Pretreatment Neutrophil-to-lymphocyte Ratio Research Articles

Prognostic value of neutrophil-lymphocyte ratio and lactate dehydrogenase in melanoma patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis.

Background:Immune checkpoint inhibitors (ICIs) showed promising therapeutic efficacy on melanoma. Neutrophil-to-lymphocyte ratio (NLR) and serum lactate dehydrogenase (LDH) showed predictive values on prognosis of various tumors, but not on melanoma yet. This meta-analysis was conducted to investigate the prognostic role of NLR and LDH levels in melanoma treated with ICIs.Methods:A search was conducted for all reports published till March 2020 in PubMed, Web of Science, Cochrane Library, EMBASE, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP). Studies were included if they investigated the association between pretreatment NLR/LDH and prognosis in melanoma patients treated with ICIs. Subgroup analysis, publication bias, and meta-regression were conducted to investigate heterogeneity.Results:A total of 6817 melanoma patients were included. Overall, high pretreatment NLR and LDH were associated with poor overall survival (OS) (P < .001) and PFS (P < .001). Subgroup analyses revealed that elevated NLR and LDH levels were associated with poor OS and PFS in patients treated with anti-CTLA-4 or anti-PD-1/PD-L1 alone. NLR level was superior in predicting OS if compared with LDH level in patients treated with anti-PD-1/PD-L1 + anti-CTLA-4. In subgroup analysis stratified by cutoff value, high NLR level was associated with poor OS and PFS regardless of cutoff value, but LDH works when cutoff value = upper normal limit (UNL). The predictive value of NLR and LDH levels on OS and PFS was partially compromised in the Asian populations, compared with the Western countries.Conclusion:Blood NLR and LDH levels showed great potential to be used as early prognostic biomarkers in melanoma patients treated with ICIs.

Pretreatment blood biomarkers combined with magnetic resonance imaging predict responses to neoadjuvant chemoradiotherapy in locally advanced rectal cancer.

AimTo investigate the value of pretreatment blood biomarkers combined with magnetic resonance imaging (MRI) in predicting the efficacy of neoadjuvant chemoradiotherapy (NCRT) in patients with locally advanced rectal cancer (LARC).MethodsThis study involved patients with LARC who received NCRT and subsequently underwent total mesenteric excision from June 2015 to June 2021 at the First Affiliated Hospital of Soochow University. Patients with incomplete courses of neoadjuvant therapy, comorbidities with other malignancies or diseases that affect the study outcome, and those who underwent unplanned surgery were ultimately excluded. Laboratory data such as albumin, CEA, various blood cell levels, and MRI related data such as tumor regression grade assessed by magnetic resonance imaging (mrTRG) were collected from the included patients one week prior to NCRT. MrTRG is a common clinical imaging metric used to assess the degree of tumor regression in rectal cancer, primarily based on morphological assessment of residual tumor. Furthermore, pretreatment blood biomarkers such as neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), albumin to fibrinogen ratio (AFR), and prealbumin to fibrinogen ratio (PFR) were assessed. The independent variables for pathologic complete response (pCR) to NCRT were determined by univariate and multivariate logistic regression analyses. Receiver operating characteristic (ROC) curve analysis was used to examine the performance of MRI with or without pretreatment blood biomarkers in predicting pCR using DeLong’s method. A nomogram was created and confirmed internally.ResultsFifty-nine individuals with LARC satisfied the inclusion criteria, among which 23 showed pCR after NCRT. Logistic regression analysis demonstrated that pretreatment CEA (≤ 3 µg/L, OR = 0.151, P = 0.039), NLR (OR = 4.205, P = 0.027), LMR (OR = 0.447, P = 0.034), and PFR (OR = 0.940, P = 0.013) were independent predictors of pCR to NCRT. The AUCs of mrTRG alone and mrTRG plus the above four pretreatment blood biomarkers were 0.721 (P =0.0003) and 0.913 (P <0.0001), respectively. The constructed nomogram showed a C-index of 0.914.ConclusionPretreatment blood biomarkers combined with MRI can help clinical efforts by better predicting the efficacy of NCRT in patients with locally advanced rectal cancer.

The prognostic value of neutrophil-to-lymphocyte ratio in cholangiocarcinoma: a systematic review and meta-analysis

The neutrophil-to-lymphocyte ratio (NLR) is used as biomarker in malignant diseases showing significant association with poor oncological outcomes. The main research question of the present study was whether NLR has also prognostic value in cholangiocarcinoma patients (CCA). A systematic review was carried out to identify studies related to NLR and clinical outcomes in CCA evaluating the literature from 01/2000 to 09/2021. A random-effects model, pooled hazard ratios (HR) and 95% confidence interval (CI) were used to investigate the statistical association between NLR and overall survival (OS) as well as disease-free survival (DFS). Subgroup analyses, evaluation of sensitivity and risk of bias were further carried out. 32 studies comprising 8572 patients were eligible for this systematic review and meta-analysis. The pooled outcomes revealed that high NLR prior to treatment is prognostic for poor OS (HR 1.28, 95% CI 1.18–1.38, p < 0.01) and DFS (HR 1.39, 95% CI 1.17–1.66, p < 0.01) with meaningful HR values. Subgroup analysis revealed that this association is not significantly affected by the treatment modality (surgical vs. non-surgical), NLR cut-off values, age and sample size of the included studies. Given the likelihood of NLR to be prognostic for reduced OS and DFS, pre-treatment NLR might serve as a useful biomarker for poor prognosis in patients with CCA and therefore facilitate clinical management.

Observation of dynamic changes in neutrophil-to-lymphocyte ratio is useful for evaluating treatment response to nivolumab in PD-L1-negative advanced oral cancer

ObjectiveNivolumab is widely used for treatment of recurrent or metastatic oral squamous cell carcinoma (OSCC), but few patients benefit from this therapy. The aim of this study was to evaluate useful predictive biomarkers in OSCC patients. MethodsThis study included seven patients who were diagnosed with OSCC and received nivolumab treatment more than twice at Yamanashi Central Hospital. We analyzed correlations of treatment efficacy with PD-L1 expression in the tumor microenvironment by immunohistochemistry, gene mutation profile of tumor, and neutrophil to lymphocyte ratio (NLR) in peripheral blood. Gene mutation profile was analyzed by PCR of microsatellite instability and whole-exome sequencing. NLR was calculated by division of absolute neutrophil and lymphocyte counts. ResultsTwo patients showed complete response (CR), while five showed no therapeutic effect. PD-L1 expression was correlated with treatment efficacy in most patients, but PD-L1 expression was absent in one patient with CR. Gene mutation analysis of tumor cells did not contribute to prediction of the treatment effect in the patient, either. Pre-treatment NLR was not correlated with treatment outcome, but NLR in responders declined gradually to < 4 after the third nivolumab treatment; this markedly differed from the findings in non-responders, who exhibited increased NLR during therapy. ConclusionsNLR changes reflect the early treatment response in OSCC patients treated with nivolumab, including patients whose immune and gene mutation profiles does not correlate with treatment efficacy.

High pre-treatment neutrophil-to-lymphocyte ratio as a prognostic marker for worse survival in patients with recurrent/metastatic cervical cancer treated with immune checkpoint inhibitors

ObjectiveTo evaluate the association between pre-treatment neutrophil-to-lymphocyte ratio (NLR) and survival outcomes among patients with recurrent/metastatic cervical cancer treated with PD-1/PD-L1 inhibitors. MethodsA retrospective analysis of patients with recurrent/metastatic cervical cancer treated with PD-1/PD-L1 inhibitors from 2016 to 2021 was conducted. Progression free survival (PFS) and overall survival (OS) outcomes were assessed for patients stratified by NLR (<8 vs ≥ 8) utilizing Kaplan-Meier method. Univariable analysis was performed to compare baseline characteristics between the two groups. ResultsA total of 49 patients were included in analysis. A majority of patients had squamous cell histology (57%), were PD-L1 positive (55%), received ≤ 1 prior lines of systemic therapy (57%), and had distant metastatic disease at the time of treatment (69%). The groups were well-balanced with respect to age, race, histology, smoking status, PD-L1 positivity, prior lines of treatment (≤1 vs > 1), prior radiation therapy, ECOG performance status, and disease distribution for patients with a NLR < 8 (n = 35) compared to those with a NLR ≥ 8 (n = 14). A pre-treatment NLR of < 8 was associated with improved survival (p < 0.01), with 57% (95% CI: 41%, 78%) probability of survival at one year compared to 26% (95% CI: 10%, 66%) for those with NLR ≥ 8. No statistically significant differences in probability of PFS at 1 year were seen between NLR < 8 compared to those with NLR ≥ 8 (p = 0.70). ConclusionsPre-treatment NLR may hold prognostic value for patients with metastatic/recurrent cervical cancer treated with PD-1/PD-L1 inhibitors, with NLR < 8 associated with improved survival.

Predictors of pathologic response to neoadjuvant chemotherapy in muscle-invasive bladder cancer

Objective: To identify factors that could predict pathologic response to neoadjuvant (NAC) therapy in muscle invasive bladder cancer (MIBC) patients and report the impact of NAC on the risk of perioperative complications after radical cystectomy at our institution. Materials and Methods: We reviewed the hospital database from January 2014 to March 2021 for MIBC patients who received NAC prior to radical cystectomy (RC). All patients were divided into a responder (pT ≤ T1) or non-responder group (&gt; pT2). Data was analyzed to determine the factors associated with pathologic response to NAC. A subgroup analysis of the gemcitabine and carboplatin (GCb) regimens was also carried out. Results: Out of the 50 patients who met the inclusion criteria, 13 (26%) were categorized as responders and 37 (74%) as non-responders. With regard to NAC variables, 12 patients (24%) received cisplatin-based NAC, and 38 patients (74%) received GCb. From the multivariate analysis, pretreatment hemoglobin (Hb) &gt; 12 g/dl (OR 16.42, 95% CI 1.78-151.86, p = 0.01) and neutrophil-to-lymphocyte ratio (NLR) &lt; 3 (OR 12.81, 95% CI 1.36-120.9, p = 0.03) were associated with significantly increased odds of pathologic response, while tumor size &lt; 4 cm (OR 12, 95% CI 1.92-75.05, p = 0.008) was associated with significantly increased odds of pathologic response in the subgroup analysis. Conclusions: Pretreatment Hb and NLR were independently associated with pathologic response to NAC. For MIBC patients who are cisplatin ineligible, GCb followed by RC may be the recommended treatment, particularly in those with tumors less than 4 cm in size. In addition, administering NAC prior to RC does not increase the risk of perioperative complications.

A novel nomogram could predict prognosis for multiple cancer patients with primary resistance to immune checkpoint inhibitors.

e14561 Background: Cancer patients with immune checkpoint inhibitors (ICIs) treatment often experience unique progression response patterns, accounting for the discordance of short-term and long-term benefits. Identifying the specific characteristics of different quality progression disease (PD) events can maximize the curative effect of ICIs and further improve the prognosis of the patients with immunotherapy. In this study, we established a neutrophil-to-lymphocyte ratio (NLR)-based nomogram model which could predict survival for NSCLC patients with primary resistance to ICIs. Methods: Univariate and multivariate Cox regression analysis were used to evaluate the ability of each parameter to predict overall survival (OS). The regression coefficients obtained in multivariate analysis were visualized in the form of a nomogram, thus a new nomogram and risk classification system were established. The discrimination ability of the new model was evaluated using area under the curve (AUC) in receiver operating characteristic curve (ROC) analysis. Survival curves were made by the Kaplan-Meier method and compared by the Log-rank test. Results: A total of 1235 patients with multiple cancer types who accepted at least one dose of ICIs treatment between 2015 and 2018 at Memorial Sloan Kettering Cancer Center were included in our study. Among them, 624 PD-patients (obtaining PD as their best response) were used to identify potential survival-related characteristics and build a nomogram model. Univariate and multivariate analysis demonstrated that pretreatment NLR, treatment lines and Eastern Cooperative Oncology Group performance status scores were independent prognostic factors and were included in the predictive model. The ROC curves implied the good discrimination ability of the predictive model with the AUC value for 1-year OS was 0.756. And, the calibration curves showed that the predicted value of the 1-year survival rate by the nomogram was in good agreement with the actual observed value of it. Based on the nomogram, we divided PD-patients into high-, med- and low-risk subgroups. The OS of cancer patients in three risk groups were accurately differentiated either in all PD-patients or PD-NSCLC-patients, but not in the patients who responded to ICIs. Importantly, the prognosis of the low-risk PD-patients was significantly better compared with the patients in med- and low-risk groups (P &lt; 0.001). Moreover, in the PD-patients with NSCLC, similar results were also found that patients had a worse OS in the high-risk group (P &lt; 0.001). Interestingly, in contrast to the results in PD-patients, a comparable OS between high-, med- and low-risk groups based on our model was verified in the patients who responded to ICIs. Conclusions: The pretreatment NLR-based nomogram could predict the prognosis for pan-cancer patients with primary resistance to ICIs treatment.

Differential prognostic effect of systemic inflammation in patients with NSCLC treated with immunotherapy or chemotherapy: A post hoc analysis of the phase III OAK trial.

9056 Background: A pro-inflammatory diathesis as measured by the neutrophil-to-lymphocyte ratio (NLR) heralds an adverse disease course in non-small cell lung cancer (NSCLC). Whether the NLR identifies patients who derive a differential degree of benefit from immunotherapy versus chemotherapy is not known. Methods: This post hoc analysis used data from the phase III OAK trial, which randomized previously treated patients with NSCLC to receive atezolizumab or docetaxel. The main objective was to assess the differential impact of pre-treatment NLR on overall survival (OS) depending on the treatment modality. In addition, we assessed patients genomic characteristics according to inflammatory status using circulating free (cf)DNA NGS analysis. Results: A total of 600 and 575 patients with an available NLR were included in the atezolizumab and docetaxel cohort, with a median NLR of 4 (IQR: 2.6-6.7) for the pooled population. NLR ≥ 4 was associated with positive smoking status (88.6% vs 78.1%, p &lt; 0.01), male sex (66.4% vs 57.6%, p = 0.01), worse performance status (71.3% vs 55.2%, p &lt; 0.01), higher number of metastatic sites (63.2% vs 51.6%, p = 0.01), squamous histology (32.1% vs 21.4%, p &lt; 0.01), and tissue KRAS mutation (30% vs 18.7%, p = 0.02), but not with PD-L1 expression, nor with tissue EGFR/ALK status. Pre-treatment NLR of ≥ 4 was more strongly associated with mortality following atezolizumab with an adjusted hazard ratio (HR) of 1.64 (95%CI:1.35-2.01) compared to docetaxel (HR 1.32, 95%CI: 1.08-1.60, multivariable (MVA) interaction p = 0.08. Exclusion of EGFR/ALK positive patients further increased the prognostic ability of baseline NLR in favor of atezolizumab (HR 1.67, 95%CI: 1.35-2.06), as compared with the docetaxel arm (HR 1.24, 95%CI: 1.02-1.52, MVA interaction p = 0.02). The HR for the risk of death for patients with NLR≥ 4/PD-L1 negative tumours (compared to NLR &lt; 4/PD-L1 positive) was significantly higher in the atezolizumab cohort (HR 2.28, 95%CI: 1.72-3.03) than in the docetaxel cohort (HR 1.42, 95%CI: 1.08-1.86, MVA interaction p = 0.01). NGS pretreatment cfDNA data showed that patients with a high blood tumor mutational burden (cut-off 16 Mut/Mb) had a higher median NLR (4.6 vs 3.7, p = 0.01). After adjusting for multiple comparisons, none among the selected variants of interest (EGFR, KRAS, TP53, KEAP1, STK11, SMARCA4, ARID1A and targeted DDR genes), were significantly associated with the NLR. Conclusions: In this post-hoc analysis, a baseline low NLR identifies patients with NSCLC who derive a greater survival benefit from atezolizumab as compared to those identified in the docetaxel cohort, irrespective of genomic features. Patients with a low NLR and PD-L1 positive tumors derive the greatest benefit with immunotherapy and the NLR could complement PD-L1 expression in tailoring treatment in this setting. Clinical trial information: NCT02008227.

Pre-Treatment and Preoperative Neutrophil-to-Lymphocyte Ratio Predicts Prognostic Value of Glioblastoma: A Meta-Analysis.

Objective: Although some meta-analyses have shown a correlation between a high neutrophil-to-lymphocyte ratio (NLR) and low survival in patients with gliomas, their conclusions are controversial, and no study has specifically explored the relationship between a high pre-treatment and pre-operative NLR and low survival in patients with glioblastoma (GBM). Therefore, we further investigated this correlation through meta-analysis. Methods: We searched the PubMed, Metstr, and Cochrane databases in March 2022 for published literature related to high pre-treatment and pre-operative NLR and low survival in patients with GBM. The literature was rigorously searched according to inclusion and exclusion criteria to calculate the overall hazard ratio (HR) and 95% confidence interval (CI) corresponding to a high NLR using a random effects model. Results: The total HR for the pre-treatment and pre-operative NLR was 1.46 (95% CI: 1.17–1.75, p = 0.000, I2 = 76.5%), indicating a significant association between a high pre-treatment and pre-operative NLR, and low overall survival in patients with GBM. Sub-group analysis was performed because of the high heterogeneity. The results for the sub-group with a cut-off value of 4 showed an HR of 1.39 (95% CI: 1.12–1.65, p = 0.000, I2 = 22.2%), with significantly low heterogeneity, whereas those for the sub-group without a cut-off value of 4 showed an HR of 1.45 (95% CI: 1.01–1.89, p = 0.000, I2 = 83.3%). Conclusions: The results of this study demonstrate that a high pre-treatment and pre-operative NLR suggests low survival in patients with GBM based on data from a large sample. Furthermore, the meta-regression analysis results indicate that underlying data, such as age and extent of surgical resection, lead to a high degree of heterogeneity, providing a theoretical basis for further research.

Modified-Dose Pembrolizumab and Prognostic Outcomes among Non-Small Cell Lung Cancer Patients: A Chart Review Study.

The modified dose (MD) regimen of pembrolizumab (2 mg/kg or 100 mg every 3 weeks) is an alternative option to reduce the financial burden resulting from the extremely high cost of the standard dose (SD) regimen (200 mg every 3 weeks). However, the clinical effectiveness and prognostic outcomes have not been fully elucidated in real-word clinical practice. Sixty-four consecutive patients in Taiwan receiving pembrolizumab for advanced NSCLC between 2018 and 2020 were recruited in this study. Comparisons of overall survival (OS) and progression-free survival (PFS) were performed using Kaplan–Meier survival curves. Additionally, 12 predictors, including pembrolizumab regimen, dose, neutrophil-to-lymphocyte ratio (NLR), age, sex, histopathology, smoking history, ECOG PS, EGFR mutation, PD-L1 expression, distant metastases and treatment line, were analyzed in multivariable Cox models for predicting OS and PFS. The results showed that the MD group and the SD group had similar OS and PFS, especially in patients beyond first-line treatment or with a pretreatment NLR < 5. The NLR was the only independent factor associated with both OS (adjusted HR = 0.052; p = 0.010) and PFS (adjusted HR = 0.259; p = 0.021). The results of this study assure the clinical effectiveness of MD pembrolizumab and suggest that the pretreatment NLR could highlight patients who may benefit from MD pembrolizumab.

THE ROLE OF NEUTROPHIL TO LYMPHOCYTE RATIO AND PLATELET TO LYMPHOCYTE RATION IN DIAGNOSIS OF SUBACUTE THYROIDITIS

Purpose: Patients with subacute thyroiditis (SAT) usually apply to clinics with thyrotoxicosis and neck pain. Hemogram is frequently applied tests in primary health care services, and it can warn physicians for SAT in a thyrotoxic patient. In our study, the role and usability of neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) in the diagnosis of SAT were evaluated. Material and Methods: Between January 2015 and January 2020, 192 SAT patients who applied to endocrinology clinics and 85 healthy control were included in the study. Neutrophil (Neu), lymphocyte (Lym), platelet (PLT) leves were recorded. Results: The median NLR and PLR values of SAT patients before treatment were 2.78 (0.91-11.33) and 168.3 (25.7-818.3), respectively, and were significantly higher than the control group (p&amp;lt;0.001). The optimum cut-off values for NLR and PLR for SAT were 1.84 (specificity 85.9% and sensitivity 90.1%; p&amp;lt;0.001; AUC=0.934; 95% CI: 0.905-0.964 ) and 140.2 (specificity 83.5% and sensitivity 77.1%, p&amp;lt;0.001, AUC=0.821 95% CI: 0.767-0.874), respectively. Pretreatment NLR, PLR, CRP, and ESR levels were significantly higher than the posttreatment levels (all p&amp;lt;0.001). Correlation analysis revealed positive linear relations between pretreatment PLR and CRP (p=0.002, r=0.220), pretreatment PLR and ESR (p=0.018, r=0.171), pretreatment NLR and CRP (p&amp;lt;0.001, r=0.330), and pretreatment NLR and ESR (p=0.001, r=0.242). Multiple linear regression analysis revealed a 0.008 unit of increment of NLR per 1 unit increase in CRP levels (B=0.008; p&amp;lt;0.001; %95 CI=0.004-0.012). Conclusion: High NLR and PLR values accompanying thyrotoxicosis are both warning and helpful parameters for the diagnosis of SAT.

The role of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in determining the prognosis of patients with testicular cancer

Background: Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), as systemic inflammatory response markers, have been shown to play a role in prognostic factors for patients with malignancies in recent years. However, their application as the prognostic factors of testicular cancer remains unknown. This study aims to evaluate the prognostic role of testicular malignancies using preoperative hematological parameters, NLR and PLR, and their pre-diagnostic role in the staging of testicular cancer. Methods: This was a cross-sectional retrospective study of thirty-nine patients who underwent radical orchiectomy due to testicular cancer at the Department of Urology Haji Adam Malik General Hospital between January 2014 and December 2018. For each patient, clinical features including age, sex, clinical stage, chemotherapy, radiology report, pre-treatment neutrophil count, lymphocyte count, platelet count, NLR, PLR, and postoperative histopathological report were collected. Then we analyzed the association between NLR, PLR and the testicular cancer metastasis incidence. Result: The mean age of the patients was 27.56 ± 17.47 years. Seventeen patients had seminoma (42.5%), 16 others were yolk sac type of cancer (40.0%), and the rest six patients were teratoma (3 patients), lymphoma (2 patients), and embryonal carcinoma (1 patient). More than half (66.48%) of the patients received chemotherapy after radical orchiectomy, with 48.70% in clinical stage III. PLR was associated with testicular cancer metastases (p=0.024), while NLR was not (p=0.729). Conclusion: High pre-treatment PLR levels are associated with the occurrence of metastasis in testicular cancer patients. Hematological parameters will become critical in the preoperative evaluation of such testicular cancer cases. The potential prognostic significance of NLR and PLR in testicular cancer should be tested with further studies.

Neutrophil to Lymphocyte ratio is significantly reduced after Sodium glucose cotransporter-2 inhibitor treatment in patients with type 2 diabetes mellitus

Background. Sodium glucose cotransporter-2 inhibitors (SGLT2i) are novel therapeutic agents that became available in the treatment of type 2 diabetes mellitus (T2DM). This group of antidiabetic agents are associated with reduced glycated hemoglobin (HbA1c), fasting glucose, body weight and body mass index (BMI) in diabetic patients. All those beneficial effects may also be associated with a reduction in inflammatory burden. The purpose of the study is to compare neutrophil to lymphocyte ratio (NLR), a novel inflammatory marker derived from hemogram, before and 6 months after SGLT2i treatment in diabetic subjects. We also aimed to compare fasting glucose, HbA1c and other metabolic parameters as well as anthropometric measures (weight, BMI) before and 6 month after initiation of SGLT2i therapy. Materials and methods. The subjects with type T2DM that show up in internal medicine outpatient clinics of Abant Izzet Baysal University Hospital between January 2021 and December 2021 were enrolled to the study. Pretreatment and posttreatment NLR and other parameters were compared. We also obtained pretreatment and posttreatment laboratory data including urea, creatinine, fasting glucose, HbA1c, glomerular filtration rate, aspartate and alanine transaminases, plasma sodium and potassium. Results. Fasting glucose was reduced from 195±72 mg/dl in pretreatment period to 146±53 mg/dl in posttreatment period (p&lt;0.001). HbA1c was reduced from 9.1±1.7% in pretreatment period to 7.7±1.7% in posttreatment period (p&lt;0.001). The NLR before treatment was 2.6±1.2% before SGLT2i treatment and was reduced to 2.2±0.6% in 6th month of SGLT2i therapy. NLR was significantly decreased after treatment (p=0.003). Conclusions. We suggest that NLR levels could be a marker of reduced inflammatory burden in T2DM subjects receiving SGLT2i treatment.

Hematological Prognosticators in Metastatic Renal Cell Cancer Treated with Immune Checkpoint Inhibitors: A Meta-Analysis

Aim: We aimed to assess the prognostic value of pretreatment hematological biomarkers in patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors (ICIs). Methods: PubMed, Web of Science and Scopus databases were searched for articles according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Results: Fifteen studies comprising 1530 patients were eligible for meta-analysis. High levels of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein and lactate dehydrogenase were significantly associated with worse progression-free survival. High NLR and PLR were significantly associated with worse overall survival. Conclusion: High pretreatment NLR andPLRappear to be hematological prognostic factors of progression andoverall mortality in mRCC patients treated with ICIs. These findings might help in the design of correlative biomarker studies to guide the clinical decision-making in the immune checkpoint inhibitor era.

Prognostic values of inflammatory indexes in bevacizumab-treated patients with advanced non-small-cell lung cancer.

Purpose:Inflammatory indexes, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII) and lymphocyte-to-monocyte ratio (LMR), have been confirmed as prognostic factors in multiple manigances. However, the prognostic value of these parameters in bevacizumab-treated non-small-cell lung cancer (NSCLC) is still not clear.Methods:We retrospectively studied 119 patients with advanced NSCLC who received bevacizumab treatment. The associations of pretreatment NLR, PLR, SII and LMR with progression-free survival (PFS) and overall survival (OS) were analyzed.Results & Conclusion:The median PFS and OS of patients with high baseline NLR, PLR and SII and low LMR were significantly decreased than those of patients with low baseline NLR, PLR and SII and high LMR. Multivariable analysis indicated that high baseline SII was independently related with inferior prognosis, and baseline LMR was an independent predictor for OS.

Prognostic value of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio on low-grade appendiceal mucinous neoplasm: A single tertiary hospital experience.

Low-grade appendiceal mucinous neoplasm (LAMN) is a rare disease, which prognostic factors were difficult to evaluate. Inflammation markers, like neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), were used as prognosticators for various cancers. This study aimed to investigate the prognostic value of pretreatment NLR and PLR on LAMN. From January 2000 to September 2018, there were 57 patients diagnosed with LAMN in Taipei Veterans General Hospital. Patients diagnosed with mucinous cystadenoma, mucinous tumor with uncertain malignant potential before 2010 were also included based on previous classification. Clinical and pathological data were collected. Patients were separated into high-NLR (NLR-H) and low-NLR (NLR-L) groups according to cutoff value of 3. Similarly, they were separated into high-PLR (PLR-H), and low-PLR (PLR-L) groups with cutoff value of 300. Overall survival (OS) and recurrence-free survival (RFS) were analyzed. Among all patients, the median follow-up time was 42 months. Age, gender, clinical manifestations, type of surgery, and T stage were similar in different NLR and PLR groups. Both NLR-H and PLR-H groups had higher rate of M1 stage of diseases (22.7% vs 9.4%, p = 0.04; 57.1% vs 8.8%, p < 0.01, respectively). PLR-H group had more presence of pseudomyxoma peritonei (PMP) (57.1% vs 15.2%, p = 0.03). In univariate analysis, factors such as age, gender, tumor perforation, and operation did not have impact on OS nor RFS. On the other hand, M1b stage is the only significantly poor prognostic factor on RFS (hazard ratio, 57.96, 95% CI, 5.16-651.23, p < 0.01). Both NLR-H and PLR-H had more M1 stage of diseases, but they were not correlated to OS nor RFS. PLR-H group had higher rate of presence PMP. Nevertheless, patients with LAMN and cellular PMP (M1b stage) had a higher rate of recurrence, and other factors showed no statistical difference in OS nor RFS.

Pretreatment Neutrophil-to-Lymphocyte Ratio as a Prognostic Biomarker in Unresectable or Metastatic Esophageal Cancer Patients With Anti-PD-1 Therapy.

BackgroundThe neutrophil-to-lymphocyte ratio (NLR) is an inflammatory index calculated by the absolute neutrophil count dividing the absolute lymphocyte count, and its prognostic role in esophageal cancer (EC) patients with anti-PD-1 therapy remains unclear.MethodsA total of 140 unresectable or metastatic EC patients receiving PD-1 inhibitor treatment were included from Jan 2016 to Mar 2020. Kaplan–Meier method and log-rank test were used for comparing overall survival (OS) and progression-free survival (PFS) between groups. Multivariate Cox analysis was performed to assess the prognostic value of NLR.ResultsThe cutoff value of NLR was set at 5, and the median follow-up time was 20.0 months. Patients with pretreatment NLR <5 had higher ORR (46.7% vs. 12.1%; p < 0.001) and DCR (85.0% vs. 69.7%; p = 0.047) than those with NLR ≥5. Kaplan–Meier curves showed that pretreatment NLR <5 was associated with longer PFS (median: 10.0 vs. 3.5 months, p < 0.0001) and OS (median: 22.3 vs. 4.9 months, p < 0.0001). Multivariate analysis demonstrated that pretreatment NLR ≥5 independently and significantly increased the risk of disease progression (hazard ratio (HR), 1.77 (95% confidence interval (CI), 1.12–2.82); p = 0.015) and death (HR, 4.01 (95% CI, 2.28–7.06); p < 0.001). Subgroup analysis showed that pretreatment NLR ≥5 was associated with poor efficacy and survival in most subsets.ConclusionsOur findings showed that pretreatment NLR was independently and significantly associated with the efficacy and prognosis of EC patients treated with PD-1 inhibitors. NLR could serve as a convenient and useful prognostic biomarker for EC patients with anti-PD-1 therapy.

The Pretreatment Systemic Inflammation Response Index as a Useful Prognostic Factor is Better Than Lymphocyte to Monocyte Ratio in Breast Cancer Patients Receiving Neoadjuvant Chemotherapy

It has been reported that the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and lymphocyte to monocyte ratio (LMR), as well as systemic inflammation response index (SIRI), are closely related with overall survival (OS) in breast cancer patients. However, which one is the optimal indicator is vague. This study incorporates 280 breast cancer patients who received NACT. A cut-off value of LMR, PLR, SIRI and NLR is determined by Youden index. The Pearson's X2 test or Fisher's exact test is applied to compare the correlation of different clinicopathologic characteristics divided by SIRI. The K-M survival curves and log-rank test were applied to determine OS. Univariate and multivariable analysis are explored by the Cox regression model. We apply the Z test to contrast the prognostic capacity of SIRI, LMR, PLR, and NLR. At the meanwhile, we construct the nomogram based on the results of multivariable analysis. All enrolled cases are divided into two parts by pretreatment SIRI (cut-off value = 0.52). Compared to high pre-treatment SIRI, high pre-treatment NLR and clinical T3 + T4 stage, the low pre-treatment SIRI, low pretreatment NLR and clinical T1 + T2 stage had longer OS time. The Z test showed that the SIRI group had bigger AUC than LMR and PLR, and the difference is statistically significant. The ability of nomogram, based on pretreatment SIRI, pre-treatment NLR and clinical T stage, to predict the 3-year, 5-year, and 8-year overall survival rates of breast malignant tumor patients is better than clinical TNM stage. Pre-treatment SIRI was a more crucial and integral prognostic index for breast malignant tumor patients receiving NACT. It could be helpful for doctors to predict the prognosis of breast malignant tumor patients and to evaluate the treatment status of patients.

Effectiveness and safety of intraoperative radiotherapy (IORT) with low-energy X-rays (INTRABEAM®) for accelerated partial breast irradiation (APBI).

To evaluate treatment outcomes in patients with early-stage breast cancer (ESBC) treated with targeted intraoperative radiation therapy (IORT) administered as accelerated partial breast irradiation (APBI). Between December 2014 and May 2019, 50 patients diagnosed with ESBC were treated with a 50 kilovoltage (kV) X-ray source with a single dose of 20Gy using the Intrabeam® radiotherapy delivery system. All patients were followed prospectively to assess local control (LC), disease-free survival (DFS), cancer-specific survival (CSS), overall survival (OS), radiation-induced toxicity, and cosmetic outcomes. We also evaluated the prognostic implications of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). Median follow-up was 53months. Mean patient age was 70years. The mean duration of radiation delivery was 22.25min. Two patients developed a recurrence. One death was recorded. Elevated pretreatment NLR levels were a significant risk factor for mortality (p = 0.0026). The most common treatment-related toxicities were breast induration (30%) and seroma (18%). Five-year LC, DFS, CSS, and OS rates were 97.1%, 93.9%, 100%, and 94.4%, respectively. Cosmesis was excellent or good in most cases (94%). These findings confirm the effectiveness of a single dose of 20Gy of IORT with the Intrabeam device as APBI. The toxicity profile was good with excellent cosmesis. These results provide further support for the clinical use of APBI in well-selected patients.

Deep regional hyperthermia combined with modern concurrent chemoradiotherapy increases T-downstaging rate in locally advanced rectal cancer

Background Deep regional hyperthermia might have an additional effect on radiotherapy in treating locally advanced rectal cancer (LARC). This study aimed to investigate the role of hyperthermia combined with modern preoperative concurrent chemoradiotherapy (CRT) for LARC. Methods and materials From 2012 to 2018, 152 consecutive patients with LARC treated with neoadjuvant chemoradiation were enrolled and analyzed retrospectively. Pelvic radiotherapy (45–50 Gy) was delivered as volumetric modulated arc therapy (VMAT), concurrently with capecitabine chemotherapy. Fifty patients received hyperthermia combined with CRT (HCRT group) twice a week. Treatment response and outcomes were compared between the two groups. Furthermore, the relationships between peripheral blood neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR) in response to hyperthermia were analyzed. Results Patients treated with hyperthermia had a significantly higher T-downstaging rate than those without hyperthermia (82.0 vs. 62.7%; p = .016). Hyperthermia was an independent favorable predictor of T-downstaging (odds ratio [OR] = 2.473; 95% confidence interval [CI] 1.050–5.826; p = .038). In the HCRT group, a pre-therapeutic elevated NLR (≥3) was associated with a higher T-downstaging rate (100.0 vs. 73.5%, p = .043). However, NLR was not associated with the T-downstaging rate in the CRT group. Five-year rates of locoregional recurrence-free survival (96.8 vs. 94.7%, p = .959), disease-free survival (DFS; 61.4 vs. 79.3%, p = .242), and overall survival (OS; 92.7 vs. 89.8%, p = .831) were not statistically different between the CRT and HCRT groups. Conclusions Hyperthermia can improve preoperative treatment response in LARC. Pretreatment NLR may be a predictive factor for hyperthermia.