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S. Hong
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MINI 06 - Quality/Prognosis/Survival (ID 111)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Localized Disease - NSCLC
- Presentations: 1
- Moderators:R. Meguid, J. Yoshida
- Coordinates: 9/07/2015, 16:45 - 18:15, 605+607
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MINI06.07 - High Incidence of PD-L1 Expression in Surgically Resected Pulmonary Lymphoepithelioma-Like Carcinoma Is Linked to Prognosis (ID 1495)
17:20 - 17:25 | Author(s): S. Hong
- Abstract
- Presentation
Background:
Pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare and distinct type of primary lung cancer which is characterized by Epstein-Barr virus (EBV) infection. The prognostic significance of programmed cell death ligand 1 (PD-L1) in pulmonary LELC remains poorly understood.
Methods:
A total of 113 surgically resected pulmonary LELC in Sun Yat-sen University Cancer Center between January 2008 and December 2012 were included. Paraffin-embedded tumor sections were stained with PD-L1 antibody. H score were calculated by multiplying the percentage of positively stained cells by an intensity score. Tumors with >5% PD-L1 expression were deemed PD-L1 positive. The mRNA level of latent membrane protein 1 (LMP1) were determined by RT-PCR. Univariate and multivariate analyses were performed to identify prognostic factors for disease-free survival (DFS) and overall survival (OS).
Results:
The positive rate of PD-L1 was 74.3%. Patients with PD-L1 (+) tumor were significantly younger than those with PD-L1 (-) (median age, 50 vs 58 years; p = 0.008). High PD-L1 expression (H-score > 30) was associated with impaired DFS (median: 33.8 months vs not reached; p = 0.008) compared with low PD-L1 expression (Figure 1). Multivariate analysis shows that PD-L1 expression level (p = 0.014), N stage (p = 0.039) and M stage (p= 0.024) were independent prognostic factors for DFS. N stage and M stage but not PD-L1 expression level were significantly associated with OS (Figure 2). Also, LMP1 mRNA level was significantly associated with PD-L1 expression level (p < 0.001).Figure 1Figure 2
Conclusion:
Our results reveal higher incidence of PD-L1 expression in pulmonary LELC than common lung cancer, which may be linked to EBV burden. PD-L1 was a negative prognostic factor for DFS but was not associated with OS in surgically resected pulmonary LELC. These findings may provide a rationale for immunotarget therapy in this virus-associated lung cancer.
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MINI 26 - Circulating Tumor Markers (ID 148)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:M. Macmanus, C. Aggarwal
- Coordinates: 9/09/2015, 16:45 - 18:15, 205+207
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MINI26.02 - Deep Sequencing Reveals the Significance of Plasma DNA Concentration and Mutational Burden in Advanced Non-Small-Cell Lung Cancer Patients (ID 1409)
16:45 - 16:50 | Author(s): S. Hong
- Abstract
- Presentation
Background:
Plasma cell-free DNA (cfDNA) contains genetic information from primary and metastatic cancer foci. We utilized multiplex deep sequencing technology to investigate the clinical significance of cfDNA concentration and mutational burden in advanced non-small-cell lung cancer patients treated with EGFR tyrosine kinase inhibitors (TKIs).
Methods:
Between January 2012 and February 2014, seventy-one eligible patients from Sun Yat-sen University Cancer Center were enrolled. All the patients provided written informed consent and donated 2 ml plasma before taking EGFR-TKIs. Plasma DNA was isolated and purified using QIAamp Circulating Nucleic Acid Kit. CfDNA concentration was determined by Qubit Fluorometer. A set of 234 primer pairs were designed to amplify sequences covering hotspots of 35 genes. The amplicon libraries were prepared and entered into deep sequencing on Ion Torrent PGM chip. Variants were called by established bioinformatics methods. Circulating DNA mutational burden was defined as the number of somatic variants other than EGFR mutations. Objective response rate (ORR) and disease control rate (DCR) between different groups were compared using Fisher’s exact test while progression-free survival (PFS) and overall survival (OS) between different groups were compared by Kaplan-Meier curves and log-rank tests. Multivariate stepwise Cox regression analyses were performed to identify independent prognostic factors.
Results:
Forty-nine out of 71 patients were observed to harbor at least one variant and at most 7 variants, involving 10 genes (totally 124 variants). Higher cfDNA concentration was associated with impaired DCR (18.6% vs 81.4%; p=0.008), PFS (median PFS, 3.5 vs 15.2 months; HR=3.03; p=0.001) and OS (median OS, 27.3 vs not-reached; HR=2.38; p=0.042) compared with low cfDNA concentration group. Higher mutational burden was associated with unfavorable ORR (31.6% vs 73.7%; p=0.004) and PFS (median PFS; 8.6 vs 17.8 months; HR=1.61; p=0.050) compared with low mutational burden group. EGFR mutation conferred better ORR, DCR and PFS compared with EGFR wild-type (Figure 1). Multivariate analyses revealed that apart from EGFR mutation status, cfDNA concentration and mutational burden were also associated with the efficacy and/or the prognosis of EGFR-TKIs.Figure 1
Conclusion:
We for the first time showed that cfDNA concentration and mutational burden might influence the efficacy and prognosis of patients receiving EGFR-TKIs. These findings call for the need for the multiplex genetic analysis of patients’ cfDNA to tailor their treatment.
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