Baseline Neutrophil-to-lymphocyte Ratio Research Articles

Predictive Factors of Chemotherapy-Induced Peripheral Neuropathy in Breast Cancer: A Decision Tree Model Approach.

Chemotherapy-induced peripheral neuropathy (CIPN) poses a substantial challenge in breast cancer (BC) chemotherapy, affecting the patient's quality of life. Recent studies have focused on exploring predictors and patterns of CIPN occurrence. We aimed to develop a prediction model for CIPN occurrence using a classification and regression tree (CART) algorithm. In this prospective study of 170 patients with BC undergoing chemotherapy, patient-reported adaptation of the Common Terminology Criteria for Adverse Events version 4.0 was used to assess CIPN occurrence. Multivariable analysis using the CART model was tuned using 10-fold cross-validation to identify baseline predictors for CIPN throughout chemotherapy. A receiver operating characteristic curve analysis was conducted for the CART model. A multivariable logistic regression was conducted from the variables included in the CART model to assess the strength and direction of the association. The prevalence of CIPN was 64.7% (n = 110). The most decisive predictor of CIPN occurrence in the CART model was the subject's C-reactive protein (CRP) level. CRP level >3.91 mg/dL, BMI >21.85 kg/m2, and a marital status of unmarried have predicted a probability of 100% in CIPN occurrence. The CART model showed an accuracy of 65.9%, sensitivity of 51.7%, specificity of 73.2%, and an area under the curve of 0.705. A CRP level of >3.91 mg/dL and a neutrophil-to-lymphocyte ratio (NLR) of >2.82 are significantly associated with the occurrence of CIPN (odds ratio [OR], 2.01 [95% CI, 1.01 to 4.01]; P = .046, OR, 2.09 [95%, CI, 1.02 to 4.24]; P = .042, respectively). Baseline CRP, NLR, BMI level, and marital status are significant predictors of CIPN occurrence throughout chemotherapy. Our CART model was better at ruling out individuals who would not experience CIPN. The CART model may provide insight into the future development of individualized patient care and prevention strategies.

Neutrophil-to-lymphocyte ratio predicts poor prognosis in patients with chronic kidney disease-related pulmonary hypertension: A retrospective study.

Inflammation plays a crucial role in chronic kidney disease (CKD) and pulmonary hypertension (PH). Considering that the neutrophil-to-lymphocyte ratio (NLR) has recently emerged as a powerful predictor of adverse outcomes in many chronic diseases, we aimed to investigate the association between NLR and all-cause mortality in patients with CKD-related PH. A total of 176 hospitalized patients with predialysis CKD-related PH were recruited retrospectively from January 2012 to June 2020 by reviewing electronic medical records. The NLR and clinical characteristics of the patients were included in the current analysis. The Kaplan-Meier method and univariate and multivariate Cox regression analyses were performed to identify the association between NLR and the incidence of all-cause mortality. Baseline NLR values were associated with hemoglobin, estimated glomerular filtration rate and C-reactive protein. During a median follow-up period of 32.5 (11.3-53.0) months, 23 patients died. Regardless of whether the NLR acted as a continuous variable with a hazard ratio of 1.408 (95% confidence interval: 1.124-1.763) or a categorical variable (NLR ≤4.3 vs NLR >4.3) with a hazard ratio of 3.100 (95% confidence interval: 1.299-7.402), an elevated NLR was significantly associated with all-cause mortality in different models. A greater NLR at baseline was remarkably associated with a higher all-cause mortality in hospitalized patients with CKD-related PH.

Impact of neutrophil-to-lymphocyte ratio on clinical outcomes in patients with or without chronic kidney disease undergoing percutaneous coronary intervention

Abstract Background Neutrophil-to-lymphocyte ratio (NLR) has recently emerged as inexpensive inflammatory biomarker associated with worse cardiovascular outcomes. However, little is known about its role in risk stratification of patients with both chronic kidney disease (CKD) and coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). Purpose We aimed to evaluate the clinical impact of baseline NLR in patients with and without CKD undergoing PCI. Methods We retrospectively evaluated all consecutive patients undergoing PCI between 2012-2022 in a large tertiary US center. We excluded patients without available NLR and those who were deemed to have active hematological or infective diseases, including patients with extremely low or high lymphocyte and neutrophil counts or with hs-CRP above 10 mg/L. Quartiles of NLR were derived in the overall population and patients were stratified according to presence of CKD (eGFR < 60 ml/min). Within each group, we estimated the risk of adverse events using the lowest NLR quartile as reference. The primary endpoint was 12-month incidence of major adverse cardiovascular events (MACE), defined as the composite of all-cause death, myocardial infarction, or stroke. Secondary endpoints included incidence of clinically relevant bleeding and contrast-associated acute kidney injury (CA-AKI), defined as ≥ 0.3 mg/dL or ≥ 50% serum creatinine increase from baseline. Results A total of 7,287 patients were included in the analysis; of these 2,008 (27.6%) had CKD and 5,279 (72.4%) did not. CKD patients (mean eGFR 40.8±16.1 ml/min) were older, had more comorbidities, and presented with higher hs-CRP levels and a greater estimated risk of CA-AKI. Overall, patients with elevated NLR had more severe CAD and underwent more complex PCI. In CKD patients, incidence of adverse events increased stepwise and those in the 4th NLR quartile had the highest adjusted risks of MACE (HRadj 1.86, 95% CI 1.12-3.08; P=0.012), all cause death (HRadj 2.44, 95% CI 1.18-5.05; P=0.003) and bleeding (HRadj 1.74, 95% CI 1.07-2.84; P=0.002) at 1 year, as compared to those in the lowest quartile (Table 1). In patients without CKD, MACE and all-cause death incidences were numerically higher in the 4th quartile but risk estimates were no longer statistically significant after adjustment. The overall incidence of CA-AKI was much greater in the CKD group. When compared to the lowest quartile, patients in the 4th NLR quartile showed a trend for higher risk of CA-AKI in CKD group, while they had a significant increased risk in non-CKD group (Figure 1). Conclusions Elevated NLR is strongly associated with higher risk of MACE and all-cause mortality in CKD patients. Conversely, the risk of bleeding and CA-AKI is increased with elevated NLR in both CKD and non-CKD patients. Thus, NLR may further inform risk stratification of CKD patients undergoing PCI.

Impact of neutrophil-to-lymphocyte ratio on clinical outcomes in patients with acute or chronic coronary syndrome undergoing percutaneous coronary intervention

Abstract Background Neutrophil-to-lymphocyte ratio (NLR) has recently emerged as an inflammatory biomarker associated with atherosclerosis and cardiovascular events. However, its role in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) remains unclear. Purpose We aimed to evaluate the clinical impact of baseline NLR in patients undergoing PCI for acute coronary syndrome (ACS) and chronic coronary syndrome (CCS). Methods We retrospectively evaluated all consecutive patients undergoing PCI between 2012-2022 in a large tertiary US hospital. We excluded patients for whom NLR was not available and those who were deemed to have active hematological or infective diseases, including patients presenting with extremely low or high lymphocyte and neutrophil counts or with hs-CRP above 10 mg/L. Quartiles of NLR were derived in the overall population and patients were stratified according to clinical presentation. Within each group, we estimated the risk of 12-month adverse events using the lowest NLR quartile as reference. The primary endpoint was major adverse cardiovascular events (MACE), defined as the composite of all-cause death, myocardial infarction (MI), or stroke. Secondary endpoints were MACE individual components and any periprocedural or post-discharge clinically relevant bleeding. Results A total of 7,201 patients were included in the analysis; of these 3,975 (55.2%) had ACS and 3,226 (44.8%) CCS. Patients in the 4th quartile (NLR > 5.0) were more frequently male, older, and presented more often with chronic kidney disease and complex coronary artery disease. Smoking, diabetes and history of CAD, as well as triglycerides, LDL, non-HDL and total cholesterol levels were lower in the 4th NLR quartile. In patients presenting with CCS, the risk of MACE, all-cause death, MI was similar across NLR quartiles, while the risk of bleeding increased stepwise (Figure 1). In patients presenting with ACS, the 4th NLR quartile had the highest adjusted risk of MACE (HRadj 1.82, 95% CI 1.25-2.67; P=0.002), all cause death (HRadj 2.56, 95% CI 1.41-4.66; P<0.001), and bleeding (HRadj 1.82 95% CI 1.25-2.63, P<0.001) at 1 year, as compared to the lowest quartile (Table 1). Conclusions Among patients undergoing PCI, elevated NLR is strongly associated with risk of MACE and all-cause mortality in patients presenting with ACS but not in those with CCS. Conversely, the risk of bleeding was augmented with higher NLR in both ACS and CCS patients undergoing PCI. In this setting, NLR may inform risk stratification at the time of PCI.

Neutrophil/lymphocyte ratio identifies low-risk polycythaemia vera patients for early Ropeginterferon alfa-2b therapy.

We investigated the effect of Ropeginterferon alfa-2b (Ropeg) versus phlebotomy-only (Phl-O) on the neutrophil-to-lymphocyte ratio (NLR) in 126 patients randomized in the low-polycythaemia vera (PV) phase II trial. Patients with a baseline NLR ≥3.5 vs. <3.5 had a longer history of PV, were more likely to have splenomegaly, higher JAK2V617F variant allele frequency (VAF) (56% vs. 20% p = 0.001) and more proliferative disease. Ropeg was superior to Phl-O in reducing NLR (p = 0.008), and the reduction was strongly influenced by the reduction in neutrophils and less by a change in lymphocytes (-59% and -14% respectively). This effect was associated with the achievement of the low-PV primary end-point (p = 0.021), symptom reduction and reduction in JAK2 VAF. Interestingly, the reduction in JAK2 VAF from baseline was linearly associated with the reduction in NLR. Patients who failed Phl-O at 12 months had characteristics that distinguished them from responders, including very high NLR and resistance to cross-over to 100 μg Ropeg every 2 weeks suggesting higher escalated doses of Ropeg. In conclusion, the study provides evidence that NLR can serve as a valuable biomarker to assess and guide treatment with Ropeg in the early stage of low-risk PV patients.

A study of pre- and post-treatment hematologic markers of immune response in patients undergoing radiotherapy for soft tissue sarcoma.

This study investigates the impact of pre- and post-treatment hematologic markers, specifically neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), on treatment outcomes in soft tissue sarcoma (STS) patients undergoing radiation therapy (RT). Data from 64 patients who underwent RT for curative management of STS were reviewed. Pre-RT and post-RT hematologic measures were evaluated for associations with survival outcomes. A normal tissue complication probability (NTCP) curve for predicting ΔPLR ≥ 75 was modeled using a probit function. Elevated baseline NLR was associated with worse overall survival (OS) and disease-free survival (DFS), while elevated PLR was associated with worse DFS. Post-RT, elevated PLR was linked to worse OS and DFS. Increasing PLR change post-RT was associated with worse OS and DFS. Receiver operating characteristics analysis determined ΔPLR ≥ 75 to be a robust cutoff associated with worse DFS. Bone V10Gy ≥362 cc corresponded to a 50% risk of developing ΔPLR ≥ 75. These results suggest that hematologic markers could serve as prognostic biomarkers in both pre- and post-treatment settings for STS patients undergoing RT. Future studies can consider using bone V10Gy < 362 cc as a potential cutoff to reduce the risk of increased PLR after RT.

Food Aversion, Systemic Inflammation and Intramuscular Adipose Tissue are Mortality Predictors in Advanced Lung Cancer Patients

ABSTRACTBackgroundCancer cachexia, systemic inflammation and muscle wasting are associated with poor survival in non–small cell lung cancer (NSCLC) patients (pts). We hypothesized whether neutrophil‐to‐lymphocyte ratio (NLR) and intramuscular adipose tissue/skeletal muscle index (IMAT/SMI) would predict prognosis in metastatic NSCLC (mNSCLC). In addition, we verified the role of a cancer cachexia questionnaire (EORTC‐QLQ‐CAX24) in the survival prediction.MethodsWe analysed a prospective cohort of 128 treatment‐naive mNSCLC pts (April 2017 to May 2020). We evaluated QoL using the EORTC‐QLQ‐C30 and EORTC‐QLQ‐CAX24 scales. We used the baseline NLR as a surrogate of systemic inflammation. We did evaluate IMAT/SMI using baseline plain computed tomography imaging. Cox multivariate regression, including age, sex, ECOG‐PS and histology as covariates, was performed.ResultsElevated NLR (hazard ratio [HR] 1.26, 95% confidence interval [CI]: 1.01–1.59, p = 0.038), IMAT/SMI ratio (HR 1.37, 95% CI: 1.03–1.84, p = 0.032) and high CAX24 scores for food aversion (HR 1.52, 95% CI: 1.13–2.03, p = 0.006) were associated with worse prognosis in mNSCLC. Indeed, higher ECOG‐PS (Spearman rho = 0.208, p = 0.027), CAX24 scores for food aversion (Spearman rho = 0.197, p = 0.036), loss of control (Spearman rho = 0.212, p = 0.024) and eating and weight loss worry domains (Spearman rho = 0.219, p = 0.020) were associated with elevated NLR levels.ConclusionsElevated NLR, IMAT/SMI ratio and CAX24 score for food aversion are independently associated with worse survival in mNSCLC. These data underscored the importance of cachexia features as negative prognostic factors in mNSCLC and revealed the EORTC‐QLQ‐CAX24 questionnaire as a new tool for helping clinical decision‐making.Trial Registration: ClinicalTrials.gov identifier: NCT03960034 and NCT04306094

Systemic Inflammation Indexes and Risk of Immune-related Adverse Events in Patients With Metastatic Urothelial Carcinoma Treated With Immunotherapy.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of metastatic urothelial carcinoma (mUC). However, they could be associated with immune-related adverse events (irAEs), which may be clinically significant. Identifying clinical characteristics that may be associated with a higher risk of irAEs is of great importance. We retrospectively collected data from all patients who received anti-PD1 or anti-PD-L1 for metastatic UC at our Institution from January 2017 to December 2022. Patients were dichotomized according to baseline neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and platelet-to-lymphocyte ratio (PLR) values. We performed univariate and multivariate logistic regression to determine the association between baseline characteristics and the development of irAEs. A total of 119 patients were identified. At a median follow-up of 29.6 months, 96 patients progressed and 82 died. Forty-five patients developed irAEs of any grade, 8 patients developed grade 3 toxicities. In the univariate analysis PS of 0 (p<0.01), baseline NLR <3.52, baseline PLR <194 (p=0.04) and baseline SII <906 (p=0.01) were significantly associated with a higher risk of developing irAEs, whereas in the multivariate analysis only PS=0 (p<0.01) and NLR <3.52 (p=0.03) maintained their correlation. Median progression-free survival (mPFS) and overall survival (mOS) were significantly longer in patients with NLR <3 (mPFS 3.8 vs. 2.6 months, p=0.01; mOS 15.3 vs. 5.6 months, p=0.002) and PS=0 (mPFS 4.8 vs. 2.1 months, p<0.001; mOS 15.3 vs. 3.8 months, p<0.001). Low baseline NLR, PLR, and SII and good PS are associated with a higher risk of developing irAEs in patients treated with ICIs for mUC.

Risk Stratification According to Baseline and Early Change in Neutrophil-to-Lymphocyte Ratio in Advanced Non-Small Cell Lung Cancer Treated with Chemoimmunotherapy: A Multicenter Real-World Study.

Chemoimmunotherapy is a standard treatment for advanced non-small-cell lung cancer (NSCLC). However, data on clinical predictive factors remain scarce. We aim to identify clinical biomarkers in patients undergoing chemoimmunotherapy. This multicenter, real-world cohort study included chemonaive patients who underwent chemoimmunotherapy between December 2018 and May 2022. Multivariate analysis was used to determine associations between survival outcomes and patient background, including baseline neutrophil-to-lymphocyte ratio (NLR) and its dynamic change (ΔNLR). To further investigate the clinical significance of NLR, patients were classified based on their peripheral immune status, defined by a combination of NLR and ΔNLR. The study included 280 patients with 30.1 months of median follow-up. Multivariate analysis revealed that older individuals, poor performance status, tumor proportion score < 1%, liver metastasis, baseline NLR ≥ 5, and ΔNLR ≥ 0 independently correlated significantly with shorter progression-free and overall survival (OS). Patients with high peripheral immune status (defined as NLR <5 and ΔNLR < 0) significantly improved long-term survival (2-year OS rate of 58.3%), whereas those with low peripheral immune status (defined as NLR ≥ 5 and ΔNLR ≥ 0) had extremely poor outcomes (2-year OS rate of 5.6%). Safety profiles did not differ significantly in terms of severe adverse events and treatment-related death rates despite the patients' peripheral immune status (P = 0.46 and 0.63, respectively). Our study provides real-world evidence regarding clinical prognostic factors for the efficacy of chemoimmunotherapy. The combined assessment of baseline NLR and ΔNLR could facilitate the identification of patients who are likely to achieve a durable response from chemoimmunotherapy.

Relative value of novel systemic immune-inflammatory indices and classical hematological parameters in predicting depression, suicide attempts and treatment response

This study compared the power of the novel inflammatory markers systemic immune inflammation index (SII) and the system inflammation response index (SIRI) versus the classical hematological indices neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and platelet counts in distinguishing between major depressive disorder (MDD) with and without suicide attempts and distinguishing the non-response to selective serotonin reuptake inhibitor (SSRI) treatment. A total of 139 young adult MDD patients and 54 healthy controls (HC) were included. We found that, in comparison to HC, baseline NLR, PLR, SII, and SIRI were significantly higher in MDD patients, but only NLR and SII had area under the ROC curve (AUC) values greater than 0.7. MDD patients with suicide attempts (SA) showed significantly higher baseline MLR and SIRI, and a tendency to increase NLR compared to those without SA. In terms of AUC, sensitivity, and specificity, NLR was better than MLR, SIRI, SII, and PLR in distinguishing SA. Non-responders to SSRI treatment showed a significant increase in baseline platelet count and PLR compared to responders with an AUC greater than 0.7. These findings highlight the potential benefit of combining novel and classical hematological indices in predicting depression, suicide attempts and treatment response.

The Influence of Circulating Immune Cell and CA125 Dynamics on Neoadjuvant Therapy Selection for Advanced Ovarian Cancer.

Background and Objectives: Ovarian cancer, including tubal and peritoneal cancer, is the third most common gynecological cancer and the leading cause of death from gynecological malignancies in developed countries. This study explores the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in determining the optimal duration of neoadjuvant chemotherapy (NACT) for advanced ovarian cancer. It also investigates the correlation between NLR dynamics and the KELIM score, a chemosensitivity marker, to enhance individualized therapeutic strategies. Materials and Methods: A total of 79 patients underwent NACT followed by interval debulking surgery (IDS) or palliative care. The data collected included demographic information, tumor characteristics, treatment modalities, and laboratory parameters. The baseline NLR (NLR-T0) and post-therapeutic NLR (NLR-T1) were calculated, and their variation (NLR∆) was analyzed. The KELIM score was determined using CA-125 values. Results: Patients with a high baseline NLR (≥2.5) had significantly worse progression-free survival (PFS) and overall survival (OS) compared to those with a low NLR (<2.5). A negative NLR∆ was associated with poorer PFS and OS. The KELIM score indicated a more effective treatment response, with higher scores correlating with better outcomes. The majority of patients achieved R0 resection, and those with favorable KELIM scores showed improved survival rates. Conclusions: The NLR is a valuable prognostic marker for assessing treatment response and guiding NACT duration in advanced ovarian cancer.

Dynamic Changes of Neutrophil-to-Lymphocyte Ratio on Predicting Response of Immune Checkpoint Inhibitors Plus Targeted Therapies for Unresectable Hepatocellular Carcinoma.

Multiple regimens of immune checkpoint inhibitors (ICIs) plus targeted therapies are commonly prescribed as first-line treatments for unresectable hepatocellular carcinoma (uHCC). Here, we aimed to investigate the correlation between dynamic changes of neutrophil-to-lymphocyte ratio (NLR) and tumor response to the combination of ICIs and targeted therapies for uHCC. Sixty-one patients who received ICIs plus targeted therapies for uHCC were enrolled in this retrospective study. The NLR before and at 3-6 weeks after treatments were assessed to calculate the dynamic NLR changes (ΔNLR). Multivariate logistic regression and Cox regression models were used to explore the relationship between dynamic NLR changes and tumor response or progression-free survival (PFS), respectively. Furthermore, we assessed the predictive effect of alpha-fetoprotein (AFP) changes in combination with dynamic NLR changes compared to AFP changes alone. The NLR at 3-6 weeks and ΔNLR after treatments significantly increased in patients who underwent progressive disease (PD), while the baseline NLR showed no significant difference between different tumor responses. Increased NLR and AFP after treatments were both independent predictors of PD (For NLR increase: OR, 2.28; 95% CI, 1.47-3.88, P < 0.001; For AFP increase: OR, 1.46; 95% CI, 1.03-2.17, P = 0.043), and correlated with worse PFS (for NLR increase: HR, 4.08; 95% CI, 1.99-8.36, P < 0.001; for AFP increase: HR, 2.10; 95% CI, 1.04-4.24, P = 0.039). The receiver operating characteristic (ROC) curve and net reclassification index (NRI) showed that the combination of dynamic NLR and AFP changes was better than AFP changes alone on predicting PD (AUC: 0.83 vs 0.68, P = 0.034; NRI: 0.340, P = 0.048) and PFS (AUC: 0.80 vs 0.70, P = 0.166; NRI: 0.431, P = 0.042). Dynamic changes of NLR might be an effective predictor of the therapeutic response to ICIs plus targeted therapies for uHCC.

Patients with High Baseline Neutrophil-to-Lymphocyte Ratio Exhibit Better Response to Filgotinib as Treatment for Rheumatoid Arthritis.

High baseline neutrophil-to-lymphocyte ratio (NLR) in rheumatoid arthritis (RA) has been associated with positive responses to biologic tumor necrosis factor inhibition and negative responses to conventional synthetic disease-modifying antirheumatic drug (csDMARD) triple therapy. Datasets from three randomized clinical trials in patients with RA were used to test the hypothesis that baseline NLR is associated with improved clinical response to filgotinib in methotrexate (MTX)-naïve or MTX-experienced RA populations. Patients from FINCH 1 (inadequate response to MTX, MTX-IR; NCT02889796), FINCH 2 (inadequate response to biologic DMARDs; NCT02873936), and FINCH 3 (MTX-naïve; NCT02886728) were classified as baseline NLR-High or baseline NLR-Low based on a previously published cut point of 2.7. In total, 3365 patients were included across the three studies. Differences in clinical outcomes and patient-reported outcomes (PROs) were determined using linear-regression models. Control-arm patients (placebo + MTX/placebo + csDMARD) classified as NLR-High exhibited worse continuous clinical and PRO responses at week 12 across clinical trials compared to NLR-Low patients. In contrast, NLR-High patients who received FIL 200mg + MTX/csDMARD exhibited consistently better responses after 12weeks compared to NLR-Low patients across clinical trials, clinical endpoints, and PROs. These trends were most prominent among the MTX-IR population. The 2.7 baseline NLR cut point could be used to enrich for patients most likely to benefit from the addition of filgotinib to background MTX/csDMARD. Use of baseline NLR as part of therapeutic decision-making would not require additional diagnostics and could contribute to improved outcomes for patients with RA. Clinicaltrials.gov: NCT02889796; NCT02873936; NCT02886728.

Efficacy and safety of regorafenib in the treatment of metastatic colorectal cancer: a retrospective cohort study.

The majority of studies of regorafenib now were small-sample and single-arm, which potentially limits the strength of evidence. We conduct the study to identify the efficacy and safety of regorafenib for patients with metastatic colorectal cancer (mCRC) in real-world applications. mCRC patients who underwent regorafenib second line or post-second line treatment with at least one assessable lesion were analyzed. Patients received different doses of regorafenib and different combination regimens. The patients were followed up with laboratory tests and imaging examinations every 3 months to evaluate the efficacy and adverse events (AEs). The primary endpoint of this study was median overall survival (mOS), and the secondary endpoints were median progression-free survival (mPFS), the objective response rate (ORR), the disease control rate (DCR), and AEs. A total of 77 patients (45 males and 32 females, aged 58.80±11.65 years) were enrolled in the study. Most primary tumors were located in the rectum (59.74%), and the vast majority of tumors (89.62%) had an adenocarcinoma histological type. The 77 patients had an mOS of 17.8 months, a progression-free survival (PFS) of 4.63 months, an ORR of 6.76%, and a DCR of 55.41%. Patients underwent regorafenib third-line therapy had significantly higher overall survival (OS) than those underwent regorafenib post- third-line treatment (P=0.03). The neutrophil to lymphocyte ratio (NLR) was an independent factor affecting the OS of the mCRC patients [hazard ratio (HR) =1.12, P=0.03]. In both univariate and multivariate analyses, discontinued use of regorafenib after progression reduced patients' PFS (HR =3.07, P<0.001; HR =2.78, P=0.007). In terms of the tolerated dose, patients receiving 120 mg regorafenib had the longest OS numbers, but there was no statistical difference. We analyzed the effect of the baseline NLR on the OS of patients receiving regorafenib combined with immunotherapy, and found that the NLR ratio cut-off value was 4.4, and patients with a NLR ratio ≤4.4 benefited significantly in terms of OS (P=0.03). The AEs included 21 (27.27%) cases of hand and foot skin reaction, 15 (19.48%) cases of fatigue, 9 (11.69%) cases of pain, 9 (11.69%) cases of nausea, 9 (11.69%) cases of fever, 9 (11.69%) cases of cough, and so on. Regorafenib is relatively effective and safe as a third-line and posterior treatment of mCRC. Patients underwent regorafenib third-line therapy had longer OS than those underwent regorafenib post- third-line treatment. Moreover, PFS benefits can still be obtained by continuing regorafenib treatment after progression. Grade 1-2 AEs were common, but these were usually tolerated by most patients.

Role of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte-ratio (PLR) in unresectable hepatocellular carcinoma (uHCC): Subgroup analysis of patients treated with camrelizumab (cam) + rivoceranib (rivo) in the CARES-310 trial.

e16197 Background: CARES-310 (NCT03764293) evaluated the combination of the PD-1 inhibitor, cam, and the VEGFR-2 tyrosine kinase inhibitor, rivo, compared to sorafenib (sor) for the treatment of 543 patients (pts) with uHCC. Cam + rivo significantly improved mOS (22.1 months [mo] [95% CI 19.1-27.2] vs 15.2 mo [13.0-18.5] HR 0.62 [95% CI 0.49-0.80]; one-sided p &lt; 0.0001) and mPFS (5.6 mo [95% CI 5.5-6.3] vs 3.7 mo [2.8-3.7]; HR 0.54 [95% CI 0.44-0.67]; one-sided p &lt; 0.0001) compared to sor. The most common (≥20%) grade ≥3 treatment-related adverse events (TRAEs) for cam + rivo were hypertension (37.5%) and increased AST (16.5%) vs palmar-plantar erythrodysesthesia syndrome (15.2%) for sor. An elevated level of inflammation, including NLR and PLR, have been associated with poor survival outcomes in pts with HCC (Lin S, et al. Trans Cancer Res. 2021). Here, we present a subgroup analysis of the CARES-310 trial evaluating the impact of baseline (BL) NLR and PLR status on pt outcomes. Methods: The subgroup of pts treated with cam+rivo and BL NLR &lt; 5 or ≥5 and PLR &lt; 300 or ≥300 were evaluated for mOS, mPFS, overall response rate (ORR), disease control rate (DCR), and safety. Results: Of 272 pts treated with cam+rivo, 64.3% of pts had extrahepatic spread, median AFP was 84.1 ng/mL, 86.8% were Child-Pugh (CP) class A5, 13.2% were CP class A6, 73.5% were ALBI grade 1, 26.5% were ALBI grade 2. Additionally, 249 pts had NLR &lt; 5, 10 pts had NLR ≥5, 252 pts had PLR &lt; 300, and 7 pts had PLR ≥300. Pts with BL NLR &lt; 5 and PLR &lt; 300 demonstrated improved outcomes in mOS, mPFS, ORR, and DCR vs pts with BL NLR ≥5 and PLR ≥300 (Table). Rates of any grade TRAEs and grade ≥ 3 TRAEs were comparable between pts with BL NLR &lt; 5 and ≥5 and PLR &lt; 300 and ≥300 (Table). Conclusions: These results suggest that NLR and PLR may serve as a prognostic marker in patients with uHCC, but larger studies are needed to validate these findings. Clinical trial information: NCT03764293 . [Table: see text]

Association of a clinical model based on skeletal muscle radiation attenuation with efficacy for patients with gastric cancer treated with chemotherapy plus PD-1 antibodies: A single-center retrospective study.

e16029 Background: Biomarkers to select gastric cancer (GC) patients who can benefit from PD-1 antibody-based treatment are under investigation. We aimed to assess the association between body composition parameters and efficacy of chemotherapy plus PD-1 antibodies in GC patients. Methods: Clinical information of GC patients receiving perioperative chemotherapy with or without PD-1 antibodies was reviewed. Tumor regression grade (TRG) of gastric cancer was recorded after resection. Radiation attenuation and index of skeletal muscle, visceral adipose tissue and subcutaneous adipose tissue were calculated based on computed tomography (CT) images at the third lumbar (L3) level using SliceOmatic software. Associations between clinical parameters and patients’ outcomes including TRG, progression-free survival (PFS), and overall survival (OS) were analyzed. Results: A total of 120 patients treated with chemotherapy plus PD-1 antibodies (IO cohort) and 82 patients treated with chemotherapy alone (CTx cohort) were enrolled. TRG0/1 rates in the IO cohort and CTx cohort were 45.8% and 32.9%. High skeletal muscle radiation attenuation (SMRA), neutrophil to lymphocyte ratio (NLR) &lt; 2.65, and weight loss &lt; 5% were associated with TRG0/1 in the IO cohort but not in the CTx cohort. High SMRA was an independent prognostic factor of PFS in the IO cohort (HR = 0.333, 95%CI 0.115-0.970, P= 0.044). A clinical model based on SMRA, NLR and weight loss was established to stratify patients into 3 groups, including group 1: High SMRA with NLR &lt; 2.65 and weight loss &lt; 5%, group 2: High SMRA with NLR≥2.65 and/or weight loss≥5%, and group 3: Low SMRA. In the IO cohort, patients in group 1 showed higher TRG0/1 rate (n = 27/40, 67.5%, P&lt; 0.001) than group 2 (n = 26/63, 41.3%) and group 3 (n = 2/17, 11.8%). The clinical model was also associated with patients’ survival. Conclusions: A clinical model combining baseline SMRA, NLR and weight loss could identify well-responding GC patients treated with chemotherapy plus PD-1 antibodies.

#2697 Association between neutrophil-lymphocyte ratio and morbidity among patients on maintenance hemodialysis with ESRD from diabetic nephropathy

Abstract Background and Aims The prevalence of end-stage renal disease (ESRD) is on the rise in the Philippines, and the prognosis for ESRD worsens with the presence of diabetes mellitus. Although the neutrophil-to-lymphocyte ratio (NLR) is a dependable prognostic marker for mortality, its applicability as a prognostic biomarker in patients with diabetes and chronic kidney disease remains uncertain. This study seeks to establish the correlation between NLR and morbidity among Filipino patients with ESRD due to diabetic nephropathy undergoing maintenance hemodialysis. To determine the association between NLR and morbidity among Filipino patients on maintenance hemodialysis due to ESRD secondary to diabetic nephropathy. Method Among the 191 screened ESRD patients on maintenance hemodialysis, 71 were attributed to diabetic nephropathy, and only 63 met the inclusion criteria for the study. Clinicodemographic information, encompassing age, sex, height, weight, body mass index (BMI), medications, and comorbidities, was extracted from the medical records of these 63 eligible patients. Subsequently, the patients were categorized into two groups based on their baseline neutrophil-to-lymphocyte ratio (NLR) values, with a cutoff set at 3.5—forming the high NLR group (≥3.5) and the low NLR group (&amp;lt;3.5). This threshold was established considering data indicating that an NLR of ≥3.5 is associated with heightened inflammatory states, leading to increased morbidity. After a 6-month follow-up, data on the primary outcome measure, i.e., the occurrence of the disease, were collected. Results Out of the 63 patients assessed, the majority (n=39, 61.9%) had a baseline NLR value of &amp;lt;3.5, and only 2 individuals in this group developed a disease. The high NLR group comprised 24 (38.1%) patients, with 15 of them developing diseases. Among these cases, 4 (0.16%) had diabetic foot, 3 (0.125%) had pneumonia, 3 (0.125%) developed catheter-related bloodstream infections, and 2 (0.08%) had pulmonary edema. Additionally, 1 case each of coronary artery disease (0.04%), hypertensive emergency (0.04%), and calciphylaxis (0.04%) were observed. NLR demonstrated a significant association with clinical outcomes (p &amp;lt; 0.05). Conclusion In conclusion, there is a significant correlation between the neutrophil-to-lymphocyte ratio (NLR) and disease development in Filipino patients undergoing maintenance hemodialysis for ESRD attributed to diabetic nephropathy. Patients with a high baseline NLR exhibit an elevated inflammatory state and a greater susceptibility to developing disease conditions compared to those with an NLR&amp;lt;3.5. Therefore, a high baseline NLR can serve as a predictive indicator for prognosis within this specific population.

Abstract PO5-25-04: Predictive value of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios in patients with triple negative breast cancer treated with pembrolizumab

Abstract Background: Immune checkpoint inhibitors (ICIs) offer new treatment possibilities for women with triple-negative breast cancer (TNBC) – one of the most challenging breast cancer subtypes. The PD-1 inhibitor pembrolizumab (pembro; Keytruda®) is approved in metastatic TNBC (mTNBC) patients with PD-L1(+) tumors, and for neoadjuvant treatment (NAT) in stage II/III TNBC [1, 2]. Residual cancer burden (RCB) after NAT is highly prognostic, with pathologic complete response (pCR, RCB 0) anticipating long-term survival [3]. In mTNBC, pembro plus chemotherapy in the 1st-line improves progression free survival (PFS), but durable responses are rare. Optimizing ICI use in TNBC thus remains an unmet need, and defining easily assessable markers of response is crucial. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are peripheral blood surrogates of tumor inflammation and have prognostic and predictive value in TNBC [4-8]. Elevated NLR (≥ 5) and PLR (≥ 200) correlate with worse outcomes upon ICIs in melanoma and non-small-cell lung cancer [9, 11-14]; however, this has not been studied in breast cancer [9, 10]. We evaluated the relationship of baseline NLR and PLR with pembro responses in TNBC patients. Methods: We retrospectively reviewed data from TNBC patients who completed pembro between 10/2/20 - 6/1/23 at Weill Cornell. Patients on NAT who did not complete treatment were excluded. RCB score (pCR/0, 1, 2, 3) was calculated from surgical resection pathology reports using the MD Anderson RCB Calculator [15, 16]. Baseline laboratory data were obtained from clinical records. Associations between NLR and PLR with RCB levels were examined using the non-parametric Kruskal-Wallis test (if &amp;gt;2 levels), the Wilcoxon rank sum test (if 2 levels), or the Spearman’s rank correlation. NLR and PLR were also correlated with PFS (measured from pembro start date to date of progression) in metastatic patients. PFS data for metastatic patients without interval imaging since pembro initiation were censored at the date of data analysis, and PFS was not calculated for patients who received only 1 cycle of pembro. Results: We identified 63 eligible patients: 24 were excluded due to lack of TNBC diagnosis (n=20), or because they only received adjuvant pembro (n=4). Of the 39 remaining patients, 5 did not complete NAT and 2 had missing data, leaving 32 evaluable patients (17 in the NAT cohort and 15 in the mTNBC cohort). Overall, the median age was 51 years, and 16% were Hispanic, 11% Asian, 57% non-Hispanic, 24% Black, and 65% Non-Black. Neoadjuvant cohort: The pCR rate was 30%. Patients with both NLR ≥ 5 and PLR ≥ 200, had a pCR rate of 0%; in patients with NLR &amp;lt; 5 or PLR &amp;lt; 200, pCR rate was 43%. Median NLR in pCR vs. non-pCR groups was 1.91 [IQR: 1.72- 2.73] vs. 2.44 [IQR: 1.97- 5.24] (p=0.3), with trends towards significance when NLR was compared between RCB levels &amp;gt;1 (2.67; IQR: 2.05, 6.49) vs. RCB levels ≤1 (1.91; IQR: 1.63, 2.58) (p=0.14). Mean PLR was higher in patients with RCB 2-3 (409) compared to those with pCR or RCB 1 (167) (p=0.146). Metastatic cohort: The overall mean PFS was 7.8 months. Visceral metastases were seen in 80% of patients (17% liver, 33% brain). In patients with brain mets, baseline NLR and PLR were higher than in the overall cohort (NLR, 4.86 vs. 2.78; PLR, 429 vs. 186). Conclusions: Our study is the first to evaluate NLR and PLR as response biomarkers in TNBC patients receiving pembro and is the first report of our real-world data of TNBC patients on pembro. In our neoadjuvant cohort, higher baseline NLR and PLR correlated with higher RCB levels, with a trend towards statistical significance. Further investigation and correlation of NLR and PLR with tumor microenvironment features will help to clarify these relationships. Citation Format: Ashley Schreier, Roberta Zappasodi, Inna Serganova, Laura Munoz Arcos, Xi Kathy Zhou, Massimo Cristofanilli, Eleni Andreopolu. Predictive value of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios in patients with triple negative breast cancer treated with pembrolizumab [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-25-04.

Predictive value of neutrophil-to-lymphocyte ratio in coronary chronic total occlusion patients.

The neutrophil to lymphocyte ratio (NLR) has been reported as a novel predictor for atherosclerosis and cardiovascular outcomes. This study aimed to determine the effects of NLR on long-term clinical outcomes of chronic total occlusion (CTO) patients. A total of 670 patients with CTO who met the inclusion criteria were included at the end of the follow-up period. Patients were divided into tertiles according to their baseline NLR levels at admission: low (n = 223), intermediate (n = 223), and high (n = 224). The incidence of major adverse cardiac events (MACEs) during the follow-up period, including all-cause death, nonfatal myocardial infarction (MI), or ischemia-driven revascularization, were compared among the three groups. Major adverse cardiac events were observed in 27 patients (12.1%) in the low tertile, 40 (17.9%) in the intermediate tertile, and 61 (27.2%) in the high NLR tertile (P < 0.001). Kaplan-Meier analysis demonstrated a significantly higher incidence of MACE, ischemia-driven coronary revascularization, non-fatal MI, and mortality in patients within the high tertile than those in the low and intermediate groups (all P < 0.001). Multivariable COX regression analysis showed that the high tertile of baseline NLR level showed a strong association with the risk of MACE (hazard ratio [HR] = 2.21; 95% confidence interval [CI]: 1.21-4.03; P = 0.009), ischemia-driven coronary revascularization (HR = 3.19; 95% CI: 1.56-6.52; P = 0.001), MI (HR = 2.61; 95% CI: 1.35-5.03; P = 0.043) and mortality (HR = 3.78; 95% CI: 1.65-8.77; P = 0.001). Our findings suggest that NLR is an inexpensive and readily available biomarker that can independently predict cardiovascular risk in patients with CTO.

Baseline and stress-induced steroid plasma levels and immune function vary annually and are associated with vocal activity in male toads (Rhinella icterica)

Theoretical models predict that elevated androgen and glucocorticoid levels in males during the reproductive season promote immunosuppression. However, some studies report decreased stress response during this season. This study investigated annual variation in plasma corticosterone and testosterone levels, plasma bacterial killing ability (BKA), and neutrophil to lymphocyte ratio (NLR) in free-living male toads (Rhinella icterica). Toads were sampled in the field (baseline) and 1 h-post restraint over five months, and we considered the occurrence of vocal activity. Baseline corticosterone, testosterone, and BKA showed higher values during the reproductive period, specifically in calling male toads. The NLR was similar throughout the year, but higher values were observed in calling toads. Moreover, baseline NLR and BKA were positively correlated with both testosterone and corticosterone, suggesting higher steroid levels during reproduction are associated with enhanced cellular and humoral immunity. Despite fluctuation of baseline values, post-restraint corticosterone levels remained uniform over the year, indicating that toads reached similar maximum values throughout the year. Testosterone levels decreased following restraint before one specific reproductive period but increased in response to restraint during and after this period. Meanwhile, BKA decreased due to restraint only after the reproductive period, indicating immune protection and resilience to immunosuppression by stressors associated with steroid hormones during reproduction. Our results show that baseline and stress-induced hormonal and immune regulation varies throughout the year and are associated with vocal activity in R. icterica males, indicating a possible compromise between steroids and immune function in anuran males.