放化疗：分割和剂量提升课件.pptx

1、Universit Campus Bio-Medico di Roma-Via lvaro del Portillo,21-00128 Roma Italiawww.unicampus.it放化疗：分割和剂量提升放化疗：分割和剂量提升 UNIVERSITA CAMPUS BIO-MEDICO DI ROMAwww.unicampus.itRADIO-CHEMOTHERAPY INCLUDING THE ISSUE OF FRACTIONATION AND DOSE ESCALATION放射肿瘤学的未来从从 2010 到到 2020:供应和需求会保持一致吗？25%Smith,JCO 201022

2、%UNIVERSITA CAMPUS BIO-MEDICO DI ROMAwww.unicampus.itIII期NSClC的联合治疗模式放化疗策略的meta分析治治疗疗策略策略试试验验数数病例病例数数3年绝对获益(%)生存率(95%可信区间)p序贯放化疗 vs 单纯单纯放放疗疗2238392.60.88(0.92-0.94)0.0001同步放化疗vs 单纯放疗1629103.20.88(0.81-0.95)0.0008Rolland E et al.J Thor Oncol 2(8):S309,2007Auperin A et al.J Thor Oncol 2(8):S310,2007RA

3、DIO-CHEMOTHERAPY INCLUDING THE ISSUE OF FRACTIONATION AND DOSE ESCALATIONUNIVERSITA CAMPUS BIO-MEDICO DI ROMAwww.unicampus.itIII期NSClC的联合治疗模式放化疗策略的meta分析治治疗疗策略策略试试验验数数病例病例数数3年绝对获益(%)生存率(95%可信区间)p序贯放化疗 vs 单纯单纯放放疗疗2238392.60.88(0.92-0.94)0.0001同步放化疗vs 单纯放疗1629103.20.88(0.81-0.95)0.0008Rolland E et al.

4、J Thor Oncol 2(8):S309,2007Auperin A et al.J Thor Oncol 2(8):S310,2007RADIO-CHEMOTHERAPY INCLUDING THE ISSUE OF FRACTIONATION AND DOSE ESCALATIONUNIVERSITA CAMPUS BIO-MEDICO DI ROMAwww.unicampus.itIII期NSClC的联合治疗模式放化疗策略的meta分析治治疗疗策略策略试试验验数数病例病例数数3年绝对获益(%)生存率(95%可信区间)p序贯放化疗 vs 单纯单纯放放疗疗2238392.60.88(0.

5、92-0.94)0.0001同步放化疗vs 单纯放疗1629103.20.88(0.81-0.95)0.0008Rolland E et al.JTO 2(8):S309,2007Auperin A et al.JTO 2(8):S310,2007同步放化同步放化疗疗vs 序序贯贯放化放化疗疗611996.60.83(0.73-0.94)0.0026RADIO-CHEMOTHERAPY INCLUDING THE ISSUE OF FRACTIONATION AND DOSE ESCALATIONUNIVERSITA CAMPUS BIO-MEDICO DI ROMAwww.unicampus

6、.it 2010年同步放化疗 vs 序贯放化疗的两篇文献711 病人 3个临床试验1.205 病人6个临床试验ORourke N.Clin Oncol 22:347355,2010Anne Auperin J Clin Oncol 28:2181-2190,2010RADIO-CHEMOTHERAPY INCLUDING THE ISSUE OF FRACTIONATION AND DOSE ESCALATIONUNIVERSITA CAMPUS BIO-MEDICO DI ROMAwww.unicampus.itORourke N.Clin Oncol 2010p=0.003结论仅适用于II

7、I期患者2年死亡风险下降14%同步放化疗序贯放化疗RADIO-CHEMOTHERAPY INCLUDING THE ISSUE OF FRACTIONATION AND DOSE ESCALATIONUNIVERSITA CAMPUS BIO-MEDICO DI ROMAwww.unicampus.itA nA na al l y ys si i s s 7 7.1 1.C C omom p pa ariri s sonon 7 7 c cononc cu ur rr re en nt tv ve ersrsu us s s se eq qu ue en nt ti i a al lt to

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17、000012)0.010.1110100f avoursconcurrentf avourssequenti alA nA na al l y ys si i s s 7 7.4 4.C C omom p pa ariri s sonon 7 7 c cononc cu ur rr re en nt tv ve ersrsu us s s se eq qu ue en nt ti i a al lt to oxixi c ci i t ty y,O O u ut tc co om m e e 4 4 n neueut tr ro op peneni i a a.Revi ew:Concurre

18、ntchem oradi otherapyi n non-sm al lcel ll ung cancerCom pari son:7 concurrentversussequenti altoxi ci tyO utcom e:4 neutropeni aStudyorsubgroupconcurrentsequenti alRi skRati oW ei ghtRi sk Rati on/Nn/NM-H,Random,95%CIM-H,Random,95%CICurran 2003117/201113/201ORourke N.Clin Oncol 2010同步放化疗序贯放化疗同步放化疗序

19、贯放化疗RADIO-CHEMOTHERAPY INCLUDING THE ISSUE OF FRACTIONATION AND DOSE ESCALATIONUNIVERSITA CAMPUS BIO-MEDICO DI ROMAwww.unicampus.itAnne Auperin J Clin Oncol 28:2181-2190.2010 by American Society of Clinical Oncology同步放化疗获益情况：HR 0.84。95%可信区间,0.74-0.95;p=0.004RADIO-CHEMOTHERAPY INCLUDING THE ISSUE OF

20、FRACTIONATION AND DOSE ESCALATIONUNIVERSITA CAMPUS BIO-MEDICO DI ROMAwww.unicampus.itAnne Auperin J Clin Oncol 28:2181-2190.20103年生存绝对获益5.7%3年生存绝对获益4.5%RADIO-CHEMOTHERAPY INCLUDING THE ISSUE OF FRACTIONATION AND DOSE ESCALATIONUNIVERSITA CAMPUS BIO-MEDICO DI ROMAwww.unicampus.itAnne Auperin J Clin O

21、ncol 28:2181-2190.2010 by American Society of Clinical Oncology同步放化疗 vs 序贯放化疗 ：4%-18%，（相对危险度，4.9 95%可信区间，3.1-7.8；p=0.001）(相对危险度，0.69；95%可信区间，0.42-1.12；p=0.13）RADIO-CHEMOTHERAPY INCLUDING THE ISSUE OF FRACTIONATION AND DOSE ESCALATIONABS 7561:局部进展期非小细胞肺癌同步放化疗后的治疗相关死亡：多个临床试局部进展期非小细胞肺癌同步放化疗后的治疗相关死亡：多个临

22、床试验的验的meta分析分析 研究目标研究目标比较局部进展期非小细胞肺癌同步放化疗与非同步放化疗的治疗相关死亡率凡是随机对照试验中有同步放化疗和非同步放化疗（序贯放化疗和单纯放疗）组患者，均纳入进行meta分析主要结果主要结果数据来自数据来自9个试验个试验(n=1831)同时包括同步放化疗与非同步放化疗组2组治疗相关死亡率相似，p=0.47放化疗方案和放射剂量与治疗相关死亡率无明显关联结论结论与序贯放化疗或单纯放疗相比，同步放化疗并未明显增加治疗相关死亡并未明显增加治疗相关死亡放疗剂量和化疗方案都未增加治疗死亡率Zhao et al.J Clin Oncol 2014;32(suppl 5;a

23、bstr 7561)2014UNIVERSITA CAMPUS BIO-MEDICO DI ROMAwww.unicampus.itCHEST 2013;143(5)(Suppl):e314Se340S浸润型III期（N2，3）NSCLC，PS 0-1分，治疗目的为根治的患者，铂类为基础的同步放化疗为推荐方案，优于序贯放化疗，（证据等级1A）指南指南根治性同步放化疗RADIO-CHEMOTHERAPY INCLUDING THE ISSUE OF FRACTIONATION AND DOSE ESCALATIONUNIVERSITA CAMPUS BIO-MEDICO DI ROMAwww.u

24、nicampus.it“胸腔放疗联合同期化疗应被应被视为视为局部进展期不可切除的III期NSCLC的治疗选择”DAddario,Annals of Oncology 19(Suppl 2):ii39ii40,2008ESMO Guidelines“同步放化疗疗效优于序贯放疗-化疗，但3-4级食管炎中度增加。同步放化疗是经过选择的患者的标准治疗方案标准治疗方案”Crin L.Annals of Oncology 21(Suppl 5):v103v115,201020082010“根治性同步放化疗同步放化疗是不可切除NSCLC的首选治疗”2013Vanstenkiste.Annals of Onc

25、ology 24(Suppl 6):vi89vi98,2013RADIO-CHEMOTHERAPY INCLUDING THE ISSUE OF FRACTIONATION AND DOSE ESCALATIONUNIVERSITA CAMPUS BIO-MEDICO DI ROMAwww.unicampus.itSEER-Medicare数据库中的治疗选择倾向12.440 病例病例 结论：与以往指出III期期NSCLC中化疗获益中化疗获益的文献一致。联合治疗总采用率提高，表明III期NSCLC逐渐倾向于更高强度的治疗更高强度的治疗Medicare人群中III期NSCLC的治疗方式0 0101

26、0202030304040505060607070808090901994199420052005RT CT RT+CT 同步 RT+CT A.B.Chen,B.ASTRO Nov 2010RADIO-CHEMOTHERAPY INCLUDING THE ISSUE OF FRACTIONATION AND DOSE ESCALATIONUNIVERSITA CAMPUS BIO-MEDICO DI ROMAwww.unicampus.itIII期不可切除NSCLC联合治疗的地域差异地域差异:来自针对tecemotide的全球III期试验的结果Nicholas Thatcher,Frances

27、 A Shepherd,Paul MitchellIASLC Sidney 2013RADIO-CHEMOTHERAPY INCLUDING THE ISSUE OF FRACTIONATION AND DOSE ESCALATIONUNIVERSITA CAMPUS BIO-MEDICO DI ROMAwww.unicampus.it肺癌肺癌(NSCLC)照射体积：选择性的淋巴结照射（ENI）VS 累及野照射（IF）分割与剂量提升更多化疗三代化疗药与靶向药物RADIO-CHEMOTHERAPY INCLUDING THE ISSUE OF FRACTIONATION AND DOSE ESC

28、ALATIONUNIVERSITA CAMPUS BIO-MEDICO DI ROMAwww.unicampus.it肺癌肺癌(NSCLC)照射体积：选择性的淋巴结照射（ENI）VS 累及野照射（IF）剂量提升分割更多化疗3代化疗药与靶向药物RADIO-CHEMOTHERAPY INCLUDING THE ISSUE OF FRACTIONATION AND DOSE ESCALATIONUNIVERSITA CAMPUS BIO-MEDICO DI ROMAwww.unicampus.it选择性淋巴结照射选择性淋巴结照射(ENI)RADIO-CHEMOTHERAPY INCLUDING TH

29、E ISSUE OF FRACTIONATION AND DOSE ESCALATIONUNIVERSITA CAMPUS BIO-MEDICO DI ROMAwww.unicampus.itSchild S,2008三期临床试验“心脏毒性的两难困境”Yuan S 等.“IF vs ENI的临床研究的临床研究”Am JCO 2007200病例，III期不可切除肺癌，同步放化疗5年局控率肺炎2年生存率5年生存率ENI 60-64Gy 36%29%25.6%18.3%IFI*68-74Gy 51%,p=0.0317%,p=0.0439.4%,p=0.04825.1%RADIO-CHEMOTHERA

30、PY INCLUDING THE ISSUE OF FRACTIONATION AND DOSE ESCALATIONUNIVERSITA CAMPUS BIO-MEDICO DI ROMAwww.unicampus.itSchild S,Int J Radiat Oncol Biol Phys 2008争议:IF代替ENI?临床未受侵淋巴结临床未受侵淋巴结的复发情况RADIO-CHEMOTHERAPY INCLUDING THE ISSUE OF FRACTIONATION AND DOSE ESCALATIONUNIVERSITA CAMPUS BIO-MEDICO DI ROMAwww.

31、unicampus.itBelderbos,Int.J.Radiat Oncol Biol.Phys.,72:335342,2008局部复局部复发发部位部位:低危区域PET孤立淋巴结复发基于基于TC的靶区的靶区RADIO-CHEMOTHERAPY INCLUDING THE ISSUE OF FRACTIONATION AND DOSE ESCALATIONUNIVERSITA CAMPUS BIO-MEDICO DI ROMAwww.unicampus.itBelderbos,Int.J.Radiat Oncol Biol.Phys.,72:335342,2008局部复局部复发发部位部位:低

32、危区域PET孤立淋巴结复发基于基于PET的靶区的靶区?RADIO-CHEMOTHERAPY INCLUDING THE ISSUE OF FRACTIONATION AND DOSE ESCALATIONUNIVERSITA CAMPUS BIO-MEDICO DI ROMAwww.unicampus.itBelderbos,Int.J.Radiat Oncol Biol.Phys.,72:335342,2008局部复局部复发发部位部位:低危区域TCPET孤立淋巴结复发RADIO-CHEMOTHERAPY INCLUDING THE ISSUE OF FRACTIONATION AND DOS

33、E ESCALATIONUNIVERSITA CAMPUS BIO-MEDICO DI ROMAwww.unicampus.it局部复局部复发发部位部位:低危区域Sulman,Radiation Oncology 2009PET1151,7%Fernandes,Radiother and Oncology 2010PET484.3%Fleckenstein,Int J Radiat Oncol Biol Phys 2011PET334%Bradley,Int J Radiat Oncol Biol Phys 2012PET472%孤立淋巴结复发RADIO-CHEMOTHERAPY INCLUD

34、ING THE ISSUE OF FRACTIONATION AND DOSE ESCALATIONUNIVERSITA CAMPUS BIO-MEDICO DI ROMAwww.unicampus.it此时.累及野放疗后的孤立淋巴结复发累及野放疗后的孤立淋巴结复发我们有PET.我们知道孤立淋巴结复发是罕见的.问题完全解决了吗?还缺了一块.RADIO-CHEMOTHERAPY INCLUDING THE ISSUE OF FRACTIONATION AND DOSE ESCALATIONUNIVERSITA CAMPUS BIO-MEDICO DI ROMAwww.unicampus.itBe

35、lderbos,Int J Radiat Oncol Biol Phys 2006PET673%De Ruysscher,Int J Radiat Oncol Biol Phys 2005PET442%Fernandes,Radiother and Oncology 2010PET484.3%Sulman,Radiation Oncology 2009PET1151,7%Fleckenstein,Int J Radiat Oncol Biol Phys 2011PET334%Bradley,Int J Radiat Oncol Biol Phys 2012PET472%靶区定义的方法学靶区定义

36、的方法学累及野放疗后的孤立淋巴结复发累及野放疗后的孤立淋巴结复发RADIO-CHEMOTHERAPY INCLUDING THE ISSUE OF FRACTIONATION AND DOSE ESCALATIONUNIVERSITA CAMPUS BIO-MEDICO DI ROMAwww.unicampus.it靶区定靶区定义义:材料与方法材料与方法GTV N=累及淋巴累及淋巴结结Fernandes,Radiot and Oncology 2010americaCT 短径1cmPET（+）淋巴结+肺门区+RADIO-CHEMOTHERAPY INCLUDING THE ISSUE OF F

37、RACTIONATION AND DOSE ESCALATIONUNIVERSITA CAMPUS BIO-MEDICO DI ROMAwww.unicampus.itSulman,Komaki,et al.Radiat Oncol 2009对右中下肺叶、左舌叶、左下叶肿物，如果纵隔淋巴结受侵，则同时照射同侧肺门和隆突下淋巴结靶区定靶区定义义:材料与方法材料与方法GTV N=CT 短径1cmPET（+）淋巴结+RADIO-CHEMOTHERAPY INCLUDING THE ISSUE OF FRACTIONATION AND DOSE ESCALATIONUNIVERSITA CAMPUS

38、BIO-MEDICO DI ROMAwww.unicampus.itSulman,Komaki,et al.Radiat Oncol 2009对右中下肺叶、左舌叶、左下叶肿物，如果纵隔淋巴结受侵，则同时照射同侧肺门和隆突下淋巴结靶区定靶区定义义:材料与方法材料与方法GTV N=右中下肺叶左下肺叶RADIO-CHEMOTHERAPY INCLUDING THE ISSUE OF FRACTIONATION AND DOSE ESCALATIONUNIVERSITA CAMPUS BIO-MEDICO DI ROMAwww.unicampus.itGTV N=Sulman,Komaki,Radia

39、t Oncol 2009对左下叶肿物，如果纵隔淋巴结受侵，照射野应包括主肺动脉窗淋巴结。靶区定靶区定义义:材料与方法材料与方法RADIO-CHEMOTHERAPY INCLUDING THE ISSUE OF FRACTIONATION AND DOSE ESCALATIONUNIVERSITA CAMPUS BIO-MEDICO DI ROMAwww.unicampus.it靶区定靶区定义义:材料与方法材料与方法GTV N=受累淋巴受累淋巴结结america从“ELECTIVE”淋巴结放疗到“SELECTIVE”淋巴结放疗CT贯化疗的情况下，照射体积按照化疗前或化疗后体积并未特别阐明待解决问

40、题：Fernandes,Radiot and Oncology 2010大部分患者(88%)均接受同步或序贯化疗。Sulman,Komaki,Radiat Oncol 200947%接受诱导化疗，53%接受同步化疗。RADIO-CHEMOTHERAPY INCLUDING THE ISSUE OF FRACTIONATION AND DOSE ESCALATIONUNIVERSITA CAMPUS BIO-MEDICO DI ROMAwww.unicampus.itPET（-）淋巴结淋巴结Fleckenstein,Int J Radiat Oncol Biol Phys 2011靶区定靶区定义

41、义:材料与方法材料与方法CTV N=1cmNO所有所有 PET阳性淋巴结阳性淋巴结PET（+）淋巴结）淋巴结YESRADIO-CHEMOTHERAPY INCLUDING THE ISSUE OF FRACTIONATION AND DOSE ESCALATIONUNIVERSITA CAMPUS BIO-MEDICO DI ROMAwww.unicampus.itFleckenstein,Int J Radiat Oncol Biol Phys 2011所有所有PET阳性淋巴引流区阳性淋巴引流区因此，所有美国癌症联合委员会（AJCC）的 淋巴引流区淋巴引流区靶区定靶区定义义:材料与方法材料与

42、方法CTV N=RADIO-CHEMOTHERAPY INCLUDING THE ISSUE OF FRACTIONATION AND DOSE ESCALATIONUNIVERSITA CAMPUS BIO-MEDICO DI ROMAwww.unicampus.it所有PET阳性的淋巴引流区诱导化疗靶区定靶区定义义:材料与方法材料与方法CTV N=De Ruysscher Int J Radiat Oncol Biol Phys 2005PET/CT化疗后化疗后GTV按照化疗后化疗后的扫描影像勾画PET/CT化疗前化疗前如果原发肿瘤或受侵淋巴结化疗后达到完全缓解，完全缓解，该部位包括在CT

43、V中RADIO-CHEMOTHERAPY INCLUDING THE ISSUE OF FRACTIONATION AND DOSE ESCALATIONUNIVERSITA CAMPUS BIO-MEDICO DI ROMAwww.unicampus.it所有PET阳性的淋巴引流区诱导化疗靶区定靶区定义义:材料与方法材料与方法CTV N=PET/CT化疗后化疗后GTV按照化疗后化疗后的扫描影像勾画PET/CT化疗前化疗前如果原发肿瘤或受侵淋巴结化疗后达到完全缓解，完全缓解，该部位包括在CTV中Belderbos,Int J Radiat Oncol Biol Phys 2006RADIO-C

44、HEMOTHERAPY INCLUDING THE ISSUE OF FRACTIONATION AND DOSE ESCALATIONUNIVERSITA CAMPUS BIO-MEDICO DI ROMAwww.unicampus.it靶区定靶区定义义:总结总结CTV NRADIO-CHEMOTHERAPY INCLUDING THE ISSUE OF FRACTIONATION AND DOSE ESCALATIONUNIVERSITA CAMPUS BIO-MEDICO DI ROMAwww.unicampus.it肺癌肺癌(NSCLC)照射体积：选择性的淋巴结照射（ENI）VS 累及

45、野照射（IF）剂量提升分割更多化疗3代化疗药与靶向药物RADIO-CHEMOTHERAPY INCLUDING THE ISSUE OF FRACTIONATION AND DOSE ESCALATIONUNIVERSITA CAMPUS BIO-MEDICO DI ROMAwww.unicampus.it剂量提升剂量提升:原理放疗后肿瘤干细胞仍存活Krause Radiother Oncol 2006RADIO-CHEMOTHERAPY INCLUDING THE ISSUE OF FRACTIONATION AND DOSE ESCALATIONUNIVERSITA CAMPUS BIO-

46、MEDICO DI ROMAwww.unicampus.it为将NSCLC局控提升到50%以上，要给予高得多的等效生物剂量.60-70%:90-100 Gy剂量提升剂量提升.等效生物剂量等效生物剂量Mehta,Int J Rad Onc Biol Phis 01NSCLC 表现为相对放射抗拒，因此传统的60-70Gy对增加局控不多，15-25%RADIO-CHEMOTHERAPY INCLUDING THE ISSUE OF FRACTIONATION AND DOSE ESCALATIONUNIVERSITA CAMPUS BIO-MEDICO DI ROMAwww.unicampus.it

47、较高等效生物剂量（BED）与局部进展期NSCLC放化疗后结局改善相关7 项RTOG试验1356病例BED增加1 Gy，生存相相对对提高提高4%Machtay,Int J Radiat Oncol Biol Phys 2012RADIO-CHEMOTHERAPY INCLUDING THE ISSUE OF FRACTIONATION AND DOSE ESCALATIONUNIVERSITA CAMPUS BIO-MEDICO DI ROMAwww.unicampus.itMEDIAN(MONTHS)1Y%2Y%3Y%4Y%5Y%标准剂量19.369.540.226.921.919.3中间剂量

48、提升20.974.947.136.629.423.9总生存按BED10治疗组分层计算Rodrigues,Int J Radiat Oncol Biol Phys,in pressIs Intermediate Radiation Dose Escalation with Concurrent Chemotherapy for Stage III Non-Small Cell Lung Cancer Beneficial?A Multi-Institutional Propensity-Score Matched Analysis.George Rodrigues MD PhD FRCPC,Ca

49、ry Oberije MSc PhD,Suresh Senan MRCP FRCR PhD,Kayoko Tsujino MD PhD,Terry Wiersma MD,Marta Moreno-Jimenez MD PhD,Tae Hyun Kim MD,Lawrence B.Marks MD,Ramesh Rengan MD PhD,Luigi De Petris MD PhD,Sara Ramella MD,Kim DeRuyck PhD,Nria Rodriguez De Dios MD PhD,Andrew Warner MSc,Jeffrey D.Bradley MD,David

50、A.Palma MD PhD FRCPC Purpose:The clinical benefits/risks of dose escalation(DE)for stage III non-small cell lung cancer(NSCLC)remain uncertain despite the results from the RTOG 0617 randomized trial.There is significant heterogeneity of practice with many clinicians prescribing intermediate dose lev