沒有照片 作者: 邱文彦
班別: 碩士班
畢業年度: 103
指導老師: 李中一
論文題目: 23價肺炎鏈球菌疫苗在老年癌症病患的效用

[ 摘要 ]
目的
肺炎鏈球菌是肺炎的首要原因,而肺炎是癌症病患死亡的主要原因之一,然而不論是23價多醣體肺炎疫苗還是結合型肺炎疫苗,都不曾研究過其對癌症病人的臨床效用,除了曾經在何杰金氏淋巴癌病人上探討過23價肺炎疫苗的效果。本篇研究主題是探討75歲以上之年長癌症病患接種23價肺炎疫苗的效用。
材料
為了探討23價肺炎疫苗在不同種類癌症上的效果,以及最佳施打時機,本研究總共包含肺癌、攝護腺癌、大腸直腸癌、所有癌症、癌症長期存活者,以及在癌症診斷後六、十二個月內、一到兩年內施打疫苗,共八個不同的世代研究。
資料分別來源於台灣健保資料庫2005年的百萬與兩百萬歸人檔,以及2000年到2010的台灣所有癌症病人及對照組個案資料,最長時間追蹤到2013年。
方法
癌症診斷使用重大傷病卡資料確認。23價肺炎疫苗施打資料來自於藥檔,因為肺炎鏈球菌使用住院診斷資料會被嚴重低估,本研究目標是所有細菌性肺炎(ICD-9-CM codes 481-482 and 485-486),排除病毒性肺炎、其他特定非肺炎鏈球菌之肺炎、流感肺炎。
使用卜瓦松迴歸模型校正年齡、性別、流感疫苗施打、施打季節、癌症治療的所有可能方式、共病和社經地位。肺癌世代中進行了次群組分析,排除曾經接受過流感疫苗的病人。在探討特定時間疫苗施打效果的世代中,校正了癌症期別並將安寧緩和排除。並分析了累積發生率與總體存活時間。
結果
在此研究中,老年癌症病患的肺炎住院發生率,最低是大腸直腸癌長期存活病人每千人年74.53次,最高是肺癌病人每千人年444.2次。肺炎住院發生率隨著觀察起始時間離癌症發生時間的越遠越低。
長期存活者也比不限長期存活者有較低的發生密度。除了大腸直腸癌的長期存活者世代,23價肺炎疫苗對所有世代都會降低肺炎住院之發生密度, 最少減少4.41 %,最多減少38.09%。對不同癌症而言,肺癌病人有最高風險,次之是攝護腺癌,其次是大腸直腸癌。.
對包含所有癌症種類的世代,23價肺炎疫苗可顯著降低肺炎發生率,校正後的發生率比值(aIRR)為0.695 (p值小於0.05);區分不同癌症分析可以發現,風險最高的肺癌世代,疫苗會顯著減少其風險(aIRR為0.740,p值小於0.05);疫苗在三個大腸直腸癌世代(一年內施打、一到兩年間施打、不限長期存活者)都明顯降低風險(aIRR分別為0.440、0.192和0.880,p值都小於0.05),但是大腸直腸癌長期存活者世代則不顯著(aIRR為1.011);在兩個攝護腺癌世代(長期與不限長期存活者),23價肺炎疫苗都沒有到達統計意義,aIRR分別為0.907和0.948,接近1);兩種癌症(大腸直腸與攝護腺)長期存活世代的aIRRs都接近1。所有世代中,流感疫苗都沒有改變肺炎住院發生率(aIRR接近1)。
結論
此研究結果顯示23價肺炎疫苗對癌症患者和接受抗癌期間施打,可降低肺炎發生率,且具統計上意義;23價肺炎疫苗對較侵略性癌症種類的病人或者肺炎風險較高的病人,例如肺癌病人或合併肺部共病的病人,以及較早期接受23價肺炎疫苗的效果較明顯,但是對長期存活者或攝護腺癌的效果較不明顯。根據本研究結果,建議癌症患者接受23價肺炎疫苗接種,尤其是上述效果明顯的特定癌症族群,而且施打時機應盡早。
 
[ 英文摘要 ]
Objective
Streptococcus pneumoniae is a leading cause of pneumonia, one of the major causes for mortality, in cancer patients. However, neither 23-valent pneumococcal polysaccharide vaccine (PPSV23) nor pneumococcal conjugate vaccine has been investigated for their effectiveness in cancer patients in the past, except that of PPSV23 in patients with Hodgkin's disease. Our aim in this study was to investigate the effectiveness of PPSV23 in elderly cancer patients ≥ 75 years of age.
Data Sources
To evaluate effectiveness of PPSV23 and best vaccination timing in patients with different cancer types, we used totally eight different study cohorts in this study, including those with lung cancer, prostate cancer, colorectal cancer, all cancer types, or long-term cancer survivors, who received vaccination within the first 6, 12, and 12 to 24 months post cancer diagnosis. The data were obtained from one- or two-million people randomly sampled in year 2005; and claim data of all study subjects from 2000 to 2010 were collected based on Taiwan National Health Insurance Research Database (NHIRD), with longest follow-up to the end of 2013.
Methods
Cancer diagnosis was validated using cross-linked data from catastrophic illness registry. PPSV23 vaccinated groups were identified by using drug codes. Because frequency of pneumococcal pneumonia hospitalization is severe under-estimated in clinical practice, primary endpoint was all-cause bacterial pneumonia (ICD-9-CM codes 481-482 and 485-486). Viral pneumonia, pneumonia due to specific bacteria other than S. pneumoniae, and influenza pneumonia were excluded.
Multivariate log-linear Poisson regression model was used, with potential confounders adjusted including age, gender, influenza vaccination, vaccination period, all possible cancer treatment modalities, co-morbidities, and sociodemographic variables. Subgroup analysis was performed in the lung cancer cohort, excluding patients who ever received influenza vaccine during study period. In cohorts of vaccination within specific time, cancer stage information was included and hospice were excluded. The Kaplan-Meier method was used to estimate cumulative incidence of pneumonia hospitalization and overall survival time.
Results
In the present study, the incidence rate in elderly cancer patients aged ≥ 75 years ranged from lowest 74.53 per 1000 person-years (PYs) for long-term colorectal cancer survivors to highest 444.2 per 1000 PYs for lung cancer patients. Incidence density (ID) of pneumonia hospitalization was higher in earlier time period after cancer diagnosis than later period). Long-term survivors had lower IDs than cohorts not limiting long-term survivors. PPSV23 decreased ID in all study cohorts, with decreased percentage ranging from 4.41 % to 38.09%, except the long-term colorectal cancer survivor cohort. For different cancers, lung cancer patients had the highest risk of pneumonia hospitalization, followed by prostate and colorectal cancer, in sequence.
PPSV23 was significantly with a lower adjusted incidence rate ratio (aIRR) of 0.695 (p < 0.05) for all cancer types cohort. Differentiating individual different cancer types, PPSV23 had significant low aIRR of 0.740 (p < 0.05) for lung cancer cohort which had the highest risk of pneumonia hospitalization. Three colorectal cohorts (vaccination within one year or one to two years, and not limiting long-term) had significant low aIRR (0.440, 0.192, 0.880, respectively, all p < 0.05); but such reduced rate was not observed for long-term survived colorectal cohort (aIRR = 1.011). In both prostate cohorts, PPSV23 did not show significantly reduced rates with an aIRR of 0.907 and 0.948, respectively, both close to 1. In long-term survivor cohorts of both colorectal and prostate cohorts, aIRRs were not statistically significant and close to 1 in. In all cohorts cohort, influenza vaccination did not significantly decrease incidence of pneumonia hospitalization, with most aIRR close to 1
Conclusion
In this study, PPSV23 showed a significant association with reduced rate of pneumonia for cancer patients; and it is also effective in the period of anti-cancer treatments. The effect was more obvious for patients who had more aggressive cancer or higher risk of pneumonia, like patients with lung cancer or lung comorbidities. Early receipt of PPSV23 was also observed effective. On the other hand, it is not so obvious in long-term survivors and in patients with prostate cancer. Based on the study findings, we recommend that cancer patients should receive PPSV23, especially for those cancer subgroups potential beneficial from vaccination; and the timing of vaccination should come sooner, if possible, after cancer diagnosis.
 
住址: 台南市大學路一號 1 University Road, Tainan, TAIWAN 701    TEL: 06-235- 3535 EXT 5561 or 5562    傳真: 06-2359033    email: em75561@email.ncku.edu.tw