Baseline Neutrophil-lymphocyte Ratio Research Articles

OR38. Hematological Parameter of Contrast Induced Acute Kidney Injury in ST Elevation Myocardial Infarction Patient Underwent Percutaneous Coronary Intervention

Abstract Aim To determine the relationship of Neutrophil/Lymphocyte Ratio (NLR), Platelet/Lymphocyte Ratio (PLR) as simple inflammatory parameter to incident of Contrast Induce - Acute Kidney Injury (CI-AKI) in ST Elevation Myocardial Infarction (STEMI) patient underwent Percutaneous Coronary Intervention (PCI). Method and Result We collected laboratory and angiographic data of 113 consecutive STEMI patient that treated with PCI in M. Djamil Hospital Padang since April 2020 – April 2021. CI-AKI define as increasing creatinine serum 25% or 0,5 gr/dl over 48 hours after contrast administration. Patient with end stage renal failure were exclude. In this study we found 17.6 % patient developed CI-AKI after PCI. These patients have older age (mean 61 ± 8.7 years) with hypertension as majority of risk factor (65%). PLR and NLR were higher in CI-AKI group (220.11 ± 144.57; 7.49 ± 5.36) with significant differences in PLR (p < 0.08). Hemoglobin was lower in CI-AKI group (mean 12.56 ± 1.50) and amount of contrast used during PCI were more in CI-AKI group (mean 135.75 ± 27.63) but there was no significant differences. Conclusion STEMI patient who underwent PCI with higher baseline PLR and NLR value have higher incident of CI-AKI. PLR have the most significant correlation to incident of CI -AKI in this population.

Prognostic impact of lymphopenia and neutrophil-lymphocyte ratio for patients with anal squamous cell carcinoma.

Outcomes after definitive chemoradiation for squamous cell carcinoma are generally favorable. However, biomarkers to further yield prognostic information are desired. Treatment-related lymphopenia as well as an elevated baseline neutrophil-lymphocyte ratio have been associated with worse survival in several cancer types. We evaluated absolute lymphocyte count and neutrophil-lymphocyte ratio at baseline and at treatment-related nadir in patients with anal cancer for associations with oncologic endpoints. We conducted a retrospective analysis of 428 consecutive patients with non-metastatic anal cancer treated with definitive, intensity-modulated radiation therapy-based chemoradiation. We analyzed absolute neutrophil and lymphocyte counts at several timepoints: pretreatment, weekly during treatment, and in the six weeks following treatment completion. Neutrophil-lymphocyte ratio was calculated at baseline and treatment-related nadir. We estimated oncologic endpoints using life tables and compared them using the log-rank test. We conducted univariate and multivariable time-to-event analyses using Cox proportional hazards. Median absolute lymphocyte count at baseline and nadir were 1.80 [interquartile range (IQR), 1.45-2.32] k/µL and 0.26 (IQR, 0.18-0.36) k/µL, respectively, and 31% developed treatment-related grade 4 lymphopenia. Median neutrophil-lymphocyte ratio at baseline and nadir were 2.34 (IQR, 1.68-3.30) and 8.80 (IQR, 5.86-12.68), respectively. Estimates of overall survival, local failure-free survival, distant metastasis-free survival (DMFS), and freedom from colostomy at 5 years were 87%, 86%, 82%, and 88%, respectively. Baseline and nadir absolute lymphocyte count were not associated with selected outcomes on univariate analysis. On multivariable analysis, factors independently associated with death included T3-T4 disease, HIV-positive status, treatment break, and baseline neutrophil-lymphocyte ratio >3. Baseline neutrophil-lymphocyte ratio showed a trend toward association with distant progression or death (P=0.07). The 5-year overall survival estimates for patients with baseline neutrophil-lymphocyte ratios ≤3 and >3 were 92.3% and 80.6%, respectively. Lymphopenia during and after chemoradiation for anal cancer is common but does not appear to be associated with worse survival, recurrence, or metastases. However, elevated baseline neutrophil-lymphocyte ratio was independently associated with overall survival, local recurrence-free survival, and DMFS. Further studies are needed to determine the clinical utility of baseline neutrophil-lymphocyte ratio to guide treatment and follow-up.

Baseline neutrophil-lymphocyte ratio is associated with outcomes in patients with castration-resistant prostate cancer treated with Docetaxel in South China.

The aim of this study is to investigate the association between baseline neutrophil-to-lymphocyte ratio (NLR) and progression-free survival (PFS), overall survival (OS) and radiological response in castration-resistant prostate cancer patients treated with docetaxel.Forty-one prostate cancer patients who were treated with docetaxel were selected. Univariable and multivariable Cox regression models were used to predict the association of baseline NLR as a dichotomous variable with PFS and OS after chemotherapy initiation.In Kaplan–Meier analysis, the median PFS (9.8 vs 7.5 months, P = .039, Fig. 1) and OS (17.6 vs 14.2 months, P = .021, Fig. 2) was higher in patients who did not have an elevated NLR than in those with an elevated NLR. In univariate analysis, the pretreatment NLR was significantly associated with PFS (P = .049) and OS (P = .023). In multivariable analysis, patients with a NLR of >3 were at significantly higher risk of tumor progress (hazard ratio 2.458; 95% confidence interval 1.186–5.093; P = .016) and death (hazard ratio 3.435; 95% CI 1.522–7.750; P = .003)than patients with a NLR of ⩽3.NLR may be an independent predictor of PFS and OS in castration-resistant prostate cancer patients treated with docetaxel. The findings require validation in further prospective, big sample-sized studies.

Trifluridine/Tipiracil in Metastatic Colorectal Cancer: A UK Multicenter Real-world Analysis on Efficacy, Safety, Predictive and Prognostic Factors

BackgroundThe orally administered combination trifluridine/tipiracil has been approved as third line treatment in mCRC, demonstrating survival benefit and acceptable toxicity profile in the phase III RECOURSE study. Patient and methodsWe performed a multicenter retrospective real-world analysis of patients with mCRC receiving trifluridine/tipiracil between 2016 and 2019 in eight cancer centers across the United Kingdom. ResultsA total of 236 patients were included with median age of 69 years. All patients had received at least 2 lines of fluoropyrimidine-based chemotherapy doublet with oxaliplatin or irinotecan. About 10% of patients had ECOG ≥ 2. Median duration of trifluridine/tipiracil treatment was 3 months with an ORR of 2.1% and disease control rate of 21.6%. Median OS was 7.6 and median PFS 3.3 months. A dose reduction was required in 27% of patients, while 7.6% discontinued treatment due to toxicity. The most common grade 3 toxicities were neutropenia (34%), fatigue (10%), anemia (9%) and febrile neutropenia (5%). Baseline NLR <5 and CEA <200 had favorable prognostic (HR: 0.52 and 0.39, P≤ .001) and predictive value (OR: 4.1 and 6.7, P< .05). Development of grade 3 neutropenia predicted treatment response (OR: 0.32, P< .001). Following treatment with trifluridine/tipiracil 41% were referred for phase I trial or rechallenged with chemotherapy. ConclusionTrifluridine/tipiracil is well tolerated in refractory mCRC patients with comparable efficacy and toxicity profile to that of the phase III RECOURSE. Pretreatment NLR and CEA could serve as potential markers for patient selection, while treatment-induced grade 3 neutropenia predicted response. Prospective validation is needed.

Predicting if lung cancer will relapse—The role of neutrophil/lymphocyte ratio

Objective/BackgroundBaseline neutrophil/lymphocyte ratio (NLR), a surrogate marker for systemic inflammation and immunosuppression, is a well-studied prognostic marker in non-small cell lung cancer (NSCLC). This study tests if interim NLR is prognostic in NSCLC patients in remission. MethodsThis single-center, retrospective cohort study analyzed 131 NSCLC patients treated from 2010 to 2015 who achieved complete remission. NLR was calculated at baseline and from the first available blood sample during remission. Kaplan–Meier estimates of overall survival (OS) and time to recurrence were compared using the log-rank test for trend. Multivariable analysis was conducted using the Cox proportional hazards model. ResultsOf the 131 cases, 63 had subsequently recurred at the last follow-up. The mean age was 64 ± 10 years. Patients with stage I (35%), II (24%), and III (41%) were included. Histology were adenocarcinoma (60%), squamous cell (33%), and unspecified (7%). The majority of patients were smokers. For the univariate analysis interim NLR was binned into tertiles, NLR < 2, 2–4.08, and > 4.08. Of those with an interim NLR > 4.08, prognosis and recurrence risk were higher. In the multivariable analysis, remission NLR was strongly prognostic for OS (p < .001) as did patient’s age (p = .002), but not stage, race, sex, and baseline NLR. ConclusionsOur study found that interim NLR, obtained in remission, was strongly prognostic for OS and recurrence.

ABCL-265: Detection of Triple Protein Expression in Diffuse Large B-Cell Lymphoma (DLBCL): A Single-Center Study

Background DLBCL is the most common type of NHL. Genetic studies have revealed that one molecular subtype that is resistant to treatment by standard protocols occurs when there are concurrent translocations in the c-Myc, BCL-2, and BCL-6 genes. Objective Our study aimed to detect the presence of triple protein expression in patients diagnosed with DLBCL at the Clinical Oncology Department in Menoufia University Hospital. We also aimed to explore the possible associations between c-Myc, BCL-2, and BCL-6 co-expression (TEL) and clinical, as well as epidemiological, data of included patients. Patients and Methods A tissue microarray platform was constructed using cores from selected areas of each specimen. 2-mm-diameter cores were duplicated and spaced 0.2 mm apart. Several four-micron-thick sections were prepared from blocks. Hematoxylin and eosin slides were reviewed to confirm pathological diagnosis according to criteria defined by WHO, and immunohistochemistry was used for the detection of c-Myc, BCL-2, and BCL-6 expression. Stained slides were assessed for the percentage of cellular expression for each marker. Median expression was used as the threshold value for defining high and low expression for each marker. DLBCL with high expression for c-Myc, BCL-2, and BCL-6 was defined as TEL. Results Tissue microarray blocks were constructed from paraffin blocks of 94 cases with confirmed diagnoses of DCBL. The median age for participants was 56 years. c-Myc, BCL-2, and BCL-6 showed high protein expression in 51% (n=47), 55% (n=51), and 52.7% (n=49), respectively. Median-based triple protein expression constituted 15% of the sample (n=14). TEL was significantly higher in patients with poor ECOG performance status (PS >2), extranodal presentation, and bone marrow infiltration. No associations between TEL and other patient or disease characteristics (age, gender, smoking history, family history, comorbidities, B symptoms, LDH, B2 microglobulin, stage, IPI, IPI risk group, and baseline neutrophil-lymphocyte ratio) were found. Conclusion Triple protein expression lymphoma is not uncommon among the studied sample, constituting around 45.1% of cases. This positive protein expression was commonly found in patients with poor performance status, creating a particular need for new treatment modalities.

Abstract 372: Association between pre-treatment biomarkers and survival in metastatic non-small cell lung cancer patients treated with first-line pembrolizumab

Abstract Background: The introduction of immune checkpoint inhibitors such as pembrolizumab has significantly improved the outcomes of patients with metastatic non-small cell lung cancer (NSCLC). Pre-treatment biomarkers and clinical parameters such as body mass index (BMI), neutrophil-lymphocyte ratio (NLR), albumin, and antibiotic exposure have been shown to be prognostic factors in other immunotherapy-treated cancers. Here we report an association between these biomarkers and survival outcomes in metastatic NSCLC patients who received first-line treatment with pembrolizumab-based regimens. Methods: We conducted a retrospective, 3-center study using electronic medical record data for patients with NSCLC treated with first-line pembrolizumab, either as monotherapy or in combination with chemotherapy. Kaplan-Meier analysis was used to describe our primary end-points, progression-free survival (PFS) and overall survival (OS) after initiation of immunotherapy. Log-rank test was used to compare the PFS and OS for antibiotics usage one month prior to therapy initiation. Univariate analysis and Cox proportional modeling were used to analyze pre-treatment BMI, NLR, and albumin relative to PFS and OS. Results: 136 patients were identified in our cohort. 50 (36.8%) patients received pembrolizumab monotherapy, and 86 (63.2%) patients received pembrolizumab with chemotherapy. 95 (69.9%) patients had exposure to antibiotics one month prior to therapy initiation, 40 (29.4%) patients had no exposure, and 1 (0.7%) patient had no reported data on antibiotics usage. Mean NLR was 7.61 (n=135), mean albumin was 3.27 g/dL (n=133), and mean BMI was 25.89 (n=134). On univariate analysis, exposure to antibiotics (log-rank p-value = 0.03), higher NLR (hazard ratio = 1.027; p-value = 0.021), and lower albumin (hazard ratio = 0.385; p-value &amp;lt; 0.001) have significant associations with worse PFS. Furthermore, univariate analysis showed that elevated NLR (hazard ratio = 1.036; p-value = 0.004), lower albumin (hazard ratio = 0.440; p-value = 0.002), and lower BMI (hazard ratio = 0.952; p-value = 0.032) are associated with worse OS. Cox proportional modeling revealed that lower albumin maintains a significant association with worse PFS (hazard ratio = 0.412; p-value&amp;lt;0.001) and worse OS (hazard ratio = 0.509; p-value = 0.004) while considering antibiotic exposure and NLR. Conclusion: Exposure to antibiotics within one month of pembrolizumab initiation, higher baseline NLR, and lower baseline albumin are associated with worse PFS. Elevated baseline NLR, lower baseline albumin, and lower BMI are associated with poorer OS. These results enhance our understanding of how these biomarkers may predict efficacy of immune checkpoint inhibitor therapy in patients with NSCLC. Larger prospective studies should further investigate the clinical utility of these biomarkers. Citation Format: Ishani Joshi, Monica Peravali, Xue Geng, Jiahua Zhang, Giuseppe Giaccone, Chul Kim. Association between pre-treatment biomarkers and survival in metastatic non-small cell lung cancer patients treated with first-line pembrolizumab [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 372.

Prognostic role of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and systemic immune inflammation index in acute ischemic stroke: A STROBE-compliant retrospective study.

The acute ischemic stroke (AIS) is a devastating disease and remains the leading cause of death and disability. This study aims to evaluate the role of hematological inflammatory markers (neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], and systemic immune inflammation index [SII]) in predicting the neurological recovery in acute cerebrovascular events over 1-year follow-up.Adult patients diagnosed with AIS within 3 hours from January 2016 to December 2018 were recruited retrospectively. The modified Rankin Scale (mRS) was recorded upon admission to the emergency department (ED) and 1, 3, 6, and 12 months after a stroke. The primary outcome measure was the neurological recovery. The neurological recovery was defined as an improvement in mRS score ≥ 1 compared with that at the ED admission baseline.A total of 277 consecutive adult patients with AIS within 3 hours were enrolled. The initial average of the National Institute of Health Stroke Scale was 9.2 ± 7.8, and 90.3% of patients had an mRS ≥ 2 at ED admission baseline. The overall neurological recovery rates of 48.7%, 53.7%, 59.2%, and 55.9% were observed at 1, 3, 6, and 12 months follow-up, respectively. The multivariate analysis revealed that the baseline NLR value was a significant predictor of neurological recovery at 3 months after a stroke (adjusted odds ratio = 0.89, 95% confidence interval = 0.80–0.99, P = .035).A low NLR at ED admission could be useful marker for predicting neurological recovery at 3 months after stroke.

Integration of circulating tumor cell and neutrophil-lymphocyte ratio to identify high-risk metastatic castration-resistant prostate cancer patients

BackgroundThe neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and circulating tumor cells (CTCs) have been associated with survival in castration-resistant prostate cancer (CRPC). However, no study has examined the prognostic value of NLR and PLR in the context of CTCs.MethodsBaseline CTCs from mCRPC patients were enumerated using the CellSearch System. Baseline NLR and PLR values were calculated using the data from routine complete blood counts. The associations of CTC, NLR, and PLR values, individually and jointly, with progression-free survival (PFS) and overall survival (OS), were evaluated using Kaplan-Meier analysis, as well as univariate and multivariate Cox models.ResultsCTCs were detected in 37 (58.7%) of 63 mCRPC patients, and among them, 16 (25.4%) had ≥5 CTCs. The presence of CTCs was significantly associated with a 4.02-fold increased risk for progression and a 3.72-fold increased risk of death during a median follow-up of 17.6 months. OS was shorter among patients with high levels of NLR or PLR than those with low levels (log-rank P = 0.023 and 0.077). Neither NLR nor PLR was individually associated with PFS. Among the 37 patients with detectable CTCs, those with a high NLR had significantly shorter OS (log-rank P = 0.024); however, among the 26 patients without CTCs, the OS difference between high- and low-NLR groups was not statistically significant. Compared to the patients with CTCs and low NLR, those with CTCs and high levels of NLR had a 3.79-fold risk of death (P = 0.036). This association remained significant after adjusting for covariates (P = 0.031). Combination analyses of CTC and PLR did not yield significant results.ConclusionAmong patients with detectable CTCs, the use of NLR could further classify patients into different risk groups, suggesting a complementary role for NLR in CTC-based prognostic stratification in mCRPC.

Elevated neutrophil-lymphocyte ratio predicts vascular remodelling outcome in spontaneous isolated superior mesenteric dissection.

The neutrophil-lymphocyte ratio (NLR) is a prognostic marker predicting in-hospital mortality and stent patency in vascular disorders. This study aimed to investigate whether the NLR obtained at admission can be used to predict vascular remodelling outcomes in spontaneous isolated superior mesenteric dissection (SISMAD) patients. A total of 109 consecutive SISMAD patients, admitted to a single centre between November 2017 and June 2019, were retrospectively enrolled. Demographics, comorbidities, imaging data, and follow-up results were recorded. NLR at admission was calculated from a routine hemogram. The study endpoint was complete vascular remodelling or follow-up deadline. Patients were divided into two groups: complete vascular remodelling (Group 1) and partial vascular remodelling (Group 2). All parameters, including NLR, were compared between the groups. Multivariate logistic regression analysis determined whether NLR is independent of vascular remodelling in SISMAD patients after conservative treatment. Complete vascular remodelling of SISMAD occurred in 26 patients (23.9%) and partial remodelling in 83 patients (76.1%). Baseline NLR was significantly higher in the partial remodelling group than in the complete remodelling group [(6.32±2.10) vs. (4.90±2.12), p=0.003]. Complete remodelling was higher in the low NLR group than in the high NLR group [(15, 34.1%) vs. (11, 16.9%), p=0.039]. NLR (odd ratio [OR], 1.631; 95% confidence interval [CI], 1.027-2.592; p=0.038) and superior mesenteric artery-distal aorta angle (OR, 9.246; 95% CI, 2.217-38.560; p=0.002) were independent predictors of complete remodelling in multivariate logistic regression analysis. From the receiver operating characteristic curve, the best NLR cut-off value to predict complete vascular remodelling was 5.37, with 72.3% sensitivity and 69.2% specificity. The inflammation marker NLR may predict worse vascular remodelling in SISMAD patients.

P215 Blood-based prognostic biomarkers in Crohn’s patients treated with biologics: a new promising tool to predict endoscopic outcomes

Abstract Background 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). Conclusion 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.

Kinetics of the neutrophil-lymphocyte ratio during PD-1 inhibition as a prognostic factor in advanced hepatocellular carcinoma.

Programmed death 1 (PD-1) inhibitors have improved survival outcomes and produced durable responses in advanced hepatocellular carcinoma (HCC) for some patients. Here, we evaluated the relationship between the baseline and kinetics of the neutrophil-lymphocyte ratio (NLR) and clinical outcomes in nivolumab-treated HCC patients. All consecutive HCC patients treated with nivolumab between July 2017 and June 2020 were screened for the eligibility. The NLRs were calculated before and at 2, 4 and 6weeks after treatment. Survival outcomes were compared based on the baseline and kinetics of NLR. We additionally analysed the association of the baseline and dynamic changes in the NLR with hyperprogression (HPD). Among the 194 included cases, most patients were male (82.0%) and had a Child-Pugh Class A disease (70.6%). Patients with a baseline NLR≥3 (hazard ratio [HR] 2.46; 95% CI 1.63-3.71) had a poorer overall survival than patients with baseline NLR<3. During the treatment, the NLR increased rapidly in patients developing HPD, and only a ΔNLR at 4weeks was predictive of HPD. The risk of HPD increased by 20% for every 20% increase in the ΔNLR at 4weeks. Accordingly, an NLR increase at 4weeks (HR 1.79; 95% CI 1.19-2.68) was associated with an increased risk of death, especially among patients with a baseline NLR≥3. The baseline and on-treatment kinetics for the NLR are effective prognostic indicators in nivolumab-treated patients with HCC. This may help to guide patient selection and on-treatment strategies for immunotherapies in advanced HCC.

Translational relevance of baseline NLR and LMR ratio in predicting response of EGFR-TKI.

e15020 Background: Neutrophil-Lymphocyte Ratio (NLR) and Lymphocyte-Monocyte Ratio (LMR) have been under scrutiny for their potential as a prognostic tool in various cancers. While there have been conflicting opinions on their reliability, NLR has shown rather near accurate predictions in previous studies. Targeted tyrosine kinase inhibitors have shown good results in improving OS and PFS of patients with EGFR-mutated NSCLC but the prognostic indicators are limited. This study aims to decipher if baseline NLR and LMR ratios are valid tools to predict prognosis of patients with EGFR-mutated NSCLC. Methods: We analyzed 78 advanced NSCLC patients harboring Exon 19 Deletion and Exon 21 L858R mutation undergoing EGFR-TKI therapy. Baseline NLR and LMR were measured in peripheral blood within two weeks prior to the initiation of TKIs. Overall survival was used as an outcome measure for TKI therapy and it is defined as from the initiation of TKIs to death by any cause. The cut-off for NLR and LMR was calculated using an X-tile plot (version 3.6.1, Yale University, New Haven, CT, USA) by dividing marker data into three populations: low, middle, and high (i.e., two divisions), with randomized 1:1 “training” and “validation” cohorts. Results: Overall median survival of the study group was 31.5 months and median age was found to be 60 years. Gefitinib (35.9%) and afatinib (34.6%) were the most commonly prescribed followed by erlotinib (21.8%) and osimertinib (7.7%). With cut-points of 1.8 and 4.9 we analyzed three populations for baseline NLR as ≤1.8, 1.9-4.9 and &gt; 4.9. Similarly, for LMR cut-points of 3.49 and 5 were found and we analyzed patients with LMR of ≤3.49, 3.5-5 and &gt;5. There was a statistically significant overall median survival observed as per the obtained NLR as well as LMR cut-off as given in the table. Conclusions: A statistically significant co-relation was observed with baseline NLR and LMR ratio in predicting response to EGFR TKIs in NSCLC. Our study further strengthens the concept of using NLR and LMR as peripheral blood biomarkers for prognostic assessment in cancer patients undergoing treatment.[Table: see text]

Associations between longitudinal pretreatment BMI and neutrophil/lymphocyte ratio(NLR) and progression-free(PFS) and overall survival(OS) in advanced NSCLC patients treated with single agent anti-PD-1/anti-PDL1 monoclonal antibodies(mAbs).

e21189 Background: Several parameters that have been associated with outcomes in patients with metastatic NSCLC treated with anti-PD1/PDL1 mAbs include tumor PD-L1 expression, tumor mutational burden, and baseline NLR. Further investigation into clinical correlates of benefit with immune checkpoint inhibitors remains an unmet need. Methods: The objective of this retrospective study was to examine the potential influence of pretreatment cachexia and chronic inflammation in patients with NSCLC that received second- or third- line single agent anti-PD1/PDL1 mAbs. Weight, BMI, and NLR, as well as longitudinal changes in these variables from at least six-weeks prior to initiation of treatment were correlated with progression-free and overall survival (PFS/OS). These associations were assessed using statistical methods for time-to-event analysis. Results: 192 patients were included: 59% female, 72% Caucasian, 18% African American, 79% current or former smokers. 185 patients had pretreatment NLR values and 63% and 42% had NLR ratios &gt; 3.5 and &gt; 5, respectively. 187 patients had pretreatment weight and BMI available. Of these, 63% had a loss in BMI prior to initiation of anti-PD1/PDL1 mAbs, 29% with &gt; 5% loss. Any BMI loss as well as BMI loss &gt; 5% over the time period prior to treatment initiation were associated with shorter PFS (p &lt; 0.01, 2.1 vs 4.37 mos for loss &gt; 5% vs ≤ 5%) and change in BMI assessed in continuous scale was also associated with PFS (HR = 0.94, p &lt; 0.05). Similarly, any BMI loss and BMI loss &gt; 5% were associated with shorter OS (p &lt; 0.01. 7.33 vs 12.23 mos for loss &gt; 5% vs ≤ 5%) and change in BMI and baseline BMI assessed in continuous scale were additionally associated with OS (HR = 0.97 and 0.94, p &lt; 0.05). Baseline NLR &gt; 5 was associated with shorter PFS (p &lt; 0.01) and baseline NLR assessed in continuous scale was negatively associated (HR = 1.01, p &lt; 0.05). Moreover, pre-treatment NLR &gt; 5 and baseline NLR &gt; 3.5 were associated with shorter OS (p &lt; 0.05). Pre-treatment NLR, baseline NLR, and %change in NLR, assessed in continuous scale, were negatively associated with OS (HR = 1.04, 1.02, 1.12, p &lt; 0.01). Conclusions: This retrospective study identified clinical features of NLR and BMI at treatment initiation and in the immediate pre-treatment period that were associated with PFS and OS on anti-PD1/PDL1 mAbs therapy. These parameters can easily be investigated in the front-line population. They may also have utility in identifying patients that would benefit from therapeutic strategies to reverse weight loss and inhibit immunosuppressive effects associated with elevated NLR in order to increase the effectiveness of immunotherapy.

Relative dose intensity (RDI) of nab-P in gem+nab-P combination in pancreatic cancer treatment and the prognostic role of baseline NLR.

e16269 Background: Combination of Gem+Nab-P is considered as a dose intense regimen which exhibits synergistic cytotoxic activity and equally effective in increasing survival as FOLFIRINOX regimen in pancreatic cancer. However, number of patients who tolerates such dose intense regimen is found to be less in Indian population. The importance of maintaining optimum RDI is well-known however a low RDI may reflect a poor tolerability. Therefore, the present study aimed to identify desired relative dose intensity and explore the potential of baseline NLR as a prognostic biomarker. Methods: A retrospective chart review was performed of 26 patients with a median age of 65.5 years who received this drug combination either as first-line or second-line treatment for pancreatic adenocarcinoma at a single institution. Treatment outcome was measured using overall survival and toxicities were classified according to CTCAE guidelines. The thresholds for RDI of Gem and Nab-P, and baseline NLR cut-off for predicting survival was calculated by constructing ROC curves. Results: Median overall survival was 11.5 months. Median RDI of Gem and Nab-P was found to be 79% (30-94) and 71% (39 –114) respectively. We estimated a RDI cut-off of 67% in Nab-P and 68% in Gem and observed a statistically significant favorable outcome in patients who received Nab-P with RDI &gt; 67% ( p-0.021). No significant relationship of Gem RDI with outcome was observed. Median overall survival was found to be higher in patients with a baseline NLR &lt; 2.35, patients on D1, D8, D15 treatment regimen and those who received Nano particle bound paclitaxel. Complete assessment of study subjects are enlisted in the table. Grade 3 neuropathy, fatigue, and hyponatremia were reported in 2, 5 and 4 patients respectively. Grade 2 skin rashes and neuropathy were seen in 3 patients each. Conclusions: Our study concludes that tolerability of Gem+Nab P is a concern and it is expected to exhibit a durable response only if it achieves an optimum RDI of Nab-P. The study indicates varied efficacy in different pharmaceutical preparations of paclitaxel favoring the use of nano-particle formulations. The study also indicates that baseline NLR is an important prognostic biomarker in pancreatic cancer[Table: see text]

Assessment of Inflammation Biomarkers in Diabetic Macular Edema Treated with Intravitreal Dexamethasone Implant

Purpose: To evaluate inflammation biomarkers in diabetic macular edema (DME) treated with intravitreal dexamethasone implant (Ozurdex®). Methods: This retrospective single-center study investigated 64 eyes of 64 patients with DME who were nonresponsive to prior antivascular endothelial growth factor and treated with intravitreal Ozurdex. The neutrophil/lymphocyte ratio (NLR), monocyte/lymphocyte ratio (MLR), and platelet/lymphocyte ratio were calculated. Visual acuity and optical coherence tomography markers, including hyper-reflective dots and subretinal fluid (SRF), were determined, and central retinal thickness was also evaluated monthly for 3 months. Results: The average age was 64.06 ± 7.81 (48-84) years. The baseline NLR and MLR were significantly higher in patients with better visual outcomes (P = 0.029 and P = 0.048, respectively). Better anatomical outcomes were observed in the presence of SRF (P = 0.027). No significant differences were observed in the rates of the presence of SRF and hyper-reflective points about the better functional outcome (P > 0.05). Conclusions: SRF as an imaging biomarker, and NLR and MLR as blood biomarkers, stand out as markers of inflammation and were found to be associated with better response to Ozurdex implantation in DME.

Glycemic and lipid variability for predicting complications and mortality in diabetes mellitus using machine learning

IntroductionRecent studies have reported that HbA1c and lipid variability is useful for risk stratification in diabetes mellitus. The present study evaluated the predictive value of the baseline, subsequent mean of at least three measurements and variability of HbA1c and lipids for adverse outcomes.MethodsThis retrospective cohort study consists of type 1 and type 2 diabetic patients who were prescribed insulin at outpatient clinics of Hong Kong public hospitals, from 1st January to 31st December 2009. Standard deviation (SD) and coefficient of variation were used to measure the variability of HbA1c, total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglyceride. The primary outcome is all-cause mortality. Secondary outcomes were diabetes-related complications.ResultThe study consists of 25,186 patients (mean age = 63.0, interquartile range [IQR] of age = 15.1 years, male = 50%). HbA1c and lipid value and variability were significant predictors of all-cause mortality. Higher HbA1c and lipid variability measures were associated with increased risks of neurological, ophthalmological and renal complications, as well as incident dementia, osteoporosis, peripheral vascular disease, ischemic heart disease, atrial fibrillation and heart failure (p < 0.05). Significant association was found between hypoglycemic frequency (p < 0.0001), HbA1c (p < 0.0001) and lipid variability against baseline neutrophil-lymphocyte ratio (NLR).ConclusionRaised variability in HbA1c and lipid parameters are associated with an elevated risk in both diabetic complications and all-cause mortality. The association between hypoglycemic frequency, baseline NLR, and both HbA1c and lipid variability implicate a role for inflammation in mediating adverse outcomes in diabetes, but this should be explored further in future studies.

High Neutrophil-Lymphocyte Ratio and Delta Neutrophil-Lymphocyte Ratio Are Associated with Increased Mortality in Patients with Hepatocellular Cancer.

The neutrophil-lymphocyte ratio (NLR) has been proposed as a prognostic biomarker for cirrhosis and non-liver malignancies. We aimed to evaluate the prognostic value of NLR in a diverse cohort of patients with hepatocellular carcinoma (HCC). We performed a retrospective study of patients diagnosed with HCC between 2008 and 2017 at two large US health systems. We used Cox proportional hazard and multivariable ordinal logistic regression models to identify factors associated with overall survival and response to first HCC treatment, respectively. Primary variables of interest were baseline NLR and delta NLR, defined as the difference between pre- and post-treatment NLR. Among 1019 HCC patients, baseline NLR was < 5 in 815 (80.0%) and ≥ 5 in 204 (20.0%). Patients with NLR ≥ 5 had a higher proportion of infiltrative tumors (36.2% vs 22.3%), macrovascular invasion (39.6% vs 25.5%), metastatic disease (20.6% vs 11.4%), and AFP > 200ng/mL (45.6% vs 33.8%). Baseline NLR ≥ 5 was independently associated with higher mortality (median survival 4.3 vs 15.1months; adjusted HR 1.70, 95%CI 1.41-2.06), with differences in survival consistent across BCLC stages. After adjusting for baseline covariates including NLR, delta NLR > 0.26 was also independently associated with increased mortality (HR 1.42, 95%CI 1.14-1.78). In a secondary analysis, high NLR was associated with lower odds of response to HCC treatment (20.2% vs 31.6%; adjusted OR 0.55, 95%CI 0.32-0.95). In a large Western cohort of patients with HCC, high baseline NLR and delta NLR were independent predictors of mortality. NLR is an inexpensive test that may be a useful component of future HCC prognostic models.

139P Association of baseline neutrophil-lymphocyte and platelet-lymphocyte ratios with disease progression in high-risk breast cancer patients

Incidence rates of breast cancer have continuously increased worldwide with higher proportion of mortality rates in developing countries. More than a third of breast cancer will develop distant metastases as the most attributable causes of mortality in malignancy. An economical but effective marker to estimate risk of disease progression might be very valuable in developing countries to improve surveillance.

A composite biomarker of neutrophil-lymphocyte ratio and hemoglobin level correlates with clinical response to PD-1 and PD-L1 inhibitors in advanced non-small cell lung cancers

BackgroundImmune checkpoint inhibitors (ICIs) have been incorporated into various clinical oncology guidelines for systemic treatment of advanced non-small cell lung cancers (aNSCLC). However, less than 50% (and 20%) of the patients responded to the therapy as a first (or second) line of therapy. PD-L1 immunohistochemistry (IHC) is an extensively studied biomarker of response to ICI, but results from this test have equivocal predictive power. In order to identify other biomarkers that support clinical decision-making around whether to treat with ICIs or not, we performed a retrospective study of patients with aNSCLC who underwent ICI-based therapy in the Mount Sinai Health System between 2014 and 2019.MethodsWe analyzed data from standard laboratory tests performed in patients as a part of the routine clinical workup during treatment, including complete blood counts (CBC) and a comprehensive metabolic panel (CMP), to correlate test results with clinical response and survival.ResultsOf 11,138 NSCLC patients identified, 249 had been treated with ICIs. We found associations between high neutrophil-to-lymphocyte ratio (NLR ≥ 5) and poor survival in ICI-treated NSCLC. We further observed that sustained high NLR after initiation of treatment had a more profound impact on survival than baseline NLR, regardless of PD-L1 status. Hazard ratios when comparing patients with NLR ≥ 5 vs. NLR < 5 are 1.7 (p = 0.02), 3.4 (p = 4.2 × 10− 8), and 3.9 (p = 1.4 × 10− 6) at baseline, 2–8 weeks, and 8–14 weeks after treatment start, respectively. Mild anemia, defined as hemoglobin (HGB) less than 12 g/dL was correlated with survival independently of NLR. Finally, we developed a composite NLR and HGB biomarker. Patients with pretreatment NLR ≥ 5 and HGB < 12 g/dL had a median overall survival (OS) of 8.0 months (95% CI 4.5–11.5) compared to the rest of the cohort with a median OS not reached (95% CI 15.9-NE, p = 1.8 × 10− 5), and a hazard ratio of 2.6 (95% CI 1.7–4.1, p = 3.5 × 10− 5).ConclusionsWe developed a novel composite biomarker for ICI-based therapy in NSCLC based on routine CBC tests, which may provide meaningful clinical utility to guide treatment decision. The results suggest that treatment of anemia to elevate HGB before initiation of ICI therapy may improve patient outcomes or the use of alternative non-chemotherapy containing regimens.