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S. Han
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MA 16 - Mediastinal, Tracheal and Esophageal Tumor: Multimodality Approaches (ID 675)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
- Presentations: 2
- Moderators:K. Shibuya, Francoise Mornex
- Coordinates: 10/17/2017, 15:45 - 17:30, Room 313 + 314
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MA 16.13 - PD-L1 Expression Is a Prognostic Factor in Patients with Esophageal Squamous Cell Carcinoma Treated with Postoperative Adjuvant Radiotherapy (ID 9831)
17:05 - 17:10 | Author(s): S. Han
- Abstract
- Presentation
Background:
Programmed death-ligand 1 (PD-L1), is reported to serve as an indicator of prognosis in many malignant tumors. The aim of this study was to determine whether PD-L1 expression status in tumor cell can predict patient’s prognosis in esophageal squamous cell carcinoma (ESCC).
Method:
246 paraffin-embedded tissue samples were detected PD-L1 expression by immunohistochemistry from ESCC patients after surgery. And we statistically analyzed the association between expression of PD-L1 and clinicopathological factors and outcomes of survival.
Result:
The rate of positive PD-L1 expression was 24.4% (60/246) . Multivariate analysis indicated positive PD-L1 expression was associated with advanced TNM stage (P=0.009). The median of overall survival (OS) for patients with positive PD-L1 expression was similar to those with negative PD-L1 expression (Median OS, 52.4 vs. 56.4 months, P=0.466). However, in the subgroup analysis, the results indicated that the prognosis of patients with positive PD-L1 expression treated with adjuvant radiotherapy was significantly better than those with negative PD-L1 expression (Median OS, 84.4 vs. 36.0 months, P=0.046), while the OS of positive PD-L1 expression patients treated with adjuvant chemotherapy was poorer than those with negative PD-L1 expression although without significant statistical differences (Median OS, 21.8 months vs. 41.0 months, P=0.765) (Figure 1). Multivariate Cox regression hazards analysis revealed PD-L1 expression statue was not an independent prognostic factor (P=0.804) for entire cohort.Figure 1 Subgroup analysis for OS in ESCC based upon PD-L1 expression. (A) Subgroup of surgery alone; (B) Subgroup of surgery plus adjuvant chemotherapy; (C) Subgroup of surgery plus adjuvant radiotherapy; (D) Subgroup of surgery plus adjuvant chemoradiotherapy.
Conclusion:
Positive PD-L1 expression was likely to be more associated with malignant biological behavior of ESCC. PD-L1 expression was not a prognostic factor of OS for entire cohort, however, it is a prognostic factor in patients treated with postoperative adjuvant radiotherapy.
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MA 16.14 - c-Met in Esophageal Squamous Cell Carcinoma: An Independent Prognostic Factor and Potential Therapeutic Target (ID 10539)
17:10 - 17:15 | Author(s): S. Han
- Abstract
- Presentation
Background:
c-Met is reported to serve as a poor prognostic factor in many malignant tumors. Previous studies have suggested the involvement of c-Met in esophageal squamous cell carcinoma (ESCC), but the correlation between c-Met status and clinical outcome remains unclear. Furthermore, the identification of a novel molecular therapeutic target might potentially help improve the clinical outcome of ESCC patients.
Method:
The expression of c-Met was immunohistochemically assessed in 180 surgically obtained tissue specimens. The correlation between c-Met expression and patients’ clinicopathological features, including survival, was evaluated. We also investigated changes in cell functions and protein expression of c-Met and its downstream signaling pathway components under treatments with c-Met inhibitor in ESCC cell line.
Result:
There was no significantly correlated between c-Met expression and patients’ clinicopathological features. However, there was a significant difference in OS (median: 41.9 vs. 56.7 months; p= 0.001) between the high c-Met and low/negative c-Met expressing groups. In subgroup of patients with adjuvant radiotherapy, high expression of c-Met was correlated with poor disease prognosis (p= 0.002), while there was no significant correlation in patients with adjuvant chemotherapy. In addition, multivariate analysis identified the high expression of c-Met as an independent prognostic factor. Treatment with c-Met inhibitor significantly inhibited the growth of an ESCC cell line with high c-Met mRNA expression. Moreover, c-Met and its downstream signaling inactivation was also detected after treatment with c-Met inhibitor.
Conclusion:
The results of our study identified c-Met expression as an independent prognostic factor in ESCC and demonstrated that c-Met could be a potential molecular therapeutic target for the treatment of ESCC with high c-Met expression.
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P3.01 - Advanced NSCLC (ID 621)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.01-058 - Impact of Different Timing of Radiotherapy in Patients with Brain Metastases from Epidermal Growth Factor Receptor-Mutant NSCLC (ID 9834)
09:30 - 09:30 | Author(s): S. Han
- Abstract
Background:
To perform a retrospective analysis of patients with brain metastases (BM) from epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) to evaluate the preferred treatment timing of EGFR-tyrosine kinase inhibitors (TKIs) in this population.
Method:
Of 94 initial or recurrent patients diagnosed BM from EGFR-mutant NSCLC between Jan 1, 2012, and Jun 31, 2016, 30 received upfront brain RT followed by EGFR-TKI, 39 EGFR-TKI combined with concurrent brain RT, and 25 upfront EGFR-TKI then brain RT. Disease-specific-graded prognostic assessment was similar among all 3 groups. The primary endpoint was overall survival (OS), and the second endpoint was intracranial progression-free survival.
Result:
Although the median OS was not significantly different among the upfront RT, concurrent treatment, and upfront EGFR-TKI groups (29.0 vs 24.0 vs 17.0 months; P=0.186), however, it was longer in the upfront RT group compared with the upfront EGFR-TKI group (P=0.035). On subgroup analysis, the exon 19 deletions patients had longer OS than the exon 21 mutations patients in upfront EGFR-TKI group (23.0 vs 15.0 months; P=0.048), but the upfront RT (34.0 vs 23.0 months; P=0.186) and the concurrent treatment groups (24.0 vs 13.0 months; P=0.827) did not. According to multivariate COX analysis, KPS (≥ 70) and intracranial metastasis alone was associated with a longer OS. The median intracranial progression-free survival was significantly improved in patients receiving upfront RT compared with those receiving concurrent treatment or upfront EGFR-TKI (not reached vs 40.0 vs 9.0 months; P=0.003).
Conclusion:
The present study suggests that the use of upfront brain radiotherapy, and the deferral of EGFR-TKI may result in superior OS in patients with brain metastases from EGFR-mutant NSCLC. Also, upfront brain radiotherapy management could significantly reduce the risk of intracranial progression. A prospective, multi-institutional, randomized trial of upfront EGFR-TKI then RT versus upfront RT followed by EGFR-TKI is urgently needed, especially based on different subgroup population.
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P3.17 - Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies (ID 733)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.17-003 - A Selective Small Molecule Inhibitor of C-Met Kinase, BPI-9016M, Has Synergistic Effects with Radiation on Esophageal Squamous Cell Carcinoma (ID 9870)
09:30 - 09:30 | Author(s): S. Han
- Abstract
Background:
c-Met is overexpressed in cancer cells and plays a crucial role in apoptosis evasion. BPI-9016M, a small-molecule inhibitor of c-Met, could enhance the cytotoxicity of various DNA-damaging agents and promote the cell apoptosis. Here, we evaluated the radiosensitizaion potential of BPI-9016M in Eca109 human esophageal squamous cell carcinoma (ESCC) cell line.
Method:
Cell viability was determined by CCK8 assay. The radiosensitization effect of BPI-9016M was evaluated by clonogenic survival and progression of tumor xenograft. Cell apoptosis were determined by flow cytometric analysis and TUNAL. Cell apoptosis regulators were detected by western blot analysis. Radiation-induced DNA double strand break (DSB) and homologous recombination repair (HRR) were detected by the activation of ATR-Chk 1/ATM-Chk2 pathways.
Result:
BPI-9016M induced radiosensitization in Eca109 cell of ESCC cell line, associated with 1) down-regulating mutation P53 and Bcl-2; 2) decreases phosphorylated ATR and ATM focus formation, and the expression of γ-H2AX; 3) up-regulates the rate of cell apoptosis protein cleaved-Caspase(Figure 1). The combination of BPI-9016M with irradiation delayed the growth of ESCC tumor xenograft to a greater extent compared with either treatment modality alone (P < 0.05). Figure 1. BPI-9016M enhanced radiation induced apoptosis and inhibited ATM- and ATR-dependent DNA damage homologous recombination repair (HRR) pathways analyzed by western blot.
Conclusion:
Our findings suggest that the enhanced apoptosis and the inhibition of HRR contribute to radiosensitization by c-Met inhibitor BPI-9016M in ESCC cell.
