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  • 學位論文

在台灣因表皮生長因子酪氨酸激酶抑制劑上市對非小細胞肺癌病人延長存活期之臨床表徵評估

Specific clinical features which contribute survival benefit of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) to non-small cell lung cancer (NSCLC) in Taiwan

指導教授 : 曹昌堯 吳文俊

摘要


動機與研究目的:利用長期健保資料庫分析標靶藥物治療對肺癌患者存活之影響。 研究方法:本研究以國家衛生研究院發行的全民健康保險資料庫為資料來源,選取2002-2010年罹患肺癌者,排除肺癌期別紀錄不明或是其他重要變項如性別及年齡等缺漏,最後納入研究的樣本共87320人。本研究依據健保將兩種標靶藥物納入給付的時間分為2002-2004年(化學療法)、2005-20010年(分無使用標靶藥及使用標靶藥)共三組,並將初次診斷為肺癌的患者歸入上述三個組別,以觀察標靶藥物納入給付的影響,並分析性別、癌症細胞型態及肺癌期別是否對患者的5年的存活情形造成影響。 結果:2001-2010年診斷肺癌者,以診斷年代及使用標靶藥分組的5年累計存活率曲線。其中第1年的累計存活率曲線有使用標靶藥為0.799顯著高於2001-2004年化療時期的0.363及2005-2010年無使用標靶藥的0.358。但至第5年時,2005-2010年有使用標靶藥反而有最低的累計存活率曲線,其值為0.084,此時的2001-2004年化療時期累計存活率曲線為0.093以及2005-2010年無使用標靶藥的0.118。2001-2010年診斷為肺鱗狀細胞癌者以診斷年代及使用標靶藥分組的5年累計存活率曲線。其中有使用標靶藥第1年的累計存活率曲線為0.791顯著高於化療時期的0.360及無使用標靶藥的0.344。但至第5年時,有使用標靶藥反而有最低的累計存活率曲線,其值為0.049,此時的化療時期累計存活率曲線為0.096以及無使用標靶藥0.102。2001-2010年診斷為肺腺癌者,有使用標靶藥第1年的累計存活率曲線為0.808顯著高於化療時期的0.434及無使用標靶藥的0.438。但至第5年時,有使用標靶藥反而有最低的累計存活率曲線,其值為0.092,此時的化療時期累計存活率曲線為0.109以及無使用標靶藥的0.169。結果發現2005-2010年被診斷肺癌者比起2001-2004年被診斷者死亡的風險下降10%,HR = 0.90 (95% CI = 0.874 - 0.926)。其中2005-2010年有使用標靶藥物者比未使用者,自肺癌診斷後死亡的風險比值(Hazard Ratio)為0.512 (95% CI = 0.498 - 0.527)。女性使用標靶藥者比男性使用標靶藥者有更低的死亡風險。 結論:使用標靶藥物治療對於女性,肺腺癌患者有延長存活期的效果,但是對於鱗狀細胞肺癌則沒有顯著效果,至第5年顯示使用標靶藥物均無法優於化學療法存活期。

並列摘要


Objective: To evaluate the effectiveness of target therapy on the survival of patients with lung cancer by using longitudinal National Health Insurance (NHI) databases. Methods: Data source of this study came from the NHI research databases published by the National Health Research Institutes. Patients from year 2002 to 2010 were included. After excluding subjects with missing cancer staging, or other important variables such as age and sex, this study included 87320 subjects in the analysis. According to the inclusion time of target therapies by the NHI, this study classified all of the subjects into 3 groups: year 2002-2004 (chemotherapy only), year 2005-2010 without target therapy and year 2005-2010 with target therapy. The newly diagnosed lung cancer patients were then assigned to the above 3 groups to examine whether the availability of target therapy as well the patient’s gender, cancer cell type and stage affect the 5-year survival of the patients. Results: First of all, we analyzed the 1-year and 5-year cumulative survival of the patients with lung cancer. The 1-year cumulative survival probability was 0.799 for the target therapy group which was higher than 0.363 for the year 2002-2004 chemotherapy group and 0.358 for the year 2005-2010 without target therapy group. However, the 5-year cumulative survival probability was 0.084 for the target therapy group which was lower than 0.093 for the year 2002-2004 chemotherapy group and 0.118 for the year 2005-2010 without target therapy group. Second, we analyzed the patients with squamous cell carcinoma. The 1-year cumulative survival probability was 0.791 for the target therapy group which was higher than 0.360 for the year 2002-2004 chemotherapy group and 0.344 for the year 2005-2010 without target therapy group. However, the 5-year cumulative survival probability was 0.049 for the target therapy group which was lower than 0.096 for the year 2002-2004 chemotherapy group and 0.102 for the year 2005-2010 without target therapy group. Third, we analyzed the patients with adenocarcinoma. The 1-year cumulative survival probability was 0.808 for the target therapy group which was higher than 0.434 for the year 2002-2004 chemotherapy group and 0.438 for the year 2005-2010 without target therapy group. However, the 5-year cumulative survival probability was 0.092 for the target therapy group which was lower than 0.109 for the year 2002-2004 chemotherapy group and 0.169 for the year 2005-2010 without target therapy group. The results also showed that lung cancer patients diagnosed in year 2005-2010 had 10% lower mortality risk (hazard ratio = 0.90 with 95% CI = 0.874 - 0.926) compared with those diagnosed in year 2002-2004. Among the patients diagnosed in year 2005-2010, those received target therapy had much lower mortality risk with HR = 0.512 (95% CI = 0.498 – 0.527) compared with those did not received target therapy. In addition, female patients receiving target therapy had lower mortality risk than male patients receiving target therapy. Conclusion: The target therapies can prolong the length of survival for female and patients with adenocarcinoma but not those with squamous cell carcinoma. However, there was no difference in the 5-year survival between target therapy and chemotherapy groups.

參考文獻


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