Baseline peripheral blood biomarkers associated with clinical outcome of advanced lung cancer in patients treated with anti-PD-1 antibody.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20599-e20599 ◽  
Author(s):  
Aixa Elena Soyano ◽  
Bhagirathbhai R. Dholaria ◽  
Julian A. Marin-Acevedo ◽  
Nancy N. Diehl ◽  
David Hodge ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Outcome ◽  
Clinical Outcomes ◽  
Peripheral Blood ◽  
Lymphocyte Count ◽  
Absolute Lymphocyte Count ◽  
Advanced Lung Cancer ◽  
Blood Biomarkers ◽  
Risk Of Death ◽  
Increased Risk

e20599 Background: The anti-PD-1 antibodies nivolumab and pembrolizumab have demonstrated improved overall survival (OS) and progression free survival (PFS) in a subset of patients with metastatic or locally advanced lung cancer (LC). To date, no blood biomarkers have been identified to predict clinical outcome to anti-PD-1 agents. Methods: A retrospective analysis of 52 patients with advanced LC and treated with anti-PD-1 antibodies in a single institution was performed. White blood cell count (WBC), absolute neutrophil count (ANC), absolute lymphocyte count (ALC), absolute neutrophil to absolute lymphocyte count ratio (ANC/ALC), absolute eosinophil count (AEC), and platelet counts at baseline before start of anti-PD-1 antibody were assessed. Kaplan–Meier and Cox regression analysis were done. Results: 48 patients were treated with nivolumab (92.3%) and 4 patients with pembrolizumab (7.7%). Median follow up was 13.6 months and median OS was 26 months. Higher baseline ANC and ANC/ALC ratio significantly correlated with worse clinical outcomes. Patients with baseline ANC > 6060/mm3 had a significantly increased risk of death [hazard ratio (HR) = 2.46; 95% CI 1.12–5.42, P = 0.025] and of progression on anti-PD-1 antibody [HR = 2.41; 95% CI 1.25–4.64, P = 0.009] compared with patients with ANC ≤6060/mm3. Similarly, patients with baseline ANC/ALC ratio ≥ 4.59 had a significantly increased risk of death [HR = 2.41; 95% CI 1.11–5.24, P = 0.027] and of progression on anti-PD-1 antibody [HR = 2.08; 95% CI 1.10–3.95, P = 0.027] compared with patients with ANC/ALC < 4.59. One year survival rate in patients who had ANC < 3390/mm3, ANC 3390-6060/mm3 and ANC > 6060/mm3 were 86.5%, 76.9% and 48.1% respectively. Conclusions: Increased baseline ANC and ANC/ALC were associated with poor PFS and OS in LC patients treated with anti-PD-1 antibodies. Although these findings need to be validated in a large sample size, our data suggested that baseline ANC and ANC/ALC ratio might help the risk stratification and assist treatment strategies. The potential predictive value of peripheral blood biomarkers for clinical outcomes to anti-PD-1 antibody should be further investigated in a prospective study.

83 The prognostic significance of peripheral blood biomarkers in patients with advanced non-small cell lung cancer treated with pembrolizumab: a clinical study

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A91-A91
Author(s):  
Kira MacDougall ◽  
Muhammad Niazi ◽  
Jeff Hosry ◽  
Sylvester Homsy ◽  
Alexander Bershadskiy
Keyword(s):  
Peripheral Blood ◽  
Lymphocyte Count ◽  
Advanced Nsclc ◽  
Cox Regression ◽  
Absolute Lymphocyte Count ◽  
Blood Biomarkers ◽  
Cox Regression Analysis ◽  
Start Date ◽  
Kaplan Meier ◽  
Significant Difference

BackgroundPembrolizumab is an anti-programmed cell death protein 1 (PD-1) antibody used for the treatment of advanced non-small cell lung carcinoma (NSCLC). Systemic inflammation has long been associated with poor outcomes in many types of solid tumors.1 Peripheral blood biomarkers such as absolute lymphocyte count (ALC) and absolute neutrophil count to absolute lymphocyte count ratio (ANC/ALC) serve as surrogate markers of inflammation. The aim of this study is to investigate ALC and ANC/ALC in patients with advanced NSCLC receiving pembrolizumab and determine if there is a correlation between these biomarkers and overall survival (OS).MethodsA total of 240 patients with advanced NSCLC treated with pembrolizumab at Northwell Health hospital centers were included. The ALC and ANC/ALC were examined at initiation of pembrolizumab and after 6 weeks on treatment. The prognostic role of these peripheral blood biomarkers on OS were examined with Kaplan-Meier curves and a multivariable cox regression analysis.ResultsOf the 240 patients, the majority were male (52%), with a median age of 67 years (interquartile range [IQR] 59–73 years), had a diagnosis of adenocarcinoma (76%), with stage IV disease (82%). PDL-1 expression was >50% in 44% of the patients. The median time on treatment with pembrolizumab was 5.7 months [IQR: 2.7–12.5]. The median ALC and ANC/ALC were significantly lower at 6 weeks of pembrolizumab compared to the start date of treatment (1.38 vs. 1.4, p<0.001) and (3.6 vs. 4.6, p<0.001) respectively. An ALC greater than 1.4 was associated with an increased OS (figure 1), at 6 weeks after initiation of pembrolizumab (p=0.046), but not at the start of treatment (p=0.095). An ANC/ALC less than 5 was associated with improved OS (figure 2), both at initiation of pembrolizumab (p=0.003) and at 6 weeks after initiation of treatment (p = 0.028). Likewise, after adjusting for potential cofounders with a multivariate analysis (table 1), a baseline ANC/ALC of 5 or higher had a significantly increased risk of death (hazards ratio (HR)=1.84; 95% confidence interval (CI), 1.21–2.79; p=0.004), compared with patients with a lower ratio.ConclusionsHigh ALC at time of diagnosis as well as low ANC/ALC at baseline and at 6 weeks on treatment correlated with an increased OS in patients with advanced NSCLC treated with pembrolizumab. These findings represent a readily available predictive biomarker for oncologists and may help with risk stratification and strategizing treatment plans.Abstract 83 Figure 1Kaplan-Meier survival estimates between groups with different ALC at the start date of pembrolizumab and at 6 weeks after initiation of pembrolizumab. There is a statistically significant difference in OS between patients with ALC < 1.4 and patients with ALC ≥ 1.4 at 6 weeks after initiation of pembrolizumab (p = 0.046), but not at the start of treatment (p = 0.095).Abstract 83 Figure 2Kaplan-Meier survival estimates between groups with different ANC/ALC ratio at the start date of pembrolizumab and at 6 weeks after initiation of pembrolizumab. There is a statistically significant difference in OS between patients with ANC/ALC < 5 and patients with ALC ≥ 5, both at the start date of pembrolizumab (p = 0.003) and at 6 weeks after initiation of pembrolizumab (p = 0.028).Abstract 83 Table 1Multivariable cox regression analysis for association of baseline peripheral blood biomarkers and overall survival.Legend: HR, hazards ratio; CI, confidence interval; CNS, central nervous system, ANC/ALC, absolute neutrophil count to absolute lymphocyte count ratio; PDL-1, programmed death-1 ligand 1; ECOG, Eastern Cooperative Oncology Group performance scale.Ethics ApprovalThe study was approved by Zucker School of Medicine at Hofstra/Northwell at Staten Island University Hospital’s IRB #: 19–0922ReferenceMantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;454(7203):436–44.

scholarly journals Peripheral Blood Biomarkers Associated with Clinical Outcome in Non–Small Cell Lung Cancer Patients Treated with Nivolumab

2018 ◽  
Vol 13 (1) ◽  
pp. 97-105 ◽  
Author(s):  
Junko Tanizaki ◽  
Koji Haratani ◽  
Hidetoshi Hayashi ◽  
Yasutaka Chiba ◽  
Yasushi Nakamura ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Outcome ◽  
Small Cell Lung Cancer ◽  
Cancer Patients ◽  
Cell Lung Cancer ◽  
Peripheral Blood ◽  
Small Cell ◽  
Blood Biomarkers ◽  
Small Cell Lung ◽  
Lung Cancer Patients

scholarly journals Deep Learning Analysis of CT Images Reveals High-Grade Pathological Features to Predict Survival in Lung Adenocarcinoma

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4077
Author(s):  
Yeonu Choi ◽  
Jaehong Aum ◽  
Se-Hoon Lee ◽  
Hong-Kwan Kim ◽  
Jhingook Kim ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Deep Learning ◽  
Cancer Patients ◽  
Clinical Outcomes ◽  
High Probability ◽  
Advanced Lung Cancer ◽  
High Grade ◽  
Lung Cancer Patients ◽  
Risk Of Death ◽  
3D Network

We aimed to develop a deep learning (DL) model for predicting high-grade patterns in lung adenocarcinomas (ADC) and to assess the prognostic performance of model in advanced lung cancer patients who underwent neoadjuvant or definitive concurrent chemoradiation therapy (CCRT). We included 275 patients with 290 early lung ADCs from an ongoing prospective clinical trial in the training dataset, which we split into internal–training and internal–validation datasets. We constructed a diagnostic DL model of high-grade patterns of lung ADC considering both morphologic view of the tumor and context view of the area surrounding the tumor (MC3DN; morphologic-view context-view 3D network). Validation was performed on an independent dataset of 417 patients with advanced non-small cell lung cancer who underwent neoadjuvant or definitive CCRT. The area under the curve value of the DL model was 0.8 for the prediction of high-grade histologic patterns such as micropapillary and solid patterns (MPSol). When our model was applied to the validation set, a high probability of MPSol was associated with worse overall survival (probability of MPSol >0.5 vs. <0.5; 5-year OS rate 56.1% vs. 70.7%), indicating that our model could predict the clinical outcomes of advanced lung cancer patients. The subgroup with a high probability of MPSol estimated by the DL model showed a 1.76-fold higher risk of death (HR 1.76, 95% CI 1.16–2.68). Our DL model can be useful in estimating high-grade histologic patterns in lung ADCs and predicting clinical outcomes of patients with advanced lung cancer who underwent neoadjuvant or definitive CCRT.

A Quantitative Ultrastructural Study of Peripheral Blood Lymphocytes Containing Parallel Tubular Arrays in Epstein-Barr Virus and Cytomegalo-Virus Mononucleosis

1981 ◽  
Vol 39 ◽  
pp. 454-455
Author(s):  
C. M. Payne ◽  
P. M. Tennican
Keyword(s):  
Peripheral Blood ◽  
Lymphocyte Count ◽  
Epstein Barr Virus ◽  
Absolute Lymphocyte Count ◽  
Peripheral Blood Lymphocytes ◽  
Clinical State ◽  
Barr Virus ◽  
The Absolute ◽  
Epstein Barr ◽  
Tubular Arrays

In the normal peripheral circulation there exists a sub-population of lymphocytes which is ultrastructurally distinct. This lymphocyte is identified under the electron microscope by the presence of cytoplasmic microtubular-like inclusions called parallel tubular arrays (PTA) (Figure 1), and contains Fc-receptors for cytophilic antibody. In this study, lymphocytes containing PTA (PTA-lymphocytes) were quantitated from serial peripheral blood specimens obtained from two patients with Epstein -Barr Virus mononucleosis and two patients with cytomegalovirus mononucleosis. This data was then correlated with the clinical state of the patient.It was determined that both the percentage and absolute number of PTA- lymphocytes was highest during the acute phase of the illness. In follow-up specimens, three of the four patients' absolute lymphocyte count fell to within normal limits before the absolute PTA-lymphocyte count.In one patient who was followed for almost a year, the absolute PTA- lymphocyte count was consistently elevated (Figure 2). The estimation of absolute PTA-lymphocyte counts was determined to be valid after a morphometric analysis of the cellular areas occupied by PTA during the acute and convalescent phases of the disease revealed no statistical differences.

scholarly journals Cross-sectional observational study of epidemiology of COVID-19 and clinical outcomes of hospitalised patients in North West London during March and April 2020

BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e044384
Author(s):  
Guduru Gopal Rao ◽  
Alexander Allen ◽  
Padmasayee Papineni ◽  
Liyang Wang ◽  
Charlotte Anderson ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Clinical Outcomes ◽  
Severe Infection ◽  
Older Age ◽  
Cross Sectional ◽  
North West ◽  
Icu Admission ◽  
Risk Of Death ◽  
Hospitalised Patients ◽  
Increased Risk

ObjectiveThe aim of this paper is to describe evolution, epidemiology and clinical outcomes of COVID-19 in subjects tested at or admitted to hospitals in North West London.DesignObservational cohort study.SettingLondon North West Healthcare NHS Trust (LNWH).ParticipantsPatients tested and/or admitted for COVID-19 at LNWH during March and April 2020Main outcome measuresDescriptive and analytical epidemiology of demographic and clinical outcomes (intensive care unit (ICU) admission, mechanical ventilation and mortality) of those who tested positive for COVID-19.ResultsThe outbreak began in the first week of March 2020 and reached a peak by the end of March and first week of April. In the study period, 6183 tests were performed in on 4981 people. Of the 2086 laboratory confirmed COVID-19 cases, 1901 were admitted to hospital. Older age group, men and those of black or Asian minority ethnic (BAME) group were predominantly affected (p<0.05). These groups also had more severe infection resulting in ICU admission and need for mechanical ventilation (p<0.05). However, in a multivariate analysis, only increasing age was independently associated with increased risk of death (p<0.05). Mortality rate was 26.9% in hospitalised patients.ConclusionThe findings confirm that men, BAME and older population were most commonly and severely affected groups. Only older age was independently associated with mortality.

scholarly journals 1075. Absolute Lymphocyte Count as a Predictor of Cytomegalovirus (CMV) Infection and Recurrence in Hematopoietic Stem Cell Transplant (HSCT) Recipients

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S565-S565
Author(s):  
Joanne Reekie ◽  
Marie Helleberg ◽  
Christina Ekenberg ◽  
Mark P Khurana ◽  
Isabelle P Lodding ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Lymphocyte Count ◽  
Absolute Lymphocyte Count ◽  
Cell Transplant ◽  
Cmv Infection ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Increased Risk ◽  
Acute Graft

Abstract Background Cytomegalovirus (CMV) is a serious complication following Hematopoietic Stem Cell Transplant (HSCT) and can lead to serious organ disease and mortality. This study aimed to investigate the association between absolute lymphocyte count (ALC) and CMV to determine whether ALC could help to identify those at an increased risk of CMV infection and recurrence Methods Adults undergoing HSCT between 2011 and 2016 at Rigshospitalet, Denmark were included. Cox proportional hazards models investigated risk factors, including ALC, for CMV infection in the first year post-transplant and recurrent CMV infection 6 months after clearance and stopping CMV treatment for the first infection. For the primary outcome ALC was investigated as a time-updated risk factor lagged by 7 days, and for recurrent CMV, ALC measured at the time at the time of stopping treatment for the first CMV infection was investigated (+/- 7 days). Results Of the 352 HSCT recipients included, 57% were male, 40% received myeloablative conditioning, 42% had high risk (D-R+) CMV IgG serostatus at transplant and the median age was 56 (IQR 43-63). 143 (40.6%) patients had an episode of CMV DNAemia a median of 47 days after transplant (IQR 35-62). A lower current ALC (≤ 0.3 x109/L) was associated with a higher risk of CMV infection in univariate analysis compared to a high current ALC (&gt; 1 x109/L). However, this association was attenuated after adjustment, particularly for acute graft versus host disease (Figure). 102 HSCT recipients were investigated for risk of recurrent CMV of which 41 (40.2%) had a recurrent CMV episode a median of 27 days (IQR 16-50) after stopping CMV treatment for the first infection. A lower ALC (≤ 0.3 x109/L) at the time of stopping CMV treatment was associated with a significantly higher risk of recurrent CMV after adjustment (Figure). A higher peak viral load (&gt; 1500 IU/ml) during the first episode of CMV infection was also associated with an increased risk of recurrent CMV (aHR 2.47, 95%CI 1.00-6.10 compared to &lt; 750 IU/ml). Association between absolute lymphocyte count (ALC) and risk of CMV infection and recurrent CMV within 6 months. **First CMV infection multivariable model also adjusted for sex, CMV serostatus, age, year of transplant, Charlson Comorbidity Index, Anti-thymocyte globulin (ATG) given, HLA donor-recipient matching, and acute graft versus host disease (time-updated) *Recurrent CMV infection multivariable model also adjusted for conditioning regimen, sex, CMV serostatus, age, year of transplant Anti-thymocyte globulin (ATG) given, HLA donor-recipient matching, and acute graft versus host disease and peak CMV viral load during the first CMV infection Conclusion A lower ALC at the time of stopping treatment for the first CMV infection was associated with an increased risk of recurrent CMV and could be used to help guide decisions for augmented CMV surveillance and clinical awareness of CMV disease symptoms in these patients. Disclosures All Authors: No reported disclosures

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