非小细胞肺癌放射治疗进展课件

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非小细胞肺癌放射治疗进展影像技术和计算机技术的进步为精确放射治疗的实现提供可能2020/11/1422020/11/1432020/11/144屏气技术举例:ElektaABC2020/11/145四维CT影像技术呼气吸气螺旋开始时相由吸转呼呼气末由呼转吸由吸转呼呼气吸气螺旋开始呼吸曲线床

位2020/11/146影像引导放射治疗技术IGRT40对叶片MLCKV级X射线球管KV级探测器阵列MV级探测器阵列2020/11/147在线校正—影像匹配2020/11/148一、放射治疗在肺癌治疗中的地位二、早期NSCL的放射治疗三、局部晚期NSCL的放疗/化疗综合治疗四、3DCRT提高NS

CLC的生存率五、术后放射治疗2020/11/149一、放射治疗在肺癌治疗中的地位⚫应用循证医学的方法评价放射治疗在肺癌治疗中的地位。2020/11/14102020/11/1411RT在SCLC治疗中的地位⚫53.6%±3.3%SCLC病例在其疾病的不同时期需要接受放射

治疗45.4%±4.3%为首程治疗(intheinitialtreatment).8.2%±1.5%为复发和进展病例的治疗(laterforrecurrenceorprogression)2020/11/1412RT在NSCLC治疗中的地位⚫64.3%±4.7%ofNSCLCcas

esrequireRT.45.9%±4.3%intheirinitialtreatment.18.3%±1.8%laterinthecouseoftheillness2020/11/1413二、早期非小细胞肺癌的放射治疗放射治疗能够使早期NSCLC获得治愈2020/11

/1414JapaneseStudiesI期NSCLC大剂量分割SRT获得满意的局部控制率InstituteDose/fx/OTTLC/Follow-upUematsu50-60/5-10/5d94%(47/50)36MKyoto48Gy/4fr/1

2d96%(49/51)20MArimoto60Gy/8fr/11d92%(22/24)24MOnimaru60Gy/8fr/11d:88%(50/57)18MNagataY,KyotoUniv,IASLC,20042020/11/1415SummaryofJapa

neseStudies⚫Totalcases:281⚫Age:39-92(median76)years⚫Pulmonarydisease:Positive:172,Negative:109⚫Histology:Sqamous:122A

deno:131,Others:28⚫Stage:IA:178,IB:103⚫Tumordiameter:7-58(median23)mm⚫MedicalOperability:Inoperable:177,Operable:104

OnishiH,ASCO20042020/11/1416LocalControlandComplication⚫Follow-upperiod2-128(median30)months⚫LocalresponseCR26.9%PR59.1%NC14.

0%⚫Pneumonitis(NCI-CTC)Grade0:33.7%Grade1:59.9%Grade2:4.0%Grade3:1.2%Grage4:1.2%⚫Esophagitis(Grade3)1.2%⚫Pleuraleffusion(tran

sient)1.6%⚫Ribfracture1.2%⚫Bonemarrowsuppression0.0%OnishiH,ASCO20042020/11/1417LocalFailureRates⚫Totalcases38/281(13.5%)BE

D<100Gy21/70(30.0%)BED>100Gy17/211(8.1%)⚫StageIA17/177(9.6%)BED<100Gy8/41(19.5%)BED>100Gy9/136(6.6%)

⚫StageIB21/102(20.6%)BED<100Gy13/29(44.8%)BED>100Gy8/73(11.0%)⚫Adenocarcinoma17/122(14.0%)⚫Squamouscellc

a.18/131(13.7%)OnishiH,ASCO20042020/11/1418Mountain*JCOG*JNCCH*StageIAStageIB67%57%80%63%74%53%STI**90%

84%*Surgery**StereotacticIrradiationComparisonof5-YrOverallSurvivalBetweenSurgery&STISurvivalcurvesofoperableptsirradiatedwithBEDof100Gyormo

reaccordingtoStagestageIA(n=47)stageIB(n=16)p=0.2OverallSurvivalTime(years)00.20.40.60.8101234567Summary

ofJapaneseStudiesOnishiH,ASCO20042020/11/1419I期非小细胞肺癌立体定向放射治疗或楔形切除后的转归SRBT(n=55)楔形切除(n=69)P肺功能(FEV-1)1.39(0.

86-2.37)1.31(0.52-3.0)NSCharlson合并症指数3(1-4)4(3-6)<0.01年龄74(69-78)78(55-89)<0.01分期T1-T2T1-T2NS病变最大直径GTV:2.3(1-5.3)手术标本:1.7(0.4-4.7)-纵隔淋巴结转移0(PET,

纵隔镜)0(手术)NS化疗16%10%NSGrillsetal:JCO2010doi:10.1200/JCO.2009.26.51572020/11/1420I期非小细胞肺癌立体定向放射治疗或楔形切除后的

转归2020/11/1421作者患者MFUTRRorLRDMOSCSSGinsberg,19951225417-6175Landreneau,1997422924-5838*602416-6538*Sienel,2007495416--67Sienel,20085645

1618-713145556-48Keenan,200454271196274El-Sherif,20062073171540-Lee,200335516304761Voynov,2005110414818-Birdas,2

00641255-54-27250---142514---I期非小细胞肺癌局部切除后的转归2020/11/1422作者患者MFUTRRorLRDMOSCSSOnisi,2007257388-14206590Negata,20054536216-3183-Uematsu,2001503

06146688Zimmerman,2006681712165173Fakiris,2009705012134382RTOG,0236552561572-I期非小细胞肺癌立体定向放射治疗后的转归2020/11/14232020/11/14242020/11/

1425早期非小细胞肺癌的放射治疗➢放射治疗成为早期NSCLC的另一根治性治疗手段➢放射治疗在早期NSCLC治疗中的地位的确立,是肺癌治疗进展中的一个里程碑2020/11/1426三、局部晚期NSCLC的治疗2020/11/1427局部晚期NSCLCEvolutionofTreatme

ntStrategy⚫Operable:SurgerySurgery±RTSurgery±RT±CTCT+SurgeryRT/CT+SurgeryRT/CT±SurgeryRT/CT2020/11/1428局部晚期N

SCLCEvolutionofTreatmentStrategy➢Inoperable:RTCT+RTSequentialCT/RTConcurrent?InductionCTCT/RTCT/RTConsolidat

ion?2020/11/1429➢Inoperable序贯放化综合治疗同步放化综合治疗➢OperableⅢa-N2RT/CT+SurgeryvsRT/CTCT+SurgeryvsCT/RT2020/11/1430序贯化放疗荟萃(META)分析22tra

ils3033casesFavorGrHRbenefit%sur%2y5y2y5yChemo0.9032R+DDP0.8742151957p=0.005DDP40-120mg/m2/cycle,totaldose120-800mg/m2radia

tiondose50Gy/20f-65Gy/30f结论:序贯放疗/化疗优于单纯放射治疗2020/11/1431同时化放疗vs序贯化放疗2020/11/1432同时化放疗vs序贯化放疗(1)序贯化放疗同时化放疗5年生存率8.9%15.8%P=0

.04。中位生存期(月)13.316.53yLRFSur.21.1%33.9%同时化放疗:提高局部控制率和生存率FuruseK,etal.JClin.Oncol.1999;17:2692-26992020/11/1433RTO

G9410:III期NSCLC同步放化疗vs序贯放化疗序贯:PV-->RT(60Gy,2GyQD)day50同步:PV/RT(60Gy,2GyQD)day1同步/HFRT:PE/HFRT(69.2Gy,1.2GyBID)day1PV:顺铂/长春花碱PE:顺铂/

oral足叶乙甙RT:放疗;QD:每日一次;HFRT:超分隔放疗Curran:ASCO,2000;updatedIASLC2000;ASTRO2001,2003RANDOMIZE2020/11/1434二.同时化放疗vs序贯化放疗(2)SEQCO

N-QDCON-BID中位生存期:14.61715.6(月)4年生存率:12%21%17%p=0.046G3急性和晚期非血液系统毒性:30%,48%,62%和14%,15%,16%。CurranWetal.Pro.AmSoc

ClinOncol.J.Clin.Oncol.2003;(abstract2499)2020/11/14352020/11/14362020/11/1437结论:同步放化疗优于序贯放化疗,但是,急性毒性反应增加2020/11/1438同步放化疗?诱导化疗?巩固化疗2020/11/1

439同步放化疗诱导化疗2020/11/1440InductionChemotherapyFollowedbyChemoradiotherapyWithChemoradio-therapyAloneforRegionallyAdvancedUnresectableSt

ageIIINon–Small-CellLung:CancerandLeukemiaGroupBCALGB39801JClinOncol.2007May1;25(13):1698-704.Epub2007Apr2020/11/1441CALGB39801studydes

ign⚫July1998andwasclosedinMay2002,Totally366patientsregistered2020/11/1442Survivalintenttotreat2020/11/1443Survivalofeligiblepatientswithaw

eightlossof≤5%2020/11/1444Discussion➢增加毒性inductionchemotherapyincreasesneutropeniaandoverallmaximaltoxicity➢没有生存优势Nos

urvivalbenefitoverconcurrenttherapyalone➢同期放化疗是标准的治疗模式Concomitantchemoradiotherapyiscurrentstandardtherapyforunresect

ablestageIIIBNSCLC2020/11/1445SimultaneousChemoradiotherapyComparedWithRadiotherapyAloneAfterInductionChemotherapyinInoperableStageIIIAorIIIBN

on–Small-CellLungCancer:StudyCTRT99/97bytheBronchialCarcinomaTherapyGroupRudolfM.Huber,MichaelFlentje,MichaelSchmidt,BarbaraPöllinger,HelgaGoss

e,JochenWillner,andKurtUlmPCx3诱导化疗RandomizeRTaloneRT+Paclitaxel60mg/m2weekly2020/11/1446paclitaxel200mg/m2carboplatinA

UC=6every3weeksX2cyclespaclitaxel60mg/m2weeklyRadiotherapyalone2020/11/14472020/11/1448Survivalafterinductionchemotherapyforpatientswithcomplete

orpartialresponse2020/11/1449同步放化疗巩固化疗2020/11/1450SWOG9504:同步放化疗后应用泰索帝巩固化疗治疗IIIb期NSCLC顺铂/VP-16XXRT泰索帝XXX顺铂50mg/m2d1,8,29,36VP-1650mg/m

2d1-5,29-33RT:61Gy:45Gy(1.8Gy/fx),16Gy缩野(2Gy/fx)泰索帝:75mg/m2cycle1-->100mg/m2cycle2-32020/11/1451SWOG9504:总生存%%%%%020406080100%01224

3648入组时间(月)NEvents中位生存834526月2年生存率:54%3年生存率:37%2020/11/1452SWOG9504和SWOG9019比较研究病例MST(月)2年生存3年生存S9019(PE/RT→PE)5015(10-22)*34%(21-47)

*17%(7-27)*S9504(PE/RT→泰索帝)8326(18-35)*54%(43-65)*37%(22-52)*2020/11/1453SWAG0023ConcurrentChemo/RadioDDP+Vp16/RTConsol

idationChemoDocetaxelMaintenanceGEFITINIBorPLACEBO2020/11/14542020/11/1455同步放化疗巩固化疗ResultsofASCO200720

20/11/1456HOGLUN01-24PhaseIIIStudyDesignHannaetal.ASCO2007:Abstract7512.ChemoRTCisplatin50mg/m2IVd1,8,29,36Etoposide50mg/m2IVd1-5&2

9-33ConcurrentRT59.4Gy(1.8Gy/fr)Stratificationatrandomization•PS0-1vs2•IIIAvsIIIB•CRvsnon-CRInclusionat

baseline•UnresectablestageIIIAorIIIBNSCLC•ECOGPS0-1atstudyentry(+PS2atrandom)•FEV-1>1literatstudyentry203patients147patients73p

atients74patientsTaxotere75mg/m2q3wk3ObservationPrimaryendpoint:OSSecondaryendpoints:PFS,toxicity2020/11/1457HOGL

UN01-24:OS(ITT)RandomizedPatients(n=147)Hannaetal.ASCO2007:Abstract7512.MonthsSinceRegistration0102030405060

Percentofpatientssurviving0%25%50%75%100%P-value:0.940Median3yearsurvivalrateObservation18.0-34.227.6%Taxotere17-34.827.2%2020/1

1/1458ComparisonofGrade3-5ToxicitiesToxicitySWOG9504SWOG0023HOG01-24FebrileNeutropenia⚫PE/XRT⚫DocetaxelNR9%~5%*~5%*9.

9%10.9%Esophagitis17%~14%17.2%Pneumonitis7%7%8.2%Docetaxel-relateddeath4.8%4%5.5%*reportedas“infectionwithneutropenia”2020/11/1459HogLU

GNo1-20/USO-023➢TheMSTwithEP/XRTwashigherthanhistoricalcontrols;➢ConsolidationDdoesnotfurtherimprovesurvival,isassociatedwit

hsignificanttoxicityincludinganincreasedrateofhospitalizationandprematuredeath,➢AndshouldnolongerbeusedforptswithunresectablestageIIINSCLCC

onclusions2020/11/1460术前同时化放疗的临床研究2020/11/1461可手术(Operable)ⅢA(N2)放/化疗vs放化疗+手术RTOG93-09INT:01392020/11/1462C

T/RT/S145/202CT/RT155/194Logrankp=0.24危险比=0.87(0.70,1.10)存活率%0255075100从随机分组开始后的月数01224364860死亡/总数INT0139试验:总生存中位FU81个月Alba

inetal.ASCO2005.Abstract7014.2020/11/1463随机分组后的月数MS3yrOS5yrOS19月36%22%CT/RT/SCT/RT存活率%025507510001224364860//////////29月45%24%死亡/总计CT/RT

/S38/51CT/RT42/51Logrankp=NSINT0139试验:肺切除亚组和相应化疗/放疗亚组的总生存的比较Albainetal.ASCO2005.Abstract7014.2020/11/1

464Logrankp=0.002CT/RT/S57/90CT/RT74/90死亡/总计存活率%0255075100随机分组后的月数01224364860///////////////////////MS34月

22月5yrOS36%18%CT/RT/SCT/RTINT0139试验:肺叶切除亚组和相应化疗/放疗亚组的总生存的比较Albainetal.ASCO2005.Abstract7014.2020/11/14

652020/11/1466EORTC08941ⅢA:UnresectablepN2不能手术的ⅢApN2病例通过诱导化疗后成为可手术病例是选择手术还是选择放疗?2020/11/14672020/11/14682020/11/14692020/11/14702020/11/147

1四、NSCLC术后放射治疗NewdatasupportsPORTinN2cases2020/11/14721998PORT⚫死亡风险增加21%⚫2年OS下降7%55%----48%⚫pN0pN1有害⚫pN2降低局部复发对OS无明确结论PORTMeta-analysisLa

ncet,1998.352:257-63UpdateofPORTLungCancer,2005.47:81-32020/11/1473NewData1回顾分析PORT➢SEER1988年~2001年Ⅱ、Ⅲ期NS

CLC7465例➢根治性术后PORT3508例(47%)SEERJClinOncol,2006.24:2998-3006预后-多因素分析HR95%CIPolderage1.0251.022-1.0280.0001T3-4disease1.2881.117-1

.4840.0005N2nodaldisease1.2811.101-1.4900.0014greaternumberofinvolvedlymphnodes1.0431.027-1.0600.0001PORT1.0480.987-1.1130.12692020/11/1474PORT在N2中的

作用N0N1N2SSRSSRSSR5yOS41%31%34%30%20%27%DSS53%39%44%38%27%36%P0.04350.01960.0077PORT既能够提高OS也能够提高DSSN0N1N22020/11/147

5NewData2ResultsfromANITA:PhaseIIIAdjuvantVinorelbineandCisplatinversusObservationinCompletelyResectedNon-Smal

l-CellLungCancerPatientsRRosell,MDeLena,FCarpagnano,RRamlau,JLGonzalez-Larriba,TGrodzki,ALeGroumelec,DAubert,JGasmi,JYDouil

lardonbehalfoftheAdjuvantNavelbineInternationalTrialAssociation2020/11/1476Seq=1LYMPHNODE=N10.000.250.500.751.00DURATIONOFSURVIVAL(

MONTHS)020406080100120STRATA:IA37_1=IVVRL+CDDPradio=NOCensoredIA37_1=IVVRL+CDDPradio=NOIA37_1=IVVRL+CD

DPradio=YESCensoredIA37_1=IVVRL+CDDPradio=YESIA37_1=NOCTradio=NOCTRTCTRTOBSPORTinN1PatientsRTisbetterthanOBS.Forp

atientwhocannottolerateCT,RTwouldberecommended.2020/11/1477CTRTCTRTOBSPORTinN2Patients0.000.250.500.751.00DURATIONOF

SURVIVAL(MONTHS)020406080100120CT&RTisthebestRTisbetterthanOBS2020/11/1478NewData3fromCancerHospital&InstituteofCAM

S✓2003.01.01-2005.12.30✓根治性切除NSCLC✓T1-3,N2✓具备完整治疗信息–一般临床资料–术中所见及术后病理–治疗模式及参数–随访资料2020/11/1479材料与方法——排除标准T4N2者pN3病例及N分期不明者

手术后3个月内死亡的患者手术后3个月内肿瘤进展者单纯探查术或纵隔镜活检术2020/11/1480材料与方法全组例数PORT无PORT术式肺叶切除19784113全肺切除241212清扫淋巴结数目总数(枚

)1-603-601-60中位数(枚)2119222020/11/1481OS例数MST(月)1年3年5年χ2P值无PORT12531.977.645.430.65.2350.046PORT9643.994.859.134.

301224364860728496020406080100NOPORTPORTχ2=5.235P=0.046时间(月)生存率(%)生存率2020/11/1482DFS1年3年5年χ2P值无PORT56.428.216.56.8910.009PORT

76.139.832.1DFS01224364860728496020406080100NOPORTPORTχ2=6.891P=0.009时间(月)无病生存率(%)2020/11/1483治疗模式与生存率01224364860728496020406080100S+C+RS+RS+CS时间(月)

生存率(%)项目例数MST(月)1年OS3年OS5年OSS+C+R6148.396.7%63.9%38.2%S+R3538.391.4%51.0%33.7%S+C10033.182.0%46.7%31.9%S2521.661.5%38.5%23.1%2020/11/1484非肿瘤死

亡项目例数无术后放疗术后放疗组心功能衰竭10心肌梗死10小脑萎缩10急性胰腺炎10脓胸10脑血管意外11肺部感染21气管食管瘘01肺栓塞01不明原因消瘦01死亡原因不明22合计107◆有无术后放疗组的非肿瘤死亡率并无差异

(p=0.493)2020/11/1485S+C+RS+CS+RS5yOS47.0%34.0%21.3%16.6%01224364860728496020406080100S+C+RS+RS+CS时间(月)生存率(%)5yOS38.2%31.

9%33.7%23.1%MST(M)47.423.822.712.7MST(M)48.333.138.321.6ANITA的结果医科院肿瘤医院的结果完全切除的ⅢAN2NCSLC推荐术后化疗+放疗2020/11/14861.00.80.60.40.20.01-S

pecificity1.00.80.60.40.20.0SensitivityAbsoluteVolumeoflungreceived30GyRP(%)≥340cm329.2(7/24)<340cm32.5(1/40)PORTcanbesafel

yusedwith3DCRTJiWeietal:ASTROmeeting2008BostonConclusion:ItwassafeforpatientswithNSCLCtoreceivepostoperative3DCRT,ifirr

adiationdosetolungtissuewaswelldefined.2020/11/14873DCRT能够提高NSCLC的治疗疗效2020/11/1488Int.J.RadiationOncologyBiol

.Phys.,Vol.66,No.1,pp.108–116,20063Dvs2DinMEDICALLYINOPERABLESTAGEINON–SMALL-CELLLUNGCANCER(a)Overallsurvival(b)Disease-

specificsurvival2020/11/1489Int.J.RadiationOncologyBiol.Phys.,Vol.66,No.1,pp.108–116,20063Dvs2DinMEDICALLYINOPERABLESTAGEINON–SMALL-CELLLUNGCA

NCERLocal-regionalcontrol2020/11/14903DCRTvs常规放疗中国医学科学院肿瘤医院2001-20062020/11/1491ⅠⅡ期NSCLC适形放疗vs常规放疗202

0/11/1492局部晚期NSCLC(ⅢA/B)3DCRTvs常规放疗012243648607284961081200204060801003-D2-DP=0.002MonthsOS(%)分组例数1年3年5年MST常规放疗27561.013.88

.015.63-DCRT21873.326.114.420.15年OS6.4%MST4.5月2020/11/1493局部晚期NSCLC(ⅢA/B)3DCRTvs常规放疗01224364860728496108120020406080100

3-D2-DP=0.000MonthsCSS(%)分组例数1年3年5年常规放疗27565.116.711.23-DCRT21879.033.320.82020/11/1494OS单因素及多因素COX分析变量

单因素多因素危险比P值危险比P值<70vs≥70岁1.0350.744------------女性vs男性1.0750.552------------体重下降(<5%vs≥5%)1.1220.370---

---------吸烟(无vs有)1.0740.522------------KPS(≥80vs<80)1.6710.0001.5630.001IIIavsIIIb1.2640.0311.2160.089非鳞癌vs鳞癌1.0510.619---

---------Hb(≥120vs<120g/L)1.6250.0001.4220.008化学治疗(无vs有)0.8660.138------------50-60vs60vs>60Gy0.7850.0010.8520.046常规放疗vs三维适形0.7370.0020.7620.009CR+

PRvsSD+PD1.6070.0001.5710.0012020/11/1495局部晚期NSCLC(ⅢA/B)3DCRTvs常规放疗2D3DX2P值例数(比例%)例数(比例%)食管炎<2级135(61.9)180(65.5)0.6560.450

≥2疾83(38.1)95(34.5)放射性肺炎<2级148(67.9)202(73.5)1.8290.194≥2疾70(32.1)73(26.5)食管炎<3级207(95.0)264(96.0)0.3120.662≥3疾11(5.0)11(4.0)放射性

肺炎<3级192(88.5)251(91.3)1.0550.363≥3疾25(11.5)24(8.7)2020/11/1496结论➢与常规放射治疗技术相比3DCRT能够提高NSCLC的生存率➢推荐3DCRT作为非小细胞肺癌的标准治疗技术2020/11/1497Thre

eClinicalResearchTopicsinRadiotherapyofLocallyAdvancedNSCLC1、CombinedTreatment:ConcurrentChemoradiotherapy

✓同时放化疗中化疗方案的选择✓诱导化疗或巩固化疗的必要性和化疗方案✓放射治疗与生物靶向治疗的联合应用2020/11/1498ThreeClinicalResearchTopicsinRadiotherapyofLocallyAdvancedNSCLC2、NewRadiat

ionTechniques:3DRT,IMRT,IGRT,4DRT3、NormalTissueProtection:RadiationPneumonitisandEsophagitis2020/11/1499谢谢2020/11/14100谢谢

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