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Song Dong



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    MA24 - Genomic Evolution, KEAP 3 and More Non-Coding RNA (ID 928)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Biology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 10:30 - 12:00, Room 205 BD
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      MA24.01 - Genomic Evolution Trajectory Depicts Invasiveness Acquisition from Pre-invasive to Invasive Adenocarcinoma (ID 11840)

      10:30 - 10:35  |  Author(s): Song Dong

      • Abstract
      • Presentation
      • Slides

      Background

      Accumulation of molecular abnormalities may depict evolution trajectories of tumor initiation and development. However, the genomic profile of early stage adenocarcinoma and molecular mechanism of invasiveness acquisition from pre-invasive to invasive adenocarcinoma remains barely explored.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We simultaneously collected 20 patients with adenocarcinoma in situ (AIS) (n=5), minimally invasive adenocarcinoma (MIA) (n=5) and stage IA adenocarcinoma (lepidic/acinar predominant) (n=10). Whole exon sequencing (WES) was performed in pre-invasive adenocarcinoma with multi-region specimens and stage IA adenocarcinoma. Analysis of genomic alteration among different pathological status was performed and tumor mutation burden (TMB) was calculated as well as six mutation types individually. Enriched pathways of each pathology were measured through KEGG analysis.

      4c3880bb027f159e801041b1021e88e8 Result

      Baseline characteristics was generated through heatmap with smokers (2/20, 10%) and EGFR mutation (13/20, 65%) among whole population. AIS/MIA indicated much lower number of mutations than invasive adenocarcinoma (IAC) while TMB revealed the same trend without statistical significance. Multi-region sequencing showed high heterogeneity of single nucleotide variation (SNV) in AIS and MIA. Unique SNV presented dominant proportion in initial status. Cluster analysis showed higher copy number variation in AIS/MIA than IAC with cell adhesion molecules (CAMs) enriched in AIS/MIA while variety pathway enrichment in IAC through KEGG analysis. C>A transversions held major proportion in early stage adenocarcinoma and a significant increase in the proportion of C>T and C>G mutation was exhibited when evolving into IAC.

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      8eea62084ca7e541d918e823422bd82e Conclusion

      Intratumor heterogeneity may occur in the very beginning of adenocarcinoma. High copy number variation was dominant event for AIS/MIA while higher tumor mutation burden was seen in IAC. Tobacco signature encompassing C>A transversions dominates the early development of adenocarcinoma and APOBEC signature may play a potential role in acquisition of cancer invasiveness.

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    MA25 - Oligometastasis: Defining, Treating, and Evaluating (ID 929)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Oligometastatic NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 13:30 - 15:00, Room 203 BD
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      MA25.06 - RPA Analysis for Oligometastatic Non-Small Cell Lung Cancer: Smoking Combine T3/4 Patients May Not Be Benefit from Local Consolidative Treatment (ID 11994)

      14:05 - 14:10  |  Author(s): Song Dong

      • Abstract
      • Presentation
      • Slides

      Background

      In the literature on oligometastasis, the relative importance of local consolidative treatment (LCT) has been gradually accepted. This study set out to investigate the prognosis heterogeneity and the effect of LCT for oligometastatic non-small cell lung cancer patients.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We identified 436 patients in Guangdong General Hospital (GGH) from 2009 to 2016 with oligometastatic disease, and the factors predictive of overall survival (OS) were evaluated using Cox regression. Risk stratifications were defined using recursive partitioning analysis (RPA) on training set (2009~2014), which were further confirmed on validation set (2015-2016). And the effect of LCT for different risk groups was further examined by Kaplan-Meier method.

      4c3880bb027f159e801041b1021e88e8 Result

      Factors predictive of OS were: T stage (p=0.001), N stage (p=0.008), metastatic sites (p=0.031) and EGFR status (p=0.043). Prognostic risk RPA model was established, 4 risk groups were identified: Group I, never smokers and N0 disease (3-year OS: 55.6%, median survival time (MST)=42.8m); Group II, never smokers and N+ disease (3-year OS: 32.8%, MST=26.5m); Group III, smokers and T1/T2 disease (3-year OS: 23.3%, MST=19.4m); and Group IV, smokers and T3/T4 disease (3-year OS: 12.5%, MST=11.1m). Among four groups, OS significant differences were observed according to LCT except group IV (p=0.45).

      8eea62084ca7e541d918e823422bd82e Conclusion

      This retrospective study identified the poor prognostic population (smoking combine T3/4 disease) of oligometastatic non-small cell lung cancer patients, and this population may not be benefit from local consolidative therapy.

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      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P1.11 - Screening and Early Detection (Not CME Accredited Session) (ID 943)

    • 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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      P1.11-18 - A Classification-Based Machine Learning Method Reveals Exosomal miRNA Biomarkers for Patients with Pulmonary Ground Glass Nodule (ID 12462)

      16:45 - 18:00  |  Author(s): Song Dong

      • Abstract

      Background

      Non-invasive detection of lung cancer is of critical importance but has proven challenging due to the rate of false-negative diagnosis with current tests. Plasma exosomes have been implicated as a non-invasive diagnostic source. However, little high throughput screening has been done in the early-stage lung cancer and problems such as bias of enrollment, less rigorous identification exists. This study aimed to reveal the plasma exosome-derived miRNA biomarkers for early-stage lung cancer patients, especially those with ground glass nodule (GGN).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Pre-operative and paired post-operative plasma samples from patients with solitary pulmonary nodule and healthy volunteers were prospectively collected. Finally 38 malignant nodules, 7 benign nodules and 5 healthy volunteers were enrolled. The malignant nodules included 9 pure GGNs, 11 mixed GGNs and 18 solid nodules. Exosomes were collected from 1mL plasma and were isolated with 3D Medicine EV isolation kit. Exosomal miRNA profiling was performed using miRNA-seq. And an exosomal miRNA diagnostic model for patients with malignant nodules was constructed by using support vector machine (SVM).

      4c3880bb027f159e801041b1021e88e8 Result

      In general, malignant nodules, benign nodules and healthy volunteers were indistinguishable based on overall clustering. Regarding to malignant nodules, pure GGNs and solid nodules could be separated under principal component analysis (PCA), and the mixed GGNs presented a transitional state between the pure GGNs and the solid nodules. Ultimately, a two-dimensional SVM diagnostic model for discriminating malignant and benign nodules was established. The optimal miRNA combination could reach an area under curve (AUC) of 0.96, with sensitivity and specificity of 94.7% and 91.7%, respectively.

      8eea62084ca7e541d918e823422bd82e Conclusion

      This preliminary analysis highlights the potential of exosomal miRNA based liquid biopsy for non-invasive detection of early-stage lung cancer. The SVM model seems could effectively distinguish pulmonary nodules, but needs further verified.

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      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P2.16 - Treatment of Early Stage/Localized Disease (Not CME Accredited Session) (ID 965)

    • 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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      P2.16-47 - “Improved aBVA Method” and “Anterior VAB Method” Result in Analogous Survival Benefits During Right Upper Lobectomy (ID 14321)

      16:45 - 18:00  |  Author(s): Song Dong

      • Abstract
      • Slides

      Background

      As concluded in recent research, compared with “Anterior VAB Method” (dissecting pulmonary vessels first, followed by the bronchus), “Improved aBVA Method” (dissecting the posterior ascending arterial branch first, followed by the bronchus and vessels) during RUL would promote surgical feasibility and postoperative recovery for lung cancer patients. This study compared their long-term survival benefits basing on propensity score matching (PSM).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Consecutive lung cancer patients undergoing RUL were grouped into aBVA and VAB groups. PSM was conducted to reduce confounding bias between groups. After PSM, DFS and OS were estimated using the Kaplan–Meier method.

      4c3880bb027f159e801041b1021e88e8 Result

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      397 patients were selected (167 in the aBVA group, and 230 in the VAB group). Before PSM, the histological subtypes, the mean number of dissected lymph node stations, operation time, amount of blood loss, number of used staplers, and the rate of conversion to thoracotomy during the operation, and the rate of pneumothorax and pneumonia, the mean duration of postoperative chest drainage after the operation were not balanced (P<0.05) between two groups. After PSM (caliper=0.02), 96 pairs of patients were successfully matched, and these 9 characters were all balanced (P>0.05) among the two groups. DFS and OS of the two groups were not significantly different (both P > 0.05). The median DFS and OS were comparable for all patients in the two groups (not arrived vs. 39 months, P > 0.05; both not arrived, P > 0.05). DFS and OS among patients with disease recurrence were not significantly different (both P > 0.05). The median DFS and OS were still similar in the two groups (16 vs. 11 months, P > 0.05; both not arrived, P > 0.05).

      8eea62084ca7e541d918e823422bd82e Conclusion

      “aBVA Method” and “VAB Method” result in analogous survival benefits during RUL for lung cancer patients basing on PSM.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P2.17 - Treatment of Locoregional Disease - NSCLC (Not CME Accredited Session) (ID 966)

    • 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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      P2.17-32 - Dynamic Monitoring Before and After Neo-Adjuvant Crizotinib in Non-Small Cell Lung Cancer: A Brief Report (ID 11829)

      16:45 - 18:00  |  Author(s): Song Dong

      • Abstract
      • Slides

      Background

      Neo-adjuvant therapy has been considered as an optional approach for locally advanced non-small-cell lung cancer (NSCLC) patients. While targeted therapy has been widely applied in advanced NSCLC, neo-adjuvant targeted therapy remains poorly explored.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We describe four ALK-positive patients with pathological confirmed locally advanced NSCLC receiving neo-adjuvant Crizotinib. All patients received Crizotinib at a starting dose of 250mg twice daily for 1-3 months before surgical resection. One patients provided dynamic monitoring before and after neo-adjuvant therapy through next generation sequencing of plasma and tissue.

      4c3880bb027f159e801041b1021e88e8 Result

      Three patients were partial response without apparent adverse event before surgery while one received pathological complete response to neo-adjuvant Crizotinib but suffering from grade 4 hepatic damage. One of them had disease recurrence but achieved long duration of response (PFS=15m) through first-line Crizotinib. Dynamic monitoring with both plasma and tissue indicated simultaneously decrease of sensitive ALK-signaling in a patient with partial response (-51%) and no ALK-dependent resistant variants were captured.

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      8eea62084ca7e541d918e823422bd82e Conclusion

      Neo-adjuvant Crizotinib may be feasible and well-tolerated in locally advanced disease for complete resection. Crizotinib prior to surgery may provide thorough elimination of circulating molecular residual disease and it did not influence the response of reusing Crizotinib in first-line setting.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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