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lu Yang
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P2.11 - Screening and Early Detection (ID 178)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Screening and Early Detection
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.11-31 - DNA Methylation Markers for Prediction of Recurrence in Stage I Non-Small Cell Lung Cancers (Now Available) (ID 2505)
10:15 - 18:15 | Author(s): lu Yang
- Abstract
Background
Surgery with curative intent is the standard of care for patients with stage I non-small cell lung cancer (NSCLC). However, many patients die of recurrent disease despite of lesion resection. The value of DNA methylation for predicting the recurrence of early-stage, resected NSCLC remains to be determined. The aim of this study was to find DNA methylation markers for recurrence prediction.
Method
39 paired tumor tissues and adjacent normal tissues from stage Ia NSCLCs were sequenced using bisulfite sequencing panel which covers 80,672 CpG sites and spans 1.05 mega base of human genome. The average sequencing depth was 1000X. Methylation blocks (MBs) were defined as the genomic region between the neighboring CpG sites and 8312 MBs were generated using the linkage disequilibrium and statistical modeling. Methylmean indicates the mean methylation value of MB, and methyentropy denotes the randomness of DNA methylation pattern of MB.
Result
A total of 726 tumor-specific MBs shared by 1098 Methylentropy and 1316 Methylmean variates were obtained from matched tumor tissues and adjacent normal tissues using t-test (P<0.05). Then the multivariable analysis, conducted via the Cox regression model, generated 15 significant disease-free survival (DFS)-related MBs which shared by 56 methylentropy and 46 methylmean variates. A final model was selected using a backward step-down process and 6 significant DFS-related MBs were selected (1 methylentropy and 5 methylmean variates). A nomogram model that incorporated the 6 MBs was established to predict the DFS, and it performed well (C index=0.729, Figure 1).
Conclusion
We established an effective nomogram that may well distinguish the potential subgroup of patients with different DFS based on DNA methylation. Further perspective study should be conducted to validate this nomogram model in larger cohorts.
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P2.16 - Treatment in the Real World - Support, Survivorship, Systems Research (ID 187)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Treatment in the Real World - Support, Survivorship, Systems Research
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.16-06 - Molecular Features and Treatment Outcome of HER2 Mutated Advanced Non-Small Cell Lung Cancer Patients in China (ID 2826)
10:15 - 18:15 | Author(s): lu Yang
- Abstract
Background
HER2 mutations are found in 1-2% of lung adenocarcinoma patients. Chemotherapy remains the standard of care for patients harboring HER2 driver mutations, while many HER2 targeted tyrosine kinase inhibitors (TKIs) have been applied to them in practice in recent years. Studies comparing chemotherapy to HER2-TKIs was limited. This study was aimed to investigate molecular and clinical patterns of HER2 mutations in advanced non-small cell lung cancer (NSCLC), and compare the different outcomes between chemotherapy and HER2-TKIs.
Method
Advanced or recurrent NSCLC patients with de novo HER2 mutations (N=75) were included in this study. Molecular information, clinical features, and treatment outcomes were retrospectively collected from a web-based patient registry and hospital chart review.
Result
Between October 2012 and December 2018, 65 patients with in-frame insertion mutations, 8 with point mutations and 2 with gene amplification were found. The most common subtypes of insertion mutations were A775_G776insYVMA, G776delinsVC, and V777_G778insGSP. HER2 mutated patients were mostly young-aged, females, never or light smokers, and adenocarcinoma. For HER2 mutated advanced NSCLC, chemotherapy achieved better outcomes than HER2-TKIs (median PFS: 5.5 vs 3.7 months in first line setting and 4.2 vs 2.0 months in second line setting, P=0.001 and 0.031, respectively). Especially for the most common subtype, YVMA insertions, PFS was significantly longer in chemotherapy than HER2-TKIs both in first line (6.0 vs 2.6 months, P=0.008) and in second line (4.2 vs 2.6 months P<0.001).
Conclusion
Compared to existed HER2-TKIs, chemotherapy might bring more benefit to HER2 mutated advanced lung cancer patients, especially the most common type of HER2 exon 20 insertions, A775_G776insYVMA subtype.
