SCORE PREDICTIF DE

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FACULTE!DE!MEDECINE!HENRI!WARENBOURG!
INTERREGION!NORD!OUEST!!
ANNÉE!2017!
MEMOIRE!POUR!LE!DIPLOME!D’ETUDES!SPECIALISÉES!
D’ONCOLOGIE!MÉDICALE!
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SCORE!PREDICTIF!DE!REALISATION!D’UNE!
DEUXIEME!LIGNE!DE!CHIMIOTHERAPIE!DANS!
LE!CANCER!DU!PANCREAS!METASTATIQUE!
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Je!remercie!le!Dr!Christophe!Desauw!de!m’avoir!permis!de!travailler!sur!ce!projet,!de!son!aide!et!écoute!
afin!de!mener!à!bien!ce!travail,!mais!également!de!m’avoir!guidée!dans!mes!premiers!pas!d’interne,!il!
y!a!déjà!6!ans…!
Je! tiens! également! à! exprimer! ma! reconnaissance! à! toutes! les! personnes! qui! m’ont! enseigné!
l’oncologie!:!Monsieur!le!Professeur!Jacques!Bonneterre,!Monsieur!le!Professeur!Mohammed!Hebbar,!
Monsieur! le! Professeur! Antoine! Adenis,! Monsieur! le! Professeur! Jean-Charles! Soria,! Monsieur! le!
Professeur!Jean!Jacques!Lafitte,!Monsieur!le!Docteur!Farid!El!Hajbi.!
Je! souhaite! également! remercier! Monsieur! le! Professeur! Ducreux,! Monsieur! le! Professeur! Romain!
Coriat!et!Monsieur!le!Dr!Vincent! Hautefeuille! d’avoir!participé! à!cette!étude! et!de!m’avoir! permis!
d’utiliser!leurs!données.!
Je!souhaite!également!remercier!ma!directrice!de!Master!2,!Madame!Nadine!Andrieu,!qui!m’a!permis!
de! découvrir! les! statistiques! appliquées,! d’appendre! à! jongler! avec! les! chiffres,! et! qui! m’a! permis!
d’affirmer!mon!goût!pour!la!recherche.!
Je! remercie! également! toutes! les! personnes! que! j’ai! pu! rencontrer! au! cours! de! mon! cursus!:! co-
internes,!médecins!et!personnel!paramédicaux.!
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QOQR<-0(;(Quality!of!Life!QuestionnaireRC30(
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B&'")8*7'/)&(;(L’objectif!de!notre!étude!était!de!déterminer!un!score!prédictif!de!la!réalisation!d’une!
2ème!ligne! de! chimiothérapie! à! partir! d’une! cohorte! de! patients! atteints! d’un! cancer! du! pancréas!
métastatique!en!vue!de!la!réalisation!d’essais!portant!sur!la!séquence!thérapeutique.(
93'#"/%+(%'(9#'=)8%(;(Nous!avons!réalisé!une!étude!multicentrique!rétrospective!sur!325!patients!
traités!par!au!moins!une!ligne!de!chimiothérapie!entre!janvier!2010!et!décembre!2015.!A!l’aide!d’une!
régression!logistique!multiple!ont!été!déterminé!les!variables!associées!au!fait!d’atteindre!8!semaines!
de!traitement!de!2ème!ligne!afin!de!modéliser!le!score.!Les!survies!ont!été!estimées!par!Kaplan-Meier.!
Les!facteurs!pronostiques!associé!à!la!survie!globale!(SG)!ont!été!analysé!par!un!modèle!de!Cox.(
@#$*+'3'$(;( L’âge! médian! était!de! 64! ans! (56-71),! 74,2%! des! patients! présentaient! un! état! général!
conservé!avec!un!score!OMS!de!0-1.!34.1%!des!patients!ont!reçu!en!1ère!ligne!une!chimiothérapie!à!
base!de!Gemcitabine!et!65.2%!à!base!de!5-Fluorouracile!associé!à!de!l’oxaliplatine!et/ou!de!l’irinotecan.!
65.2%! des!patients! ont! reçu! une! 2ème!ligne!de! chimiothérapie.! Le! score! déterminé! comporte! 2!
variables!:!!le!score!OMS!et!le!fait!d’avoir!des!douleurs!liées!à!la!maladie.!Ce!score!présente!un!c-index!
de!0.68!et!un!R2!de!6,5%.!Tous!traitements!confondus!la!survie!sans!progression!médiane!est!de!4.5!
mois!et!la!SG!médiane!de!notre!cohorte!est!de!11.5!mois.!Un!nombre!de!sites!métastatiques!≥!3,!un!
score!OMS!≥!2,!l’utilisation!d’antalgique!de!palier!3,!un!NLR!>5!et!une!absence!de!chirurgie!de!la!tumeur!
primitive!sont!des!facteurs!indépendants!de!mauvais!pronostic!de!la!SG(
<)&7+*$/)&(;( ( Nous! ne!sommes! pas! parvenus! à! établir! un! score! pertinent! pour! permettre! de!
sélectionner!des!patients!aptes!à!recevoir!2!lignes!de!chimiothérapie.!La!mise!en!place!prospective!du!
recueil! de! données! permettrait! une! meilleure! sensibilité! ainsi! que! l’utilisation! de! données!de!type!
qualité!de!vie.(
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BL!BCD@J6T<DBJC(LLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLL(2!
FL!A!B6A9BJOJPBA(LLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLL(2!
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1.!1ERE!LIGNE!DE!TRAITEMENT!.....................................................................................................................!7!
2.!2EME!LIGNE!DE!TRAITEMENT!.....................................................................................................................!8!
3.!ESSAIS!DE!STRATEGIE!THERAPEUTIQUE!......................................................................................................!9!
<L!VF<DAT@E(!@JCJEDBQTAW(BC6AX(!@JCJEDBQTA(LLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLL(K!
1.!FACTEURS!PRONOSTIQUES!.....................................................................................................................!9!
2.!INDEX!PRONOSTIQUE!...........................................................................................................................!10!
6L!JGYA<DBV(6T(9A9JB@A(LLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLL(10!
BBL!9FDA@BAO(AD(9AD4J6AE(LLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLL(1,!
FL!!J!TOFDBJC(6ZADT6A(LLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLL(1,!
1.!CRITERES!D’INCLUSION!........................................................................................................................!12!
2.!CRITERES!D’EXCLUSION!........................................................................................................................!12!
GL!@A<TABO(6A(6JCCAAE(LLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLL(1,!
<L!JGYA<DBVE(AD(<@BDA@AE(6ZAIFOTFDBJC(LLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLL(1S!
1.!OBJECTIF!PRINCIPAL!............................................................................................................................!14!
2.!OBJECTIFS!SECONDAIRES!.....................................................................................................................!14!
!"!#$!%&'()%*!++,-.!/.,0)1*!&/('+)2!-/'&(+)!$'-)%')-(./'(')1')3&4'5'0/)6(.0-.6!%!...............................!14!
7"!#$!%&'()%!)89)'/)%!)88:)'0);<(')'/)=<5')%.40'!................................................................................!14!
-"!#$!%&'()%'+)2!-/'&(+)6(,0,+/.>&'+)!++,-.?)!)%!)89)'0);<(')%.40'!.....................................................!14!
6L!9AD4J6AE(EDFDBEDBQTAE(LLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLL(1M!
1.!REALISATION!DU!SCORE!PREDICTIF!.........................................................................................................!15!
2.!ANALYSE!DES!OBJECTIFS!SECONDAIRES!...................................................................................................!16!
BBBL!@AETODFDE(LLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLL(12!
FL!FCFO[EA(6AE<@B!DBIA(LLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLL(12!
1.!CARACTERISTIQUES!DES!PATIENTS!..........................................................................................................!17!
2.!DESCRIPTION!DE!LA!PRISE!EN!CHARGE!THERAPEUTIQUE!.............................................................................!19!
!"!;<(')%.40')1')/(!./'5'0/!................................................................................................................!19!
7"!=<5')%.40')1')/(!./'5'0/!..............................................................................................................!20!
-"!8?>&'0-'+)/@'(!6'&/.>&'+!.............................................................................................................!21!
1"!A<5')%.40')/@'(!6'&/.>&'!..............................................................................................................!21!
GL!E<J@A(!@A6B<DBV(LLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLL(,1!
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1.!EN!1ERE!LIGNE!...................................................................................................................................!22!
2.!EN!2EME!LIGNE!..................................................................................................................................!23!
6L!VF<DAT@E(!@JCJEDBQTAE(FEEJ<BAE(F(OF(ET@IBA(POJGFOA(LLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLL(,-!
BIL!6BE<TEEBJC(LLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLLL(,\!
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