esophageal caner ahmed md [compatibility mode]
DESCRIPTION
Comprehensive overview of esophageal carcinoma: diagnosis, staging and treatmentTRANSCRIPT
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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