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  • 1
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    Genomic and tumour microenvironmental biomarkers of immune checkpoint inhibitor response in advanced Taiwanese melanoma
    Wiley ; 2023
    In:  Clinical & Translational Immunology Vol. 12, No. 8 ( 2023-01)
    Details
    In: Clinical & Translational Immunology, Wiley, Vol. 12, No. 8 ( 2023-01)
    Abstract: Genomic biomarkers predicting immune checkpoint inhibitor (ICI) treatment outcomes for Asian metastatic melanoma have been rarely reported. This study presents data on next‐generation sequencing (NGS) and tumour microenvironment biomarkers in 33 cases. Methods Thirty‐three patients with advanced melanoma, who underwent ICI treatment at the Chang Gung Memorial Hospital in Taiwan, were recruited. The study evaluated clinical outcomes, including response rate, disease control rate, progression‐free survival (PFS) rate and overall survival (OS) rate. Archived tissue samples from 33 cases were subjected to NGS by ACTOnco, and ACTTME was employed in 25 cases. Results The most prevalent driver mutations were BRAF mutations (24.2%), followed by NRAS (15.2%), KIT (12.1%), KRAS (9.1%) and NF1 (9.1%) mutations. Acral/mucosal melanomas exhibited distinct mutation patterns compared to non‐acral melanomas. Tumour mutational burden estimated using ACTOnco was not associated with ICI efficacy. Notably, genetic alterations in the p53 pathway ( CDKNA2 loss, MDM2 gain/amplification and TP53 mutation) accounted for 36.4% and were significantly associated with unfavourable PFS (median PFS 2.7 months vs. 3.9 months, P =  0.0394). Moreover, 26 genes were identified as differentially expressed genes that were upregulated in patients with clinical benefits compared to those without benefits. Four genes, GZMH , GZMK , AIM2 and CTLA4 , were found to be associated with both PFS and OS. Conclusion Genetic alterations in the p53 pathway may be critical in Asian patients with melanoma undergoing ICI treatment. Further investigation is required to explore this mechanism and validate these findings.
    Type of Medium: Online Resource
    ISSN: 2050-0068 , 2050-0068
    URL: Issue
    URL: Article
    DOI: 10.1002/cti2.v12.8
    DOI: 10.1002/cti2.1465
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2694482-0
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  • 2
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    Comprehensive assessment of pretreatment sarcopenia impacts on patients with EGFR ‐mutated NSCLC treated with afatinib
    Wiley ; 2023
    In:  Thoracic Cancer Vol. 14, No. 25 ( 2023-09), p. 2548-2557
    Details
    In: Thoracic Cancer, Wiley, Vol. 14, No. 25 ( 2023-09), p. 2548-2557
    Abstract: This study aimed to comprehensively evaluate the efficacy and toxicity of afatinib in patients with sarcopenia, an important prognostic factor for treatment efficacy and toxicity in patients with cancer. Methods The clinical features of patients with advanced NSCLC treated with frontline afatinib between 2014 and 2018 at a medical center in Taiwan were retrospectively reviewed. Sarcopenia was evaluated based on the total cross‐sectional area of skeletal muscles assessed by computed tomography (CT) imaging at the L3 level. Baseline characteristics, response rates, survival rates, and adverse events (AEs) were compared between sarcopenic and nonsarcopenic patients. Results A total of 176 patients evaluated for sarcopenia by CT and treated with afatinib were enrolled in the current study. Sarcopenia was significantly associated with good performance status, low body mass index (BMI), low body surface area (BSA), and low total mass area (TMA). Sarcopenia did not influence the response rate (69.2% vs. 72.0%, p  = 0.299), progression‐free survival (median 15.9 vs. 14.9 months, p  = 0.791), or overall survival (median 26.5 vs. 27.2 months, p  = 0.441). However, BSA ≤ 1.7 and the 40 mg afatinib dose were associated with dose reduction. TMA was the only independent factor for afatinib discontinuation due to AEs. Conclusion Sarcopenia was not associated with treatment efficacy or toxicity among patients with NSCLC harboring common mutations treated with afatinib, indicating sarcopenic patients should not be excluded from afatinib treatment. Other factors, such as BSA and TMA, were associated with dose reduction and afatinib discontinuation, respectively, which may require additional evaluations in future studies.
    Type of Medium: Online Resource
    ISSN: 1759-7706 , 1759-7714
    URL: Issue
    URL: Article
    DOI: 10.1111/tca.v14.25
    DOI: 10.1111/1759-7714.15017
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2559245-2
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  • 3
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    A cost‐utility analysis of avelumab for metastatic Merkel cell carcinoma in Taiwan
    Wiley ; 2021
    In:  Cancer Reports Vol. 4, No. 6 ( 2021-12)
    Details
    In: Cancer Reports, Wiley, Vol. 4, No. 6 ( 2021-12)
    Abstract: Metastatic Merkel cell carcinoma (mMCC) has traditionally been managed with palliative chemotherapy regimens or best supportive care (BSC). Avelumab, a novel anti‐programmed death‐ligand 1 (PD‐L1) human monoclonal antibody for mMCC treatment, is being studied in the pivotal JAVELIN Merkel 200 trial. Aim Incorporating trial results, this analysis aimed to evaluate the cost‐utility of avelumab in Taiwan. Methods and results A de novo partitioned‐survival model with three key health states related to survival (progression‐free disease, progressed disease, and death) was applied in this study. The data of clinical efficacy, safety, and patient utilities were obtained from the JAVELIN Merkel 200 trial, literature review, and Taiwanese clinical expert opinion. Cost‐utility analysis was performed, and results were presented as cost per quality‐adjusted life year (QALY) gained. For treatment‐naïve patients, the incremental cost‐effectiveness ratios (ICERs) for avelumab vs BSC and avelumab vs chemotherapy were US$44885.06 and US$42993.06 per QALY gained, respectively. As to treatment‐experienced mMCC patients, avelumab was associated with ICERs of US$27243.06 (vs BSC)/US$26557.43 (vs chemotherapy) per QALY gained. All ICERs remained consistently within the willingness‐to‐pay (WTP) threshold of US$53,333.33 per QALY gained. Conclusion This study demonstrated avelumab to be a cost‐effective treatment option for both treatment‐experienced and treatment‐naïve mMCC patients with very poor prognosis in Taiwan.
    Type of Medium: Online Resource
    ISSN: 2573-8348 , 2573-8348
    URL: Issue
    URL: Article
    DOI: 10.1002/cnr2.v4.6
    DOI: 10.1002/cnr2.1399
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2920367-3
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  • 4
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    Using betaxolol for the prevention of paronychia induced by epidermal growth factor receptor inhibitors: a case–control cohort study
    Wiley ; 2021
    In:  International Journal of Dermatology Vol. 60, No. 2 ( 2021-02), p. 179-184
    Details
    In: International Journal of Dermatology, Wiley, Vol. 60, No. 2 ( 2021-02), p. 179-184
    Abstract: High rates of posttreatment discomfort, infection, recurrence, and increased time to return to work have been noted after nail plate avulsion resulting from epidermal growth factor receptor tyrosine kinase inhibitor(EGFR‐TKI)‐induced paronychia, which may even interrupt the course of treatment for EGFR‐TKI therapy. Thus, we conducted this study to determine how effectively a topical β‐blocker, betaxolol, prevents EGFR‐TKI‐induced paronychia. Methods This case–control cohort study included a total of 131 non‐small‐cell lung cancer patients. The prevention group comprised 40 patients treated with topical betaxolol 0.25% solution to prevent paronychia while they received EGFR‐TKI therapy. The control group comprised 91 patients who did not preventively use topical betaxolol 0.25% solution while receiving EGFR‐TKI therapy. The patients’ age, gender, antineoplastic regimen, duration of antineoplastic treatment before the appearance of lesions, number of involved digits (fingernails or toenails) with lesions, grading of paronychia, and pain score were recorded. Results In terms of the cumulative incidence of paronychia, significant differences ( P   〈  0.01) were noted at both the 2nd and 3rd months after starting EGFR‐TKIs. Furthermore, the average visual analogue scale scores were 3.125 and 6.29 in the prevention group and control group, respectively ( P   〈  0.01). The average grades of paronychia were 1.5 and 2.12 in the prevention group and control group, respectively ( P   〈  0.01). The average numbers of involved digits were 2.25 (range: 1–5 digits) in the prevention group and 3.03 (range: 1–7) in the control group ( P  = 0.07). Conclusions Preventively using topical betaxolol can significantly decrease the incidence, VAS score, and grading of EGFR‐TKI‐induced paronychia.
    Type of Medium: Online Resource
    ISSN: 0011-9059 , 1365-4632
    URL: Issue
    URL: Article
    DOI: 10.1111/ijd.v60.2
    DOI: 10.1111/ijd.15099
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2020365-2
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  • 5
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    A comparison of immunohistochemical and molecular methods used for analyzing the BRAF V600E gene mutation in malignant melanoma in Taiwan
    Wiley ; 2016
    In:  Asia-Pacific Journal of Clinical Oncology Vol. 12, No. 4 ( 2016-12), p. 403-408
    Details
    In: Asia-Pacific Journal of Clinical Oncology, Wiley, Vol. 12, No. 4 ( 2016-12), p. 403-408
    Abstract: The BRAF V600 mutation has been shown to be clinically meaningful in terms of both the prognosis and sensitivity of BRAF inhibitors in patients with metastatic melanoma. Recently, a BRAF V600E mutation‐specific antibody, VE1, was generated for the detection of tumors bearing BRAF V600E mutations. To determine the clinical value of immunohistochemical testing, we compared the prevalence of mutant BRAF detected by VE1 with direct sequencing results. Methods Paraffin‐embedded, formalin‐fixed melanoma biopsies were analyzed for the BRAF mutation status by immunohistochemistry with the VE1 antibody. Sanger sequencing was applied to verify the immunohistochemical results. Results A total of 73 melanoma cases with tumor samples from primary lymph nodes and metastatic sites were selected for this study. Direct sequencing demonstrated that 18 of 73 cases (24.6%) harbored the BRAF V600 mutation: 17 with V600E and one with V600K. All 18 tumors shown to harbor the BRAF V600E/K mutations were VE1‐positive. One additional case was false‐positive for VE1. The sensitivity and specificity of VE1 was 100% (18/18) and 98% (54/55), respectively. The overall concordance between the immunohistochemical method and direct sequencing was excellent (98.6%). Conclusions Our findings demonstrate that immunohistochemical analysis using VE1 constitutes a highly sensitive test for the detection of BRAF mutations and suggest that this cost‐effective method is suitable as a rapid diagnostic approach complementary to molecular testing.
    Type of Medium: Online Resource
    ISSN: 1743-7555 , 1743-7563
    URL: Issue
    URL: Article
    DOI: 10.1111/ajco.2016.12.issue-4
    DOI: 10.1111/ajco.12574
    Language: English
    Publisher: Wiley
    Publication Date: 2016
    detail.hit.zdb_id: 2187409-8
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  • 6
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    Epidermal growth factor receptor tyrosine kinase inhibitors for de novo T790M mutation: A retrospective study of 44 patients
    Wiley ; 2022
    In:  Thoracic Cancer Vol. 13, No. 13 ( 2022-07), p. 1888-1897
    Details
    In: Thoracic Cancer, Wiley, Vol. 13, No. 13 ( 2022-07), p. 1888-1897
    Abstract: This study aimed to evaluate possible treatment strategies for patients with de novo T790M mutation‐positive (T790M+) non‐small‐cell lung cancer (NSCLC). Methods Patients diagnosed with de novo T790M+ NSCLC and treated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) between 2011 and 2018 at a regional hospital in Taiwan were retrospectively reviewed. Their clinicopathological characteristics and subsequent treatment information were collected, and potential prognostic factors were identified using univariate and multivariate analyses. Results All tumors with T790M mutations coexisted with sensitizing mutations. Through the last follow‐up in May 2021, afatinib and osimertinib demonstrated better progression‐free survival (PFS, p   〈  0.01) and overall survival (OS, p   〈  0.01) than gefitinib and erlotinib. Additionally, patients with low T790M ratios had better PFS than those with high T790M ratios, implying that the proportion of T790M+ tumors determined the response to EGFR‐TKIs. Multivariate analysis confirmed that both EGFR‐TKI treatment (osimertinib hazard ratio [HR] 0.06, 95% confidence interval [CI] 0.01–0.30; afatinib HR 0.09, 95% CI 0.02–0.39) and a low T790M ratio (HR 0.29, 95% CI 0.12–0.69) were independently favorable prognostic factors for patients with de novo T790M+ NSCLC. Median PFS was 6.1 (95% CI 4.4–7.8) months. In addition, patients treated with first‐generation (1G)/second‐generation (2G) EGFR‐TKIs followed by osimertinib ( n  = 8) demonstrated the best OS compared with patients treated with frontline osimertinib ( n  = 5) or 1G/2G EGFR‐TKIs without osimertinib ( n  = 28, p   〈  0.01). Conclusion Sequential TKIs may represent an alternative option for de novo T790M mutation, particularly frontline afatinib and tumors with low T790M ratios.
    Type of Medium: Online Resource
    ISSN: 1759-7706 , 1759-7714
    URL: Issue
    URL: Article
    DOI: 10.1111/tca.v13.13
    DOI: 10.1111/1759-7714.14272
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2559245-2
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  • 7
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    Mechanisms of ceramide-induced COX-2-dependent apoptosis in human ovarian cancer OVCAR-3 cells partially overlapped with resveratrol
    Wiley ; 2013
    In:  Journal of Cellular Biochemistry Vol. 114, No. 8 ( 2013-08), p. 1940-1954
    Details
    In: Journal of Cellular Biochemistry, Wiley, Vol. 114, No. 8 ( 2013-08), p. 1940-1954
    Type of Medium: Online Resource
    ISSN: 0730-2312
    URL: Issue
    URL: Article
    DOI: 10.1002/jcb.v114.8
    DOI: 10.1002/jcb.24539
    Language: English
    Publisher: Wiley
    Publication Date: 2013
    detail.hit.zdb_id: 1479976-5
    SSG: 12
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  • 8
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    Zinc deficiency associated with cutaneous toxicities induced by epidermal growth factor receptor tyrosine kinase inhibitor therapy in patients with lung adenocarcinoma
    Wiley ; 2023
    In:  Journal of the European Academy of Dermatology and Venereology Vol. 37, No. 2 ( 2023-02), p. 328-339
    Details
    In: Journal of the European Academy of Dermatology and Venereology, Wiley, Vol. 37, No. 2 ( 2023-02), p. 328-339
    Abstract: Cutaneous toxicities are common adverse effects following epidermal growth factor receptor tyrosine kinase inhibitor (EGFR‐TKI) therapy. Zinc deficiency causes diverse diseases, including skin toxicities. Therefore, this study aimed to investigate the role of zinc deficiency in patients with EGFR‐TKI‐induced skin toxicities. Experimental Design This retrospective study enrolled 269 patients with diverse skin disorders who visited our hospital between January 2016 and December 2017. The skin toxicity severities and plasma zinc levels of 101 EGFR‐TKI‐treated cancer patients were analysed and compared with those of 43 non‐EGFR‐TKI‐treated cancer patients and 125 patients without cancer but presenting cutaneous manifestations. Additionally, the role of zinc in erlotinib‐induced skin eruptions was established in a 14‐day‐murine model. Clinical features were further evaluated following systemic zinc supplementation in EGFR‐TKI‐treated cancer patients. Results EGFR‐TKI‐treated patients demonstrated severe cutaneous manifestations and a significant decrease in plasma zinc levels than those of the control groups. The serum zinc level and Common Terminology Criteria for Adverse Events (CTCAE) 5.0 grading of EGFR‐TKI‐induced skin toxicities showed a significant negative correlation ( r  = −0.29; p   〈  0.0001). Moreover, erlotinib treatment decreased the plasma zinc levels and induced periorificial dermatitis in rats confirming zinc deficiency following EGFR‐TKI treatment. Zinc supplementation to the EGFR‐TKI‐treated cancer patients showed a significant decrease in the CTCEA grading ( p   〈  0.0005 for mucositis and p   〈  0.0.0001 for all other cases) after 8 weeks. Conclusions Skin impairment following EGFR‐TKI therapy could be ameliorated through zinc supplementation. Thus, zinc supplementation should be considered for cancer patients undergoing EGFR‐TKI therapy.
    Type of Medium: Online Resource
    ISSN: 0926-9959 , 1468-3083
    URL: Issue
    URL: Article
    DOI: 10.1111/jdv.v37.2
    DOI: 10.1111/jdv.18703
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2022088-1
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  • 9
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    The survival after discontinuation of EGFR‐TKIs due to intolerable adverse events in patients with EGFR ‐mutated non–small cell lung cancer
    Wiley ; 2023
    In:  Thoracic Cancer Vol. 14, No. 4 ( 2023-02), p. 348-356
    Details
    In: Thoracic Cancer, Wiley, Vol. 14, No. 4 ( 2023-02), p. 348-356
    Abstract: Epidermal growth factor receptor‐tyrosine kinase inhibitors (EGFR‐TKIs) are standard treatments for advanced non–small cell lung cancer (NSCLC) patients harboring the EGFR mutation. Patients experiencing intolerable adverse events (AEs) would discontinue EGFR‐TKIs. This study aimed to evaluate the impact of intolerable AEs and subsequent treatment on the survival of patients who discontinued EGFR‐TKIs. Patients The data of advanced NSCLC patients treated with EGFR‐TKIs as frontline treatment at Chang Gung Memorial Hospitals from June 2014 to March 2018 were retrospectively reviewed. Results A total of 2190 patients were enrolled and treated with frontline EGFR‐TKIs. In August 2021, 114 (5.2%) patients experienced intolerable AEs requiring discontinuation of EGFR‐TKIs. The time median of EGFR‐TKIs discontinuation was 2.56 months. Age 〉 65 years, females, body weight, and body surface area were associated with the occurrence of intolerable AEs for patients treated with afatinib. Patients experiencing skin/paronychia/mucositis and abnormal liver function test had favorable survivals results. Patients who received subsequent EGFR‐TKIs treatment, experienced better progression‐free survival (PFS), total PFS (from frontline line EGFR‐TKIs), and overall survival (OS) compared to patients receiving chemotherapy or no treatment. Patients undergoing subsequent EGFR‐TKIs had better total PFS (median, 14.9 vs. 11.3 months, p  = 0.013) and OS (median, 31.3 vs. 20.1 months, p  = 0.001) than patients who did not discontinue because of AEs. Favorable OS was validated by propensity score matching. Conclusion Patients experiencing intolerable AEs during EGFR‐TKI treatment should consider switching to an alternative EGFR‐TKI, which increase the survival results as compared to those patients who did not experience intolerable AEs.
    Type of Medium: Online Resource
    ISSN: 1759-7706 , 1759-7714
    URL: Issue
    URL: Article
    DOI: 10.1111/tca.v14.4
    DOI: 10.1111/1759-7714.14674
    Language: English
    Publisher: Wiley
    Publication Date: 2023
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  • 10
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    Establishment of a novel gene panel as a biomarker of immune checkpoint inhibitor response
    Wiley ; 2020
    In:  Clinical & Translational Immunology Vol. 9, No. 7 ( 2020-01)
    Details
    In: Clinical & Translational Immunology, Wiley, Vol. 9, No. 7 ( 2020-01)
    Abstract: Immune checkpoint inhibitors (ICIs) have become the standard of care in various cancers, although the predictive tool is still unknown. Methods This study aimed to develop a novel gene panel by selecting DNA damage response (DDR) genes from the Catalogue of Somatic Mutations in Cancer (COSMIC) databank and validating them in previously reported cohorts. This association between DDR gene mutations and tumor mutation burden or microsatellite status was analysed from The Cancer Genome Atlas (TCGA) databank. Furthermore, we made the gene panel clinically accessible and predicted the response in clinical patients receiving ICIs by using cell‐free DNA. Results The top 20 mutated DDR genes in various cancers (total 37 genes) were taken from the COSMIC databank, and the DDR genes found to individually predict a response rate 〉  50% in Van Allen's cohort were selected ( Science , 350 , 2015 and 207). Eighteen DDR genes were selected as the gene panel. The prevalence and predicted response rate were validated in the other three reported cohorts. Tumor mutational burden‐high was positively associated with mutations of the 18 DDR genes for most cancers. We used cell‐free DNA to test the DDR gene panel and validated by our patients receiving ICIs. This DDR gene panel accounted for approximately 30% of various cancers, achieving a predicted response rate of approximately 60% in patients with a mutated gene panel receiving ICIs. Conclusion This gene panel is a novel and reliable tool for predicting the response to ICIs in cancer patients and guides the appropriate administration of ICIs in clinical practice.
    Type of Medium: Online Resource
    ISSN: 2050-0068 , 2050-0068
    URL: Issue
    URL: Article
    DOI: 10.1002/cti2.v9.7
    DOI: 10.1002/cti2.1145
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2694482-0
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