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Xu Wang



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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  |  Presenting Author(s): Xu Wang

      • 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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    P1.09 - 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): Xu Wang

      • 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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    P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)

    • 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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      P2.01-26 - Association of Base Excision Repair Gene Polymorphisms with Response to Chemotherapy of Advanced Non Small-Cell Lung Cancer (ID 13805)

      16:45 - 18:00  |  Presenting Author(s): Xu Wang

      • Abstract
      • Slides

      Background

      Base excision repair (BER) plays an important role in the maintenance of genome integrity and anti-cancer drug resistance. This study aims to explore the role of BER genes polymorphisms in response to chemotherapy of advanced non small-cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy.

      Method

      During the period from November 2009 to January 2016, a total of 152 patients diagnosed with IIIB or IV stage NSCLC in the First Hospital of Jilin University were admitted into our study. The XRCC1 G28152A, MUTYH G972C, HOGG1 C1245G, PARP1 T2444C polymorphisms of all the patients were detected by the mass spectrometry. And the relationship between BER genes polymorphisms and the response of platinum-based chemotherapy is analyzed by Logistic regression.

      Result

      Logistic regression model shows that the response rate of chemotherapy of the PARP1 T2444C polymorphisms, CC genotype (OR: 5.216, 95%CI: 1.568-17.352, P= 0.007) and TC genotype (OR: 2.692, 95%CI: 1.007-7.198, P=0.048) is significantly higher than that of TT wild type, as well as the genotype of TC together with CC (OR: 3.178, 95%CI:1.229-8.219, P = 0.017). There is no relationship between G28152A, MUTYH G972C, XRCC1 HOGG1 C1245G gene polymorphism and chemosensitivity.

      Conclusion

      PARP1 2444 mutation allele C might be associated with the decreased sensitivity to platinum based chemotherapy in advanced NSCLC. Our findings may be helpful towards designing individualized cancer treatment.

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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): Xu Wang

      • 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  |  Presenting Author(s): Xu Wang

      • 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): Xu Wang

      • 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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