1

Esophageal CanerEsophageal Caner

Ahmed Ahmed ZeeneldinZeeneldinAss. Prof Medical OncologyAss. Prof Medical Oncology

NCINCI--CairoCairo20092009

Case ScenarioCase Scenario

nn MaleMale

nn 65 65 yearsyears

nn CO: CO: dysphagiadysphagia

nn How will you proceed?How will you proceed?

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nn What are the causes of What are the causes of dysphagiadysphagia??

nn What about male What about male 65 65 y?y?

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Esophageal AnatomyEsophageal Anatomy

Upper EsophagealSphincter (UES)

Lower EsophagealSphincter (LES)

Esophageal Body(cervical & thoracic)

18 to 24 cm

Tumor as seen via endoscopeTumor as seen via endoscope

endosonographyendosonography

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Histology of esophagusHistology of esophagus

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EpidemiologyEpidemiologyWorldwideWorldwide

Worldwide estimates for Worldwide estimates for 20002000

nn EightEight mostmost commoncommon cancercancerwithwith 412412,,000000 newnew casescases

nn SixthSixth mostmost commoncommon causecause ofofcancercancer deathdeath withwith 338338,,000000deathsdeaths

nn 20022002 updateupdate

462462,,000000 newnew casescases

386386,,000000 deathsdeaths

Parkin DM, Lancet Oncol 2001; 2: 533-543

Parkin DM, CA Cancer J Clin. 2005;55:74-108

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EpidemiologyEpidemiologyUSUS

US estimates for 2005

• 14,520 new cases- 11,220 male- 3,300 female

• 13,570 deaths

Jemal A CA Cancer J Clin. 2005;55:10-30

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Incidence in EgyptIncidence in Egyptyear year 20022002

nn 00..88% of all cancers% of all cancers

nn 1919thth in males and in males and 2222ndnd in femalesin females

nn Male to female: Male to female: 11..99::11

nn Median age Median age 60 60 yearsyears

nn Site: U (Site: U (1010%), M (%), M (2020%), L (%), L (6161%), ?%), ?

nn Pathology: Pathology: nn SCC: SCC: 6565%%

nn Adeno: Adeno: 2222%%

GPCR (GPCR (20072007))

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NCI CairoNCI Cairo

nn 11..3 3 % of all cancers% of all cancers

nn Male: female: Male: female: 11..77::11

nn Median age Median age 60 60 yy

NCI report (NCI report (20022002, , 20032003))

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LNs along the esophagusLNs along the esophagus

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StagingStagingnn TT::

nn 11: : nn 11a: Lamina a: Lamina PropriaPropria oror

nn 11b: b: submucosasubmucosa

nn 22: : MusclarisMusclaris

nn 33: Adventitia: Adventitia

nn 44: adjacent: adjacent

nn NN::nn 11: regional LN: regional LN

nn M:M:nn 11a: cervical LN in upper a: cervical LN in upper

thoracic thoracic esophesoph, , celiac LN in lower thoracic celiac LN in lower thoracic esoeso

nn 11b: other distant sitesb: other distant sites

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Stage groupingStage grouping

TT11 TT22 TT33 TT44 MM1 1 (a/b)(a/b)

NN00 II IIAIIA IIAIIA IIIIII IV (a/b)IV (a/b)

NN11 IIBIIB IIBIIB IIIIII IIIIII IV (a/b)IV (a/b)

MM1 1 (a/b)(a/b)

IV (a/b)IV (a/b) IV (a/b)IV (a/b) IV (a/b)IV (a/b) IV (a/b)IV (a/b) IV (a/b)IV (a/b)

55y OSy OS 11: : 8080 22a: a: 404022b: b: 2020

33: : 1010 44a: <a: <5544b: <b: <11

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Prognostic factorsPrognostic factors

nn Definition:Definition:nn Stage: TNMStage: TNMnn Weight lossWeight lossnn CC--reactive protein* [Ikeda, Ann surg, reactive protein* [Ikeda, Ann surg, 20032003, , 238238: : 179179]]nn Others:Others:

nn PS PS nn AgeAgenn ComorbiditiesComorbiditiesnn SexSexnn othersothers

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WorkWork--up up

nn H&PH&Pnn EGD (+EGD (+BxBx))nn CT Chest and Abdomen e contrastCT Chest and Abdomen e contrastnn CBCD and chemistryCBCD and chemistrynn Barium swallow (optional)Barium swallow (optional)nn If no MIf no M11::

nn BronchoscopyBronchoscopy ((T at/above carina)T at/above carina)nn EUSEUSnn Laparoscopy (T at EG junction)Laparoscopy (T at EG junction)nn PETPETnn Biopsy of suspected MBiopsy of suspected M1 1 diseasedisease

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TreatmentTreatment

nn Multidisciplinary evaluation:Multidisciplinary evaluation:nn SurgeonSurgeon

nn Medical oncologistMedical oncologist

nn Radiation oncologistRadiation oncologist

nn RadiologistRadiologist

nn GastroenterologistGastroenterologist

nn pathologistpathologist

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Outcome of initial assessmentOutcome of initial assessment

nn Metastatic Metastatic ((Stage IV B) = MStage IV B) = M11bb

nn Very early Very early ((stagestage I): I): TT1 1 & N& N00//NxNx & M& M00

nn locoloco--regionally advanced (regionally advanced (Stage II, III,IVA) Stage II, III,IVA) MM11a or Na or N1 1 or Tor T22--TT44) )

Factors that govern decision• Tumor extent: resectable or not• Patient:

• Choice • Fitness for radical surgery• Fitness for chemoradiation

• Clinical setting:• Surgical expertise and facilities • Medical and radiation oncology

expertise and facilities

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Stage IVB (metastatic)Stage IVB (metastatic)nn Performance status:Performance status:nn PS >PS >22: BSC: BSC

nn PS PS 00--22: BSC +/: BSC +/-- CThCTh

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Metastatic ECMetastatic EC

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BSCBSC

nn DysphagiaDysphagia::nn Restore Restore lumenallumenal passagepassage

nn Endoscopic: dilatation, stent, LaserEndoscopic: dilatation, stent, Lasernn Radiotherapy: EBRT, Radiotherapy: EBRT, BrachtherapyBrachtherapynn ChemotherapyChemotherapy

nn Bypass the obstructionBypass the obstructionnn Stoma: Stoma: gastrostomygastrostomy*, *, jejenostomyjejenostomynn SurgerySurgery

nn PainPainnn bleedingbleeding

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Chemotherapy Chemotherapy

nn Primary : Primary : nn Metastatic setting, stage IVBMetastatic setting, stage IVB

nn Regimen: CFRegimen: CF

nn PrePre

nn PostPost

nn PeriPeri (pre and post)(pre and post)

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Chemotherapy for metastatic diseaseChemotherapy for metastatic disease

nn Compared to adenoCA, Compared to adenoCA, nn SCC is more sensitive to chemo, radio, and chemoradiationSCC is more sensitive to chemo, radio, and chemoradiation

nn But the long term outcome is the sameBut the long term outcome is the same

nn EvolvingEvolving

nn No powered phase III trialsNo powered phase III trials

nn No survival benefitNo survival benefit

nn Improves QOL Improves QOL

nn No preference of any specific regimenNo preference of any specific regimen

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Agents Agents

nn CisplatinCisplatin: : 2020% RR% RR

nn Older: Older: nn 55FUFU DoxoDoxo MTXMTX

nn MitomycinMitomycin BleomycinBleomycin

nn Newer:Newer:nn DocetaxelDocetaxel PaclitaxelPaclitaxel IrinotecanIrinotecan

nn OxaliplatinOxaliplatin CapecitabineCapecitabine

nn Targeted:Targeted:nn GefitinibGefitinib ErlotinibErlotinib CetuximabCetuximab

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CombinationsCombinationscisplatincisplatin--containingcontaining

nn CisplatinCisplatin-- 55FU (CF): FU (CF): RR RR 2020--5050%%

nn PaclitaxelPaclitaxel-- cisplatincisplatin-- 55FU (PCF): SCC and FU (PCF): SCC and AdenoAdeno

nn IrinotecanIrinotecan--cisplatincisplatin: : SCCSCC

nn DocetaxelDocetaxel--cisplatincisplatin--irinotecanirinotecan: RR : RR 6363% (ph II, #% (ph II, #1616))

nn GemcitabieGemcitabie--cisplatincisplatin: : RR RR 4545%%

nn MitomycinMitomycin-- cisplatincisplatin-- 55FU (MCF) equivalent to FU (MCF) equivalent to epirubicinepirubicin--cisplatincisplatin-- 55FU (ECF): EG CA, lower QOLFU (ECF): EG CA, lower QOL

nn CapecitabineCapecitabine regimens (ECX)regimens (ECX)

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NonNon--Cisplatin combinationsCisplatin combinations

nn IrinotecanIrinotecan--55FUFU--LV: LV: RR RR 2929% in platinum % in platinum resistantresistant

nn PaclitaxelPaclitaxel-- carboplatin: RR carboplatin: RR 4343% (neutropenia % (neutropenia GG33,,4 524 52%)%)

nn Oxaliplatin regimens (EOX, EOP)Oxaliplatin regimens (EOX, EOP)

nn CapecitabineCapecitabine

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Phase III trialsPhase III trials

nn German study groupGerman study groupnn Metastatic GE CAMetastatic GE CAnn FLO vs. FLO vs. FLP:FLP:nn Overall:Overall:

nn Less toxicityLess toxicitynn PFS: PFS: 55..8 8 vs. vs. 33..9 9 m* (trend)m* (trend)nn OS: OS: 1010..7 7 vs. vs. 88..8 8 (NS)(NS)

nn Over Over 65 65 years:years:nn RR: RR: 41 41 vs vs 1717%%nn TTF: TTF: 55..4 4 vs vs 22..3 3 mmnn PFS: PFS: 6 6 vs vs 3 3 mmnn OS: OS: 14 14 vs vs 7 7 mm

AlAl--Batran JCO Batran JCO 2626((99). ). 20082008`̀

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Phase III trialsPhase III trials

nn REALREAL--2 2 trialtrialnn 1002 1002 patients with advanced GE CA (patients with advanced GE CA (3030% E)% E)nn AdenoAdeno, SCC, or undifferentiated, SCC, or undifferentiatednn ECFECF, EOF, ECX, , EOF, ECX, EOXEOXnn RR:RR: 4141 42 46 42 46 5858 %%nn 11YOS:YOS: 3838 40 41 40 41 4747%%nn EOX>>>ECFEOX>>>ECFnn XelodaXeloda= = 55FUFUnn OxaliOxali = = CisplatinCisplatin

CuninghamCuningham NEJM NEJM 358358((11). ). 20082008

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Phase IIPhase IIààIII trialIII trial

nn Inoperable E CAInoperable E CA

nn FOLFOXFOLFOX4 4 vs. vs. CFCF

nn Median OS Median OS 2222..77 1414..7 7 mm

nn Median TTPMedian TTP 1515 99..5 5 mm

nn Median EFSMedian EFS 1111..66 77..8 8 MM

Conory ASCO Conory ASCO 2007 2007 # # 45324532

Very early (stage I)Very early (stage I)TT1 1 & N& N11//NxNx & M& M00

nn TisTis and Tand T11a: Lamina a: Lamina propriapropriann Endoscopic mucosal resectionEndoscopic mucosal resection

nn AblationAblation

nn EsophagectomyEsophagectomynn (non(non--cervical, > cervical, > 5 5 cm from cm from cricopharyngeuscricopharyngeus muscle)muscle)

nn TT11b : b : nn EsophagectomyEsophagectomy ( as above) ( as above)

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PostPost--esophagectomyesophagectomy therapytherapy

nn Depends on:Depends on:nn R (residual): RR (residual): R00= no, R= no, R1 1 = microscopic, R= microscopic, R2 2 =macro=macro

nn HistologyHistology

nn LN statusLN status

nn SiteSite

nn T stageT stage

PostPost--esophagectomyesophagectomy therapytherapynn RR22: :

nn chemoradiationchemoradiation ((fluoropyrimidinefluoropyrimidine based) or based) or

nn palliative therapypalliative therapy

nn RR11: : nn chemoradiationchemoradiation (FPB)(FPB)

nn RR00::nn SquamousSquamous (N+, N(N+, N--): observe): observe

nn AdenocarcinomaAdenocarcinoma: :

nn N+: N+: nn proximal or mid E: observe proximal or mid E: observe or or chemoradiationchemoradiation

nn distal E or EGJ : distal E or EGJ : chemoradiationchemoradiation or chemo or chemo (ECF if given preoperative)(ECF if given preoperative)

nn NN--::nn TisTis /T/T11: observe: observe

nn TT33//44: : chemoradiationchemoradiation

nn TT22: observe or : observe or chemoradiationchemoradiation

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Stage IIStage II--IVA IVA (Loco(Loco--regionally advanced, Mregionally advanced, M11a, Na, N11, T, T22--TT44))

nn Site and histologySite and histologynn Distal E/EG junction Distal E/EG junction ANDAND adenocarcinomaadenocarcinoma::

nn NeoNeo--adjuvantadjuvant chemochemo therapytherapy

nn ECF x ECF x 33 -->>Surgery Surgery -->> ECF x ECF x 33

nn Other sites or Other sites or squamoussquamous histology:histology:nn NeoNeo--adjuvant or definitiveadjuvant or definitive ChemoChemo--radiationradiation

nn DefinitiveDefinitive: followed by observation or palliative surgery: followed by observation or palliative surgery

nn NeoNeo--adjuvantadjuvant: to be followed by radical surgery if CR or PR : to be followed by radical surgery if CR or PR or palliative therapy/ BSC if SD or PDor palliative therapy/ BSC if SD or PD

Some scenariosSome scenariosnn IrresectableIrresectable: : chemoradiationchemoradiation then assess then assess

resectabilityresectability

nn Unfit for surgery or Refused surgeryUnfit for surgery or Refused surgerynn ChemoradiationChemoradiation (FPB)(FPB)

nn Unfit for Unfit for chemoradiationchemoradiation: radiotherapy alone: radiotherapy alone

nn Unfit for radiotherapy: chemo Unfit for radiotherapy: chemo

nn Unfit for any thing: BSC Unfit for any thing: BSC

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Stage IIStage II--VIA, VIA, resectableresectable and fitand fit

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Stage IIStage II--IVA IVA (Loco(Loco--regionally advanced, Mregionally advanced, M11a, Na, N11, T, T22--TT44))

nn Applicable to Applicable to resectableresectable::nn T: T: TisTis-- TT4 4 (some T(some T4 4 are are unresectableunresectable))

nn N: N: 00,,11,X,X

nn MM11a: a: cervialcervial and celiac LN (some Mand celiac LN (some M1 1 celiac are celiac are unresectableunresectable ))

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Surgery Surgery

nn Gold standardGold standard

nn All patients should be assessed for respectabilityAll patients should be assessed for respectability

nn Considered for Considered for nn ALLALL

nn FITFIT

nn RESECTABLERESECTABLE

nn Abdominal and thoracic (> Abdominal and thoracic (> 5 5 cm from cricopharyngyeus m)cm from cricopharyngyeus m)

nn NB: cervical and thoracic < NB: cervical and thoracic < 55cm CPM: definitive CRTcm CPM: definitive CRT

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Surgery Surgery

nn Type of surgery:Type of surgery:nn Tumor locationTumor locationnn Surgeon: experience and preferenceSurgeon: experience and preferencenn Patient preferencePatient preference

nn Indications:Indications:nn TisTis TT11a (mucosa): EMR, ablation, surgerya (mucosa): EMR, ablation, surgerynn TT11b, Tb, T22, T, T33: surgery: surgerynn TT4 4 (pericardium, pleura or diaphragm): (pericardium, pleura or diaphragm): resectableresectable

nn NB: NB: irresectableirresectable TT4 4 (heart, great vessels, trachea, liver, spleen, pancreas, lung): (heart, great vessels, trachea, liver, spleen, pancreas, lung): : CRT: CRT

nn NN11: : resectableresectable (LN#=(LN#=1515))nn MM11a lower esophagus and a lower esophagus and resectableresectable celiac LNceliac LN

nn NB: MNB: M11b: systemic treatmentb: systemic treatment

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Limitations of surgeryLimitations of surgery

nn Resection of tumor and nodesResection of tumor and nodes

nn Margin: circuferential and longitudinalMargin: circuferential and longitudinal

nn Anatomic locationAnatomic location

nn Restoration of continuityRestoration of continuity

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Radiotherapy Radiotherapy

nn Definitive and palliativeDefinitive and palliative

nn PrePre-- or postor post--operativeoperative

nn Types:Types:nn External beam (EB)External beam (EB)

nn Brachytherapy (BT): Brachytherapy (BT): nn PalliationPalliation

nn Not superior to EBNot superior to EB

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Combined modality treatmentCombined modality treatment

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PeriPeri--operative CToperative CT

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MAGIC trialMAGIC trial

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nn MRC (MAGIC trial)MRC (MAGIC trial)

nn Resectable gastric (Resectable gastric (7474%) , lower esophagus (%) , lower esophagus (1414%), %), EGJ (EGJ (1111%)%)

nn S vs ECFxS vs ECFx33ààSSààECFxECFx33nn ## 253253 250250

nn 55y OSy OS 2323 3636%%

nn PFS PFS HR HR 00..6666

nn DownDown--staging staging CunninghamCunningham N Engl J M N Engl J M 355355((11). ). 20062006

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Neoadjuvant chemotherapyNeoadjuvant chemotherapy

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Neoadjuvant chemotherapyNeoadjuvant chemotherapyRandomized TrialsRandomized Trials

Study (year)Study (year) PatientsPatients ChemotherapyChemotherapy pCR (%)pCR (%) Median Median Survival (mo)Survival (mo)

55--year year Survival (%)Survival (%)

PP valuevalue

Roth (Roth (19881988)) C + S C + S 1919S S 2020

Neo: C,Vin, Bleo Neo: C,Vin, Bleo Adjuvant: C, VinAdjuvant: C, Vin

NANA 9999

NANANANA

NSNS

Nygaard (Nygaard (19921992)) C + S C + S 5050S S 4141

C, BleoC, Bleo NANA 8888

33--y y 3399

NSNS

Ancona (Ancona (20012001)) C + S C + S 4747S S 4747

CF X CF X 2 2 or or 33 1313%% 25252424

34342222

NSNS

Schlag (Schlag (19921992)) C + S C + S 2222S S 2424

CF X CF X 33 NANA 10101010

NANA NSNS

INT INT 0113 0113 ((19981998)) C + S C + S 213213S S 227227

Neo CF X Neo CF X 33Adj CF X Adj CF X 22

22..55%% 1414..991616..11

2 2 y y 353537 37

NSNS

MRC (MRC (20022002)) C + S C + S 400400S S 402402

CF X CF X 22 44%% 1616..881313..33

2 2 y y 434334 34

PP = = 00..004004

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Preoperative CTPreoperative CT

nn RTOG RTOG 8911 8911 (INT (INT 01130113))

nn Potentailly resctable E CA Potentailly resctable E CA

nn S vs CT (CF)S vs CT (CF)ààSS

nn OSOS samesame

nn RR00 5959 63 63 %%

nn RR11 1515 4 4 %%

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Preoperative CTPreoperative CT

nn MRC OEOMRC OEO2 2 (INT (INT 01130113))

nn 802 802 Potentially resctable E CA Potentially resctable E CA

nn S vs S vs CT (CFxCT (CFx2 2 ))ààSS

nn Median OSMedian OS 1313..33 1616..8 8 mm

nn 66yOSyOS 1717 23 23 %%

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Preoperative CTPreoperative CT

nn French study group (FFCD French study group (FFCD 97039703))

nn 244 244 Potentially resectable lower E & G CA Potentially resectable lower E & G CA

nn S vs S vs CT (CF )CT (CF )ààSS

nn 55y PFSy PFS 2121 34 34 %%

nn 55yOSyOS 2424 38 38 %%

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Neoadjuvant chemotherapyNeoadjuvant chemotherapyMetaMeta--analysisanalysis

Cochrane Database Cochrane Database 20032003

nn 1111 RandomizedRandomized trialstrials involvinginvolving 20512051 patientspatientsnn ClinicalClinical relevancerelevance basedbased onon medianmedian survivalsurvival andand 11 toto

55 yearyear survivalsurvivalnn WhenWhen specificspecific survivalsurvival waswas notnot available,available, itit waswas

calculatedcalculated fromfrom thethe publishedpublished survivalsurvival curvescurves

-- PooledPooled responseresponse raterate toto chemotherapychemotherapy waswas aboutabout3636%% withwith 33%% pCRpCR

-- NoNo differencedifference inin survivalsurvival atat 11 andand 22 yearsyears-- SurvivalSurvival advantageadvantage startsstarts atat 33 yearsyears andand reachesreaches

statisticalstatistical significancesignificance atat 55 yearsyears

Cochrane Database Syst Rev Cochrane Database Syst Rev 20032003; ; 44: CD: CD001556001556

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Neoadjuvant ChemoradiotherapyNeoadjuvant Chemoradiotherapy

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NonNon--Randomized TrialsRandomized Trialsnn 46 46 trials from trials from 1981 1981 to to 19991999nn 2704 2704 patients patients –– 6969% SCC, % SCC, 3131% Adenocarcinoma% Adenocarcinomann RT dose from RT dose from 30 30 to to 60 60 GyGynn Majority of studies used Majority of studies used 55--FU and cisplatinFU and cisplatinnn Resection rate Resection rate 7474%%nn Pathologic CR: Pathologic CR: 2424% (% (3232% surgical patients)% surgical patients)nn Patterns of recurrence after surgical resectionPatterns of recurrence after surgical resection

-- LocoregionalLocoregional 99%%-- Distant Distant 3131%%-- Both Both 66%%

Geh JI, Br J Surg 2001; 88:338-356.

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Randomized TrialsRandomized TrialsStudyStudy PatientsPatients HistologyHistology ChemotherapyChemotherapy

RTRTSurgical Surgical mortality (%)mortality (%)

pCR (%)pCR (%) Median Median Survival (mo)Survival (mo)

33--year survival (%)year survival (%) P valueP value

Nygaard (Nygaard (19921992)) S S 4141CS CS 4747

SS Cis + BleoCis + Bleo35 35 GyGy

13132424

NANA 77..5577..55

991717

NSNS

Le Prise (Le Prise (19941994)) S S 4545CS CS 4141

SS Cis + Cis + 55--FUFU20 20 GyGy

7788..55

1010 10101010

14141919

NSNS

Apinop (Apinop (19941994)) S S 3434CS CS 35 35

SS Cis + Cis + 55--FUFU40 40 GyGy

15151414

771010

20202626

NSNS

Walsh (Walsh (19961996)) S S 5555CS CS 58 58

AA Cis + FUCis + FU40 40 GyGy

4488

2222 11111616

663232

P = P = 00..0101

Law (Law (19981998)) S S 30 30 CS CS 3030

SS Cis + Cis + 55--FUFU40 40 GyGy

0000

2525 27272626

NANANANA

NSNS

Bosset (Bosset (19971997)) S S 139139CS CS 143143

SS CisCis37 37 GyGy

441212..33

2626 19191919

37373939

NSNS

Urba (Urba (20012001)) S S 5050CS CS 5050

S (S (2525%)%)A (A (7575%)%)

Cis + Cis + 55--Fu + VinFu + Vin45 45 GyGy

2277

2828 18181717

16163030

NSNS

Burmeister Burmeister ((20022002))

S S 128 128 CS CS 128128

S (S (3636%)%)A (A (6161%)%)

Cis + Cis + 55--FUFU35 35 GyGy

NANA 1515%% 22221919

NANANANA

NSNS

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Primary CRTPrimary CRT

nn RTOG RTOG 8585--0101

nn Esophageal Esophageal squamoussquamous or or adenocarcinomaadenocarcinoma

nn TT11--3 3 NN00--1 1 MM0 0

nn RT (RT (6464Gy Gy 22xx3232): # ): # 6262

nn CRT: # CRT: # 134 134 RT (RT (50 50 GyGy 22xx2525)+ CF (Cd)+ CF (Cd1 1 F dF d11--4 4 q q 44w x w x 33))nn CisCis: : 100 100 mg/mmg/m22/d/d2 2 ((ciscis 5050mg/mmg/m2 2 dd1 1 and dand d88))

nn FU: FU: 800 800 mg/mmg/m22/d/d11--4 4 CICI

nn Q Q 4 4 or or 3 3 wkswks

nn For For 22--3 3 cyclescycles

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nn RTOG RTOG 8585--01 01 resultsresultsCRT CRT RTRT

nn 55yOSyOS 2626 00 %%nn Residual Residual 2626 3737 %%nn LifeLife--threatening toxicitythreatening toxicitynn 1010 22 %%nn acute tox Highacute tox High lowlownn Late toxLate tox samesame samesame

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INT INT 0123 0123 trialtrial

nn Follow up of RTOG Follow up of RTOG 8585--0101

nn CF+CF+nn LD RT: LD RT: 50 50 GyGy

nn HD RT: HD RT: 64 64 GyGy

nn No difference in OS or treatment failureNo difference in OS or treatment failure

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Preoperative CRTPreoperative CRT

nn Resectable CA and fit patient: Resectable CA and fit patient: nn Most commonMost common

nn Still investigationalStill investigational

nn UnresectableUnresectablenn May facilitate resectionMay facilitate resection

nn Resectable but unfit: definitive CRTResectable but unfit: definitive CRT

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Surgery vs. CRTSurgery vs. CRTàà SurgerySurgeryCALGB CALGB 97819781

nn Stage IStage I--IIIIII

nn # # 5656

nn CRTS CRTS S S

nn Median OSMedian OS 44..55 11..8 8 yy

nn 55yOSyOS 3939 16 16 %%

Tepper JCO Tepper JCO 2626((77). ). 20082008

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PostPost--operative CRToperative CRT

nn Resectable adeno CA of stomach and GEJResectable adeno CA of stomach and GEJ

nn ##556556

nn S S vs vs S+CRT (FU/LV)S+CRT (FU/LV)

nn Median OSMedian OS 2727 36 36 mm

nn 33yOSyOS 4141 50 50 %%

nn 33yRFSyRFS 3131 48 48 %%

nn Significant in high recurrence riskSignificant in high recurrence risk

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Neoadjuvant CRT MetaNeoadjuvant CRT Meta--analysesanalysesUrschelUrschel J,J, AmAm JJ SurgSurg 20032003;; 185185:: 538538--543543-- -- NeoadjuvantNeoadjuvant chemoradiationchemoradiation improvesimproves 33--yearyear survival,survival, withwith

moremore significantsignificant benefitbenefit inin thethe concurrentconcurrent studiesstudies (OR(OR 00..4545,,9595%% CICI 00..2626 toto 00..7979,, pp == 00..005005))

-- -- DecreaseDecrease LRLR butbut notnot distantdistant recurrencesrecurrences

FioricaFiorica F,F, GutGut 20042004;;5353:: 925925--930930-- -- NeoadjuvantNeoadjuvant chemoradiotherapychemoradiotherapy significantlysignificantly reducesreduces thethe 33--

yearyear mortalitymortality raterate (OR(OR 00..5353,, 9595%% CICI 00..2626 toto 00..7272,, pp == 00..0303))-- -- RiskRisk ofof postoperativepostoperative mortalitymortality isis higherhigher inin thethe neoadjuvantneoadjuvant

groupgroup (( OROR 22..1010,, 9595%% CICI 11..1818--33..7373,, pp == 00..0101))

GreerGreer SE,SE, SurgerySurgery 20052005;; 137137:: 172172--177177-- -- NeoadjuvantNeoadjuvant chemoradiotherapychemoradiotherapy isis associatedassociated withwith aa small,small,

nonnon--statisticallystatistically significantsignificant improvementimprovement inin overalloverall survivalsurvival(RR(RR ofof deathdeath inin neoadjuvantneoadjuvant groupgroup 00..8686,, 9595%% CICI 00..7474 toto 11..0101,, pp== 00..0707))

MalthanerMalthaner RA,RA, BMCBMC MedMed 20042004;; 22:: 3535-- AA significantsignificant differencedifference inin thethe riskrisk ofof mortalitymortality atat 33--yearsyears favorsfavors

neoadjuvantneoadjuvant chemoradiationchemoradiation (RR(RR 00..8787,, 9595%% CICI 00..8080--00..9696,, pp==00..004004))

*None of the meta-analysis included Burmeister’s study, which has been recently published (Lancet Oncol 2005) and at that time was available only in abstract form

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The Role of Surgery after The Role of Surgery after ChemoradiotherapyChemoradiotherapy

GOCSGGOCSG Stahl M, J Stahl M, J ClinClin OncolOncol 20052005; ; 2323: : 23102310--23172317

FLEP X FLEP X 3 3 →→ EP + EP + 40 40 GyGy →→ surgery (surgery (89 89 patients)patients)

FLEP X FLEP X 3 3 →→ EP + > EP + > 6666Gy Gy ((88 88 patients)patients)

SS CRTCRT

33--year OSyear OS 3131..33%% 2424..44%%

Median survivalMedian survival 1616..4 4 mm 1414..9 9 mm

-- CRT resulted in equivalent survival with preserved esophagusCRT resulted in equivalent survival with preserved esophagus

-- Surgery significantly increased local controlSurgery significantly increased local control

-- Survival curves appear to spread after Survival curves appear to spread after 3 3 years but without years but without reaching statistical significancereaching statistical significance

-- Patients responding to induction therapy appear to have good Patients responding to induction therapy appear to have good prognosis regardless of surgical interventionprognosis regardless of surgical intervention

OS

S

CRT

FLRP

S

CRT

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Initial management Initial management

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ConclusionsConclusions

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nn EC is a rare diseaseEC is a rare diseasenn Male predominanceMale predominancenn Old ageOld agenn Poor outcomePoor outcomenn Surgical constrains and secondary tumor effectsSurgical constrains and secondary tumor effectsnn CT in met disease has little survival benefit (CF, EOX, FOLFOX)CT in met disease has little survival benefit (CF, EOX, FOLFOX)nn Multimodality therapy is very essentialMultimodality therapy is very essentialnn CCRT supersedes C and RT alone and can be used as CCRT supersedes C and RT alone and can be used as

definitive, preoperative or post operative modalitydefinitive, preoperative or post operative modalitynn BSC is importantBSC is important