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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 林家齊 | zh_TW |
dc.contributor.advisor | Chia-Chi Lin | en |
dc.contributor.author | 林士森 | zh_TW |
dc.contributor.author | Shih-Sen Lin | en |
dc.date.accessioned | 2023-05-19T08:45:16Z | - |
dc.date.available | 2023-11-10 | - |
dc.date.copyright | 2023-09-22 | - |
dc.date.issued | 2023 | - |
dc.date.submitted | 2023-03-30 | - |
dc.identifier.citation | 1.Zhao, Y., D. Chen, and Y. Chen, [Research Progress of Lymph Node Micrometastasis in Non-small Cell Lung Cancer]. Zhongguo Fei Ai Za Zhi, 2018. 21(7): p. 547-552.
2.Zhao, Y., et al., The Optimal Treatment for Stage IIIA-N2 Non-Small Cell Lung Cancer: A Network Meta-Analysis. Ann Thorac Surg, 2019. 107(6): p. 1866-1875. 3.Ettinger, D.S., et al., Non-Small Cell Lung Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw, 2022. 20(5): p. 497-530. 4.Zhong, W.Z., et al., Erlotinib Versus Gemcitabine Plus Cisplatin as Neoadjuvant Treatment of Stage IIIA-N2 EGFR-Mutant Non-Small-Cell Lung Cancer (EMERGING-CTONG 1103): A Randomized Phase II Study. J Clin Oncol, 2019. 37(25): p. 2235-2245. 5.Zhong, W., et al., Phase II study of biomarker-guided neoadjuvant treatment strategy for IIIA-N2 non-small cell lung cancer based on epidermal growth factor receptor mutation status. J Hematol Oncol, 2015. 8: p. 54. 6.Xiong, L., et al., Efficacy of erlotinib as neoadjuvant regimen in EGFR-mutant locally advanced non-small cell lung cancer patients. J Int Med Res, 2020. 48(4): p. 300060519887275. 7.Lv, C., et al., Does neoadjuvant targeted therapy provide an opportunity for resectable EGFR-mutant lung cancer: a real-world retrospective study. J Thorac Dis, 2020. 12(10): p. 5324-5335. 8.McInnes, M.D.F., et al., Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies: The PRISMA-DTA Statement. Jama, 2018. 319(4): p. 388-396. 9.Eisenhauer, E.A., et al., New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer, 2009. 45(2): p. 228-47. 10.Hellmann, M.D., et al., Pathological response after neoadjuvant chemotherapy in resectable non-small-cell lung cancers: proposal for the use of major pathological response as a surrogate endpoint. Lancet Oncol, 2014. 15(1): p. e42-50. 11.Corsini, E.M., et al., Pathological nodal disease defines survival outcomes in patients with lung cancer with tumour major pathological response following neoadjuvant chemotherapy. Eur J Cardiothorac Surg, 2021. 59(1): p. 100-108. 12.Milleron, B., et al., [Pathological complete response: A predictive survival factor after neoadjuvant chemotherapy in lung cancer]. Bull Cancer, 2016. 103(1): p. 66-72. 13.Akyıl, M., et al., Prognostic significance of pathological complete response in non-small cell lung cancer following neoadjuvant treatment. Turk Gogus Kalp Damar Cerrahisi Derg, 2020. 28(1): p. 166-174. 14.Chen, X. and K. Ma, Neoadjuvant Therapy in Lung Cancer: What Is Most Important: Objective Response Rate or Major Pathological Response? Curr Oncol, 2021. 28(5): p. 4129-4138. 15.Chaft, J.E., et al., Preoperative and Postoperative Systemic Therapy for Operable Non-Small-Cell Lung Cancer. J Clin Oncol, 2022. 40(6): p. 546-555. 16.Yee, D., et al., Association of Event-Free and Distant Recurrence-Free Survival With Individual-Level Pathologic Complete Response in Neoadjuvant Treatment of Stages 2 and 3 Breast Cancer: Three-Year Follow-up Analysis for the I-SPY2 Adaptively Randomized Clinical Trial. JAMA Oncol, 2020. 6(9): p. 1355-1362. 17.Gagliasso, M., G. Migliaretti, and F. Ardissone, Assessing the prognostic impact of the International Association for the Study of Lung Cancer proposed definitions of complete, uncertain, and incomplete resection in non-small cell lung cancer surgery. Lung Cancer, 2017. 111: p. 124-130. 18.Tsuboi, M., et al., Neoadjuvant osimertinib with/without chemotherapy versus chemotherapy alone for EGFR-mutated resectable non-small-cell lung cancer: NeoADAURA. Future Oncol, 2021. 17(31): p. 4045-4055. 19.Bade, B.C. and C.S. Dela Cruz, Lung Cancer 2020: Epidemiology, Etiology, and Prevention. Clin Chest Med, 2020. 41(1): p. 1-24. 20.Rapp, E., et al., Chemotherapy can prolong survival in patients with advanced non-small-cell lung cancer--report of a Canadian multicenter randomized trial. J Clin Oncol, 1988. 6(4): p. 633-41. 21.van Meerbeeck, J.P. and V.F. Surmont, Stage IIIA-N2 NSCLC: a review of its treatment approaches and future developments. Lung Cancer, 2009. 65(3): p. 257-67. 22.Robinson, L.A., et al., Treatment of non-small cell lung cancer-stage IIIA: ACCP evidence-based clinical practice guidelines (2nd edition). Chest, 2007. 132(3 Suppl): p. 243s-265s. | - |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/87381 | - |
dc.description.abstract | 研究目的:
在術前治療中使用標靶治療來治療由致癌基因驅動的非小細胞肺癌(NSCLC)的效用仍存在爭議。在本研究中,我們旨在評估術前標靶治療與國家綜合癌症網絡(NCCN)指南推薦的標準術前化療方案相比的療效。 材料和方法: 我們在三個資料庫(PubMed、Cochrane Library 和 Embase)中對於2021年10月之前發表的術前治療研究中進行了系統搜索。為了確保更客觀的療效評估,我們選擇了客觀反應(OR)、病理反應(PR)、病理分期降低率和手術切除率等終點。由於整體生存(OS)和無疾病進展生存(PFS)的非硬終點特性以及高統計偏倚的可能性,我們未對生存結果進行評估。我們使用R進行統計分析和偏倚評估。 結果: 我們的統合分析包括了一個隨機對照試驗,兩個非隨機對照試驗和一個回溯性觀察研究的共213名患者。對於EGFR突變陽性的NSCLC患者,統合分析顯示EGFR-TKI與化療相比顯著改善了OR(比值比[OR]:3.01,95%信賴區間[CI]:1.70-5.30)。然而,在病理反應方面,兩種治療選擇之間沒有顯著差異(比值比1.52,95%信賴區間[CI]:0.34-6.84)。此外,病理分期降低和手術切除率在兩種治療選擇之間也沒有顯著差異。 結論: 我們的統合分析結果顯示,對於局部晚期EGFR突變陽性的NSCLC患者,應將由致癌基因驅動的標靶治療作為誘導治療的首選。儘管在某些情況下,有限的樣本量限制了統計顯著性,但在我們對所包括研究的分析中,每個術前標靶治療(NTT)組的OR始終較高。EGFR突變狀態可以預測在接受EGFR-TKI治療後的腫瘤縮小,EGFR突變陽性患者接受NTT與EGFR突變陰性患者接受術前化療(NCT)相比,觀察到更明顯的縮小。本研究表明,在本研究中分析的其他主要結果,如病理反應和手術率,在統合分析中並未顯示出顯著差異。 | zh_TW |
dc.description.abstract | Purpose:
The utility of targeted therapy in the preoperative setting for oncogene-driven non-small cell lung cancer (NSCLC) remains a matter of debate. In this study, we aimed to assess the efficacy of neoadjuvant targeted therapy compared with standard neoadjuvant chemotherapy regimens recommended by the National Comprehensive Cancer Network (NCCN) guidelines. Materials and Methods: We conducted a systematic search in three databases (PubMed, Cochrane Library, and Embase) for studies on neoadjuvant therapy published before October 2021. To ensure a more objective efficacy assessment, we selected endpoints such as objective response (OR), pathological response (PR), pathological downstaging rate, and surgical resection rate. Survival outcomes, including overall survival (OS) and progression-free survival (PFS), were not evaluated due to their non-hard endpoint nature and the potential for high statistical bias. Statistical analysis and bias assessment were performed using R. Results: Our meta-analysis included a total of 213 patients from one randomized controlled trial, two non-randomized controlled trials, and one retrospective cohort study. For EGFR mutation-positive NSCLC patients, the meta-analysis showed that EGFR-TKIs significantly improved OR compared to chemotherapy (odds ratio [OR]: 3.01, 95% confidence interval [CI]: 1.70-5.30). However, no significant difference was observed in pathological response between the two treatment options (odds ratio 1.52, 95% confidence interval [CI]: 0.34-6.84). Additionally, pathological downstaging and surgical resection rates did not show significant differences between the two treatment options. Conclusion: Our meta-analysis suggests that oncogene-driven targeted therapy should be prioritized as induction therapy for locally advanced EGFR mutation-positive NSCLC patients. The OR for each neoadjuvant targeted therapy (NTT) group was consistently higher in our analysis of the included studies, although limited sample sizes restricted the statistical significance in some cases. EGFR mutation status can predict tumor regression following EGFR-TKI treatment, with more substantial regression observed in EGFR mutation-positive patients receiving NTT compared to EGFR mutation-negative patients receiving neoadjuvant chemotherapy (NCT). The current study demonstrates that other primary outcomes analyzed in this study, such as pathological response and surgery rate, did not exhibit significant differences in the meta-analysis. | en |
dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2023-05-19T08:45:16Z No. of bitstreams: 0 | en |
dc.description.provenance | Made available in DSpace on 2023-05-19T08:45:16Z (GMT). No. of bitstreams: 0 | en |
dc.description.tableofcontents | 口試委員會審定書 #
誌謝 i 中文摘要 ii ABSTRACT iv CONTENTS vi 1 Introduction 1 2 Materials and Methods 3 2.1 Searching Strategy 3 2.2 Inclusion Criteria of Studies 3 2.3 Data Extraction 3 2.4 Statistical Analysis 4 3 Result 5 4 Discussion 7 5 Figures and Tables 11 5.1 Figure 1 illustrates the study retrieval process 11 5.2 Figure 2, OR 3.01, 95% CI: 1.70– 5.30, I2 = 0% 11 5.3 Figure 3, OR 1.52, 95% CI: 0.34– 6.84, I2 = 42% 11 5.4 Figure 4, OR 1.93, 95% CI: 0.58– 6.39, I2 = 32% 12 5.5 Figure 5, OR 2.01, 95% CI: 0.90– 4.47, I2 = 16% 12 5.6 Figure 6. Comparison of chemotherapy regimen, 12 reference: Erlotinib 12 5.7 Figure 6. Comparison of chemotherapy regimen, 13 reference: Gefitinib 13 5.8 Table 1. Illustration of the characteristics of included studies 13 Appendix: Clinical Trial Protocol 14 Summary of study Protocol 15 Schedule of Activities 21 1 Study background and principle 28 1.1 Non-small cell lung cancer 28 1.2 Current status of incidence and treatment of stage IIIA N2 non-small cell lung cancer 29 2 Study objectives 32 2.1 Primary objective 32 2.2 Secondary objectives 32 3 Study design 33 3.1 Study design and planning 33 3.2 Randomization 34 3.3 Patient selection 35 3.3.1 Inclusion Criteria 35 3.3.2 Exclusion criteria 37 3.4 Study period 38 3.5 Patients withdraw from study 38 3.6 Treatment plan 40 3.6.1 Treatment arrangement 40 3.6.2 Auxiliary medication 43 3.6.3 Delay in drug delivery and dose adjustment of chemotherapy drugs 44 3.6.4 Delay in administration and dose adjustment of target therapy 45 3.6.5 Dose adjustment 45 3.6.6 Concomitant treatment and smoking 48 3.6.7 Concomitant medication 49 3.6.7.1 Drugs permitted 49 3.6.7.2 Drugs prohibited 49 3.6.8 Treatment compliance 49 3.7 Study endpoints 50 3.7.1 Efficacy endpoint 50 3.7.2 Patients’ self-assessment 51 3.7.3 Safety parameters and Definitions 51 3.7.4 Evaluation period 52 3.7.4.1 Research visit 52 3.7.4.2 Tumor and Response Evaluations 52 3.7.4.3 Observation and measurement 53 3.8 Study process 54 3.8.1 Screening period and baseline 54 3.8.2 Neoadjuvant treatment period and surgery period 55 3.8.3 Post-operation adjuvant treatment period 56 3.8.4 Recurrence visit follow-up 57 3.8.5 Survival follow-up 58 3.8.6 Temporary visit 58 3.9 Quality of data 58 3.10 Archive 59 4 Ethical and consideration 60 4.1 Independent ethics committee (IEC) 60 4.2 Ethical guidance for this study 60 4.3 Patient notice and informed consent 60 4.4 Confidentiality 61 4.5 Conditions for protocol amendment 61 4.6 Conditions for termination of study 62 4.7 Preservation of research documents, medical report forms and records 62 4.7.1 Preservation of investigators’ documents 62 4.7.2 Raw record and background data information 63 4.7.3 Audit and inspection 63 4.7.4 Case report form 63 5 Research audit 65 6 Publication of research data and protection of trade secrets 66 7 Statistics and analysis plan 67 7.1 Primary and secondary variables 67 7.1.1 Primary variable 67 7.1.2 Secondary variables 67 7.2 Statistics analysis 68 7.2.1 Baseline and demographic characteristics 68 7.2.2 Primary efficacy 68 7.2.3 Secondary efficacy 68 7.3 Hypothesis Testing 69 7.4 Analysis type 70 7.5 Interim analysis 70 7.6 Safety analysis 70 7.7 Determination of sample size 71 8 Safety principle 72 8.1 Precautions/ warnings 72 8.1.1 Interstitial lung disease (ILD)-like adverse events 72 8.1.2 Diarrhea, dehydration, electrolyte imbalance and kidney failure 73 8.1.3 Hepatitis, liver failure 74 8.1.4 Gastrointestinal perforation 74 8.1.5 Bullous and exfoliative skin disorders 74 8.1.6 Ocular disorders 74 8.1.7 Toxicity caused by interaction between drugs 74 8.2 Adverse events 75 8.2.1 Definition of adverse events 75 8.2.2 Grade of adverse events 76 8.2.3 Monitoring of adverse events 77 8.2.4 Relationship between adverse events and study drug 77 8.2.5 Serious adverse event (SAE): 79 8.2.6 Non-serious adverse events of special interest (AESI) 80 8.2.7 Tumor progression 80 8.2.8 Unexpected adverse event 81 8.2.9 Reporting of adverse events 82 8.2.10 Treatment and follow up of adverse events 83 8.2.11 Laboratory test abnormalities 84 8.3 Pregnancy 85 9 Independent review committee (IRC) 87 10 Appendix of Protocol 88 10.1 General condition (ECOG Performance status) 88 10.2 Lung cancer international TNM staging classification 88 10.3 RECIST1.1 tumor response evaluation criteria 90 10.4 NCI Common Terminology Criteria, Version 4.0 109 10.5 Effective treatment of target therapy-related skin adverse events 109 10.6 Sample Analysis 110 10.7 The New York Heart Association (NYHA) Functional Classification 110 10.8 Calculation of creatinine clearance 111 REFERENCE 112 | - |
dc.language.iso | en | - |
dc.title | 標靶治療加化療對於可能可切除的致癌基因驅動型非小細胞肺癌(NSCLC)作為術前輔助療法:系統性回顧、整合分析以及後續之傘形設計、隨機、雙盲、安慰劑對照試驗 | zh_TW |
dc.title | Targeted Therapy Plus Chemotherapy versus Chemotherapy Alone as Neoadjuvant Treatment for Potentially Resectable Oncogene Driven Non-Small-Cell Lung Cancer (NSCLC): Systemic Review and Meta-Analysis and an Umbrella Design, Double Blind, Randomized, Placebo Controlled Trial | en |
dc.type | Thesis | - |
dc.date.schoolyear | 111-2 | - |
dc.description.degree | 碩士 | - |
dc.contributor.oralexamcommittee | 何肇基;葉育雯 | zh_TW |
dc.contributor.oralexamcommittee | Chao-Chi Ho;Yu-Wung Yeh | en |
dc.subject.keyword | 肺癌,腺癌,術前,標靶治療,致癌基因驅動,表皮生長因子受體,酪氨酸激酶抑制劑, | zh_TW |
dc.subject.keyword | lung cancer,adenocarcinoma,neodadjuvant,target therapy,ncogene driven,epidermal growth factor receptor,tyrosine kinase inhibitor, | en |
dc.relation.page | 114 | - |
dc.identifier.doi | 10.6342/NTU202300707 | - |
dc.rights.note | 同意授權(限校園內公開) | - |
dc.date.accepted | 2023-03-31 | - |
dc.contributor.author-college | 醫學院 | - |
dc.contributor.author-dept | 臨床醫學研究所 | - |
dc.date.embargo-lift | 2028-03-30 | - |
顯示於系所單位: | 臨床醫學研究所 |
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