在台灣罹患局部進行期直腸癌病患接受術前合併化學及放射線治療的有效性及安全性之研究

A Observational Study of the Efficacy and Safety of Chemoradiotherapy in the Pre-operative Treatment of Taiwanese Patients with Locally Advanced Rectal Cancer

陳欽凡(Chin-Fan Chen)

指導教授 ： 王照元

高雄醫學大學/醫學院/臨床醫學研究所/碩士(2012年)

https://doi.org/10.6832/KMU.2012.00013

摘要

主題一
研究背景及目的 這個研究的目的是對於在台灣局部進行期直腸癌(T3 or T4 or lymph node metastasis)的病患， 安排其接受手術前化學治療同時合併放射線治療， 評估其治療的有效性及安全性。
研究材料及方法 共有74位病患被收錄在此研究中， 所有的病患均接受相同的術前放射線治療處方(總劑量45-50.4 Gy， 分成25次給予， 每個星期接受放射線治療5天， 總治療時間為5星期) ， 在術前化學治療方面， 其中27位病患接受5-FU(350 mg/m2， 靜脈注射， 1天1次， 1星期治療5天， 只在給予放射線治療的第1及第5週給予化學治療)及leucovorin (20mg/m2， 靜脈注射， 給予時間同5-FU); 另外的47位病患接受口服Capecitabine(每次850mg/m2， 一天給予兩次， 一週內有5天服用， 總治療時間為5星期)， 病患在術前化學治療合併放射線治療療程結束後第6-8週時接受直腸癌切除手術。在治療過程中， 相關的資料均被記錄下來並接受統計學上的分析比較。
結果 嚴重的併發症(Grade 3 or 4)發生在40.7%的5-FU組病患及19.1%的capecitabine組病患(p=0.044)。在5-FU組中有6位病患(22.2%)， 以及在capecitabine組中有6位病患(14%)接受治療後， 於外科切除手術的病理組織中已看不到任何的癌症細胞(Pathological complete response)。治療後腫瘤的T分期改善(T stage down-staging)發生在51.9%的5-FU組病患及69.8%的capecitabine組病患。治療後病理T分期為ypT0-2的狀況發生在40.7%的5-FU組病患及67.4%的capecitabine組病患 (p=0.028)。
結論 考量到治療後有較高比例的病患達到ypT0-2分期、 較少的急性治療併發症， 加上不需要置入注射化學治療藥物所需的靜脈導管而避免了導管帶來的不便及相關併發症， 因此我們認為在局部進行期直腸癌病患接受術前化學治療同時合併放射線治療時， 使用口服capecitabine合併放射線治療， 相較於5-FU合併放射線治療， 前者是一個較佳的選擇。

主題二
研究背景及目的 這個研究的目的是對於在台灣罹患局部進行期直腸癌病患安排其接受術前口服capecitabine合併螺旋斷層放射線治療， 評估其治療的有效性及安全性， 並與術前口服capecitabine合併2-dimentional(2D)放射線治療病患的治療結果做比較。
研究材料及方法 共有29位病患被收錄在此研究中， 所有的病患均接受術前口服capecitabine(每次850mg/m2， 一天給予兩次， 一週內有5天服用， 總治療時間為5週)合併螺旋斷層放射線治療(針對腫瘤病灶之放射線總劑量50.4 Gy， 分成25次給予; 針對腫瘤周圍淋巴結及癌轉移高危險區之放射線總劑量45 Gy， 分成25次給予; 每個星期接受放射線治療5天， 總治療時間為5星期) ， 病患在術前化學合併放射線治療療程結束後第6-8週時接受直腸癌切除手術。在治療過程中， 相關的資料均被記錄下來， 並將結果與過去文獻資料加以比較。
結果 有10.3%的病患發生嚴重的(NCI CTC grade 3 or 4)急性併發症， 而在所有的急性併發症中， 以腹瀉最為常見(72.4%病患)。共有28位病患在化學治療合併放射線治療後接受手術。在22位直腸腫瘤距離肛門緣5公分以內的病患中， 有19位病患在接受術前放射合併化學治療及手術後可以保留住肛門(肛門保留率86.4%)。 共有23位病患(82.1%)之病理腫瘤萎縮分級 (tumor regression grade)達到第2-4級。 腫瘤的T分期及N分期改善分別呈現在67.9%以及53.6%之病患，有18位病患(64.3%)接受治療後達到ypT0-2N0分期。 在術後追蹤的過程中有14.3%的病患發生嚴重的晚期併發症。在與同在高雄醫學大學附設醫院， 術前接受capecitabine合併2D放射線治療的28位病患其治療結果比較後，我們發現接受capecitabine合併螺旋斷層放射線治療的病患在移除腸造瘻恢復腸道通暢後， 有較高的比率可以恢復正常的腸道排便功能(每天排便1至3次)。
結論 考量到治療後有較高比例的病患達到ypT0-2N0分期， 以及移除腸造瘻後有較高比例的病患可以恢復正常的腸道功能， 我們認為使用口服capecitabine合併螺旋斷層放射線治療， 可以作為局部進行期直腸癌病患接受傳統術前化學合併放射線治療處方之外的另一個選擇。

關鍵字

直腸癌 ； 術前化學治療 ； 放射線治療, 螺旋斷層放射線治療

並列摘要

Topic 1

Background and Objectives: This study is to evaluate the safety and efficacy of preoperative radiotherapy (RT), combined with bolus infusional 5-fluorouracil (5-FU) or oral capecitabine, in patients with locally advanced rectal cancer (LARC).

Materials and Methods: Seventy-four patients were retrospectively analyzed. Twenty-seven patients were treated with 5-FU (350 mg/m2 IV bolus) and leucovorin (20 mg/m2 IV bolus) for 5 days/week during week 1 and 5 of RT. Forty-seven patients were treated with capecitabine (850 mg/m2, twice daily for 5 days/week). Both groups received the same RT course (45-50.4 Gy/25 fractions, 5 days/week, for 5 weeks). Patients underwent surgery in 6 weeks after completion of the chemoradiotherapy. Data of the observational study were collected.

Results: Grade 3 or 4 toxicities occurred in 40.7% (5-FU) and 19.1% (capecitabine) of the patients (P = 0.044). Six patients in the 5-FU group (22.2%) and six patients in the capecitabine group (14%) achieved complete response. Primary tumor (T) downstaging were achieved in 51.9% (5-FU) and 69.8% (capecitabine) of the patients. The pathological ypT0-2 stage was 40.7% (5-FU) and 67.4% (capecitabine) (P = 0.028).

Conclusions: In consideration of the better ypT0-2 downstaging rate, less severe toxicities, and no need for indwelling intravenous device on oral capecitabine regimen, the administration of oral capecitabine with RT may be a more favorable option in the neoadjuvant treatment for LARC.

Topic 2

Background and Objectives: The objective of this study was to identify the efficacy and safety profile of preoperative helical tomotherapy in combination with oral capecitabine in Taiwanese patients with locally advanced rectal cancer, with the additional analysis on low-lying tumors (tumor located ≦ 5cm from the anal verge).

Materials and Methods: Twenty-nine patients receiving treatment were retrospectively analyzed. All patients were treated with oral capecitabine (850 mg/m2 twice daily for 5 days/week) received the helical tomotherapy with 45 Gy in daily fractions of 1.8 Gy was delivered to the presacral space, regional lymph nodes and areas at risk for harboring microscopic disease. The dose was increased by a simultaneous integrated boost to 50.4 Gy to the gross tumor. Patients underwent surgery in 6-8 weeks after completion of the chemoradiotherapy. Data of the observational study were collected and the results were compared with the previous literature.

Results: Grade 3 or 4 acute toxicities occurred in 10.3% of the patients. Diarrhea was the most frequently encountered toxicity in the study (72.4%). Except one patient who declined the operation, 28 patients received surgery after chemoradiotherapy. Of the 22 patients who had distal rectal cancer (≦ 5cm from anal verge), 19 patients received sphincter-sparing operation (anal preserving rate = 86.4%). Pathological tissue regression grade 2-4 was noted in 23 patients (82.1%). Four patients (14.3%) achieved pathological complete response. Primary tumor (T) and node (N) down-staging were achieved in 67.9% and 53.6% of the patients. Eighteen patients (64.3%) achieved ypT0-2N0 stage. Grade 3 or 4 late morbidity occurred in 14.3% of the patients. Better function outcome of the intestine after restoring the bowel continuity was noted in the present study in comparison with the treatment results of preoperative capecitabine plus 2-dimentional radiotherapy in the same hospital.

Conclusions: In consideration of the better ypT0-2N0 rate and a better functional outcome after restoring the bowel continuity, oral capecitabine in combination with helical tomotherapy provides an alternative option in LARC other than conventional chemoradiotherapy.

並列關鍵字

Rectal Cancer ； Preoperative chemotherapy ； Radiotherapy ； Helical tomotherapy

參考文獻

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