NSCLC 同步放化進(jìn)展 01

局部晚期非小細(xì)胞肺癌的同步放化療進(jìn)展中國(guó)醫(yī)學(xué)科學(xué)院北京協(xié)和醫(yī)學(xué)院腫瘤醫(yī)院王綠化2同步放化療治療模式的確立誘導(dǎo)化療、鞏固化療的作用同步放化療中化療方案的選擇同步放化療聯(lián)合靶向治療同步放化療中不同放療劑量和照射技術(shù)研究同步放化療與放射性肺炎3一、同期放化療是局部晚期NSCLC的標(biāo)準(zhǔn)治療序貫放化療VS.單純放療序貫放化療VS.同步放化療局部晚期不可切除NSCLC

FavorGrHRbenefit(%)OS(%)

2y5y2y5yChemo0.9032R+DDP0.8742151957

p=0.005

DDP40-120mg/m2/cycle,totaldose120-800mg/m2

radiationdose50Gy/20f-65Gy/30f結(jié)論：序貫放化療優(yōu)于單純放射治療薈萃（META）分析：22trails3033cases序貫化放療VS.單純放療序貫化放療VS.同步放化療

序貫:PV-->RT(60Gy,2GyQD)day50

同步:PV/RT(60Gy,2GyQD)day1

同步/HFRT:PE/HFRT(69.2Gy,1.2GyBID)day1 PV:順鉑/長(zhǎng)春花堿

PE:順鉑/oral足葉乙甙

RT:放療;QD:每日一次;HFRT:超分隔放療Curran:ASCO,2000;updatedIASLC2000;ASTRO2001,2003RANDOMIZERTOG9410:III期NSCLCSeqCon-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統(tǒng)毒性：

30%，48%，62%和14%，15%，16%。CurranWetal.Pro.AmSocClinOncol.J.Clin.Oncol.2003;(abstract2499)

RTOG9410:III期NSCLC序貫化放療VS.同步放化療小結(jié)同步放化療優(yōu)于序貫放化療急性反應(yīng)增加二、誘導(dǎo)化療、鞏固化療的作用InductionChemotherapyFollowedbyChemoradiotherapyWithChemoradiotherapyAloneforRegionallyAdvanced

UnresectableStageIIINSCLC

Lung:CancerandLeukemiaGroupB

CALGB39801JClinOncol.2007May1;25(13):1698-704.Epub2007Apr誘導(dǎo)化療+同步放化療VS.同步放化療CALGB39801studydesignJuly1998andwasclosedinMay2002,Totally366patientsregisteredSurvival

intent

to

treatSurvivalofeligiblepatientswitha

weightlossof≤5%Discussion

增加毒性inductionchemotherapyincreasesneutropeniaandoverallmaximaltoxicity

沒(méi)有生存優(yōu)勢(shì)

Nosurvivalbenefitoverconcurrenttherapyalone同期放化療是標(biāo)準(zhǔn)的治療模式

ConcomitantchemoradiotherapyiscurrentstandardtherapyforunresectablestageIIIBNSCLCSWOG9504同步放化療+鞏固化療VS.同步放化療順鉑/VP-16 X XRT泰索帝

XXX

順鉑50mg/m2d1,8,29,36VP-1650mg/m2d1-5,29-33RT:61Gy45Gy(1.8Gy/fx)+16Gy縮野(2Gy/fx)泰索帝:75mg/m2cycle1-->100mg/m2cycle2-3

泰索帝鞏固化療治療IIIb期NSCLC%%%%%020406080100%012243648入組時(shí)間（月）

NEvents 中位生存83 45 26月2年生存率:54%3年生存率:37%SWOG9504:總生存-Promising

SWOG9504和SWOG9019比較研究病例MST(月)2年生存3年生存S9019(PE/RTPE)5015(10-22)*

34%(21-47)*17%(7-27)*S9504(PE/RT泰索帝)8326(18-35)*54%(43-65)*37%(22-52)**95%CIHannaetal.ASCO2007:Abstract7512.ChemoRTCisplatin50mg/m2IVd1,8,29,36

Etoposide50mg/m2IVd1-5&29-33

ConcurrentRT59.4Gy(1.8Gy/fr)Stratification

atrandomization

PS0-1vs2IIIAvsIIIBCRvsnon-CR

InclusionatbaselineUnresectablestageIIIAorIIIB

NSCLCECOGPS0-1atstudyentry

(+PS2atrandom)FEV-1>1literatstudyentry203patients147patients73patients74patientsTaxotere

75mg/m2q3wk3ObservationPrimaryendpoint:OSSecondaryendpoints:PFS,toxicityHOGLUN01-24同步放化療+鞏固化療VS.同步放化療HOGLUN01-24:OS(ITT)

RandomizedPatients(n=147)Hannaetal.ASCO2007:Abstract7512.MonthsSinceRegistration0102030405060Percentofpatientssurviving0%25%50%75%100%P-value:0.940Median3year

survivalrateObservation18.0-34.227.6%Taxotere17-34.827.2%ComparisonofGrade3-5ToxicitiesToxicitySWOG9504SWOG0023HOG01-24FebrileNeutropenia

PE/XRT

Docetaxel

NR9%~5%*~5%*9.9%10.9%Esophagitis17%~14%17.2%Pneumonitis7%7%8.2%Docetaxel-relateddeath4.8%4%5.5%*reportedas“infectionwithneutropenia”

HOGLUN01-24TheMSTwithEP/XRTwashigherthanhistoricalcontrolsConsolidationDdoesnotfurtherimprovesurvivalAssociatedwithsignificanttoxicityincludinganincreasedrateofhospitalizationandprematuredeathAndshouldnolongerbeusedforptswithunresectablestageIIINSCLCConclusionsGermanIntergroupLungTrialgroup（GILT）

口服長(zhǎng)春瑞濱+順鉑聯(lián)合同步放療后鞏固治療III期NSCLC的III期臨床研究

HuberRM,etal.2012ASCOAbstract7001.鞏固治療：口服長(zhǎng)春瑞濱+順鉑+bestsupportivecare(BSC)VS.BSCGILT：研究設(shè)計(jì)HuberRM,etal.2012ASCOAbstract7001.主要終點(diǎn)：PFS根據(jù)分期分層口服長(zhǎng)春瑞濱60mg/m2d1,8;80mg/m2d22,29+順鉑80mg/m2d1,d22;q3w×2+BSC(n=96，76例可評(píng)估)RBSC(n=105,89例可評(píng)估)CR/PR/SDN=201口服長(zhǎng)春瑞濱50mg/m2d1,8,15+順鉑20mg/m2d1-4;q4w×2放療化療第一天起開始2Gy/d×6.5w；至少66Gy+GILT：基線特征HuberRM,etal.2012ASCOAbstract7001.隨機(jī)化(N=201)CT-RTN=可評(píng)估242/279CT+BSCN=可評(píng)估76/96BSCN=可評(píng)估89/105男性(%)71.071.971.4中位年齡[歲，范圍]60.3[33.9-75.7]60.3[34.1-75.9]59.5[40.4-75.1]中位KPS(%)(范圍)90(80-100)90(50-100)90(70-100)鱗癌/腺癌/大細(xì)胞癌/NOS(%)53.0/36.2/6.8/5.054.2/36.5/7.3/2.152.4/37.1/7.6/3.9IIIA期/IIIB期(%)17.6/82.420.8/79.219.0/81.0合并疾?。?/1/2/3(%)17.6/37.3/36.9/8.220.8/41.7/30.2/7.319.0/33.3/40.0/7.6GILT：研究結(jié)果–療效HuberRM,etal.2012ASCOAbstract7001.CT+BSCN=可評(píng)估76/96BSCN=可評(píng)估89/105PORRITT95%CI(%)29.2[20.4-39.4]24.8[16.8-34.2]0.48

鱗癌/腺癌34.6/25.723.6/28.9IIIA/IIIB20.0/31.630.0/23.5

體重減輕>5%：是/否16.7/36.729.3/21.9ORR評(píng)估95%CI(%)36.8[26.0-48.6]29.2[20.0-39.8]0.30DCRITT(%)66.7[56.3-76.0]56.2[46.2-65.9]0.12DCR可評(píng)估患者(%)84.2[74.0-91.6]66.3[55.4-76.0]0.0084注冊(cè)-隨機(jī)中位時(shí)間(月)3.02.9中位PFS(月）6.4[5.0-8.7]5.5[3.8-7.4]0.63*OR/SD6.6/6.45.8/4.4中位OS(月)20.8[13.5-25.3]18.5[13.6-24.7]0.872/4年生存(%)41.6/25.241.1/21.4*HR=0.93;95%CI=0.69-1.26DCR:diseasecontrolrateGILT：研究結(jié)果–PFS與OSPFSOSPFS00.20.01.0204060CT+BSC(n=96)：中位6.4個(gè)月BSC(n=105)：中位5.5個(gè)月OS00.20.01.0204060時(shí)間(月)時(shí)間(月)CT+BSC(n=96)：中位20.8個(gè)月BSC(n=105)：中位18.5個(gè)月HuberRM,etal.2012ASCOAbstract7001.GILT：研究結(jié)果–3/4級(jí)毒性HuberRM,etal.2012ASCOAbstract7001.同步放化療化療鞏固BSC鞏固3/4級(jí)貧血(%)3/4級(jí)白細(xì)胞減少(%)18.326.7-3/4級(jí)中性粒細(xì)胞減少(%)11.222.1-3/4級(jí)血小板減少(%)2.51.2-3/4級(jí)發(fā)熱性中性粒細(xì)胞減少(%)1.41.0-3級(jí)惡心(%)5.02.3-3級(jí)嘔吐(%)3.23.5-3級(jí)厭食(%)3.6--3級(jí)肺炎(%)2.6-2.0GILT：研究結(jié)論同步口服長(zhǎng)春瑞濱與順鉑聯(lián)合放療后行鞏固治療高度有效毒性較低，是不可切除III期NSCLC的有效治療選擇放化療階段：ORR55.6%，DCR78.5%(ITT)毒性資料與其他方案相比有優(yōu)勢(shì)口服長(zhǎng)春瑞濱可能減少放化療期間計(jì)劃中的約束長(zhǎng)春瑞濱聯(lián)合順鉑鞏固治療顯著提高DCR(P=0.0084)延長(zhǎng)放化療后SD患者的PFS在未經(jīng)選擇患者中，沒(méi)有顯著的生存獲益總生存期與既往公布的結(jié)果一致HuberRM,etal.2012ASCOAbstract7001.局部晚期NSCLC同步放化療后鞏固化療能否帶來(lái)獲益？

MetaanalysisYamamotoS,etal.2012ASCOAbstract7000.研究方法與結(jié)果研究方法：Pubmed檢索1995年1月1日-2011年10月31日上發(fā)表的評(píng)價(jià)同步放化療治療局部晚期NSCLC生存的II/III期試驗(yàn)研究結(jié)果：共檢索到41項(xiàng)研究：III期研究7項(xiàng)；II期研究34項(xiàng)；共45組有鞏固化療25組(N=1707)；無(wú)鞏固化療20組(N=1740)兩組臨床分期、體力狀態(tài)、組織學(xué)類型、性別、中位年齡可比YamamotoS,etal.2012ASCOAbstract7000.研究結(jié)果：中位OSYamamotoS,etal.2012ASCOAbstract7000.CCT-:無(wú)鞏固化療CCT+:有鞏固化療亞組分析：

有鞏固化療vs.無(wú)鞏固化療HR(95%CI)鞏固化療更好無(wú)鞏固化療更好10.52HR(95%CI)P階段地區(qū)臨床研究總計(jì)0.98(0.84-1.13)0.7571995-20002001-20052006-2011亞洲非亞洲II期III期1.15(0.82-1.60)0.4280.96(0.72-1.29)0.7910.91(0.68-1.22)0.5430.84(0.68-1.04)0.1051.01(0.83-1.24)0.8911.03(0.84-1.26)0.8020.94(0.77-1.16)0.566YamamotoS,etal.2012ASCOAbstract7000.研究結(jié)果：毒性3-5級(jí)毒性無(wú)鞏固化療有鞏固化療P平均數(shù)標(biāo)準(zhǔn)差平均數(shù)標(biāo)準(zhǔn)差中性粒細(xì)胞減少(%)50.5028.4145.3624.410.634白細(xì)胞減少(%)58.1033.1254.7022.400.743食管炎(%)14.7914.6815.9712.170.776肺炎(%)7.976.937.0567.300.674治療相關(guān)死亡(%)2.302.041.962.680.628YamamotoS,etal.2012ASCOAbstract7000.討論與結(jié)論本項(xiàng)基于發(fā)表文獻(xiàn)的匯總分析未能證明鞏固化療能夠改善局部晚期NSCLC的總生存除了臨床研究外，不應(yīng)推薦同步放化療后的鞏固化療整個(gè)治療過(guò)程中兩組的毒性可比，可能的解釋是實(shí)際鞏固化療的周期數(shù)低于預(yù)計(jì)根據(jù)基因改變，將分子靶向治療結(jié)合到該治療模式中可能是未來(lái)臨床研究的方向需要評(píng)估鞏固化療影響的臨床研究YamamotoS,etal.2012ASCOAbstract7000.小結(jié)同步放化療基礎(chǔ)上的誘導(dǎo)化療、鞏固化療沒(méi)有明顯增加療效除臨床研究外，不應(yīng)常規(guī)使用三、同步放化療中化療方案的選擇Cisplatin/etoposide(EP)vs.weeklypaclitaxol/carboplatin(PC)withradiotherapyforpatientswithlocallyadvancedNSCLCPhaseIIstudyOralpresentationinASTRO2010LungCancer77(2012)89–96TreatmentDesignLegend:ChemotherapyEPCisplatin:50mg/m2,day1,8,29,36VP-16:50mg/m2,day1to5and29to33PC(day1,8,15,22,28)CarboplatinAUC2Paclitaxol45mg/m2ConsolidationtreatmentOverallsurvivalEPPC1yrOS65.6%54.5%2yrOS36.4%16.2%3yrOS33.1%13%MST(m)20.2m13.5mP=0.037EParmPCarmProgressFreeSurvivalP=0.14EParmPCarmEPPC1yrOS46.9%42.4%2yrOS21.9%13.6%3yrOS21.9%10.2%MST(m)11.7m10.6mTreatment-relatedtoxicitiesPEPCPValueNeutropeniaGrade1and27(25%)16(48.5%)Grade3and425(78.1%)17(51.5%)0.05HemoglobinGrade1and228(87.5%)29(87.9%)Grade3and44(12.5%)4(12.1%)0.74PLTGrade1and227(84.4%)29(87.9%)Grade3and45(15.6%)4(12.1%)0.26EsophagitisGrade1and220(62.5%)20(60.1%)Grade3and412(37.5%)13(39.9%)0.94RadiationpneumonitisGrade0，124(75%)17(51.5%)Grade≥28(25%)16(48.5%)0.09ConclusionThistrialshowsAfavorablesurvivalAdifferenttoxicityprofileofthePE-basedCRTprogramcomparingtothatofweeklyPC-basedCRTprogram培美曲塞與卡鉑或順鉑聯(lián)合同步放療后以培美曲塞鞏固治療預(yù)后良好的不可手術(shù)IIIA/B期NSCLC患者的II期研究ChoyH,etal.2012ASCOAbstract7002.培美曲塞+順鉑同步放化療VS.培美曲塞+卡鉑同步放化療研究設(shè)計(jì)ChoyH,etal.2012ASCOAbstract7002.IIIA/B期NSCLC所有組織學(xué)類型N-=98培美曲塞500mg/m2+順鉑75mg/m2;q3w×3+放療64-68Gy(2Gy/d,5d/wd1-45)R培美曲塞500mg/m2+卡鉑AUC5;q3w×3+放療64-68Gy(2Gy/d,5d/wd1-45)鞏固治療培美曲塞500mg/m2q21d×3放化療結(jié)束3周后主要終點(diǎn)：2年OS率次要終點(diǎn)：OSTTPORR毒性研究結(jié)果：劑量與療效卡鉑組(n=46)順鉑組(n=52)平均給藥依從性培美曲塞(%)95.789.7鉑類(%)97.189.1放化療平均給藥依從性(%)95.788.1放化療劑量中斷發(fā)生率(%)32.640.42年OS(%)(主要終點(diǎn))45.257.6*中位OS(月)18.727.0中位TTP(月)8.813.1**ORR(%)52.246.2CR(%)6.53.8PR(%)45.742.3ChoyH,etal.2012ASCOAbstract7002.*P=0.270;**P=0.057研究結(jié)果：4級(jí)毒性卡鉑組(n=46)順鉑組(n=52)貧血(%)01.9中性粒細(xì)胞減少(%)6.53.8血小板減少(%)4.31.9食管炎(%)01.9ChoyH,etal.2012ASCOAbstract7002.沒(méi)有發(fā)生藥物相關(guān)死亡本研究提示培美曲塞聯(lián)合順鉑的OS與TTP有優(yōu)勢(shì)兩種同步放化療方案的耐受性都較好研究結(jié)論：比較標(biāo)準(zhǔn)胸部放療聯(lián)合或不聯(lián)合每日

低劑量卡鉑同步治療老年局部晚期NSCLC的III期研究的更新結(jié)果：JCOG0301OkamotoH,etal.2012ASCOAbstract7017.LancetOncol2012May21老年局部晚期NSCLC：RTVS.RT+卡鉑同步放化療JCOG0301：研究設(shè)計(jì)III期NSCLC年齡>70歲不可切除N=200CRT(n=100)：RT+同步卡鉑30mg/m2/d，5d/w×20dRRT(60Gy)(n=100)主要終點(diǎn)：OS期望中位OS從RT組的10個(gè)月提高到CRT組的15個(gè)月（計(jì)劃樣本量?jī)山M各100例，一側(cè)α值為5%，把握度80%）基線特征RTCRT中位年齡(歲)7777IIIB期(n)4649PS0/1/2(n)41/55/441/56/3OkamotoH,etal.2012ASCOAbstract7017.LancetOncol2012May21JCOG0301：OS(主要終點(diǎn))OkamotoH,etal.2012ASCOAbstract7017.中位OS(月)HR=0.6495%CI=0.46-0.89p(onesided)=0.0033研究結(jié)果：3年生存率2年生存率(%)P=0.0033OkamotoH,etal.2012ASCOAbstract7017.研究結(jié)果：ORRORR(%)P=0.201OkamotoH,etal.2012ASCOAbstract7017.研究結(jié)果：PFS中位PFS(月)P=0.003OkamotoH,etal.2012ASCOAbstract7017.研究結(jié)果：3/4級(jí)不良事件OkamotoH,etal.2012ASCOAbstract7017.RTCRT中性粒細(xì)胞減少(%)057.3感染(%)4.112.5吞咽困難(%)01.0遲發(fā)性放療毒性(%)7.47.5兩組間復(fù)發(fā)部位與方案制定后的治療情況相似通過(guò)Cox回歸分析對(duì)6個(gè)變量(分期、PS、性別、年齡、組織學(xué)、吸煙狀態(tài))調(diào)整后，CRT組仍顯示出更好的生存(HR=0.71;P=0.038)研究結(jié)論：每日卡鉑的同步放化療是老年局部晚期NSCLC的標(biāo)準(zhǔn)治療局部晚期NSCLC同步放化療選用多西他賽+鉑類每周方案與三周方案的比較：隨機(jī)Ⅱ期臨床研究ASTR02013目的：比較CCRT中使用多西他賽+鉑類每周與三周方案的療效及毒性研究方案治療及毒性3度RE2-3度RP3-4度WBC↓RR1y-OS2y-OS3y-OS每周方案組54673.3%96%54.9%43.9%三周方案組3101366.7%80%49.4%21.9%是否有統(tǒng)差有有有無(wú)無(wú)無(wú)無(wú)結(jié)論在局部晚期的NSCLC行同步放化療的病例中化療方案選擇多西他賽+鉑類時(shí)，每周方案較三周方案更加安全但需要進(jìn)一步開展相關(guān)研究FinaloverallsurvivalresultsofthephaseIIIPROCLAIMtrial:Pemetrexed,cisplatinoretoposide,cisplatinplusthoracicradiationtherapyfollowedbyconsolidationcytotoxicchemotherapyinlocallyadvancednonsquamousnon-smallcelllungcancerPresentedBySureshSenanat2015ASCOAnnualMeetingPROCLAIM:BackgroundPresentedBySureshSenanat2015ASCOAnnualMeetingPROCLAIM:StudyDesignPresentedBySureshSenanat2015ASCOAnnualMeetingSlide4PresentedBySureshSenanat2015ASCOAnnualMeetingPROCLAIM:StudyDesignPresentedBySureshSenanat2015ASCOAnnualMeetingSlide6PresentedBySureshSenanat2015ASCOAnnualMeetingPROCLAIM:ConsortDiagramPresentedBySureshSenanat2015ASCOAnnualMeetingSlide8PresentedBySureshSenanat2015ASCOAnnualMeetingSlide9PresentedBySureshSenanat2015ASCOAnnualMeetingSlide10PresentedBySureshSenanat2015ASCOAnnualMeetingSlide11PresentedBySureshSenanat2015ASCOAnnualMeetingSlide12PresentedBySureshSenanat2015ASCOAnnualMeetingPROCLAIM:PFSPresentedBySureshSenanat2015ASCOAnnualMeetingSlide14PresentedBySureshSenanat2015ASCOAnnualMeetingSlide15PresentedBySureshSenanat2015ASCOAnnualMeetingSlide16PresentedBySureshSenanat2015ASCOAnnualMeetingSlide17PresentedBySureshSenanat2015ASCOAnnualMeetingSlide18PresentedBySureshSenanat2015ASCOAnnualMeetingSlide19PresentedBySureshSenanat2015ASCOAnnualMeetingSlide20PresentedBySureshSenanat2015ASCOAnnualMeetingSlide21PresentedBySureshSenanat2015ASCOAnnualMeetingSlide22PresentedBySureshSenanat2015ASCOAnnualMeeting四、同步放化療聯(lián)合分子靶向治療RTOG0617

AnintergrouprandomizedphaseIIIcomparisonof

standarddose(60Gy)VS.highdose(74Gy)chemoradiotherapy

+/-cetuximabforunresectable

stageIIINSCLC同步放化療不同照射劑量聯(lián)合或不聯(lián)合西妥昔單抗的比較StudyDesignRTOG0617Treatment-relatedAdverseEventsSurvival(Cetuximab)ProgressionFreeSurvivalOverallSurvivalEGFRH-ScoreanalysisIHCanalysisoftumorEGFRbyH-scoremayhelpselectforsensitivitytocetuximabasshowninananalysisoftheFLEXtrialinstageIV203(43.7%)oftumorswereavailableforEGFRH-Scoreanalysis(high≥200VS.low＜200）

ConclusionsCetuximabdidnotimproveOSorPFSwhenaddedtostandardchemoradiotheraptCetuximabincreasedoverallgrade3-5toxicitiesandgrade3-5non-hemetoxicitiesCetuximabmayhaveamorebeneficialeffectinpatientswithhigh-EGFRexpressionRandomizedPhaseIIStudyofPemetrexed,Carboplatin,andThoracicRadiationWithorWithoutCetuximabinPatientsWith

LocallyAdvancedUnresectableNSCLCCALGB：30407培美曲塞+卡鉑同步放化療VS.培美曲塞+卡鉑同步放化療+西妥昔靶向治療Govindan,etal.2011.JCO,29(23).StudyDesignResultsofTreatmentOSPFS≥III度不良反應(yīng)治療相關(guān)死亡同步放化組：2例

（放射性肺炎，肺出血各1例）靶向組：3例（放射性肺炎2例，肺栓塞1例）結(jié)論西妥昔聯(lián)合同步放化療未增加總生存率西妥昔組總體不良反應(yīng)發(fā)生率高該研究的OS比其他研究高，可能與放療劑量高或新的化療方案（培美曲塞）有關(guān)需RTOG0617進(jìn)一步闡明西妥昔的作用同步放化療聯(lián)合西妥昔單抗的

II期研究有著較好的中位生存和總生存結(jié)果需進(jìn)一步驗(yàn)證同步放化療聯(lián)合EGFR-TKI的

I/II期研究中位生存不高，TKI對(duì)EGFR突變型患者可能更有效TKI可能使EGFR野生型細(xì)胞停止在G1期，導(dǎo)致對(duì)化療敏感性下降放化療聯(lián)合抗血管生成藥物的研究ECOG3858：紫杉醇+卡鉑序貫化放療VS.紫杉醇+卡鉑同步放化療±thalidomidePC+RT/CRTPC+CRT+thalidomide中位OS(mon)15.316PFS(mon)7.47.8Thromboembolicevents3%11%(p＜0.001)Hang,etal,2012,JCO血管生成抑制劑未提高生存，增加了血栓風(fēng)險(xiǎn)貝伐單抗增加了氣管食管瘺風(fēng)險(xiǎn)紫杉醇+卡鉑聯(lián)合貝伐單抗同步放化療II期臨床研究III期NSCLC:2/8發(fā)生了氣管食管瘺；研究提前終止Spigel,etal,2010,JCO小結(jié)同步放化療聯(lián)合靶向治療沒(méi)有明顯增加療效除臨床研究外，不應(yīng)常規(guī)使用五、同步放化療中不同放療劑量和照射技術(shù)的研究RTOG0617

AnintergrouprandomizedphaseIIIcomparisonof

standarddose(60Gy)VS.highdose(74Gy)chemoradiotherapy

+/-cetuximabforunresectable

stageIIINSCLC同步放化療不同照射劑量聯(lián)合或不聯(lián)合西妥昔單抗的比較RTOG0617：TrialDesignSurvivalbydoseOverallSurvivalLocalfailurerateDistantfailureTreatment-relatedAdverseEventsConclusion74Gy比60Gy有著更差的生存和局控原因需要進(jìn)一步分析：劑量學(xué)因素；治療抗拒；生活質(zhì)量評(píng)分表分析該研究結(jié)果支持開展更多的劑量/體積方面的研究留下一連串的問(wèn)題？？？？HyperfractionatedorAcceleratedRadiotherapyinLungCancer:

AnIndividualPatientData

Meta-Analysis不同劑量分割模式放療的薈萃分析Mauguen,etal,2012,JCOSelectionCriteriaNonmetastaticNSCLCTrialscomparemodifiedRT(accelerated,hyperfractionated,orboth)withconventionalRTTrialsbetween1970.1~2005.12ChemotherapyscheduleanddoseswerethesameintwoarmsNSCLCtrialsEachtrialdatabasewascheckedandcollected10trialsincludedMedianfollow-up:6.9yearRiskofdeathwassignificantlyreducedby12%withtheuseofmodifiedRT.(HR0.88;95%CI,0.80to0.97;P.009)EffectofmodifiedRTonsurvivalModifiedRThadabettersurvivalModifiedRThadalower

failureanddeathToxicities六、同步放化療與放射性肺炎R(shí)eceivedMar8,2012,andinrevisedformApr19,2012.AcceptedforpublicationApr29,2012PredictingRadiationPneumonitis

afterChemoradiationTherapyforLungcancer:

AnInternationalIndividualPatientDataMeta-analysis化療方案，V20是放射性肺炎獨(dú)立的相關(guān)因素ConclusionPneumonitisriskisassociatedwiththetypeofchemotherapyregimen,dosimetricparameters,andpatientage.Fatalpneumonitisisassociatedwithlargedosesperfraction,largeV20,andlower-lobetumors.Furtherresearchisneededtoevaluatemethodstomitigatepneumonitisriskinpatientsundergoingcurative-intentCCRT.PoorBaselinePulmonaryFunctionMayNotIncreasetheRisk