指肠癌术后三维适形/调强放疗联合化疗与单纯辅助化疗的疗效比较
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摘要
目的：直肠癌是较为常见的恶性肿瘤，手术是直肠癌的主要治疗手段。尽管外科技术不断进步，其5年生存率仍徘徊于50%，治疗失败的原因主要为局部复发和远处转移。多年来实践证明，各期直肠癌术后辅助放化疗是直肠癌综合治疗的标准手段。但目前直肠癌术后辅助放化疗尚存在一些问题，术后辅助放化疗的经典研究均是在常规放疗的基础上完成。随着放射治疗技术的进展，采用精确放疗技术如三维适形/调强放疗是否较常规术后放疗能进一步提高局控率，减少毒副作用。哪些患者是辅助放化疗的最佳获益人群？本研究回顾性分析226例直肠癌Ⅱ、Ⅲ期患者术后TNM分期、辅助放化疗与辅助化疗、同步放化疗与序贯放化疗、手术与放疗间隔时间、化疗周期数等因素对局部复发率、总生存率（OS）和无病生存率（DFS）的影响，同时对其预后影响因素进行分析，观察三维适形/调强放疗技术进行盆腔预防性照射的毒副作用，以期更深入地了解直肠癌的局部复发、生存情况及治疗副反应，为临床制定更科学的、个体化的治疗方案提供一定理论依据。
方法：收集2006年6月至2010年12月于河北医科大学第四医院行直肠癌根治术患者226例，其中pTNM分期Ⅱ期51例，Ⅲ期患者175例。辅助化疗组116例，辅助放化疗组110例，放疗剂量45～54Gy，中位剂量50Gy，其中采用三维适形放疗88例，调强放疗22例。全组患者化疗周期数为2～8周期，中位4周期。191例以FOLFOX方案（奥沙利铂+亚叶酸钙+5-氟尿嘧啶/替加氟）化疗，24例行LF方案（亚叶酸钙+5-氟尿嘧啶/替加氟）化疗，11例口服单药希罗达。中位随访期30月。分析TNM分期、辅助放化疗与辅助化疗、同步放化疗与序贯放化疗、手术与放疗间隔时间、化疗周期数等因素对局部复发率、OS和DFS的影响，并进一步探讨Ⅱ～Ⅲ期直肠癌根治术后影响预后的主要因素。
结果：
1全组治疗状况：全组1、2、3年局部复发率和远处转移率分别为9.8%、20.7%、22.8%和15.2%、31.2%、39.4%，全组1、2、3年OS和DFS分别为94.4%、71.7%、61.5%和78.8%、59.8%、53.1%。全组59.3%患者出现1～2级胃肠道毒副反应，46.9%患者出现1～2级血液学毒副反应，无3级及以上毒副反应发生。术后放化组的胃肠道、血液学毒副反应发生率分别为78.2%和64.5%，明显高于术后化疗组的41.4%和30.2%（χ~2=31.683，P=0.000；χ~2=26.786，P=0.000）。术后放化组中，20.9%患者出现放射性肠炎，其中1级占11.8%，2级占9.1%；10%患者出现放射性膀胱炎，1级占8.2%，2级占1.8%。
2T_2期、T_3期患者的1、2、3年局部复发率、DFS无明显差异（χ~2=1.041，P=0.314；χ~2=2.295，P=0.130），T_2期患者OS高于T_3期患者（χ~2=4.278，P=0.039）。
3N_0期、N_1期、N_2期患者的1、2、3年局部复发率、OS及DFS均有显著差异（χ~2=14.599，P=0.001；χ~2=47.196，P=0.000；χ~2=38.885，P=0.000），随N分期增加，局部复发率高，OS及DFS均有下降。
4Ⅱ期患者的1、2、3年局部复发率明显低于Ⅲ期患者（χ~2=13.800，P=0.000）。OS、DFS均明显高于Ⅲ期患者（χ~2=18.610，P=0.000；χ~2=14.993，P=0.000）。
5术后放化组1、2、3年局部复发率分别为3.8%、10.5%、10.5%，明显低于术后化疗组的15.5%、29.7%、33.2%（χ~2=11.213，P=0.001），术后放化组与术后化疗组1、2、3年OS分别为94.2%、76%、70.7%和95.6%、68.4%、53.5%，1、2、3年DFS分别为81.9%、60%、54.1%和76%、59.2%、52.3%，组间差异不显著（χ~2=3.579，P=0.059；χ~2=0.263，P=0.608），但术后放化组有延长OS的趋势。
6化疗周期数：化疗≥4周期组1、2、3年局部复发率低于化疗＜4周期组（χ~2=4.631，P=0.031），化疗≥4周期组OS、DFS均高于化疗＜4周期组，统计学有显著性差异（χ~2=5.306，P=0.021；χ~2=3.941，P=0.047）。
7将手术与放疗时间间隔分为≤30天（26例）、31～60天（36例），＞60天（48天）三组，结果显示不同时间间隔组1、2、3年局部复发率、OS、DFS均无明显差异（χ~2=1.170，P=0.557；χ~2=3.831，P=0.147；χ~2=4.051，P=0.132）。
8同步放化组和序贯放化组1、2、3年局部复发率、OS、DFS均无明显差异（χ~(22)=0.000，P=0.992；χ~2=1.596，P=0.207；χ~2=0.230，P=0.631）。
9Ⅱ期患者术后放化组和术后化疗组1、2、3年OS、DFS均无显著差异（χ~2=0.058，P=0.810；χ~2=3.356，P=0.067）。Ⅲ期患者术后放化组1、2、3年局部复发率分别为3.8%、13%、13%，明显低于术后化疗组的19.8%、39.2%、44.9%（χ~2=13.230，P=0.000）。术后放化组的1、2、3年OS高于术后化疗组，统计学差异显著（χ~2=3.875，P=0.047）。术后放化组1、2、3年DFS与术后化疗组差异不明显（χ~2=1.632，P=0.201）
10多因素分析显示：淋巴结转移数目、术后辅助治疗方式是直肠癌术后局部复发的独立影响因素；肿瘤浸润深度、淋巴结转移数目是直肠癌术后OS的独立影响因素；淋巴结转移数目是直肠癌术后DFS的独立影响因素。
结论：
1术后放化疗组可显著降低Ⅲ期患者的局部复发率，提高OS，是Ⅲ期直肠癌患者术后综合治疗的最佳模式。
2Ⅱa期患者术后局部复发率低，术后放化疗价值不显著，建议术后辅助化疗作为综合治疗模式。
3术后放化疗血液学及胃肠道毒副作用显著高于术后单纯化疗。
4放疗与手术间隔时间、同步放化疗和序贯放化疗对本组患者未显示出局控率和生存率的差别。
5化疗周期数对Ⅱ期和Ⅲ期患者的局部复发和生存影响显著，若化疗周期数不足，局部复发率高，生存状况差。
6术后盆腔照射采用三维适形或调强放疗技术，可显著降低盆腔复发率，在提高疗效的同时可显著降低放射性膀胱炎和放射性肠炎的发生机率和程度。
7淋巴结转移数目、术后辅助治疗方式是直肠癌术后局部复发的独立影响因素；肿瘤浸润深度、淋巴结转移数目是直肠癌术后OS的独立影响因素；淋巴结转移数目是直肠癌术后DFS的独立影响因素。
Objectives: Rectal cancer is a common malignant tumor, whose maintherapy is surgery. Despite of development of surgical technique, the5-yearoverall survival rate is still about50%, and local recurrence and distantmetastasis are main causes of treatment failure. It has been testified thatpostoperative adjuvant radiochemotherapy is a standard mean to rectal cancer.However, there are still some problems about it. All classical studies arecompleted based on conventional radiotherapy. With the improvement ofradiotherapy technology, whether accurate radiotherapy such as three-dimensional conformal/intensity modulated radiotherapy (IMRT) used canenhance local control rate and lower toxic reactions? Which patients areoptimum benefited villagers?226cases with stage II and stage III rectalcancer are retrospectively analyzed, and effects of TNM stage, adjuvantradiochemotherapy and chemotherapy, concurrent and sequentialradiochemotherapy, interval between surgery and radiotherapy, cycles ofchemotherapy on local recurrence, overall survival (OS) and disease freesurvival (DFS) are also analyzed. Meanwhile, their prognostic factors areanalyzed as well. To investigate side effect of three-dimensionalconformal/IMRT used for preventional irradiation on pelvic cavity, in order tofurther understand the local recurrence, survival conditions and side effects oftreatment, and Provide a theoretical basis for making a more scientific andreasonable therapeutic scheme.
Methods:226rectal cancer cases after resection in the fourth hospital ofHebei medical university from June2006to December2010, including51cases in II stage, and175cases in III stage, according to PTNM.116casesunderwent adjuvant chemotherapy, and110cases underwent adjuvant radiochemotherapy. The total dose was45~54Gy (median50Gy), including88cases underwent three-dimensional conformal radiation, and22casesunderwent IMRT. The total cycles of chemotherapy was2~8(median4).191cases received FOLFOX chemotherapy,24cases received LF,11casesreceived xelox orally. The median follow-up was30months. Effects of TNMstage, adjuvant radiochemotherapy and chemotherapy, concurrent andsequential radiochemotherapy, interval between surgery and radiotherapy,cycles of chemotherapy on local recurrence, OS and DFS were analyzed, andfurther to exlore the prognostic factors for rectal cancer with II~III stages.
Results:
1Treatment status: The1-,2-,3-year local recurrent rates and distantmetastasis were9.8%,20.7%,22.8%, and15.2%,31.2%,39.4%respectively.The1-,2-,3-year OS and DFS were94.4%,71.7%,61.5%, and78.8%,59.8%,53.1%respectively. I~II grades of gastrointestinal reaction occurred in59.3%cases, and I~II grades of hematological reaction in46.9%, no III gradeoccurred. The incidence of gastrointestinal and hematological reaction in casesunderwent postoperative radiochemotherapy was78.2%and64.5%, whichwere higher than those underwent chemotherapy (χ~2=31.683, P=0.000andχ~2=26.786, P=0.004). Radiation enteritis occurred in20.9%cases underwentpostoperative radiochemotherapy, including I grade (8.2%) and II grade(9.1%). Radiocystitis occurred in10%, including I grade (8.2%) and II grade(1.8%).
2The1-,2-,3-year local recurrent rates and distant metastasis between T_2and T_3had no significant difference (χ~2=1.014, P=0.314and χ~2=2.295,P=0.130), but OS was higher (χ~2=4.278, P=0.039).
3The1-,2-,3-year local recurrent rates, OS and DFS had significantdifference (χ~2=14.599, P=0.001, χ~2=47.196, P=0.000, and χ~2=38.885,P=0.000). With N stage raised, local recurrent rates enhanced, and OS andDFS lowered.
4The1-,2-,3-year local recurrent rates of cases in II stage were lower thanthose in III stage (P=0.000), while OS and DFS higher (P=0.000, P=0.000).
5The1-,2-,3-year local recurrent rates of cases underwent postoperativeradiochemotherapy were3.8%,10.5%and10.5%, which were lower thanthose underwent postoperative chemotherapy (P=0.001). The1-,2-,3-year OSwere94.2%,76%,70.7and95.6%,68.4%,53.3, and1-,2-,3-year DFS were81.9%,60%,54.1%and76%,59.2%and52.3%, respectively, which had nosignificant difference (P=0.059, P=0.608), but there was prolong trend aboutOS.
6Cycles of chemotherapy: The1-,2-,3-year local recurrent rates of caseswith cycle≥4were lower than those with cycle＜4(χ~2=4.631, P=0.031), andOS and DFS were higher (χ~2=5.306, P=0.021and χ~2=3.941, P=0.047).
7The1-,2-,3-year local recurrent rates, OS, and DFS of cases whose intervalbetween surgery and radiation≤30days,31~60days and＞60days had nosignificant difference (χ~2=1.126, P=0.557, χ~2=3.831, P=0.147, and χ~2=4.051,P=0.132).
8The1-,2-,3-year local recurrent rates, OS, and DFS of cases underwentconcurrent or sequential radiochemotherapy had no significant difference(χ~2=0.000, P=0.992, χ~2=1.596, P=0.207, and χ~2=0.230, P=0.631).
9The1-,2-,3-year OS and DFS in cases in II stage underwentradiochemotherapy or chemotherapy had no significant difference (χ~2=0.058,P=0.810, and χ~2=3.356, P=0.067). The1-,2-,3-year local recurrent rates were3.8%,13%and13%, which were lower than those underwent chemotherapy(χ~2=13.230, P=0.000). The1-,2-,3-year OS were higher (χ~2=3.875, P=0.047),but the1-,2-,3-year DFS had no significant difference (χ~2=1.632, P=0.201).
10Multivariate analysis: Metastatic lymph node number and adjuvanttreatment modality were independent prognostic factors for local recurrence ofrectal cancer after surgery; Invasive depth and metastatic lymph node numberwere independent prognostic factors for OS; Metastatic lymph node numberwere independent prognostic factors for DFS.
Conclusions:
1Postoperative radiochemotherapy can lower local recurrent rate, andincrease OS, so it is optimum choice for patients in III stage.
2Local recurrent rate in II a stage is low, and postoperativeradiochemotherapy is not helpful to it, and postoperative chemotherapy isrecommended for this stage.
3Gastrointestinal and hematological reactions were higher in casesunderwent radiochemotherapy than those underwent chemotherapy alone.
4Interval between surgery and radiation, concurrent or sequentialradiochemotherapy has no difference for local control and survival.
5Cycles of chemotherapy have effect on local control and survival. If cyclesare insufficient, they are both Poor.
6Three-dimensional conformal/IMRT used for preventional irradiation onpelvic cavity can lower pelvic recurrence, meanwhile, radiocystitis andradiation enteritis are also lowered.
7Metastatic lymph node number and adjuvant treatment modality wereindependent prognostic factors for local recurrence of rectal cancer aftersurgery; Invasive depth and metastatic lymph node number were independentprognostic factors for OS; Metastatic lymph node number were independentprognostic factors for DFS.
方法：收集2006年6月至2010年12月于河北医科大学第四医院行直肠癌根治术患者226例，其中pTNM分期Ⅱ期51例，Ⅲ期患者175例。辅助化疗组116例，辅助放化疗组110例，放疗剂量45～54Gy，中位剂量50Gy，其中采用三维适形放疗88例，调强放疗22例。全组患者化疗周期数为2～8周期，中位4周期。191例以FOLFOX方案（奥沙利铂+亚叶酸钙+5-氟尿嘧啶/替加氟）化疗，24例行LF方案（亚叶酸钙+5-氟尿嘧啶/替加氟）化疗，11例口服单药希罗达。中位随访期30月。分析TNM分期、辅助放化疗与辅助化疗、同步放化疗与序贯放化疗、手术与放疗间隔时间、化疗周期数等因素对局部复发率、OS和DFS的影响，并进一步探讨Ⅱ～Ⅲ期直肠癌根治术后影响预后的主要因素。
结果：
1全组治疗状况：全组1、2、3年局部复发率和远处转移率分别为9.8%、20.7%、22.8%和15.2%、31.2%、39.4%，全组1、2、3年OS和DFS分别为94.4%、71.7%、61.5%和78.8%、59.8%、53.1%。全组59.3%患者出现1～2级胃肠道毒副反应，46.9%患者出现1～2级血液学毒副反应，无3级及以上毒副反应发生。术后放化组的胃肠道、血液学毒副反应发生率分别为78.2%和64.5%，明显高于术后化疗组的41.4%和30.2%（χ~2=31.683，P=0.000；χ~2=26.786，P=0.000）。术后放化组中，20.9%患者出现放射性肠炎，其中1级占11.8%，2级占9.1%；10%患者出现放射性膀胱炎，1级占8.2%，2级占1.8%。
2T_2期、T_3期患者的1、2、3年局部复发率、DFS无明显差异（χ~2=1.041，P=0.314；χ~2=2.295，P=0.130），T_2期患者OS高于T_3期患者（χ~2=4.278，P=0.039）。
3N_0期、N_1期、N_2期患者的1、2、3年局部复发率、OS及DFS均有显著差异（χ~2=14.599，P=0.001；χ~2=47.196，P=0.000；χ~2=38.885，P=0.000），随N分期增加，局部复发率高，OS及DFS均有下降。
4Ⅱ期患者的1、2、3年局部复发率明显低于Ⅲ期患者（χ~2=13.800，P=0.000）。OS、DFS均明显高于Ⅲ期患者（χ~2=18.610，P=0.000；χ~2=14.993，P=0.000）。
5术后放化组1、2、3年局部复发率分别为3.8%、10.5%、10.5%，明显低于术后化疗组的15.5%、29.7%、33.2%（χ~2=11.213，P=0.001），术后放化组与术后化疗组1、2、3年OS分别为94.2%、76%、70.7%和95.6%、68.4%、53.5%，1、2、3年DFS分别为81.9%、60%、54.1%和76%、59.2%、52.3%，组间差异不显著（χ~2=3.579，P=0.059；χ~2=0.263，P=0.608），但术后放化组有延长OS的趋势。
6化疗周期数：化疗≥4周期组1、2、3年局部复发率低于化疗＜4周期组（χ~2=4.631，P=0.031），化疗≥4周期组OS、DFS均高于化疗＜4周期组，统计学有显著性差异（χ~2=5.306，P=0.021；χ~2=3.941，P=0.047）。
7将手术与放疗时间间隔分为≤30天（26例）、31～60天（36例），＞60天（48天）三组，结果显示不同时间间隔组1、2、3年局部复发率、OS、DFS均无明显差异（χ~2=1.170，P=0.557；χ~2=3.831，P=0.147；χ~2=4.051，P=0.132）。
8同步放化组和序贯放化组1、2、3年局部复发率、OS、DFS均无明显差异（χ~(22)=0.000，P=0.992；χ~2=1.596，P=0.207；χ~2=0.230，P=0.631）。
9Ⅱ期患者术后放化组和术后化疗组1、2、3年OS、DFS均无显著差异（χ~2=0.058，P=0.810；χ~2=3.356，P=0.067）。Ⅲ期患者术后放化组1、2、3年局部复发率分别为3.8%、13%、13%，明显低于术后化疗组的19.8%、39.2%、44.9%（χ~2=13.230，P=0.000）。术后放化组的1、2、3年OS高于术后化疗组，统计学差异显著（χ~2=3.875，P=0.047）。术后放化组1、2、3年DFS与术后化疗组差异不明显（χ~2=1.632，P=0.201）
10多因素分析显示：淋巴结转移数目、术后辅助治疗方式是直肠癌术后局部复发的独立影响因素；肿瘤浸润深度、淋巴结转移数目是直肠癌术后OS的独立影响因素；淋巴结转移数目是直肠癌术后DFS的独立影响因素。
结论：
1术后放化疗组可显著降低Ⅲ期患者的局部复发率，提高OS，是Ⅲ期直肠癌患者术后综合治疗的最佳模式。
2Ⅱa期患者术后局部复发率低，术后放化疗价值不显著，建议术后辅助化疗作为综合治疗模式。
3术后放化疗血液学及胃肠道毒副作用显著高于术后单纯化疗。
4放疗与手术间隔时间、同步放化疗和序贯放化疗对本组患者未显示出局控率和生存率的差别。
5化疗周期数对Ⅱ期和Ⅲ期患者的局部复发和生存影响显著，若化疗周期数不足，局部复发率高，生存状况差。
6术后盆腔照射采用三维适形或调强放疗技术，可显著降低盆腔复发率，在提高疗效的同时可显著降低放射性膀胱炎和放射性肠炎的发生机率和程度。
7淋巴结转移数目、术后辅助治疗方式是直肠癌术后局部复发的独立影响因素；肿瘤浸润深度、淋巴结转移数目是直肠癌术后OS的独立影响因素；淋巴结转移数目是直肠癌术后DFS的独立影响因素。
Objectives: Rectal cancer is a common malignant tumor, whose maintherapy is surgery. Despite of development of surgical technique, the5-yearoverall survival rate is still about50%, and local recurrence and distantmetastasis are main causes of treatment failure. It has been testified thatpostoperative adjuvant radiochemotherapy is a standard mean to rectal cancer.However, there are still some problems about it. All classical studies arecompleted based on conventional radiotherapy. With the improvement ofradiotherapy technology, whether accurate radiotherapy such as three-dimensional conformal/intensity modulated radiotherapy (IMRT) used canenhance local control rate and lower toxic reactions? Which patients areoptimum benefited villagers?226cases with stage II and stage III rectalcancer are retrospectively analyzed, and effects of TNM stage, adjuvantradiochemotherapy and chemotherapy, concurrent and sequentialradiochemotherapy, interval between surgery and radiotherapy, cycles ofchemotherapy on local recurrence, overall survival (OS) and disease freesurvival (DFS) are also analyzed. Meanwhile, their prognostic factors areanalyzed as well. To investigate side effect of three-dimensionalconformal/IMRT used for preventional irradiation on pelvic cavity, in order tofurther understand the local recurrence, survival conditions and side effects oftreatment, and Provide a theoretical basis for making a more scientific andreasonable therapeutic scheme.
Methods:226rectal cancer cases after resection in the fourth hospital ofHebei medical university from June2006to December2010, including51cases in II stage, and175cases in III stage, according to PTNM.116casesunderwent adjuvant chemotherapy, and110cases underwent adjuvant radiochemotherapy. The total dose was45~54Gy (median50Gy), including88cases underwent three-dimensional conformal radiation, and22casesunderwent IMRT. The total cycles of chemotherapy was2~8(median4).191cases received FOLFOX chemotherapy,24cases received LF,11casesreceived xelox orally. The median follow-up was30months. Effects of TNMstage, adjuvant radiochemotherapy and chemotherapy, concurrent andsequential radiochemotherapy, interval between surgery and radiotherapy,cycles of chemotherapy on local recurrence, OS and DFS were analyzed, andfurther to exlore the prognostic factors for rectal cancer with II~III stages.
Results:
1Treatment status: The1-,2-,3-year local recurrent rates and distantmetastasis were9.8%,20.7%,22.8%, and15.2%,31.2%,39.4%respectively.The1-,2-,3-year OS and DFS were94.4%,71.7%,61.5%, and78.8%,59.8%,53.1%respectively. I~II grades of gastrointestinal reaction occurred in59.3%cases, and I~II grades of hematological reaction in46.9%, no III gradeoccurred. The incidence of gastrointestinal and hematological reaction in casesunderwent postoperative radiochemotherapy was78.2%and64.5%, whichwere higher than those underwent chemotherapy (χ~2=31.683, P=0.000andχ~2=26.786, P=0.004). Radiation enteritis occurred in20.9%cases underwentpostoperative radiochemotherapy, including I grade (8.2%) and II grade(9.1%). Radiocystitis occurred in10%, including I grade (8.2%) and II grade(1.8%).
2The1-,2-,3-year local recurrent rates and distant metastasis between T_2and T_3had no significant difference (χ~2=1.014, P=0.314and χ~2=2.295,P=0.130), but OS was higher (χ~2=4.278, P=0.039).
3The1-,2-,3-year local recurrent rates, OS and DFS had significantdifference (χ~2=14.599, P=0.001, χ~2=47.196, P=0.000, and χ~2=38.885,P=0.000). With N stage raised, local recurrent rates enhanced, and OS andDFS lowered.
4The1-,2-,3-year local recurrent rates of cases in II stage were lower thanthose in III stage (P=0.000), while OS and DFS higher (P=0.000, P=0.000).
5The1-,2-,3-year local recurrent rates of cases underwent postoperativeradiochemotherapy were3.8%,10.5%and10.5%, which were lower thanthose underwent postoperative chemotherapy (P=0.001). The1-,2-,3-year OSwere94.2%,76%,70.7and95.6%,68.4%,53.3, and1-,2-,3-year DFS were81.9%,60%,54.1%and76%,59.2%and52.3%, respectively, which had nosignificant difference (P=0.059, P=0.608), but there was prolong trend aboutOS.
6Cycles of chemotherapy: The1-,2-,3-year local recurrent rates of caseswith cycle≥4were lower than those with cycle＜4(χ~2=4.631, P=0.031), andOS and DFS were higher (χ~2=5.306, P=0.021and χ~2=3.941, P=0.047).
7The1-,2-,3-year local recurrent rates, OS, and DFS of cases whose intervalbetween surgery and radiation≤30days,31~60days and＞60days had nosignificant difference (χ~2=1.126, P=0.557, χ~2=3.831, P=0.147, and χ~2=4.051,P=0.132).
8The1-,2-,3-year local recurrent rates, OS, and DFS of cases underwentconcurrent or sequential radiochemotherapy had no significant difference(χ~2=0.000, P=0.992, χ~2=1.596, P=0.207, and χ~2=0.230, P=0.631).
9The1-,2-,3-year OS and DFS in cases in II stage underwentradiochemotherapy or chemotherapy had no significant difference (χ~2=0.058,P=0.810, and χ~2=3.356, P=0.067). The1-,2-,3-year local recurrent rates were3.8%,13%and13%, which were lower than those underwent chemotherapy(χ~2=13.230, P=0.000). The1-,2-,3-year OS were higher (χ~2=3.875, P=0.047),but the1-,2-,3-year DFS had no significant difference (χ~2=1.632, P=0.201).
10Multivariate analysis: Metastatic lymph node number and adjuvanttreatment modality were independent prognostic factors for local recurrence ofrectal cancer after surgery; Invasive depth and metastatic lymph node numberwere independent prognostic factors for OS; Metastatic lymph node numberwere independent prognostic factors for DFS.
Conclusions:
1Postoperative radiochemotherapy can lower local recurrent rate, andincrease OS, so it is optimum choice for patients in III stage.
2Local recurrent rate in II a stage is low, and postoperativeradiochemotherapy is not helpful to it, and postoperative chemotherapy isrecommended for this stage.
3Gastrointestinal and hematological reactions were higher in casesunderwent radiochemotherapy than those underwent chemotherapy alone.
4Interval between surgery and radiation, concurrent or sequentialradiochemotherapy has no difference for local control and survival.
5Cycles of chemotherapy have effect on local control and survival. If cyclesare insufficient, they are both Poor.
6Three-dimensional conformal/IMRT used for preventional irradiation onpelvic cavity can lower pelvic recurrence, meanwhile, radiocystitis andradiation enteritis are also lowered.
7Metastatic lymph node number and adjuvant treatment modality wereindependent prognostic factors for local recurrence of rectal cancer aftersurgery; Invasive depth and metastatic lymph node number were independentprognostic factors for OS; Metastatic lymph node number were independentprognostic factors for DFS.
引文
1Thomas PR, Lindblad AS. Adjuvant postoperative radiotherapy andchemotherapy in rectal carcinoma: a review of the Gastro-intestinal Tu-mor Study Group experience. Radiother Oncol.1988Dec;13(4):245-252
2Krook JE,Moertel CG,Gunderson LL, et al. Effective surgical adjuvanttherapy for high-risk rectal carcinoma. N Engl J Med.1991Mar14;324(11):709-715
3Wolmark N,Wieand HS,Hyams DM,etal.Randomized trial ofpostoperative adjuvant chemotherapy with or without radiotherapy forcarcinoma of the rectum:national Surgical Adjuvant Breast and BowelProject Protocol R-02J Natl Cancer Inst.2000Mar1;92(5):388-396
4Marcin Hetna,Krzysztof Ma ecki,Stanis aw Korzeniowski. postoperativeadjuvant chemoradiotherapy in patients with rectal cancer. prognosticfactors for locoregional control and survival. Rep pract Oncol Radiother,2006;11(4):175-182
5GundersonL L,SargentD J,Tepper JE,etal. Impact of T and N stage andtreatment on survival and relapse in adjuvant rectal cancer: a Pooledanalysis[J].J Clin Oncol,2004,22(10):1785-1796
6王晓娜，梁寒，王家仓等.1829例结直肠癌患者的临床病理特征及预后分析.中华胃肠外科杂志.2004,11;7(6):439-442
7汪鑫,聂绍发.应用COX比例风险模型对大肠癌切除术后预后影响因素的分析.肿瘤防治研究.2006;33(4):286-287
8Huh JW,Lim SW,Kim HR,etal.Effects of postoperative AdjuvantRadiotherapy on Recurrence and Survival in Stage III Rectal Cancer. JGastrointest Surg.2011Jun;15(6):963-970
9Baqatzounis A,Willner J,Oppitz U,etal.The postoperative adjuvantradiation therapy and radiochemotherapy for UICC stage II and III rectalcancer.A retrospective analysis. Strahlenther Onkol.2000Mar;176(3):112-117
10刘彦龙,杨艳梅,徐海涛等.直肠癌术后复发的形式及预后分析.第五届中国肿瘤学术大会.2008,9;590
11Wong JH,Steinemann S,Tom P,etal.Volume of lymphatic metastases doesnot independently influence prognosis in colorectal cancer[J].J ClinOncol,2002,20(6):1506-1511
12O’Connell JB,Maggard MA,Clifford Y. Colon cancer survival rates withthe new Ameriean Joint Committee On Cancer Sixth edition staging[J].JNatl Cancer Inst,2004,96(19):1420-1425
13钱立庭,宋永文,刘新帆.Ⅱ和Ⅲ期肠癌根治术后放射治疗的疗效观察.中华放射肿瘤学杂志2003;12:101-105
14周毅,王凤玮,张锡朋,直肠癌Miles术后放化疗同步与单纯化疗效果分析.癌症进展杂志.2007,5(5):489-491
15陆忠华,王建华,许锡元等.Ⅱ、Ⅲ期直肠癌根治术后放疗同步希罗达化疗的疗效.世界华人消化杂.2009;17(32):3351-3354
16孙清,福林,赵伟,等.贯放化疗治疗进展期直肠癌的疗效分析.肿瘤研究与临床.2003,8;15（4）:245-247
17陈光烈.同步放化疗与序贯放化疗对直肠癌术后患者局部控制率和生存率的影响.当代医学.2012，1;18(2）:265
18Lee JH,Ahn JH,Bahng H,etal. Randomized trial of postoperative adjuvanttherapy in stage II and III rectal cancer to define the optimal sequence ofchemotherapy and radiotherapy: a preliminary report. J Clin Oncol.2002APr1;20(7):1751-1758
19Kim TW,Lee JH,Lee JH,etal. Randomized trial of postoperative adjuvanttheraPy in Stage II and III rectal cancer to define the optimal sequence ofchemotherapy and radiotherapy:10-year follow-up.Int J Radiat Oncol BiolPhys.2011Nov15;81(4):1025-1031
20冯瑞,李明焕,于金明.158例Ⅱ和Ⅲ期直肠癌根治术后不同治疗方法疗效分析.中华放射肿瘤学杂志.2009;18(3):224-225
21Rich T,Gunderson LL,Lew R,etal.Patterns of recurrence of rectal cancerafter potentially curative surgery.Cancer.1983Oct1;52(7):1317-1329
22Mendenhall WM,Million RR,Pfaff WW.Patterns of recurrence inadenocarcinoma Of the rectum and rectosigmoid treated with surgeryalone： implieations in treatment planning with adiuvant radiationtheraPy.Int J Radiat Oncol Biol Phys.1983Jul;9(7):977-985
23Walz BJ,Green MR,Lindstrom ER,etal.Anatomical prognostic factors afterabdominal perineal resection.Int J Radiat Oncol Biol Phys1981;7:477-484
24Pilipshen SJ,Heilweil M,Quan SH,etal Patterns of pelvic recurrencefoIlowing definitive resections of rectal cancer.Cancer.1984Mar15;53(6):1354-1362
25Preoperative short-term radiation therapy in operable rectal carcinoma.Aprospective randomized randomized trial.Stockholm Rectal Cancer StudyGroup.Cancer1990Jul1;66(1):49-55
26Merchant NB,Guillem JG,Paty PB,etal.T3N0rectal cancer: resultsfollowing sharp mesorectal excision and no adjuvant theraPy.JGastrointest Surg.1999Nov-Dec;3(6):642-647
27Willett CG,Badizadegan K,Ancukiewicz M,etal. Prognostic factors in stageT3N0rectal cancer: do all patients require postoperative Pelvic irradiationand chemotheraPy[J].Dis Colon Rectum.1999Feb;42(2):167-173
28Tokoro T,Okuno K,Hida J,etal. Depth of mesorectal invasion hasprognostic significance in T3N0low rectal cancer[J]. Hepatogastroenterology.2009Jan-Feb;56(89):124-127
29刘振洋,胡英,周慧俊,等,257例Ⅱa期直肠癌根治术后不同治疗方法的疗效比较.医学临床研究.2009,26(7):1238-1240
30Chung YL,Jian JJ,Cheng SH,etal.Extended-field radiotherapy andhigh-dose-rate brachytherapy with concurrent and adjuvant cisPlatin-basedchemotherapy for locally advanced cervical cancer: a Phase I/II study.Gynecol Oncol2005APr;97(1)126-135
31Martenson JA Jr, Willett CG,Sargent DJ,etal. Phase III Study of AdjuvantChemotherapy and Radiation Therapy Compared With ChemotherapyAlone in the Surgical Adjuvant Treatment of Colon Cancer: Results ofIntergrouP Protocol0130J Clin Oncol.2004Aug15;22(16):3277-3283
32Baglan KL, Frazier RC, Yan D,etal. The dose-volume relationship of acutesmall bowel toxicity from concurrent5-FU-based chemotherapy andradiation therapy for rectal cancer. Int J Radiat Oncol Biol Phys.2002Jan1;52(1):176-183
1Ailouni M. The role of radiation therapy in the adjuvant treatment of rectalcancer. Curr Opin Gastroenterol.2001Jan;17(1):86-90
2Anonymous. Swedish Rectal Cancer Trial: Improved survival withpreoperative radiation in resectable rectal cancer. N Engl J Med,1997Apr3,336(14):980-987
3Pahlman L. Neoadjuvant and adjuvant radio-and radio-chemotherapy ofrectal carcinomas. Int J Colorectal Dis.2000;15:1-8
4Sauer R,Becker H,Hohenberger W,etal.Preoperative versus postoperativechemoradiotherapy for rectal cancer [J].N Engl J Med.2004Oct21,351(17):1731-1740
5Park JH,Yoon SM,Yu CS,etal.Randomized phase3trial comparingpreoperative and postoperative chemoradiotherapy with capecitabine forlocally advanced rectal cancer. Cancer.2011Aug15;117(16):3703-3712
6Rivera S, Villa J, Quero L, etal. Adjuvant radiotherapy for rectal cancer:Recent results, new questions. Clin Res Hepatol Gastroenterol.2011Jan;35(1):17-22
7Folkesson J,Birgisson H,Pahlman L,etal. Swedish Rectal Cancer Trial:long lasting benefits from radiotherapy on survival and local recurrencerate. J Clin Oncol.2005Aug20;23(24):5644-5650
8Kapiteijn E,Marijnen CA,Nagtegaal ID,etal.Preoperative radiotherapycombined with total mesorectal excision for resectable rectal cancer. NEngl J Med.2001Aug30;345(9):638-646
9Marijnen CA,Nagtegaal ID,Klein Kranenbarg E,etal.No downstaging aftershort-term preoperative radiotherapy in rectal cancer patients. J ClinOncol.2001Apr1;19(7):1976-1984
10Ahmad NR,Nagle D,etal. Long-term results of preoperative radiationtherapy alone for stage T3and T4rectal cancer. Br J Surg.1997Oct;84(10):1445-1448
11Bujko K,Nowacki MP,Nasierowska-Guttmejer A,etal.Sphincter preserva-tion following preoperative radiotherapy for rectal cancer: report of arandomised trial comparing short-term radiotherapy vs. conventionallyfractionated radiochemotherapy. Radiother Oncol.2004Jul;72(1):15-24
12胡伟民,邓晓芳,王进.结直肠癌术前化疗进展.现代肿瘤医学.2007,1;15(1):132-134
13Bosset JF,Collette L,Calais G,etal.Chemotherapy with preoperativeradiotherapy in rectal cancer. N Engl J Med.2006Sep14;355(11):1114-23
14Bosset JF,Calais G,Mineur L,etal.Enhanced tumorocidal effect ofchemotherapy with preoperative radiotherapy for rectal cancer:preliminary results--EORTC22921J Clin Oncol.2005Aug20;23(24):5620-5627
15Gérard JP，Conroy T，Bonnetain F，et al.Preoperative radiotherapy withor without concurrent fluorouracil and leucovorin in T３-４rectalcancers：results of FFCD9203[J]．J ClinOncol，2006，24(28)：4620-4625
16Ceelen WP,Van Nieuwenhove Y,Fierens K. Preoperative chemoradiationversus radiation alone for stage II and III resectable rectal cancer: asystematic review and meta-analysis. Int J Cancer.2009Jun15;124(12):2966-2972.
17Sawada N,Ishikawa T,Sekiguchi F,etal.X-ray irradiation induces thymidinephosphorylase and enhances the efficacy of capecitabine （Xeloda） inhuman cancer xenografts ［J］．Clin Cancer Res，1999,5(10):2948-2953
18Janjan NA, Khoo VS, Abbruzzese J etal.Tumor downstaging and sphincterpreservation with preoperative chemoradiation in locally advanced rectalcancer: the M. D. Anderson Cancer Center experience. Int J Radiat OncolBiol Phys1999Jul15;44(5):1027-1038
19Pucciarelli S,Friso ML,Toppan P,etal.Preoperative combined radiotherapyand chemotherapy for middle and lower rectal cancer: preliminary results.2000Jan-Feb;7(1):38-44
20Ciabattoni A,Cavallaro A,Potenza AE,etal.Preoperative concomitantradiochemotherapy with a5-fluorouracil plus folinic acid bolus in thecombined treatment of locally advanced extraperitoneal rectal cancer: along-term analysis on27patients. Tumori.2003Mar-Apr;89(2):157-163
21Lam CW, Chen WT, Liu MT et al (2005) Effect of preoperativeconcurrent chemoradiotherapy in locally advanced low rectal cancer afterradical resection surgery. Int Surg2005Jan-Mar;90(1):53-59
22Carraro S,Roca EL,Cartelli C,etal.Radiochemotherapy with short dailyinfusion of low-dose oxaliplatin, leucovorin, and5-FU in T3-T4unresectable rectal cancer: a phase II IATTGI study.Int J Radiat OncolBiol Phys.2002Oct1;54(2):397-402
23Gerard JP,Chapet O,Nemoz C,etal.Preoperative concurrent chemoradio-therapy in locally advanced rectal cancer with high-dose radiation andoxaliplatin-containing regimen: the Lyon R0-04phase II trial. J ClinOncol.2003Mar15;21(6):1119-1124
24Sebag-Montefiore D,Glynne-Jones R,Falk S,etal. A phase I/II study ofoxaliplatin when added to5-fluorouracil and leucovorin and pelvicradiation in locally advanced rectal cancer: a Colorectal Clinical OncologyGroup (CCOG) study. Br J Cancer.2005Oct31;93(9):993-998
25刘鲁迎,朱远,吴列,等.局部晚期直肠癌术前含草酸铂同步放化疗Ⅱ期临床研究.腹部肿瘤，2007年第六届全国放射肿瘤学学术年会,392
26Aschele C,Friso ML,Pucciarelli S,etal. A phase I-II study of weeklyoxaliplatin,5-fluorouracil continuous infusion and preoperativeradiotherapy in locally advanced rectal cancer. Ann Oncol.2005Jul;16(7):1140-1146
27Turitto G,Panelli G,Frattolillo A,eral. Phase II study of neoadjuvantconcurrent chemioradiotherapy with oxaliplatin-containing regimen inlocally advanced rectal cancer. Front Biosci.2006May1;11:1275-1279
28Rosenthal DI,Catalano PJ,Haller DG,etal. Phase I study of preoperativeradiation therapy with concurrent infusional5-fluorouracil and oxaliplatinfollowed by surgery and postoperative5-fluorouracil plus leucovorin forT3/T4rectal adenocarcinoma: ECOG E1297Int J Radiat Oncol BiolPhy.2008Sep1;72(1):108-113
29Aschele C,Cionini L,Lonardi S,etal.Primary tumor response topreoperative chemoradiation with or without oxaliplatin in locallyadvanced rectal cancer: pathologic results of the STAR-01randomizedphase III trial. J Clin Oncol.2011Jul10;29(20):2773-2780
30殷蔚伯、余子豪、徐国镇等.肿瘤放射治疗学，第四版，中国协和医科大学出版社，2007:855-881
31Kim JS,Kim JS,Cho MJ,etal.Comparison of the efficacy of oralcapecitabine versus bolus5-FU in preoperative radiotherapy of locallyadvanced rectal cancer. J Korean Med Sci2006Feb;21(1):52-57
32Ramani VS,Sun Myint A,Montazeri A,etal.Preoperative chemoradiotherapy for rectal cancer: a comparison between intravenous5-fluorouracil andoral capecitabine. Colorectal Dis.2010Aug;12Suppl2:37-46
33Dunst J,Reese T,Sutter T,etal.Phase I trial evaluating the concurrentcombination of radiotherapy and capecitabine in rectal cancer. J ClinOncol.2002Oct1;20(19):3983-3991
34Ngan SY,Michael M,Mackay J,etal.A phase I trial of preoperativeradiotherapy and capecitabine for locally advanced, potentially resectablerectal cancer. Br J Cancer.2004Sep13;91(6):1019-1024
35Kim JS,Kim JS,Cho MJ,etal. Preoperative chemoradiation using oralcapecitabine in locally advaneed rectal cancer.Int J Radiat Oneol BiolPhys.2002Oct1;54(2):403-408
36Zampino MG,Magni E,Leonardi MC,etal.Capecitabine initiallyconcomitant to radiotherapy then perioperatively administered in locallyadvanced rectal cancer.Int J Radiat Oncol Biol Phys.2009Oct1;75(2):421-427
37Dunst J,Debus J,Rudat V,etal.Neoadjuvant capecitabine combined withstandard radiotherapy in patients with locally advanced rectal cancer:mature results of a phase II trial. Strahlenther Onkol.2008Sep;184(9):450-456
38Swellengrebel HA,Marijnen CA,Verwaal VJ,etal.Toxicity andcomplications of preoperative chemoradiotherapy for locally advancedrectal cancer. Br J Radiol.2011Mar;98(3):418-426
39Bajetta E,Beretta E,Di Bartolomeo M,etal.Capecitabine chemoradiationfor rectal canecer after curative surgery.J Chemother.2006Feb;18(1):85-89
40Glynne-Jones R,Sebag-Montefiore D,Maughan TS,etal.A phase I doseescalation study of continuous oral capecitabine in combination withoxaliplatin and pelvic radiation (XELOX-RT) in patients with locallyadvanced rectal cancer. Ann Oncol.2006Jan;17(1):50-56
41Fakih MG,Rajput A,Yang GY,etal.A phase I study of weekly intravenousoxaliplatin in combination with oral daily capecitabine and radiationtherapy in the neoadjuvant treatment of rectal adenocarcinoma. Int JRadiat Oncol Biol Phys.2006Aug1;65(5):1462-1470
42Aristu JJ,Arbea L,Rodriguez J,etal.phase Ⅱ-Ⅲ Trial of ConcurrentCapecitabine and Oxaliplatin247with Preoperative Intensity-ModulatedRadiotherapy in Patients with locally advanced Rectal Cancer.Int J RadiatOncol Biol Phys.2008Jul1;71(3):748-755
43Arbea L,Martinez-Monge R,Diaz-Gonzalez JA,etal.Four-Week Neoadjuv-ant Intensity-Modulated Radiation Therapy with Concurrent Capecitabineand Oxaliplatin in Locally Advanced Rectal Cancer Patients: A ValidationPhase II Trial. Int J Radiat Oncol Biol Phys.2011Nov11
44Rodel C,Grabenbauer GG,Papadopoulos T, etal. Phase I/II trial ofcapecitabine, oxaliplatin, and radiation for rectal cancer. J Clin Oncol.2003Aug15;21(16):3098-3104
45Rodel C,Lierseh T,Hermann RM,etal.Multicenter phase Ⅱ trial ofchemoradiation with oxaliplatin for rectal cancer.J Clin Oncol.2007Jan1;25(1):110-117
46G é rard JP, Azria D,Gourgou-Bourgada S,etal.Comparison of twoneoadjuvant chemoradiotherapy regimens for locally advanced rectalcancer: results of the phase III trial ACCORD12/0405-Prodige2J ClinOncol.2010Apr1;28(10):1638-1644
47Klautke G,Feyerherd P,Ludwig K,etal.Intensified concurrentchemoradio-therapy with5-fluorouracil and irinotecan as neoadjuvanttreatment in patients with locally advanced rectal cancer[J].Br J Cancer.2005Apr11;92(7):1215-1220
48Navarro M,Dotor E,Rivera F,etal. A Phase II study of preoperativeradiotherapy and concomitant weekly irinotecan in combination withprotracted venous infusion5-fluorouracil, for resectable locally advancedrectal cancer.2006Sep1;66(1):201-205
49Hong YS,Kim DY,Lim SB,etal.Preoperative chemoradiation withirinotecan and capecitabine in patients with locally advanced resectablerectal cancer: long-term results of a Phase II study.2011Mar15;79(4):1171-1178
50Gollins S,Sun Myint A,Haylock B,etal.Preoperative chemoradiotherapyusing concurrent capecitabine and irinotecan in magnetic resonanceimaging-defined locally advanced rectal cancer: impact on long-termclinical outcomes.2011Mar10;29(8):1042-1049
51Hofheinz RD,Horisberger K,Woernle C,etal. Phase I trial of cetuximab incombination with capecitabine, weekly irinotecan, and radiotherapy asneoadjuvant therapy for rectal cancer.Int J Radiat Oncol Biol Phys.2006Dec1;66(5):1384-1390
52Horisberger K,Treschl A,Mai S,etal. Cetuximab in combination withcapecitabine, irinotecan, and radiotherapy for patients with locallyadvanced rectal cancer: results of a Phase II MARGIT trial. Int J RadiatOncol Biol Phys.2009Aug1;74(5):1487-1493
53Machiels JP, Sempoux C,Scalliet P,etal.Phase I/II study of preoperativecetuximab, capecitabine, and external beam radiotherapy in patients withrectal cancer. Ann Oncol.2007Apr;18(4):738-744
54Rodel C,Arnold D,Hipp M,etal. Phase I-II trial of cetuximab, capecitabine,oxaliplatin, and radiotherapy as preoperative treatment in rectal cancer.IntJ Radiat Oncol Biol Phys.2008Mar15;70(4):1081-1086
55Bertolinl F,Chiara S,Bengala C,etal.Neoadjuvant treatment withsingle-agent cetuximab followed by5-FU,cetuximab,and pelvicradiotherapy: a phase II study in locally advanced rectal cancer. Int JRadiat Oncol Biol Phys.2009Feb1;73(2):466-472
56Crane CH,Eng C,Feig BW, etal.Phase II trial of neoadjuvant bevacizumab,capecitabine, and radiotherapy for locally advanced rectal cancer. Int JRadiat Oncol Biol Phys.2010Mar1;76(3):824-830
57Velenik V,Ocvirk J,Music M,etal.Neoadjuvant capecitabine, radiotherapy,and bevacizumab (CRAB) in locally advanced rectal cancer: results of anopen-label phase II study. Radiat Oncol.2011Aug31;6:105
58Marquardt F,Rodel F,Capalbo G,etal.Molecular targeted treatment andradiation therapy for rectal cancer.Strahlenther Onkol.2009Jun;185(6):371-378
2Krook JE,Moertel CG,Gunderson LL, et al. Effective surgical adjuvanttherapy for high-risk rectal carcinoma. N Engl J Med.1991Mar14;324(11):709-715
3Wolmark N,Wieand HS,Hyams DM,etal.Randomized trial ofpostoperative adjuvant chemotherapy with or without radiotherapy forcarcinoma of the rectum:national Surgical Adjuvant Breast and BowelProject Protocol R-02J Natl Cancer Inst.2000Mar1;92(5):388-396
4Marcin Hetna,Krzysztof Ma ecki,Stanis aw Korzeniowski. postoperativeadjuvant chemoradiotherapy in patients with rectal cancer. prognosticfactors for locoregional control and survival. Rep pract Oncol Radiother,2006;11(4):175-182
5GundersonL L,SargentD J,Tepper JE,etal. Impact of T and N stage andtreatment on survival and relapse in adjuvant rectal cancer: a Pooledanalysis[J].J Clin Oncol,2004,22(10):1785-1796
6王晓娜，梁寒，王家仓等.1829例结直肠癌患者的临床病理特征及预后分析.中华胃肠外科杂志.2004,11;7(6):439-442
7汪鑫,聂绍发.应用COX比例风险模型对大肠癌切除术后预后影响因素的分析.肿瘤防治研究.2006;33(4):286-287
8Huh JW,Lim SW,Kim HR,etal.Effects of postoperative AdjuvantRadiotherapy on Recurrence and Survival in Stage III Rectal Cancer. JGastrointest Surg.2011Jun;15(6):963-970
9Baqatzounis A,Willner J,Oppitz U,etal.The postoperative adjuvantradiation therapy and radiochemotherapy for UICC stage II and III rectalcancer.A retrospective analysis. Strahlenther Onkol.2000Mar;176(3):112-117
10刘彦龙,杨艳梅,徐海涛等.直肠癌术后复发的形式及预后分析.第五届中国肿瘤学术大会.2008,9;590
11Wong JH,Steinemann S,Tom P,etal.Volume of lymphatic metastases doesnot independently influence prognosis in colorectal cancer[J].J ClinOncol,2002,20(6):1506-1511
12O’Connell JB,Maggard MA,Clifford Y. Colon cancer survival rates withthe new Ameriean Joint Committee On Cancer Sixth edition staging[J].JNatl Cancer Inst,2004,96(19):1420-1425
13钱立庭,宋永文,刘新帆.Ⅱ和Ⅲ期肠癌根治术后放射治疗的疗效观察.中华放射肿瘤学杂志2003;12:101-105
14周毅,王凤玮,张锡朋,直肠癌Miles术后放化疗同步与单纯化疗效果分析.癌症进展杂志.2007,5(5):489-491
15陆忠华,王建华,许锡元等.Ⅱ、Ⅲ期直肠癌根治术后放疗同步希罗达化疗的疗效.世界华人消化杂.2009;17(32):3351-3354
16孙清,福林,赵伟,等.贯放化疗治疗进展期直肠癌的疗效分析.肿瘤研究与临床.2003,8;15（4）:245-247
17陈光烈.同步放化疗与序贯放化疗对直肠癌术后患者局部控制率和生存率的影响.当代医学.2012，1;18(2）:265
18Lee JH,Ahn JH,Bahng H,etal. Randomized trial of postoperative adjuvanttherapy in stage II and III rectal cancer to define the optimal sequence ofchemotherapy and radiotherapy: a preliminary report. J Clin Oncol.2002APr1;20(7):1751-1758
19Kim TW,Lee JH,Lee JH,etal. Randomized trial of postoperative adjuvanttheraPy in Stage II and III rectal cancer to define the optimal sequence ofchemotherapy and radiotherapy:10-year follow-up.Int J Radiat Oncol BiolPhys.2011Nov15;81(4):1025-1031
20冯瑞,李明焕,于金明.158例Ⅱ和Ⅲ期直肠癌根治术后不同治疗方法疗效分析.中华放射肿瘤学杂志.2009;18(3):224-225
21Rich T,Gunderson LL,Lew R,etal.Patterns of recurrence of rectal cancerafter potentially curative surgery.Cancer.1983Oct1;52(7):1317-1329
22Mendenhall WM,Million RR,Pfaff WW.Patterns of recurrence inadenocarcinoma Of the rectum and rectosigmoid treated with surgeryalone： implieations in treatment planning with adiuvant radiationtheraPy.Int J Radiat Oncol Biol Phys.1983Jul;9(7):977-985
23Walz BJ,Green MR,Lindstrom ER,etal.Anatomical prognostic factors afterabdominal perineal resection.Int J Radiat Oncol Biol Phys1981;7:477-484
24Pilipshen SJ,Heilweil M,Quan SH,etal Patterns of pelvic recurrencefoIlowing definitive resections of rectal cancer.Cancer.1984Mar15;53(6):1354-1362
25Preoperative short-term radiation therapy in operable rectal carcinoma.Aprospective randomized randomized trial.Stockholm Rectal Cancer StudyGroup.Cancer1990Jul1;66(1):49-55
26Merchant NB,Guillem JG,Paty PB,etal.T3N0rectal cancer: resultsfollowing sharp mesorectal excision and no adjuvant theraPy.JGastrointest Surg.1999Nov-Dec;3(6):642-647
27Willett CG,Badizadegan K,Ancukiewicz M,etal. Prognostic factors in stageT3N0rectal cancer: do all patients require postoperative Pelvic irradiationand chemotheraPy[J].Dis Colon Rectum.1999Feb;42(2):167-173
28Tokoro T,Okuno K,Hida J,etal. Depth of mesorectal invasion hasprognostic significance in T3N0low rectal cancer[J]. Hepatogastroenterology.2009Jan-Feb;56(89):124-127
29刘振洋,胡英,周慧俊,等,257例Ⅱa期直肠癌根治术后不同治疗方法的疗效比较.医学临床研究.2009,26(7):1238-1240
30Chung YL,Jian JJ,Cheng SH,etal.Extended-field radiotherapy andhigh-dose-rate brachytherapy with concurrent and adjuvant cisPlatin-basedchemotherapy for locally advanced cervical cancer: a Phase I/II study.Gynecol Oncol2005APr;97(1)126-135
31Martenson JA Jr, Willett CG,Sargent DJ,etal. Phase III Study of AdjuvantChemotherapy and Radiation Therapy Compared With ChemotherapyAlone in the Surgical Adjuvant Treatment of Colon Cancer: Results ofIntergrouP Protocol0130J Clin Oncol.2004Aug15;22(16):3277-3283
32Baglan KL, Frazier RC, Yan D,etal. The dose-volume relationship of acutesmall bowel toxicity from concurrent5-FU-based chemotherapy andradiation therapy for rectal cancer. Int J Radiat Oncol Biol Phys.2002Jan1;52(1):176-183
1Ailouni M. The role of radiation therapy in the adjuvant treatment of rectalcancer. Curr Opin Gastroenterol.2001Jan;17(1):86-90
2Anonymous. Swedish Rectal Cancer Trial: Improved survival withpreoperative radiation in resectable rectal cancer. N Engl J Med,1997Apr3,336(14):980-987
3Pahlman L. Neoadjuvant and adjuvant radio-and radio-chemotherapy ofrectal carcinomas. Int J Colorectal Dis.2000;15:1-8
4Sauer R,Becker H,Hohenberger W,etal.Preoperative versus postoperativechemoradiotherapy for rectal cancer [J].N Engl J Med.2004Oct21,351(17):1731-1740
5Park JH,Yoon SM,Yu CS,etal.Randomized phase3trial comparingpreoperative and postoperative chemoradiotherapy with capecitabine forlocally advanced rectal cancer. Cancer.2011Aug15;117(16):3703-3712
6Rivera S, Villa J, Quero L, etal. Adjuvant radiotherapy for rectal cancer:Recent results, new questions. Clin Res Hepatol Gastroenterol.2011Jan;35(1):17-22
7Folkesson J,Birgisson H,Pahlman L,etal. Swedish Rectal Cancer Trial:long lasting benefits from radiotherapy on survival and local recurrencerate. J Clin Oncol.2005Aug20;23(24):5644-5650
8Kapiteijn E,Marijnen CA,Nagtegaal ID,etal.Preoperative radiotherapycombined with total mesorectal excision for resectable rectal cancer. NEngl J Med.2001Aug30;345(9):638-646
9Marijnen CA,Nagtegaal ID,Klein Kranenbarg E,etal.No downstaging aftershort-term preoperative radiotherapy in rectal cancer patients. J ClinOncol.2001Apr1;19(7):1976-1984
10Ahmad NR,Nagle D,etal. Long-term results of preoperative radiationtherapy alone for stage T3and T4rectal cancer. Br J Surg.1997Oct;84(10):1445-1448
11Bujko K,Nowacki MP,Nasierowska-Guttmejer A,etal.Sphincter preserva-tion following preoperative radiotherapy for rectal cancer: report of arandomised trial comparing short-term radiotherapy vs. conventionallyfractionated radiochemotherapy. Radiother Oncol.2004Jul;72(1):15-24
12胡伟民,邓晓芳,王进.结直肠癌术前化疗进展.现代肿瘤医学.2007,1;15(1):132-134
13Bosset JF,Collette L,Calais G,etal.Chemotherapy with preoperativeradiotherapy in rectal cancer. N Engl J Med.2006Sep14;355(11):1114-23
14Bosset JF,Calais G,Mineur L,etal.Enhanced tumorocidal effect ofchemotherapy with preoperative radiotherapy for rectal cancer:preliminary results--EORTC22921J Clin Oncol.2005Aug20;23(24):5620-5627
15Gérard JP，Conroy T，Bonnetain F，et al.Preoperative radiotherapy withor without concurrent fluorouracil and leucovorin in T３-４rectalcancers：results of FFCD9203[J]．J ClinOncol，2006，24(28)：4620-4625
16Ceelen WP,Van Nieuwenhove Y,Fierens K. Preoperative chemoradiationversus radiation alone for stage II and III resectable rectal cancer: asystematic review and meta-analysis. Int J Cancer.2009Jun15;124(12):2966-2972.
17Sawada N,Ishikawa T,Sekiguchi F,etal.X-ray irradiation induces thymidinephosphorylase and enhances the efficacy of capecitabine （Xeloda） inhuman cancer xenografts ［J］．Clin Cancer Res，1999,5(10):2948-2953
18Janjan NA, Khoo VS, Abbruzzese J etal.Tumor downstaging and sphincterpreservation with preoperative chemoradiation in locally advanced rectalcancer: the M. D. Anderson Cancer Center experience. Int J Radiat OncolBiol Phys1999Jul15;44(5):1027-1038
19Pucciarelli S,Friso ML,Toppan P,etal.Preoperative combined radiotherapyand chemotherapy for middle and lower rectal cancer: preliminary results.2000Jan-Feb;7(1):38-44
20Ciabattoni A,Cavallaro A,Potenza AE,etal.Preoperative concomitantradiochemotherapy with a5-fluorouracil plus folinic acid bolus in thecombined treatment of locally advanced extraperitoneal rectal cancer: along-term analysis on27patients. Tumori.2003Mar-Apr;89(2):157-163
21Lam CW, Chen WT, Liu MT et al (2005) Effect of preoperativeconcurrent chemoradiotherapy in locally advanced low rectal cancer afterradical resection surgery. Int Surg2005Jan-Mar;90(1):53-59
22Carraro S,Roca EL,Cartelli C,etal.Radiochemotherapy with short dailyinfusion of low-dose oxaliplatin, leucovorin, and5-FU in T3-T4unresectable rectal cancer: a phase II IATTGI study.Int J Radiat OncolBiol Phys.2002Oct1;54(2):397-402
23Gerard JP,Chapet O,Nemoz C,etal.Preoperative concurrent chemoradio-therapy in locally advanced rectal cancer with high-dose radiation andoxaliplatin-containing regimen: the Lyon R0-04phase II trial. J ClinOncol.2003Mar15;21(6):1119-1124
24Sebag-Montefiore D,Glynne-Jones R,Falk S,etal. A phase I/II study ofoxaliplatin when added to5-fluorouracil and leucovorin and pelvicradiation in locally advanced rectal cancer: a Colorectal Clinical OncologyGroup (CCOG) study. Br J Cancer.2005Oct31;93(9):993-998
25刘鲁迎,朱远,吴列,等.局部晚期直肠癌术前含草酸铂同步放化疗Ⅱ期临床研究.腹部肿瘤，2007年第六届全国放射肿瘤学学术年会,392
26Aschele C,Friso ML,Pucciarelli S,etal. A phase I-II study of weeklyoxaliplatin,5-fluorouracil continuous infusion and preoperativeradiotherapy in locally advanced rectal cancer. Ann Oncol.2005Jul;16(7):1140-1146
27Turitto G,Panelli G,Frattolillo A,eral. Phase II study of neoadjuvantconcurrent chemioradiotherapy with oxaliplatin-containing regimen inlocally advanced rectal cancer. Front Biosci.2006May1;11:1275-1279
28Rosenthal DI,Catalano PJ,Haller DG,etal. Phase I study of preoperativeradiation therapy with concurrent infusional5-fluorouracil and oxaliplatinfollowed by surgery and postoperative5-fluorouracil plus leucovorin forT3/T4rectal adenocarcinoma: ECOG E1297Int J Radiat Oncol BiolPhy.2008Sep1;72(1):108-113
29Aschele C,Cionini L,Lonardi S,etal.Primary tumor response topreoperative chemoradiation with or without oxaliplatin in locallyadvanced rectal cancer: pathologic results of the STAR-01randomizedphase III trial. J Clin Oncol.2011Jul10;29(20):2773-2780
30殷蔚伯、余子豪、徐国镇等.肿瘤放射治疗学，第四版，中国协和医科大学出版社，2007:855-881
31Kim JS,Kim JS,Cho MJ,etal.Comparison of the efficacy of oralcapecitabine versus bolus5-FU in preoperative radiotherapy of locallyadvanced rectal cancer. J Korean Med Sci2006Feb;21(1):52-57
32Ramani VS,Sun Myint A,Montazeri A,etal.Preoperative chemoradiotherapy for rectal cancer: a comparison between intravenous5-fluorouracil andoral capecitabine. Colorectal Dis.2010Aug;12Suppl2:37-46
33Dunst J,Reese T,Sutter T,etal.Phase I trial evaluating the concurrentcombination of radiotherapy and capecitabine in rectal cancer. J ClinOncol.2002Oct1;20(19):3983-3991
34Ngan SY,Michael M,Mackay J,etal.A phase I trial of preoperativeradiotherapy and capecitabine for locally advanced, potentially resectablerectal cancer. Br J Cancer.2004Sep13;91(6):1019-1024
35Kim JS,Kim JS,Cho MJ,etal. Preoperative chemoradiation using oralcapecitabine in locally advaneed rectal cancer.Int J Radiat Oneol BiolPhys.2002Oct1;54(2):403-408
36Zampino MG,Magni E,Leonardi MC,etal.Capecitabine initiallyconcomitant to radiotherapy then perioperatively administered in locallyadvanced rectal cancer.Int J Radiat Oncol Biol Phys.2009Oct1;75(2):421-427
37Dunst J,Debus J,Rudat V,etal.Neoadjuvant capecitabine combined withstandard radiotherapy in patients with locally advanced rectal cancer:mature results of a phase II trial. Strahlenther Onkol.2008Sep;184(9):450-456
38Swellengrebel HA,Marijnen CA,Verwaal VJ,etal.Toxicity andcomplications of preoperative chemoradiotherapy for locally advancedrectal cancer. Br J Radiol.2011Mar;98(3):418-426
39Bajetta E,Beretta E,Di Bartolomeo M,etal.Capecitabine chemoradiationfor rectal canecer after curative surgery.J Chemother.2006Feb;18(1):85-89
40Glynne-Jones R,Sebag-Montefiore D,Maughan TS,etal.A phase I doseescalation study of continuous oral capecitabine in combination withoxaliplatin and pelvic radiation (XELOX-RT) in patients with locallyadvanced rectal cancer. Ann Oncol.2006Jan;17(1):50-56
41Fakih MG,Rajput A,Yang GY,etal.A phase I study of weekly intravenousoxaliplatin in combination with oral daily capecitabine and radiationtherapy in the neoadjuvant treatment of rectal adenocarcinoma. Int JRadiat Oncol Biol Phys.2006Aug1;65(5):1462-1470
42Aristu JJ,Arbea L,Rodriguez J,etal.phase Ⅱ-Ⅲ Trial of ConcurrentCapecitabine and Oxaliplatin247with Preoperative Intensity-ModulatedRadiotherapy in Patients with locally advanced Rectal Cancer.Int J RadiatOncol Biol Phys.2008Jul1;71(3):748-755
43Arbea L,Martinez-Monge R,Diaz-Gonzalez JA,etal.Four-Week Neoadjuv-ant Intensity-Modulated Radiation Therapy with Concurrent Capecitabineand Oxaliplatin in Locally Advanced Rectal Cancer Patients: A ValidationPhase II Trial. Int J Radiat Oncol Biol Phys.2011Nov11
44Rodel C,Grabenbauer GG,Papadopoulos T, etal. Phase I/II trial ofcapecitabine, oxaliplatin, and radiation for rectal cancer. J Clin Oncol.2003Aug15;21(16):3098-3104
45Rodel C,Lierseh T,Hermann RM,etal.Multicenter phase Ⅱ trial ofchemoradiation with oxaliplatin for rectal cancer.J Clin Oncol.2007Jan1;25(1):110-117
46G é rard JP, Azria D,Gourgou-Bourgada S,etal.Comparison of twoneoadjuvant chemoradiotherapy regimens for locally advanced rectalcancer: results of the phase III trial ACCORD12/0405-Prodige2J ClinOncol.2010Apr1;28(10):1638-1644
47Klautke G,Feyerherd P,Ludwig K,etal.Intensified concurrentchemoradio-therapy with5-fluorouracil and irinotecan as neoadjuvanttreatment in patients with locally advanced rectal cancer[J].Br J Cancer.2005Apr11;92(7):1215-1220
48Navarro M,Dotor E,Rivera F,etal. A Phase II study of preoperativeradiotherapy and concomitant weekly irinotecan in combination withprotracted venous infusion5-fluorouracil, for resectable locally advancedrectal cancer.2006Sep1;66(1):201-205
49Hong YS,Kim DY,Lim SB,etal.Preoperative chemoradiation withirinotecan and capecitabine in patients with locally advanced resectablerectal cancer: long-term results of a Phase II study.2011Mar15;79(4):1171-1178
50Gollins S,Sun Myint A,Haylock B,etal.Preoperative chemoradiotherapyusing concurrent capecitabine and irinotecan in magnetic resonanceimaging-defined locally advanced rectal cancer: impact on long-termclinical outcomes.2011Mar10;29(8):1042-1049
51Hofheinz RD,Horisberger K,Woernle C,etal. Phase I trial of cetuximab incombination with capecitabine, weekly irinotecan, and radiotherapy asneoadjuvant therapy for rectal cancer.Int J Radiat Oncol Biol Phys.2006Dec1;66(5):1384-1390
52Horisberger K,Treschl A,Mai S,etal. Cetuximab in combination withcapecitabine, irinotecan, and radiotherapy for patients with locallyadvanced rectal cancer: results of a Phase II MARGIT trial. Int J RadiatOncol Biol Phys.2009Aug1;74(5):1487-1493
53Machiels JP, Sempoux C,Scalliet P,etal.Phase I/II study of preoperativecetuximab, capecitabine, and external beam radiotherapy in patients withrectal cancer. Ann Oncol.2007Apr;18(4):738-744
54Rodel C,Arnold D,Hipp M,etal. Phase I-II trial of cetuximab, capecitabine,oxaliplatin, and radiotherapy as preoperative treatment in rectal cancer.IntJ Radiat Oncol Biol Phys.2008Mar15;70(4):1081-1086
55Bertolinl F,Chiara S,Bengala C,etal.Neoadjuvant treatment withsingle-agent cetuximab followed by5-FU,cetuximab,and pelvicradiotherapy: a phase II study in locally advanced rectal cancer. Int JRadiat Oncol Biol Phys.2009Feb1;73(2):466-472
56Crane CH,Eng C,Feig BW, etal.Phase II trial of neoadjuvant bevacizumab,capecitabine, and radiotherapy for locally advanced rectal cancer. Int JRadiat Oncol Biol Phys.2010Mar1;76(3):824-830
57Velenik V,Ocvirk J,Music M,etal.Neoadjuvant capecitabine, radiotherapy,and bevacizumab (CRAB) in locally advanced rectal cancer: results of anopen-label phase II study. Radiat Oncol.2011Aug31;6:105
58Marquardt F,Rodel F,Capalbo G,etal.Molecular targeted treatment andradiation therapy for rectal cancer.Strahlenther Onkol.2009Jun;185(6):371-378