Pre-treatment hematological markers as a predictive biomarker for survival in patients with non-small cell lung cancer treated with nivolumab.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11547-11547 ◽  
Author(s):  
Pradnya Dinkar Patil ◽  
Monica Khunger ◽  
Sagar Rakshit ◽  
James Stevenson ◽  
Nathan A. Pennell ◽  
...  

11547 Background: The absolute neutrophil count (ANC), absolute monocyte count (AMC) and neutrophil to lymphocyte ratio (NLR) are known markers of inflammation. We evaluated whether ANC, AMC and NLR are prognostic for overall survival (OS) and evaluated change in NLR as a predictive marker of response per RECIST in non -small cell lung cancer (NSCLC) patients treated with nivolumab. Methods: A total of 115 patients with NSCLC treated with nivolumab were included. ANC, AMC and NLR were examined at initiation of nivolumab therapy and after two cycles. The prognostic role of ANC, AMC and NLR on OS and changes in NLR ratio in responders was assessed using Cox regression model. Results: ANC > 6, AMC > 0.5 and NLR > 2.8 at baseline were independently associated with shorter OS (Hazard ratio (HR) 1.17 (1.08-1.27), p = .00001; HR 4.53 (1.99-10.31), p = 0.04 and HR 1.09 (1.04-1.13), p = 0.0002 . Responders had a decrease in NLR by (median (range) -0.93 (-14.7-52.95), p = 0.03) whereas non-responders had an increase in NLR by (median (range) 0.85 (-8.6-132.9), p = 0.03). Conclusions: ANC, AMC andNLR are independent prognostic factors in NSCLC patients treated with nivolumab. Changes in NLR can be an early biomarker for response with nivolumab in NSCLC patients. [Table: see text]

2012 ◽  
Vol 23 ◽  
pp. v15
Author(s):  
T.A. Bogush ◽  
E.A. Dudko ◽  
M.V. Nureev ◽  
A.A. Kamensky ◽  
B.E. Polotsky ◽  
...  

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2800
Author(s):  
Amir Onn ◽  
Teodor Gottfried ◽  
Amos Stemmer ◽  
Sarit Appel ◽  
Yaacov R. Lawrence ◽  
...  

Background: Immunotherapy (IO) provides a significant benefit for a subgroup of non-small cell lung cancer (NSCLC) patients. Radiotherapy (XRT) might enhance the efficacy of IO. We evaluated the impact of the specifics of XRT treatments on the OS of IO-treated NSCLC patients. Methods: Metastatic NSCLC patients treated with IO were retrospectively identified. Parameters included demographics, tumor characteristics, IO and XRT details. Correlation between the parameters and OS was tested with Cox regression. Results: 453 patients were included. No XRT was given to 167 (36.9%) patients, whereas XRT prior and after IO had 182 (40.2%) and 104 (22.9%) patients, respectively. XRT total doses between 30 and 40 Gy had better overall survival (OS) compared to non-irradiated patients (hazard ratio (HR) 0.5, 95% CI 0.25–1.0, p = 0.049). Worse outcome was seen with total doses ≤ 10 Gy (HR 1.67, 95% 1.13–2.5, p = 0.01), XRT fractions of 4.1–8 Gy (HR 1.48, 95% CI 1.05–2.1, p = 0.027) and XRT to the bone (HR 1.36, 95% CI 1.01–1.8, p = 0.04). Several clinical parameters correlated with OS in the univariate analysis of the IO-treated patients. While, in the multivariate analysis, only ECOG-PS, treatment line, type of IO, albumin and NLR remained statistically significant. Conclusion: Specific doses, fractions and sites of XRT correlated with the OS of IO-treated NSCLC patients in the univariate analysis, although not in the multivariate analysis.


2021 ◽  
Vol 12 ◽  
Author(s):  
Dani Xiong ◽  
Chuanlin Wang ◽  
Zhaohui Yang ◽  
Fusen Han ◽  
Huaibing Zhan

Background: In this study, we aimed to explore the diagnostic potential of serum-based exosomal long intergenic noncoding RNA 917 (LINC00917) in non-small cell lung cancer (NSCLC).Methods: Exosomes were extracted from NSCLC patients’ serum samples. Exosomal LINC00917 expression levels were compared, by qRT-PCR, between cancer patients and healthy controls, as well as sub-populations of cancer patients. The association between exosomal LINC00917 expression and NSCLC patients’ clinicopathologic factors were investigated, and receiver operating characteristic (ROC) curves were drawn. In addition, NSCLC patients’ overall survivals (OSs) was examined based on exosomal LINC00917 expression and further evaluated by the cox regression analysis.Results: Serum-derived exosomal LINC00917 was highly expressed in NSCLC patients, and further upregulated in stage III/IV cancer patients. Exosomal LINC00917 yielded modestly good under the curve (AUC) values. Upregulated exosomal LINC00917 expression was closely associated with cancer patients’ advanced stages and shorter OSs.Conclusion: Serum-derived exosomal LINC00917 may hold diagnostic potential for patients with non-small cell lung cancer.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21732-e21732
Author(s):  
Lin Wu ◽  
Meilin Jiang ◽  
Wenying Peng ◽  
Xingxiang Pu ◽  
Bolin Chen ◽  
...  

e21732 Background: Selecting patients that potentially benefit from immune checkpoint inhibitors (ICIs) is critical. Programmed death ligand-1 (PD-L1) protein immunohistochemical expression on cancer cells or immune cells and Next generation sequencing based tumor mutational burden (TMB) are the hot spots in studies on ICIs, but there is still confusion in the testing methods. Due to blood samples are much easier for clinical application, many potential peripheral biomarkers have been proposed. This study identify blood parameters that associated with outcome of non-small cell lung cancer (NSCLC) patients with ICIs monotherapy. Methods: Data of 76 NSCLC patients were analyzed retrospectively. To assess the connection between survival and peripheral blood markers measured before and after treatment, we utilized COX regression model survival analysis and receiver operating characteristic (ROC) curve to assess the markers. Results: In the nivolumab cohort, the optimal cutoff for predicting 11 month overall survival (OS) were 168.13 and 43g/L in Plateletto-lymphocyte ratio (PLR) and albumin, respectively. When patients are grouped with PLR and albumin the cut-offs, a significant difference in SD-PR vursus PD rate were found between high and low groups, separately. which was not found when grouped by PD-L1 expression. Patients with high PLR ( > 168.13) or low albumin ( < = 43g/L) before ICI had a significantly raised hazard of progression, separately (for PLR, P = 0.006; for albumin, P = 0.033) and of death (for PLR, P = 0.014; for albumin, P = 0.009) compared with those patients who had low PLR or albumin level. More importantly, we found that higher PLR ( > 168.13) after the fourth cycle of ICIs was also an prognostic biomarker, which significantly correlated with shorter OS in both Nivolumab (P = 0.046) and durvalumab cohort (P = 0.028). Conclusions: PLR and albumin may help the stratification of high progression and death risk group in advanced NSCLC patients treated with nivolumab and durvalumab monotherapy.


2018 ◽  
Vol 13 (4) ◽  
pp. S35
Author(s):  
N. Karachaliou ◽  
J. Berenguer ◽  
I. Chaib ◽  
J.L. Ramírez Serrano ◽  
M.T. Moran Bueno ◽  
...  

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Zhonghai Du ◽  
Jun Wu ◽  
Juan Wang ◽  
Yan Liang ◽  
Sensen Zhang ◽  
...  

Abstract Background MicroRNAs (miRNAs) have been reported to serve pivotal roles in tumorigenesis. This study sough to assess the expression and clinical significance of microRNA-1298 (miR-1298) in patients with non-small cell lung cancer (NSCLC), and explore the functional role of miR-1298 in tumorigenesis. Methods One hundred and twenty-one NSCLC patients were recruited in this study. The expression of miR-1298 was estimated using quantitative real-time PCR. Kaplan-Meier survival curves and Cox regression analysis were used to evaluate the prognostic value of miR-1298. Gain- and loss-of-function experiments were preformed to explore the biological function of miR-1298 in NSCLC cells. Results Expression levels of miR-1298 were downregulated in NSCLC tissues and cells compared with the corresponding normal controls. The decreased expression of miR-1298 was associated with patients’ lymph node metastasis and TNM stage. The low expression of miR-1298 predicted poor overall survival and served as an independent prognostic indicator in NSCLC patients. According to the cell experiments, NSCLC cell proliferation, migration and invasion were inhibited by the overexpression of miR-1298. Conclusion All the data indicated that the downregulation of miR-1298 predicts poor prognosis of NSCLC, and the overexpression of miR-1298 in NSCLC cells leads to inhibited tumorigenesis. The aberrant miR-1298 may serve as a novel biomarker and therapeutic target in NSCLC.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Deirdre Cronin-Fenton ◽  
Tapashi Dalvi ◽  
Naimisha Movva ◽  
Lars Pedersen ◽  
Hanh Hansen ◽  
...  

AbstractProgrammed cell death receptor ligand-1 (PD-L1) expression, KRAS (KRASm) and EGFR (EGFRm) mutations may influence non-small cell lung cancer (NSCLC) prognosis. We aimed to evaluate PD-L1 expression, KRASm, and EGFRm and survival among stage III unresected NSCLC patients. Using Danish registries, we collected data on stage III unresected NSCLC patients diagnosed 2001–2012 and paraffin-embedded tumor tissue from pathology archives. We assessed PD-L1 expression in tumors and tumor-infiltrating immune cells (ICs) by immunohistochemistry ($$\ge$$ ≥  1% threshold for PD-L1+). We genotyped KRAS and EGFR. Follow-up extended from 120 days post-diagnosis to death, emigration, or 31/12/2014. We computed median survival using Kaplan–Meier methods, and hazard ratios (HRs) using Cox regression associating the biomarkers with death, adjusting for confounders. Among 305 patients, 48% had adenocarcinoma; 38% squamous cell carcinoma. Forty-nine percent had PD-L1+ tumors—51% stage IIIA and 26% KRASm. Few (2%) patients had EGFRm. Median survival in months was 14.7 (95% CI = 11.8–17.9) and 13.4 (95% CI = 9.5–16.3) in PD-L1+ and PD-L1− tumors, respectively. KRASm was not associated with death (HR = 1.06, 95% CI = 0.74–1.51 versus wildtype). PD-L1+ tumors yielded a HR = 0.83 (95% CI = 0.63–1.10); PD-L1+ ICs a HR = 0.51 (95% CI = 0.39–0.68). Tumor expression of PD-L1 did not influence survival. PD-L1+ ICs may confer survival benefit in stage III unresected NSCLC patients.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chenlu Li ◽  
Jingjing Pan ◽  
Jing Luo ◽  
Xupeng Chen

Abstract Background Non-small cell lung cancer (NSCLC) was usually associated with poor prognosis and invalid therapeutical response to immunotherapy due to biological heterogeneity. It is urgent to screen reliable biomarkers, especially immunotherapy-associated biomarkers, that can predict outcomes of these patients. Methods Gene expression profiles of 1026 NSCLC patients were collected from The Cancer Genome Atlas (TCGA) datasets with their corresponding clinical and somatic mutation data. Based on immune infiltration scores, molecular clustering classification was performed to identify immune subtypes in NSCLC. After the functional enrichment analysis of subtypes, hub genes were further screened using univariate Cox, Lasso, and multivariate Cox regression analysis, and the risk score was defined to construct the prognostic model. Other microarray data and corresponding clinical information of 603 NSCLC patients from the GEO datasets were applied to conduct random forest models for the prognosis of NSCLC with 100 runs of cross-validation. Finally, external datasets with immunotherapy and chemotherapy were further applied to explore the significance of risk-scores in clinical immunotherapy response for NSCLC patients. Results Compared with Subtype-B, the Subtype-A, associated with better outcomes, was characterized by significantly higher stromal and immune scores, T lymphocytes infiltration scores and up-regulation of immunotherapy markers. In addition, we found and validated an eleven -gene signatures for better application of distinguishing high- and low-risk NSCLC patients and predict patients’ prognosis and therapeutical response to immunotherapy. Furthermore, combined with other clinical characteristics based on multivariate Cox regression analysis, we successfully constructed and validated a nomogram to effectively predict the survival rate of NSCLC patients. External immunotherapy and chemotherapy cohorts validated the patients with higher risk-scores exhibited significant therapeutic response and clinical benefits. Conclusion These results demonstrated the immunological and prognostic heterogeneity within NSCLC and provided a new clinical application in predicting the prognosis and benefits of immunotherapy for the disease.


2021 ◽  
Author(s):  
Haizhen Zhu ◽  
Lin Zhou ◽  
Yi Guo ◽  
Guangrong Yang ◽  
Qiang Dong ◽  
...  

Background: We aimed to investigate the epidemiology of synchronous brain metastasis (SBM) in non-small-cell lung cancer (NSCLC) patients. Methods: Logistic regression and Cox regression were used to identify the related factors of SBM incidence and cancer-specific survival (CSS). A nomogram for predicting CSS was developed and validated. Results: The incidence of SBM in NSCLC patients was 12.58%. The median CSS was 5 months. Patients with younger age, female gender, and adenocarcinoma had higher odd ratios for developing SBM. In addition, a nomogram was developed based on significant factors from Cox regression. The validation of the nomogram showed that it had good calibration and discrimination. Conclusions: SBM was highly prevalent in NSCLC patients, who also had poor survival.


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