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H. Jiang
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P2.05 - Poster Session with Presenters Present (ID 463)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Radiotherapy
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.05-027 - Effects of Thermo-Chemotherapy for Lung Cancer Induced by Nano-Paclitaxel Magnetic Fluid (ID 3781)
14:30 - 14:30 | Author(s): H. Jiang
- Abstract
Background:
The aim of this study was to investigated the effects of thermo-chemotherapy induced by nano-paclitaxel magnetic fluid for lung cancer A549 proliferation, apoptosis and cell cycle in vitro, and therapeutic effect of human carcinoma A549 xenograft in nude mice in vivo.
Methods:
In vitro, nano-paclitaxel magnetic liquid was synthesised by chemical coprecipitation and ultrasound emulsification. Lung cancer A549 cells were set up the control group (group A), thermal therapy group (group B), chemotherapy group (group C) and thermo-chemotherapy group (group D), which exposed to an alternative magnetic field (AMF) for 30 min. And then the optical density (OD) of viable cell, cytotocixity index, growth curve of cells, morphologic changes of cell, cell cycle and aposptosis were measured. When tumor length to diameter (6 ~ 8 mm), they were randomly divided into 4 groups: control group, magnetic heat treatment group, paclitaxel magnetic thermo-chemotherapy group and chemotherapy group, the tumor was heated in an AMF for 30 min. Tumor volumes were then measured every week. The therapeutic effect was assessed by measuring the tumor volume and weight. Pathological examination was performed with a light microscope following treatment. Immunohistochemical detecting tumor after treatment tumor cell apoptosis, calculate the apoptosis index to compare the efficacy of treatment.
Results:
In 43 ℃, with the increase of paclitaxel concentrations, are more obvious A549 lung cancer cell proliferation inhibition, the number of cells in living cells of optical density value, the killing rate (cytotoxity index, CI). Cell apoptosis rate increased. Heat treatment group the stagnation of the cell cycle in S phase, S phase cells and G2 phase increases, S phase decreased in the chemotherapy group, after heat treatment of lung cancer cells in electron microscope magnetic apoptotic changes. The temperature inside the tumor can be quickly rise to 43 ℃. Tumors in three experimental groups are suppressed, magnetic thermo-chemotherapy group tumor growth inhibition is more obvious, immunohistochemical confirmed the tumor cell apoptosis in change, apoptosis index increased.
Conclusion:
In vitro, with the increase of paclitaxel concentrations, are more obvious A549 lung cancer cells proliferation inhibition in 43 ℃. The number of cells in living cells of optical density value, the killing rate (cytotoxity index, CI), cell apoptosis rate increased. Thermo-chemotherapy induced by nano-paclitaxel magnetic fluid can inhibit the growth of A549 lung cancer nude mice transplantation tumor, nano paclitaxel magnetic thermo-chemotherapy can enhance the anti-tumor effect in vivo.
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P3.02b - Poster Session with Presenters Present (ID 494)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02b-098 - Plasma T790M Mutation Associates with Extensive Progression in Non-small Cell Lung Cancer with Acquired Resistance to EGFR Inhibitors (ID 5598)
14:30 - 14:30 | Author(s): H. Jiang
- Abstract
Background:
T790M mutation is a major mechanism for clinical failure in non-small cell lung cancer (NSCLC) patients with EGFR-TKI therapy. Acknowledgement of its frequency/abundance and its correlation with clinical characteristics will be of significant importance for the management of those patients in clinical practice and future trial design. Due to the difficulty of rebiopsy, plasma ctDNA is an ideal biopsy for detection of T790M mutation.
Methods:
314 patients with advanced or recurrent NSCLC who had progressed during EGFR-TKIs treatment were enrolled prospectively. T790M mutation was determined in plasma samples by ARMS and ddPCR assay. Disease failure site was defined into three types of chest limited (CP), brain limited (BP) and extensive progression (EP). The T790M mutation status was analyzed for their correlations with failure site and clinical characteristics.
Results:
T790M mutations were detected in 30.9% and 46.8% of the patients by ARMS and ddPCR. The concordance rate was 78.3% between two methods. Compared to patients with CP and BP, EP patients showed significant higher rate for T790M[+] determined by both ARMS and ddPCR (73.8% and 54.7%, p<0.001). In T790M positive population, the median T790M abundance was 1.2% (range, 0.04%-70.3%), and the median abundance of CP, BP, and EP was 0.66%, 1.52%, and 2.61%, respectively (p＝0.062). When adjusting for TKI response, worse PFS was found correlated with the plasma T790M mutation by ddPCR.
Conclusion:
Plasma T790M status correlates the extensive progression in NSCLC patients with EGFR-TKI therapy, which may provide the important ancillary information for treatment decision-making.
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P3.02b-100 - Comparison of Three T790M Testing Methods for the Detection of Non-Small Cell Lung Cancer after Tyrosine Kinase Inhibitor Failure (ID 4958)
14:30 - 14:30 | Author(s): H. Jiang
- Abstract
Background:
The third generation of TKI showed promising activities in patients with acquired T790M mutation. However, many patients in this setting are unable to undergo rebiopsy due to limited tissue availability and procedural feasibility. Mutation detection in plasma has shown promises to conquer the clinical challenging of re-biopsy, with advantage of non-invasiveness and accessibility. Here, we chose and evaluated the performance of three methods, amplification refractory mutation system (ARMS), modified amplification refractory mutation system (SuperARMS), and droplet digital PCR (ddPCR), to assess their concordance and feasibility for the detection of mutations in plasma samples.
Methods:
This study was performed between March 2015 and March 2016. Patients were considered eligible and were enrolled in this study if they met the following criteria: 1) histologically confirmed stage IIIB/IV NSCLC; 2) clinically resistant to first-generation EGFR-TKIs according to Jackman’s criteria. Blood samples were collected within 14 days after TKI resistance. Each sample was simultaneously detected by three methods.
Results:
In total, 169 patients were enrolled. 54.4% were female and 72.2% were diagnosed as stage IV; 97.6% were adenocarcinoma. The rates of patients in response to EGFR-TKI treatment were 35.5% for stable disease, 52.1% for partial response and 12.4% for complete response, respectively. T790M mutations were detected in 54 of 169 (32.0%) samples by ARMS, 33 of which simultaneously carried exon19 deletions and 21 of which carried L858R. For SuperARMS assay, 59 (34.9%) samples were detected T790M mutation and 110 (65.1%) were not detected. ddPCR results showed that 61 (36.1%) samples were with detectable T790M mutation and 108 (63.9%) samples were detected with wildtype T790M. T790M abundance ranged from 0.04% to 38.2%. The median T790M abundance was 0.15% for total samples and 2.98% for T790M mutation samples. The overall concordance was 81.1% (137/169) among ARMS, SuperARMS, and ddPCR. The crude and adjust agreement between ARMS and SuperARMS was 87.6% and 86.1%, 88.8% and 87.7% between ARMS and ddPCR, 85.8% and 84.5% between SuperARMS and ddPCR, respectively. We also found that detection of T790M with ddPCR showed a sensitivity of 94.6% (95%CI: 90%-97.5%) and a specificity of 59.9% (95%CI: 51.2%-67.9%) when took ARMS as reference.
Conclusion:
Liquid biopsy showed promises with advantage of non-invasiveness and accessibility. T790M detection based on plasma circulation tumor DNA showed high concordance. Compared with non-digital platforms, ddPCR showed higher sensitivity and provided both frequency and abundance information, which might be important for treatment decision-making.
