臺灣口腔癌病人延遲治療對存活率之影響

The Effect of Delayed Treatment on Survival of Oral Cancer in Taiwan

李怡樺(Yi-Hua Lee)

指導教授 ： 陳秀熙

國立臺灣大學/公共衛生學院/流行病學與預防醫學研究所/碩士(2019年)

https://doi.org/10.6342/NTU201904018

摘要

研究背景
口腔癌在許多區域包含美拉尼西亞、東亞及東南亞、中東歐等都有相當高的發生率，究其原因為菸、飲酒及檳榔嚼食之盛行。由於半數口腔癌診斷時均為晚期口腔癌，而晚期癌5年存活率僅約20-30%，欲改善口腔癌之存活，早期診斷及治療為策略之一，然而診斷至接受口腔癌治療的時間若時間拖的太長，往往會造成惡化及期別變差，也影響了其存活。
研究目的 本研究目的如下：
(1)探索臺灣地區口腔癌病人治療延遲之描述性分析；
(2)分析延遲治療對口腔癌存活率之影響；
(3)考慮時間相依治療特性，評估延遲治療對口腔癌存活率之影響。
材料與方法
本論文分析臺灣地區2004年至2015年診斷之30歲以上口腔癌病患，並追蹤至2016年，分析性別、性齡、口腔癌期別、診斷期間、診斷醫院層級及不同部位口腔癌在診斷至治療之延遲時間之差異，並得到其口腔癌累積存活曲線。利用冦斯比例風險模式及時間相依冦斯比例風險模式得到不同延遲治療狀況及前述相關因子之風險對比值與其95%信賴區間。
結果
本研究共分析73,829名口腔癌個案，其中約九成有治療紀錄，在接受治療的個案中，從診斷到治療時間間隔(diagnosis-to-treatment interval, DTI)的中位數為20天 (四分位範圍為12至30天)。相較於未治療組，在3週內、3-6週及超過6週以上治療的病患其死亡口腔癌的風險比(Hazard Ratio, HR)分別為0.57 (95% CI: 0.55-0.59), 0.69 (95% CI: 0.66-0.72), and 0.86 (95% CI: 0.82-0.90)，而此效應會被病患是否曾暴露於口腔黏膜篩檢所修飾(p=0.042)。在調整性別、年齡、不良口腔習慣(包括吸菸、飲酒及嚼食檳榔，此變項僅適用於暴露組)、治療醫院層級等干擾因子，暴露組個案在三週內接受治療其死於口腔癌的風險最低(相較於未治療組之調整風險比aHR [adjusted hazard ratio]=0.58, 95% CI: 0.54-0.63)，延遲3-6週者次之(aHR=0.65, 95% CI: 0.60-0.70)，再者為延遲6週以上(HR=0.75, 95% CI: 0.69-0.81)，對從未暴露篩檢的口腔癌個案，以上三組的調整風險比則分別為(3週以下：aHR=0.56, 95% CI: 0.53-0.59；3-6週aHR=0.59, 95% CI: 0.56-0.62；6週以上aHR=0.71, 95% CI: 0.66-0.75)。值得注意的是，若考慮治療的時間相依特性，超過6週以上才治療的個案其死於口腔癌的風險與未治療組並未達統計上顯著意義(暴露組：aHR=1.02, 95% CI: 0.94-1.11)，非暴露組：aHR=1.00, 95% CI: 0.94-1.06)。
結論
口腔癌個案在診斷後的6週內接受治療之個案其存活率明顯較佳，在醫學中心接受治療者之存活狀況也有較好的存活狀況，本研究之結果可提供專科醫師在轉介及安排病患治療之參考。

關鍵字

口腔癌 ； 延遲治療 ； 篩檢 ； 抽菸 ； 嚼食檳榔 ； 診斷至接受口腔癌治療時間區間

並列摘要

Background:
The incidence of oral squamous cell carcinoma (OSCC) is highest in areas such as Melanesia, South-Central/Southeast Asia, and Central and Eastern Europe where habits of cigarette smoking, alcohol drinking, and betel quid chewing are prevalent. Since more than 50% of the oral cancer is diagnosed at advanced stages (stage III or IV) which has a poor 5-year survival of around 20-30%, the strategy toward early diagnosis and treatment is thus upmost for further improvement of survival. However, significant tumor progression was reported during the period between diagnosis and the initiation of treatment and tumor upstaging may result in decreased survival for those receiving treatment after the prolonged diagnosis-to-treatment interval (DTI).
Aims: My thesis was
(1)to report the DTI among oral cancer patients exposed or not exposed to nationwide screening program;
(2)to evaluate the impact of DTI on overall survival (OS) in a nationwide scale data source; and
(3)to elucidate the impact of DTI making allowance for its time varying property.
Materials and Methods:
Patients of oral cancer diagnosed at age of 30 years or older between 2004 and 2015 were included for analyses. Demographic characteristics were collected at baseline and survival of oral cancer were ascertained by following up until the end of 2015. Univariate and multivariable Cox proportional hazards regression model was used to compute hazard ratio (HR) and 95% confidence interval (CI). The Kaplan-Meier method was used to compare OS. The time-dependent Cox proportional hazards regression model was used to estimate the hazard ratio for treatment after the time of the inception of treatment.
Results:
A total of 73,829 oral/oropharyngeal cancers were diagnosed and treated after the screening with a median DTI of 20 days (interquartile range 12 to 30 days). Compared to non-treated group, those receiving treatment within 3 weeks, 3-6 weeks, and longer than 6 weeks had hazard ratios of 0.57 (95% CI: 0.55-0.59), 0.69 (95% CI: 0.66-0.72), and 0.86 (95% CI: 0.82-0.90), respectively. There exists interaction between exposure and DTI groups (p=0.042). After adjusting for sex, age, unhealthy oral habits [(betel quid chewing, cigarette smoking, alcohol drinking), only available for those attending screening], and hospital level for treatment, DTI shorter than three weeks still had lowest risk of oral cancer death (aHR=0.58, 95% CI: 0.54-0.63), followed by those in 3-6 weeks (HR=0.65, 95% CI: 0.60-0.70), and longer than 6 weeks (HR=0.75, 95% CI: 0.69-0.81) in patients exposed to screen. For those never attended screening, DTI less than three weeks still had lowest risk of oral cancer death (aHR=0.56, 95% CI: 0.53-0.59), followed by those in 3-6 weeks (HR=0.59, 95% CI: 0.56-0.62), and longer than 6 weeks (HR=0.71, 95% CI: 0.66-0.75). Note that with time-dependent Cox model, treatment delayed for longer than 6 weeks became insignificantly different from the untreated group in both exposed (aHR=1.02, 95% CI: 0.94-1.11) and unexposed group (aHR=1.00, 95% CI: 0.94-1.06).
Conclusions:
DTI shorter than 6 weeks is associated with a significant favorable survival in oral cancer. These subjects had more favorable overall survival when treated at medical center. Specialists receiving referral should refer to this information while arranging treatment for the patients.

並列關鍵字

oral cancer ； delayed treatment ； screening ； cigarette smoking ； betel quid chewing ； diagnosis-to-treatment interval

參考文獻

References

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