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.

Switching from Tenofovir Disoproxil Fumarate (TDF) or Other Oral Antiviral Therapy (OAV) to Tenofovir Alafenamide (TAF) in Virally Suppressed CHB Patients with Hepatic Impairment

( Sang Hoon Ahn ),( Young-Suk Lim ),( Pietro Lampertico ),( Ho Bae ),( Wan-Long Chuang ),( Jeong Heo ),( Yi-Hsiang Huang ),( Aric Josun Hui ),( Chun-Yen Lin ),( Claire Fournier ),( Chien-Hung Chen ),( 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: TAF, a novel tenofovir (TFV) prodrug, has greater plasma stability, more targeted delivery of TFV to hepatocytes, and reduced circulating levels of TFV compared to TDF. We evaluated efficacy and safety when virally suppressed CHB (Chronic Hepatitis B) patients with hepatic impairment were switched to TAF. Methods: In this Phase 2 study (NCT03180619) CHB patients with a ChildTurcottePugh (CTP) score of ³7 and £12 at screening (or past history of CTP ³7 and any score £12 at screening) who were taking TDF and/or other OAVs for ³48 weeks, with HBV DNA <LLOQ for ³24 weeks and <20 IU/mL at screening were eligible. All patients were switched to TAF 25 mg QD and treated for 96 weeks. The co-primary endpoints were proportion with HBV DNA <20 IU/mL and graded adverse events (AEs)/lab abnormalities at Week 24. Results: 31 patients were enrolled at 18 sites in 7 countries. At baseline, 19 (61%), 9 (29%) and 3 (10%) were CTP Class A, B, or C, respectively. Median age was 57 y (19% ³65 y), 68% male, 81% Asian, 90% HBeAg-negative, median fibrotest score 0.81, and median eGFR_CG 98 mL/min; up to 48% had low BMD at hip and/or spine, and 68% had prior TDF exposure. Key efficacy/safety results at Week 24 are summarized in the Table. All patients had HBV DNA <20 IU/mL and a high proportion had normal ALT. Switching to TAF resulted in increases in hip/spine BMD, decreases in bone turnover markers, an increase in eGFR_CG with decreases in tubular markers. TAF was well tolerated with few having Grade 3 or 4 AEs (2 patients) and no discontinuations for and AE. ^aHBV DNA results are missing=failure. ^bALT normal is the proportion with ALT ≤ULN at Week 48, regardless of baseline ALT level; ^cULN 35 U/L males, 25 U/L females; ^dPatients with ALT >ULN at baseline; ^eHBeAg-positive at baseline. ^fSerum C-type collagen sequence (bone resorption marker); ^gSerum procollagen type 1 N-terminal propeptide (bone formation marker); ^hUrine retinol binding protein/creatinine (tubular marker); ⁱUrine beta-2 microglobulin/creatinine (tubular marker). BMD, bone mineral density by DXA scan; sCr, serum creatinine; PO₄, serum phosphorus; eGFR_CG, estimated creatinine clearance (Cockcroft-Gault method) Conclusions: In CHB patients with hepatic impairment switched to TAF from TDF or other OAVs, viral suppression was well maintained and improved bone and renal safety was seen at Week 24.

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.

Metal Chloride Precursor Synthesization of Cu2ZnSnS4 Solar Cell Materials

Min Yen Yeh,Yu-Fong Huang,Cheng-Liang Huang,Chyi-Da Yang,Dong-Sing Wuu,Po-Hsun Lei 한국물리학회 2014 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.65 No.2

Cu2ZnSnS4 (CZTS) thin films with kesterite structures were prepared by directly sol-gel synthesizingspin-coated precursors on soda-lime-glass (SLG) substrates. The CZTS precursors wereprepared by using solutions of copper (II) chloride, zinc (II) chloride, tin (IV) chloride, and thiourea. The ratio of SnCl4 in the precursors was found to play a critical role in the synthesization of CZTS. CZTS phases of SnS and SnS2 were observed in the synthesized films as prepared using precursorswith a close to stoichiometric ratio of CuCl2:ZnCl2:SnCl4:CH4N2S = 4:1:1:8, where SnCl4 was 1mol/l. The amounts of the educed SnS and SnS2 phases observed in the SEM images could bereadily reduced by decreasing the volume of SnCl4 in the mixed solution. With decreasing amountof SnCl4 from 1 mol/l, the as prepared CZTS reveals a significant improvement in its crystallineproperties. In this work, CZTS with an average absorption coefficient and an optical energy gapof over 104 cm−1 and 1.5 eV, respectively, was obtained using precursors of copper (II) chloride,zinc (II) chloride, tin (IV) chloride, and thiourea mixed in a ratio of 2:1:0.25:8, and it had goodcrystallinity revealing a Cu-poor composition.

The Ca _V 3.2 T-Type Ca ²⁺ Channel Is Required for Pressure Overload-Induced Cardiac Hypertrophy in Mice

Chiang, Chien-Sung,Huang, Ching-Hui,Chieng, Hockling,Chang, Ya-Ting,Chang, Dory,Chen, Ji-Jr,Chen, Yong-Cyuan,Chen, Yen-Hui,Shin, Hee-Sup,Campbell, Kevin P.,Chen, Chien-Chang Ovid Technologies Wolters Kluwer -American Heart A 2009 Circulation research Vol.104 No.4

<P>Voltage-gated T-type Ca(2+) channels (T-channels) are normally expressed during embryonic development in ventricular myocytes but are undetectable in adult ventricular myocytes. Interestingly, T-channels are reexpressed in hypertrophied or failing hearts. It is unclear whether T-channels play a role in the pathogenesis of cardiomyopathy and what the mechanism might be. Here we show that the alpha(1H) voltage-gated T-type Ca(2+) channel (Ca(v)3.2) is involved in the pathogenesis of cardiac hypertrophy via the activation of calcineurin/nuclear factor of activated T cells (NFAT) pathway. Specifically, pressure overload-induced hypertrophy was severely suppressed in mice deficient for Ca(v)3.2 (Ca(v)3.2(-/-)) but not in mice deficient for Ca(v)3.1 (Ca(v)3.1(-/-)). Angiotensin II-induced cardiac hypertrophy was also suppressed in Ca(v)3.2(-/-) mice. Consistent with these findings, cultured neonatal myocytes isolated from Ca(v)3.2(-/-) mice fail to respond hypertrophic stimulation by treatment with angiotensin II. Together, these results demonstrate the importance of Ca(v)3.2 in the development of cardiac hypertrophy both in vitro and in vivo. To test whether Ca(v)3.2 mediates the hypertrophic response through the calcineurin/NFAT pathway, we generated Ca(v)3.2(-/-), NFAT-luciferase reporter mice and showed that NFAT-luciferase reporter activity failed to increase after pressure overload in the Ca(v)3.2(-/-)/NFAT-Luc mice. Our results provide strong genetic evidence that Ca(v)3.2 indeed plays a pivotal role in the induction of calcineurin/NFAT hypertrophic signaling and is crucial for the activation of pathological cardiac hypertrophy.</P>

Thin-film electronics based on all-2D van der Waals heterostructures

Liu Xinling,Yang Xiaomin,Sang Weihui,Huang Hai,Li Wenwu,Lin Yen-Fu,Chu Junhao 한국정보디스플레이학회 2021 Journal of information display Vol.22 No.4

Two-dimensional (2D) layered materials including metal, semiconductor, and insulator have received extensive attention in recent years. The weak van-der-Waals (vdW) interactions between 2D materials layers enable them to isolate monolayers and restack into artificial 2D vdW heterostructures in the desired sequence. These assembled all-2D vdW heterostructures are promising platforms for fabricating next-generation electronics as well as optoelectronics. In particular, the all-2D vdW heterostructure devices composed entirely of 2D layered material have received extensive attention due to their natural thickness, atomically sharp heterointerfaces, and excellent mechanical flexibility. Herein, we firstly introduce 2D vdW heterostructures and their preparation methods. Secondly, the recent progress of field-effect transistors (FETs) and photodetectors based on all-2D vdW heterostructures are summarized. Finally, we discuss some challenges of all-2D vdW heterostructure-based devices for practical applications and offer personal perspectives toward the future development of thin-film electronics.

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.

Ni Germanide Utilizing Ytterbium Interlayer for High-Performance Ge MOSFETs

Zhang, Ying-Ying,Oh, Jungwoo,Li, Shi-Guang,Jung, Soon-Yen,Park, Kee-Young,Shin, Hong-Sik,Lee, Ga-Won,Wang, Jin-Suk,Majhi, Prashant,Tseng, Hsing-Huang,Jammy, Raj,Bae, Tae-Sung,Lee, Hi-Deok The Electrochemical Society 2009 Electrochemical and solid-state letters Vol.12 No.1

Imaging Spectrum after Pancreas Transplantation with Enteric Drainage

Jian-Ling Chen,Rheun-Chuan Lee,Yi-Ming Shyr,Sing-E Wang,Hsiuo-Shan Tseng,Hsin-Kai Wang,Shan-Su Huang,Cheng-Yen Chang 대한영상의학회 2014 Korean Journal of Radiology Vol.15 No.1

Since the introduction of pancreas transplantation more than 40 years ago, surgical techniques and immunosuppressive regiments have improved and both have contributed to increase the number and success rate of this procedure. However, graft survival corresponds to early diagnosis of organ-related complications. Thus, knowledge of the transplantation procedure and postoperative image anatomy are basic requirements for radiologists. In this article, we demonstrate the imaging spectrum of pancreas transplantation with enteric exocrine drainage.

Nuclear Theranostics in Taiwan

Ko-Han Lin,Yi-Wei Chen,Rheun-Chuan Lee,Ling-Wei Wang,Fong-In Chou,Chi-Wei Chang,Sang-Hue Yen,Wen-Sheng Huang 대한핵의학회 2019 핵의학 분자영상 Vol.53 No.2

Boron neutron capture therapy and Y-90 radioembolization are emerging therapeutic methods for uncontrolled brain cancers and hepatic cancers, respectively. These advanced radiation therapies are heavily relied on theranostic nuclear medicine imaging before the therapy for the eligibility of patients and the prescribed-dose simulation, as well as the post-therapy scanning for assessing the treatment efficacy. In Taiwan, the Taipei Veterans General Hospital is the only institute performing the BNCT and also the leading institute performing Y-90 radioembolization. In this article, we present our single institute experiences and associated theranostic nuclear medicine approaches for these therapies.