scholarly journals PD-L1 expression as a predictor of postoperative recurrence and the association between the PD-L1 expression and EGFR mutations in NSCLC

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kensuke Kojima ◽  
Tetsuki Sakamoto ◽  
Takahiko Kasai ◽  
Tomoko Kagawa ◽  
Hyungeun Yoon ◽  
...  
Keyword(s):  
Multivariate Analyses ◽  
Postoperative Recurrence ◽  
Continuous Variable ◽  
Therapeutic Strategies ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Increased Risk ◽  
L858r Mutation ◽  
Nsclc Patients

AbstractAlthough information on the PD-L1 expression and EGFR mutations in non-small cell lung cancer (NSCLC) is important for therapeutic strategies, the effect of these factors on postoperative recurrence and the association between each factor have remained unclear. We retrospectively assessed the PD-L1 expression and EGFR mutations in 280 NSCLC patients, and analyzed the associations by multivariate analyses. The hazard ratio (HR) of postoperative recurrence in cases with high (≥ 50%) PD-L1 expression regarding negative expression was 4.83 (95% confidence interval [CI] 1.51–15.5). The HR for the PD-L1 expression, considered a continuous variable, was 1.016 (95% CI 1.01–1.03). The HRs in cases with EGFR major and minor mutations were 0.42 (95% CI 0.14–1.25) and 0.63 (95% CI 0.18–2.15), respectively. The high PD-L1 (≥ 50%) expression was significantly associated with exon 21 L858R mutation (Ex21) of EGFR (odds ratio, 0.10; 95% CI 0.01–0.87). The risk of postoperative recurrence increased 1.016-fold for every 1% increase in the PD-L1 expression, and a marked increase in risk was observed for expression levels of ≥ 50%. Whereas EGFR mutations were not an independent risk factor. The high PD-L1 (≥ 50%) expression was negatively associated with Ex21. These findings may help identify NSCLC patients with an increased risk of postoperative recurrence.

Coexistence of MET exon 14 mutations with EGFR mutations in non-small cell lung cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20636-e20636
Author(s):  
Wen-Feng Li ◽  
Jin Kang ◽  
Xu-Chao Zhang ◽  
Su Jian ◽  
Huajun Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Point Mutations ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Relative Resistance ◽  
L858r Mutation ◽  
Nsclc Patients

e20636 Background: Activation of MET oncogene as the result of amplification or activation MET exon 14 mutations represents an emerging molecular target for non-small cell lung cancer (NSCLC) treatment. MET exon 14 mutations account for 1.0% in Chinese NSCLC patients. However, few data have been reported on the coexisting of MET exon 14 mutations and EGFR mutations in NSCLC. Moreover, the clinicopathological characteristics and targeted therapy of these MET/ EGFR-coexisting patients remain elusive. Methods: Next-generation sequencing was performed on the DNA of 969 patients and Sanger sequencing was conducted on cDNA of 621 patients for MET exon 14 mutations in NSCLCs. EGFR mutations were determined by direct DNA sequencing. Results: Fifteen patients harbored positive MET exon 14 mutations. Frequency of concomitant EGFR and MET exon 14 mutations was 0.2%(3/1590). 3 patients with concomitant MET exon 14 mutation and EGFR activating mutation were all female, never smokers and adenocarcinoma. Their stagings were stageⅠB (n = 1) and stage Ⅳ(n = 2). The stage ⅠB patient harboring concomitant MET exon 14 skipping and EGFR L858R mutation did not relapse 2 years after operation. The other two stage Ⅳ patients received first-line gefitinib. Case one harbored concomitant MET exon 14 point mutations (IVS13-36G > A) and EGFR exon 19 deletion, and showed resistance to gefitinib with progression free survival(PFS) of 2 weeks and overall survival(OS) of 1 month. Case two had concomitant MET exon 14 point mutations (IVS13-36G > A) and EGFR L858R mutation. Meanwhile, she also had both METamplification and c-Met overexpression at the baseline. She showed partial response (PR) to gefitinib with 3.8 months PFS. Then she was enrolled in a clinical trial (NCT02374645) to receive volitinib plus gefitinib on December 20, 2016. Initial response was good PR on January 24, 2017. Only grade 1 rash was observed. Conclusions: Coexisting MET exon 14 /EGFR mutation is an uncommon molecular event in NSCLC patients. Such coexisted patients might show relative resistance to EGFR inhibitor. However, combination of MET and EGFR inhibitors will be potentially a good strategy to overcome such a relative resistance for MET exon 14 /EGFR co-mutant patients.

Causal Relationship between Postoperative Recurrence and PD-L1 and EGFR Mutations in NSCLC: A Retrospective Cohort Study

2021 ◽  
Author(s):  
Kensuke Kojima ◽  
Tetsuki Sakamoto ◽  
Takahiko Kasai ◽  
Tomoko Kagawa ◽  
Hyungeun Yoon ◽  
...  
Keyword(s):  
Multinomial Logistic Regression ◽  
Hazard Analysis ◽  
Postoperative Recurrence ◽  
High Expression ◽  
Egfr Mutations ◽  
Multinomial Logistic Regression Analysis ◽  
Increased Risk ◽  
Two Factors ◽  
L858r Mutation ◽  
Nsclc Patients

Abstract Although information on the PD-L1 expression and EGFR mutations in non-small cell lung cancer (NSCLC) is important for determining therapeutic strategies, the causality between these two factors and postoperative recurrence and the association between each factor have remained unclear. We retrospectively assessed the PD-L1 expression and EGFR mutations in tumors of 280 NSCLC patients. The causality between the PD-L1 expression, EGFR mutations and postoperative recurrence were evaluated by a multivariate Cox proportional hazard analysis. The association between the PD-L1 expression and EGFR mutations was evaluated by a multinomial logistic regression analysis. The adjusted hazard ratio (HR) in cases with high (≥ 50%) PD-L1 expression was 4.83 (95% confidence interval [CI]: 1.51–15.5). The adjusted HRs in cases with EGFR major and minor mutations were 0.42 (95% CI: 0.14–1.25) and 0.63 (95% CI: 0.18–2.15), respectively. The high expression of PD-L1 (≥ 50%) was significantly associated with exon 21 L858R mutation (Ex21) of EGFR (adjusted odds ratio, 0.10; 95% CI, 0.01–0.87). The high expression of PD-L1 was an independent risk factor for postoperative recurrence in NSCLC, whereas EGFR mutations were not. The high expression of PD-L1 was negatively associated with Ex21. These findings may help identify NSCLC patients with an increased risk of postoperative recurrence.

A novel mutant-enriched liquidchip for detection of circulating EGFR mutations in advanced non-small cell lung cancer patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e14526-e14526
Author(s):  
S. Lu ◽  
H. Yang ◽  
X. Ye ◽  
X. Xu ◽  
Z. Li ◽  
...  
Keyword(s):  
Egfr Mutation ◽  
Direct Sequencing ◽  
Small Cell ◽  
Egfr Mutations ◽  
Wild Type ◽  
Small Cell Lung ◽  
Exon 19 Deletion ◽  
L858r Mutation ◽  
Nsclc Patients ◽  
Exon 19

e14526 Background: We developed a novel technology, Mutant-enriched liquidchip (MEL), which integrates the sensitive mutant enriched PCR and quantitative high throughput liquidchip (suspension array), to detect circulating EGFR mutations (Exon 19 deletion and exon 21 L858R mutation) in patients with advanced non-small cell lung cancer (NSCLC). Methods: To enrich mutant EGFR, a unique restriction site is introduced into the mutation alleles so that the wild type sequence can be selectively removed by restriction digestion, and the undigested mutated DNA is amplified by PCR. The product is then hybridized to complementary probes (including 15 types of exon 19 deletion and exon 21 L858R mutation) which had been conjugated to beads coding with different fluorescent dye, followed by measuring through Luminex 200 system. Plasmid DNA mixture with different EGFR genotypes was applied to determine the sensitivity and accuracy of MEL. Afterwards, the MEL was validated in 49 patients whose EGFR genotypes of tissue specimen had been tested with direct sequencing The circulating genomic DNA was obtained from serum sample of other 201 Chinese stage IIIB or IV NSCLC patients without EGFR-TKI administration, and the EGFR mutation status was analyzed by using of MEL. Results: The results shows that MEL is capable of detecting as few as 20 copies of mutant EGFR alleles with a sensitivity limit of at least mutant/wild-type ratio of 0.1%. It also shows that MEL can not only confirm EGFR mutations status in tissue specimens already known by direct sequencing (13/49), but also detect mutations in some of those showing wild type by sequencing (16/49). Overall, 54% of patients had circulating EGFR mutation. 34% of patients had an exon 19 deletion and 29.6% had L858R. 63.1% of mutations were found in females and 67.6% in never-smokers. Conclusions: This novel MEL method allows for highly sensitive and reproducible detection of human somatic mutations in heterogeneous specimens, and could be applicable to test EGFR mutations non-invasively in advanced NSCLC patients for predicting response to targeted therapy. No significant financial relationships to disclose.

Predictive and prognostic impact of plasma vascular endothelial growth factor levels in non-small-cell lung cancer patients treated with gefitinib

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13030-13030
Author(s):  
T. Sone ◽  
K. Kasahara ◽  
Y. Tanbo ◽  
S. Tamori ◽  
T. Araya ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Growth Factor ◽  
Small Cell ◽  
Egfr Mutations ◽  
Vascular Endothelial ◽  
Small Cell Lung ◽  
Gefitinib Treatment ◽  
Nsclc Patients ◽  
Endothelial Growth Factor ◽  
Vegf Level

13030 Background: In non-small cell lung cancer (NSCLC), sensitivity to gefitinib is associated with activating mutations of the epidermal growth factor receptor (EGFR). Tumor samples obtained for diagnosis of NSCLC are limited and often unsuitable for analysis of mutations. Other biomarkers are thus needed. We previously reported that serum vascular endothelial growth factor (VEGF) levels were significantly lower in responders to gefitinib than non-responders. To assess levels of circulating VEGF as a predictive and prognostic marker of gefitinib treatment in NSCLC patients, we examined the associations between plasma VEGF levels before gefitinib treatment and clinical outcome. Methods: Eighty four NSCLC patients treated with gefitinib were enrolled into this investigation. Plasma VEGF levels were measured in blood samples before gefitinib administration. Patients were grouped according to VEGF level around a cut-off of 80.7 pg/ml, based on results from normal controls. Response to gefitinib was judged using RECIST guidelines. Time to progression (TTP) and overall survival (OS) following gefitinib treatment were calculated using Kaplan-Meier methods. Groups were compared using log-rank test. We evaluated the immunohistochemical expression of VEGF and EGFR mutations in tumor samples from 37 patients. Results: Response rate was significantly higher with low VEGF level than with high VEGF level (p = 0.0010). Multivariate analysis for response to gefitinib including sex, histology, smoking status, performance status and plasma VEGF level identified only low VEGF level as predictive of response to gefitinib. Low VEGF level was also correlated with prolonged median TTP (4.1 months vs. 1.1 months, p = 0.0081) and OS (11.1 months vs. 5.4 months, p = 0.0290). Multivariate analysis for survival revealed low VEGF level as associated with prolonged TTP (p = 0.0081) and OS (p = 0.0708). Plasma VEGF level was not associated with either VEGF expression or EGFR mutations of tumor tissue. Conclusions: Our results suggest that plasma VEGF levels before gefitinib treatment are predictive of response to gefitinib and prognostic of patients who receive gefitinib. [Table: see text]

Increased incidence of brain metastases in ERCC1-negative NSCLC patients treated with adjuvant cisplatin-based chemotherapy

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7581-7581
Author(s):  
B. Besse ◽  
C. Massard ◽  
V. Haddad ◽  
F. André ◽  
A. Dunant ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adjuvant Chemotherapy ◽  
Brain Metastases ◽  
Small Cell ◽  
Clinical Parameters ◽  
Small Cell Lung ◽  
Resected Nsclc ◽  
Increased Risk ◽  
Metastatic Sites ◽  
Nsclc Patients

7581 Background: We have recently demonstrated that ERCC1 is a predictor of the benefit of cisplatin-based adjuvant chemotherapy in resected non-small cell lung cancer (NSCLC). Non-squamous carcinomas have an increased risk of brain metastases (BM). Since brain is considered as a sanctuary site for chemotherapy, we hypothesised that there was an increased incidence of BM in ERCC1- negative non-squamous NSCLC patients treated with adjuvant cisplatin-based chemotherapy. Methods: Incidence of BM and histo- clinical parameters were analyzed in a population of 783 patients enrolled in the IALT trial. A subgroup analysis was performed in ERCC1 negative non-squamous NSCLC patients. Results: One hundred and one patients out of 783 (13%) developed BM alone or in association with other metastatic sites. In multivariate analysis, the clinical parameters associated with the occurrence of BM were nodal status (p=0.02), histological type (p=0.001) and pleural invasion (p=0.02). There is no effect of chemotherapy on BM (HR 1.38 [0.91–2.07], p=0.13). In patients with non-squamous histology (n=335) adjuvant chemotherapy was associated with an increased risk of BM (HR=2.10, [1.01–4.32], p=0.04) for ERCC1-negative tumours whereas there was no evidence of an effect on brain metastasis for ERCC1-positive tumours (HR=1.07 [0.38–2.99] p=0.90). These 2 effects are nevertheless not different (p for interaction=0.30) possibly by lack of power in this subsample. Conclusions: This study would suggest that cisplatin-based adjuvant chemotherapy is associated with an increased risk of BM in resected NSCLC patients with chemosensitive tumors. This data, if confirmed, could provide a rationale to evaluate prophylactic strategies in this subset of patients. No significant financial relationships to disclose.

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