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Seung Joon Kim
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P2.03 - Biology (Not CME Accredited Session) (ID 952)
- 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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P2.03-16 - TGF-β Induced EMT and Stemness Characteristics are Associated with Epigenetic Regulation in Lung Cancer (ID 12725)
16:45 - 18:00 | Presenting Author(s): Seung Joon Kim
- Abstract
Background
Transforming growth factor-β (TGF-β) promotes tumor invasion and metastasis by inducing an epithelial-mesenchymal transition (EMT). EMT is often associated with acquisition of stem-like characteristics. In this study, we investigated whether EMT and stem-like characteristics induced by TGF-β could associated with epigenetic regulation in lung cancer.
a9ded1e5ce5d75814730bb4caaf49419 Method
Human normal epithelial (BEAS-2B) and cancer (A549, H292, H226 and H460) cell lines were incubated with 10 ng/ml of TGF-β for 3 days. Transcriptome analysis of BEAS-2B and A549 cells treated with TGF-β were performed by using next-generation sequencing (HiSeq 2500 system). Western blotting was performed to analyze the expression of epithelial marker (E-cadherin) and mesenchymal markers (N-cadherin, fibronectin, vimentin and α-SMA). Wound healing assay, Matrigel invasion assay, sphere formation assay and in vivo mice tumor model were used to assess functional characteristics of EMT and stemness acquisition. TGF-β induced DNA demethylation was identified by methylation-specific PCR and bisulfite sequencing.
4c3880bb027f159e801041b1021e88e8 Result
Next-generation sequencing revealed significant changes in the expression of stem cell markers, CD44, CD87 and CD90 in both BEAS-2B and A549 cells. Functional analysis revealed increased wound healing, Matrigel invasion, sphere formation and in vivo mice tumor formation after TGF-β treatment. TGF-β induced EMT was associated with acquisition of stem-like characteristics. CD44, CD87 and CD90 were activated by either TGF-β and treatment with AZA. MSP showed decreased CD44, CD87 and CD90 promoter methylation after TGF-β treatment.
8eea62084ca7e541d918e823422bd82e Conclusion
These results suggest that TGF-β induces stem cell characteristics which are related with CD44, CD87 and CD90 reactivation by promoter demethylation.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P2.06 - Mesothelioma (Not CME Accredited Session) (ID 955)
- 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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P2.06-01 - Short-Term Outcome of Entire Pleural Intensity-Modulated Radiotherapy in a Neoadjuvant Setting for Malignant Mesothelioma (ID 13114)
16:45 - 18:00 | Author(s): Seung Joon Kim
- Abstract
Background
The purpose of this study is to evaluate the safety and efficacy of the tri-modality treatment with neoadjuvant intensity-modulated radiotherapy (IMRT) for a resectable clinical T1-3N0-1M0 malignant pleural mesothelioma (MPM).
a9ded1e5ce5d75814730bb4caaf49419 Method
A total of ten malignant mesothelioma patients who received neoadjuvant radiotherapy between March 2016 and April 2018 were reviewed. Patients received 25Gy in five fractions to entire ipsilateral hemithorax including clinically suspicious lymph nodes. All patients were treated with helical tomotherapy.
4c3880bb027f159e801041b1021e88e8 Result
All of the patients were men with a median age of 60 years. Epitheloid subtype was found in nine patients (90%) and type was unknown in one patient (10%). All patients received neoadjuvant chemotherapy with Alimta-cisplatin(AP) regimen. Nine patients (90%) completed 25Gy/5fxs radiotherapy and one (10%) completed 20Gy/4fxs. IMRT was well tolerated with only one acute grade 3 radiation pneumonitis. Surgery was performed one week (1 - 15 days, median 7.5) after completing IMRT. Extrapleural pneumonectomy (EPP) was performed in three patients (30%), and pleurectomy and decortications (PD) in six (60%). There was no grade 3+ surgical complication except one patient died from septic shock after EPP in one-month. Based on operative findings and pathologic stagings, adjuvant chemotherapy was delivered in six patients (60%), and one (10%) was decided to start adjuvant radiotherapy. After a median follow-up of 10.6 months (range 1.7 - 24.2), there is no evidence of local recurrence or distant metastasis.
8eea62084ca7e541d918e823422bd82e Conclusion
Neoadjuvant intensity-modulated radiotherapy (IMRT) can be safely delivered with a favorable radiation complication. An optimal strategy has to be made in resectable MPM patients who would benefit from neoadjuvant radiation and surgery. Further studies need to look at long-term outcomes.
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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P2.17-25 - Post-Treatment Neutrophil to Lymphocyte Ratio in Locally Advanced NSCLC Patients Treated with Concurrent Chemoradiotherapy (ID 12815)
16:45 - 18:00 | Author(s): Seung Joon Kim
- Abstract
Background
We aimed to investigate the relationship between NLR and prognosis in patients with locally advanced NSCLC who received concurrent chemoradiotherapy as the first line treatment.
a9ded1e5ce5d75814730bb4caaf49419 Method
We retrospectively analyzed 62 patients with locally advanced NSCLC treated with definitive CCRT between 2008 and 2016 at Seoul St. Mary’s hospital. We excluded patients who received induction chemotherapy to eliminate their influence on NLR. CCRT consisted of weekly chemotherapy using paclitaxel/carboplatin, docetaxel/cisplatin, docetaxel/carboplatin, and etoposide/cisplatin. Radiotherapy was performed with intensity-modulated radiotherapy (IMRT) or three-dimensional conformal RT (3D-CRT). The median radiation dose was 66 Gy in 33 fractions (range, 52 – 70 Gy). The pre-CCRT NLR was calculated from the nearest CBC within 1 week before CCRT and post-CCRT NLR was calculated using CBC 4 weeks after CCRT. Change of NLR before/after CCRT was also analyzed. The maximally selected log rank test was used to acquire the most significant NLR level related with overall survival (OS).
4c3880bb027f159e801041b1021e88e8 Result
The pre-, post-CCRT NLR, and NLR change (post-CCRT NLR/pre-CCRT NLR) cut-off levels were 1.9, 3.15, and 1.6, respectively. The median follow up duration was 11 months (range, 2–71 months). The 3-year OS, loco-regional progression free survival (LRPFS), and distant metastasis free survival (DMFS) were 45.4%, 9.3%, and 6.2%, respectively. The post-CCRT NLR and NLR change were significantly associated with OS and LRPFS. The high post-CCRT NLR group (> 3.15) showed significantly worse OS and LRPFS compared to the low post-CCRT NLR group (≤ 3.15) (3-year OS: 21.2% vs. 46.9%, p=0.005; median LRPFS: 7.7 months vs. 11.3 months, p=0.04). The high NLR change group (> 1.6) had significantly worse OS and LRPFS than the low NLR change group (≤ 1.6) (3-year OS: 32.7% vs. 36.9%, p=0.026; median LRPFS 7.7 months vs. 10.4 months, p=0.025). The pre-CCRT NLR showed a marginally significant difference in OS (3-year OS: 29.1% vs. 56.9%, p=0.062). There was no correlation between NLR and DMFS.
8eea62084ca7e541d918e823422bd82e Conclusion
The pre-, post-CCRT high NLR and increased NLR after CCRT are associated with poor prognosis of survival in patients for locally advanced NSCLC. An elevated NLR after CCRT might be an indicator of an increased risk of loco-regional failure. Further studies are needed to confirm the predictive value of NLR and the treatment strategies using NLR.
6f8b794f3246b0c1e1780bb4d4d5dc53
