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Yaping Xu
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MA 09 - The Current Status of Radiation Oncology (ID 666)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Locally Advanced NSCLC
- Presentations: 1
- Moderators:Tomoki Kimura, Yong Chan Ahn
- Coordinates: 10/17/2017, 11:00 - 12:30, Room 316
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MA 09.01 - A Propensity-Matched Analysis of Lobectomy and Stereotactic Body Radiotherapy for Early Stage Non-Small Cell Lung Cancer (ID 10452)
11:00 - 11:05 | Presenting Author(s): Yaping Xu
- Abstract
- Presentation
Background:
Lobectomy is the preferred treatment for patients with early stage non-small cell lung cancer (NSCLC). However, stereotactic body radiation therapy (SBRT) is an attractive option due to its promising efficacy reported recently. Given that prospective comparative data on lobectomy and SBRT are limited, we compared the two treatments for early stage NSCLC.
Method:
All patients undergoing treatment with lobectomy or SBRT for clinical early stage (T size≤5cm) NSCLC between January 2012 and June 2017 were reviewed. Age, gender, tumor characteristics, Charson Comorbidity Index, pulmonary function, local control rate (LCR), recurrence-free survival (RFS), overall survival (OS) data were collected and propensity matching performed.
Result:
For the entire lobectomy cohort, 3-year OS, DFS, and LCR were 87.9%, 84.9%, and 96.4% respectively. For the entire SBRT cohort, 3-year OS, RFS and LCR were 84.4%, 60.7% and 93.4%, respectively. A total of 246 patients underwent surgery, and 117 received SBRT. There were statistically difference between surgical patient and SBRT patients in tumor histology(P<0.000). Surgical patients had tendency that have longer tumor size than SBRT patients (2.4±1.0 vs. 2.1±0.8, P=0.092). There were no statistically difference between lobectomy and SBRT group with age (68.9±6.6 vs.69.0±9.2, P=0.980), Eastern Coorperative Oncology Group performance scores, Charlson comorbidity Index, pulmonary function test result (FEV1 and predict FEV1), gender, T stage, and tumor location. A propensity matched comparison in a blinded manner (1:1 ratio, caliper distance=0.0025) based on age, gender, WHO performance status score, pulmonary function (forced expiratory volume in 1 second [FEV1] % and FEV1), and T stage resulted in 49 matched pairs. The follow-up period ranged from 0.3 to 60.0 months, with a median of 21.4 months. There were no differences between lobectomy and SBRT in LCR, respectively 97.1% and 100% (p=0.355) at 4 year. Also the 4-year RFS was comparable between groups, as 68.6% after lobectomy, versus 81.9% at 4 year after SBRT (p=0.963). The 4-year OS was similar in both groups, with 58.1% vs. 75.2% for lobectomy and SBRT (p=0.774). No patient experienced treatment-related death in both groups.
Conclusion:
This retrospective analysis found no significant difference in LCR, RFS and OS between lobectomy and SBRT. This study indicated matching these disparate cohorts of patients remains challenging. Participation in clinical trials is essential to define the indications and relative efficacy of lobectomy and SBRT in a high-risk population.
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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 | Presenting Author(s): Yaping Xu
- 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 | Presenting Author(s): Yaping Xu
- 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 | Presenting Author(s): Yaping Xu
- 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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P3.14 - Radiotherapy (ID 730)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Radiotherapy
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.14-015 - A Propensity Matched Analysis of SBRT and Sublobar Resection for Stage I Non-Small Cell Lung Cancer in Patients at High Risk for Lobectomy (ID 9862)
09:30 - 09:30 | Presenting Author(s): Yaping Xu
- Abstract
Background:
The aim of this study was to perform a survival comparison between stereotactic body radiotherapy (SBRT) and sublobar resection (SLR) in patients with stage I non-small cell lung cancer (NSCLC) at high risk for lobectomy.
Method:
All patients who underwent SBRT or SLR because of medical comorbidities for clinical stage I NSCLC from January 2008 to December 2015 were reviewed retrospectively. Propensity score matching was performed to reduce selection bias between SBRT and SLR patients based on age, gender, performance status, tumour characteristics, pulmonary function. Overall survival (OS) and recurrence-free survival (RFS) were estimated with Kaplan–Meier method.
Result:
Forty-nine patients were matched into each group of SBRT and SLR (include 27 underwent segmentectomy, 22 underwent wedge resection). There were 32 and 30 men with median age of 67 and 69 years, respectively. Median follow-up was 25 months. In terms of treatment-related mortality, the 30- day mortality rates for the SBRT and SLR groups were 0 and 2.0 %, respectively. Patients treated by SBRT had a tendency to increase 3-year OS compared with SLR (94.0% versus 78.1%; P= 0.064).There was no difference between two groups in 3-year RFS (61.8% versus 65.7%; P=0.864). In a subanalysis, 3-year OS after SBRT was greatly better than wedge resection subgroup (94.0% versus 67.4%; P= 0.026), but there was no significant difference between SBRT and segmentectomy in 3-year OS (94.0% versus 88.0%; P= 0.212).
Conclusion:
SBRT had a tendency to increase OS compared with sublobar resection in patients who are not medically fit for lobectomy with clinical stage I NSCLC. However, OS after SBRT was better than wedge resection subgroup. SBRT can be an alternative treatment option to segmentectomy for patients who cannot tolerate lobectomy because of medical comorbidities. A randomized prospective study is necessary to determine survival in compromised SBRT and sublobar resection.
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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 | Presenting Author(s): Yaping Xu
- 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.
