2022版食管癌NCCN指南更新：非HER2過表達(dá)患者一線治療首選方案全面修訂

2022版食管癌NCCN指南更新：非HER2過表達(dá)患者一線治療首選

方案全面修訂(全文)

2022版NCCN食管癌和食管胃結(jié)合部(EGJ)癌指南已更新至V2版本，與

2022.V1版相比，V2版僅對討論做了部分的更新，沒有進(jìn)行治療路徑和用

藥推薦的修訂。而2022.VI版與2021.V4版相比則存在較大的改動，醫(yī)脈通

編輯將更新要點整理如下，與讀者一同分享。

ESOPH-1一查、分期及組織學(xué)分類

檢查

修訂第10條由〃若發(fā)生或疑似發(fā)生轉(zhuǎn)移性疾病采用PCR法檢測MSI/IHC

法檢測MMR并進(jìn)行PD-L1檢測”修訂為〃若發(fā)生或疑彳以發(fā)生轉(zhuǎn)移性疾

病，進(jìn)行MSI和PD-L1檢測”；

修訂第12條，由〃如果完成上述檢測后有足夠的組織可用，可考慮使用二

代測序(NGS)〃修訂為〃可考慮使用二代測序(NGS)〃；

增加新條目，〃如果懷疑貧血，參見NCCN造血生長因子指南〃。

WORKUPCLINICALSTAGEDHISTOLOGICCLASSIFICATION。

?H&P

,UpperGlend(?sc<>pyandbiopsy*

?Chest/abdominalCTwithoralandIVcontrast

?PelvicCTwithcontrastasclinicallyindicated

,FD(；-PET/CTvvaluation<skullbasetomld4high>IfnoevidenceufMldiseaseSquamousediaSMESOPH-2

?CBCandcomprehensivechemistryprofilefcarcinoma

*Endoscopicultrasound(EUS).StageMVA?>/

ifnoovldoncoofMlunrosoctablodfsoaso(locoregionai/

,Endoscopicresoction(EK)Iscssontlalfortheaccuratestagingofearty-stagecancersdtsease.(、

(Tl?orTib).-EartyAlagecancemcanbestbediagnciscdbyERexceptT4bor\

unresoctabloN3n)\

,BIOPSYofmetastaticdisease"clinic______________________\Adenocarcinoma?SeeESOPH-11

I*Microsalellrteinstability(MSI)andPCTLItestingifmetastaticdisease1is

docunwnted/suspectM

,HER2testingIfmetastaticadonooirdnomaisdocumontod/

ANextgeneralionsequencing<NGS)mayboconsidered*

,Bronchoscopy,iftumorisatdrabovethecarinawithnoevidenceofMldisease

?AssignSiewertcat喀ory”SquamousceilESQPH-10

1carcinoma

?NutritionalassessmentandcounselingStageIVA?(incluctes

,Smokingcessationadvice,counseling,andpharmacotherapyasindicated*T4borunr?sectableN3

,Scrgnforfamilyhtstor"only)andIVB(metastatic

聞enocarclnoma---------------?

ES0PH-3——適合手術(shù)的鱗癌

pTis患者

修訂了內(nèi)鏡治療的方案排序，“ER,隨后消融〃由最末位移動到第二位。

"ES0PH-8——不適合手術(shù)的嶙癌〃、"ES0PH-12——適合手術(shù)的腺癌'和

"ES0PH-17一不適合手術(shù)的腺癌〃也更新了這一修訂。

HISTOLOGYTUMORPRIMARYTREATMENTOPTIONSFORMEDICALLYFITPATIENTS

CLASSIFICATION?

Endoscopictherapies(preferred):?ER?

ERfollnwedbyablaUon1，AAblation,

Endoscopicsurveillance

ESOPHAK。咐

Endoscopicsuneillance

SM_ESQPHA(4JQL5)

Stt_SufaicaLQulG.QmMAftef

teSQPHA)

ESOPH-IO——鱗癌的姑息治療

KPS評分＞60%或ECOG評分《2

"若疑似發(fā)生轉(zhuǎn)移性鱗癌，采用PCR法檢測MSI/IHC法檢測MMR并進(jìn)行

PD-L1檢測（如果既往未進(jìn)行）〃修訂為〃若疑似發(fā)生轉(zhuǎn)移性鱗癌，進(jìn)行

MSI和PD-L1檢測（如果既往未進(jìn)行）”；

〃如果上述檢測完成后有足夠的組織可用，可考慮NGS”修訂為〃可考慮通

過有效的檢測方法進(jìn)行NGS檢測

“ES0PH-19——腺癌的姑息治療''也更新了這兩處修訂。

EORSQUAMQUS-CELLPALLIATIVE

CARCINOMAMANAGEMENT

inicrosatollitQ>nd

PD-L1totting(tf

notdoneiSystomk

previously)H,nd/or

fT)6(AStStiCIs

performancescoreS2IPallatlve/Bestsupportivecare"

suspected',NGS

mayboconsidered

viavafedawdawy*'

Unresecl.'btolocallyadvanced.

Locallyrpcumnt,orMetasUUc

disease

Aaqiofskyperformancetcoro<60%

lor?Palftative/BestsupportivecareM

ECOGporformancoscore23

ESOPH-15——未行術(shù)前放化療或化療的腺癌患者的術(shù)后管理

R0切除

對于淋巴結(jié)陰性的pT3.pT4a患者，新增〃化療”這一術(shù)后治療選

擇；

SURGICALOUTCOMES/CLINICALTUMORPOSTOPERATIVEMANAGEMENT

PATHOLOGICFINDINGSFORCLASSIFICATIONS

Surveillance

Surveillance

or

c-‘、聲m〃

Considerchcmoradiation(category28//、

Surveillance*

or

Chemoradiation"y-(fluoropyrimldine-bascd)

Chemotherapy"I

(SwESOPH-18)

SurveillanceI

or

NodopositiveChemoradiationAyA(nuoropyrimidine4)ased)or

(AnyT)

Chemotherapy*

Chemoradiation"y(fluuropyrimidlnc-bascd)

ChomoradialionAy(fluoropyrimldino-based)or

K2resectionAPalliativemanagement(See6SQPII19>

ESOPH-B3/6—理學(xué)評估和生物標(biāo)志物檢測原則

食管和EGJ癌中HER2過表達(dá)或擴(kuò)增的評估

〃應(yīng)該注意的是，NGS有某些固有的局限性，因此在可能的情況下，應(yīng)首先使

用金標(biāo)準(zhǔn)分析(IHC/ISH),如果有足夠的組織可用，可以考慮額外的NGS檢測

〃修訂為〃應(yīng)首先考慮使用IHC/ISH然后酌情進(jìn)行NGS測試。對于晚期/轉(zhuǎn)

移性食管/EGJ腺癌患者，可在臨床或影像學(xué)進(jìn)展中考慮重新進(jìn)行生物標(biāo)記物

檢測

ESOPH-B4/6一理學(xué)評估和生物標(biāo)志物檢測原則

微衛(wèi)星不穩(wěn)定性(MSI)或錯配修復(fù)(MMR)檢測

"MMR或MSI檢測可能只能在CLIA批準(zhǔn)的實驗室進(jìn)行〃修訂為〃檢測必須

只能在CLIA批準(zhǔn)的實驗室進(jìn)行〃；腳注L"采用PCR檢測MSI”修訂為〃采

用PCR/NGS檢測MSI”。

ESOPH-B5/6—理學(xué)評估和生物標(biāo)志物檢測原則

二代測序(NGS)

"三種靶向治療’修訂為"多種靶向治療“刪除了〃Ramucirumab,,,〃HER2陽

性〃修訂為"HER2過表達(dá)〃，〃采用PCR檢測MSI"修訂為“采用PCR/NGS檢

測MSI7MMR突變〃修訂為〃MMR缺陷〃；〃應(yīng)該注意的是,NGS有某些固

有的局限性，因此在可能的情況下，應(yīng)首先使用金標(biāo)準(zhǔn)分析（IHC/FISH/IE向

PCR）,如果有足夠的組織可用，可以考慮進(jìn)行額外的NGS檢測'修訂為〃應(yīng)首

先考慮使用IHC/FISH/IG向PCR,然后酌情進(jìn)行NGS檢測〃。

液體活檢

〃液體活檢越來越多地用于那些無法進(jìn)行臨床活檢以進(jìn)行疾病監(jiān)測和管理的

晚期患者〃修訂為〃液體活檢越來越多地用于晚期疾病患者，尤其是那些無

法進(jìn)行臨床活檢以進(jìn)行疾病監(jiān)測和管理的患者〃，〃對于患有轉(zhuǎn)移性或晚期

食管/EGJ癌且無法進(jìn)行傳統(tǒng)活檢的患者〃修訂為〃對于無法進(jìn)行傳統(tǒng)活檢或

疾病進(jìn)展監(jiān)測的轉(zhuǎn)移性或晚期食管/EGJ癌患者

ESOPH-D1/2——遺傳風(fēng)險評估原則

高危綜合征的進(jìn)一步風(fēng)險評估標(biāo)準(zhǔn)

新增〃識別家族中致病基因突變的最有效策略是對患癌的近親進(jìn)行檢測。如果

親屬不愿或不能進(jìn)行檢測，則考慮對未受影響的親屬進(jìn)行檢測。遺傳咨

詢和檢測的詳細(xì)討論請參見《NCCN遺傳/家族高風(fēng)險評估指南：結(jié)直腸》

和《NCCN遺傳/家族高風(fēng)險評估指南：乳腺、卵巢和胰腺》

ESOPH-F1/17——全身治療原則

第4條，刪除〃三細(xì)胞毒性藥物方案應(yīng)保留給具有良好PS和頻繁毒性評估

機(jī)會的健康患者〃，新增〃三細(xì)胞毒性藥物方案的使用應(yīng)保留給具有良好PS

且便于進(jìn)行頻繁毒性評估的健康患者〃。

PRINCIPLESOFSYSTEMICTHERAPY

,SystemictherapyroglmonsrecommendedforadvancedosophagealandEGJadenorarcinoma,SCCoftheesophagus,andgastrkadenootrcinomamaybeusedinterchangoably

(oxceptasIndicated).

,RegimensshouldbechosvnInthecontext<jfperformancestatus(PS),comorbidities,andtoxicityprofile.

,Trasluzumub*shouldbeodtlcdtofirsMincchcmothcniDvforHER2ovcrexprwsionpositiveHdcnocHrciiwmH*

|?cytotoxicroginwnsarepreferredforpatientsOthadvanceddiseasebeca&sooflowertoxicity.Th@useofthreecytotoxicdrugsin

incationsofcategoryIreginionoruseofcategory2Aor

favorabletoxicityprofilew?houtcompromisingefficacy.1

:Desosandschedulesforanyrogimenthatisnotderivedfromcategory1evidenceisasuggestion,andsubjecttoappropriatemodificationsdepending<)nthncircumstancos.

：.Alternatecombinationsandschedulesofcytotoxicsbasedontheavailabilityoftheagents,practicepreferences,andcontraindicationsarcpermitted.

?PreoperativechemoradiationisthepreferredapproachforlocalizedadenocarcinomaofthethoracicesophagusorEGJ.2Perioperativechemotherapyisanalternativeoptionfor

distalesophagusandEGJ."'

;Intheadjuvantsotting,uponcompletionofchemotherapyorchemoradiation,pationtsshouldbomonttorodforanylong-termtroatmenbrelatedcomplications.

ESOPH-F3/17——不可切除的局部晚期、復(fù)發(fā)性或轉(zhuǎn)移性疾病的一線治

一線治療-首選方案-非HER2過表達(dá)

原方案修訂為5個方案，分別為"僅限腺癌，氟曉哇類（5-FU或卡培他

濱）、

奧沙利鉗聯(lián)合納武利尤單抗（PD-L1CPS>5為1類證據(jù)；PD-LICPS<5為

2B類證據(jù)）”方案、"氟曉喧類（5-FU或卡培他濱）、奧沙利鉗聯(lián)合帕博利珠

單抗（PD-LICPS210為2A類證據(jù)；PD?LICPSvIO為2B類證據(jù)）〃方

案、“氟唯呢類（5-FU或卡培他濱）、順鉗聯(lián)合帕博利珠單抗（PD-L1

CPS21O為1類證據(jù);PD-L1CPSvIO為2B類證據(jù)）〃方案、

"氟嚅呢類（5-FU或卡培他濱）聯(lián)合奧沙利鉗〃方案和〃氟唯嗯類（5?FU或

卡培他濱）聯(lián)合順鉗方案。

PRINCIPLESOFSYSTEMICTHERAPY

SY宣tgm虹ThefapxfocUniaMCtaM。LMIHY

EirslI.ImJhofMx

IOxaliplatinIsgenerallypreferredovercisplatinduotolowertoxicity.

PratcrasLRfiKimMi

?HERZoverexpressionpositiveadenocarcinoma?

?Fluonipyrimidinc(fluorouracil"orcaptxitabine)andoxaliplatinandtrastuzumab*

?Fluoropyrimidine(fluorounwiPorcaoecitabine)andctspiatinandtrastuzumab(category

r>IER2ovorcxprMSlunrwK?tivA

?Fluon)pyrlmidin?(fluuruuraciPorcapodllbino),oxaliplatin.?ndnivolumabforact?n<xrarcincxnaonly

由〃〃

(categoryIforPD-LlCPSZ5;category2BforPD-LlCPS<3f

>Fluoropjriinidine(fluorouraciPorcapedtabine>.oxaliplatin,andpeinbrolizumab

(c?togor)2AforPD-LlCPSZ10:catogory2BforPO-L1CPS<10f'2c

?Fluontpyrlmidino(fluorouracil,'orcapocltiblnohcisplatin,andpAmbrollzumab

(category1forPD-LlCPS210;catcgovy2BforPD-LlCPS<10TUo

?Eluoropyrimidine(nunrouracilorcapecitablne)andoxalkplatin"”

?Fluoropyrimidkne(fiuorouraciPorcapedtabine)andcisplatin"煙

QtherHRomnwndedRgqfmens

;HERZovoroxprMSionpositiveadwocarcinofnAo

?Fluoropyrimidine(fluorouracilorcapecttabine)andcisplatinandtrastuzumab4andpemhroltzumah??J,:?

?Fluoropyrimidine(Duorouradl^orcapecttabine)andoxaKplatinandtrastuzumab*andpe?iibrolizuinabIJ,”

;FluoroHraciP*1andlrtnotecanA-2*

?PadiL'xolwithorwithoutcisplatinorcarboptatin

;DocetaxelwithorwithoutcisplatinJ?

?Fluoropyrimidinc(fluorouracil"orcapwilabinc)

?Docetaxel,cisplatinoroxulbptattn.andfluorouraciPJ-4A

?Docetaxel,carboptotin.andfluorouracil(citMorj2B)l”

ESOPH-F4/17——不可切除的局部晚期.復(fù)發(fā)性或轉(zhuǎn)移性疾病的二線治

二線或后續(xù)治療-在某些情況下有用

新增〃Dostarlimab-gxly治療MSLH或dMMR腫瘤〃；新腳注k:〃對于

既往治療期間或治療后（不包括檢查點抑制劑，如PD-1抑制劑、PD-L1抑制

劑或CTLA4抑制劑）疾病進(jìn)展且無滿意的替代治療選擇的患者。既往使用

過腫瘤免疫治療的患者將不適合使用Dostardolimab-gxly\

PRINCIPLESOFSYSTEMICTHERAPY

SvstcmicThcramforU'nrssectablcLocall、'Advanced.RodcrMetastaticDisease(wher，>localtheranvisnetIndicated)

?DependentonpriortherapyandPS

PreferredRegimons

Nivolumabforesophagealsquamouscellcarcinoma(category

Pembrolizumabf,h

AForJitcond-linctherapyforesophagealsquamouscellcarcinomawithPD-L1expressionlevelsbyCPSof210(catepinI)44

Kamucirumabandpaclitaxelforadenocarcinoma

(category1forEGJadenocarcinoma;category2Aforesophagealadenocarcinoma)49

Eam-trastuzuniabderuNtecan*nxkiforHER2overexpressionpositive

adenocarcinoma41

Docetaxel(category1),37

PaclitaxelUategorj'i),，M'

Irinotecantcategory1)47*SC

Fluorouracil1"*andIrinotecan4?s,52

TrifhiridineandtiplracllforthircMineorsubsequenttherapyforEGJadenocarcinoma(category1產(chǎn)

Kanwcirumabforadviiwarcinoma(categoryIforEGJadenocarcinoma;category2\foresophagealadenocarcinoma產(chǎn)

Irinotecanandcisplatin"M

Fluorouracilandirinotecan?ramucirumabforadenocarcinoma"」-"

Irinotecanandramucirumabf<?rudcnocarcinoma'7

Doceiaxelandirinotecan(catcuorv2B158

,EntrectlniborlarotrectinibforNTRKgenerusionjxraitivetumors"**

?PembroUzumab?"orMSI-HordMMRtumors6'*

iiWh企IQmutations/me￡abasc)tumors*4KDnstarlimab-

UsefulInCertainCircumslunccs

ESOPH-F5/17——全身治療原則■術(shù)前放化療

術(shù)前放化療-其他推薦方案

〃伊立替康+順鉗'’方案給藥周期更改為每35天為一個周期。"ESOPH-F

7/17—全身治療原則-方案和給藥計劃’也更新了這一修訂。

PRINCIPLESOFSYSTEMICTHERAPY-REGIMENSANDDOSINGSCHEDULES'

PR￡f￡RR￡DREGIMENSREGIESOTHERRECCMVENDEDREGIMENAcontincd

PacMAjwlandcarboolatinFluorouracilandctaiW^inP?ciillxol4M0mgfVVIVonDayIwwkly

Cisplatin75-100ing/m:fVonDays1and29

Paclll.'xel50mg/mUVnnDay1FluorouracilJOOmg/in*(Vcontinuous

CarboplatinAUC2IVonDay1Fluorouracil750-1(M)0my/m2IVcontinuousInfusion

Weeklyfor5wetks1over24hoursdailyonDays1-4and29-3235Alaycycle4infusiondailyonDays1-6

Weeklyfor5weeks'

EluotmirKII^An(l.Qxalidaiio

Oxaliplatin85mgfm'!VonDay1LeucovorinCisptatin15mtfm1IVdaHyonDays1-5Paclitaxel4s-50mgfm1IVonDayI

400onDay1Fluorouracil800rngrni7IVcontinuousInfusionCap?cttabine625-825ing/m'POBIDonDayst-5

Fluorouracil44)0mg/m1IVPushonDay1over24hoursdaityonDays1-5Woeklyfor5weeks7

Fluorouracil800mg/m,IVcontinuousinfusionCycledevery21daysfor2cycles'

nvprhnurvdsiilvnnIV?vcIand)

Cycledevery14daysfoe3cycleswithradiation'CuoecHablnvandWDWm

Cisptotin30m.JnVIVonDayI

Fluorouracil300ing/ni1IVcontinuousInfusionovorCapectubing800ma/in'IX)BIDonDays1-524

boondailyfor4days(over96hours)for5

Oxaliplatin8$rn"m2IVow2hounonDay1

Cycledevery14daysfor3cycleswithnidiatl(?nH

dnocgnS5mg/m'IVon

I)?ys1,8.22.and29

Oxaliphitin85ing/m'IVonDays1.15.?nd29Cisptotin30IVonDays1.

for3dOMS8.22.and29、cydodovory

C?po€itobin?S25mg/WPOBID35ctu、、

nnDays1-6weeklyfor5wooks*7

ESOPH-F6/17——全身治療原貝卜圍手術(shù)期化療

圍手術(shù)期化療（用于胸段腺癌或EGJ）-首選方案

〃氟嚅呢類+奧沙利鉗〃的給藥方案由〃術(shù)前3個周期，術(shù)后3個周期〃修改

為〃術(shù)前4個周期，術(shù)后4個周期”。

PRINCIPLESOFSYSTEMICTHERAPY-REGIMENSANDDOSINGSCHEDL'LES1

lEkQDbLeucovorin400mgAm*IVonD*y1

Fluorouracil400mgfmIVPushonDay1

(4cyclespcooperativoand4cycles1

(4cyclesprooxEivoand4cyclespostoporativo)Fluorouracil20tX)mg/m1IVFluorouracil120()mg/mIVcontinuous

postoperative)FluorouracM2?00rn/WIVcont