Conclusions: A reduction in ALC and an increase in NLR was seen with ICI myocarditis. A greater decrease in ALC or increase in NLR were associated with subsequent MACE.

162P Evaluation of neutrophil/lymphocyte ratio (NLR) in monitoring anastomotic leakage after radical total gastrectomy for gastric cancer

It was unclear whether neutrophil/lymphocyte ratio (NLR) in gastric cancer patients are related to anastomotic leakage (AL). We aimed to evaluate the monitoring value of NLR for AL after radical gastrectomy for gastric cancer. Two thousand eight hundred and fifty-five patients receiving radical total gastrectomy with Roux-en-Y esophagojejunal anastomosis for gastric cancer were included, and the cumulative sum (CUSUM) curve was used to dynamically monitor NLR changes. The incidence of AL was 2.6% (75/2855). The median diagnosis time for AL was 7 (2-17) days, and the median healing time was 19 (5-98) days. According to the CUSUM exceeded the limit value (3σ: 3 standard deviations) or not, the patients were divided into ≥3σ group and <3σ group. The 5 dead patients were in the ≥3σ group, and the median healing time of the other patients was 32 (7-98) days, which was longer than that of patients in the <3σ group [11 (5-28) days, p<0.001]. And 43.5% of patients in the ≥3σ group had severe complications (Clavien-Dindo grade ≥3), which were higher than those in the <3σ group (17.2%, p=0.019). Baseline NLR <2.5, AL occurred <7 days, and CUSUM change ≥3σ were independent risk factors affecting delayed healing (>19 days) or death. The area under curve (AUC) of receiver operating characteristic (ROC) of the scoring system was 0.913. The healing rate of patients in low, medium and high-risk group ≤19 days was 95.7%, 47.4% and 6.1%, respectively. NLR can dynamically monitor the healing process of AL. The scoring system constructed based on NLR can effectively identify high-risk populations with delayed AL healing or death, providing an objective basis to develop a reasonable treatment plan.

Hematological Indices of Distant Metastases and Prognostic Nomogram in Gastro-Pancreatic and Biliary Tract Cancers.

PurposeThe predictive value of inflammatory parameters as indicators of poor overall survival (OS) has been well studied in various tumors. This study aimed to explore the association of neutrophil-lymphocyte ratio (NLR), among other parameters in upper gastro-intestinal tract tumors with distant metastases and OS.Patients and MethodsRetrospective analysis was done for 945 patients (males n= 539, 57.0%) with a median of 57 years (range 19–90 years) treated at King Hussein Cancer Center (KHCC) for gastric (n=501), pancreatic (n=355), and biliary (n=89) carcinoma. NLR, and other parameters were calculated at primary presentation, and the association between the parameters with baseline distant metastases and OS was studied. The optimal cutoff value of NLR was based on receiver operating characteristic curve (ROC) analysis. A prognostic nomogram was then constructed to explore how accurately the OS can be predicted.ResultsPatients with high baseline NLR (>3.2) had more distant metastases on presentation than patients with low NLR (≤3.2), (p-value <0.001). Age older than 57 years was associated with poor median OS (8.7 versus 10.6 months, p-value= 0.04). In addition, the location of the tumor as stomach versus biliary tract (Odds Ratio 0.443 95% CI 0.281–0.699), and pancreas versus biliary tract (Odds Ratio 1.193, 95% CI 0.749–1.902, p-value <0.001) proved to be significant. In multivariate analysis, age older than 57 years (p-value =0.0033, HR 0.792, 95% CI 0.678–0.925), location of the tumor (p-value <0.0001), presence of distant metastasis (p-value <0.0001, HR 2.063, 95% CI 1.760–2.419), and NLR (p-value <0.0001, HR 1.045, 95% CI 1.028–1.062) remained significant. Nomogram confirmed the significance of NLR as an independent prognostic factor for OS (HR = 1.62, 95% CI: 1.31–2.01, p-value <0.0001).ConclusionOur results suggested that high baseline inflammatory markers are associated with distant metastases and poor OS. The utilization of this association in management of cancer patients still warrants further investigation.

A Novel Tool for Predicting Outcomes after Immune Checkpoint Inhibitors Therapy in Patients with Lung Cancer

Background: The development of immune checkpoint inhibitors (ICI) has resulted in a shift in the treatment of lung cancer (LC); however, biomarkers of clinical efficacy have not been fully validated. In this study, a novel nomogram with immune factors was used for monitoring the response to ICI therapy. Methods: Patients with LC who received programmed cell death 1/programmed cell death-ligand 1 (PD-1/PD-L1) inhibitor treatment were included in this analysis. The immune biomarkers and clinicopathological characteristics at baseline were used to estimate the tumor response. The nomogram was based on the factors determined by univariate and multivariate Cox hazard analyses. The C-index and calibration curve were used to determine the predictive accuracy and discriminative ability of the nomogram. Overall survival (OS) was estimated using the Kaplan–Meier method. Results: Patients with lung metastasis (P=0.010), higher baseline neutrophil–lymphocyte ratio (P<0.001), lower baseline lymphocyte–monocyte ratio (P=0.019), and higher CD3+CD8+ T cell count (P=0.009) were significantly related to tumor response. The above biomarkers were contained into the nomogram. The calibration plot for the probability of OS showed an optimal agreement between the actual observation and prediction by the nomogram at 3 or 5 years after therapy. The C-index of the nomogram for the prediction of OS was 0.804 (95% confidence interval [CI]: 0.739–0.869). Decision curve analysis demonstrated that the nomogram was clinically useful. Moreover, patients were divided into two distinct risk groups according to the OS determined by the nomogram: low-risk group (OS: 17.27 months, 95% CI: 14.75–19.78) and high-risk group (OS: 6.11 months, 95% CI: 3.57–8.65). Conclusions: A nomogram constructed using the lung metastasis baseline neutrophil–lymphocyte ratio, lymphocyte–monocyte ratio, and CD3+CD8+ T cells count could be used to monitor and predict clinical benefit and prognosis in patients with LC during ICI therapy. Funding Statement: There was no funding in our study. Declaration of Interests: The authors declare that they have no conflict of interest. Ethics Approval Statement: All patients provided written informed consent. The Institute Research Ethics Committee of the Sun Yat-Sen University Cancer Center approved this study.