scholarly journals PD-L1 Polymorphism Can Predict Clinical Outcome of Brazilian Non-Small Cell Lung Cancer Patients After Postoperative Adjuvant Treatment

2020 ◽  
Author(s):  
Juliana Machado-Rugolo ◽  
Tabatha Gutierrez Prieto ◽  
Alexandre Todorovic Fabro ◽  
Edwin Roger Parras Cuentas ◽  
Vanessa Karen Sá ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Outcome ◽  
Small Cell Lung Cancer ◽  
Cell Carcinoma ◽  
Cell Lung Cancer ◽  
Adjuvant Treatment ◽  
Small Cell ◽  
Small Cell Lung ◽  
Programmed Death ◽  
Nsclc Patients

Abstract BackgroundAlthough the incidence and mortality of non-small cell lung cancer (NSCLC) remains high with poor prognosis, programmed death‐1 (PD‐1) and programmed death‐ligand 1 (PD‐L1) pathway are promising prognostic and predictive biomarker of NSCLC. The polymorphisms on PD‐L1 gene may be associated with their protein expressions and affect the adjuvant treatment and outcome of NSCLC patients. The goal of this study was to evaluate the clinicopathologic values of PD-L1 expression and single-nucleotide polymorphisms (SNPs) in the PD-L1 gene in lung adenocarcinoma (ADC), squamous cell carcinoma (SqCC), and large cell carcinoma (LCC). MethodsThe 70 NSCLC samples consisted of 33 samples of ADC, 24 of SqCC and 13 of LCC. All tissue microarray paraffin blocks were used for PD-L1 multiplex immunofluorescence assays with Cell Signaling E1L3N clone. Fifteen polymorphisms in the PD-L1 gene were investigated by deep targeted sequencing.ResultsThe PD-L1 expression was higher in ADC than in SqCC and LCC. Three polymorphisms rs4742098, rs4143815, and rs7041009 were significantly associated with tumor recurrence (P=0.01; P=0.05; P=0.02, respectively). According to the recurrence of the disease, carriers of the G allele were less likely to relapse (P=0.01) compared to the homozygous AA genotype for rs4742098. As in rs4143815, individuals with the C allele were also less likely to relapse (P=0.05). As for rs7041009, individuals with AG or GG genotypes were more likely to relapse. The G allele of rs7041009 also showed a significant correlation with age, younger patients, 16 (41.0%) and status, among 11 (39.3%) compared to carriers of the A allele (P=0.02 and P<0.01, respectively). The rs7041009 AG genotype was inversely associated with E1L3N clone PD-L1 labeling in NSCLCs but did not reach statistical significance. Kaplan-Meier survival curves showed that the prognosis of patients with NSCLC was strongly dependent on the alternative allele G (genotype AG or GG) of rs4742098, alternative allele C (genotype CG or CC) of rs4143815 and individuals with GG genotype of rs7041009 (P=0.02; P=0.05 and P<0.01, respectively). Multivariate analysis by the Cox Regression model showed genotype GG of rs7041009 independently associated with cancer recurrence and patients without adjuvant radiotherapy (hazard ratio [HR] = 7.59, 95% confidence interval [CI] = 1.06-54.03, and HR = 9.24, CI = 1.13-75.16).ConclusionsPD-L1 rs7041009 GG polymorphisms may be useful for the prediction of clinical outcome of radiotherapy in NSCLC. Further studies are needed to confirm our findings and to understand the role of PD-L1 in the radiotherapy outcome of NSCLC patients.

Effect of BIM and mTOR expression on clinical outcome to erlotinib in EGFR-mutant non-small cell lung cancer (NSCLC) patients (p).

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 8072-8072
Author(s):  
Niki Karachaliou ◽  
Ana Drozdowskyj ◽  
Ana Gimenez Capitan ◽  
Andres Felipe Cardona Zorrilla ◽  
Radj Gervais ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Outcome ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Egfr Mutant ◽  
Nsclc Patients

Effect of BRCA1 Haplotype on Survival of Non–Small-Cell Lung Cancer Patients Treated With Platinum-Based Chemotherapy

2008 ◽  
Vol 26 (36) ◽  
pp. 5972-5979 ◽  
Author(s):  
Hong-Tae Kim ◽  
Jong-Eun Lee ◽  
Eun-Soon Shin ◽  
Yeon-Kyeong Yoo ◽  
Jae-Hwa Cho ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
Small Cell Lung Cancer ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cell Lung Cancer ◽  
Combination Chemotherapy ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

Purpose To determine whether germ-line variations in BRCA1 affect outcome in non–small-cell lung cancer (NSCLC) patients treated with platinum combination chemotherapy. Patients and Methods We evaluated the associations of four tagging BRCA1 polymorphisms and their haplotypes with treatment outcome in 300 NSCLC patients at stages IIIA (16%), IIIB (31%), and IV (53%). Results The median age was 63 years (range, 28 to 89 years). Histologically, 139 (46.3%) of the patients had squamous cell carcinomas and 137 (45.7%) had adenocarcinomas. Patient median survival time (MST) was 13.0 months. We observed no significant association between any of the tagging polymorphisms [S1613G, IVS13-1893 (A>C), IVS12-1207 (C>T), and IVS12+112 (C>A)] and overall survival. Of the five haplotypes evaluated (AACC, AACA, GCTC, GATC, and AATC), the survival of patients with two copies of the AACC (wild-type) haplotype was significantly shorter than that of patients with zero to one copies (MST, 8.47 v 14.57 months; log-rank P = .0066), even after adjustment for body weight loss, performance status, stage, second-line treatment, and radiation therapy (hazard ratio = 2.097; 95% CI, 1.339 to 3.284). The survival of patients with squamous cell carcinoma and two copies was significantly shorter than that of other patients with squamous cell carcinoma (MST, 6.8 v 15.3 months; log-rank P = 3.6 × 10−5), whereas differences in survival between the two adenocarcinoma groups was not significant (log-rank P = .677). Conclusion These findings suggest that the AACC haplotype of the BRCA1 gene is an important prognostic marker in NSCLC patients treated with platinum combination chemotherapy.

Updated outcomes of previously irradiated non-small-cell lung cancer (NSCLC) patients (pts) receiving programmed death 1 (PD-1) inhibitors.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e15158-e15158
Author(s):  
Maria Bassanelli ◽  
Diana Giannarelli ◽  
Biagio Ricciuti ◽  
Valentina Magri ◽  
Fabiana Letizia Cecere ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Nsclc Patients

scholarly journals P14.97 High risk of venous thromboembolism in patients with brain metastases from non-small cell lung cancer

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii91-iii91
Author(s):  
P Mir Seyed Nazari ◽  
C Ay ◽  
A Steindl ◽  
B Gatterbauer ◽  
J M Frischer ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Venous Thromboembolism ◽  
High Risk ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Cell Carcinoma ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

Abstract BACKGROUND Venous thromboembolism (VTE) is a common complication in patients with cancer. In general, patients with metastatic disease are at highest risk. Lung cancer belong to those tumor entities with a particularly high risk of VTE, ranging between 3–13.8%. However, little is known about the VTE rate in lung cancer patients with brain metastases. MATERIAL AND METHODS Our study was conducted in the framework of the Vienna Brain Metastasis Registry. Clinical data and VTE events during the course of the disease were recorded via retrospective chart review. In this analysis, non-small cell lung cancer (NSCLC) patients with a resection of brain metastases at the Medical University of Vienna between 2006 and 2010 were included. RESULTS In total, 69 NSCLC patients with brain metastases were analyzed. Overall, 69.6% (48/69) patients had an adenocarcinoma, 13% (9/69) a squamous cell carcinoma, 8.7% (6/69) a large cell carcinoma and 8.7% (6/69) other primary tumor histologies. After cancer diagnosis, 20.3% (14/69) patients developed VTE during the course of the disease. Of those, 85.7% (12/14) thromboembolic events occurred after the diagnosis of brain metastases. CONCLUSION Based on our data, patients with brain metastases from NSCLC have a very high VTE risk. Further investigations are needed in order to identify patients with distinct VTE risk profiles. Patients at high risk might potentially benefit from primary thromboprophylaxis over the high risk of intracerebral bleeding.

scholarly journals Small Extracellular Vesicles in Pre-Therapy Plasma Predict Clinical Outcome in Non-Small-Cell Lung Cancer Patients

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2041
Author(s):  
Eleni-Kyriaki Vetsika ◽  
Priyanka Sharma ◽  
Ioannis Samaras ◽  
Alexandra Markou ◽  
Vassilis Georgoulias ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Outcome ◽  
Small Cell Lung Cancer ◽  
Extracellular Vesicles ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Response To Therapy ◽  
Small Cell Lung ◽  
Western Blots ◽  
Nsclc Patients

The potential use of plasma-derived small extracellular vesicles (sEV) as predictors of response to therapy and clinical outcome in chemotherapy-naïve patients with non-small-cell lung cancer (NSCLC) was explored. sEV were isolated by size-exclusion chromatography from the plasma of 79 chemotherapy-naïve NSCLC patients and 12 healthy donors (HD). sEV were characterized with regard to protein content, particle size, counts by qNano, morphology by transmission electron microscopy, and molecular profiles by Western blots. PD-1 and PD-L1 expression on circulating immune cells was analysed by flow cytometry. Pre-treatment levels of total sEV protein (TEP) were correlated with overall (OS) and progression-free survival (PFS). The sEV numbers and protein levels were significantly elevated in the plasma of NSCLC patients compared to HD (p = 0.009 and 0.0001, respectively). Baseline TEP levels were higher in patients who developed progressive disease compared to patients with stable disease (p = 0.007 and 0.001, stage III and IV, respectively). Patient-derived sEV were enriched in immunosuppressive proteins as compared to proteins carried by sEV from HD. TEP levels were positively correlated with CD8+PD-1+ and CD8+PD-L1+ circulating T cell percentages and were independently associated with poorer PFS (p < 0.00001) and OS (p < 0.00001). Pre-therapy sEV could be useful as non-invasive biomarkers of response to therapy and clinical outcome in NSCLC.

scholarly journals Oncogene-specific differences in tumor mutational burden, PD-L1 expression, and outcomes from immunotherapy in non-small cell lung cancer

2021 ◽  
Vol 9 (8) ◽  
pp. e002891
Author(s):  
Marcelo V Negrao ◽  
Ferdinandos Skoulidis ◽  
Meagan Montesion ◽  
Katja Schulze ◽  
Ilze Bara ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Outcome ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Clinical Benefit ◽  
Multivariable Analysis ◽  
Immune Checkpoint Blockade ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

BackgroundNon-small cell lung cancer (NSCLC) patients bearing targetable oncogene alterations typically derive limited benefit from immune checkpoint blockade (ICB), which has been attributed to low tumor mutation burden (TMB) and/or PD-L1 levels. We investigated oncogene-specific differences in these markers and clinical outcome.MethodsThree cohorts of NSCLC patients with oncogene alterations (n=4189 total) were analyzed. Two clinical cohorts of advanced NSCLC patients treated with ICB monotherapy [MD Anderson (MDACC; n=172) and Flatiron Health-Foundation Medicine Clinico-Genomic Database (CGDB; n=894 patients)] were analyzed for clinical outcome. The FMI biomarker cohort (n=4017) was used to assess the association of oncogene alterations with TMB and PD-L1 expression.ResultsHigh PD-L1 expression (PD-L1 ≥50%) rate was 19%–20% in classic EGFR, EGFR exon 20 and HER2-mutant tumors, and 34%–55% in tumors with ALK, BRAF V600E, ROS1, RET, or MET alterations. Compared with KRAS-mutant tumors, BRAF non-V600E group had higher TMB (9.6 vs KRAS 7.8 mutations/Mb, p=0.003), while all other oncogene groups had lower TMB (p<0.001). In the two clinical cohorts treated with ICB, molecular groups with EGFR, HER2, ALK, ROS1, RET, or MET alterations had short progression-free survival (PFS; 1.8–3.7 months), while BRAF V600E group was associated with greater clinical benefit from ICB (CGDB cohort: PFS 9.8 months vs KRAS 3.7 months, HR 0.66, p=0.099; MDACC cohort: response rate 62% vs KRAS 24%; PFS 7.4 vs KRAS 2.8 months, HR 0.36, p=0.026). KRAS G12C and non-G12C subgroups had similar clinical benefit from ICB in both cohorts. In a multivariable analysis, BRAF V600E mutation (HR 0.58, p=0.041), PD-L1 expression (HR 0.57, p=0.022), and high TMB (HR 0.66, p<0.001) were associated with longer PFS.ConclusionsHigh TMB and PD-L1 expression are predictive for benefit from ICB treatment in oncogene-driven NSCLCs. NSCLC harboring BRAF mutations demonstrated superior benefit from ICB that may be attributed to higher TMB and higher PD-L1 expression in these tumors. Meanwhile EGFR and HER2 mutations and ALK, ROS1, RET, and MET fusions define NSCLC subsets with minimal benefit from ICB despite high PD-L1 expression in NSCLC harboring oncogene fusions. These findings indicate a TMB/PD-L1-independent impact on sensitivity to ICB for certain oncogene alterations.

Pneumonitis in non-small cell lung cancer (NSCLC) patients treated with programmed death 1 (PD1) axis inhibitors.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 9030-9030 ◽  
Author(s):  
Scott N. Gettinger ◽  
Xuchen Zhang ◽  
Robert Homer ◽  
Jennifer Possick ◽  
Anna Wurtz ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Nsclc Patients

scholarly journals Association of BTLA Polymorphisms with Susceptibility to Non-Small-Cell Lung Cancer in the Chinese Population

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Jusi Wang ◽  
Zhan Chen ◽  
Rui Cao ◽  
Qiang Zhang ◽  
Tingyu Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Carcinoma ◽  
T Lymphocyte ◽  
Cell Lung Cancer ◽  
Chinese Population ◽  
Small Cell ◽  
Small Cell Lung ◽  
Subgroup Analyses ◽  
Nsclc Patients

Studies have reported that B- and T-lymphocyte attenuator (BTLA) polymorphisms may be associated with the risk to different cancers. However, the correlation between those variations and non-small-cell lung cancer (NSCLC) is still unclear. A total of 1,003 NSCLC patients and 901 noncancer controls were recruited in the study, to confirm the association of variations in BTLA gene with the risk of NSCLC. The SNPscan™ genotyping assay was used to obtain the genotypes of the four BTLA polymorphisms (BTLA rs1982809 G>A, rs16859629 T>C, rs2171513 G>A, and rs3112270 A>G). It was found that BTLA rs1982809 polymorphism reduced the risk of NSCLC (GA vs. GG: adjusted   odds   ratio   OR = 0.81 , 95 % confidence   interval   CI = 0.66 ‐ 0.99 , and P = 0.043 ). However, the BTLA rs16859629, rs2171513, and rs3112270 polymorphisms showed no significant association between NSCLC patients and controls in overall comparison. In subgroup analyses, we found that BTLA rs1982809 polymorphism reduced the risk of NSCLC (nonsquamous cell carcinoma: GA vs. GG: adjusted   OR = 0.79 , 95 % CI = 0.64 ‐ 0.97 , and P = 0.026 ; AA/GA vs. GG: adjusted   OR = 0.81 , 95 % CI = 0.66 ‐ 0.99 , and P = 0.037 ; ≥59 years: GA vs. GG: P = 0.036 ; never alcohol consumption: GA vs. GG: P = 0.013 ; GA/AA vs. GG: P = 0.016 ; body   mass   index   BMI ≥ 24  kg/m2: GA vs. GG: P = 0.030 ; GA/AA vs. GG: P = 0.041 ). The BTLA rs16859629 polymorphism increased the risk of the development of squamous cell carcinoma (CC vs. TT: adjusted   OR = 9.85 , 95 % CI = 1.37 ‐ 71.03 , and P = 0.023 ; CC vs. TT/TC: adjusted   OR = 9.55 , 95 % CI = 1.32 ‐ 68.66 , and P = 0.025 ). Taken together, the findings of the present suggest that BTLA rs1982809 and rs16859629 polymorphisms may influence the susceptibility to NSCLC in the Chinese population.

Sign in / Sign up

Export Citation Format

Share Document