直腸癌新輔助

直腸癌中保留直腸的治療應(yīng)用及爭議進(jìn)展期直腸癌規(guī)范治療模式放療/化療/放化療局部控制新輔助治療TME手術(shù)輔助化療腫瘤降期cCR(pCR)完全消退—等待&觀察療效評估時間方法療效預(yù)測失敗–復(fù)發(fā)如何提高cCR延長間期間期化療提高治療強(qiáng)度完全消退—等待&觀察療效評估時間方法療效預(yù)測失敗–復(fù)發(fā)如何提高cCR延長間期間期化療提高治療強(qiáng)度評估：退縮時間127完全消退—等待&觀察療效評估時間方法療效預(yù)測失敗–復(fù)發(fā)如何提高cCR延長間期間期化療提高治療強(qiáng)度評估：MR預(yù)測ypT0Maastricht（荷蘭）標(biāo)準(zhǔn)方法：

方法：

MSKCC標(biāo)準(zhǔn)方法：

活檢

活檢陰性≠腫瘤完全消退biopsyNon-cCRcCRtotalpositive25025negative11314total36339PerezROetal.ColorectalDis2012Useforconfirmregrowth腫瘤退縮的空間異質(zhì)性DisColonRectum2013完全消退—等待&觀察療效評估時間方法療效預(yù)測失敗–復(fù)發(fā)如何提高cCR延長間期間期化療提高治療強(qiáng)度療效預(yù)測

95基因預(yù)測準(zhǔn)確率85%存在問題15studies,17gene-signature1000

genes,<=2%gene-overlap療效預(yù)測–DNA損傷相關(guān)療效預(yù)測

療效預(yù)測–II期結(jié)腸癌RFS療效預(yù)測-ctDNA影像組學(xué)

TrainingTesting

RadiomicsClinicalBothRadiomicsClinicalBothLocalControl0.6430.6920.7330.5630.6370.651[0.6220.665][0.6800.705][0.7190.748][0.4650.660][0.5360.737][0.5540.747]DistantControl/0.6570.657/0.6400.640/[0.6450.669][0.6450.669]/[0.5770.703][0.5770.703]OverallSurvival0.6750.7130.7450.6550.6720.730[0.6630.687][0.7010.726][0.7310.760][0.5890.722][0.6170.728][0.6580.801]Disease-freeSurvival/0.6780.683/0.6580.643/[0.6700.658][0.6750.692]/[0.5850.731][0.5710.714]完全消退—等待&觀察療效評估時間方法療效預(yù)測失敗–復(fù)發(fā)如何提高cCR延長間期間期化療提高治療強(qiáng)度復(fù)發(fā)

58%

cCRsustanined@2y15%LR@1y26%LR@2y復(fù)發(fā)

復(fù)發(fā)率:15.7%MaximevanderValk.ASCO

2017

Abs521復(fù)發(fā)TheinternationalWatch&Waitdatabase(IWWD)forrectalcancer:Anupdate679例cCR隨訪2年，中位隨訪

2.6年25%

(n=167)

局部復(fù)發(fā)，其中84%在2年內(nèi)復(fù)發(fā)96%:腔內(nèi)復(fù)發(fā)

4%:局部區(qū)域淋巴復(fù)發(fā)7%:遠(yuǎn)處轉(zhuǎn)移3yOS:整組病人：91%;復(fù)發(fā)病人：87%MaximevanderValk.ASCO

2017

Abs521完全消退—等待&觀察療效評估時間方法療效預(yù)測失敗–復(fù)發(fā)如何提高cCR延長間期間期化療提高治療強(qiáng)度提高新輔助治療療效模式5*5Gy5*5GySintervalS5*5GychemoSCRTintervalSSSCRT/intensifyCRT/intensifyintervalintervalchemoCRT/intensifyintervalchemoSClinicalphaseIISwedishstudy(6.5%)Lithuanianstudy（pCR13.1%)McGillstudy(pCR+almost16%)StochholmIIITrial1998-2010,657ptsArm15x5Gy1周內(nèi)手術(shù)(SRT)Arm25x5Gy4-8周后手術(shù)(SRT-delay)Arm325x2Gy4-8周后手術(shù)(LRT-delay)延長間隔期pCR11.8%vs1.7%N=1593JClinOncol1999;17:2396.AnnalsofSurgicalOncology15(10):2661–2667.AnnSurg.2009Oct;250(4):582-9.JCO2016：34：3773ESMO2016延長間隔期trialNoIntervalResultsLyon90-0119992014w8w7%14%Tulchinsky2008132<7w>7w17%35%(pCR+nearpCR)Kalady2009306<8w>8w16%31%GRECCAR-62657W11W15%17.4%Adams20162376W12W9%20%完全消退—等待&觀察療效評估時間方法療效預(yù)測失敗–復(fù)發(fā)如何提高cCR延長間期間期化療提高治療強(qiáng)度間期化療WashU(II)PolishIIIRAPIDO

(III)MSKCC(II)OPERA(II)TNT短程放療長程放化療WashUstudyGroupNypT0ypT0-2PvalueAll7621(28%)53(70%)cTstagecT36920(29%)49(71%)cT471(14%)IntervalfromRTtoS<=17wks3510(29%)26(74%)>17wks4111(27%)27(66%)毒性Grade3Grade4Grade5非血液學(xué)毒性(包括消化道毒性)14(18%)2(3%)0胃腸道7(9%)00血液學(xué)11(14%)10(13%)0pCR19(25%)降期:T71%,N59%MyersonRJ,etal.IJROBP2014;88:829-836S5.5wks(25x16-8wksRT+Fu+Oxali1wk12wksS5x5FOLFOX*31wkoptionaloptionalPolishIII不可切除局部進(jìn)展期或復(fù)發(fā)性直腸癌累及或鄰近附近的器官或結(jié)構(gòu)可觸及固定性病灶PolishIII5x5Gy+chemoCRTppCR16%12%0.17DFS(3-y)53%52%0.85LR22%21%0.82DM30%27%0.26OS73%65%0.046Latetoxicity20%22%0.54S5.5wks(25x16-8wks6-8wks24wks(optional)RT+CAPECAPE+OXALIPLATIN1wk18wks2-4wksS5x5CAPE+OXALIPLATIN1wkRAPIDOstudyRAPIDO高危因素（>=1）cT4MRF<1mmN2側(cè)方

LNEMVI(+)group

（%）ypT0-249ypT344ypT47ypN072ypN119ypN29ypT0N019W&W3CRM<=1mm11Riskfactors12345%35342182MSKCC-間期化療

pCRG3G4Group118%Group225%3%1%Group330%18%Group438%28%8%誘導(dǎo)化療/鞏固化療SmithJJ,BMCCancer20151st:3-yRFS2nd:organpreservationQoL

NOMphaseIITNTstudyfromMSKCCTNT策略：moreCTdelivered,morecCRachieved,moreoperationsavoidedASCOabstr3519,20172009~2015年

評估628位進(jìn)展期直腸癌TNTConventionalTxPvaluePlanned5-Fucompletion94.4%75.2%<0.001PlannedOxacompletin78.3%41.6%<0.001CR(pCR+cCR)36.0%20.6%NApCR18.7%15.9%NANoSduetoCR21.8%5.9%NAcCRmaintained@12M92%79%NADMfreesurvivalNosignificantdifferenceSurgery

XRT+Capecitabine+LocallyAdvancedRectalCancerNRG-GI002(TNT)SchemaNon-comparativeexperimentalarmsAdditionalarmsaddedthroughprotocolamendmentsNCT02921256XRT+CapecitabineFOLFOXx8

Surgery

XRT+Capecitabine+VeliparibFOLFOXx8

Surgery

FOLFOX+x8

R完全消退—等待&觀察療效評估時間方法療效預(yù)測失敗–復(fù)發(fā)如何提高cCR延長間期間期化療提高治療強(qiáng)度放化療強(qiáng)度增加OxaliplatinSTARACCORDCAO/ARO/AIO-04NSABOR-04PETCC-6CPT-11ARISTOTLECinClareAristotlestudy多中心、前瞻性III期臨床研究RLARCN=600RT45GyCap900mg/m2bidd1-5qwRT45GyCap650mg/m2bidd1-5qwIri60mg/m2(week1,2,3,4)GroupAGroupB主要研究終點(diǎn)：DFS次要研究終點(diǎn)：LC、PCR、OS、CRM、毒性反應(yīng)、手術(shù)并發(fā)癥、生活質(zhì)量CinClarestudyNCT02605265RAdeno,AV<12cmT3/4and/or

N+，N=360RT50Gy+CapRT50Gy+CapIriTMETMEf/uXELOX×5XELOXXEL