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Yung-Hung Luo
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P1.11 - Patient Advocacy (ID 697)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Patient Advocacy
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.11-002 - Lung Cancer in Nonagenarian Patients (ID 7981)
09:30 - 09:30 | Author(s): Yung-Hung Luo
- Abstract
Background:
More than half lung cancer patients were aged more than 65-year-old. However the information in elderly patients is few, especially in nonagenarian (more than 90 year old).
Method:
We retrospectively collected clinical data of the lung cancer patient aged more than 90 year old between 2010 and 2014 in single medical center in Taiwan. The characteristics, treatment modality, and survival time were analyzed.
Result:
Eighty-three patients were enrolled: 76 patients (91.6%) were non-small cell carcinoma (NSCLC), and 7 patients (8.4%) were small cell carcinoma (SCLC), with the median overall survival (OS) of 30 and 13 weeks, p=0.005. Nine patients were stage I (10.8%), 4 patients were stage II (4.8%), 11 patients were stage III (13.3%), and 59 patients were stage IV (71.7%), with the median OS of 142, 79, 33, and 21 weeks for stage I, II, III, and IV, p<0.001. Better performance status (PS) had longer OS (median OS of 79, 66, 24, 12, and 3 weeks in PS of 0, 1, 2, 3, 4, p<0.001). Patients of simplified comorbidity score (SCS) >9 had shorter OS, but no statistical significance (median OS of 12 and 32 weeks in >9 and ≤ 9 group, p=0.065). For first-line treatment, 61.5% (8 in 13 stage I and II patients) received curative radiotherapy. For stage III patients, 63.6% (7 in 11 patients) received either radiotherapy or chemotherapy alone without concurrent chemo-radiotherapy; in stage IV, 59.3% (35 in 59 patients) received either chemotherapy or targeted therapy. Tumor EGFR mutation status in 30 of 46 stage IV non-squamous NSCLC patients: 55.6% was wild type and L858R was the most frequent. The response patterns in the E19D/L858R/G719X EGFR mutation under EGFR-TKI were 4 partial response, 5 stable disease, 1 progressive disease, and 3 patients were unevaluable (the response rate of 33.3% and the control rate of 75%). In 19 stage IV non-squamous NSCLC patients under EGFR-TKI, the EGFR mutated patients had longer OS than the wild type or unknown status (median OS of 36, 3, 22 weeks in EGFR mutated, wild type, and unknown status, p=0.018).
Conclusion:
Histology, staging, and ECOG PS had statistical significance affecting OS of nonagenarian patients. The lower SCS score patients had insignificant longer OS. The stage IV EGFR mutated non-squamous NSCLC patients under EGFR-TKI had longer OS than wild type or unknown status. Majority of nonagenarian patients could receive first line treatment, and it is important to find out the appropriate treatment for the “fit” patient.
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P3.02 - Biology/Pathology (ID 620)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 2
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.02-043 - Clinical and Genetic Features in Lung Adenocarcinoma Without EGFR Mutation and ALK Rearrangement in Taiwan (ID 9314)
09:30 - 09:30 | Author(s): Yung-Hung Luo
- Abstract
Background:
For the majority of advanced lung adenocarcinoma patients, absence of epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearrangement usually means platinum based doublet chemotherapy would be the standard treatment. However, treatment result of chemotherapy is suboptimal. Several driver mutations, although not common, are potential therapeutic targets which may significantly influence patients’ outcome.
Method:
Lung adenocarcinoma patients with neither EGFR mutation nor ALK fusion were recruited in this study. KRAS, NRAS and BRAF mutations were examined by mass spectrometry. Other 53 gene fusions and mutations were analyzed by Archer FusionPlex Solid Tumor Kit on Ion Torrent PGM next generation sequencer.
Result:
Forty patients were enrolled. Demographics showed a median age of 62.5 (39-88), male predominance (M/F, 24/16), and non-smoking history dominance (never/past/current, 19/9/12). The average pack-year of smoking was 22.1 (0-120). The specimens examined were from lung (20), bone (1), brain (3), pleura (1), pleural effusion (11), lymph node (2) and soft tissue (2), respectively. Collectively, we identified eight KRAS mutations (20%), one NRAS mutation (2.5%), one BRAF mutation (2.5%), one CD74-ROS-1 fusion (2.5%), two MET exon 14 splicing (5%), and all of them were mutually exclusive. There were three invasive mucinous adenocarcinomas, and two of them harbored KRAS mutation. The majority of patients had received chemotherapy and two had received immunotherapy. The patient with CD74-ROS-1 fusion, a female non-smoker, was enrolled in an entrectinib clinical trial (STARTRK2) and experienced a rapid and dramatic response.
Conclusion:
Survey for other driver mutations brings treatment options for lung adenocarcinoma patients without EGFR mutation and ALK rearrangement.
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P3.02-070 - Investigation of Whether HIF-1α Inhibitors Can Increase EGFR-TKI Effect for Non-Small Cell Lung Cancer Cell Lines (ID 9492)
09:30 - 09:30 | Presenting Author(s): Yung-Hung Luo
- Abstract
Background:
Hypoxia-inducible factor-1α (HIF-1α) plays a crucial role in cancer progression, metastasis and angiogenesis. Activation HIF–1α pathway is also associated with epithelial growth factor receptor (EGFR) pathways. This study was to investigate whether inhibitors of HIF–1α increase the cytotoxicity of EGFR-tyrosine kinase inhibitors (TKI) on non-small cell lung cancer (NSCLC) and its mechanism.
Method:
NSCLC lines, including A549, Hcc827, Hcc827R, H460, PC-9, H23, H1299, C339, H3255, and H1975 were used as in vitro experiments. Western blot was used to observe expression of HIF-1α. MTT assay was used to investigate effects of different drug concentrations. The combination of EGFR-TKI (gefitinib) and HIF-1α inhibitors was used in EGFR wild-type, and EGFR- mutant cell lines. The combination index (CI) was used to determine the effect of drug combination. The mean CI (mCI) values more than 1.05 or less than 0.95 were defined as antagonism or synergism, respectively.
Result:
Western blot showed that HIF-1α expression was relatively high in EGFR- mutant cell lines and relatively low in EGFR wild-type cell lines. Under normoxia, HIF-1α expression increased in Hcc827 and H460 cell lines. Under hypoxia, HIF-1α expression increased in Hcc827R and H1975 cell lines. MTT assay showed that gefitinib was found to be superior to HIF-1α inhibitors in cytotoxicity effect on EGFR-TKI-sensitive NSCLC lines (PC9, Hcc827, C339, H3255). HIF-1α inhibitor was relatively better than gefitinib in cytotoxicity effect on EGFR-TKI-insensitive NSCLC cell lines (A549, H23, H460, H1299, Hcc827R, H1975). Under normoxia or hypoxia, cytotoxicity effect of HIF-1α inhibitor on EGFR-TKI-insensitive NSCLC cell lines (Hcc827R, H1975, A549, H460) was relatively better than gefitinib. Of five cell lines, including A549, Hcc827, Hcc827R, H460 and PC-9, their CI values for Gefitinib/HIF-1α inhibitor were 1.00, 0.925, 1.32, 0.76 and 1.23, respectively under normoxia. Data showed that cytotoxicity effect of HIF-1α inhibitor antagonized with gefitinib in Hcc827R and PC-9 cell lines. However, cytotoxicity effect of HIF-1α inhibitor synergized with gefitinib in the Hcc827, and H460 cell line. Of four cell lines, including A549, Hcc827, Hcc827R, and H460, their CI values for Gefitinib/HIF-1α inhibitor were 1.23, 1.17, 1.02, and 1.08, respectively under hypoxia. In this study, increased expression of HIF-1α in Hcc827 and H460 under normoxia may be related to synergistic cytotoxicity effect of HIF-1α inhibitors and gefitinib.
Conclusion:
HIF-1α inhibitors demonstrated anti-NSCLC activity in vitro and a selectively synergistic effect with gefitinib in EGFR-TKI-insensitive NSCLC cell line (H460). Our study suggested a potential treatment approach using HIF-1α inhibitors plus gefitinib.
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P3.07 - Immunology and Immunotherapy (ID 723)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.07-011 - Investigation of Autologous Tumor-Killing Effect of Effusion-Associated Lymphocytes in Malignant Pleural Effusion of Lung Cancer (ID 9513)
09:30 - 09:30 | Presenting Author(s): Yung-Hung Luo
- Abstract
Background:
Many lung cancer patients developed malignant pleural effusion during the course of the disease. Previous studies revealed that the effusion associated lymphocytes (EAL) were in dysfunctional state which appeared to be immunosuppressed and unable to kill tumor cells. This study will evaluate the combined effects of IL-2, IL-12, αCD3 antibody (ab), and PD-1 ab on antitumor activity of lymphocytes. The underlying mechanism and relevant immune biomarkers will also be investigated.
Method:
We choose the malignant pleural effusion from lung cancer patients to analyze the association among lymphocytes, cancer cells, and cytokines in order to realize the lymphocyte immunity in the malignant pleural effusion of lung cancer patients. Flow cytometry was used to determined lymphocyte subpopulation. The Proliferation assay was performed to evaluate the effect of medication on lymphocytes. ELISA was used to evaluate cytokine level. Cell-mediated cytotoxicity assay was performed to evaluate the tumor-killing effect of EAL.
Result:
EAL were isolated from 21 malignant pleural effusions. Lymphocyte subpopulation was determied by flow cytometry, and total lymphocytes were composed of 8.9% exhausted T cells (CD3+/CD8+/ PD-1+), and 27.8% PD1+ NK cells. IL-2+αCD3 ab+pembrolizumab has demonstrated the trend toward to enhance the proliferation of EAL. IL-2+αCD3 ab or IL-2+IL-12+αCD3 ab or IL-2+IL-12+αCD3 ab+pembrolizumab demonstrated the trend for EAL to produce more IFN-γ. IL-2+αCD3 ab or IL-2+IL-12+αCD3 ab demonstred the trend for EAL to produce more IL-10. IL-2+αCD3+pembrolizumab did not demonstrated the trend for EAL to produce more IL-10. The addition of IL-2+αCD3 ab or IL-2+pembrolizumab showed the trend toward increased EAL cytolytic activity against autologous tumors (effector:target cells= 30:1). The addition of IL-2+αCD3 ab did not show the trend toward increased EAL cytolytic activity against autologous tumors in different conditions (effector:target cells= 10:1). The addition of IL-2+αCD3 ab or IL-12+αCD3 ab or IL-2+IL-12+αCD3 ab showed the trend toward increased EAL cytolytic activity against autologous tumors (effector:target cells= 3:1).
Conclusion:
The depressed cellular function of EAL may be potentially reversed with multiple signal stimulation, including IL-2 plus αCD3 ab, IL-2 plus pembrolizumab, IL-12 plus αCD3 ab or IL-2 plus IL-12 and αCD3 ab. Further studies are warranted in order to confirm the synergistic cytotoxicity effect of cytokines plus PD-1 inhibitors.
