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Y. Wu
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P1.01 - Advanced NSCLC (ID 757)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.01-047 - Analysis of EGFR Mutation Status in CSF and Blood in Lung Adenocarcinoma Patients with EGFR Mutation and CNS Metastasis (ID 9717)
09:30 - 09:30 | Author(s): Y. Wu
- Abstract
Background:
Patients with non-small cell lung cancer（NSCLC）harboring epidermal growth factor receptor (EGFR) mutations benefit a great deal from EGFR tyrosine kinase inhibitors(TKIs). However, most patients get recrudesced within one or two years, and many of them progressed in central nerve system（CNS）.Owing to the blood– brain barrier, detecting tumor-derived cell-free DNA (cfDNA) in the blood of brain metastasis tumor patients is challenging. Detecting tumor-specific mutations in cerebral spinal fluid (CSF) became an alternative method.
Method:
41 initial or progressed lung adenocarcinoma patients with EGFR mutation and CNS metastasis from Henan Cancer Hospital were included in this study. 41 patients were all detected EGFR mutation status in CSF with dropplet digital PCR (ddPCR) and 37 in 41 patients were detected EGFR mutation status in blood with the same method. Their clinical informations were also collected at the same time.
Result:
The rate of EGFR mutations in CSF （15/41，36.6%）were obviously lower than that in blood（24/37，64.9%）（P=0.013), especially in those with EGFR exon 19del mutation patients (7/18 vs 13/16, P = 0.017), without TKIs treated patients (3/13 vs 8/11,P = 0.038) and less than 60 years patients (10/25 vs 17/22, P = 0.010). In patients with CNS symptoms positive, the rate of EGFR mutations in CSF was higher than those negative (13/27 vs 2/14 , P=0.033). In patients with MRI indicating leptomeningeal metastasis, the rate of EGFR mutations in CSF was higher than those not indicating(8/11 vs 7/30 , P=0.003).Clinical characteristics, EGFR mutation status in CSF and plasma (n = 41)
Characteristic n(%) Gender Male 23 (56.1) Female 18 (43.9) Age ≥ 60 16 (39) < 60 25 (61) Smoking status Yes 12 (29.3) No 29 (70.7) Brain metastases (MRI) Only metastatic tumors 30 (73.2) With meningeal lesions 11 (26.8) Brain metastatic tumor number Single 10 (24.4) Multiple 31 (75.6) Neurological symptoms Positive 15 (36.6) Negtive 26 (63.4) Prior TKIs treat Yes 28 (68.3) No 13 (31.7) CSF EGFR mution 19 7 (17.1) 21 6 (14.6) Both 2 (4.9) Negtive 26 (63.4) Blood EGFR mution 19 13 (31.7) 21 10 (24.4) Both 1 (2.4) Negtive 13 (31.7)
Conclusion:
The EGFR mutations status in CSF is different from that in blood in patients with EGFR mutation and CNS metastasis. This warrants confirmation in larger cohorts and further more studies are needed to find out the internal mechanism. Detecting EGFR mutations status in both blood and CSF will be helpful to make individualized treatment.
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P1.15 - SCLC/Neuroendocrine Tumors (ID 701)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: SCLC/Neuroendocrine Tumors
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.15-006 - Enriched Environment and Anti-Depressants Enhance Platinum Chemosensitivity of Small Cell Lung Cancer (ID 7377)
09:30 - 09:30 | Author(s): Y. Wu
- Abstract
Background:
Small cell lung cancer (SCLC) is one of the most lethal malignancies with rapid chemoresistance. Based on our previous study, enriched environment (EE) has a clear effect on improving the mental state of mice and can reduce chemoresistance caused by platinum regimens. In this study we investigated the complex links between benign mental stress (EE) and chemosensitivity of SCLC, and use anti-depressants to improve the mental state of mice to observe its impact on chemosensitivity to platinum regimens, and the underlying mechanism was explored.
Method:
The mental state of mice was evaluation by behavior tests include: elevated plus maze (EPM), open field experiment (OF), forced swimming (FS). Then, the mice were transplanted subcutaneously and treated with cisplatin, carboplatin and oxaliplatin. The tumor was analyzed by gene expression profiling and the differential genes were screened. The expression level of differential genes were examed by real-time PCR, and verified by western bolt and immunohistochemistry, respectively. And then ABCG2 blocker was used for chemosensitivity verification in vivo and in vitro.
Result:
EE significantly increased the movement on openarms in the EPM (35.24 sec V.S. 16.78 sec, P<0.01), increased the center area time in OF test (54.25 sec V.S. 35.24 sec, P<0.05), significantly increased the struggling time in the FS test (46.02 sec V.S. 25.81 sec, P<0.01). Antidepressants can also significantly improve the state of depression of mice, but can not achieve the effect of EE. For platinum chemosensitivity test, the antidepressant drugs (Diazepam, Quetiapine and Clomipramine) have no direct inhibition to tumor cells. A can significantly increased the sensitivity of chemotherapy in mice, but can not achieve the inhibitory effect of EE. Next we found the serum BDNF levels significantly decreased in EE mice. Similarly, antidepressants also significantly reduced serum BDNF levels in mice. Gene expression profiles showed that a variety of genes were downregulated mainly in ABC transporters and drug metabolic pathways by EE and antidepressants. The expression level of ABCB1, ABCC2, ABCG2, ABCC9, PPARa, DPYD, GST-P1 and GSTM1 in SCLC sample were examed by real-time PCR, and verified by western bolt and immunohistochemistry, respectively. ABCG2 expression in tumor of EE and antidepressants mice were even 3 fold higher than control (P<0.001). Nicardipine blocks ABCG2 expression can restore chemosensitivity to platinum based drugs (P<0.001).
Conclusion:
Antidepressants can partially mimic the chemotherapeutic effect of EE and we confirm that the mechanism is partially achieved by increasing BDNF and reducing the expression of ABCG2.
