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X. Yang



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    OA 10 - Liquid Biopsy for Genomic Alterations (ID 678)

    • Event: WCLC 2017
    • Type: Oral
    • Track: Advanced NSCLC
    • Presentations: 1
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      OA 10.02 - Unique Genetic Profiles from Circulating Cell-Free DNA of Cerebrospinal Fluid in Leptomeningeal Metastases of EGFR Mutant NSCLC (ID 8258)

      11:00 - 12:30  |  Author(s): X. Yang

      • Abstract
      • Presentation
      • Slides

      Background:
      Leptomeningeal metastases (LM) are more frequent in non-small cell lung cancer (NSCLC) with EGFR mutations. Resistance mechanisms of LM remained unclear due to limited access to leptomeningeal lesions.

      Method:
      Primary tumor, cerebrospinal fluid (CSF) and plasma in patients with suspected LM of NSCLC were tested by Next-Generation Sequencing with 168 genes panel. Thirty patients diagnosed as LM and harboring EGFR mutation were enrolled in this cohort, and CSF cfDNA and plasma of two patients and CSF precipitates of another two patients were not available

      Result:
      Driver genes were detected in 100% (28/28) , 85.7% (24/28) and 75% (21/28) patients of CSF cfDNA, CSF precipitates and plasma, respectively; and 92.9% (26/28) patients had much higher allele fractions in CSF cfDNA than the other two media. Unique genetic profiles were captured in CSF cfDNA when compared with those in plasma and primary tissue. Multiple copy number variations (CNVs) were privately detected in CSF cfDNA, and CNVs in patients after TKI failure were more complicated when compared to those TKI naïve before LM. MET copy number gain identified in 44.0% (11/25) patients was the most frequent one, other CNVs included ERBB2, KRAS, ALK, MYC and FGFR1. Moreover, loss of heterozygosity (LOH) of TP53 was identified in 67.9% (19/28) CSF cfDNA, which was much higher than that in plasma (2/28, 7.1%; p<0.001), and there was a trend towards higher rate of concomitant resistance mutations in patients with TP53 LOH than those without one (70.6% vs. 25%; p=0.036 ). EGFR T790M was identified in 28% (7/25) patients with progression to TKIs in CSF cfDNA.

      Conclusion:
      CSF cfDNA could reveal the unique genetic profiles of LM, and it should be the most representative medium of liquid biopsy for LM in NSCLC harboring EGFR mutations.

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    P1.07 - Immunology and Immunotherapy (ID 693)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Immunology and Immunotherapy
    • Presentations: 1
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      P1.07-042 - PD-L1 and CD8 Expression in EGFR-Mutant or ALK-Rearranged Patients with Lung Cancer (ID 10407)

      09:30 - 16:00  |  Author(s): X. Yang

      • Abstract
      • Slides

      Background:
      Several studies indicate no response to check-point inhibitors on non-small-cell lung cancer with either EGFR-mutant or ALK-rearranged patients,of whom majority of international clinical trials involving PD-1/L1 inhibitors excluded. No solid evidences to interpret the underlying mechanism of poor clinical benefit to patients through PD-1/L1 inhibitors with driver genes mutation.

      Method:
      From 2010 to 2016, 482 patients and 263 patients with clinically operable lung cancer and advanced lung cancer respectively were collected at Guangdong Lung Cancer Institute (GLCI). All patients have detected for EGFR as well as ALK status. CD8 and PD-L1 expression was scored by immunohistochemistry with SP142 antibody. Five years survival rate was also analyzed.

      Result:
      Patients were assigned to EGFR/ALK positive group (344 cases) or negative group (401 cases). EGFR/ALK positive group contains 5.52% PD-L1+/CD8+; 11.92% PD-L1-/CD8+; 18.90% PD-L1+/CD8- and 63.66% PD-L1-/CD8-. EGFR&ALK negative group contains 13.97% PD-L1+/CD8+; 6.98% PD-L1-/CD8+; 30.42% PD-L1+/CD8- and 48.63% PD-L1-/CD8-. In EGFR/ALK positive group, PD-L1+/CD8+ is lower but PD-L1-/CD8- is higher than that of EGFR&ALK negative group (P<0.001). Significant statistical differences of 5 years survival rate were observed between four subgroups in EGFR/ALK positive group (PD-L1+/CD8+:41.9%, PD-L1-/CD8+: 91.0%, PD-L1+/CD8-: 75.4%, PD-L1-/CD8-: 69.7%; P=0.003). And there were no survival differences in EGFR&ALK negative group((PD-L1+/CD8+: 66.5%, PD-L1-/CD8+: 76.9%, PD-L1+/CD8-: 62.3%, PD-L1-/CD8-: 70.6%; P=0.341).

      Conclusion:
      Immunotherapy with PD-1/L1 inhibitors may not be suitable for EGFR-mutant or ALK-rearranged lung cancer patients with little co-expression of PD-L1 and CD8. However, these patients with such diver genes mutation reveal the best survival in PD-L1-/CD8+ subgroup and the worst survival in PD-L1+/CD8+ subgroup. Figure 1



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    P1.13 - Radiology/Staging/Screening (ID 699)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Radiology/Staging/Screening
    • Presentations: 1
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      P1.13-001 - T1 Tumor(≪3cm) with Visceral Pleural Invasion Should Be Classified as T2a in the 8th TNM Classification for Lung Cancer (ID 9004)

      09:30 - 16:00  |  Author(s): X. Yang

      • Abstract
      • Slides

      Background:
      The eighth edition TNM classification for lung cancer subclassified T2 into T2a (>3 to ≤4cm) and T2b (>4 to ≤5cm). T1 tumor(<3cm) with visceral pleural invasion(VPI) should be classified as T2a or T2b remain unclear. To elucidate this, we analyzed the survival of non–small-cell lung cancer(NSCLC) patients from Surveillance, Epidemiology and End Results (SEER) registry and our institute.

      Method:
      Within the SEER database, we selected 24245 resected pN0 NSCLC patients from 2010 to 2013 with a special interest in the prognostic impact of VPI. The VPI was defined as including PL1 and PL2 according to the TNM system. The classification of T1 tumor with VPI was investigated via discriminative power of survival curves. The further validation set was selected from Guangdong Lung Cancer Institute (GLCI).

      Result:
      The overall survival (OS) and lung cancer specific survival (LCSS) of T1-VPI and each stage (size only) were compared. The survival differences were statistically significant between T1-VPI and T1c, as well as T1-VPI and T2b. There were no significant survival differences between T1-VPI and T2a (OS: p=0.706; LCSS: p=0.792). And we retrospectively collected pN0 NSCLC patients between 2011-2013 from GLCI. The progression-free survival(PFS) and OS differences were also observed between T1-VPI and other groups except T2a (PFS: p=0.852; OS: p=0.970).

      Conclusion:
      In the 8th TNM classification for lung cancer, in which T1 tumors with VPI are upgraded to T2a, rather than T2b. Figure 1



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    P2.08 - Locally Advanced Nsclc (ID 709)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Locally Advanced NSCLC
    • Presentations: 1
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      P2.08-002 - A Nomogram for Predicting Underlying Beneficiaries for Resectable IIIA/N2 NSCLC Patients (ID 9260)

      09:30 - 16:00  |  Author(s): X. Yang

      • Abstract
      • Slides

      Background:
      Stage IIIA/N2 non-small-cell lung cancer (NSCLC) is a heterogeneous condition with multidisciplinary approaches involved. For operable IIIA/N2 NSCLC, surgery combined with chemotherapy is considered as an optimal management. Yet no solid evidences to conduct appropriate treatment modality for operable IIIA/N2 NSCLC and patients through curative treatment still surfer unsatisfactory prognosis.

      Method:
      329 pathologically confirmed IIIA/N2 NSCLC patients through curative treatment were enrolled. Multivariate analysis was performed to select highly correlated clinical characters for nomogram. C-index and further survival analysis were given to validate the efficacy of the model.

      Result:
      Multivariate analysis indicate independent factors for overall survival including clinical stage, T stage, N stage, N2 status and tumor position which were then integrated into the model. The calibration curves showed moderate concordance between nomogram prediction and actual observation. Linear predictor of 3.5 was set to be the cutoff of the model through X-tile plot, and patients with linear predictor over 3.5 revealed significant longer median survival than those under 3.5 (59.90 vs. 24.90, log-rank P=0.0005). Figure 1Figure 2





      Conclusion:
      We established a nomogram that may well distinguish the potential subgroup of patients benefit from curative treatment modalities. Further perspective study should rigorously clarify the issue of which multimodality treatment to be chosen for IIIA/N2 NSCLC patients.

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