High dNLR Research Articles

Derived neutrophil-to-lymphocyte ratio has the potential to predict safety and outcomes of durvalumab after chemoradiation in non-small cell lung cancer

The usefulness of the derived neutrophil-to-lymphocyte ratio (dNLR) and its dynamics before/after durvalumab consolidation therapy to predict safety or efficacy remains unclear. We retrospectively reviewed patients with locally advanced non-small cell lung cancer treated with durvalumab consolidation therapy after chemoradiotherapy (D group) or chemoradiotherapy alone (non-D group) at multiple institutions. We investigated the association between dNLR, or its dynamics, and pneumonitis, checkpoint inhibitor-related pneumonitis (CIP), irAEs, and efficacy. Ninety-eight and fifty-six patients were enrolled in the D and non-D groups, respectively. The dNLR at baseline was significantly lower in patients who experienced irAEs or CIP than in those who did not. The low dNLR group, 28 days following durvalumab consolidation therapy (dNLR28 ≤ 3), demonstrated longer progression-free survival (PFS) and overall survival (OS) than the high dNLR group (dNLR28 > 3) (PFS, hazard ratio [HR] 0.44, 95% confidence interval [CI] 0.22–0.88, p = 0.020; OS, HR 0.39, 95% CI 0.16–0.94, p = 0.037). Among patients with high dNLR at baseline (dNLR > 3), the dNLR28 ≤ 3 group showed longer PFS than the dNLR28 > 3 group (p = 0.010). The dNLR is a predictive factor for irAEs and CIP in patients receiving durvalumab consolidation therapy. The dNLR at 28 days after durvalumab consolidation therapy and its dynamics predict favorable outcomes.

Serum albumin and derived neutrophil-to-lymphocyte ratio are potential predictive biomarkers for immune checkpoint inhibitors in small cell lung cancer.

Immune checkpoint inhibitors (ICIs) have reshaped the treatment landscape of small cell lung cancer (SCLC), but only a minority of patients benefit from this therapy. Therefore, it is critical to identify potential risk factors that could predict the efficacy of ICI treatment in SCLC patients and identify patient subgroups who may benefit the most from ICI therapy. Our study included a total of 183 SCLC patients who had received at least one dose of ICI treatment. We utilized both logistic regression and Cox proportional hazard regression to evaluate whether various patient clinical factors and serum biomarkers could serve as predictors of patient response to treatment and overall survival (OS) during ICI therapy. Logistic regression showed that patients with a history of surgery (p=0.003, OR 9.06, 95% CI: (2.17, 37.9)) and no metastasis (p=0.008, OR 7.82, 95% CI: (1.73, 35.4)) exhibited a higher odds of response to ICI treatment. Cox regression analyses demonstrated that pretreatment blood albumin (p=0.003, HR 1.72, 95% CI: (1.21, 2.45)) and derived neutrophil to lymphocyte ratio (dNLR) (p=0.003, HR 1.71, 95% CI: (1.20-2.44)) were independent predictors for OS in SCLC patients. By establishing a pre-treatment prognostic scoring system based on baseline albumin and dNLR, we found that patients with high albumin and low dNLR exhibited a significantly better prognosis than those with low albumin and high dNLR in both the full (P<.0001, HR 0.33, 95% CI: 0.20-0.55) and the metastatic cohort (P<.0001, HR 0.28, 95% CI: 0.15-0.51). The better prognostic group also had younger age, higher BMI and lower systemic inflammatory biomarker values than the unfavorable group (P<.0001). Our data reveals the significant role of metastasis status and treatment history in predicting the initial response of SCLC patients to ICI treatment. However, baseline serum albumin and dNLR provide a more precise prognostic prediction for patient OS. The scoring system based on albumin and dNLR enhances the ability to stratify patient prognosis and holds the potential to guide clinical decision-making for SCLC patients undergoing ICI therapy.

Abstract PO5-13-08: Impact of systemic inflammation markers in response to neoadjuvant pembrolizumab and chemotherapy in triple-negative breast cancer - a retrospective analysis

Abstract Background: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment landscape for triple-negative breast cancer (TNBC). Systemic inflammation has been linked to cancer development and overall poor outcomes. Routine blood parameters have been investigated as potential inflammatory biomarkers in patients (pts) with various types of cancer, such as the derived NLR (neutrophils/(leucocytes-neutrophils) ratio (dNLR). A high dNLR has been associated with worse survival in several types of cancer. Specifically, it has been linked to lower pathologic complete response (pCR) rates after neoadjuvant chemotherapy (CTx). We investigated the association between systemic inflammation markers (dNLR, LIPI score and platelet-to-lymphocyte ratio [PLR]) and pCR in early TNBC pts treated with CTx + pembrolizumab (Pemb). Methods: Retrospective analysis of pts with early TNBC treated with Pemb + CTx from April 2022 to March 2023. dNLR was estimated from analytical values of peripheral blood collected before treatment (baseline). dNLR was calculated as the ratio of the absolute neutrophil number to the difference between absolute total leukocyte and absolute neutrophil counts. Univariate and multivariate logistic regression analyses were used to explore the association of dNLR with main clinical characteristics and dNLR capability (distributed as a continuous variable, using median cut-off) to predict pCR. Results: The study included 86 TNBC pts with a median age of 51 years (IQR: 42.2 – 56-7). Most pts had stage II disease (64%) and presented grade 3 tumours (n=66; 78.5%). HER2 low tumours represented 27% (n=23) of the cohort. Germline mutations were present in 20 pts (23%) with the following distribution: BRCA1 (n=14), BRCA 2 (n=5) and PALB2 (n=1). The median stromal tumor infiltrating lymphocytes (TILs) was 20% (IQR: 10-30%). The median Ki67 was 70% (IQR:50%-80%). All pts received Pemb. The majority of pts received carboplatin plus paclitaxel, followed by EC90 (n=77 (90%), while 10% (n=9) did not receive anthracyclines. Data concerning surgical outcomes was available in 80 pts. Pathological complete response rate was 61.2% (n=49). Pts achieving pCR presented significantly higher TILs (p&amp;lt; 0.01). Residual cancer burden (RCB) class (n=80) was distributed as follows: 0: 61% (n=49); I: 13% (n=10); II: 20% (n=16); III: 1% (n=1) and non-assigned: 5% (n=4). In pts with germline mutations (n=20), the pCR rate was 85% (n=17). Median dNLR at baseline was 1.30 (interquartile range (IQR): 0.99 – 1.86). High baseline dNLR levels considered a continuous variable was associated with a higher likelihood of achieving a pCR in univariate (OR: 2.59; 95% CI: 1.01–6.6; p-value = 0.046) but not in multivariate (OR: 2.33; 95%; CI: 0.85–6.33; p-value = 0.097) logistic regression analysis (adjusted for stage and histologic grade). High baseline dNLR, defined by the median cut-off, was associated with an increased likelihood of achieving pCR in both univariate (OR: 3.85; 95% CI: 1.47–10.1; p-value = 0.006) and multivariate (OR: 3.72; 95% CI: 1.28–10.8; p-value = 0.016) logistic regression analysis (adjusted for stage and histologic grade). Conclusion: In this real-life cohort of early TNBC pts treated with Pemb and CTx we found similar pCR rates (61.2%) to the ones reported in the KN522 trial. No association between PLR or LIPI score with pCR was evidenced. High baseline dNLR (assessed as a continuous variable or by the median cut-off) was associated with a higher likelihood of pCR in the univariate analysis. In the multivariate analysis, only high baseline dNLR defined by the median cut-off retained an association with pCR after stage and histologic grade adjustment. Despite several limitations, these exploratory data provide initial evidence of a potential association between dNLR values and independent prediction of pCR. Further research to assess the role of dNLR as a predictive marker for pCR in early TNBC pts treated with CTx + immunotherapy is needed. Citation Format: Martina Spotti, Elie Rassy, Alessandro Viansone, Fiona Pham, Layal Rached, Barbara Pistilli, Charles-Antoine Dutertre, Joana Mourato Ribeiro. Impact of systemic inflammation markers in response to neoadjuvant pembrolizumab and chemotherapy in triple-negative breast cancer - a retrospective analysis [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 PO5-13-08.

Abstract 7621: Serum albumin and derived neutrophil-to-lymphocyte ratio are potential predictive biomarkers for immune checkpoint inhibitors in small cell lung cancer

Abstract Background: Immune checkpoint inhibitors (ICIs) have reshaped the treatment landscape of small cell lung cancer (SCLC), but only a minority of patients benefit from this therapy. Therefore, it is critical to identify potential risk factors that could predict the efficacy of ICI treatment in SCLC patients and identify patient subgroups who may benefit the most from ICI therapy. Methods: Our study included a total of 183 SCLC patients who had received at least one dose of ICI treatment. We utilized both logistic regression and Cox proportional hazard regression to evaluate whether various patient clinical factors and serum biomarkers, could serve as predictors of patient response to treatment and overall survival (OS) during ICI therapy. Results: Logistic regression showed that patients with a history of surgery (p=0.003, OR 9.06, 95% CI: (2.17, 37.9)) and no metastasis (p=0.008, OR 7.82, 95% CI: (1.73, 35.4)) exhibited a higher odds of response to ICI treatment. Cox regression analyses demonstrated that pretreatment blood albumin (p=0.003, HR 1.72, 95% CI: (1.21, 2.45)) and derived neutrophil to lymphocyte ratio (dNLR) (p=0.003, HR 1.71, 95% CI: (1.20-2.44)) were independent predictors for OS in SCLC patients. By establishing a pre-treatment prognostic scoring system based on baseline albumin and dNLR, we found that patients with high albumin and low dNLR exhibited a significantly better prognosis than those with low albumin and high dNLR in both the full (P&amp;lt;.0001, HR 0.33, 95% CI: 0.20-0.55) and the metastatic cohort (P&amp;lt;.0001, HR 0.28, 95% CI: 0.15-0.51). The better prognostic group also had younger age, higher BMI and lower systemic inflammatory biomarker values than the unfavorable group (P&amp;lt;.0001). Conclusion: Our data reveals the significant role of metastasis status and treatment history in predicting the initial response of SCLC patients to ICI treatment. However, baseline serum albumin and dNLR provide a more precise prognostic prediction for patient OS. The scoring system based on albumin and dNLR enhances the ability to stratify patient prognosis and holds the potential to guide clinical decision-making for SCLC patients undergoing ICI therapy. Citation Format: Zhanpeng Kuang, Jessica Miao, Xiaoli Zhang. Serum albumin and derived neutrophil-to-lymphocyte ratio are potential predictive biomarkers for immune checkpoint inhibitors in small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7621.

Association between immune-inflammatory indexes and lower urinary tract symptoms: an analysis of cross-sectional data from the US National Health and Nutrition Examination Survey (2005–2008)

ObjectiveThis study aimed to systematically investigate the relationship between immune-inflammatory indexes with lower urinary tract symptoms (LUTSs).DesignCross-sectional study.SettingNational Health and Nutrition Examination Survey (NHANES) (2005–2008).ParticipantsA total of 2709 men with...

Retreatment with nivolumab and ipilimumab with or without chemotherapy in patients with metastatic non-small cell lung cancer after progression on immune checkpoint inhibitor therapy.

e21192 Background: The advent of immune checkpoint inhibitor (ICI) has revolutionized the therapeutic arsenal for metastatic non-small cell lung cancer. However, better therapeutic options after a progression on frontline ICIs are urgently needed and remain to be defined. ICI retreatment (rt) may constitute a rational therapeutic alternative in these patients. However prospective studies evaluating such opportunity are still lacking. Methods: We retrospectively collected data from 30 metastatic NSCLC patients (pts) having progressed on ICI (anti-PD-1, anti-PD-L1 or anti-PD-1/anti-CTLA4 combined or not with histologydriven chemotherapy) who were retreated by double-agent ICI (ipilimumab and nivolumab) combined or not with histology-driven ChT in order to evaluate rt overall survival (OS) and rt progression-free-survival (PFS). The rt PFS was calculated from rt ICI initiation to death, last follow-up or disease progression. An assessment of correlation between certain clinical variables like sex, age, smoking history and others; and survival variables was performed. Results: The median age of the 30 pts included in the analysis was 64 years (63% of pts were &lt; 70 years old and 37% ≥ 70 years old) and 53% (n = 16) of the pts were male. Most suffered from a non-sq NSCLC (73%), with bone mets (66%), and were current or former smokers (90%). Median OS and median PFS in the whole group were 9 months (m) [95% confidence interval (CI): 5.7 - 14] and 2.5 m [95% CI: 2 - 4.6] respectively. Retreatment PFS was higher in pts having received dual ICI combined with ChT than dual ICI only [95% CI: 4.3 (3.7 – 6) versus 2.1 (1.5 – 2.9) m; hazard ratio (HR): 0.51 (0.24 – 1.10); p – value (p) = 0.085]. Retreatment OS and PFS were numerically higher in pts having received single- or double- ICI as prior therapy compared to ICI plus ChT [9.6 (6.4 – not reached) m versus 8.4 (3.7 – 13.5) m; HR: 0.53 (0.22 – 1.29), p = 0.15], and [4.2 (2.2 – not reached) m versus 2.4 (2 – 4.5 m); HR: 0.56 (0.25 – 1.24); p = 0.14), respectively], regardless of the rt. When we assessed the correlation between prior therapy and rt, we found the association of ChT to dual-ICI after prior single- or dual-ICI as first line treatment leads to a significantly higher PFS [4.5 (4 – NR) m versus 2.5 (1.6 – NR) m] compared to pts having received first ChT plus ICI then dual-ICI alone as second line treatment [HR 0.35 (95% CI: 0.13 – 0.93); p: 0.03]. The trend in OS benefit probably also favored ChT with dual-ICI as rt after prior single- or dual-ICI (HR 0.55; p = 0.23). Binary variables such as sex, histology, PD-L1 expression, smoking history, therapeutic discontinuation interval (TDI), baseline derived neutrophil-to-lymphocyte ratio dNLR) and baseline absolute lymphocyte counts (ALC) influenced positively the PFS in pts receiving dual ICI combined with ChT [ sex HR: 0.28; non-squamous histology HR: 0.26; PDL1 expression HR:0.22; former smoker HR: 0.23; never-smoker HR: 0.40; TDI less than 30 days HR: 0.09; high (≥ 3) dNLR HR: 0.22; and low (&lt;1000) ALC HR: 0.37]. Conclusions: Patients previously treated by ICI could be retreated by ICI combined with histology-driven chemotherapy in an individual approach, under certain circumstances, which are yet to be formally evaluated and determined.

Metabolic parameters on baseline 18F-FDG PET/CT are potential predictive biomarkers for immunotherapy in patients with head and neck squamous cell carcinoma.

PurposeWe evaluated baseline 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) metabolic parameters for predicting prognosis in patients with head and neck squamous cell carcinoma (HNSCC) who were receiving immune checkpoint inhibitors (ICIs). In addition, we also investigated the relationships between immunohistochemical (IHC) biomarkers and metabolic parameters.Materials and methodsA total of 39 patients with HNSCC who underwent 18F-FDG PET/CT prior to ICI therapy between November 2015 and December 2020 were enrolled. PET parameters of tumor lesions included standardized uptake values, metabolic tumor volume (MTV), total lesion glycolysis (TLG), and spleen-to-liver ratio (SLR). Clinical variables, IHC markers, and derived neutrophil-to-lymphocyte ratio (dNLR) were also obtained. Analysis was performed using Cox proportional hazard model, Kaplan-Meier method with log-rank test, and Spearman's correlation.ResultsTotal MTV (TMTV), total TLG (TTLG), and a combined parameter consisting of TMTV and dNLR were significant predictors for progression-free survival (PFS) in univariable analysis (TMTV, p = 0.018; TTLG, p = 0.027; combined parameter, p = 0.021). Above all, the combined parameter was an independent prognostic factor for PFS in multivariable analysis. The group with low TMTV and low dNLR had longer PFS than the group with high TMTV and high dNLR (p = 0.036). SLR was the only significant predictor for overall survival (p = 0.019). Additionally, there was a negative correlation between programmed cell death-ligand 1 expression (one of the IHC markers) and MTV in subgroup analysis.ConclusionPET parameters on baseline 18F-FDG PET/CT were predictive biomarkers for prognosis in patients with HNSCC undergoing ICI therapy. With dNLR, more accurate prognostic prediction could be possible.

Effect of dNLR and LIPI scores on the prognosis of elderly patients with non-surgical treatment of non-small cell lung cancer

Objective: To investigate the effects of derived neutrophil to lymphocyte ratio (dNLR) and lung immune prognostic index (LIPI) score on the overall survival (OS) of non-surgical elderly non-small cell lung cancer (NSCLC) patients. Methods: Clinical and pathological data of NSCLC patients in Hebei General Hospital from January 2014 to June 2018 were collected retrospectively. The dNLR value was calculated based on the results of blood routine before treatment, and the optimal cut-off value of dNLR was obtained by ROC curve. The patients were divided into low dNLR level group and high dNLR level group based on the optimal dNLR cut-off value. The groups were classified as good, intermediate and poor based on the LIPI score consisting of lactate dehydrogenase (LDH) and dNLR tested before treatment. The Kaplan-Meier method and Log rank test were used for survival analysis, and the Cox risk proportional regression model was used for analysis of prognostic influences. Results: The area under the ROC curve for dNLR predicting prognosis in non-surgical elderly NSCLC patients was 0.591 (95% CI: 0.491, 0.692; P=0.093). The optimal cut-off value for dNLR predicting prognosis in elderly NSCLC patients was 2.515, with a sensitivity of 45.5% and a specificity of 81.8%. The gender, BMI, pathological type and degree of tumor differentiation were associated with dNLR levels (P<0.05). The median survival times were 16 and 10 months for patients in the low dNLR level group (dNLR<2.51) and high dNLR level group (dNLR≥2.51), respectively (P<0.001), and 15, 10 and 6 months for patients with good, intermediate and poor LIPI scores, respectively (P<0.001). The age, gender, smoking, pathological type, tumor differentiation, clinical stage, BMI, dNLR level, LDH level and LIPI scores were all associated with patient prognosis (P<0.05), and age≥76 years, tumor differentiation and clinical stage Ⅲ and Ⅳ were independent factors influencing patient prognosis (P<0.05). Conclusion: No matter what treatment measures are taken, dNLR level and LIPI score are related to patients' prognosis, and non-surgical elderly NSCLC patients with high dNLR level and poor LIPI score before treatment have worse prognoses.

P1.12-04 The FLARE score and circulating neutrophils are associated with poor Covid-19 outcomes in patients with thoracic cancers

P1.12-04 The FLARE score and circulating neutrophils are associated with poor Covid-19 outcomes in patients with thoracic cancers

Clinical Significance of Serum Biomarkers in Stage IV Non-Small-Cell Lung Cancer Treated with PD-1 Inhibitors: LIPI Score, NLR, dNLR, LMR, and PAB.

Background To assess the prognostic value of pretreatment serum biomarkers in stage IV non-small-cell lung cancer (NSCLC) patients treated with PD-1 (programmed cell death protein 1) inhibitors and their value as a predictor of benefit. Methods We performed a retrospective study including patients with stage IV NSCLC who were treated with anti-PD-1 drugs in first or advanced lines of therapy in the Affiliated Tumor Hospital of Nantong University. Serum biomarkers such as NLR, dNLR, LMR, PAB, ALB, and LIPI scores were calculated and analyzed in detail. Results A total of 85 patients with stage IV NSCLC treated with PD-1 inhibitors in the first or advanced lines of therapy were included in this subject. According to the tumor response of PD-1-based treatment, ORR was 42.4% (36/85) and DCR was 68.2% (58/85). The median OS and PFS were 20.0 months and 7.0 months, respectively. The ROC curves showed that the serum biomarkers of NLR, dNLR, LDH, LMR, PAB, and ALB were significantly associated with overall survival and helped to determine the cut-off value. The multivariate Cox proportional hazard analyses for stage IV NSCLC patients treated with PD-1 inhibitors indicated that dNLR (P < 0.001) and ALB (P = 0.033) were independent prognostic indicators of PFS, while liver metastasis (P = 0.01), NLR (P = 0.01), dNLR (P = 0.001), and LMR (P = 0.006) were independent prognostic indicators of OS. Moreover, patients of the good LIPI group showed prolonged PFS and OS than those with intermediate/poor LIPI score (P < 0.001 and P = 0.006, respectively). Conclusions Pretreatment dNLR is an independent prognostic indicator of both PFS and OS in stage IV NSCLC patients treated with PD-1 inhibitors. Pretreatment LIPI, combining dNLR > 3 and LDH>ULN, was correlated with worse outcome for stage IV NSCLC patients treated with ICI. High NLR, high dNLR, low LMR, and low ALB at baseline might be useful as an early predictive biomarker of benefit.

The FLARE score, circulating neutrophils, and association with COVID-19 outcomes in patients with solid tumors.

2551 Background: Inflammation and neutrophils play a central role in severe Covid-19 disease. In previous data, we showed that the FLARE score, combining both tumor and Covid-19-induced proinflammatory status (proinflam-status), predicts early mortality in cancer patients (pts) with Covid-19 infection. We aimed to assess the impact of this score in a larger cohort and characterize the immunophenotype (IF) of circulating neutrophils. Methods: Multicenter retrospective cohort (RC) of pts with cancer and Covid-19 infection across 14 international centers. Circulating inflammatory markers were collected at two timepoints: baseline (-15 to -45d before Covid-19 diagnosis) and Covid-19 diagnosis. Tumor-induced proinflam-status was defined by high dNLR (neutrophils/(leucocytes-neutrophils)&gt;3) at baseline. Covid-19-induced proinflam-status was defined by +100% increase of dNLR between both timepoints. We built the FLARE score combining both Tumor and Infection-induced inflammation: T+/I+ (poor), if both proinflam-status; T+/I- (T-only), if inflammation only due to tumor; T-/I+ (I-only), if inflammation only due to Covid; T-/I- (favorable), if no proinflam-status. The IF of circulating neutrophils by flow cytometry was determined in a unicenter prospective cohort (PC) of pts with cancer during Covid-19 infection and in healthy volunteers (HV). Primary endpoint was 30-day mortality. Results: 524 pts were enrolled in the RC with a median follow-up of 84d (95%CI 78-90). Median age was 69 (range 35-98), 52% were male and 78% had baseline PS &lt;1.Thoracic cancers were the most common (26%). 70% had active disease, 51% advanced stage and 57% were under systemic therapy. dNLR was high in 25% at baseline vs 55% at Covid-19 diagnosis. The median dNLR increase between both timepoints was +70% (IQR: 0-349%); 42% had +100% increase of dNLR. Pts distribution and mortality across FLARE groups is resumed in the Table. Overall mortality rate was 26%. In multivariate analysis, including gender, stage and PS, the FLARE poor group was independently associated with 30-day mortality [OR 5.27; 1.37-20.3]. 44 pts were enrolled in the PC. Median circulating neutrophils were higher in pts with cancer (n=10, 56.7% [IQR: 39-78.4%]) vs HV (n=6, 35.8% [IQR: 25.6-21%]), and particularly higher in pts with cancer and severe Covid-19 infection (n=7, 88.6% [IQR: 80.9-94%] (p=0.003). A more comprehensive characterization of the IF of circulating neutrophils, including Lox1/CD62/CD64, will be presented at ASCO. Conclusions: The FLARE score, combining tumor and Covid-19-induced proinflam-status, can identify the population at higher risk for mortality. A better characterization of circulating neutrophils may help improve the prediction of Covid-19 outcomes in pts with cancer. [Table: see text]

Evaluation of the Predictive Role of Blood-Based Biomarkers in the Context of Suspicious Prostate MRI in Patients Undergoing Prostate Biopsy.

The aim of this study was to assess the predictive value of pre-biopsy blood-based markers in patients undergoing a fusion biopsy for suspicious prostate magnetic resonance imaging (MRI). We identified 365 consecutive patients who underwent MRI-targeted and systematic prostate biopsy for an MRI scored Prostate Imaging–Reporting and Data System Version (PI-RADS) ≥ 3. We evaluated the neutrophil/lymphocyte ratio (NLR), derived neutrophil/lymphocyte ratio (dNLR), platelet/lymphocyte ratio (PLR), systemic immune inflammation index (SII), lymphocyte/monocyte ratio (LMR,) de Ritis ratio, modified Glasgow Prognostic Score (mGPS), and prognostic nutrition index (PNI). Uni- and multivariable logistic models were used to analyze the association of the biomarkers with biopsy findings. The clinical benefits of biomarkers implemented in clinical decision-making were assessed using decision curve analysis (DCA). In total, 69% and 58% of patients were diagnosed with any prostate cancer and Gleason Grade (GG) ≥ 2, respectively. On multivariable analysis, only high dNLR (odds ratio (OR) 2.61, 95% confidence interval (CI) 1.23–5.56, p = 0.02) and low PNI (OR 0.48, 95% CI 0.26–0.88, p = 0.02) remained independent predictors for GG ≥ 2. The logistic regression models with biomarkers reached AUCs of 0.824–0.849 for GG ≥ 2. The addition of dNLR and PNI did not enhance the net benefit of a standard clinical model. Finally, we created the nomogram that may help guide biopsy avoidance in patients with suspicious MRI. In patients with PI-RADS ≥ 3 lesions undergoing MRI-targeted and systematic biopsy, a high dNLR and low PNI were associated with unfavorable biopsy outcomes. Pre-biopsy blood-based biomarkers did not, however, significantly improve the discriminatory power and failed to add a clinical benefit beyond standard clinical factors.

Prognostic value of preoperative inflammatory markers among different molecular subtypes of lower-grade glioma

BackgroundThe inflammatory response is closely related to cancer progression and prognosis. The aim of this study was to determine the prognostic value of preoperative inflammatory markers among different molecular subtypes of lower-grade glioma (LGG). MethodsWe performed a retrospective analysis of 214 patients with LGG from 2001 to 2013, evaluating the effect of the neutrophil/lymphocyte ratio (NLR), lymphocyte/monocyte ratio (LMR), platelet/lymphocyte ratio (PLR) and derived NLR (dNLR) on prognosis among different molecular subtypes. Isocitrate dehydrogenase (IDH) and telomerase reverse transcriptase (TERT) promotor mutations were detected by gene sequencing, and Chromosome arms 1p and 19q (1p/19q) codeletion was estimated via fluorescence in situ hybridization. ResultsSurvival analysis showed that a high NLR, low LMR, and high dNLR were associated with poor prognosis, while the PLR had no prognostic significance. The subsequent molecular subtype analysis indicated that a high NLR and dNLR predicted worse survival in the IDH mutation only group, a high NLR and PLR predicted worse survival in the IDH and TERT promoter mutation group, and a high PLR was associated with shorter survival in the triple-positive group. Furthermore, univariate and multivariate Cox regression analysis suggested that the dNLR was an independent prognostic factor for LGG. Finally, the prognostic nomogram was developed by integrating the inflammatory marker dNLR and independent clinical risk factors. ConclusionThe results of this study indicated that a high dNLR was an independent risk factor for overall survival rates in patients with LGG, which may increase prognostic accuracy and improve patient outcomes.

Prognostic impact of immune inflammation biomarkers in predicting survival and radiosensitivity in patients with non-small-cell lung cancer treated with chemoradiotherapy.

The purpose of this retrospective study was to investigate the prognostic impact of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), derived NLR (dNLR) and systemic immune-inflammation index (SII) in predicting outcomes for patients with locally advanced non-small-cell lung cancer (NSCLC). The secondary endpoint was to evaluate the radiosensitivity in terms of response rate. Newly diagnosed locally advanced NSCLC patients were enrolled. Immune inflammation biomarkers were calculated from baseline blood samples. Patients were stratified in two groups based on optimal cut-off values for each biomarker. The associations between biomarkers and overall survival (OS), progression-free survival (PFS), local regional recurrence-free survival (LRRFS), and also response to radiotherapy were analysed. A total of 392 patients were included. Five-year OS, PFS and LRRFS rates were 14.6%, 12.1%, and 13.4% respectively. Optimal cut-off values for NLR, PLR, dNLR and SII were 3.07, 166, 2.02 and 817 respectively. Low NLR (HR 1.73, 95% CI 1.34-2.24, P < 0.001), low PLR (HR 1.37, 95% CI 1.06-1.76, P = 0.013), low dNLR (HR 1.66, 95% CI 1.29-2.13, P < 0.001) and low SII (HR 1.63, 95% CI 1.18-2.04, P < 0.001) were independent prognostic factors for OS. Low NLR, PLR, dNLR and SII were also significant prognostic factors for PFS and LRRFS. Low NLR, low dNLR and low SII groups had better radiosensitivity than compared with high NLR, high dNLR and high SII groups (P = 0.001, P = 0.001 and P = 0.012). NLR, PLR, dNLR and SII were independently associated with improved OS, PFS and LRRFS. Low NLR, dNLR and SII groups had better radiosensitivity. Immune inflammation biomarkers are promising prognostic predictors which can be obtained easily and inexpensively.

Dynamic Changes in Neutrophil-to-Lymphocyte Ratio are Associated with Survival and Liver Toxicity Following Stereotactic Body Radiotherapy for Hepatocellular Carcinoma.

PurposeImmune response to antitumor therapies has been correlated with oncologic outcomes. This study aimed to determine whether dynamic changes in immune parameters could predict survival outcomes and assess their relationship with liver toxicity in hepatocellular carcinoma (HCC) patients treated with stereotactic body radiation therapy (SBRT).MethodsData on pre- and post-SBRT (within 3 months) peripheral blood cell counts, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were retrospectively collected. Kinetic changes in these immune parameters and delta-NLR (dNLR) and delta-PLR (dPLR) in response to SBRT were evaluated. Overall survival (OS) and progression-free survival (PFS) were compared based on baseline NLR/PLR and dNLR/dPLR. Additionally, the association of these dynamic measures with liver toxicity was determined.ResultsThe study included 93 patients with a median 10.7-month follow-up. Significant increases in NLR (p<0.001) and PLR (p=0.003) were observed after SBRT. In the multivariable analysis, elevated pre-SBRT NLR (p<0.001) and dNLR (p=0.011) were predictive of worse OS. dNLR was not associated with PFS. Neither PLR nor dPLR was predictive of survival outcomes. Patients with Child–Turcotte–Pugh class B had higher dNLR and greater risk of liver toxicity than class A counterparts. Receiver operating characteristic curve analysis found that dNLR ≥1.9 was an optimal cut-off value for determining liver toxicity risk (35.1% vs 7.5%, p=0.002).ConclusionBaseline NLR and dNLR can complementarily predict OS in HCC patients treated with SBRT. Elevated dNLR is associated with worse OS and development of liver toxicity, possibly through their relationship with baseline liver function. Dynamic changes in NLR should be monitored in HCC care.

Predictor Role of Systemic Inflammation in Ovarian Cancer

Objective: The study aims to investigate the diagnostic value of hemogram derived systemic inflammation parameters in ovarian cancer.Methods: Totally, the study group consisted of 60 patients with suspected ovarian masses who underwent surgery between February 1th, 2020, and May 1th, 2021, in Ordu University Training and Research Hospital. The patients included in the study were divided into two groups according to postoperative histopathological diagnosis, benign group (consisting of 39 patients) and malign group (consisting of 21 patients). The analysis of the receiver operating characteristic (ROC) curve was used to discover the optimal cut-off values of the hemogram derived blood parameters to predict ovarian cancer.Results: In the cancer group; 85% of the patients were diagnosed with epithelial ovarian cancer and 62% at late stage. As compares with benign ovarian mass group, the ovarian cancer group had higher neutrophil counts (6.67+3.17 vs 4.64+1.94) (p=0.006), but lower lymphocyte counts (1.60+0.68 vs 2.22+0.64) (p=0.003). The high NLR values (cut-off 2.557) predict ovarian cancer with 71.4% sensitivity and 69.2% specificity (AUC 0.817, p=0.000, CI=0.712-0.922). The high dNLR values (cut- off 1.881) also predict cancer with similar sensitivity and specificity as NLR (AUC 0.814, p=0.000, CI 0.708-0.921). Significant cut-off values for the other hemogram derived parameters were 0.26, 0.0165, 159.66 and 770.611 for MLR, NPR, PLR and SII, respectively. Additionally, the high values of CA 125 (cut-off 34.45) and CA 15-3 (cut-off 16.4) was founded to be related with ovarian cancer.Conclusions: This paper revealed that high inflammatory parameters such as NLR and dNLR in patients with ovarian masses are mainly associated with ovarian cancer. In the study, it was emphasized that simple and easily accessible hemogram parameters should be used in addition to tumor biomarkers such as CA 125, CA 15-3, which are routinely used in predicting ovarian cancers. We think that more valuable results will be achieved with comprehensive studies designed prospectively.

Prognostic value of inflammatory response biomarkers using peripheral blood and [18F]-FDG PET/CT in advanced NSCLC patients treated with first-line chemo- or immunotherapy

ObjectivesWe aimed to compare the prognostic value of inflammatory biomarkers extracted from pretreatment peripheral blood and [18F]-FDG PET for estimating outcomes in non-small cell lung cancer (NSCLC) patients treated with first-line immunotherapy (IT) or chemotherapy (CT). Materials and methodsIn this retrospective multicenter study, we evaluated 111 patients with advanced NSCLC who underwent baseline [18F]-FDG PET/CT before IT or CT between 2016 and 2019. Several blood inflammatory indices were evaluated: derived neutrophil-to-lymphocyte ratio (dNLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP) and systemic immune-inflammation index (SII). FDG-PET inflammatory parameters were extracted from lymphoid tissues (BLR and SLR: bone marrow or spleen-to-Liver SUVmax ratios). Association with survival and relationships between parameters were evaluated using Cox prediction models and Spearman's correlation respectively. ResultsOverall, 90 patients were included (IT:CT) (51:39pts). Median PFS was 8.6:6.6 months and median OS was not reached:21.2 months. In the IT cohort, high dNLR (>3), high SII (≥1,270) and high SLR (0.77) were independent statistically significant prognostic factors for one-year progression-free survival (1y-PFS) and two-year overall survival (2y-OS) on multivariable analysis. In the CT cohort, high BLR (≥0.80) and high dNLR (>3) were associated with shorter 1y-PFS (HR 2.2, 95% CI 1.0–4.9) and 2y-OS (HR 3.4, 95CI 1.1–10.3) respectively, on multivariable analysis. Finally, BLR significantly but moderately correlated with most blood-based inflammatory indices (CRP, PLR and SII) while SLR was only associated with CRP (p < 0.01 for all). ConclusionIn advanced NSCLC patients undergoing first-line IT or CT, pretreatment blood and inflammatory factors evaluating the spleen or bone marrow on [18F]-FDG PET/CT provided prognostic information for 1y-PFS and 2y-OS. These biomarkers should be further evaluated for potential clinical application.

Impact of pre-treatment derived neutrophil-lymphocyte-ratio on outcomes in patients with triple-negative breast cancer.

e12556 Background: There is an ambiguity of data regarding the predictive and prognostic significance of pre-treatment-derived neutrophil-lymphocyte-ratio (DNLR) to attain pathologic complete response (pCR) after neo-adjuvant chemotherapy (NACT) and survival in patients with triple-negative breast cancer (TNBC). Methods: In this ambispective study, conducted at Dr. B.R.A., I.R.C.H., AIIMS, New Delhi, 328 patients of TNBC registered from a period of May 2013 to June 2020, who received treatment with curative intent were included. Patients with oligometastatic TNBC who received NACT with curative intent were also included in the analysis. Survival analysis to evaluate the correlation of pre-treatment DNLR with relapse-free survival (RFS) and overall survival (OS) was done. Logistic regression analysis was done to evaluate the association of DNLR with pCR among the subset of the sample who completed NACT and underwent surgery. Results: The median age of our cohort was 45 (18-74) years. Study cohort comprised of 165 (50.3%) pre-menopausal, 150 (45.7%) post-menopausal and 12 (3.7%) peri-menopausal patients respectively. Stage distribution as per AJCC 7th edition was stage-I 8 (2.4%), stage-II 127 (38.7%), stage-III 171(52.1%), and stage-IV 22 (6.7%) patients respectively. The median duration of symptoms was 3 (0.25-36) months. One seventy-three (52.7%) patients received NACT and underwent surgery, out of which 52 (30.1%) patients achieved pCR. Median DNLR in the overall population was 1.7 (0.4-10.1) and the median derived lymphocyte count of 2290 (370-11700) with &lt; 5%(n = 14) having baseline lymphopenia( &lt; 1000). Based on the maximum sensitivity and specificity, a DNLR cut-off point of 1.77 in the overall population and 1.88 among those patients who underwent surgery following NACT were used to categorize low and high DNLR. Median RFS was 73.5 months in our sample, whereas median OS was not reached. The 3-year RFS and OS rates were 65.8% (59.0-71.8) and 85.1% (79.5-89.2%) respectively. High DNLR( &gt; 1.77) was not associated with RFS [HR (95%CI): 1.36 (0.90-2.06)] and OS [HR (95% CI): 0.97 (0.52-1.81)]. In a subset analysis of patients (173) undergoing surgery following NACT, high DNLR ( &gt; 1.88) was not found to be associated with pCR [OR (95% CI): 0.81 (0.42-1.57)]. Conclusions: Pre-treatment DNLR is an easily available inflammatory marker. Indian patients of TNBC usually have raised baseline lymphocyte count, hence, pre-treatment DNLR may not be a reliable predictor of pCR and survival outcomes in these patients. Association of DNLR at various treatment and post-treatment time points with survival outcomes needs further exploration.

Predicting immunotherapy outcomes under therapy in patients with advanced NSCLC using dNLR and its early dynamics

BackgrounddNLR at the baseline (B), defined by neutrophils/[leucocytes-neutrophils], correlates with immune-checkpoint inhibitor (ICI) outcomes in advanced non–small-cell lung cancer (aNSCLC). However, dNLR is dynamic under therapy and its longitudinal assessment may provide data predicting efficacy. We sought to examine the impact of dNLR dynamics on ICI efficacy and understand its biological significance. Patients and methodsaNSCLC patients receiving ICI at 17 EU/US centres were included [Feb/13-Jun/18]. As chemotherapy-only group was evaluated (NCT02105168). dNLR was determined at (B) and at cycle2 (C2) [dNLR≤3 = low]. B+C2 dNLR were combined in one score: good = low (B+C2), poor = high (B+C2), intermediate = other situations. In 57 patients, we prospectively explored the immunophenotype of circulating neutrophils, particularly the CD15+CD244-CD16lowcells (immature) by flow cytometry. ResultsAbout 1485 patients treatment with ICI were analysed. In ICI-treated patients, high dNLR (B) (~1/3rd) associated with worse progression-free (PFS)/overall survival (OS) (HR 1.56/HR 2.02, P < 0.0001) but not with chemotherapy alone (N = 173). High dNLR at C2 was associated with worse PFS/OS (HR 1.64/HR 2.15, P < 0.0001). When dNLR at both time points were considered together, those with persistently high dNLR (23%) had poor survival (mOS = 5 months (mo)), compared with high dNLR at one time point (22%; mOS = 9.2mo) and persistently low dNLR (55%; mOS = 18.6mo) (P < 0.0001). The dNLR impact remained significant after PD-L1 adjustment. By cytometry, high rate of immature neutrophils (B) (30/57) correlated with poor PFS/OS (P = 0.04; P = 0.0007), with a 12-week death rate of 49%. ConclusionThe dNLR (B) and its dynamics (C2) under ICI associate with ICI outcomes in aNSCLC. Persistently high dNLR (B+C2) correlated with early ICI failure. Immature neutrophils may be a key subpopulation on ICI resistance.

Association of Physical Activity and Derived Neutrophilto-Lymphocyte Ratio with Outcome in Patients with Recurrent and/or Metastatic Squamous Cell Carcinoma of Head and Neck Treated with Immunotherapy

Regular Physical Activity (PA) improves the outcomes of patients with cancer mainly by enhancing the immune system. The relationship of PA and the derived Neutrophil-to-Lymphocyte Ratio (dNLR) with the evolution of 31 consecutive patients with Recurrent and/or Metastatic Squamous Cell Carcinoma of Head and Neck (R/M SCCHN) treated with immunotherapy was determined in this retrospective study. Seventeen patients (55%) performed PA and 14 (45%) did not. The time to progression and Overall Survival (OS) was significantly better in the first compared to the second group (p=0.002 and 0.0019, respectively). In patients with a dNLR less than 3.5 the survival was significantly longer than in patients with a higher dNLR (p=0.004). Our results suggest that there is an association between PA and improved outcomes in R/M SCCHN patients treated with immunotherapy and that the dNLR is a predictive marker of good response to treatment.