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J. Ni
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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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MINI26.14 - Noninvasive Identification of EGFR-T790M Mediated Resistant NSCLC Patients Using Plasma CfDNA (ID 1208)
16:45 - 18:15 | Author(s): J. Ni
- Abstract
- Presentation
Background:
EGFR-T790M mutation, which is the valuable target for the next generation of EGFR-TKI, accounts for about half of the acquired resistance to current EGFR-TKI therapy in the EGFR sensitive mutation positive NSCLC patients. Due to clinical challenge in obtaining re-biopsy tumor tissues, noninvasive detection of EGFR-T790M in plasma circulating free DNA (cfDNA) has been proved to be feasible. Yet a highly sensitive assay needs to be developed to avoid false-negative detection. We here explored whether droplet digital PCR (ddPCR) of cfDNA can an alternative assay to identify the EGFR-TKI resistance mediated by EGFR-T790M in the clinical practice.
Methods:
The digital PCR method was recently developed for EGFR sensitive mutations, and its high sensitivity and specificity were validated in plasma cfDNA from EGFR-TKI-naïve NSCLC patients. In this study, we applied this method to detect EGFR-T790M in plasma cfDNA from metastatic NSCLC patients who initially responded but acquired resistance to current EGFR-TKI treatment. For the concordance analysis, the paired re-biopsy or pleural effusion cytology samples after failed EGFR-TKI were also collected for EGFR-T790M testing.
Results:
25 consecutive NSCLC patients were enrolled and analyzed in this study according to these criteria: 1. Metastatic NSCLC patients with acquired EGFR-TKI resistance. 2. The re-biopsy tissue or cytology samples and paired plasma samples were available after disease progression on EGFR-TKI. Among these 25 patients, 13 were positive and 9 were negative for EGFR-T790M mutation in both tumor tissue and plasma samples. 3 patients positive for EGFR-T790M mutation in tumor tissue were detected negative in their plasma. The overall concordance rate between plasma and tumor tissue testing was 88.00% (22/25) (Kappa=0.757, 95%CI: 0.4996-1.0). The sensitivity and specificity for plasma testing of EGFR-T790M mutation by ddPCR were 81.25% (13/16) (95%CI: 54.35%-96.00%) and 100.00% (9/9) (95%CI: 66.37%-100%), respectively. Figure 1
Conclusion:
Detection of EGFR-T790M in plasma cfDNA by ddPCR is highly sensitive and specific when compared to the pairedre-biopsy tissue or cytology samples. This noninvasive method could complement current invasive biopsy approach or provide an alternative method to identify specific mutation mediated resistance in clinic.
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P1.08 - Poster Session/ Thymoma, Mesothelioma and Other Thoracic Malignancies (ID 224)
- Event: WCLC 2015
- Type: Poster
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.08-027 - Clinicopathologic Study and Prognostic Analysis of Bronchial Mucoepidermoid Carcinoma (ID 1133)
09:30 - 17:00 | Author(s): J. Ni
- Abstract
Background:
Bronchial mucoepidermoid carcinoma (MEC) is a rare type of lung cancer. The present study tried to establish the clinicopathologic characteristics and prognostic factors of patients with this cancer who were treated in Shanghai Pulmonary Hospital. In addition, the common genetic changes were analyzed here.
Methods:
Sixty-four cases of bronchial MEC treated in Shanghai Pulmonary Hospital between 1995 and 2013 were collected for our study. Retrospective cohort study was performed to analyze the relationship between clinical characteristics and prognosis. The common genetic changes of non-small cell lung cancer, such as EGFR, ALK ,ROS1,BRAF, KRAS status were tested.
Results:
All 64 MECs were reconfirmed by pathologists and tumor staging of all patients were reevaluated according to AJCC 7th edition system. There were 35male patients and 29 females with median age of 40.5 years old. Cough and hemoptysis were the most common clinical manifestations. The mean time between symptom appearance and going to see doctors was 8.7months. Fibre optic bronchoscopy confirmed the presence of bronchial tumor in 48 of 64 patients, but only half of them were diagnostic of MEC by endobronchial biopsies. The pathological findings were cellular mixture consisting of mucus-secreting cells, squamous cells and mesenchymal cells. There were 52 and 4 patients who were in an early stage (stage I-II) and stage IIIA at the time of diagnosis. All those patients underwent surgical resection with lymph node sampling and dissection and 10 patients received adjuvant chemotherapy, 2 patients adjuvant radiocherapy. There were 5 and 3 patients in stage IIIB and IV. Among them, 4 were treated by chemotherapy. The median survival time for patients with stage I-II ,IIIA and IIIB-IV were 71months (10-223months), 35 months (5.3-126months) and 4 months (1-51months) respectively. Single factor analysis showed that the early TNM staging (p=0.000), no mediastinal lymph node involvement or N1 involvement (p=0.000) and surgery (p=0.001) were the positive prognostic factors for MEC patients. There was a trend that shorter disease course might benefit for survival (p=0.09). Multi-factor analysis showed that TNM staging was an independent prognostic factor for the patients suffering from bronchial MEC. Genetic testing showed that 1of 38 patient presented T790M mutation, 17 of 32 patients had KRAS positive staining and no BRAF mutation was found. Interestingly, we found 3 ALK rearrangement which accounted for 7.5% of all tested patients.
Conclusion:
TNM staging is an independent prognostic factor for bronchial MEC patients. Mediastinoscopy should be performed on patients who are clinically N2 stage to get precise stage and treatment decision. Early diagnosis and early surgery may improve patients’ survival. For advanced MEC patients, ALK fusion gene may be routinely tested so as to provide patients with more therapy options.
