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Kewei Ma



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    JCSE01 - Perspectives for Lung Cancer Early Detection (ID 779)

    • Event: WCLC 2018
    • Type: Joint IASLC/CSCO/CAALC Session
    • Track: Screening and Early Detection
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/23/2018, 07:30 - 11:15, Room 202 BD
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      JCSE01.14 - Effects of Neoadjuvant Chemotherapy on the Expression of Programmed Death Ligand-1 and Tumor Infiltrating Lymphocytes in Lung Cancer Tissues (ID 14703)

      11:15 - 11:15  |  Author(s): Kewei Ma

      • Abstract

      Background
      Immune checkpoints programmed death 1(PD1)and its ligand PD-L1,PD-L2 pathways can mediate negative synergistic stimulation signals.Immunotherapy combined with chemotherapy can increase the objective response rate of cancer patients,but the mechanism of combination therapy is not clear.This study aims to analyze the changes of PD-L1,PD-L2 in lung cancer tissues and the changes of TILs ( CD4+,CD8+,CD28+,and CD56+ lymphocytes ) surrounding the tumor before and after neoadjuvant chemotherapy(platinum-based),in order to provide a theoretical basis for relevant clinical studies.Tumor samples were obtained from 26 patients who confirmed primary lung cancer before and after NAC from 2009 to 2016 in the First Hospital of Jilin University. The expression of PD-L1, PD-L2 in lung cancer specimens were assessed by IHC. 5%,10%,20%,30%,50% expression thresholds were used to define PD-L1, PD-L2 positive status, respectively. Of 16 patients ( since the biopsy tissue specimens were limited, only 16 cases of biopsy and postoperative tissue specimens were collected), the expression of TILs around the tumor before and after NAC were assessed by IHC. We analyze the changes of PD-L1 and PD-L2 in lung cancer tissues before and after NAC, the correlation between the changes of PD-L1 in lung cancer tissues and tumor shrink rate, the interval from the end of NAC to operation, pathological type, gender and smoking status. Of 16 patients, the changes of TILs around the tumor before and after NAC were also evaluated. P<0.05 was considered statistically significant.

      1. When using 5%, 10%, and 20% as expression threshold to define PD-L1 positive status, PD-L1 was up-regulated after NAC (P=0.008,P=0.016,P=0.016). However, there were no obviously statistical significance about the expression of PD-L1 when using 30%, 50% expression threshold. The expression of PD-L2 were not show any statistical significance before and after NAC.

      2. Of 16 patients, the expression of CD4+, CD8+ and CD28+ lymphocytes increased after NAC (P=0.014,P=0.038,P=0.021), whereas the change of CD56+ lymphocytes was not statistical significant.

      3. There were no significant difference between the changes of PD-L1 and tumor shrink rate, interval from the end of NAC to operation, pathological type, gender and smoking status .

      1. NAC up-regulates the expression of PD-L1 in lung cancer tissues when the expression thresholds are 5%, 10%, and 20%.

      2. NAC up-regulates the expression of CD4+, CD8+, and CD28+ lymphocytes.

      3. No correlation exists between the variation of PD-L1 and tumor shrink rate, interval from the end of NAC to operation, pathological type, gender and smoking status.

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    P1.03 - Biology (Not CME Accredited Session) (ID 935)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.03-17 - Functional Mechanism of GLDC Gene Alternative Splicing in Non-Small Cell Lung Cancer (ID 12270)

      16:45 - 18:00  |  Presenting Author(s): Kewei Ma

      • Abstract

      Background

      Lung cancer is the leading cause of death in the world and non-small cell lung cancer (NSCLC) accounts for approximately 85%.While, the mechanism is not fully understood.Therefore,exploring new molecules is of great significance to clarify the mechanism.Glycine decarboxylase (GLDC) is an oncogene associated with lactic acid metabolism,highly expressed in cancer stem cell-riched NSCLC.Both growth and tumorigenicity are dependent on the expression of high levels of GLDC, so which can be used as a stem cell surface marker to identify cancer stem cells.Alternative splicing (AS) is one of the important mechanisms of human gene regulation,which is closely related to the occurrence of tumor.However,the mechanism of AS regulation for GLDC in NSCLC has not been reported.Therefore,understanding the biological role of GLDC and its regulatory mechansim can lay a theoretical foundation for the early diagnosis and treatment of tumors.This experiment aims to clone human GLDC gene AS,analyze biological activity,and provide guidance for NSCLC development mechanism

      Method

      1.Construction of cloning vectors:Primers were designed based on the full length of GLDC (GLDCfl) and GLDC varient 1 (GLDCV1) cDNA,and mRNA expression in A549 and MRC5 cells was determined by RT-PCR combined with DNA sequencing;
      2.Functional experiments:MRC5 cells were transfected with overexpression plasmids,MTT assay,plate clone,western blot,lactic acid formation assay,and tumor-bearing test in vivo were used to detect MRC5 cells viability and proliferation.

      Result

      1.Both GLDCfl and GLDCV1 of A549 and MRC5 existed at the RNA level,the expression of which only in A549.Transfection of the target gene in MRC5 cells showed increased expression of both GLDCfl and GLDCV1.

      2.GLDCfl and GLDCV1 were over-expressed in MRC5 cells,and the cell viability was increased by MTT assay.Plate clone experiments proved the proliferation of MRC5 cells,and the expression of P-ERK and P-P38 proteins on the ERK/MAPK signaling pathway were increased.The supernatants of the cells for 24 hours were collected and assayed for lactic acid,then both GLDCV1 and GLDCfl promoted lactic acid production. Meanwhile,in vivo nude mice tumor test,each 100 μl dose was inoculated subcutaneously at the back shoulder of 4-6 week old nude mouse,and the GLDCV1 group shown the tumorigenicity

      Conclusion

      1This study first analyzed the expression pattern of GLDC gene AS in tumor cells and revealed the biological effects in tumor cells;

      2.Both GLDCV1 and GLDCfl can enhance the cell viability,promote luciferase activity,enhance cell clonal formation,and also find that GLDCV1 can enhance the tumorigenic ability.

      3.Both GLDCV1 and GLDCfl have effect on the expression of ERK/MAPK pathway protein.

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    P1.09 - Pathology (Not CME Accredited Session) (ID 941)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.09-14 - Analysis of Real-Word Mutations of Lung Cancer Driver Genes in 3081 Patients from China (ID 13649)

      16:45 - 18:00  |  Author(s): Kewei Ma

      • Abstract
      • Slides

      Background

      Patients with different races and regions have different mutation characteristics in driver genes. This study included 3081 lung cancer patients that were detected for three major driver genes from five regions of China.

      Method

      EGFR, EML4-ALK and ROS1 gene mutations were detected by fluorescence quantitative PCR (all use the same kit from AmoyDx). Chi-square test and logistic regressive analysis were used to analyze the clinicopathological features.

      Result

      From January 1 to December 31, 2017, a total of 1,449 driver genes were detected mutations (47.03%). The EGFR gene mutation rate was 40.1% (1259/3081), the EML4-ALK was 5.5% (169/3081), and the ROS1 was 1.3% (39/3081). EGFR and EML4-ALK coexistence in 17 cases (0.5%), 1 case of EGFR and ROS1 coexistence (0.03%). The EGFR gene mutation sites were mainly 19Del (557/3081) and 21 exon L858R (575/3081). The proportions of EGFR mutation sites are shown in the figure. EGFR gene mutation was negatively correlated with EML4-ALK and ROS1. Patients with EGFR, EML4-ALK, and ROS1 mutations have different population characteristics, which were listed in the table.egfr mutation.jpg

      logistic.jpg

      Conclusion

      The real-word driver gene mutations in large population of China are far higher than in the US and Europe, slightly less than in other reports of specially screened Asian populations.

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    P2.04 - Immunooncology (Not CME Accredited Session) (ID 953)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.04-07 - Effects of Neoadjuvant Chemotherapy on the Expression of Programmed Death Ligand-1 and Tumor Infiltrating Lymphocytes in Lung Cancer Tissues (ID 12138)

      16:45 - 18:00  |  Author(s): Kewei Ma

      • Abstract

      Background

      Immune checkpoints programmed death 1(PD1)and its ligand PD-L1,PD-L2 pathways can mediate negative synergistic stimulation signals.Immunotherapy combined with chemotherapy can increase the objective response rate of cancer patients,but the mechanism of combination therapy is not clear.This study aims to analyze the changes of PD-L1,PD-L2 in lung cancer tissues and the changes of TILs ( CD4+,CD8+,CD28+,and CD56+ lymphocytes ) surrounding the tumor before and after neoadjuvant chemotherapy(platinum-based),in order to provide a theoretical basis for relevant clinical studies.

      Method

      Tumor samples were obtained from 26 patients who confirmed primary lung cancer before and after NAC from 2009 to 2016 in the First Hospital of Jilin University. The expression of PD-L1, PD-L2 in lung cancer specimens were assessed by IHC. 5%,10%,20%,30%,50% expression thresholds were used to define PD-L1, PD-L2 positive status, respectively. Of 16 patients ( since the biopsy tissue specimens were limited, only 16 cases of biopsy and postoperative tissue specimens were collected), the expression of TILs around the tumor before and after NAC were assessed by IHC. We analyze the changes of PD-L1 and PD-L2 in lung cancer tissues before and after NAC, the correlation between the changes of PD-L1 in lung cancer tissues and tumor shrink rate, the interval from the end of NAC to operation, pathological type, gender and smoking status. Of 16 patients, the changes of TILs around the tumor before and after NAC were also evaluated. P<0.05 was considered statistically significant.

      Result

      1. When using 5%, 10%, and 20% as expression threshold to define PD-L1 positive status, PD-L1 was up-regulated after NAC (P=0.008,P=0.016,P=0.016). However, there were no obviously statistical significance about the expression of PD-L1 when using 30%, 50% expression threshold. The expression of PD-L2 were not show any statistical significance before and after NAC.

      2. Of 16 patients, the expression of CD4+, CD8+ and CD28+ lymphocytes increased after NAC (P=0.014,P=0.038,P=0.021), whereas the change of CD56+ lymphocytes was not statistical significant.

      3. There were no significant difference between the changes of PD-L1 and tumor shrink rate, interval from the end of NAC to operation, pathological type, gender and smoking status .

      Conclusion

      1. NAC up-regulates the expression of PD-L1 in lung cancer tissues when the expression thresholds are 5%, 10%, and 20%.

      2. NAC up-regulates the expression of CD4+, CD8+, and CD28+ lymphocytes.

      3. No correlation exists between the variation of PD-L1 and tumor shrink rate, interval from the end of NAC to operation, pathological type, gender and smoking status.

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    P2.09 - Pathology (Not CME Accredited Session) (ID 958)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.09-16 - Heterogeneity Analyses of MSLCs——Especially in the EGFR Mutation-Positive Ones (ID 12914)

      16:45 - 18:00  |  Author(s): Kewei Ma

      • Abstract
      • Slides

      Background

      Multiple synchronous lung cancers (MSLCs) are diagnosed as multiple tumor nodules in the same or different lung lobes. MSLCs present a clinical dilemma whether they are primary tumors or metastases. Recent studies showed that MSLCs shared an identical germline genetic background and environmental exposure in the same individual patient, however, different tumor nodules showed highly different heterogeneity, even in all the EGFR mutation-positive focuses. Therefore, we performed this study to further analyze MSLCs as to estimate the pathology and molecule heterogeneity among these nodules.

      Method

      Tumor samples were obtained from nine patients diagnosed with MSLCs. Immunohistochemistry were performed by professional pathologists. Whole-exome sequencing (WES) was conducted by IlluminaNovaseq with sequencing depth of 200X. NeoTyping was used to describe the dispersion of sequencing data among MSLCs of the same patient.

      Result

      We found different tumor nodules showed obviously pathological and molecular heterogeneities in the same individual (Figure 1). More different dispersion was observed among the nodules with more different pathologies in the same patient. The dispersion of 20%, 50% and 100% were observed in MSLCs with the same driver genes (such as EGFR exon21 L858R and L861Q) of lung adenocarcinoma, different evolutional stages (AAH, MIA and IA) and completely different pathologies (adenocarcinoma and squamous cancer), respectively. All the sequencing data showed MSLCs had different gene information, even in all the EGFR mutation-positive nodules, maybe similar, but not the same, which supported that each nodule in one patient was independent with others.

      figure1.tif

      Conclusion

      MSLCs could be independent with each other due to their pathological and molecular heterogeneities, even for EGFR mutation-positive nodules which hold the same driver gene, but different mutation site in just one patient. WES should be an effective way to recognize this heterogeneous characteristic, which would be helpful for the whole precise management of one MSLC patient.

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    P2.12 - Small Cell Lung Cancer/NET (Not CME Accredited Session) (ID 961)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.12-12 - Plasma Vitamin D Level is an Independent Prognosis Factor in SCLC Patients Treated with Platinum Plus Etoposide as First-Line Chemotherapy (ID 12569)

      16:45 - 18:00  |  Author(s): Kewei Ma

      • Abstract

      Background

      Small cell lung cancer accounts for approximately 13.6% of all lung cancer cases, which is a very aggressive form of lung cancer and associated with a very poor prognosis.Investigations into the prognostic factors of SCLC may help in the development of new biotherapeutic regimens.VD deficiency has been well documented to be unfavorable for the prognosis of patients with several types of cancer.However,there is no study focus on the relationship between the plasma VD level and the prognosis of SCLC patients. The primary objective of this study was to examine the prognostic role of the plasma 25-hydroxyvitamin D (25(OH)D) level in SCLC patients treated with platinum plus etoposide as first-line chemotherapy.

      Method

      A total of 178 SCLC patients were consecutively and prospectively hospitalized to receive platinum plus etoposide as first-line chemotherapy. The baseline 25(OH)D level was measured at the time of diagnosis. Main outcome measures included overall survival (OS) and progression-free survival (PFS).

      Result

      The median OS values of patients with 25(OH)D < 10ng/mL and ≥10ng/mL were 12.5 months (95% confidence interval[CI], 9.4–18.0 months) and 21.3 months (95%CI,12.8–29.1months),respectively; the median PFS values were 6.6 months(95%CI,5.1–7.6months) and 12.7months (95%CI,9.1–17.7months), respectively. Both univariate and multivariate analyses showed that having a plasma 25(OH)D level < 10 ng/mL was associated with a significantly shorter OS(P = 0.000; P =0.000) and PFS(P = 0.000; P =0.000).The median OS values of patients with 25(OH)D < 20ng/mL and ≥20ng/mL were 14.7 months (95% confidence interval[CI], 10.7–22.1 months) and 29.1 months (95%CI, 26.9–38.9 months), respectively; the median PFS values were 8.2months(95%CI, 6.5–10.7 months) and 22.4 months (95%CI, 21.2–24.2 months), respectively. Both univariate and multivariate analyses showed that having a plasma 25(OH)D level <20 ng/mL was associated with a significantly shorter OS (P = 0.000), while the baseline plasma 25(OH)D level was not significantly associated with PFS.

      Conclusion

      Plasma vitamin D level is an independent prognosis factor in small cell lung cancer patients treated with platinum plus etoposide as first-line chemotherapy.

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    P3.08 - Oligometastatic NSCLC (Not CME Accredited Session) (ID 974)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.08-15 - Lung Squamous Cell Carcinoma with Solitary Ocular Metastasis,Successful Treatment: An Interesting and Rare Case Report (ID 13697)

      12:00 - 13:30  |  Author(s): Kewei Ma

      • Abstract
      • Slides

      Background

      The incidence of ocular metastases from lung cancer is reported to be 0.1%-7% according to the international literature. Adenocarcinoma and small-cell lung cancer occupied the most proportion. Lung squamous cell carcinoma with solitary symptomatic ocular metastasis as the initial manifestation who accepted the multidisciplinary team (MDT)treatment has never been reported.

      Method

      In the diagnosis of intracranial disease, ophthalmofundoscopy can be used for follow-up observation and evaluation of therapeutic effects. Whole body PET -CT imaging can be used to identify the primary cancer and determine the disease staging.

      Result

      A 62-year-old woman presented to ophthalmology of hospital with a 1-week history of left eye pain, blurred vision. The ophthalmologist performed ophthalmofundoscopy and optical coherence tomography on the patient(Fig.1A). The ophthalmologist initial diagnosis is metastatic carcinoma to the eye. The diagnostic work was completed with PET-CT which confirmed the central lung cancer in the lower lobe of the right lung with ocular metastasis.After multiple disciplinary team consultations, including surgery, internal medicine, ophthalmology, radiotherapy and imaging department, the patient underwent the right lower lobe resection and lymph node dissection in December 2016. Postoperative pathology diagnose the right lung-squamous-cell carcinoma staged T2aN1. In February 2017, the patient reviewed the eye examination and indicated that the ocular lesions were enlarged. The patient received 4 courses of gemcitabine plus cisplatin regimen chemotherapy. The eye symptoms disappeared completely after 4 courses(Fig.2B). The progression-free time was 11.9 months. There're 16.5 months for the patients has been followed up(March,2018) from surgery, and the lesion of ocular was still controlled very well without any specific ocular treatment.

      fig.jpg

      Conclusion

      It's the first report of a rare case with solitary ocular metastasis as the initial manifestation of lung squamous cell carcinoma. The successful treatment of this case was reported to provide a new therapeutic reference for clinicians to encounter similar cases in the future.

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    P3.13 - Targeted Therapy (Not CME Accredited Session) (ID 979)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.13-34 - RET Gene, a New Choice for NSCLC (ID 13654)

      12:00 - 13:30  |  Author(s): Kewei Ma

      • Abstract
      • Slides

      Background

      RET gene, accounting for 1-2% of non-small cell lung cancer (NSCLC), has been identified as a novel target molecule which has been reported that could not coexist with other gene mutations such asrejected with the other mutation like KRAS, EGFR, BRAF, MEK1, HER2 and ALK.The emerging targeted agents Cabozantinib and Vandetanib have been recommended by NCCN guidelines for non-small cell lung cancer with RET fusion, based on a series of clinical trials.

      Method

      We presented a case of lung adenocarcinoma with KIF5B/RET fusion. The patient was a 50-year-old, male, non-smoker, diagnosed as left upper lobe adenocarcinoma lung cancer. We performed a radical resection of pulmonary carcinoma for two years ago. Subsequently,he completed four cycles of chemotherapy with gemcitabine and cisplatin. However, half years later, pleural metastasis made him have to receive systemic treatment but no chemotherapy due to his worse tolerance. We then performed a gene examination with the PCR method using the intraoperative specimen, and finally found positive KIF5B/RET fusion gene. From then on June 10,2017, he started to take cabozantinib for treatment.

      Result

      He started to take cabozantinib (140 mg orally, once daily) for about nine months. His disease sustained SD during that period (please see Figure 1). No serious adverse events (AEs) except rash (Ⅱ grade) occurred in the whole treatment process.

      Conclusion

      We found that the RET gene is a new alternative for lung adenocarcinoma patients without common mutations such as EGFR, ALK, ROS1 and so on. This case report supports a useful reference for the therapy of lung adenocarcinoma patients with RET mutation and may provide a new choice for this kind of NSCLC patients.

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