Copyright © National Comprehensive Cancer …csjfyy.com/articles/E/020/170.pdfSachin M. Apte, MD,...
Transcript of Copyright © National Comprehensive Cancer …csjfyy.com/articles/E/020/170.pdfSachin M. Apte, MD,...
Copyright © National Comprehensive Cancer Network 2011. All rights reserved. “NCCN”, the NCCN logo, and “National Comprehensive Cancer Network” are registered trademarks of the National Comprehensive Cancer Network. The Chinese edition of NCCN Clinical Practice Guidelines in Oncology-Cervical Cancer Guideline 2011 is the Chinese adapted version of NCCN Clinical Practice Guidelines in Oncology-Cervical Cancer Guideline, V.1.2011 as permitted and endorsed by NCCN. It is the collaborative outcome of the National Comprehensive Cancer Network and Chinese key opinion leaders of the field.
The original guideline and Chinese edition are both available at: http://www.nccn.org. To view the most recent and complete version of the guideline, go online to www.nccn.org. These Guidelines and illustrations herein may not be reproduced in any form for any purpose without the express written permission of the NCCN. These Guidelines are a work in progress that will be refined as often as new significant data becomes available. The NCCN Guidelines are a statement of consensus of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN guideline is expected to use independent medical judgment in the context of individual clinical circumstance to determine any patient's care or treatment. The National Comprehensive Cancer Network makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. This publication should not be used for commercial purpose. It is provided for free to Chinese medical professions.
© National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.The Chinese edition 2011 is the collaborative outcome of the National Comprehensive Cancer Network and Chinese key opinion leaders of the field. Translated and adapted with permission and endorsement from the National ComprehensiveCancer Network. To view the most recent and complete version of this or any other guideline, visit www.nccn.org.
宫颈癌
NCCN宫颈癌专家组成员
妇科肿瘤
肿瘤内科
血液科
放疗科/放射肿瘤科
病理科
编委会成员
Ω†‡§≠*
*BenjaminE.Greer,MD/Co-ChairΩFred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance
* Wui-Jin Koh, MD/Co-Chair §Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance
NadeemR.Abu-Rustum,MDΩMemorial Sloan-Kettering Cancer Center
SachinM.Apte,MD,MSΩH.LeeMoffittCancerCenter&ResearchInstitute
Susana M. Campos, MD, Mph, MS †Dana-Farber/BrighamandWomen′sCancer Center
JohnChan,MDΩUCSF Helen Diller Family Comprehensive Cancer Center
KathleenR.Cho,MD≠University of Michigan Comprehensive Cancer Center
LarryCopeland,MDΩThe Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute
MartaAnnCrispens,MDΩVanderbilt-Ingram Cancer Center
NefertitiDuPont,MD,MPHΩRoswell Park Cancer Institute
Patricia J. Eifel, MD §The University of Texas MD Anderson Cancer Center
David K. Gaffney, MD, PhD §Huntsman Cancer Institute at the University of Utah
WarnerK.Huh,MDΩUniversity of Alabama at Birmingham Comprehensive Cancer Center
Daniel S. Kapp, MD, PhD §Stanford Comprehensive Cancer Center
JohnR.Lurain,IIIMDΩRobert H. Lurie Comprehensive CancerCenter of Northwestern University
Lainie Martin, MD †Fox Chase Cancer Center
MarkA.Morgan,MDΩFox Chase Cancer Center
Robert J. Morgan, Jr., MD † ‡City of Hope ComprehewsiveCancer Center
DavidMutch,MDΩSiteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
StevenW.Remmenga,MDΩUNMC Eppley Cancer Center at The Nebraska Medical Center
R.KevinReynolds,MDΩUniversity of Michigan Comprehensive Cancer Center
William Small, Jr., MD §Robert H. Lurie Comprehensive CancerCenter of Northwestern University
NelsonTeng,MD,PhDΩStanford Comprehensive Cancer Center
FidelA.Valea,MDΩDuke Comprehensive Cancer Center
NCCN StaffMiranda Hughes, PhDNicole McMillian, MS
宫颈癌
© National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.The Chinese edition 2011 is the collaborative outcome of the National Comprehensive Cancer Network and Chinese key opinion leaders of the field. Translated and adapted with permission and endorsement from the National ComprehensiveCancer Network. To view the most recent and complete version of this or any other guideline, visit www.nccn.org.
NCCN特别鸣谢
NCCN指南中国版专家组
召集人:
孙 燕 中国医学科学院北京协和医学院
肿瘤医院
NCCN代表:
Robert J. Morgan, Jr., MDCity of Hope Comprehensive Cancer Center
NCCN宫颈癌临床实践指南(中国版)专家组
组 长:
沈 铿中国医学科学院北京协和医学院北京协和医院
成 员(按拼音排序):
曹泽毅清华大学第二附属医院
崔 恒北京大学人民医院
狄 文上海交通大学医学院附属仁济医院
丰有吉上海市第一人民医院
高雨农北京大学临床肿瘤学院、北京肿瘤医院
郭丽娜中国医学科学院北京协和医学院北京协和医院
郝 权天津医科大学附属肿瘤医院
孔北华山东大学齐鲁医院
郎景和中国医学科学院北京协和医学院北京协和医院
李 力广西医科大学附属肿瘤医院
李子庭复旦大学附属肿瘤医院
林仲秋中山大学附属第二医院
执笔人:吴小华
复旦大学附属肿瘤医院
刘继红中山大学附属肿瘤医院
刘丽影中国医学科学院北京协和医学院肿瘤医院
马 丁华中科技大学同济医学院附属同济医院
盛修贵山东省肿瘤医院
宋 磊中国人民解放军总医院(三○一医院)
魏丽惠北京大学人民医院
吴令英中国医学科学院北京协和医学院肿瘤医院
吴 鸣中国医学科学院北京协和医学院北京协和医院
吴 强江苏省肿瘤医院
向 阳中国医学科学院北京协和医学院北京协和医院
谢 幸浙江大学医学院附属妇产科医院
张福泉中国医学科学院北京协和医学院北京协和医院
© National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.The Chinese edition 2011 is the collaborative outcome of the National Comprehensive Cancer Network and Chinese key opinion leaders of the field. Translated and adapted with permission and endorsement from the National ComprehensiveCancer Network. To view the most recent and complete version of this or any other guideline, visit www.nccn.org.
宫颈癌
目录
NCCN宫颈癌专家组成员
NCCN特别鸣谢
指南更新概要
临床分期(CERV-1)
IA1、IA2期(CERV-2)
IB1期和IIA1期(CERV-2)
IB2期和IIA2期(CERV-2)
IB2、IIA2期和IIB、IIIA、IIIB、IVA期(CERV-4)
单纯子宫切除时意外发现的宫颈浸润癌(CERV-7)
监测(CERV-8)
局部/区域复发(CERV-9)
远处转移(CERV-10)
宫颈癌的放疗原则(CERV-A)
复发或转移性宫颈癌的化疗方案(CERV-B)
分期(ST-1)
讨论(MS-1)
参考文献(REF-1)
临床试验:NCCN认为任何肿瘤患者都可以在临床试验中得到最
佳处理,因此特别鼓励肿瘤患者参加临床试验研究。
NCCN对证据和共识的分类:
除非特别指出,NCCN对所有建议均达成2A类共识。 见NCCN对证据和共识的分类
NCCN宫颈癌指南包括了对宫颈鳞状细胞癌、宫颈腺鳞癌和宫颈腺癌的处理。
作为共识,NCCN肿瘤学临床实践指南反映了作者们对目前认可的治疗方法的观点,欲参考或应用这些指南的临床医师应根据个人具体的临床情况做出独立的医疗判断,以决定患者所需的护理和治
疗。任何寻求使用这些指南的患者或非医生人员应咨询医生关于它们的合理应用。
NCCN肿瘤学临床实践指南编译力求精确表达反映原版英文指南。NCCN不保证指南编译的有效性,也不承认任何无限制性的担保、表达及暗示。NCCN不担保指南编译或指南本身的精确性和完整
性。NCCN不保证或担保或陈述指南的应用及应用结果。NCCN及其成员不对涉及指南无限制性应用的任何偶然的、间接的、特殊的、惩罚性或作为结果的补偿费承担任何责任。
声明:
本指南中标注“※”处为中国专家根据国内实际情况进行明显
改动或补充之处,内容有别于英文版,参考时请注意。
宫颈癌
© National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.The Chinese edition 2011 is the collaborative outcome of the National Comprehensive Cancer Network and Chinese key opinion leaders of the field. Translated and adapted with permission and endorsement from the National ComprehensiveCancer Network. To view the most recent and complete version of this or any other guideline, visit www.nccn.org.
指南更新概要
总体变更:● 新增“放疗原则”,给出贯穿整本N C C N宫颈癌指南的具体建议及放疗剂量
(CERV-A)。
CERV-1● 检查:对“全血细胞计数”及“影像检查”条目做了修订,使语义更为明确。
(CERV-7做了同样修订)
CERV-2● IA1期;初始治疗:第3条选择更改为“如果脉管间隙受侵,行改良根治性子宫切除
术或根治性宫颈切除术+盆腔淋巴结切除术(淋巴结切除术为2B类)”。● IA2期;初始治疗:第2条选择由“近距离放疗+盆腔放疗……”更改为“近距离放疗
±盆腔放疗……”● IB1期和I I A1期;初始治疗:“对IB1期患者行根治性宫颈切除术以保留生育功能
……”更改为“对肿瘤≤2 cm(IB1期)的患者行根治性宫颈切除术……”
CERV-3● 手术发现:“盆腔淋巴结阳性或手术切缘阳性或宫旁组织阳性”更改为“盆腔淋巴
结阳性和/或手术切缘阳性和/或宫旁组织阳性”(CERV-7做了同样修订)● “腹主动脉旁淋巴结阳性……”;底部路径:
➤ “胸部CT/PET扫描”明确为“胸部CT或PET-CT扫描”。
➤ “全身治疗/个体化放疗”更改为“全身治疗±个体化放疗”。(C E RV-5和
CERV-6做了同样修订)
CERV-4● 仅影像学检查;淋巴结阳性:“如果有临床指征,行细针穿刺活检”更改为“考虑
针吸活检”。
CERV-5● “盆腔淋巴结阳性/腹主动脉旁淋巴结……”更改为“盆腔淋巴结阳性且腹主动脉
旁淋巴结……”
CERV-6● “腹膜后淋巴结切除术”更改为“腹膜后淋巴结切除术(首选腹膜外淋巴结切
除术)”。 ※
CERV-7● “ I A1期有脉管间隙浸润”路径中,删除了原推荐中的“选择性检查项目
(≥IB2期):麻醉下盆腔检查,膀胱镜/直肠镜检查”。
CERV-8● 监测:增添了“针对症状对患者进行宣教”。● 检查:“盆腔/腹腔/胸部CT/PET扫描”更改为“如有临床指征另行影像学检查”。● 针对PET-CT扫描,新增脚注“h”。
CERV-9● 非中心性复发:删除了“肿瘤切除并对切缘临近肿瘤或切缘阳性者给予术中放疗”
之前的“盆腔廓清术”。● “铂类为主的化疗”更改为“化疗”。
CERV-10 ● 可切除:“放疗+同步化疗”更改为“放疗±同步化疗”。
CERV-B 复发或转移性宫颈癌的化疗方案● 一线联合方案:“顺铂/紫杉醇”从“1类”推荐更改为“2A类”。● 二线方案:
➤ 说明更改为“下列均为2B类,除非另外注明”。
➤ 删除了“表柔比星”和“多柔比星脂质体”。
➤ “培美曲塞”和“长春瑞滨”从“2B类”推荐更改为“3类”。
● 引用NCCN卵巢癌指南中药物反应的处理(OV-C)页的脚注为本页新增。
NCCN宫颈癌指南2011年中国版与2010年中国版相比,更新之处主要包括:
UPDATES
© National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.The Chinese edition 2011 is the collaborative outcome of the National Comprehensive Cancer Network and Chinese key opinion leaders of the field. Translated and adapted with permission and endorsement from the National ComprehensiveCancer Network. To view the most recent and complete version of this or any other guideline, visit www.nccn.org.
宫颈癌
检查 临床分期
● 病史和体检
● 血常规
● 宫颈活检,病理检查
● 如有指征,行锥切活检a
● 肝/肾功能检查
● 影像学检查 ※➤ 胸片
➤ C T或P E T/C T扫描(对于
≤IB1期者为可选性)
➤ 如有指征,做M R I(对于
≤IB1期者为可选性)
选择性检查项目(≥IB2期):
● 麻醉下盆腔检查,膀胱镜/直肠
镜检查b
IA1期
IA2期IB1期IIA1期
IB2期IIA2期
IIB期IIIA、IIIB期IVA期
单纯子宫切除术后意外
发现的宫颈浸润癌
见初始治疗(CERV-2)
见初始治疗(CERV-2)
见初始治疗(CERV-2)和(CERV-4)
见初始治疗(CERV-4)
见初始治疗(CERV-7)
a 见讨论部分锥切活检的指征(MS-2)。b 对可疑膀胱/肠管受侵,需要做膀胱镜/直肠镜下活检。
CERV-1
指南中的所有分期均依据更新的2009 FIGO分期。(见ST-1)
宫颈癌
© National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.The Chinese edition 2011 is the collaborative outcome of the National Comprehensive Cancer Network and Chinese key opinion leaders of the field. Translated and adapted with permission and endorsement from the National ComprehensiveCancer Network. To view the most recent and complete version of this or any other guideline, visit www.nccn.org.
CERV-2
临床分期 初始治疗
IA1期
IA2期
IB1期和IIA1期
IB2期和IIA2期(也见CERV-4)
筋膜外子宫切除术或如果患者要求生育或不宜手术(仅当锥切活检切缘阴性时)可观察或如果脉管间隙受侵,行改良根治性子宫切除术或根治性宫颈切除术+盆腔淋巴结切除术(淋巴结切除术为2B类)
根治性子宫切除术+盆腔淋巴结切除术±腹主动脉旁淋巴结取样或近距离放疗±盆腔放疗(A点总剂量:75~80 Gy)c
或根治性宫颈切除术+盆腔淋巴结切除术±腹主动脉旁淋巴结取样
根治性子宫切除术+盆腔淋巴结切除术±腹主动脉旁淋巴结取样(1类)或盆腔放疗+近距离放疗(A点总剂量:80~85 Gy)c
或对肿瘤≤2 cm(IB1期)的患者行根治性宫颈切除术+盆腔淋
巴结切除术±腹主动脉旁淋巴结取样
盆腔放疗+含顺铂的同步化疗 d+近距离放疗(A点总剂量:≥85 Gy)c(1类)或根治性子宫切除术+盆腔淋巴结切除术+腹主动脉旁淋巴结取样(2B类)或盆腔放疗+含顺铂的同步化疗d+近距离放疗(A点总剂量:75~80 Gy)c+辅助性子宫全切术(3类)
见监测(CERV-8)
见手术发现(CERV-3)
见手术发现(CERV-3)
见监测(CERV-8)
见手术发现(CERV-3)
见监测(CERV-8)
见监测(CERV-8)
见手术发现(CERV-3)
见监测(CERV-8)
c 这些剂量系根据传统外照射单次分割剂量和低剂量率(40~70 cGy/h)近距离放疗等效剂量之和确定,对大多数患者可推荐使用。可根据正常组织耐受性调整治疗。[见讨论(MS-10)]d 采用顺铂单药或顺铂+氟尿嘧啶方案的以顺铂为基础的同步化疗联合放疗。
© National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.The Chinese edition 2011 is the collaborative outcome of the National Comprehensive Cancer Network and Chinese key opinion leaders of the field. Translated and adapted with permission and endorsement from the National ComprehensiveCancer Network. To view the most recent and complete version of this or any other guideline, visit www.nccn.org.
宫颈癌
手术发现 辅助治疗
淋巴结阴性
盆腔淋巴结阳性
和/或手术切缘阳性
和/或宫旁组织阳性
手术分期发现腹主
动脉旁淋巴结阳性
或
髂总淋巴结阳性※
盆腔放疗e(如果合并高危因素如原发
肿瘤大、间质浸润深、和/或脉管间隙
受侵)(1类)±顺铂为基础的同步化
疗d(化疗为2B类)
或
观察
盆腔放疗e+含顺铂的同步化疗d(1类)
±阴道近距离放疗e
无远处转移
有远处转移如有指征,对可疑
转移部位考虑活检
胸部CT或PET-CT扫描 阴性
阳性
见监测(CERV-8)
腹主动脉旁淋巴结放疗e
+含顺铂的同步化疗d+
盆腔放疗e±近距离放疗e
全身治疗f±个体化放疗e
见监测(CERV-8)
d 采用顺铂单药或顺铂+5-氟尿嘧啶方案的以顺铂为基础的同步化疗联合放疗。e 见宫颈癌的放疗原则(CERV-A)。f 见复发或转移性宫颈癌的化疗方案(CERV-B)。
CERV-3
宫颈癌
© National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.The Chinese edition 2011 is the collaborative outcome of the National Comprehensive Cancer Network and Chinese key opinion leaders of the field. Translated and adapted with permission and endorsement from the National ComprehensiveCancer Network. To view the most recent and complete version of this or any other guideline, visit www.nccn.org.
临床分期 初始治疗
IB2期IIA2期
IIB、IIIA、IIIB、IVA期
仅影像学检查
或
手术分期:
腹膜外或腹腔镜下
淋巴结切除术
(2B类)
c 采用顺铂单药或顺铂+5-氟尿嘧啶方案的以顺铂为基础的同步化疗联合放疗。e 见宫颈癌的放疗原则(CERV-A)。
CERV-4
阴性
阳性
盆腔放疗e+含顺铂的同步化疗d(1类)
+近距离放疗e
见淋巴结状况
(CERV-5)
淋巴结阴性
淋巴结阳性
盆腔放疗e+含顺铂的同步化疗d(1类)
+近距离放疗e
考虑行针吸活检见影像学检查结果
(CERV-6)
见监测(CERV-8)
© National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.The Chinese edition 2011 is the collaborative outcome of the National Comprehensive Cancer Network and Chinese key opinion leaders of the field. Translated and adapted with permission and endorsement from the National ComprehensiveCancer Network. To view the most recent and complete version of this or any other guideline, visit www.nccn.org.
宫颈癌
IB2、IIA2期;IIB、IIIA、IIIB、IVA期
淋巴结状况
初始治疗
手术分期发现
腹主动脉旁
淋巴结阳性
如有临床指征,
行进一步影像学
评估
无远处转移
有远处转移
如有指征,对
可疑部位考虑
活检
阴性
阳性
盆腔放疗e+含顺铂的
同步化疗d(1类)+
近距离放疗e
盆腔放疗e+腹主动脉旁
淋巴结放疗e+含顺铂的
同步化疗d+近距离放疗e
全身治疗f±个体化放疗e
见监测(CERV-8)
手术分期发现盆腔淋巴结阳性
且腹主动脉旁淋巴结阴性
CERV-5
d 采用顺铂单药或顺铂+5-氟尿嘧啶方案的以顺铂为基础的同步化疗联合放疗。e 见宫颈癌的放疗原则(CERV-A)。f 见复发或转移性宫颈癌的化疗方案(CERV-B)。
宫颈癌
© National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.The Chinese edition 2011 is the collaborative outcome of the National Comprehensive Cancer Network and Chinese key opinion leaders of the field. Translated and adapted with permission and endorsement from the National ComprehensiveCancer Network. To view the most recent and complete version of this or any other guideline, visit www.nccn.org.
IB2、IIA2期;IIB、IIIA、
IIIB、IVA期 影像学检查结果
初始治疗
CT、MRI和 /或PET发现阳性
淋巴结
盆腔淋巴结阳性;
腹主动脉旁淋巴结
阴性
盆腔淋巴结阳性;
腹主动脉旁淋巴结
阳性
远处转移;
如有临床指征则
同时行活检证实
盆腔放疗e+
近距离放疗e+
含顺铂的同步
化疗d(1类)
±腹主动脉旁
淋巴结放疗e
或
腹膜后淋巴结 切除术(首选腹
膜外淋巴结切 除术) ※
考虑腹膜后淋巴
结切除术(首选
腹膜外淋巴结切 除术) ※
腹主动脉旁
淋巴结阴性
腹主动脉旁
淋巴结阳性
盆腔放疗e+
近距离放疗e+含顺铂
的同步化疗d(1类)
延伸野放疗e+近距离
放疗e+含顺铂的同步
化疗d
延伸野放疗e+含顺铂
的同步化疗d+近距离
放疗e
见监测
(CERV-8)
全身治疗f±个体化放疗e
见监测(CERV-8)
CERV-6
※
d 采用顺铂单药或顺铂+5-氟尿嘧啶方案的以顺铂为基础的同步化疗联合放疗。e 见宫颈癌的放疗原则(CERV-A)。f 见复发或转移性宫颈癌的化疗方案(CERV-B)。
© National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.The Chinese edition 2011 is the collaborative outcome of the National Comprehensive Cancer Network and Chinese key opinion leaders of the field. Translated and adapted with permission and endorsement from the National ComprehensiveCancer Network. To view the most recent and complete version of this or any other guideline, visit www.nccn.org.
宫颈癌
单纯子宫切除术时 初始治疗意外发现的宫颈浸润癌
I A 1期有脉管
间隙浸润
或≥IA2期
● 病史和体检
● 血常规
● 肝/肾功能检查
● 影像学检查 ※➤ 胸片
➤ CT或PET/CT扫描(对于≤I B1期者为可选性)
➤ 如 有 指 征 ,
做M R I(对于
≤I B1期者为可
选性)
IA1期 病理检查 无脉管间隙受侵
切缘阴性;
影像学检查阴性
切缘阳性g,肉眼
见残留病灶,或
影像学检查阳性
盆腔放疗e+
近距离放疗e±
含顺铂的同步
化疗d
或
完全宫旁组织及
阴道上部切除 +盆腔淋巴结切除 ±腹主动脉旁淋巴结
取样
影像学检查
淋巴结阴性
影像学检查
淋巴结阳性
见监测(CERV-8)
淋巴结阴性
淋巴结阳性
和/或手术切缘阳性
和/或宫旁组织阳性
观察
或
如原发肿瘤大、间质浸润深、
和 /或脉管间隙受侵,可选 盆腔放疗e±阴道近距离放疗e
盆腔放疗e(如腹主动脉旁淋
巴结阳性给予腹主动脉旁淋
巴结放疗)+含顺铂的同步 化疗d±个体化近距离放疗e
(如果阴道切缘阳性)
d 采用顺铂单药或顺铂+5-氟尿嘧啶方案的以顺铂为基础的同步化疗联合放疗。e 见宫颈癌的放疗原则(CERV-A)。g 手术切缘见浸润性癌。
见监测(CERV-8)
CERV-7
肉眼可见的增
大淋巴结可考
虑手术减瘤
宫颈癌
© National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.The Chinese edition 2011 is the collaborative outcome of the National Comprehensive Cancer Network and Chinese key opinion leaders of the field. Translated and adapted with permission and endorsement from the National ComprehensiveCancer Network. To view the most recent and complete version of this or any other guideline, visit www.nccn.org.
● 定期询问病史和体检
● 宫颈/阴道细胞学检查:
前2年,每3~6个月1次; 之后3~5年,每6个月1次; 然后,每年1次
● 每年1次胸片(2B类)※
● 每6个月1次血常规,
尿素氮,肌酐检查(选择性)
● 如有临床指征,行PET-CT扫描h
● 建议放疗后使用阴道扩张器 ● 如有指征,行鳞状细胞癌抗原检查 ※● 针对症状对患者进行宣教
疾病持续
或复发
● 如有临床指征另行影像
学检查
● 部分病例可行手术探查
见复发的治疗(局部区域复发)
(CERV-9)
见复发的治疗(远处转移)
(CERV-10)
CERV-8
h PET-CT可能有助于检测出适于潜在治愈性挽救治疗的孤立性复发或持续性宫颈癌。
监测 检查
© National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.The Chinese edition 2011 is the collaborative outcome of the National Comprehensive Cancer Network and Chinese key opinion leaders of the field. Translated and adapted with permission and endorsement from the National ComprehensiveCancer Network. To view the most recent and complete version of this or any other guideline, visit www.nccn.org.
宫颈癌
复发的治疗
局部/区域
复发
无放疗史或既往放疗
部位之外的复发
放疗后
复发
中心性复发
非中心性复发
盆腔廓清术±
术中放疗(IORT)
或
严格挑选的、病灶小
(<2 cm)的患者
再复发
再复发
根治性子宫切除术
或
近距离放疗e
化疗f
或
最 佳 支 持 治 疗 ( 见
NCCN姑息治疗指南)
或
入组临床试验
肿瘤切除并对切缘临近肿瘤或切缘阳性者给
予术中放疗
或
针对肿瘤局部的放疗e±化疗d,f
或
化疗f
或
最佳支持治疗(见NCCN姑息治疗指南)
或
入组临床试验
如果可行,
考虑行手术切除
针对肿瘤局部的放疗e
+铂类为主的化疗d
±近距离放疗e
CERV-9
d 采用顺铂单药或顺铂+5-氟尿嘧啶方案的以顺铂为基础的同步化疗联合放疗。e 见宫颈癌的放疗原则(CERV-A)。f 见复发或转移性宫颈癌的化疗方案(CERV-B)。
宫颈癌
© National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.The Chinese edition 2011 is the collaborative outcome of the National Comprehensive Cancer Network and Chinese key opinion leaders of the field. Translated and adapted with permission and endorsement from the National ComprehensiveCancer Network. To view the most recent and complete version of this or any other guideline, visit www.nccn.org.
复发的治疗
远处转移
多灶或
无法切除
可切除
病灶
化疗f
或
最佳支持治疗
(见NCCN姑息治疗指南)
考虑切除±术中放疗
或
针对肿瘤局部的
放疗e±同步化疗d
或
化疗f
CERV-10
放疗e(选择性)
或
辅助化疗f(选择性)
或
最佳支持治疗
(见NCCN姑息治疗指南)
※※
d 采用顺铂单药或顺铂+5-氟尿嘧啶方案的以顺铂为基础的同步化疗联合放疗。e 见宫颈癌的放疗原则(CERV-A)。f 见复发或转移性宫颈癌的化疗方案(CERV-B)。
© National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.The Chinese edition 2011 is the collaborative outcome of the National Comprehensive Cancer Network and Chinese key opinion leaders of the field. Translated and adapted with permission and endorsement from the National ComprehensiveCancer Network. To view the most recent and complete version of this or any other guideline, visit www.nccn.org.
宫颈癌
宫颈癌的放疗原则
外照射放疗(EBRT)
● 采用计算机断层扫描(CT)定位的治疗计划和适形设野被视为EBRT的标准。MRI是确定晚期肿瘤患者软组织和宫旁累及范围的最佳影像检查方式。对于未行手术
分期的患者,PET扫描有助于明确照射的淋巴结范围。
● EBRT的靶区应当包括可见病灶(如果存在)、宫旁组织、宫骶韧带、距离可见病灶足够长的阴道边缘(至少3 cm)、骶前淋巴结,和其他存在风险的淋巴结区。对于手
术或放射影像学检查淋巴结阴性的患者,放疗靶区应包括髂外、髂内和闭孔淋巴结区。对于被视为存在淋巴结受累高风险的患者(例如,较大肿瘤,或可疑/确定的
下部真骨盆的淋巴结转移),放疗靶区应扩大至包括髂总淋巴结区。对于已证实髂总和/或主动脉旁淋巴结受累者,则需要盆腔和主动脉旁延伸野的放疗,上达肾血
管水平(甚或更高,视受累淋巴结分布而定)。
● 镜下淋巴结受累需要的EBRT剂量约为45 Gy(常规分割,1.8~2.0 Gy/d),对于小体积肉眼可见未切除淋巴结区域可考虑高适形下10~15 Gy的加量。对于绝大部分接
受EBRT治疗宫颈癌的患者,在EBRT期间给予含顺铂(或者单用顺铂,或者顺铂+5-氟尿嘧啶)的同步化疗。
近距离放疗
● 对所有子宫完整的宫颈癌患者来说,近距离放疗是治疗中至关重要的组成部分。通常通过腔内途径,采用宫腔内管和阴道施源器实施。根据患者和肿瘤的解剖情况,
未行手术切除的宫颈癌患者近距离放疗的阴道放射源可采用卵圆体、环或者圆柱体(与宫腔内管联合使用)。当与EBRT联合时,近距离放疗通常于治疗后期阶段启
用,此时原发肿瘤已发生充分消退,可以满足近距离放疗仪器几何外形要求。对于严格选择的极早期(即,IA2期)患者,单用近距离放疗不加外照射,可作为一种治
疗选择。
● 对于由于肿瘤外形导致近距离放疗不能实施的罕见病例,最好采用组织间插植的方式;然而,这种组织间插植近距离放疗只允许由具有一定经验的专家在相应医院
内个体化实施。
● 对于经选择的子宫切除术后患者(尤其是阴道粘膜手术切缘阳性者),可采用阴道圆柱体近距离放疗作为EBRT的辅助。
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CERV-A4-1
宫颈癌
© National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.The Chinese edition 2011 is the collaborative outcome of the National Comprehensive Cancer Network and Chinese key opinion leaders of the field. Translated and adapted with permission and endorsement from the National ComprehensiveCancer Network. To view the most recent and complete version of this or any other guideline, visit www.nccn.org.
宫颈癌的放疗原则
设定放疗剂量的注意事项
● 最常用的近距离放疗传统剂量参数所采用的系统包括了明确指出的A点剂量,并整合了基于解剖学考虑的子宫和阴道的“放射源的装置和剂量分布”的具体指南。
同时计算标准化的B点、膀胱和直肠位点的剂量。目前的三维影像技术指导下的近距离放疗致力于寻求对肿瘤的最佳植入剂量覆盖,同时有可能减少对邻近的膀
胱、直肠和肠道脏器的剂量[1]。然而,大量的经验和肿瘤控制结果,以及大部分不断开展的临床实践,均基于A点剂量系统[2]。相对于A点剂量系统推荐剂量,通过影
像技术指导下的近距离放疗来改进剂量设定的尝试需要谨慎,不要造成肿瘤受量不足。
● NCCN指南TM给出的A点剂量推荐是基于传统的并已被广泛证实了的剂量分割及低剂量率近距离治疗依据之上的。在这些指南所提供的剂量推荐中,对于EBRT,剂
量分割为1.8~2.0 Gy/d;对于近距离放疗,A点剂量设定为一个40~70 cGy/h的低剂量率(LDR)。应用高剂量率(HDR)近距离放疗的临床医生应当依据线性二次型
方程来把HDR A点名义剂量转化成生物等效LDR A点剂量(http://www.americanbrachytherapy.org/guidelines/)。当与EBRT联合时,有多种近距离治疗方案可用。然
而,最常用的HDR方法之一为5次插入宫腔内管和阴道施源器,每次给出6 Gy的名义剂量至A点。于是,30 Gy的HDR A点名义剂量被分割为5次照射,这被普遍认可
为等同于采用低剂量率近距离放疗时A点(代表肿瘤所受剂量)40 Gy的剂量。
完整宫颈癌的根治性放疗
● 对于子宫完整的宫颈癌患者(即未接受过手术的患者)来说,针对原发肿瘤和处于转移风险中的区域淋巴系统的常规治疗方案为根治性EBRT,剂量约为45 Gy
(40~50 Gy)。EBRT的靶区需依照由手术或放射影像学确定的(如前所述)淋巴结状态而定。原发宫颈肿瘤采用近距离放疗加量照射,对A点行30~40 Gy(LDR的
等效剂量)的额外照射,A点总剂量(如指南所推荐)达80 Gy(小体积宫颈肿瘤)至85 Gy或更高(大体积宫颈肿瘤)。可对肉眼可见的残余淋巴结进行评估,追加
10~15 Gy的高适形(缩野)EBRT。采用更高剂量,尤其是EBRT时,必须要注意排除或严格限制被纳入高剂量区域中的正常组织体积(见讨论)。
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CERV-A4-2
© National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.The Chinese edition 2011 is the collaborative outcome of the National Comprehensive Cancer Network and Chinese key opinion leaders of the field. Translated and adapted with permission and endorsement from the National ComprehensiveCancer Network. To view the most recent and complete version of this or any other guideline, visit www.nccn.org.
宫颈癌
宫颈癌的放疗原则
子宫切除术后的辅助放疗
● 初始子宫切除术后,如存在1个或更多的病理风险因素则提示有必要进行辅助放疗。至少要包括如下范围:3~4 cm的阴道残端,宫旁组织,最近的淋巴结区(例如髂
外和髂内淋巴结)。对于确定为淋巴转移的区域,放射野的上界需要适当延伸(如前所述)。通常推荐为标准分割的40~50 Gy的剂量。可对肉眼可见残余淋巴结进行
评估,追加10~15 Gy的高适形(缩野)EBRT。采用更高剂量,尤其是EBRT时,必须要注意排除或严格限制被纳入高剂量区域中的正常组织体积(见讨论)。
术中放疗(IORT)
● IORT是一项在开放性手术过程中,针对高危瘤床或孤立的未切除残余灶给予单次、精确定位放疗的专业技术[3]。尤其适用于在既往放疗野内发生复发病灶的患者。
在IORT过程中,可以把所覆盖的正常组织(如肠或其他内脏)人工移位以避开放疗野。IORT通常通过不同型号(配合手术确定的放疗野)的限光筒引入的电子束完
成,这样就进一步限制了放射野的范围和深度,以避开周围正常组织结构。
CERV-A4-3
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宫颈癌
© National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.The Chinese edition 2011 is the collaborative outcome of the National Comprehensive Cancer Network and Chinese key opinion leaders of the field. Translated and adapted with permission and endorsement from the National ComprehensiveCancer Network. To view the most recent and complete version of this or any other guideline, visit www.nccn.org.
CERV-A4-4
宫颈癌的放疗原则参考文献
1 Pötter R, Haie-Meder C, Van Limbergen E, et al. Recommendations from gynaecological (GYN) GEC ESTRO working group (II): concepts and terms in 3D
imagebased treatment planning in cervix cancer brachytherapy-3D dose volume parameters and aspects of 3D image-based anatomy, radiation physics,
radiobiology. Radiother Oncol 2006;78(1):67-77. Epub 2006 Jan 5.2 Viswanathan AN, Erickson BA. Three-dimensional imaging in gynecologic brachytherapy: a survey of the American Brachytherapy Society. Int J Radiat
Oncol Biol Phys 2010;76(1):104-109.3 del Carmen MG, McIntyre JF, Goodman A. The role of intraoperative radiation therapy (IORT) in the treatment of locally advanced gynecologic
malignancies. Oncologist 2000;5(1):18-25.
© National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.The Chinese edition 2011 is the collaborative outcome of the National Comprehensive Cancer Network and Chinese key opinion leaders of the field. Translated and adapted with permission and endorsement from the National ComprehensiveCancer Network. To view the most recent and complete version of this or any other guideline, visit www.nccn.org.
宫颈癌
复发或转移性宫颈癌的化疗方案†
(积极参加临床试验)
一线联合方案
● 顺铂/紫杉醇[1,2]
● 卡铂/紫杉醇[3]
● 顺铂/托泊替康[4]
● 顺铂/吉西他滨(2B类)[5]
可供选择的一线单药方案
● 顺铂(作为单药治疗首选)[2]
● 卡铂[6]
● 紫杉醇[7]
二线方案††
(下列均为2B类,除非另外注明)
● 贝伐珠单抗§
● 多西他赛
● 5-氟尿嘧啶
● 吉西他滨
● 异环磷酰胺
● 伊立替康
● 丝裂霉素
● 托泊替康
● 培美曲塞(3类)
● 长春瑞滨(3类)
† 顺铂、卡铂、多西他赛和紫杉醇有可能引发药物反应[见NCCN卵巢癌指南——药物反应的处理(OV-C)]。†† 二线治疗的参考文献见讨论部分。§ 国内尚未批准。 ※
CERV-B2-1
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宫颈癌
© National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.The Chinese edition 2011 is the collaborative outcome of the National Comprehensive Cancer Network and Chinese key opinion leaders of the field. Translated and adapted with permission and endorsement from the National ComprehensiveCancer Network. To view the most recent and complete version of this or any other guideline, visit www.nccn.org.
CERV-B2-2
复发或转移性宫颈癌的化疗方案参考文献
1 Monk BJ, Sill MW, McMeekin DS, et al. Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical
carcinoma: A Gynecologic Oncology Group Study. J Clin Oncol 2009; 27:4649-4655.2 Moore DH, Blessing JA, McQuellon RP, et al. Phase III study of cisplatin with or without paclitaxel in stage IVB, recurrent, or persistent squamous cell
carcinoma of the cervix: a gynecologic oncology group study. J Clin Oncol. 2004;22:3113-3119.3 Moore KN, Herzog TJ, Lewin S, et al. A comparison of cisplatin/paclitaxel and carboplatin/paclitaxel in stage IVB, recurrent or persistent cervical cancer.
Gynecol Oncol 2007;105:299-303.4 Long HJ, 3rd, Bundy BN, Grendys EC, Jr., et al. Randomized phase III trial of cisplatin with or without topotecan in carcinoma of the uterine cervix: a
Gynecologic Oncology Group Study. J Clin Oncol. 2005;23:4626-4633.5 Brewer CA, Blessing JA, Nagourney RA, et al. Cisplatin plus gemcitabine in previously treated squamous cell carcinoma of the cervix. Gynecol Oncol
2006;100:385-388.6 Weiss GR, Green S, Hannigan EV, et al. A phase II trial of carboplatin for recurrent or metastatic squamous carcinoma of the uterine cervix: a Southwest
Oncology Group study. Gynecol Oncol. 1990;39:332-336.7 Kudelka AP, Winn R, Edwards CL, et al. An update of a phase II study of paclitaxel in advanced or recurrent squamous cell cancer of the cervix. Anticancer
Drugs 1997;8:657-661.
© National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.The Chinese edition 2011 is the collaborative outcome of the National Comprehensive Cancer Network and Chinese key opinion leaders of the field. Translated and adapted with permission and endorsement from the National ComprehensiveCancer Network. To view the most recent and complete version of this or any other guideline, visit www.nccn.org.
宫颈癌
分期 ※
表1宫颈癌的国际妇产科联盟(FIGO)分期(2009)†
I期 肿瘤严格局限于宫颈(扩展至宫体可以被忽略)
IA期 镜下浸润癌。间质浸润深度≤5 mm,水平浸润范围≤7 mm IA1期 间质浸润深度≤3.0 mm,水平浸润范围≤7.0 mm IA2期 间质浸润深度>3.0 mm,但不超过5.0 mm,水平浸润范围≤7.0 mm IB期 临床肉眼可见病灶局限于宫颈,或是临床前病灶>IA期* IB1期 临床肉眼可见病灶最大直径≤4.0 cm IB2期 临床肉眼可见病灶最大直径>4.0 cm II期 肿瘤已经超出子宫颈,但未达盆壁,或未达阴道下1/3 IIA期 无宫旁组织浸润
IIA1期 临床肉眼可见病灶最大直径≤4.0 cm IIA2期 临床肉眼可见病灶最大直径>4.0 cm IIB期 有明显宫旁组织浸润
III期 肿瘤侵及盆壁和/或侵及阴道下1/3和/或导致肾盂积水或无功能肾** IIIA期 肿瘤侵及阴道下1/3,未侵及盆壁
IIIB期 肿瘤侵及盆壁和/或导致肾盂积水或无功能肾
IV期 肿瘤超出真骨盆或(活检证实)侵及膀胱或直肠粘膜。泡状水肿不能分 为IV期
IVA期 肿瘤侵及邻近器官
IVB期 肿瘤侵及远处器官
ST-1
*所有肉眼可见病灶即便是浅表浸润也都定义为 IB期。浸润癌局限于测量到的间质浸润范围,最大深
度为5 mm,水平范围不超过7 mm。无论从腺上皮或
者表面上皮起源的病变,从上皮的基底膜量起浸润深
度不超过5 mm。浸润深度总是用mm来报告,即便那
些早期(微小)间质浸润(~1 mm)。血管/淋巴间
隙受侵不改变分期。
**直肠检查时,肿瘤与盆腔壁间没有无肿瘤浸润间
隙。任何不能找到其他原因的肾盂积水及无功能肾病
例都应包括在内。
† 经国际妇产科联盟允许引自:Pecorelli S. Revised FIGO staging for carcinoma of the vulva, cervix and endometrium. FIGO Committee on Gynecologic Oncology. Int J Gynaecol Obstet 2009;105:103-104. Copyright 2009.
宫颈癌
© National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.The Chinese edition 2011 is the collaborative outcome of the National Comprehensive Cancer Network and Chinese key opinion leaders of the field. Translated and adapted with permission and endorsement from the National ComprehensiveCancer Network. To view the most recent and complete version of this or any other guideline, visit www.nccn.org.
讨论
概述
美国2010年预计将有大约12,200例新发宫颈癌患者,并且将有4,200例患者
死亡[1]。虽然西班牙/拉丁裔、黑色人种,以及亚洲女性的宫颈癌发病率仍居高
不下,但美国女性宫颈癌的发病率在下降[2-5]。尽管如此,宫颈癌仍然是威胁全
世界女性健康的重要问题。2002年全球宫颈癌发病人数为493,200例,每年死
亡人数为273,500例。宫颈癌是世界范围内女性最常见的第三大肿瘤[6,7],78%的病例发生于发展中国家,在那里宫颈癌是女性肿瘤致死的第二位原因。
人乳头瘤病毒(HPV)的持续感染被认为是引发宫颈癌的最重要原因。
人群中HPV的感染率和宫颈癌的发病率相关。在宫颈癌高发病率的国家,慢
性HPV感染率为10%~20%,而在低发病率国家,感染率只有5%~10%[6]。针对
HPV的免疫接种可以预防某些亚型的HPV持续感染,因而有望用来预防HPV感染引起的宫颈癌(见NCCN宫颈癌筛查指南)[8-12]。其他与宫颈癌有关的流行
病学危险因素包括吸烟史、经产、使用避孕药、性交年龄过早、多个性伴侣、性
传播疾病史以及长期免疫力低下[13]。
鳞状细胞癌约占全部宫颈癌的80%,而腺癌约占20%。在发达国家,宫颈
鳞癌发病率和死亡率的大幅度下降被认为要归功于有效的筛查,尽管存在
种族、民族、以及地理方面的差异[2,3,14,15]。然而,过去30年来宫颈腺癌有所增
加,可能是因为宫颈细胞学筛查方法对于腺癌来说不那么有效[16-19]。采用检测
HPV的筛查方法或许能提高腺癌的检出率。HPV疫苗免疫接种或许能同时降
低鳞癌和腺癌的发病率[18,20]。
严格来讲,NCCN临床实践指南并不能涵盖所有可能的临床情况,也无意
取代好的临床判断以及个体化治疗措施。在制定本指南的过程中,宫颈癌专家
组成员讨论了许多一般规律之外的情况。
诊断和检查
本NCCN指南讨论了宫颈鳞状细胞癌、腺鳞癌和腺癌。神经内分泌癌、小
细胞肿瘤、透明细胞癌、肉瘤以及其他病理类型不在本指南范畴之内。
目前,国际妇产科联盟(FIGO)对分期的评价措施限于阴道镜、活检、宫
颈锥切、膀胱镜和乙状结肠镜。更多更复杂的影像学检查和手术结果未列入
MS-1
NCCN对证据和共识的分类
1类:基于高水平证据(如随机对照试验)提出的建议,专家组一致
同意。
2A类:基于低水平证据提出的建议,专家组一致同意。
2B类:基于低水平证据提出的建议,专家组基本同意,无明显
分歧。
3类:基于任何水平证据提出的建议,专家组意见存在明显的分歧。
除非特别指出,NCCN对所有建议均达成2A类共识。
© National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.The Chinese edition 2011 is the collaborative outcome of the National Comprehensive Cancer Network and Chinese key opinion leaders of the field. Translated and adapted with permission and endorsement from the National ComprehensiveCancer Network. To view the most recent and complete version of this or any other guideline, visit www.nccn.org.
宫颈癌
FIGO分期。然而,在美国,CT、MRI、正电子发射成像(PET)-CT和手术分期经
常被用来指导治疗方案的选择和设计[21-23]。
宫颈癌极早期可以没有症状或有水样阴道分泌物和性交后出血或阴道间
歇点滴出血。这些早期症状经常被患者忽略。由于宫颈的可触及性,通常采用
宫颈细胞学检查或巴氏(Pap)涂片和宫颈活检就可以得出准确诊断(见NCCN宫颈癌筛查指南)。如果宫颈活检不足以确定肿瘤浸润情况,或者需要对宫颈
的微小浸润进行准确评价时,建议使用锥切术。然而,由于宫颈原位腺癌累犯
的宫颈部位(例如,宫颈管内)比较难以取样,宫颈细胞学筛查方法对于宫颈
腺癌诊断的帮助不大[5,19]。
存在可疑症状患者的检查包括询问病史、体格检查、血常规、肝肾功能检
查。放射影像学检查包括胸片、CT或PET-CT,以及有指征时做MRI检查(如,
为排除颈管高位病变);然而对IB1期或期别更早的患者,除胸片外的影像学检
查为可选(见CERV-1)※。对于临床上怀疑膀胱或直肠累及的患者,应该为其
预约膀胱镜检查和直肠镜检查。
NCCN宫颈癌专家组成员讨论了腹腔镜操作和机器人手术是否应该作为
NCCN指南中分期和治疗的一部分。这些技术的应用越来越频繁,但目前尚未
获得长期随访数据。在一些NCCN成员机构,腹腔镜下分期术、淋巴结清扫和
根治性子宫切除已经在一些有指征的患者中常规应用,并且达到了满意的效
果[24-26]。国外研究的数据提示:接受腹腔镜下根治性子宫切除术的患者,术后
随访3~6年的肿瘤复发率低[27,28]。机器人根治性子宫切除术作为另一种微创手
术技术,目前被用于早期宫颈癌患者的治疗。腹腔镜及机器人手术技术的潜在
优势为患者的住院时间缩短,恢复更快[29-31]。
分期
考虑到各地的无创性影像学检查资源不同及其在世界范围的广泛应用,
FIGO分期系统将影像学检查仅限于胸片、静脉肾盂造影(IVP)和钡灌肠。宫
颈癌分期主要依靠临床评价。尽管手术分期比临床分期更为精确,但是在一些
医疗资源并不丰富的国家,手术分期通常难被采用[22,32,33]。指南专家组目前采用
了FIGO 2009年的定义和分期系统(见表1)[32,34]。该FIGO分期系统已被美国癌
症联合委员会(AJCC)批准[35]。根据新分期,IIA期现在被进一步划分为IIA1期(肿瘤直径≤4 cm)和IIA2期(肿瘤直径>4 cm),这是较之前的1994 FIGO分
期系统的唯一变动之处。
有必要指出的是,脉管间隙受侵(LVSI)不会影响FIGO分期[32]。FIGO分
期不包括脉管间隙受侵,是因为病理医生对组织标本中是否存在LVSI有时候
不能达成一致意见。一些专家组成员认为IA1期患者若存在明确的LVSI,则不
能按照IA1期治疗计划,而应该按照IB1期的指南进行治疗。
MRI、CT或PET-CT扫描可以用来帮助制定治疗计划,但并不正式用于 分期[22,33,36,37]。而且,FIGO一直主张分期只是用来比较,并不是用来指导治
疗。因此,专家组采用FIGO定义作为指南的分层体系,而影像学检查(例如CT和MRI)结果被用于指导治疗方案的选择和设计。MRI有助于排除颈管高位 病变。
初始治疗
早期宫颈癌的初始治疗可选择手术或放疗(RT)。手术通常适用于低分期
和小病灶的患者,如IA和IB1和部分IIA1期。基于5项随机临床试验的结果(见
MS-2
宫颈癌
© National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.The Chinese edition 2011 is the collaborative outcome of the National Comprehensive Cancer Network and Chinese key opinion leaders of the field. Translated and adapted with permission and endorsement from the National ComprehensiveCancer Network. To view the most recent and complete version of this or any other guideline, visit www.nccn.org.
表2),NCCN专家组一致认为同步化放疗应成为IB2~IVA期宫颈癌患者的初
始治疗选择。化放疗同样可用于不能进行子宫切除术的患者。尽管很少有研究
专门评价针对腺癌的治疗,但一项最近的分析提示可以采用同鳞癌类似的手
段有效治疗腺癌[38,39]。
临床试验及治疗选择的依据
意大利的一项随机试验比较了单纯放疗与根治性子宫切除加淋巴清扫
术的疗效[40]。在这项试验的手术组患者中手术分期为pT2b(相当于FIGO分期
IIB)或以上,未受侵的宫颈间质小于3 mm,切缘阳性或淋巴结阳性的患者给
予了术后辅助放疗。结果发现,放疗与手术(加或没有加术后放疗)的效果一
样,但是联合治疗后的并发症发生率较高。这项试验的手术组因为术后放疗指
征过宽和并发症发生率过高而受到了外科医生的指责。
根据5项随机临床试验的结果(见表2)[41-46],目前采用含顺铂化疗 [顺铂单
药或顺铂/5-氟尿嘧啶(5-FU)联用] 的同步化放疗是IB2、II、III及IVA期宫颈
癌患者的治疗选择。这5项试验表明,与单纯放疗相比,同步化放疗使死亡风
险降低了30%~50%。尽管哪种化疗方案与放疗同步联用为最佳尚需进一步探
索,但这5项试验确证了以顺铂为基础的同步化放疗的作用。基于这些数据,
美国癌症研究院发布了告诫声明:对于浸润性宫颈癌,应强烈考虑采用化放疗
而不是单纯放疗(http://www.nih.gov/news/pr/feb99/nci-22.htm)。其中3项临
床试验的长期随访数据证实:与放疗联合(或不联合)羟基脲相比,以顺铂为
基础的同步化放疗可以改善患者的无进展生存和总生存结果[47-49]。根据最近
的一项荟萃分析报道:化放疗可以使5年生存率提高6%[风险比(HR)=0.81,
P<0.001][50]。加拿大的一项大样本的基于人群的登记处分析(n=4,069)也证实
了化放疗的疗效优于单纯放疗[51]。
尽管化放疗在多数情况下是可被耐受的,有关化放疗的急性期和长期
副作用仍可见诸报道[50,52,53]。一些肿瘤医生认为同步放化疗时,顺铂单药优
于顺铂加5-FU,因为后者毒性反应更重[54]。对于无法耐受含顺铂化放疗的
患者,可选择卡铂或其他不含铂类的同步化放疗方案[50,55-59]。需注意,当采用
同步化放疗时,典型的用法是盆腔外照射期间给予化疗[54]。NCCN专家组认
为“系统性巩固治疗”(即,化放疗后追加化疗)只能用于临床试验中(如, RTOG 0724)[50,60,61] 。
早期病变
在详细的临床评价和分期后,早期宫颈癌的初始治疗可选择手术或放疗。
治疗计划根据FIGO分期系统分层(见表1)。
IA1期
对临床IA1期的宫颈癌患者,通常建议行筋膜外(即,单纯)子宫切除术;
若脉管受侵,则可选择改良根治性子宫切除加盆腔淋巴结清扫术(淋巴结清扫
术是2B类)。不宜手术或有生育要求的患者,如果锥切活检切缘阴性,可以选
择观察[62,63]。希望保留生育功能的患者,IA期者可以选择根治性宫颈切除加盆
腔淋巴结清扫加(或不加)腹主动脉旁淋巴结取样(见CERV-2)[64-67]。
IA2期
对于IA2期患者可采取根治性子宫切除或根治性宫颈切除,加盆腔淋巴
结清扫术加(或不加)腹主动脉旁淋巴结取样。腹主动脉旁淋巴结切除适用于
盆腔淋巴结阳性或可疑阳性者。
MS-3
© National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.The Chinese edition 2011 is the collaborative outcome of the National Comprehensive Cancer Network and Chinese key opinion leaders of the field. Translated and adapted with permission and endorsement from the National ComprehensiveCancer Network. To view the most recent and complete version of this or any other guideline, visit www.nccn.org.
宫颈癌
近距离放疗加(或不加)盆腔放疗(A点总剂量:75~80 Gy)是IA2期患
者的另一种治疗选择。该剂量系根据传统外照射单次分割剂量和低剂量率
(40~70 cGy/h)近距离放疗等效剂量之和确定,对大多数患者可推荐使用。当
采用高剂量率近距离放疗时,应根据正常组织的耐受量或生物学等效剂量来
调整治疗(见MS-9“放疗”章节)。
IB和IIA期
根据各自分期和病灶大小的不同,IB或IIA期患者可采用手术、放疗或同
步化放疗治疗。制定治疗决策前可采用PET-CT扫描用以排除盆腔外病变。手
术治疗包括根治性子宫切除加双侧盆腔淋巴结清扫加或不加腹主动脉旁淋巴
结取样[40],腹主动脉旁淋巴结清扫适用于肿瘤较大及已知或可疑盆腔淋巴结
阳性者。部分专家组成员认为应首先实施盆腔淋巴结清扫,如为阴性,则继行
根治性子宫切除术;如淋巴结阳性,则应放弃子宫切除术,接受化放疗。
对于希望保留生育功能的患者,IB1期肿瘤直径≤2 cm者可考虑采用
根治性宫颈切除加盆腔淋巴结清扫加(或不加)腹主动脉旁淋巴结取样 (见CERV-2)[64-68]。在一项研究中,比较IB1期宫颈癌患者接受根治性宫颈
切除术与根治性子宫切除术后4年的肿瘤学结果显示相似[68]。一项研究发
现,早期宫颈癌根治性宫颈切除术后试图怀孕的患者,5年内的累计妊娠率为
52.8%,肿瘤复发率低,但流产率高[69]。选择保留卵巢(即,仅切除子宫)的年轻
(<45岁)的绝经前早期宫颈鳞癌患者,其卵巢转移率低[70,71]。
近期有数据提示早期宫颈癌患者接受前哨淋巴结活检可能有助于降
低对盆腔淋巴结切除术的需求,但专家组成员认为该项技术尚未得到充分 验证[72-74]。然而,这是值得进一步探索的有趣领域[75-78]。
对于IB或IIA期患者(包括不适合进行子宫切除术的患者),另一项治疗选
择为盆腔放疗联合近距离放疗加或不加含顺铂的同步化疗(见CERV-2)。尽管同步化放疗在更晚期患者的根治性治疗中已被证实有效,但该方法对于IB1或IIA1期患者的效果尚无专门研究。对于这些肿瘤较小的患者,应慎重衡量风
险/获益比。
对接受放疗的临床IB2或IIA2期患者,加用含顺铂的同步化疗已被证实可
以显著改善患者生存[41,42]。对IB2或IIA2期的患者,专家组在推荐初始化放疗后
辅以子宫切除术的方案上意见不一致(3类)[41]。
晚期病变
该类患者传统上包括IIB~IVA期病变(即,局部晚期)。然而,现在许多
肿瘤医生把IB2和IIA2期也归于晚期病变。对更晚期且拟行初始化放疗的患
者,放疗靶区很关键,应该根据盆腔和腹主动脉旁淋巴结受累的情况设定照射
野。对于IB2期或更晚期别的患者,推荐进行放射影像学检查(包括PET-CT)。MRI有助于排除颈管高位病变。但对于影像学检查结果不确定的患者,可考虑
采用细针穿刺活检。对于这类患者,手术分期(即,腹膜外或腹腔镜下淋巴结
清扫)亦为治疗选择之一(2B类)。手术分期亦可能发现放射影像学所不能发
现的镜下阳性淋巴结[79]。
手术分期发现没有淋巴结转移或病灶限于盆腔的患者,治疗包括盆腔放疗
加以顺铂为基础的同步化疗和近距离放疗(1类)[42,44-46,54]。然而对影像学检查
发现腹主动脉旁和盆腔淋巴结阳性的患者,应该考虑做腹膜后淋巴结清扫(首
选腹膜外淋巴结清扫)※,然后做延伸野放疗加含顺铂的同步化疗加近距离放
疗(见CERV-6)。对腹主动脉旁淋巴结阳性且有远处转移的患者,应该给予全
MS-4
宫颈癌
© National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.The Chinese edition 2011 is the collaborative outcome of the National Comprehensive Cancer Network and Chinese key opinion leaders of the field. Translated and adapted with permission and endorsement from the National ComprehensiveCancer Network. To view the most recent and complete version of this or any other guideline, visit www.nccn.org.
身化疗(见CERV-B)和个体化的放疗。
转移性病变
对出现远处转移的患者(即,IVB期),初始治疗通常采用以顺铂为基础的
化疗[见“转移性病变的全身治疗”(MS-6)]。在此情况下,可考虑采用个体化
的放疗来控制盆腔病变和所有其他症状。
辅助治疗
宫颈癌根治性子宫切除术后是否加辅助治疗取决于手术发现和疾病分
期。对于IA2、IB1或IIA1期、手术发现淋巴结阴性且无危险因素的患者,根治
性子宫切除术后可以选择观察。然而,如发现病理高危因素,根治性子宫切除
术后应行辅助治疗。对于IA2、IB1或IIA1期、手术发现淋巴结阴性但原发肿瘤
大、间质浸润深、和/或LVSI的患者,推荐盆腔放疗(1类)加(或不加)以顺铂为
基础的同步化疗(化疗为2B类)[80-83]。
一项随机试验[妇科肿瘤组(GOG)92]在经选择的淋巴结阴性的IB期宫
颈癌患者中比较了子宫切除加盆腔淋巴结清扫术后给予辅助放疗与不行进
一步治疗的情况[83]。入选条件是根治性子宫切除术加盆腔淋巴结清扫术后至
少合并以下危险因素中的2项:(1)间质浸润超过1/3;(2)毛细血管淋巴管间
隙受侵;或(3)宫颈肿瘤直径>4 cm。淋巴结阳性或手术切缘阳性者被剔除。 2年时,无复发率在术后放疗组为88%,在无进一步治疗组为79%。长期随访后 (12年),更新的分析结果证实盆腔放疗延长了无进展生存期,而且总生存也
有得到改善的明显趋势(P=0.07)[84]。
对于盆腔淋巴结阳性、手术切缘阳性和/或宫旁组织阳性的患者应该给
予术后盆腔放疗加含顺铂的同步化疗(1类)[43]加(或不加)阴道近距离放疗
(见CERV-3)。阴道近距离放疗对于阴道粘膜切缘阳性者可能是有益的补量
照射。同步化放疗的采用显著改善了早期高危患者(淋巴结阳性、宫旁累及、 和/或切缘阳性)根治性子宫切除术加盆腔淋巴结清扫术后的总生存[43]。组间
试验0107已经表明,对于手术发现淋巴结阳性、切缘阳性、和/或宫旁组织显微
镜下受侵的IA2、IB或IIA期患者,可以从辅助盆腔放疗加顺铂/5-FU同步化疗
中显著获益[43]。
如果手术分期发现腹主动脉旁淋巴结阳性,必须进一步行胸部CT或PET-CT扫描明确有无其他转移。对有远处转移的患者,只要有指征就应该考虑在
可疑部位取活检以明确诊断(见CERV-3)。无远处转移的患者,推荐行延伸野
放疗(包括盆腔和腹主动脉旁淋巴结)加含顺铂的同步化疗加(或不加)近距
离放疗。有远处转移的患者,推荐行全身化疗(见CERV-B)和个体化的放疗。
监测
因为宫颈癌治疗后监测的最佳方法还没有明确的研究结果或统一意见,专
家组结合了NCCN成员机构的临床监测模式,最后达成了一致的建议。对患者
的随诊内容包括定期询问病史和体格检查,及进行宫颈/阴道细胞学检查,前 2年每3~6个月1次,之后的3~5年每6个月1次,以后每年1次(见CERV-8)。有些
医生认为,严格的细胞学随访并无必要,因为一些研究显示:对于I~II期治疗
后无症状的宫颈癌患者,巴氏涂片并没能检测出疾病的复发[85,86]。由于单用宫
颈和阴道细胞学检查检出复发性宫颈癌的概率较低[87],将重点放在做好临床
评估并保持高度怀疑的警觉性是非常重要的。告知患者与复发相关的症状、对
其进行宣教是很妥当的做法。
MS-5
© National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.The Chinese edition 2011 is the collaborative outcome of the National Comprehensive Cancer Network and Chinese key opinion leaders of the field. Translated and adapted with permission and endorsement from the National ComprehensiveCancer Network. To view the most recent and complete version of this or any other guideline, visit www.nccn.org.
宫颈癌
对于存在局部-区域(中心性或腹主动脉旁)复发高风险的患者,PET-CT扫描可能有助于发现有治愈可能的无症状病变[88-90]。可选择每年进行1次胸片
检查[87,91]。根据临床指征可以有选择地进行一些其他检查,例如每半年行1次血常规、血尿素氮和血肌酐检查(见CERV-8)。对于肿瘤持续或复发的患者,
如有临床指征需要另行影像学检查来进行评估,某些病例可行手术探查,然后
再行针对复发的治疗(见下一章节)[92]。
盆腔放疗后推荐使用阴道扩张器,因为接受放疗的患者易于发生阴道狭
窄,而这可能影响性功能。患者可以使用阴道扩张器来预防或治疗阴道狭窄。
放疗结束后的2~4周就可开始应用,并且可以无限期地使用(http://www.ukons.org/storage/dilators_guidelines.pdf)。
宫颈癌幸存患者存在发生继发癌症的风险[93]。研究数据提示因盆腔癌症
接受放疗的患者有发生放疗-诱发继发癌症的风险,尤其是在邻近宫颈的放射
部位(如,结肠、直肠/肛门、膀胱);因此,对于此类患者需行严密监测[94,95]。
复发后的治疗
局部/区域治疗
初始治疗后局部复发的宫颈癌患者应予评估,以确定放疗或手术是否可
用于复发的治疗。已有人报道某些情况下长期无病生存率可达约40%[96]。
而对于既往未行放疗的局部/区域复发患者或既往放疗部位之外发生复发
的患者,治疗方案包括针对肿瘤局部的放疗联合以铂类为基础的化疗加(或不
加)近距离放疗;可能的情况下可考虑手术切除(见CERV-9)。针对复发的化
放疗通常采用顺铂单药或顺铂加5-FU[97,98]。
放疗后盆腔中心性复发的患者应该考虑给予盆腔廓清术加(或不加)术
中放疗(IORT)[99-105];手术死亡率通常为5%或更小,生存率接近50%[101]。根治
性手术后还应该针对患者因为手术产生的社会心理和性心理影响给予适当的
康复训练和重建手术[100,106-108]。尽管盆腔廓清术是常用于放疗后患者的手术方
式,对于经严格挑选的小中心性复发病灶(小于2 cm)患者,还可以考虑根治
性子宫切除术或近距离放疗。
对那些非中心性复发的患者,治疗选择包括:肿瘤切除并对切缘邻近肿瘤
或切缘阳性者给予IORT;针对肿瘤局部的放疗联合(或不联合)化疗;化疗;
最佳支持治疗(见NCCN姑息治疗指南);或入组临床试验。二线根治性治疗
(不管是手术还是放疗)后复发的患者预后差。可予化疗、或最佳支持治疗、或
入组临床试验。
针对转移性病灶的全身治疗
不管是初诊时还是复发时发生远处转移的患者,都很难治愈。对于出现孤
立远处转移灶的高度选择性患者,偶见有采用以下手段获得长期生存的报告:
1)手术切除,联合(或不联合)IORT;2)放疗加(或不加)同步化疗;或 3)化疗
(见CERV-10)。对于其他发生远处转移的绝大部分患者来讲,合适的治疗是
化疗(见CERV-B)或最佳支持治疗。
盆腔高强度放疗部位的复发采用局部镇痛技术或手术切除等姑息治疗
都无效,是目前临床无法解决的难题。这些部位通常对化疗也不敏感。对这
种复发造成的疼痛、瘘管等并发症进行足够的姑息治疗仍是临床工作中的难
MS-6
宫颈癌
© National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.The Chinese edition 2011 is the collaborative outcome of the National Comprehensive Cancer Network and Chinese key opinion leaders of the field. Translated and adapted with permission and endorsement from the National ComprehensiveCancer Network. To view the most recent and complete version of this or any other guideline, visit www.nccn.org.
题(http://emedicine.medscape.com/article/270646-overview)。然而,短程放
疗有可能减轻骨转移、痛性腹主动脉旁淋巴结或锁骨上淋巴结转移患者的 症状[109,110]。
化疗对延长生存期或提高生活质量作用有限,因此仅推荐用于不适合放疗
或廓清手术的盆腔外转移或复发的患者。对化疗有反应的患者可以暂时缓解
疼痛。根据几项III期随机试验的结果(见下一段),对于既往将顺铂作为放疗
增敏剂使用过的转移性患者,含铂类联合方案优于单药[111,112]。
一线联合化疗
顺铂一直被视为治疗转移性宫颈癌最有效的药物[113]。然而,发生转移性
病变的患者大多已接受过同步顺铂/放疗的初始治疗,对铂类单药治疗不再敏
感[111,112]。顺铂/紫杉醇和顺铂/托泊替康等以顺铂为主的联合化疗方案已经在
临床试验中被广泛研究过[111,112,114-116]。一项随机III期试验(GOG 169)在264例合格患者中比较了紫杉醇联合顺铂与顺铂单药的疗效,结果表明两药联合
可以提高缓解率(36% vs 19%),延长无进展生存期(4.8个月 vs 2.8个月,
P<0.001),尽管中位生存期未获改善 [111]。对顺铂/紫杉醇有反应的患者,生活
质量获得显著改善。尽管卡铂/紫杉醇方案尚未在前瞻性随机研究中进行探
究,但由于其用药方便,耐受性良好,已被许多医生采用。
另一项GOG随机III期试验(GOG 179)研究了顺铂联合托泊替康和顺铂
单药治疗复发或持续性宫颈癌的疗效。共294例患者入选,结果表明联合托泊
替康的化疗方案在缓解率(27% vs 13%,P=0.004)、无进展生存期(4.6个月 vs 2.9个月,P=0.014)和中位生存期(9.4个月 vs 6.5个月,P=0.017)方面都优于
单药化疗[112]。FDA已批准顺铂/托泊替康用于晚期宫颈癌。然而,与之相比,
MS-7
顺铂/紫杉醇或卡铂/紫杉醇方案毒性更低,用药也更方便。
最近一项III期试验(GOG 204)在513例患者中评价了含顺铂的4种两药化
疗方案(顺铂/紫杉醇、顺铂/托泊替康、顺铂/吉西他滨、顺铂/长春瑞滨)在晚
期转移性或复发性宫颈癌中的疗效 [116]。试验提前关闭,因为很明显顺铂/托泊
替康、顺铂/吉西他滨以及顺铂/长春瑞滨并不优于顺铂/紫杉醇。两组总生存
结果未见显著差异;然而,缓解率、无进展生存期以及总生存期(12.9个月 vs 10个月)方面的趋势表明,顺铂/紫杉醇方案优于其他方案。与其他方案相比,
顺铂/紫杉醇组血小板减少和贫血更少发生(但恶心、呕吐、感染和脱发更
多)。尽管GOG 204试验未能证明顺铂/吉西他滨方案更优,但耐受性满意。基
于一项局部晚期宫颈癌的III期随机试验,NCCN指南将顺铂/吉西他滨作为治
疗选择之一[117]。对于有神经病变并且不能耐受其他方案的患者来说,顺铂/吉西他滨或可做为一种有用的方案。
很多临床医生优先选择卡铂而非顺铂,因为前者用药更方便,耐受性更
好,对肾功能损害更小。一项比较顺铂/紫杉醇与卡铂/紫杉醇的回顾性试验证
实了上述观点[118]。有试验评价了紫杉醇联合卡铂在复发性或持续性宫颈癌患
者中的疗效。一项研究中,25例患者接受了紫杉醇和卡铂治疗,中位总生存期
为21个月[119]。最近一项采用紫杉醇和卡铂联合化疗的研究显示,51例患者的中
位总生存期为13个月[120]。一项比较卡铂/紫杉醇和顺铂/紫杉醇的III期试验目前
正在进行中[121]。不含铂的双药方案也正在研究中[122]。
单药
顺铂被普遍认为是最有效的药物,并被推荐作为可能的一线单药化疗治
疗复发或转移性宫颈癌患者。目前报道的缓解率约在20%~30%,偶有患者达
© National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.The Chinese edition 2011 is the collaborative outcome of the National Comprehensive Cancer Network and Chinese key opinion leaders of the field. Translated and adapted with permission and endorsement from the National ComprehensiveCancer Network. To view the most recent and complete version of this or any other guideline, visit www.nccn.org.
宫颈癌
到完全缓解[111,113,123,124]。接受顺铂治疗的总生存期约为6~9个月。有报道称卡铂
或紫杉醇也可耐受且有效,也是可供选择的一线单药化疗方案[125-128]。因此,对
于无法接受手术或者放射治疗的复发患者,单药顺铂、卡铂或紫杉醇姑息化疗
都是合理的治疗方法。使用托泊替康和紫杉醇都有达到完全缓解的患者,然而
托泊替康较卡铂和紫杉醇的毒性反应更大。其他已被证实有效或能延长PFS因此可用于二线治疗的药物(除非注明,均为2B类)包括,贝伐珠单抗[129]、
多西他赛[130]、5-FU[131]、吉西他滨[132]、异环磷酰胺[133,134]、伊立替康[135]、丝裂霉
素[136] 、托泊替康[137,138]、培美曲塞(3类)[139] 和长春瑞滨(3类)[140] 。
药物反应
实际上所有药物都有引起不良反应的可能,或者发生在药物输注过程中
或者在输注完成之后[141]。在宫颈癌的治疗中,比较容易引起不良反应的药物
包括卡铂、顺铂、多西他赛、多柔比星脂质体和紫杉醇。多数的药物反应只是
轻度输液反应(即,皮肤反应、心血管反应、气短或喉咙发紧),但更为严重的
过敏反应(即,危及生命的过敏性休克)也有可能发生[142,143]。此外,患者可能
发生严重的输液反应和轻度的过敏反应。输液反应更常见于紫杉醇[144] ,过敏
反应(即,真正的药物过敏)则更常见于铂类药物(即,卡铂、顺铂)[144,145]。
药物反应的处理在NCCN卵巢癌指南中予以了讨论(见OV-C)[144]。需要
注意,发生过严重的危及生命的反应的患者,可能与反应相关的药物均不应
被再次使用。如果以前发生过轻度的过敏反应,而患者的情况适合再次给药,
即使症状已经消失,也需接受脱敏治疗方案。多种脱敏方案已发布,应予遵 循[145-147]。如果患者有过敏反应史,每次输注给药均需行脱敏治疗。几乎所有患
者均可被脱敏[141]。为最大限度地保证安全,患者应在重症监护室中接受脱敏
治疗[141]。
其他药物
疫苗疗法在宫颈癌治疗中的作用目前尚未在临床试验之外得到确立[148-150]。
靶向治疗(采用小分子或单克隆抗体)目前尚处于临床试验中[60,129,151,152]。
最佳支持治疗
对于难治性全身转移的患者,应该给予综合性个体化对症治疗,包括临终
关怀、镇痛、情绪和精神支持(见NCCN姑息治疗指南)。
意外发现的宫颈癌
有时会在筋膜外子宫切除术后意外发现浸润性宫颈癌。对这些患者的检
查包括询问病史和体格检查、血常规、肝肾功能检查。影像学检查包括胸片、
CT或PET-CT扫描,或有指征时MRI检查(如,为排除颈管高位病变)。而对
IB1期或期别更早的患者,除胸片外的影像学检查为可选(见CERV-7)。※
关于这部分患者的恰当的初始治疗,目前尚缺乏肯定的数据。专家组认为
对有LVSI的IA1期、或≥IA2期(病理学发现)的患者,应该根据手术切缘状态
决定合理的治疗方案。如果切缘阳性且影像检查未发现淋巴结转移,应推荐盆
腔放疗加含顺铂的同步化疗加或不加个体化的近距离放疗(见CERV-7)。不伴
LVSI的IA1期患者应予监测随访。
≥IA2期的患者,如果切缘或影像学检查为阴性,治疗选择包括:(1)盆腔
放疗加(或不加)含顺铂的同步化疗加近距离放疗;或(2)全部宫旁组织切除,
阴道上端切除,加盆腔淋巴结切除加(或不加)腹主动脉旁淋巴结取样。淋巴
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宫颈癌
© National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.The Chinese edition 2011 is the collaborative outcome of the National Comprehensive Cancer Network and Chinese key opinion leaders of the field. Translated and adapted with permission and endorsement from the National ComprehensiveCancer Network. To view the most recent and complete version of this or any other guideline, visit www.nccn.org.
结阴性的患者应予观察,同时伴有高危因素者(如原发肿瘤大、间质浸润深 和/或LVSI)可选盆腔放疗加(或不加)阴道近距离放疗(见CERV-7)[83]。对肉
眼残留病灶、影像学检查阳性、淋巴结和/或宫旁转移和/或手术切缘阳性的患
者推荐行以顺铂为基础的同步化放疗;阴道切缘阳性是个体化近距离放疗的
明确指征。
放疗
放疗是宫颈癌治疗中的常用手段,其或者用于不能手术的完整宫颈癌患者
(如,对局部晚期或不宜手术患者的根治性治疗),或者用于根治性子宫切除
术后(即,辅助放疗)存在一个或多个病理危险因素(如,淋巴结阳性、宫旁浸
润、手术切缘阳性、肿瘤体积大、间质浸润深、LVSI)的患者。
NCCN指南流程图中给出了大致的放疗剂量推荐,在放疗的原则章节中已
行详述(见CERV-A)。这些放疗剂量不应该被解释为独立的推荐,因为放疗技
术和临床判断是构成一项恰当的治疗方案的必要组成部分。
对IB2、IIA2期或晚期患者,推荐通过盆腹腔影像学检查(CT、MRI或PET-CT扫描)精确描述原发肿瘤的体积和淋巴结引流区状况来作出更适宜的
肿瘤分期。现代影像学检查必须与仔细评价临床表现相结合,以确定肿瘤侵及
的范围,尤其是阴道或宫旁扩散。
放射治疗计划
影像技术、计算机治疗计划制定系统、直线加速器技术的进步,使更精确
地实施盆腔放射剂量成为可能。然而,剂量实施的物理精确性必须与对肿瘤
范围、潜在的扩散途径、局部-区域复发历史模式的清晰了解相配合,以避免靶
区遗漏。
采用CT定位适形设野和剂量计算的放疗计划被认为是外照射的标准。对
所有子宫完整的宫颈癌患者来说,近距离放疗是治疗中至关重要的组成部分,
通常在综合治疗计划中与外照射相联合。
对于局部晚期肿瘤患者,为使肿瘤缩小后进行满意的腔内放疗,常常必须
先对全盆腔进行40 Gy的初始照射。低剂量率腔内照射下,对于小肿瘤,目前
推荐的近距离放疗和外照射的A点总剂量至少为80 Gy,较大肿瘤为85 Gy或 更高。
对肿瘤侵及阴道下1/3的患者,治疗范围应该包括腹股沟淋巴结。对隐匿性
或肉眼可见的腹主动脉旁淋巴结转移灶进行延伸野放疗时,制定计划应该认真
仔细,以保证足够的实施剂量(显微镜下病变:45 Gy),并且保证不超出肠道、
脊髓或肾脏的耐受量[153]。放射靶区和照射剂量的大致推荐已在流程图中讨论
(见CERV-A)。
调强放疗(IMRT)的应用目前已越来越广泛,但有关靶区勾画、患者和靶
区的固定、靶区变形以及位置的重复性等方面的问题仍待验证[154-158] 。有几项
前瞻性多中心临床试验继续对IMRT在宫颈癌中的作用进行积极探讨。
几项回顾性分析已经发现延长治疗时间对患者转归有不利影响[159-163]。总
治疗时间超过6~8周者,每额外增加1天,就可以使盆腔控制和原因特异性生存
期缩短约0.5%~1%。因此,虽然尚未进行相关的前瞻性随机试验,人们还是普
遍认为应该及时(小于8周)完成全部放疗(包括外照射和近距离放疗);放疗
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© National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.The Chinese edition 2011 is the collaborative outcome of the National Comprehensive Cancer Network and Chinese key opinion leaders of the field. Translated and adapted with permission and endorsement from the National ComprehensiveCancer Network. To view the most recent and complete version of this or any other guideline, visit www.nccn.org.
宫颈癌
延迟和间歇也应尽可能避免。
关于正常组织应考虑的事项
宫颈癌放疗计划的制定必须要顾及对周围重要脏器的潜在影响,如直
肠、膀胱、乙状结肠、小肠和骨。接受放疗的大多数患者会出现某种程度的急
性期反应(即,腹泻、膀胱刺激、乏力),而同步化疗通常会使这些反应加重。
然而,急性期反应常常可为药物或支持治疗控制,并一般会在放疗结束后很快 消失。
意义更为重要的晚期反应(即,梗阻、纤维化/坏死、或瘘管)的发生风险
与照射野、总剂量、分次剂量、以及受辐照的正常组织本身固有的放疗敏感性
相关[153]。应该仔细地遮挡以在尽可能减少正常组织放射曝露的同时保证肿瘤
受照不受影响,这对于获得最佳的治疗结果非常关键。另外,患者自身的身体
状况(即,炎性肠病、胶原血管病、多次腹/盆腔手术、盆腔炎性疾病史、糖尿
病)会影响放疗剂量和放射靶区的确定。
对于大多数患者来说,一般认为全盆腔可耐受45~50 Gy的外照射剂量。宫
旁肉眼可见病灶或未切除的淋巴结使用紧扣靶区的外照射补量可使能耐受的
剂量达60~65 Gy。腔内近距离照射补量需注意施源器在宫内的正确放置,并要
顶住宫颈和阴道顶,同时正确放置充填物,以最大限度地推开膀胱和直肠。
妊娠与宫颈癌
宫颈癌是妊娠合并癌症中最多见者;但妊娠合并宫颈癌者多数为I期[164]。
妊娠期罹患浸润性宫颈癌使临床决策陷于两难。患者需作出艰难决择——或
者推迟治疗直到所谓的成熟胎龄,或者马上接受与其疾病分期相对应的治疗。
对孕期诊断为早期宫颈癌且希望继续妊娠的女性,推迟癌症治疗直至胎儿成
熟的成功病例已有报道[164]。此类患者生产方式需选择剖宫产术。对于早期病
变患者,应首先选择根治性子宫切除加淋巴结清扫术而不是放疗,以避免放射
性纤维化及保护卵巢。对于早期病变并推迟治疗直至胎儿成熟的患者,要实
施剖宫产加根治性子宫切除加盆腔淋巴结清扫术。对于选择放疗的患者,传统
放疗加(或不加)化疗方案(前已详述)可能需加以改良[164]。少数妊娠合并早
期病变的女性已经成功接受了经阴根治性宫颈切除术 [165-168]。
总结
因为筛查的普遍开展,美国宫颈癌的发病率正在下降;然而发展中国家宫
颈癌的发病率呈上升趋势(每年死亡约270,000人),原因是许多女性得不到筛
查服务。经过有效的治疗后(即,手术、同步化放疗),早期宫颈癌(I和II期)的
治愈率为80%,III期宫颈癌为60%。但愿针对HPV的免疫治疗(使用新疫苗)
能够预防某些型别的HPV持续感染,并因此有望用于预防某些特定HPV引起
的宫颈癌[11,12,169]。
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宫颈癌
© National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.The Chinese edition 2011 is the collaborative outcome of the National Comprehensive Cancer Network and Chinese key opinion leaders of the field. Translated and adapted with permission and endorsement from the National ComprehensiveCancer Network. To view the most recent and complete version of this or any other guideline, visit www.nccn.org.
表2:关于同步化放疗的5个临床试验中的相对死亡风险评估
试验
Keys et al.*
Rose, Bundy, Watkins et al.*
Morris et al.*
Whitney et al.
Peters et al.
FIGO分期
IB2
IIB~IVA
IB2~IVA
IIB~IVA
IB或IIA(部分为术后)
对照组
放疗
放疗加羟基脲
延伸野放疗
放疗加羟基脲
放疗
试验组
放疗加顺铂周疗
放疗加顺铂周疗
放疗加顺铂、氟尿嘧啶和羟基脲
放疗加顺铂和氟尿嘧啶
放疗加顺铂和氟尿嘧啶
放疗加顺铂和氟尿嘧啶
试验组的相对死亡风险
0.54
0.61
0.58
0.52
0.72
0.50
缩写:FIGO:国际妇产科联盟。
*:这些试验结果已更新(见讨论)。
经过允许,引自:Thomas GM. Improved treatment for cerv ical cancer concurrent chemotherapy and radiotherapy. N Engl J Med 1999;340(15):1198-1200. Copyright© 1999 Massachusetts Medical Society. All rights reserved.
MS-11
© National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.The Chinese edition 2011 is the collaborative outcome of the National Comprehensive Cancer Network and Chinese key opinion leaders of the field. Translated and adapted with permission and endorsement from the National ComprehensiveCancer Network. To view the most recent and complete version of this or any other guideline, visit www.nccn.org.
宫颈癌
参考文献
1. Jemal A, Siegel R, Xu J and Ward E. Cancer statistics, 2010. CA Cancer J Clin 2010;60:277-300.
Available at: http://www.ncbi.nlm.nih.gov/pubmed/20610543
2. Barnholtz-Sloan J, Patel N, Rollison D, et al. Incidence trends of invasive cervical cancer in the
United States by combined race and ethnicity. Cancer Causes Control 2009;20:1129-1138. Available
at: http://www.ncbi.nlm.nih.gov/pubmed/19253025
3. Wang SS, Carreon JD, Gomez SL and Devesa SS. Cervical cancer incidence among 6 asian ethnic
groups in the United States, 1996 through 2004. Cancer 2010;116:949-956. Available at: http://www.
ncbi.nlm.nih.gov/pubmed/20029972
4. Howe HL, Wu X, Ries LAG, et al. Annual report to the nation on the status of cancer, 1975-2003,
featuring cancer among U.S. Hispanic/Latino populations. Cancer 2006;107:1711-1742. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/16958083
5. Sherman ME, Wang SS, Carreon J and Devesa SS. Mortality trends for cervical squamous and
adenocarcinoma in the United States. Relation to incidence and survival. Cancer 2005;103:1258-
1264. Available at: http://www.ncbi.nlm.nih.gov/pubmed/15693030
6. Parkin DM, Bray F, Ferlay J and Pisani P. Global cancer statistics, 2002. CA Cancer J Clin
2005;55:74-7108. Available at: http://www.ncbi.nlm.nih.gov/pubmed/15761078
7. Kamangar F, Dores GM and Anderson WF. Patterns of cancer incidence, mortality, and prevalence
across five continents: defining priorities to reduce cancer disparities in different geographic
regions of the world. J Clin Oncol 2006;24:2137-2150. Available at: http://www.ncbi.nlm.nih.gov/
pubmed/16682732
8. Villa LL, Costa RL, Petta CA, et al. Prophylactic quadrivalent human papillomavirus (types 6,
11, 16, and 18) L1 virus-like particle vaccine in young women: a randomised double-blind placebo-
controlled multicentre phase II efficacy trial. Lancet Oncol 2005;6:271-278. Available at: http://www.
ncbi.nlm.nih.gov/pubmed/15863374
9. Ault KA. Effect of prophylactic human papillomavirus L1 virus-likeparticle vaccine on risk of
cervical intraepithelial neoplasia grade 2, grade 3, and adenocarcinoma in situ: a combined analysis
of four randomised clinical trials. Lancet 2007;369:1861-1868. Available at: http://www.ncbi.nlm.
nih.gov/pubmed/17544766
10. Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N
Engl J Med 2007;356:1915-1927. Available at: http://www.ncbi.nlm.nih.gov/pubmed/17494925
11. Arbyn M and Dillner J. Review of current knowledge on HPV vaccination: an appendix to the
European Guidelines for Quality Assurance in Cervical Cancer Screening. J Clin Virol 2007;38:189-
197. Available at: http://www.ncbi.nlm.nih.gov/pubmed/17258503
12. Rambout L, Hopkins L, Hutton B and Fergusson D. Prophylactic vaccination against human
papillomavirus infection and disease in women: a systematic review of randomized controlled trials.
CMAJ 2007;177:469-479. Available at: http://www.ncbi.nlm.nih.gov/pubmed/17671238
13. Comparison of risk factors for invasive squamous cell carcinoma and adenocarcinoma of the
cervix: collaborative reanalysis of individual data on 8,097 women with squamous cell carcinoma and
1,374 women with adenocarcinoma from 12 epidemiological studies. Int J Cancer 2007;120:885-891.
Available at: http://www.ncbi.nlm.nih.gov/pubmed/17131323
14. Bray F, Loos AH, McCarron P, et al. Trends in cervical squamous cell carcinoma incidence in 13
European countries: changing risk and the effects of screening. Cancer Epidemiol Biomarkers Prev
2005;14:677-686. Available at: http://www.ncbi.nlm.nih.gov/pubmed/15767349
15. Watson M, Saraiya M, Benard V, et al. Burden of cervical cancer in the United States, 1998-2003.
Cancer 2008;113:2855-2864. Available at: http://www.ncbi.nlm.nih.gov/pubmed/18980204
16. Bray F, Carstensen B, Moller H, et al. Incidence trends of adenocarcinoma of the cervix in
13 European countries. Cancer Epidemiol Biomarkers Prev 2005;14:2191-2199. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/16172231
17. Wang SS, Sherman ME, Hildesheim A, et al. Cervical adenocarcinoma and squamous cell
carcinoma incidence trends among white women and black women in the United States for 1976-
2000. Cancer 2004;100:1035-1044. Available at: http://www.ncbi.nlm.nih.gov/pubmed/14983500
18. Castellsague X, Diaz M, de Sanjose S, et al. Worldwide human papillomavirus etiology of
cervical adenocarcinoma and its cofactors: implications for screening and prevention. J Natl Cancer
Inst 2006;98:303-315. Available at: http://www.ncbi.nlm.nih.gov/pubmed/16507827
19. Sasieni P, Castanon A and Cuzick J. Screening and adenocarcinoma of the cervix. Int J Cancer
2009;125:525-529. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19449379
20. Dahlstrom LA, Ylitalo N, Sundstrom K, et al. Prospective study of human papillomavirus and
risk of cervical adenocarcinoma. Int J Cancer 2010;127:1923-1930. Available at: http://www.ncbi.
REF-1
宫颈癌
© National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.The Chinese edition 2011 is the collaborative outcome of the National Comprehensive Cancer Network and Chinese key opinion leaders of the field. Translated and adapted with permission and endorsement from the National ComprehensiveCancer Network. To view the most recent and complete version of this or any other guideline, visit www.nccn.org.
nlm.nih.gov/pubmed/20473898
21. ACOG practice bulletin. Diagnosis and treatment of cervical carcinomas. Number 35, May
2002. American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet 2002;78:79-91.
Available at: http://www.ncbi.nlm.nih.gov/pubmed/12197489
22. Gold MA, Tian C, Whitney CW, et al. Surgical versus radiographic determination of para-
aortic lymph node metastases before chemoradiation for locally advanced cervical carcinoma: a
Gynecologic Oncology Group Study. Cancer 2008;112:1954-1963. Available at: http://www.ncbi.
nlm.nih.gov/pubmed/18338811
23. Monk BJ, Tian C, Rose PG and Lanciano R. Which clinical/pathologic factors matter in the era of
chemoradiation as treatment for locally advanced cervical carcinoma? Analysis of two Gynecologic
Oncology Group (GOG) trials. Gynecol Oncol 2007;105:427-433. Available at: http://www.ncbi.nlm.
nih.gov/pubmed/17275889
24. Ramirez PT, Slomovitz BM, Soliman PT, et al. Total laparoscopic radical hysterectomy and
lymphadenectomy: the M. D. Anderson Cancer Center experience. Gynecol Oncol 2006;102:252-
255. Available at: http://www.ncbi.nlm.nih.gov/pubmed/16472844
25. Abu-Rustum NR, Gemignani ML, Moore K, et al. Total laparoscopic radical hysterectomy with
pelvic lymphadenectomy using the argonbeam coagulator: pilot data and comparison to laparotomy.
Gynecol Oncol 2003;91:402-409. Available at: http://www.ncbi.nlm.nih.gov/pubmed/14599873
26. Chi DS. Laparoscopy in gynecologic malignancies. Oncology (Williston Park) 1999;13:773-782.
Available at: http://www.ncbi.nlm.nih.gov/pubmed/10378217
27. Chen Y, Xu H, Li Y, et al. The outcome of laparoscopic radical hysterectomy and
lymphadenectomy for cervical cancer: a prospective analysis of 295 patients. Ann Surg Oncol
2008;15:2847-2855. Available at: http://www.ncbi.nlm.nih.gov/pubmed/18649105
28. Puntambekar SP, Palep RJ, Puntambekar SS, et al. Laparoscopic total radical hysterectomy by the
Pune technique: our experience of 248 cases. J Minim Invasive Gynecol 2007;14:682-689. Available
at: http://www.ncbi.nlm.nih.gov/pubmed/17980327
29. Lowe MP, Chamberlain DH, Kamelle SA, et al. A multi-institutional experience with robotic-
assisted radical hysterectomy for early stage cervical cancer. Gynecol Oncol 2009;113:191-194.
Available at: http://www.ncbi.nlm.nih.gov/pubmed/19249082
30. Nezhat FR, Datta MS, Liu C, et al. Robotic radical hysterectomy versus total laparoscopic
radical hysterectomy with pelvic lymphadenectomy for treatment of early cervical cancer. JSLS
2008;12:227-237. Available at: http://www.ncbi.nlm.nih.gov/pubmed/18765043
31. Cantrell LA, Mendivil A, Gehrig PA and Boggess JF. Survival outcomes for women undergoing
type III robotic radical hysterectomy for cervical cancer: a 3-year experience. Gynecol Oncol
2010;117:260-265. Available at: http://www.ncbi.nlm.nih.gov/pubmed/20153886
32. Pecorelli S, Zigliani L and Odicino F. Revised FIGO staging for carcinoma of the cervix. Int J
Gynaecol Obstet 2009;105:107-108. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19342051
33. Moore DH. Surgical staging and cervical cancer: after 30 years, have we reached a conclusion?
Cancer 2008;112:1874-1876. Available at: http://www.ncbi.nlm.nih.gov/pubmed/18348308
34. Pecorelli S. Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. Int J
Gynaecol Obstet 2009;105:103-104. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19367689
35. Edge SB, Byrd DR, Compton CC, et al. AJCC Cancer Staging Manual, 7th ed. New York:
Springer; 2010.
36. Park JY, Kim EN, Kim DY, et al. Comparison of the validity of magnetic resonance imaging and
positron emission tomography/computed tomography in the preoperative evaluation of patients with
uterine corpus cancer. Gynecol Oncol 2008;108:486-492. Available at: http://www.ncbi.nlm.nih.gov/
pubmed/18201753
37. Boughanim M, Leboulleux S, Rey A, et al. Histologic results of paraaortic lymphadenectomy
in patients treated for stage IB2/II cervical cancer with negative [18F]fluorodeoxyglucose positron
emission tomography scans in the para-aortic area. J Clin Oncol 2008;26:2558-2561. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/18487573
38. Baalbergen A, Veenstra Y, Stalpers LL and Ansink AC. Primary surgery versus primary radiation
therapy with or without chemotherapy for early adenocarcinoma of the uterine cervix. Cochrane
Database Syst Rev 2010:CD006248. Available at: http://www.ncbi.nlm.nih.gov/pubmed/20091590
39. Park JY, Kim DY, Kim JH, et al. Outcomes after radical hysterectomy in patients with early-stage
adenocarcinoma of uterine cervix. Br J Cancer 2010;102:1692-1698. Available at: http://www.ncbi.
nlm.nih.gov/pubmed/20531414
40. Landoni F, Maneo A, Colombo A, et al. Randomised study of radical surgery versus radiotherapy
for stage Ib-IIa cervical cancer. Lancet 1997;350:535-540. Available at: http://www.ncbi.nlm.nih.
gov/pubmed/9284774
REF-2
© National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.The Chinese edition 2011 is the collaborative outcome of the National Comprehensive Cancer Network and Chinese key opinion leaders of the field. Translated and adapted with permission and endorsement from the National ComprehensiveCancer Network. To view the most recent and complete version of this or any other guideline, visit www.nccn.org.
宫颈癌
41. Keys HM, Bundy BN, Stehman FB, et al. Cisplatin, radiation, and adjuvant hysterectomy
compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma. N Engl J
Med 1999;340:1154-1161. Available at: http://www.ncbi.nlm.nih.gov/pubmed/10202166
42. Morris M, Eifel PJ, Lu J, et al. Pelvic radiation with concurrent chemotherapy compared with
pelvic and para-aortic radiation for high-risk cervical cancer. N Engl J Med 1999;340:1137-1143.
Available at: http://www.ncbi.nlm.nih.gov/pubmed/10202164
43. Peters WA, Liu PY, Barrett RJ, et al. Concurrent chemotherapy and pelvic radiation therapy
compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk
early-stage cancer of the cervix. J Clin Oncol 2000;18:1606-1613. Available at: http://www.ncbi.nlm.
nih.gov/pubmed/10764420
44. Whitney CW, Sause W, Bundy BN, et al. Randomized comparison of fluorouracil plus cisplatin
versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix
with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology
Group study. J Clin Oncol 1999;17:1339-1348. Available at: http://www.ncbi.nlm.nih.gov/
pubmed/10334517
45. Rose PG, Bundy BN, Watkins EB, et al. Concurrent cisplatin-based radiotherapy and
chemotherapy for locally advanced cervical cancer. N Engl J Med 1999;340:1144-1153. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/10202165
46. Thomas GM. Improved treatment for cervical cancer—concurrent chemotherapy and radiotherapy.
N Engl J Med 1999;340:1198-1200. Available at: http://www.ncbi.nlm.nih.gov/pubmed/10202172
47. Rose PG, Ali S, Watkins E, et al. Long-term follow-up of a randomized trial comparing
concurrent single agent cisplatin, cisplatin-based combination chemotherapy, or hydroxyurea during
pelvic irradiation for locally advanced cervical cancer: a Gynecologic Oncology Group Study. J Clin
Oncol 2007;25:2804-2810. Available at: http://www.ncbi.nlm.nih.gov/pubmed/17502627
48. Eifel PJ, Winter K, Morris M, et al. Pelvic irradiation with concurrent chemotherapy versus pelvic
and para-aortic irradiation for high-risk cervical cancer: an update of radiation therapy oncology
group trial (RTOG) 90-01. J Clin Oncol 2004;22:872-880. Available at: http://www.ncbi.nlm.nih.
gov/pubmed/14990643
49. Stehman FB, Ali S, Keys HM, et al. Radiation therapy with or without weekly cisplatin for bulky
stage 1B cervical carcinoma: follow-up of a Gynecologic Oncology Group trial. Am J Obstet Gynecol
2007;197:1-6. Available at: http://www.ncbi.nlm.nih.gov/pubmed/17980189
50. Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer: a systematic
review and meta-analysis of individual patient data from 18 randomized trials. J Clin Oncol
2008;26:5802-5812. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19001332
51. Pearcey R, Miao Q, Kong W, et al. Impact of adoption of chemoradiotherapy on the outcome of
cervical cancer in Ontario: results of a population-based cohort study. J Clin Oncol 2007;25:2383-
2388. Available at: http://www.ncbi.nlm.nih.gov/pubmed/17557951
52. King M, McConkey C, Latief TN, et al. Improved survival after concurrent weekly cisplatin and
radiotherapy for cervical carcinoma with assessment of acute and late side-effects. Clin Oncol (R Coll
Radiol) 2006;18:38-45. Available at: http://www.ncbi.nlm.nih.gov/pubmed/16477918
53. Tan LT and Zahra M. Long-term survival and late toxicity after chemoradiotherapy for cervical
cancer--the Addenbrooke's experience. Clin Oncol (R Coll Radiol) 2008;20:358-364. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/18395427
54. Monk BJ, Tewari KS and Koh W-J. Multimodality therapy for locally advanced cervical
carcinoma: state of the art and future directions. J Clin Oncol 2007;25:2952-2965. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/17617527
55. Cetina L, Garcia-Arias A, Uribe MdJ, et al. Concurrent chemoradiation with carboplatin for
elderly, diabetic and hypertensive patients with locally advanced cervical cancer. Eur J Gynaecol
Oncol 2008;29:608-612. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19115688
56. Dubay RA, Rose PG, O'Malley DM, et al. Evaluation of concurrent and adjuvant carboplatin with
radiation therapy for locally advanced cervical cancer. Gynecol Oncol 2004;94:121-124. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/15262129
57. Higgins RV, Naumann WR, Hall JB and Haake M. Concurrent carboplatin with pelvic radiation
therapy in the primary treatment of cervix cancer. Gynecol Oncol 2003;89:499-503. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/12798718
58. Lorvidhaya V, Chitapanarux I, Sangruchi S, et al. Concurrent mitomycin C, 5-fluorouracil,
and radiotherapy in the treatment of locally advanced carcinoma of the cervix: a randomized trial.
Int J Radiat Oncol Biol Phys 2003;55:1226-1232. Available at: http://www.ncbi.nlm.nih.gov/
pubmed/12654431
59. Wong LC, Ngan HY, Cheung AN, et al. Chemoradiation and adjuvant chemotherapy in
REF-3
宫颈癌
© National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.The Chinese edition 2011 is the collaborative outcome of the National Comprehensive Cancer Network and Chinese key opinion leaders of the field. Translated and adapted with permission and endorsement from the National ComprehensiveCancer Network. To view the most recent and complete version of this or any other guideline, visit www.nccn.org.
cervical cancer. J Clin Oncol 1999;17:2055-2060. Available at: http://www.ncbi.nlm.nih.gov/
pubmed/10561258
60. Poveda A and Gonzalez-Martin A. Multimodality treatment in locoregional gynecological cancer:
cervical cancer treatment update. Ann Oncol 2008;19 Suppl 7:vii70-76. Available at: http://www.
ncbi.nlm.nih.gov/pubmed/18790983
61. Duenas-Gonzalez A, Zarba JJ, Alcedo JC, et al. A phase III study comparing concurrent
gemcitabine (Gem) plus cisplatin (Cis) and radiation followed by adjuvant Gem plus Cis versus
concurrent Cis and radiation in patients with stage IIB to IVA carcinoma of the cervix. J Clin Oncol
(Meeting Abstracts) 2009;27:CRA5507-. Available at: http://meeting.ascopubs.org/cgi/content/
abstract/27/18S/CRA5507
62. Koliopoulos G, Sotiriadis A, Kyrgiou M, et al. Conservative surgical methods for FIGO stage
IA2 squamous cervical carcinoma and their role in preserving women's fertility. Gynecol Oncol
2004;93:469-473. Available at: http://www.ncbi.nlm.nih.gov/pubmed/15099964
63. Wright JD, NathavithArana R, Lewin SN, et al. Fertility-conserving surgery for young women
with stage IA1 cervical cancer: safety and access. Obstet Gynecol 2010;115:585-590. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/20177290
64. Bernardini M, Barrett J, Seaward G and Covens A. Pregnancy outcomes in patients after radical
trachelectomy. Am J Obstet Gynecol 2003;189:1378-1382. Available at: http://www.ncbi.nlm.nih.
gov/pubmed/14634572
65. Boss EA, van Golde RJT, Beerendonk CCM and Massuger LFAG. Pregnancy after radical
trachelectomy: a real option? Gynecol Oncol 2005;99:152-156. Available at: http://www.ncbi.nlm.
nih.gov/pubmed/16140367
66. Plante M, Renaud M-C, Hoskins IA and Roy M. Vaginal radical trachelectomy: a valuable
fertility-preserving option in the management of early-stage cervical cancer. A series of 50
pregnancies and review of the literature. Gynecol Oncol 2005;98:3-10. Available at: http://www.ncbi.
nlm.nih.gov/pubmed/15936061
67. Marchiole P, Benchaib M, Buenerd A, et al. Oncological safety of laparoscopic-assisted vaginal
radical trachelectomy (LARVT or Dargent's operation): a comparative study with laparoscopic-
assisted vaginal radical hysterectomy (LARVH). Gynecol Oncol 2007;106:132-141. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/17493666
68. Diaz JP, Sonoda Y, Leitao MM, et al. Oncologic outcome of fertility-sparing radical trachelectomy
versus radical hysterectomy for stage IB1 cervical carcinoma. Gynecol Oncol 2008;111:255-260.
Available at: http://www.ncbi.nlm.nih.gov/pubmed/18755500
69. Shepherd JH, Spencer C, Herod J and Ind TEJ. Radical vaginal trachelectomy as a fertility-
sparing procedure in women with early-stage cervical cancer-cumulative pregnancy rate in a series of
123 women. BJOG 2006;113:719-724. Available at: http://www.ncbi.nlm.nih.gov/pubmed/16709216
70. Landoni F, Zanagnolo V, Lovato-Diaz L, et al. Ovarian metastases in early-stage cervical cancer
(IA2-IIA): a multicenter retrospective study of 1965 patients (a Cooperative Task Force study). Int J
Gynecol Cancer 2007;17:623-628. Available at: http://www.ncbi.nlm.nih.gov/pubmed/17309669
71. Shimada M, Kigawa J, Nishimura R, et al. Ovarian metastasis in carcinoma of the uterine cervix.
Gynecol Oncol 2006;101:234-237. Available at: http://www.ncbi.nlm.nih.gov/pubmed/16300819
72. Lecuru F, Bats A, Mathevet P, et al. Impact of sentinel lymph node biopsy on staging of early
cervical cancer: Results of a prospective, multicenter study [abstract]. J Clin Oncol 2009;27(Suppl
18):Abstract CRA5506. Available at: http://meeting.ascopubs.org/cgi/content/abstract/27/18S/
CRA5506
73. Altgassen C, Hertel H, Brandstadt A, et al. Multicenter validation study of the sentinel lymph
node concept in cervical cancer: AGO Study Group. J Clin Oncol 2008;26:2943-2951. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/18565880
74. Fader AN, Edwards RP, Cost M, et al. Sentinel lymph node biopsy in early-stage cervical cancer:
utility of intraoperative versus postoperative assessment. Gynecol Oncol 2008;111:13-17. Available
at: http://www.ncbi.nlm.nih.gov/pubmed/18684499
75. Selman TJ, Mann C, Zamora J, et al. Diagnostic accuracy of tests for lymph node status in
primary cervical cancer: a systematic review and meta-analysis. CMAJ 2008;178:855-862. Available
at: http://www.ncbi.nlm.nih.gov/pubmed/18362381
76. van de Lande J, Torrenga B, Raijmakers PGHM, et al. Sentinel lymph node detection in early
stage uterine cervix carcinoma: a systematic review. Gynecol Oncol 2007;106:604-613. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/17628644
77. Schneider A. The sentinel concept in patients with cervical cancer. J Surg Oncol 2007;96:337-
341. Available at: http://www.ncbi.nlm.nih.gov/pubmed/17726665
78. Pandit-Taskar N, Gemignani ML, Lyall A, et al. Single photon emission computed tomography
REF-4
© National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.The Chinese edition 2011 is the collaborative outcome of the National Comprehensive Cancer Network and Chinese key opinion leaders of the field. Translated and adapted with permission and endorsement from the National ComprehensiveCancer Network. To view the most recent and complete version of this or any other guideline, visit www.nccn.org.
宫颈癌
SPECT-CT improves sentinel node detection and localization in cervical and uterine malignancy.
Gynecol Oncol 2010;117:59-64. Available at: http://www.ncbi.nlm.nih.gov/pubmed/20117827
79. Goff BA, Muntz HG, Paley PJ, et al. Impact of surgical staging in women with locally advanced
cervical cancer. Gynecol Oncol 1999;74:436-442. Available at: http://www.ncbi.nlm.nih.gov/
pubmed/10479506
80. Monk BJ, Wang J, Im S, et al. Rethinking the use of radiation and chemotherapy after radical
hysterectomy: a clinical-pathologic analysis of a Gynecologic Oncology Group/Southwest Oncology
Group/Radiation Therapy Oncology Group trial. Gynecol Oncol 2005;96:721-728. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/15721417
81. Chernofsky MR, Felix JC, Muderspach LI, et al. Influence of quantity of lymph vascular space
invasion on time to recurrence in women with early-stage squamous cancer of the cervix. Gynecol
Oncol 2006;100:288-293. Available at: http://www.ncbi.nlm.nih.gov/pubmed/16182347
82. Marchiole P, Buenerd A, Benchaib M, et al. Clinical significance of lympho vascular space
involvement and lymph node micrometastases in early-stage cervical cancer: a retrospective case-
control surgico-pathological study. Gynecol Oncol 2005;97:727-732. Available at: http://www.ncbi.
nlm.nih.gov/pubmed/15943983
83. Sedlis A, Bundy BN, Rotman MZ, et al. A randomized trial of pelvic radiation therapy versus no
further therapy in selected patients with stage IB carcinoma of the cervix after radical hysterectomy
and pelvic lymphadenectomy: A Gynecologic Oncology Group Study. Gynecol Oncol 1999;73:177-
183. Available at: http://www.ncbi.nlm.nih.gov/pubmed/10329031
84. Rotman M, Sedlis A, Piedmonte MR, et al. A phase III randomized trial of postoperative pelvic
irradiation in Stage IB cervical carcinoma with poor prognostic features: follow-up of a gynecologic
oncology group study. Int J Radiat Oncol Biol Phys 2006;65:169-176. Available at: http://www.ncbi.
nlm.nih.gov/pubmed/16427212
85. Bodurka-Bevers D, Morris M, Eifel PJ, et al. Posttherapy surveillance of women with cervical
cancer: an outcomes analysis. Gynecol Oncol 2000;78:187-193. Available at: http://www.ncbi.nlm.
nih.gov/pubmed/10926801
86. Morice P, Deyrolle C, Rey A, et al. Value of routine follow-up procedures for patients with stage
I/II cervical cancer treated with combined surgery-radiation therapy. Ann Oncol 2004;15:218-223.
Available at: http://www.ncbi.nlm.nih.gov/pubmed/14760112
87. Elit L, Fyles AW, Devries MC, et al. Follow-up for women after treatment for cervical cancer: a
systematic review. Gynecol Oncol 2009;114:528-535. Available at: http://www.ncbi.nlm.nih.gov/
pubmed/19560188
88. Brooks RA, Rader JS, Dehdashti F, et al. Surveillance FDG-PET detection of asymptomatic
recurrences in patients with cervical cancer. Gynecol Oncol 2009;112:104-109. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/18929403
89. Schwarz JK, Siegel BA, Dehdashti F and Grigsby PW. Association of posttherapy positron
emission tomography with tumor response and survival in cervical carcinoma. JAMA 2007;298:2289-
2295. Available at: http://www.ncbi.nlm.nih.gov/pubmed/18029833
90. Sironi S, Picchio M, Landoni C, et al. Post-therapy surveillance of patients with uterine cancers:
value of integrated FDG PET/CT in the detection of recurrence. Eur J Nucl Med Mol Imaging
2007;34:472-479. Available at: http://www.ncbi.nlm.nih.gov/pubmed/17106701
91. Zanagnolo V, Ming L, Gadducci A, et al. Surveillance procedures for patients with cervical
carcinoma: a review of the literature. Int J Gynecol Cancer 2009;19:194-201. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/19395993
92. Chung HH, Jo H, Kang WJ, et al. Clinical impact of integrated PET/CT on the management of
suspected cervical cancer recurrence. Gynecol Oncol 2007;104:529-534. Available at: http://www.
ncbi.nlm.nih.gov/pubmed/17049971
93. Chaturvedi AK, Kleinerman RA, Hildesheim A, et al. Second cancers after squamous cell
carcinoma and adenocarcinoma of the cervix. J Clin Oncol 2009;27:967-973. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/19114696
94. Chaturvedi AK, Engels EA, Gilbert ES, et al. Second cancers among 104,760 survivors of
cervical cancer: evaluation of long-term risk. J Natl Cancer Inst 2007;99:1634-1643. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/17971527
95. Kumar S, Shah JP, Bryant CS, et al. Radiation-associated endometrial cancer. Obstet Gynecol
2009;113:319-325. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19155901
96. Thomas GM, Dembo AJ, Myhr T, et al. Long-term results of concurrent radiation and
chemotherapy for carcinoma of the cervix recurrent after surgery. Int J Gynecol Cancer 1993;3:193-
198. Available at: http://www.ncbi.nlm.nih.gov/pubmed/11578344
97. Kim JS, Kim SY, Kim KH and Cho MJ. Hyperfractionated radiotherapy with concurrent
REF-5
宫颈癌
© National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.The Chinese edition 2011 is the collaborative outcome of the National Comprehensive Cancer Network and Chinese key opinion leaders of the field. Translated and adapted with permission and endorsement from the National ComprehensiveCancer Network. To view the most recent and complete version of this or any other guideline, visit www.nccn.org.
chemotherapy for para-aortic lymph node recurrence in carcinoma of the cervix. Int J Radiat Oncol
Biol Phys 2003;55:1247-1253. Available at: http://www.ncbi.nlm.nih.gov/pubmed/12654434
98. Chung YL, Jian JJ, Cheng SH, et al. Extended-field radiotherapy and high-dose-rate
brachytherapy with concurrent and adjuvant cisplatin-based chemotherapy for locally advanced
cervical cancer: a phase I/II study. Gynecol Oncol 2005;97:126-135. Available at: http://www.ncbi.
nlm.nih.gov/pubmed/15790448
99. Berek JS, Howe C, Lagasse LD and Hacker NF. Pelvic exenteration for recurrent gynecologic
malignancy: survival and morbidity analysis of the 45-year experience at UCLA. Gynecol Oncol
2005;99:153-159. Available at: http://www.ncbi.nlm.nih.gov/pubmed/16054678
100. Goldberg GL, Sukumvanich P, Einstein MH, et al. Total pelvic exenteration: the Albert Einstein
College of Medicine/Montefiore Medical Center Experience (1987 to 2003). Gynecol Oncol
2006;101:261-268. Available at: http://www.ncbi.nlm.nih.gov/pubmed/16426668
101. Morley GW, Hopkins MP, Lindenauer SM and Roberts JA. Pelvic exenteration, University of
Michigan: 100 patients at 5 years. Obstet Gynecol 1989;74:934-943. Available at: http://www.ncbi.
nlm.nih.gov/pubmed/2586960
102. Fleisch MC, Pantke P, Beckmann MW, et al. Predictors for long-term survival after
interdisciplinary salvage surgery for advanced or recurrent gynecologic cancers. J Surg Oncol
2007;95:476-484. Available at: http://www.ncbi.nlm.nih.gov/pubmed/17192947
103. Tran PT, Su Z, Hara W, et al. Long-term survivors using intraoperative radiotherapy for recurrent
gynecologic malignancies. Int J Radiat Oncol Biol Phys 2007;69:504-511. Available at: http://www.
ncbi.nlm.nih.gov/pubmed/17560736
104. Rutledge FN, Smith JP, Wharton JT and O'Quinn AG. Pelvic exenteration: analysis of 296
patients. Am J Obstet Gynecol 1977;129:881-892. Available at: http://www.ncbi.nlm.nih.gov/
pubmed/930972
105. Symmonds RE, Pratt JH and Webb MJ. Exenterative operations: experience with 198 patients.
Am J Obstet Gynecol 1975;121:907-918. Available at: http://www.ncbi.nlm.nih.gov/pubmed/1115180
106. Soper JT, Secord AA, Havrilesky LJ, et al. Comparison of gracilis and rectus abdominis
myocutaneous flap neovaginal reconstruction performed during radical pelvic surgery: flap-specific
morbidity. Int J Gynecol Cancer 2007;17:298-303. Available at: http://www.ncbi.nlm.nih.gov/
pubmed/17291272
107. Mirhashemi R, Averette HE, Lambrou N, et al. Vaginal reconstruction at the time of pelvic
exenteration: a surgical and psychosexual analysis of techniques. Gynecol Oncol 2002;87:39-45.
Available at: http://www.ncbi.nlm.nih.gov/pubmed/12468340
108. Turns D. Psychosocial issues: pelvic exenterative surgery. J Surg Oncol 2001;76:224-236.
Available at: http://www.ncbi.nlm.nih.gov/pubmed/11276026
109. Spanos WJ, Jr., Perez CA, Marcus S, et al. Effect of rest interval on tumor and normal tissue
response--a report of phase III study of accelerated split course palliative radiation for advanced
pelvic malignancies (RTOG-8502). Int J Radiat Oncol Biol Phys 1993;25:399-403. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/7679668
110. Lutz ST, Chow EL, Hartsell WF and Konski AA. A review of hypofractionated palliative
radiotherapy. Cancer 2007;109:1462-1470. Available at: ht tp://www.ncbi.nlm.nih.gov/
pubmed/17330854
111. Moore DH, Blessing JA, McQuellon RP, et al. Phase III study of cisplatin with or without
paclitaxel in stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix: a gynecologic
oncology group study. J Clin Oncol 2004;22:3113-3119. Available at: http://www.ncbi.nlm.nih.gov/
pubmed/15284262
112. Long HJ, 3rd, Bundy BN, Grendys EC, Jr., et al. Randomized phase III trial of cisplatin with or
without topotecan in carcinoma of the uterine cervix: a Gynecologic Oncology Group Study. J Clin
Oncol 2005;23:4626-4633. Available at: http://www.ncbi.nlm.nih.gov/pubmed/15911865
113. Thigpen T, Shingleton H, Homesley H, et al. Cis-platinum in treatment of advanced or recurrent
squamous cell carcinoma of the cervix: a phase II study of the Gynecologic Oncology Group. Cancer
1981;48:899-903. Available at: http://www.ncbi.nlm.nih.gov/pubmed/7196794
114. Moore DH. Chemotherapy for advanced, recurrent, and metastatic
cervical cancer. J Natl Compr Canc Netw 2008;6:53-57. Available at: http://www.ncbi.nlm.nih.gov/
pubmed/18267059
115. Tao X, Hu W, Ramirez PT and Kavanagh JJ. Chemotherapy for recurrent and metastatic
cervical cancer. Gynecol Oncol 2008;110:67-71. Available at: http://www.ncbi.nlm.nih.gov/
pubmed/18533239
116. Monk BJ, Sill MW, McMeekin DS, et al. Phase III trial of four cisplatin-containing doublet
combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology
REF-6
© National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.The Chinese edition 2011 is the collaborative outcome of the National Comprehensive Cancer Network and Chinese key opinion leaders of the field. Translated and adapted with permission and endorsement from the National ComprehensiveCancer Network. To view the most recent and complete version of this or any other guideline, visit www.nccn.org.
宫颈癌
Group study. J Clin Oncol 2009;27:4649-4655. Available at: http://www.ncbi.nlm.nih.gov/
pubmed/19720909
117. Duenas-Gonzalez A, Zarba JJ, Alcedo JC, et al. A phase III study comparing concurrent
gemcitabine (Gem) plus cisplatin (Cis) and radiation followed by adjuvant Gem plus Cis versus
concurrent Cis and radiation in patients with stage IIB to IVA carcinoma of the cervix [abstract]. J
Clin Oncol 2009 27(Suppl 18):Abstract CRA5507. Available at: http://meeting.ascopubs.org/cgi/
content/abstract/27/18S/CRA5507
118. Moore KN, Herzog TJ, Lewin S, et al. A comparison of cisplatin/paclitaxel and carboplatin/
paclitaxel in stage IVB, recurrent or persistent cervical cancer. Gynecol Oncol 2007;105:299-303.
Available at: http://www.ncbi.nlm.nih.gov/pubmed/17303230
119. Tinker AV, Bhagat K, Swenerton KD and Hoskins PJ. Carboplatin and paclitaxel for advanced
and recurrent cervical carcinoma: the British Columbia Cancer Agency experience. Gynecol Oncol
2005;98:54-58. Available at: http://www.ncbi.nlm.nih.gov/pubmed/15904950
120. Pectasides D, Fountzilas G, Papaxoinis G, et al. Carboplatin and paclitaxel in metastatic or
recurrent cervical cancer. Int J Gynecol Cancer 2009;19:777-781. Available at: http://www.ncbi.nlm.
nih.gov/pubmed/19509587
121. Saito I, Kitagawa R, Fukuda H, et al. A phase III trial of paclitaxel plus carboplatin versus
paclitaxel plus cisplatin in stage IVB, persistent or recurrent cervical cancer: Gynecologic Cancer
Study Group/Japan Clinical Oncology Group Study (JCOG0505). Jpn J Clin Oncol 2010;40:90-93.
Available at: http://www.ncbi.nlm.nih.gov/pubmed/19825815
122. Tewari KS and Monk BJ. Recent achievements and future developments in advanced and
recurrent cervical cancer: trials of the Gynecologic Oncology Group. Semin Oncol 2009;36:170-180.
Available at: http://www.ncbi.nlm.nih.gov/pubmed/19332251
123. Thigpen JT, Blessing JA, DiSaia PJ, et al. A randomized comparison of a rapid versus
prolonged (24 hr) infusion of cisplatin in therapy of squamous cell carcinoma of the uterine cervix: a
Gynecologic Oncology Group study. Gynecol Oncol 1989;32:198-202. Available at: http://www.ncbi.
nlm.nih.gov/pubmed/2910782
124. Pectasides D, Kamposioras K, Papaxoinis G and Pectasides E. Chemotherapy for recurrent
cervical cancer. Cancer Treat Rev 2008;34:603-613. Available at: http://www.ncbi.nlm.nih.gov/
pubmed/18657909
125. McGuire WP, Arseneau J, Blessing JA, et al. A randomized comparative trial of carboplatin and
iproplatin in advanced squamous carcinoma of the uterine cervix: a Gynecologic Oncology Group
study. J Clin Oncol 1989;7:1462-1468. Available at: http://www.ncbi.nlm.nih.gov/pubmed/2674333
126. Weiss GR, Green S, Hannigan EV, et al. A phase II trial of carboplatin for recurrent or metastatic
squamous carcinoma of the uterine cervix: a Southwest Oncology Group study. Gynecol Oncol
1990;39:332-336. Available at: http://www.ncbi.nlm.nih.gov/pubmed/2258080
127. Kudelka AP, Winn R, Edwards CL, et al. An update of a phase II study of paclitaxel in advanced
or recurrent squamous cell cancer of the cervix. Anticancer Drugs 1997;8:657-661. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/9311440
128. McGuire WP, Blessing JA, Moore D, et al. Paclitaxel has moderate activity in squamous
cervix cancer. A Gynecologic Oncology Group study. J Clin Oncol 1996;14:792-795. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/8622025
129. Monk BJ, Sill MW, Burger RA, et al. Phase II trial of bevacizumab in the treatment of persistent
or recurrent squamous cell carcinoma of the cervix: a gynecologic oncology group study. J Clin
Oncol 2009;27:1069-1074. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19139430
130. Garcia AA, Blessing JA, Vaccarello L and Roman LD. Phase II clinical trial of docetaxel in
refractory squamous cell carcinoma of the cervix: a Gynecologic Oncology Group Study. Am J Clin
Oncol 2007;30:428-431. Available at: http://www.ncbi.nlm.nih.gov/pubmed/17762444
131. Look KY, Blessing JA, Gallup DG and Lentz SS. A phase II trial of 5-fluorouracil and high-
dose leucovorin in patients with recurrent squamous cell carcinoma of the cervix: a Gynecologic
Oncology Group study. Am J Clin Oncol 1996;19:439-441. Available at: http://www.ncbi.nlm.nih.
gov/pubmed/8823469
132. Schilder RJ, Blessing J and Cohn DE. Evaluation of gemcitabine in previously treated
patients with non-squamous cell carcinoma of the cervix: a phase II study of the Gynecologic
Oncology Group. Gynecol Oncol 2005;96:103-107. Available at: http://www.ncbi.nlm.nih.gov/
pubmed/15589587
133. Coleman RE, Harper PG, Gallagher C, et al. A phase II study of ifosfamide in advanced and
relapsed carcinoma of the cervix. Cancer Chemother Pharmacol 1986;18:280-283. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/3802384
134. Sutton GP, Blessing JA, McGuire WP, et al. Phase II trial of ifosfamide and mesna in patients
REF-7
宫颈癌
© National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.The Chinese edition 2011 is the collaborative outcome of the National Comprehensive Cancer Network and Chinese key opinion leaders of the field. Translated and adapted with permission and endorsement from the National ComprehensiveCancer Network. To view the most recent and complete version of this or any other guideline, visit www.nccn.org.
with advanced or recurrent squamous carcinoma of the cervix who had never received chemotherapy:
a Gynecologic Oncology Group study. Am J Obstet Gynecol 1993;168:805-807. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/8456884
135. Verschraegen CF, Levy T, Kudelka AP, et al. Phase II study of irinotecan in prior chemotherapy-
treated squamous cell carcinoma of the cervix. J Clin Oncol 1997;15:625-631. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/9053486
136. Wagenaar HC, Pecorelli S, Mangioni C, et al. Phase II study of mitomycin-C and cisplatin in
disseminated, squamous cell carcinoma of the uterine cervix. A European Organization for Research
and Treatment of Cancer (EORTC) Gynecological Cancer Group study. Eur J Cancer 2001;37:1624-
1628. Available at: http://www.ncbi.nlm.nih.gov/pubmed/11527687
137. Bookman MA, Blessing JA, Hanjani P, et al. Topotecan in squamous cell carcinoma of the
cervix: A Phase II study of the Gynecologic Oncology Group. Gynecol Oncol 2000;77:446-449.
Available at: http://www.ncbi.nlm.nih.gov/pubmed/10831357
138. Muderspach LI, Blessing JA, Levenback C and Moore JL. A Phase II study of topotecan in
patients with squamous cell carcinoma of the cervix: a gynecologic oncology group study. Gynecol
Oncol 2001;81:213-215. Available at: http://www.ncbi.nlm.nih.gov/pubmed/11354055
139. Miller DS, Blessing JA, Bodurka DC, et al. Evaluation of pemetrexed (Alimta, LY231514) as
second line chemotherapy in persistent or recurrent carcinoma of the cervix: a phase II study of the
Gynecologic Oncology Group. Gynecol Oncol 2008;110:65-70. Available at: http://www.ncbi.nlm.
nih.gov/pubmed/18455781
140. Muggia FM, Blessing JA, Method M, et al. Evaluation of vinorelbine in persistent or recurrent
squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol
2004;92:639-643. Available at: http://www.ncbi.nlm.nih.gov/pubmed/14766259
141. Castells MC, Tennant NM, Sloane DE, et al. Hypersensitivity reactions to chemotherapy:
outcomes and safety of rapid desensitization in 413 cases. J Allergy Clin Immunol 2008;122:574-580.
Available at: http://www.ncbi.nlm.nih.gov/pubmed/18502492
142. Sampson HA, Munoz-Furlong A, Campbell RL, et al. Second symposium on the definition and
management of anaphylaxis: summary report--second National Institute of Allergy and Infectious
Disease/Food Allergy and Anaphylaxis Network symposium. Ann Emerg Med 2006;47:373-380.
Available at: http://www.ncbi.nlm.nih.gov/pubmed/16546624
143. Manivannan V, Decker WW, Stead LG, et al. Visual representation of National Institute of
Allergy and Infectious Disease and Food Allergy and Anaphylaxis Network criteria for anaphylaxis.
Int J Emerg Med 2009;2:3-5. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19390910
144. Lenz HJ. Management and preparedness for infusion and hypersensitivity reactions. Oncologist
2007;12:601-609. Available at: http://www.ncbi.nlm.nih.gov/pubmed/17522249
145. Markman M, Zanotti K, Peterson G, et al. Expanded experience with an intradermal skin test to
predict for the presence or absence of carboplatin hypersensitivity. J Clin Oncol 2003;21:4611-4614.
Available at: http://www.ncbi.nlm.nih.gov/pubmed/14673050
146. Lee CW, Matulonis UA and Castells MC. Rapid inpatient/outpatient desensitization for
chemotherapy hypersensitivity: standard protocol effective in 57 patients for 255 courses. Gynecol
Oncol 2005;99:393-399. Available at: http://www.ncbi.nlm.nih.gov/pubmed/16054201
147. Lee CW, Matulonis UA and Castells MC. Carboplatin hypersensitivity: a 6-h 12-step protocol
effective in 35 desensitizations in patients with gynecological malignancies and mast cell/IgE-
mediated reactions. Gynecol Oncol 2004;95:370-376. Available at: http://www.ncbi.nlm.nih.gov/
pubmed/15491759
148. Monie A, Tsen S-WD, Hung C-F and Wu TC. Therapeutic HPV DNA vaccines. Expert Rev
Vaccines 2009;8:1221-1235. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19722895
149. Hung C-F, Ma B, Monie A, et al. Therapeutic human papillomavirus vaccines: current clinical
trials and future directions. Expert Opin Biol Ther 2008;8:421-439. Available at: http://www.ncbi.
nlm.nih.gov/pubmed/18352847
150. Huang CF, Monie A, Weng WH and Wu T. DNA vaccines for cervical cancer. Am J Transl Res
2010;2:75-87. Available at: http://www.ncbi.nlm.nih.gov/pubmed/20182584
151. Gonzalez-Cortijo L, Carballo N, Gonzalez-Martin A, et al. Novel chemotherapy approaches in
chemoradiation protocols. Gynecol Oncol 2008;110:S45-48. Available at: http://www.ncbi.nlm.nih.
gov/pubmed/18678399
152. Gonzalez Martin A. Molecular biology of cervical cancer. Clin Transl Oncol 2007;9:347-354.
Available at: http://www.ncbi.nlm.nih.gov/pubmed/17594948
153. Erickson-Whitmann B, Rownd J and Khater K. Biologic and physical aspects of radiation
oncology. In: Barakat R, Markman M and Randall M, eds. Principles and Practice of Gynecology
Oncology, 5th ed. Philadelphia: Lippincott Williams & Wilkins; 2009:325-380.
REF-8
© National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.The Chinese edition 2011 is the collaborative outcome of the National Comprehensive Cancer Network and Chinese key opinion leaders of the field. Translated and adapted with permission and endorsement from the National ComprehensiveCancer Network. To view the most recent and complete version of this or any other guideline, visit www.nccn.org.
宫颈癌
154. Beriwal S, Gan GN, Heron DE, et al. Early clinical outcome with concurrent chemotherapy and
extended-field, intensity-modulated radiotherapy for cervical cancer. Int J Radiat Oncol Biol Phys
2007;68:166-171. Available at: http://www.ncbi.nlm.nih.gov/pubmed/17321070
155. Chen M-F, Tseng C-J, Tseng C-C, et al. Clinical outcome in posthysterectomy cervical cancer
patients treated with concurrent Cisplatin and intensity-modulated pelvic radiotherapy: comparison
with conventional radiotherapy. Int J Radiat Oncol Biol Phys 2007;67:1438-1444. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/17394944
156. Chen M-F, Tseng C-J, Tseng C-C, et al. Adjuvant concurrent chemoradiotherapy with intensity-
modulated pelvic radiotherapy after surgery for high-risk, early stage cervical cancer patients. Cancer
J 2008;14:200-206. Available at: http://www.ncbi.nlm.nih.gov/pubmed/18536561
157. Salama JK, Mundt AJ, Roeske J and Mehta N. Preliminary outcome and toxicity report of
extended-field, intensity-modulated radiation therapy for gynecologic malignancies. Int J Radiat
Oncol Biol Phys 2006;65:1170-1176. Available at: http://www.ncbi.nlm.nih.gov/pubmed/16730136
158. Small W, Mell LK, Anderson P, et al. Consensus guidelines for delineation of clinical target
volume for intensity-modulated pelvic radiotherapy in postoperative treatment of endometrial and
cervical cancer. Int J Radiat Oncol Biol Phys 2008;71:428-434. Available at: http://www.ncbi.nlm.
nih.gov/pubmed/18037584
159. Fyles A, Keane TJ, Barton M and Simm J. The effect of treatment duration in the local control
of cervix cancer. Radiother Oncol 1992;25:273-279. Available at: http://www.ncbi.nlm.nih.gov/
pubmed1480773
160. Girinsky T, Rey A, Roche B, et al. Overall treatment time in advanced cervical carcinomas: a
critical parameter in treatment outcome. Int J Radiat Oncol Biol Phys 1993;27:1051-1056. Available
at: http://www.ncbi.nlm.nih.gov/pubmed8262826
161. Lanciano RM, Pajak TF, Martz K and Hanks GE. The influence of treatment time on outcome for
squamous cell cancer of the uterine cervix treated with radiation: a patterns-of-care study. Int J Radiat
Oncol Biol Phys 1993;25:391-397. Available at: http://www.ncbi.nlm.nih.gov/pubmed8436516
162. Perez CA, Grigsby PW, Castro-Vita H and Lockett MA. Carcinoma of the uterine cervix. I.
Impact of prolongation of overall treatment time and timing of brachytherapy on outcome of radiation
therapy. Int J Radiat Oncol Biol Phys 1995;32:1275-1288. Available at: http://www.ncbi.nlm.nih.
gov/pubmed7635767
163. Petereit DG, Sarkaria JN, Chappell R, et al. The adverse effect of treatment prolongation in
cervical carcinoma. Int J Radiat Oncol Biol Phys 1995;32:1301-1307. Available at: http://www.ncbi.
nlm.nih.gov/pubmed7635769
164. Swenson RE, Goff BA, Koh W-J, et al. Cancer in the pregnant patient. In: Hoskins WJ, Perez
CA and Young RC, eds. Principles and Practice of Gynecologic Oncology, 4th ed. Philadelphia:
Lippincott Williams & Wilkins; 2004 1279-1311.
165. van de Nieuwenhof HP, van Ham MAPC, Lotgering FK and Massuger LFAG. First case of
vaginal radical trachelectomy in a pregnant patient. Int J Gynecol Cancer 2008;18:1381-1385.
Available at: http://www.ncbi.nlm.nih.gov/pubmed/18298565
166. Ben-Arie A, Levy R, Lavie O, et al. Conservative treatment of stage IA2 squamous cell
carcinoma of the cervix during pregnancy. Obstet Gynecol 2004;104:1129-1131. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/15516424
167. Abu-Rustum NR, Tal MN, DeLair D, et al. Radical abdominal trachelectomy for stage IB1
cervical cancer at 15-week gestation. Gynecol Oncol 2010;116:151-152. Available at: http://www.
ncbi.nlm.nih.gov/pubmed/19878979
168. Gurney EP and Blank SV. Postpartum radical trachelectomy for IB1 squamous cell carcinoma of
the cervix diagnosed in pregnancy. Am J Obstet Gynecol 2009;201:e8-e10. Available at: http://www.
ncbi.nlm.nih.gov/pubmed/19695559
169. Chan JK and Berek JS. Impact of the human papilloma vaccine on cervical cancer. J Clin Oncol
2007;25:2975-2982. Available at: http://www.ncbi.nlm.nih.gov/pubmed/17617529
REF-9
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