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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 楊泮池(Pan-Chyr Yang) | |
| dc.contributor.author | Chia-Lin Hsu | en |
| dc.contributor.author | 許嘉林 | zh_TW |
| dc.date.accessioned | 2022-11-24T03:19:01Z | - |
| dc.date.available | 2022-02-16 | |
| dc.date.available | 2022-11-24T03:19:01Z | - |
| dc.date.copyright | 2022-02-16 | |
| dc.date.issued | 2022 | |
| dc.date.submitted | 2022-02-09 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/80850 | - |
| dc.description.abstract | "雖然近年來在肺癌的致病機轉及治療上已有許多突破性的進展，肺癌的發生及死亡率仍然相當高。肺癌於年輕族群並不常見，而且其臨床特性也與年紀較長之肺癌患者不同。另外，老年肺癌常因為共病及較差之日常體能狀態而無法進入臨床試驗造成人數上之低估。無論年輕或老年肺癌病患，他們都需要組織切片的診斷來提供診斷及後續的追蹤。液態切片提供另一個臨床診斷與追蹤的方式。循環腫瘤細胞為實體腫瘤的細胞掉落至血液中，其已被證實與一些實體腫瘤的預後是有相關的。 針對年輕肺癌族群，我們收了144位年紀不大於45歲的晚期非小細胞肺癌病患。相對於其他年齡層，年輕肺癌患者擁有最高比例的肺腺癌病患。年輕患者的中位數存活期低於46-55歲患者(p = 0.02)，但優於76歲以上患者(p < 0.001)。於多變數分析中，我們發現男性(HR, 1.70; 95% CI: 1.08-2.68)、身體質量指數低於25 kg/m2 (HR, 2.72; 95% CI: 1.39-5.30)、第四期患者(HR, 2.62; 95% CI: 1.50-4.57)以及貧血(HR, 2.08; 95% CI: 1.15-3.77)與較差之預後有相關。 針對老年肺癌族群，我們收了576位年齡70歲以上晚期非小細胞肺癌患者。其中419位(72.7%)有接受全身性治療，包含182位(31.6%)接受化學治療、237位(41.1%)接受標靶藥物治療。相比於70-79歲患者，年齡大於80歲之患者較少接受化學治療(12.3% vs. 40.9%, p <0.001)。於多變數分析中，我們發現抽菸(HR: 1.73, 95% CI: 1.36 – 2.21)、年齡超過80歲(HR: 1.30, 95% CI: 1.01 – 1.67)、日常體能狀態分數大於2(HR: 3.07, 95% CI: 2.37 – 3.98)，與較短之存活時間有關。 於循環腫瘤細胞研究，我們收了29位表皮生長因子受體陽性之晚期非小細胞肺癌患者，偵測血中vimentin陽性之循環腫瘤細胞及循環腫瘤幹細胞，於治療前、治療後2周、12周及疾病惡化時做系列檢測。大部分病患之循環腫瘤細胞及循環腫瘤幹細胞於治療12周後會出現下降，但在疾病惡化時卻不會上升。治療前較高之循環腫瘤細胞及循環腫瘤幹細胞與較差之預後有關。 年輕及老年患者特殊的臨床特性及預後因子分析提供臨床醫師對於不同族群患者提供適當的照護。循環腫瘤細胞的資料也提供另一個晚期非小細胞肺癌預後因子的評估。" | zh_TW |
| dc.description.provenance | Made available in DSpace on 2022-11-24T03:19:01Z (GMT). No. of bitstreams: 1 U0001-0602202220505000.pdf: 3285229 bytes, checksum: 74b3ef38e72249b1058768998d9d0158 (MD5) Previous issue date: 2022 | en |
| dc.description.tableofcontents | "口試委員會審定書…………………………………………………………………… i 誌謝…………………………………………………………………………………… ii 中文摘要……………………………………………………………………………… iii Abstract……………………………………………………………………………… iv Chapter 1. General introduction ……………………………………………………… 1 1.1. Incidence and Mortality of Non-Small Cell Lung Cancer (NSCLC) …… 2 1.2. Role of Age and Gender in Lung Cancer………………………………………… 2 1.3. Lung Cancer in Young Age ………………………………………………………… 3 1.4. Lung Cancer in Elderly Patients………………………………………………… 5 1.4.1. Elderly Patients with Early Stage Lung Cancer…………………………… 6 1.4.2. Elderly Patients with Locally Advanced Lung Cancer …………………… 8 1.4.3. Elderly Patients with Late Stage Lung Cancer …………………………… 9 1.5. Liquid Biopsy in Non-Small Cell Lung Cancer………………………………… 13 1.5.1. Circulating Tumor Cells (CTCs) ……………………………………………… 14 1.5.2. Circulating Free and Tumor DNA ……………………………………………… 18 1.5.3. ctDNA in NSCLC Patients with EGFR mutations……………………………… 20 1.6. Specific Aims of the Thesis……………………………………………………… 22 Chapter 2. Material and Methods ……………………………………………………… 23 2.1. Prognostic Factors of Advanced Non-small Cell Lung Cancer in Young Aged Patients……… 24 2.1.1. Patients Enrollment……………………………………………………………… 24 2.1.2. Data Collection…………………………………………………………………… 24 2.1.3. Statistical Analysis …………………………………………………………… 25 2.2. Advanced Non-Small Cell Lung Cancer in the Elderly: The Impact of Age and Comorbidities on Treatment Modalities and Patient Prognosis……………… 26 2.2.1. Study Population ………………………………………………………………… 26 2.2.2. Data Collection…………………………………………………………………… 26 2.2.3. Statistical Analysis …………………………………………………………… 27 2.3. Vimentin-Positive Circulating Cancer Stem Cells and Tumor Cells in Patients with Advanced EGFR-mutated Non-small Cell Lung Cancer…………………… 28 2.3.1. Patients Enrollment……………………………………………………………… 28 2.3.2. Measurement of CCSC and CTC Levels ………………………………………… 29 2.3.3. Treatment Effectiveness of EGFR-TKI………………………………………… 30 2.3.4. Statistics Analysis……………………………………………………………… 31 Chapter 3. Results………………………………………………………………………… 32 3.1. Prognostic Factors of Advanced Non-Small Cell Lung Cancer in Young Aged Patients………… 33 3.1.1. Clinical Characteristics ……………………………………………………… 33 3.1.2. Treatment Modalities and Response ………………………………………… 34 3.1.3. Survival and Prognostic Factors …………………………………………… 34 3.1.4. EGFR Mutation and Prognosis ………………………………………………… 35 3.2. Advanced Non-Small Cell Lung Cancer in the Elderly: The Impact of Age and Comorbidities on Treatment Modalities and Patient Prognosis………… 36 3.2.1. Clinical Characteristics……………………………………………………… 36 3.2.2. Treatment Modalities…………………………………………………………… 37 3.2.3. Survival and Prognostic Factors …………………………………………… 39 3.3. Vimentin-Positive Circulating Cancer Stem Cells and Tumor Cells in Patients with Advanced EGFR-mutated Non-small Cell Lung Cancer……………… 40 3.3.1. Patients Characteristics……………………………………………………… 40 3.3.2. CCSC and CTC Levels at Diagnosis…………………………………………… 41 3.3.3. Changes in CCSC and CTC Levels during EGFR-TKI Therapy……………… 41 3.3.4. Association between Pretreatment CCSC and CTC Levels, and Treatment Effectiveness of EGFR-TKI……………………………………………………………… 43 Chapter 4. Discussions…………………………………………………………………… 44 4.1. Prognostic Factors of Advanced Non-Small Cell Lung Cancer in Young Aged Patients…………………………………………………………………………………… 45 4.2. Advanced Non-Small Cell Lung Cancer in the Elderly: The Impact of Age and Comorbidities on Treatment Modalities and Patient Prognosis …………… 50 4.3. Vimentin-Positive Circulating Cancer Stem Cells and Tumor Cells in Patients with Advanced EGFR-mutated Non-small Cell Lung Cancer ………………… 60 Chapter 5. Perspectives ………………………………………………………………… 66 5.1. Lung Cancer in Young Adults……………………………………………………… 67 5.2. Advanced NSCLC in the Elderly…………………………………………………… 70 5.3. Vimentin-Positive Circulation Tumor Cells in Advanced EGFR-mutated NSCLC…………………… 73 Chapter 6. Summary………………………………………………………………………… 77 6.1. Prognostic Factors of Advanced Non-small Cell Lung Cancer in Young Aged Patients………… 78 6.2. Advanced Non-Small Cell Lung Cancer in the Elderly: The Impact of Age and Comorbidities on Treatment Modalities and Patient Prognosis……………… 81 6.3. Vimentin-Positive Circulating Cancer Stem Cells and Tumor Cells in Patients with Advanced EGFR-mutated Non-small Cell Lung Cancer…………………… 85 References…………………………………………………………………………………… 90 Tables Table 1. The clinical characteristics of 144 young patients with advanced non-small cell lung cancer………………………………………………………………… 108 Table 2. Univariate prognostic factor analysis of advanced non-small cell lung cancer in young adults ……………………………………………………………… 109 Table 3. Multivariate analysis of prognostic factors in young advanced NSCLC………………………………………………………………………………………………… 110 Table 4. Clinical characteristics of the 576 elderly patients with advanced NSCLC in different treatment groups ………………………………………………… 111 Table 5. A two-step multivariate analyses for prognostic factors in elderly patients with advanced NSCLC who received systemic therapy…………………… 112 Table 6. A multivariate analysis for prognostic factors in elderly patients with advanced NSCLC who received supportive care………………………………… 113 Table 7. Clinicodemographic characteristics of treatment-nave patients with advanced EGFR-mutated non-small cell lung cancer who received EGFR-TKI therapy…… 114 Table 8. CCSC and CTC levels at diagnosis in patients stratified by various clinicodemographic characteristics…………………………………………………… 115 Figures Figure 1. Immunostaining of circulating cancer stem cells (Upper, CD45 (-), CSV (+), Hoechst (+), CD133 (+)) and circulating tumor cells (Lower, CD45 (-), CSV (+), Hoechst (+), CD133 (-))………………………………………………………… 116 Figure 2. Incidence of non-small cell lung cancer among young patients between 2000 and 2009… 117 Figure 3a. Proportion of adenocarcinoma in different age groups ……………… 118 Figure 3b. Proportion of squamous cell carcinoma in different age groups…… 118 Figure 4a. Progression-free survival after chemotherapy and epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy in patients with the EGFR mutation ……… 119 Figure 4b. Progression-free survival after chemotherapy and epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy in patients without the EGFR mutation…… 119 Figure 5a. Treatment modalities in different age groups and comorbidity severity classified by the Charlson comorbidity index (CCI)……………………………… 121 Figure 5b. Treatment modalities in different age groups and comorbidity severity classified by the simplified comorbidity score (SCS)…………………………… 121 Figure 6. The proportions of second-line treatments in patients receiving initial treatments with (a) chemotherapy, and (b) epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI)………………………………………… 123 Figure 7. The flowchart for patient inclusion and measurements of circulating cancer stem cells (CCSCs) and circulating tumor cells (CTCs) levels. NSCLC denotes non-small-cell lung cancer, and EGFR-TKI epidermal growth factor receptor-tyrosine kinase inhibitor……… 124 Figure 8. The levels of (a) circulating cancer stem cells (CCSCs) and (b) circulating tumor cells (CTCs) at diagnosis. CCSC and CTC levels were measured as cell number per 4 mL of blood…………………………………………………………… 126 Figure 9. The median levels and interquartile ranges of (a) circulating cancer stem cells (CCSCs) and (b) circulating tumor cells (CTCs) at diagnosis (n = 29), after 2 weeks (n = 28) and 12 weeks (n = 26) of EGFR-TKI therapy, and at disease progression (n = 13). CCSC and CTC levels were measured as cell number per 4 mL of blood………… 127 Figure 10. Changes in levels of circulating cancer stem cells (CCSCs) and circulating tumor cells (CTCs) after 2 weeks of treatment (a), after 12 weeks of treatment (b), and at disease progression (c), compared with those at diagnosis. The red lines indicated increase of cell numbers, whereas the blue lines decrease or no change…… 129 Figure 11. Progression-free survival in patients with high and low levels of (a)circulating cancer stem cells (CCSCs) and (b) circulating tumor cells (CTCs) at diagnosis…………… 131 Appendix……………………………………………………………………………………… 132" | |
| dc.language.iso | en | |
| dc.subject | 循環腫瘤細胞 | zh_TW |
| dc.subject | 肺癌 | zh_TW |
| dc.subject | 預後因子 | zh_TW |
| dc.subject | 年輕病患 | zh_TW |
| dc.subject | 老年病患 | zh_TW |
| dc.subject | Circulating tumor cell | en |
| dc.subject | Elderly patients | en |
| dc.subject | Young patients | en |
| dc.subject | Prognostic factor | en |
| dc.subject | Lung cancer | en |
| dc.title | 非小細胞肺癌之預後因子 – 聚焦於年輕及年老病患以及循環腫瘤細胞 | zh_TW |
| dc.title | Prognostic Factors of Non-Small Cell Lung Cancer – Focused on Young and Old Age Patients and Circulation | en |
| dc.date.schoolyear | 110-1 | |
| dc.description.degree | 博士 | |
| dc.contributor.coadvisor | 余忠仁(Chong-Jen Yu) | |
| dc.contributor.oralexamcommittee | 楊偉勛(Hsun-Chuan Chan),李崗遠(Shao-Hua Xu),邱昭華(Chao-Jin BAI),陳冠宇 | |
| dc.subject.keyword | 肺癌,預後因子,年輕病患,老年病患,循環腫瘤細胞, | zh_TW |
| dc.subject.keyword | Lung cancer,Prognostic factor,Young patients,Elderly patients,Circulating tumor cell, | en |
| dc.relation.page | 132 | |
| dc.identifier.doi | 10.6342/NTU202200308 | |
| dc.rights.note | 同意授權(限校園內公開) | |
| dc.date.accepted | 2022-02-09 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 臨床醫學研究所 | zh_TW |
| 顯示於系所單位： | 臨床醫學研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| U0001-0602202220505000.pdf 授權僅限NTU校內IP使用（校園外請利用VPN校外連線服務） | 3.21 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。