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P. Krawczyk
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OA 08 - Neuroendocrine Carcinoma: Translational (ID 667)
- Event: WCLC 2017
- Type: Oral
- Track: SCLC/Neuroendocrine Tumors
- Presentations: 1
- Moderators:David S Ettinger, S. Zöchbauer-Müller
- Coordinates: 10/17/2017, 11:00 - 12:30, Room 311 + 312
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OA 08.03 - Effect of TOP2A and ERCC1 Genes Polymorphism on the Efficacy and Toxicity of Cisplatin and Etoposide Therapy in SCLC Patients (ID 8367)
11:20 - 11:30 | Author(s): P. Krawczyk
- Abstract
- Presentation
Background:
Small cell lung cancer (SCLC) shows an aggressive course with early metastases to distant organs. The main treatment regimen for SCLC patients involves platinum based chemotherapy (cisplatin or carboplatin) and etoposide. Genetic alternations, as single-nucleotide polymorphisms (SNPs) in TOP2A (topoisomerase II alpha) and in ERCC1 (endonuclease non-catalytic subunit) genes, were tested as a prognostic and predictive factors in patients with non-small cell lung cancer (NSCLC) treated with chemotherapy. However, there is limited data about clinical relevance of these genetic alternations in SCLC. Therefore, we undertook the present retrospective study to determine the influence of SNPs in TOP2A (rs34300454; rs13695; rs11540720) and ERCC1 (rs11615; rs3212986) genes on efficiency and toxicity of chemotherapy with platinum and etoposide in patients with SCLC.
Method:
The studied group included 103 Caucasian SCLC patients (65 male, 38 female, median age 65 ± 7,5 years). We collected detailed clinical-demographical data including: smoking history, environmental/occupational exposure to carcinogens, performance status, disease stage, and the presence of distant metastases. The response to the treatment was carefully monitored according to RECIST criteria, as well as side effects as anemia, neutropenia or weight loss were noted. For SNPs genotyping, we used DNA isolated from peripheral blood leukocytes using Qiamp DNA Mini Kit (Qiagen, Germany) and TaqMan hydrolyzing probes (Applied Biosystem, USA) in real-time PCR technique on Eco Illumina (Illumina, USA) device.
Result:
Patients with C/C genotype in rs13695 of TOP2A gene had significantly lower risk of neutropenia during chemotherapy than C/T heterozygous patients (p=0,01894; χ²=5.51; OR=2,676; 95% CI=1,165-6,143). Patients harbouring homozygous C/C genotype in rs3212986 of ERCC1 gene had significantly higher risk of anaemia during chemotherapy than heterozygous C/A patients (p=0,04531; χ²=4,01; OR=0,417; 95% CI=0,175-0,991). Furthermore, homozygous A/A genotype in rs11615 of ERCC1 gene was associated with significant prolongation of overall survival (12 vs. 9 months) compared to heterozygous G/A genotype of this gene (p=0,0120; χ²=6,3063; HR=1,657; 95% CI=1,0710-2,5633).
Conclusion:
SNPs in ERCC1 and TOP2 genes are associated with the toxicities and overall survival of SCLC patients treated with platinum and etoposide based chemotherapy.
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P3.02 - Biology/Pathology (ID 620)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.02-045 - Prevalence of ALK Gene Abnormalities in Routine Diagnostics of Polish NSCLC Patients (ID 9524)
09:30 - 09:30 | Author(s): P. Krawczyk
- Abstract
Background:
In NSCLC patients, ALK gene rearrangement should be diagnosed using fluorescence in situ hybridisation (FISH) method. However, immunohistochemistry (IHC) is considered as screening method for expression of ALK abnormal protein. There are discrepancies regarding the specificity of both methods and result interpretation.
Method:
1102 Polish NSCLC patients (85,7% of adenocarcinoma, 443 female, 659 male, median age: 65 years) were analysed for EGFR gene mutations using real-time PCR, after that for ALK abnormalities using IHC technique with D5F3 antibody, followed by FISH method using Vysis molecular probe.
Result:
ALK rearrangements detected by FISH method were confirmed in 49 (4.5% of all patients) out of 203 cases (18.4% of all patients) with ALK abnormal protein expression (specificity of IHC test – 85.4%). The median age of patients with EGFR gene mutations was 65 years, with ALK rearrangement 64 years (p=0.1040) and without these changes - 65 years (p=0.4932). ALK rearrangement was significantly more frequently detected in women (28 cases, 6.3%) than in men (21 cases, 3.2%; p=0.0134) and in FFPE tissue (46 case, 5.9%) than in cell-blocks (3 cases, 0.95%; p=0.0003). Median percentage of nuclei with ALK rearrangement in ALK-positive patients was 25%. In ALK-positive cases, ALK rearrangement defined as coexistence of single red and split signals were observed in 27 cases (55.1%), only split signals were observed in 1 case (2%) and only single red signals were diagnosed in 21 patients (42.9%). In this group of patients, median percentage of single red signals per nuclei was 45%, split signals – 8%, and fused signals – 47%. The polysomy (≥4 gene copy number per nuclei) of ALK gene was observed in 43 (36% of all FISH diagnosed patients) cases.
Conclusion:
The IHC method as a screening method is characterized by relatively low specificity. Cell blocks are a rather difficult material for ALK abnormalities analyzes (probably high risk of false negative results). The interpretation of FISH results with predominant single red signals requires considerable attention.
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P3.07 - Immunology and Immunotherapy (ID 723)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.07-013a - PD-L1 Expression, Using SP142 and 22C3 Antibody Clones, in NSCLC Patients with Known Status of EGFR and ALK Genes (ID 8323)
09:30 - 09:30 | Presenting Author(s): P. Krawczyk
- Abstract
Background:
Currently available immune-checkpoint inhibitor therapies in NSCLC patients have different, approved PD-L1 expression assays. These assays have similarities, but also some differences. In our study, we estimated usefulness of two immunohistochemical (IHC) tests in patients with different pathological diagnosis of lung cancer and known most common genetic abnormalities.
Method:
The study included 48 NSCLC patients (median age: 65 years old) with known status of EGFR and ALK genes. PD-L1 expression examination was carried out using two IHC assays with SP142 (Ventana) and 22C3 (Dako) antibodies. The analysis was performed in histological (resected tissue) and cytological (cellblocks from bronchoscopy biopsies) material in a form of formalin-fixed paraffin-embedded blocks, on corresponding analysis platforms.
Result:
The expression of PD-L1 of ≥5% and ≥50% on tumour cells (TCs) was significantly (p<0.05) higher in assay with 22C3 (66.7% and 45.8%) than with SP142 antibody (39.6% and 22.9%). The median percentage of PD-L1-expressing TCs was significantly (p<0.0001) higher in test with 22C3 than with SP142 antibody. PD-L1 expression on TCs was observed significantly higher in squamous cell carcinoma (SCC) patients than in PD-L1-positive non-SCC patients (p=0,0224). We have observed low percentage of PD-L1-positive cases among patients with common EGFR mutations and ALK rearrangement.
Conclusion:
Our results support that the highest PD-L1 expression on TCs occurs in SCC patients and in adenocarcinoma patients without common, druggable genetic abnormalities. The obtained results were clearly visible in assays with 22C3 antibody, whereas the SP142 antibody showed more diverse results in the same cases.
