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Chao-Chi Ho
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P2.13 - Targeted Therapy (Not CME Accredited Session) (ID 962)
- 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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P2.13-20 - The Comparative Effectiveness of Gefitinib Versus Erlotinib on the Intracranial Progression-Free Survival in Patients with Brain Metastasis (ID 11173)
16:45 - 18:00 | Author(s): Chao-Chi Ho
- Abstract
Background
The high peak plasma concentrations and better blood-brain barrier permeability of erlotinib compared with gefitinib was reported. However, there were few researches comparing their treatment effect for brain metastasis. This study aimed to investigate the comparative effectiveness of gefitinib versus erlotinib on the survival in patients with brain metastasis from lung adenocarcinoma.
a9ded1e5ce5d75814730bb4caaf49419 Method
Incident lung adenocarcinoma patients at National Taiwan University Hospital between Jan 2013 and May 2015 were reviewed and analyzed. The inclusion criteria were: (1) tumor harboring either EGFR exon 19 deletion or L858R mutation (2) patient taking gefitinib or erlotinib as their first-line treatment (3) patients with brain metastasis. Kaplan-Meier analyses with long-rank testing were used to estimate the intracranial progression-free survival (PFS) and overall survival between the gefitinib and erlotinib group. A Cox proportional hazard model was used to calculate the hazard ratio (HR) and 95% confidence intervals (CI) for age, gender, gefitinib vs. erlotinib, Eastern Cooperative Oncology Group performance status(ECOG), and pre-treatment for brain metastasis. Cumulative incidence of intracranial progression using competing risks regression model was also conducted.
4c3880bb027f159e801041b1021e88e8 Result
A total of 84 patients were included; 61 patients were female. 37 patients harbored EGFR exon 19 deletion. 39 patients received erlotinib as their first-line treatment.73 patients had Eastern Cooperative Oncology Group performance status scores of 0-1. 48 patients had multiple brain metastases (number >5) and 14 patients had brain metastasis ≥ 3 cm in size. 25 patients received whole brain radiation therapy and 7 patients received stereotactic radiosurgery before taking the tyrosine kinase inhibitors.
The median overall survival for the gefitinib group and the erlotinib group was 874 vs. 750 days (p=0.86, Fig 1), and the median intracranial PFS 652 vs. 833 days (p=0.38, Fig 2). Multivariable analysis indicated that erlotinib was associated with a better intracranial PFS. (HR: 0.34, 95% CI: 0.12-0.97). The competing risks regression model showed erlotinib was associated with a trend toward lower probability of intracranial progression, with adjusted subdistribution hazard ratio of 0.40 (95% CI, 0.16-1.03; p=0.06, Fig 3).
8eea62084ca7e541d918e823422bd82e Conclusion
In patients with brain metastasis from lung adenocarcinoma, this study showed the beneficial effectiveness of erlotinib on the intracranial progression-free survival compared with gefitinib.
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P3.03 - Biology (Not CME Accredited Session) (ID 969)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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P3.03-11 - Lung Cancer Stem Cells on Immune Modulation in Tumorous Microenvironment (ID 13866)
12:00 - 13:30 | Author(s): Chao-Chi Ho
- Abstract
Background
Cancer immunotherapy has made a big advance on benefit for cure the patients from malignancy. Recent hypothesis indicates that the crosstalk between cancer cells and tumor microenvironment can regulate the innate and adaptive immune system drives immunosuppressive condition for the immune escape of cancer cells.
a9ded1e5ce5d75814730bb4caaf49419 Method
Using genome-wide microarray and RNA-sequencing analysis, the immune-related gene profiling has been identified in the lung cancer stem cells (CSCs). The CSCs-condition medium was collected from the CSCs or CSCs/CAFs co-culture system to treat and analyze the functional responses of the tumor-associated macrophage (TAMs)/M2 macrophage and T cells populations. The flow cytometry and Q-PCR were used to validate the markers and related gene expression.
4c3880bb027f159e801041b1021e88e8 Result
We found that the tumor microenvironment is crucial to support the tumor malignancy and cancer stemness through paracrine networks (e.g., IGFII, HGF, LIF, IL-4/6/17, BMP-1/2, and CXCL6); as well as, the niche showed the impacts on the immune regulation. According to the genome-wide microarray and RNA-sequencing transcriptomic analysis of the lung cancer stem cells (CSCs), we have identified a cluster of genes and signaling involved in the immune modulation under the tumor microenvironment. Such CSCs-condition medium could significantly induce the interferon signaling, and immune checkpoints, CD274 and CD273 (PDL1 and PDL2), expression in CSCs. The population of tumor-associated macrophage (M2 population) from the malignant pleural effusion could be maintained via the CSCs-condition medium concentration-dependently. Most importantly, the population of the regulatory T cells (Treg) and the TAMs could be increased via the condition medium from CSCs; whereas, the CD8+ T-cells was significantly reduced. According to the transcriptomic/proteomic analysis of the CSCs and the niche, we have identified several important immune modulating signaling; affecting the paracrine and cytosine networks, which modulate the T cells population and may correlate with the immune escape of lung CSCs.
8eea62084ca7e541d918e823422bd82e Conclusion
Our results have identified the roles of CSCs on the immune modulation in the tumorous microenvironment, targeting on CSCs and related immune modulating signaling could be benefit for improving the antigen presentation and inhibit the immune checkpoints PDL1 and PDL2 expression in the combinatory anti-cancer immunotherapy.
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