頭頸部癌症病人接受放射線治療或化學治療後缺血性腦中風之流行學與風險關係

Epidemiology and risk of ischemic stroke in head and neck cancer patients treated with radiotherapy or chemotherapy

吳郁婷(Yu-Ting Wu)

指導教授 ： 黃耀斌

高雄醫學大學/藥學院/藥學研究所/碩士(2014年)

https://doi.org/10.6832/KMU.2014.00147

摘要

研究背景：
目前台灣對於探討頭頸部癌(head and neck cancer)病人其缺血性腦中風流行病學之研究非常有限且結果差異性大，因此本研究將利用國衛院全民健保資料庫來探討癌症與放射線治療(放療)或化學治療(化療)對於缺血性腦中風之流行病學與風險關係。

研究方法：
本研究將利用1999年至2009年國衛院全民健保資料庫，以國際疾病分類診斷碼篩選出於2000年至2008年新診斷之頭頸癌病人，排除年紀小於20歲、先前有缺血性腦中風或癌症病史、納入日後30天內即死亡者。所有病人將依照其癌症類型分組，而後再依其醫療處置分為三組，第一組：單獨手術(Surgery alone)、第二組：放射線治療或合併放射化學治療(RT alone, CT alone, or CCRT，簡稱RT/CT/CCRT)、與第三組：手術合併輔助性放療或化療(簡稱Surgery+RT/CT)，觀察病人發生缺血性中風事件，並追蹤至病人發生事件、死亡、退出健保、或至2009年底。另外，亦以頭頸癌病人1：1方式配對於對照組，以探討癌症與缺血性腦中風之關係。
以Cox proportional hazard model分析有無癌症及不同醫療處置對於缺血性腦中風之風險比，並以Kaplan-Meier Estimate分析無腦中風發生比例(Stroke free rate)之存活曲線。

研究結果與討論：
有癌症病人相較於沒有癌症者，其發生缺血性腦中風之風險約介於3.79-4.87 (p<0.001)；進一步比較不同醫療處置與風險關係，RT/CT/CCRT相較於Surgery alone有較高的風險發生缺血性腦中風(HR約介於1.25-1.58)，且皆達統計學上意義，儘管Surgery with adjuvant therapy相較於Surgery alone卻沒有明顯之差異。而在分析RT/CT/CCRT與Surgery alone間不同變項與缺血性腦中風的關係中，同樣為年紀小於40歲病人，接受RT/CT/CCRT治療之風險更可高達2.63倍 (95% CI: 1.12-6.15)。

結論：
本研究發現一旦病人診斷有癌症，發生缺血性腦中風的風險則增加為一般人的3.79至4.87倍之多；而在接受放療或化療後，相較於手術切除之病人又有較高的風險，尤其年紀小於40歲者風險更可高達2.63至2.93倍。除了醫療處置與年齡，其他因素還包括：共病症、化療處方組合，亦會影響缺血性腦中風發生的可能。

關鍵字：頭頸部癌、缺血性腦中風、放射線治療、化學治療

關鍵字

頭頸部癌 ； 缺血性腦中風 ； 放射線治療 ； 化學治療

並列摘要

Background:
In recently, the studies evaluated the risks of ischemic stroke in head and neck cancer patients are limited and with variation. The purposes of this study are to evaluate epidemiology and risks of ischemic stroke in head and neck cancer and the relationship to radiotherapy or chemotherapy by using the National Health Insurance (NHI) database.

Methods:
We conducted a population based retrospective cohort study in National Health Insurance Research Database (NHIRD) in Taiwan from 1999 to 2009. Our study included patients newly diagnosed with head and neck cancer in 2000 to 2008. Patients aged less than 20 years, with prior ischemic stroke or cancer history, or death within 30 days from diagnosis were excluded.
All the populations were subgroup by their cancer type and then according to treatment modalities divided into group1: Surgery alone; group2: RT alone, CT alone, or CCRT (RT/CT/CCRT); group3: Surgery+RT/CT. Each subject was followed from index date to the occurrence of ischemic stroke, death, withdrawn from the insurance policy, or until 31 December 2009. Besides, to investigate the relationship between cancer and ischemic stroke, we also used a ratio 1:1 to match cancer cohort with control cohort.
Cox proportional hazard model was used to estimate hazard ratios (HR) of ischemic stroke not only between cancer cohort and control cohort but also among different treatment modalities. We also calculate the survival analysis of stroke-free survival rate by using Kaplan-Meier method.

Results and discussion:
The HRs of ischemic stroke between cancer cohort and control cohort about ranged from 3.79 to 4.87 (p<0.001). Further, patients received RT/CT/CCRT compared with surgery alone had higher risk of ischemic stroke (HRs ranged from 1.25 to 1.58), with significantly difference. However, there were no difference between Surgery+RT/CT and surgery alone. In subgroup analysis, the HR of ischemic stroke was 2.63-folds higher in patients received RT/CT/CCRT compared with patients received surgery alone when patients aged less than 40 years old (95% CI: 1.12-6.15).

Conclusions:
Our study demonstrated that once patients diagnosed with head and neck cancer, then the risk of ischemic stroke would increase to 3.79- 4.87 folds. And patients treated with radiation or chemotherapy compared with surgery alone had a higher risk for occurrence of ischemic stroke, especially in patients who aged less than 40 years old had a 2.63-2.93 folds risk. Despite of treatment modalities and age, other factors such as comorbidities, chemotherapy regimens may probably influence the risk.

Key words:
Head and neck cancer, ischemic stroke, radiotherapy, chemotherapy

並列關鍵字

head and neck cancer ； ischemic stroke ； radiotherapy ； chemotherapy

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