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.

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.

Creatine Kinase (CK)-MB-to-Total-CK Ratio: a Laboratory Indicator for Primary Cancer Screening

Chang, Chih-Chun,Liou, Ching-Biau,Su, Ming-Jang,Lee, Yi-Chen,Liang, Chai-Ting,Ho, Jung-Li,Tsai, Huang-Wen,Yen, Tzung-Hai,Chu, Fang-Yeh Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.15

Background: For the determination of creatine kinase (CK)-MB, the immunoinhibition method is utilized most commonly. However, the estimated CK-MB activity may be influenced by the presence of CK isoenzymes in some conditions like cancer. Thus, a CK-MB-to-total-CK ratio more than 1.0 could be found in such a situation. The study aimed to explore the relationship of cancer to high CK-MB-to-total-CK ratio. Materials and Methods: From January 2011 to December 2014, laboratory data on all CK-MB and total CK test requests were extracted at Far Eastern Memorial Hospital (88,415 requests). Patients with a CK-MB-to-total-CK ratio more than 1.0 were registered in this study. Clinical data including tumor location, tumor TNM stage and metastatic status were also collected. Results: A total of 846 patients were identified with a CK-MB-to-total-CK ratio more than 1.0. Of these, 339 (40.1%) were diagnosed with malignancies. The mean CK-MB-to-total-CK ratio was significantly higher in malignancy than in non-malignancy ($1.35{\pm}0.28$ vs $1.25{\pm}0.23$, p<0.001) groups. The most frequent malignancy with a CK-MB-to-total-CK ratio more than 1.0 was colorectal cancer ($1.42{\pm}0.28$, 16.5%, n=56), followed by lung cancer ($1.38{\pm}0.24$, 15.9%, n=54) and hepatocellular carcinoma (14.5%, n=49). Higher CK-MB-to-total-CK ratios in hematological malignancies ($1.44{\pm}0.41$)were also noted. Additionally, the CK-MB-to-total-CK ratio was markedly higher in advanced stage malignancy than in early stage ($1.37{\pm}0.26$ vs. $1.29{\pm}0.31$, p=0.014) and significantly higher in liver metastasis than in non-liver metastasis ($1.48{\pm}0.30$ vs. $1.30{\pm}0.21$, p<0.001). Conclusions: The CK-MB-to-total-CK ratio is an easily available indicator and could be clinically utilized as a primary screening tool for cancer. Higher ratio of CK-MB-to-total-CK was specifically associated with certain malignancies, like colorectal cancer, lung cancer and hepatocellular carcinoma, as well as some cancer-associated status factors such as advanced stage and liver metastasis.

Improving discharge uniformity of industrial-scale very high frequency plasma sources by launching a traveling wave

Hsin-Liang Chen,Yen-Cheng Tu,Cheng-Chang Hsieh,Deng-Lain Lin,Chin-Jung Chang,Keh-Chyang Leou 한국물리학회 2016 Current Applied Physics Vol.16 No.7

Very high frequency (VHF) PECVD has been demonstrated to be able to significantly increase the deposition rate without compromising the film quality for the manufacture of silicon heterojunction and silicon thin film solar cells. To further reduce the production costs by enhancing the throughput, larger electrode and higher frequency are often required at the same time. Nevertheless, raising frequency in large-area PECVD results in non-uniform discharge caused by the standing wave effect and deteriorates the processing uniformity. In this study, a technique that generates a traveling wave via superposing two specific standing waves launched simultaneously is proposed to resolve this issue. An industrial-scale linear plasma reactor with length and width of 125 and 10 cm, respectively, is adopted for experimental tests and two 80 MHz power supplies are utilized to separately control the standing waves. The experimental results show that the discharge gap is only partially covered by plasma discharge when only one standing wave is applied. However, as both standing waves are launched, the non-uniformity of plasma discharge can be effectively reduced to <±5%. In addition, numerical simulation is also conducted in this study to clarify whether the proposed technique can be applied to large-area rectangular PECVD (substrate size: 1.4 m 1.1 m). By arranging multiple feeding points on opposite sides of the powered electrode, the simulation results indicate the non-uniformity of electric field can be maintained within ±10%.

Influence of doping and annealing temperature on the structural and optical properties of Mg2SiO4:Eu3þ synthesized by combustion method

Hsin-Liang Chen,Yen-Cheng Tu,Cheng-Chang Hsieh 한국물리학회 2016 Current Applied Physics Vol.16 No.7

This paper presents the structural and optical properties of europium doped magnesium orthosilicate nanophosphor prepared by combustion method and further annealed at varying temperatures. The structural and optical properties were investigated by using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Field emission scanning electron microscope (FESEM), High resolution Transmission electron microscope (HRTEM), Diffuse Reflectance Spectra (DRS) and Photoluminescence spectra (PL) together with decay time. The XRD results confirmed the phase formation of Mg2SiO4. FESEM and TEM results indicated spherical particles in nanometer size. Photoluminescence spectra of Mg2SiO4:Eu3þ nanophosphors exhibited five groups of peaks 5D0 / 7FJ (J ¼ 0, 1, 2, 3, 4) transitions. Intensity parameters (U2 U4) and other radiative properties such as radiative transition probability, total radiative transition probability, radiative life time, branching ratio and stimulated emission cross-section were calculated using Judd- Ofelt theory. The lifetime measurement indicates a decreasing trend up to 5 mol% of Eu3þ concentration.

Light-Emitting Diode-Assisted Narrow Band Imaging Video Endoscopy System in Head and Neck Cancer

Hsin-Jen Chang,Wen-Hung Wang,Yen-Liang Chang,Tzuan-Ren Jeng,Chun-Te Wu,Ludovic Angot,Chun-Hsing Lee,Pa-Chun Wang 대한소화기내시경학회 2015 Clinical Endoscopy Vol.48 No.2

Background/Aims: To validate the effectiveness of a newly developed light-emitting diode (LED)-narrow band imaging (NBI) system for detecting early malignant tumors in the oral cavity. Methods: Six men (mean age, 51.5 years) with early oral mucosa lesions were screened using both the conventional white light and LED-NBI systems. Results: Small elevated or ulcerative lesions were found under the white light view, and typical scattered brown spots were identified after shifting to the LED-NBI view for all six patients. Histopathological examination confirmed squamous cell carcinoma. The clinical stage was early malignant lesions (T1), and the patients underwent wide excision for primary cancer. This is the pilot study documenting the utility of a new LED-NBI system as an adjunctive technique to detect early oral cancer using the diagnostic criterion of the presence of typical scattered brown spots in six high-risk patients. Conclusions: Although large-scale screening programs should be established to further verify the accuracy of this technology, its lower power consumption, lower heat emission, and higher luminous efficiency appear promising for future clinical applications.

The EGF/hnRNP Q1 axis is involved in tumorigenesis via the regulation of cell cycle-related genes

Yu-Chu Wang,Kung-Chao Chang,Bo-Wen Lin,Jenq-Chang Lee,Chien-Hsien Lai,Li-Jyuan Lin,Yun Yen,Chang-Shen Lin,Shiang-Jie Yang,Peng-Chan Lin,Chung-Ta Lee,Liang-Yi Hung 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-

Heterogeneous nuclear ribonucleoprotein (hnRNP) Q1, an RNA-binding protein, has been implicated in many posttranscriptional processes, including RNA metabolism and mRNA splicing and translation. However, the role of hnRNP Q1 in tumorigenesis remains unclear. We previously performed RNA immunoprecipitation (RIP)-seq analysis to identify hnRNP Q1-interacting mRNAs and found that hnRNP Q1 targets a group of genes that are involved in mitotic regulation, including Aurora-A. Here, we demonstrate that altering the hnRNP Q1 level influences the expression of the Aurora-A protein, but not its mRNA. Stimulation with epidermal growth factor (EGF) enhances both binding between hnRNP Q1 and Aurora-A mRNA as well as the efficacy of the hnRNP Q1-induced translation of Aurora-A mRNA. The EGF/hnRNP Q1-induced translation of Aurora-A mRNA is mediated by the mTOR and ERK pathways. In addition, we show that hnRNP Q1 up-regulates the translation of a group of spindle assembly checkpoint (SAC) genes. hnRNP Q1 overexpression is positively correlated with the levels of Aurora-A and the SAC genes in human colorectal cancer tissues. In summary, our data suggest that hnRNP Q1 plays an important role in regulating the expression of a group of cell cycle-related genes. Therefore, it may contribute to tumorigenesis by up-regulating the translation of these genes in colorectal cancer.

The Outcome of Antipsychotics-induced Tardive Syndromes: A Ten-year Follow-up Study

Pei-Chien Chou,Yu Lee,Yung-Yee Chang,Pao-Yen Lin,Liang-Jen Wang 대한정신약물학회 2023 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.21 No.3

Objective: Tardive syndrome (TS) is an umbrella term used to describe a group of abnormal movement disorders caused by chronic exposure to dopamine receptor blocking agents. Few follow-up studies have been performed on the outcome of TS in patients using antipsychotics. The purpose of our study was to investigate the prevalence, incidence, remission rate, and factors associated with remission in patients using antipsychotics. Methods: This retrospective cohort study consisted of 123 patients who received continuous treatment of antipsychotics in a medical center in Taiwan, from April 1, 2011 to May 31, 2021. We assessed the demographic and clinical characteristics, prevalence, incidence, remission rate, and factors associated with remission in patients using antipsychotics. TS remission was defined as a Visual Analogue Scale score ≤ 3. Results: Of the 92 patients who completed the 10-year follow-up, 39 (42.4%) were found to have at least one episode of TS, with tardive dyskinesia (TD) being the most prevalent subtype (51.3%). With regard to concurrent physical illness, a history of extrapyramidal symptoms were significant risk factors for TS. During the 10-year follow-up period, the remission rate of TS was 74.3%. The use of antioxidants including vitamin B6 and piracetam was related to the remission of TS. Patients with tardive dystonia had a higher remission rate (87.5%) compared to TD (70%). Conclusion: Our study suggests that TS may be a treatable condition, and the key to a better outcome is early detection and prompt intervention, including closely monitoring antipsychotics-related TS symptoms and using antioxidants.

Preparation and characterization of superhydrophobic coatings

Hsing-I Hsiang,Ming-Tsai Liang,Yu-Lun Chang,Hung-Chin Huang,Fu-Su Yen 한양대학교 세라믹연구소 2010 Journal of Ceramic Processing Research Vol.11 No.3

To obtain a surface with water-repelling and self-cleaning abilities attracts much interest in the nanotechnology age. In this study, a perfluroalkyl surfactant (perflurodecanoic acid, PFDA) was coated on nano-sized boehmite surfaces to obtain hydrophobic nano-particles via surface modification. Then the hydrophobic boehmite was coated on a transparent plastic film using spin-coating to obtain a hydrophobic film. The effects of various amounts of hydrophobic polymer on the adsorption behavior and contact angle for hydrophobic properties were investigated using FTIR, and a contact-angle meter. The adsorption of PFDA onto the surface of boehmite takes place through ionic bonding. The contact angles of the thin film prepared by spin coating PFDA-modified-boehmite on glass substrates were above 150o as the adsorption of PFDA onto the surface of boehmite reached saturation.

Sexual Abuse Is Associated With an Abnormal Psychological Profile and Sleep Difficulty in Patients With Irritable Bowel Syndrome in Taiwan

( Hsing-feng Lee ),( Pei-yi Liu ),( Yen-po Wang ),( Chia-fen Tsai ),( Full-young Chang ),( Ching-liang Lu ) 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2018 Journal of Neurogastroenterology and Motility (JNM Vol.24 No.1

Background/Aims Both sexual and physical abuse history have been reported to be associated with irritable bowel syndrome (IBS) in Western countries. The impact of abuse history in IBS patients in Asia remains unclear. We aim to determine the prevalence of abuse history, its associated psychological profiles, and sleep problems among IBS patients in Taiwan. Methods In total, 194 Rome III-defined IBS patients were invited to participate. Age- and sex- matched healthy carriers of chronic hepatitis B or hepatitis C without chronic abdominal symptoms were identified as disease-controls. We administered a validated questionnaire to evaluate bowel symptoms, physical/sexual abuse history, anxiety/depression (Hospital Anxiety and Depression Scale [HADS]), and sleep quality. Results IBS patients had a significantly higher prevalence of sexual abuse history than the disease-control group both before (16.5% vs 6.7%, P < 0.05) and after (16.0% vs 6.6%, P < 0.05) adolescence. These significant differences were mainly observed in women (13.4% vs 3.4%, P < 0.05). No difference was noted in history of physical abuse between the 2 groups. IBS patients with a history of sexual abuse had significantly higher HADS scores and higher frequencies of sleep difficulty than those without. Conclusions In Taiwan, sexual abuse history was more prevalent in female IBS patients than controls. Sexual abuse history may contribute to higher anxiety/depression levels and sleep difficulties, which are commonly experienced in IBS patients. In Asia, abuse history should be obtained when approaching IBS patients to facilitate better management. (J Neurogastroenterol Motil 2018;24:79-86)