The Association of Acquired T790M Mutation with Clinical Characteristics after Resistance to First-Line Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor in Lung Adenocarcinoma

Yen-Hsiang Huang,Kuo-Hsuan Hsu,Jeng-Sen Tseng,Kun-Chieh Chen,Chia-Hung Hsu,Kang-Yi Su,Jeremy J. W. Chen,Huei-Wen Chen,Sung-Liang Yu,Tsung-Ying Yang,Gee-Chen Chang 대한암학회 2018 Cancer Research and Treatment Vol.50 No.4

Purpose The main objective of this study was to investigate the relationship among the clinical characteristics and the frequency of T790M mutation in advanced epidermal growth factor receptor (EGFR)mutant lung adenocarcinoma patients with acquired resistance after firstline EGFRtyrosine kinase inhibitor (TKI) treatment. Materials and Methods We enrolled EGFR-mutant stage IIIB-IV lung adenocarcinoma patients, who had progressed to prior EGFR-TKI therapy, and evaluated their rebiopsy EGFRmutation status. Results A total of 205 patients were enrolled for analysis. The overall T790M mutation rate of rebiopsy was 46.3%. The T790M mutation rates among patients with exon 19 deletion mutation, exon 21 L858R point mutation, and other mutations were 55.0%, 37.3%, and 27.3%, respectively. Baseline exon 19 deletion was associated with a significantly higher frequency of T790M mutation (adjusted odds ratio, 2.14; 95% confidence interval [CI], 1.20 to 3.83; p=0.010). In the exon 19 deletion subgroup, there was a greater prevalence of T790M mutation than other exon 19 deletion subtypes in patients with the Del E746-A750 mutation (61.6% vs. 40.6%; odds ratio, 2.35; 95% CI, 1.01 to 5.49; p=0.049). The progression- free survival (PFS) of first-line TKI treatment > 11 months was also associated with a higher T790M mutation rate (54.1% vs. 39.3%; adjusted odds ratio, 1.82; 95% CI, 1.02 to 3.25; p=0.044). Patients who underwent rebiopsy at metastatic sites had more chance to harbor T790M mutation (52.6% vs. 33.8%; adjusted odds ratio, 1.97; 95% CI, 1.06 to 3.67; p=0.032). Conclusion PFS of first-line EGFR-TKI, rebiopsy site, EGFR exon 19 deletion and its subtype Del E746- A750 mutation are associated with the frequency of T790M mutation.

The Clinical Outcomes of Different First-Line EGFR-TKIs Plus Bevacizumab in Advanced EGFR-Mutant Lung Adenocarcinoma

Yen-Hsiang Huang,Kuo-Hsuan Hsu,Chun-Shih Chin,Jeng-Sen Tseng,Tsung-Ying Yang,Kun-Chieh Chen,Kang-Yi Su,Sung-Liang Yu,Jeremy J.W. Chen,Gee-Chen Chang 대한암학회 2022 Cancer Research and Treatment Vol.54 No.2

Purpose The aim of this study was to investigate the efficacy of various epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitors (TKIs) plus bevacizumab in advanced EGFR-mutant lung adenocarcinoma patients. Materials and Methods From August 2016 to October 2020, we enrolled advanced lung adenocarcinoma patients harboring exon 19 deletion or L858R receiving gefitinib, erlotinib and afatinib plus bevacizumab as the first-line treatment for the purposes of analysis. Results A total of 36 patients were included in the final analysis. Three patients received gefitinib, 17 received erlotinib, and 16 received afatinib combined with bevacizumab as the first-line treatment. The objective response rate was 77.8%, and disease control rate was 94.4%. The overall median progression-free survival (PFS) was 16.4 months, while the median PFS was 17.1 months in patients with exon 19 deletion, and 16.2 months in patients with L858R mutation (p=0.311). Regarding the use of different EGFR-TKIs, the median PFS was 17.1 months in the erlotinib group and 21.6 months in the afatinib group (p=0.617). In patients with brain metastasis at baseline, the median PFS was 18.9 months in the erlotinib group and 16.4 months in the afatinib group (p=0.747). Amongst patients harboring exon 19 deletion, the median PFS was 16.2 months in the erlotinib group and not-reached in the afatinib group (p=0.141). In patients with L858R mutation, the median PFS was 18.9 months in the erlotinib group and 16.2 months in the afatinib group (p=0.481). Conclusion Our research demonstrates that not only erlotinib combined with bevacizumab, but also afatinib plus bevacizumab as first-line treatment, provides solid clinical efficacy in advanced EGFR-mutant lung adenocarcinoma patients. PurposeThe aim of this study was to investigate the efficacy of various epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitors (TKIs) plus bevacizumab in advanced <i>EGFR</i>-mutant lung adenocarcinoma patients.Materials and MethodsFrom August 2016 to October 2020, we enrolled advanced lung adenocarcinoma patients harboring exon 19 deletion or L858R receiving gefitinib, erlotinib and afatinib plus bevacizumab as the first-line treatment for the purposes of analysis.ResultsA total of 36 patients were included in the final analysis. Three patients received gefitinib, 17 received erlotinib, and 16 received afatinib combined with bevacizumab as the first-line treatment. The objective response rate was 77.8%, and disease control rate was 94.4%. The overall median progression-free survival (PFS) was 16.4 months, while the median PFS was 17.1 months in patients with exon 19 deletion, and 16.2 months in patients with L858R mutation (p=0.311). Regarding the use of different EGFR-TKIs, the median PFS was 17.1 months in the erlotinib group and 21.6 months in the afatinib group (p=0.617). In patients with brain metastasis at baseline, the median PFS was 18.9 months in the erlotinib group and 16.4 months in the afatinib group (p=0.747). Amongst patients harboring exon 19 deletion, the median PFS was 16.2 months in the erlotinib group and not-reached in the afatinib group (p=0.141). In patients with L858R mutation, the median PFS was 18.9 months in the erlotinib group and 16.2 months in the afatinib group (p=0.481).ConclusionOur research demonstrates that not only erlotinib combined with bevacizumab, but also afatinib plus bevacizumab as first-line treatment, provides solid clinical efficacy in advanced <i>EGFR</i>-mutant lung adenocarcinoma patients.

Determining Genome Size and Ploidy in Morus by Flow Cytometry

Lan-Yen Chang,Jer-Chia Chang,Mei-Chu Chung,Wen-Ju Yang,Kuo-Tan Li,Ming-Wen Chang 한국원예학회 2008 한국원예학회 기타간행물 Vol.- No.-

Simulation of Axisymmetric Scramjet Combustion Flowfields Using Weno Navier-Stokes Solvers

Jaw-Yen Yang,J.C. Huang,Y S. Lai,C. S. Kuo 한국전산유체공학회 2014 한국전산유체공학회 학술대회논문집 Vol.2014 No.10

This study is based on the theory of gas dynamics and uses the Navier-Stokes equations as the governing equations to solve the fluid flow field problems of the scramjet. For the turbulent flow, we use the simple Spalart-Allmaras one equation turbulence model (S-A model) which produces better results for near wall and boundary layer flow field problems. The lower-upper symmetric Gauss-Seidel (LU-SGS) implicit scheme, whose results converge efficiently under steady state conditions, is combined with the Weighted Essentially Non-Oscillatory (WENO) scheme to construct a numerical model of the scramjet. Using the WENO scheme’s high-order accuracy and its non-oscillatory solution at discontinuous areas, we can solve supersonic flow field problems with multiple shock wave interactions. This simulation procedure is verified against two partial examples from literature to ensure its accuracy, and is then applied to a complete geometric model of a scramjet with different initial conditions for a full flow field analysis. The Mach number, density, static temperature and pressure are found and the results discussed. It is found that even when the shock waves are very close to each other, the WENO scheme produces better simulation results than other numerical approaches.

Serotonin Modulates the Correlations between Obsessive-compulsive Trait and Heart Rate Variability in Normal Healthy Subjects: A SPECT Study with [123I]ADAM and Heart Rate Variability Measurement

Che Yu Kuo,Kao Chin Chen,I Hui Lee,Huai-Hsuan Tseng,Nan Tsing Chiu,Po See Chen,Yen Kuang Yang,Wei Hung Chang 대한정신약물학회 2022 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.20 No.2

Objective: The impact of serotonergic system on obsessive-compulsive disorder (OCD) is well studied. However, the correlation between OC presentations and autonomic nervous system (ANS) is still unclear. Furthermore, whether the correlation might be modulated by serotonin is also uncertain. Methods: We recruited eighty-nine healthy subjects. Serotonin transporter (SERT) availability by [123I]ADAM and heart rate variability (HRV) tests were measured. Symptoms checklist-90 was measured for the OC presentations. The interaction between HRV and SERT availability were calculated and the correlation between HRV and OC symptoms were analyzed after stratified SERT level into two groups, split at medium. Results: The interactions were significant in the factors of low frequency (LF), high frequency (HF), and root mean square of successive differences (RMSSD). Furthermore, the significantly negative correlations between OC symptoms and the above HRV indexes existed only in subjects with higher SERT availability. Conclusion: OC symptoms might be correlated with ANS regulations in subjects with higher SERT availability.

Intercalated Treatment Following Rebiopsy Is Associated with a Shorter Progression-Free Survival of Osimertinib Treatment

Jeng-Sen Tseng,Tsung-Ying Yang,Kun-Chieh Chen,Kuo-Hsuan Hsu,Yen-Hsiang Huang,Kang-Yi Su,Sung-Liang Yu,Gee-Chen Chang 대한암학회 2018 Cancer Research and Treatment Vol.50 No.4

Purpose Epidermal growth factor receptor (EGFR) T790M mutation serves as an important predictor of osimertinib efficacy. However, little is known about how it works among patients with various timings of T790M emergence and treatment. Materials and Methods Advanced EGFR-mutant lung adenocarcinoma patients with positive T790M mutation in tumor were retrospectively enrolled and observed to determine the outcomes of osimertinib treatment. We evaluated the association between patients’ characteristics and the efficacy of osimertinib treatment, particularly with respect to the timing of T790M emergence and osimertinib prescription. Results A total of 91 patients were enrolled, including 14 (15.4%) with primary and 77 (84.6%) with acquired T790M mutation. The objective response rate and disease control rate were 60.9% and 85.1%, respectively. The median progression-free survival (PFS) and overall survival were 11.5 months (95% confidence interval [CI], 9.0 to 14.0) and 30.4 months (95% CI, 11.3 to 49.5), respectively. There was no significant difference in response rate and PFS between primary and acquired T790M populations. In the acquired T790M subgroup, patients who received osimertinib after T790M had been confirmed by rebiopsy had a longer PFS than those with intercalated treatments between rebiopsy and osimertinib prescription (14.0 months [95% CI, 9.0 to 18.9] vs. 7.2 months [95% CI, 3.7 to 10.8]; adjusted hazard ratio, 0.48 [95% CI, 0.24 to 0.98; p=0.043]). Rebiopsy timing did not influence the outcome. Conclusion Osimertinib prescription with intercalated treatment following rebiopsy but not the timing of T790M emergence influenced the treatment outcome. We suggest that it is better to start osimertinib treatment once T790M mutation has been confirmed by biopsy.

FDG PET or PET/CT in Evaluation of Renal Angiomyolipoma

Chun-Yi Lin,Hui-Yi Chen,Hueisch-Jy Ding,Kuo-Yang Yen,Chia-Hung Kao 대한영상의학회 2013 Korean Journal of Radiology Vol.14 No.2

Objective: Angiomyolipoma is the most common benign kidney tumor. However, literature describing FDG PET findings on renal angiomyolipoma (AML) is limited. This study reports the FDG PET and PET/CT findings of 21 cases of renal AML. Materials and Methods: The study reviews FDG PET and PET/CT images of 21 patients diagnosed with renal AML. The diagnosis is based on the classical appearance of an AML on CT scan with active surveillance for 6 months. The study is focused on the observation of clinical and radiographic features. Results: Six men and 15 women were included in our study. The mean age of the patients was 57.14 ± 9.67 years old. The mean diameter of 21 renal AML on CT scans was 1.76 ± 1.00 cm (Min: 0.6 cm; Max: 4.4 cm). CT scans illustrated renal masses typical of AMLs, and the corresponding FDG PET scans showed minimal FDG activities in the area of the tumors. None of the 21 AMLs showed a maximum standardized uptake value (SUVmax) greater than 1.98. No statistically significant correlation was present between SUVmax and tumor size. Conclusion: Renal AMLs demonstrate very low to low uptake on FDG PET and PET/CT imaging in this study. When a fatcontaining tumor in the kidney is found on a CT scan, it is critical to differentiate an AML from a malignant tumor including an RCC, liposarcoma, and Wilms tumor. This study suggests that FDG PET or PET/CT imaging is useful for differentiating a renal AML from a fat-containing malignant tumor.

Effect of Active Synthetic 2-Substituted Quinazolinones on Anti-Platelet Aggregation and the Inhibition of Superoxide Anion Generation by Neutrophils

Chang, Fang-Rong,Wu, Chin-Chung,Hwang, Tsong-Long,Patnam, Ramesh,Kuo, Reen-Yen,Wang, Wei-Ya,Lan, Yu-Hsuan,Wu, Yang-Chang The Pharmaceutical Society of Korea 2003 Archives of Pharmacal Research Vol.26 No.7

Quinazolinones, 2-substituted and 3-substituted, mainly synthesized by microwave irradiation, were subjected to anti-platelet aggregation and inhibition of superoxide anion generation assays. Interestingly, 2-phenyl-4-quinazolinone (4) exhibited significant inhibitory activities toward platelet aggregation and neutrophil activation, and it might therefore serve as a prototype lead compound.

Detecting small lung tumors in mouse models by refractive-index microradiology

Chien, Chia-Chi,Zhang, Guilin,Hwu, Y.,Liu, Ping,Yue, Weisheng,Sun, Jianqi,Li, Yan,Xue, Hongjie,Xu, Lisa X.,Wang, Chang Hai,Chen, Nanyow,Lu, Chien Hung,Lee, Ting-Kuo,Yang, Yuh-Cheng,Lu, Yen-Ta,Ching, Y Springer-Verlag 2011 ANALYTICAL AND BIOANALYTICAL CHEMISTRY Vol.401 No.3