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  • 學位論文

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

Prognostic Factors of Non-Small Cell Lung Cancer – Focused on Young and Old Age Patients and Circulation

指導教授 : 楊泮池
共同指導教授 : 余忠仁(Chong-Jen Yu)
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摘要


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。

並列摘要


Although several breakthroughs have been achieved in mechanism and treatment of lung cancer, lung cancer is a common cancer and related to high mortality. Lung cancer in young patients is uncommon and they had different clinical characteristics compared with older patients. In contrast, elderly patients were often under-representation in clinical trial due to comorbidities and poor performance status (PS). Both young and old patients need tissue biopsy for diagnosis and post-treatment follow-up. Liquid biopsy provided a tool for diagnosis and serial follow-up cancer status. Circulating tumor cells (CTCs) were cancer cells shedding from solid tumor. CTCs are correlated with the outcomes of patients with some advanced-stage cancers. In young population, we enrolled 144 patients with advanced non-small cell lung cancer (NSCLC) aged less or equal to 45 years. Compare to other age groups (46-55, 56-65, 66-75, and 76 years or older), younger patients (≤ 45 years) of both genders had the highest proportion of adenocarcinoma. The median survival of patients ≤ 45 years old was significantly shorter than that of patients aged 46 to 55 years (p = 0.02) and longer than that of patients ≥ 76 years old (p < 0.001). In multivariate analysis, we found that male gender (HR, 1.70; 95% CI: 1.08-2.68), BMI of less than 25 kg/m2 (HR, 2.72; 95% CI: 1.39-5.30), stage IV disease (HR, 2.62; 95% CI: 1.50-4.57), and anemia (HR, 2.08; 95% CI: 1.15-3.77) were associated with a poor prognosis. In elderly population, we enrolled 576 patients with advanced NSCLC aged over 70 years for analysis. Four hundred and nineteen patients (72.7%) received systemic therapy, including 182 (31.6%) patients who received chemotherapy, and 237 (41.1%) patients who received epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) as initial treatment. Patients aged ≥ 80 were less likely to receive chemotherapy as initial treatment than those aged 70-79 (12.3% vs. 40.9%, p <0.001). In the multivariate analysis, cigarette smoking (HR: 1.73, 95% CI: 1.36 – 2.21), age  80 (HR: 1.30, 95% CI: 1.01 – 1.67), and PS 2 (HR: 3.07, 95% CI: 2.37 – 3.98) were associated with a shorter survival period. In CTCs study, we enrolled 29 patients with EGFR-mutated advanced NSCLC. We check vimentin-positive CTCs and circulating cancer stem cells (CCSCs) at the timing of before treatment, at 2 and 12 weeks after EGFR-TKI therapy, and at disease progression. CCSC and CTC levels became lower after 12 weeks of EGFR-TKI therapy and remained low at disease progression in most patients. High pre-treatment CCSC and CTC levels may be related to poor treatment outcomes. The clinical characteristics and prognostic factors analysis of young and old age patients could help physician to provide adequate care to special population. CTC data also provided prognostic prediction for patients with advanced NSCLC.

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