Radiothérapie adjuvante mammaire avec modulation d’intensité par Tomothérapie : Evaluation prospective de la toxicité et de la

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UNIVERSITE!DU!DROIT!ET!DE!LA!SANTE!-!LILLE!2!!
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MEMOIRE!DE!DES!D’ONCOLOGIE!OPTION!RADIOTHERAPIE!
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Présenté!et!soutenu!le!24!juin!2017!!
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TUTEUR
Monsieur le Docteur David Pasquier
3 rue Frédéric Combemale
BP 307
59020 LILLE CEDEX
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ALARA! ! As!Low!As!Reasonably!Achievable!
ASTRO! ! American!Society!for!Radiation!Oncology!
Cm3!! ! Centimètre!cube!
CMI! ! Chaine!Mammaire!Interne!
CNIL!! ! Commission!Nationale!Informatique!et!Libertés!
CRF! ! Case!Report!Form!
CT! ! Chimiothérapie!
CTV! ! Clinical!Target!Volume!
D2%! ! Dose!reçue!par!2%!du!volume!en!question!
D50%!! ! Dose!reçue!par!50%!du!volume!en!question!
D95%!! ! Dose!reçue!par!95%!du!volume!en!question!
DICOM!!! Digital!Information!and!Communication!in!Medicine!
Dmoy! ! Dose!moyenne!
EORTC! ! European!Organisation!for!Research!and!Treatment!of!Cancer!
ESTRO! ! European!Society!for!Radiotherapy!and!Oncology!
Gy! ! Gray!
HDV! ! Histogramme!Doses-Volumes!
IMC! ! Indice!de!Masse!Corporelle!
MV! ! Megavolt!
MVCT! ! Megavolt!Computed!Tomography!
N!! ! Nombre!de!patientes!
NCI-CTCAE!!National!Cancer!Institute-!Common!Terminology!Criteria!for!Adverse!Events!
OAR! ! Organes!à!Risque!
OR! ! Odds!Ratio!
PTV!! ! Planning!Target!Volume!
RCMI!! ! Radiothérapie!Conformationnelle!en!Modulation!d’Intensité!
RE! ! Récepteurs!aux!Œstrogènes!
RH! ! Récepteurs!Hormonaux!
RP! ! Récepteurs!à!la!progestérone!
RT! ! Radiothérapie!
RT2D!! ! Radiothérapie!conventionnelle!en!2!Dimensions!
RT3D!! ! Radiothérapie!conventionnelle!en!3!Dimensions!
RTE!! ! Radiothérapie!Externe!
RTOG!! ! Radiation!Therapy!Oncology!Group!
SBR!! ! Scarff,!Bloom!et!Richardson!
Sous-clav!!Sous-claviculaire!
Sus-clav!!Sus-claviculaire!
TDM!! ! Tomodensitométrie!
TNM! ! Tumor,!Nodes,!Metastasis!
UH!! ! Unité!Hounsfield!
V15!! ! Volume!de!l’organe!en!question!recevant!une!dose!totale!≥!15!Gy!
V20!! ! Volume!de!l’organe!en!question!recevant!une!dose!totale!≥!20!Gy!
V30!! ! Volume!de!l’organe!en!question!recevant!une!dose!totale!≥!30!Gy!
V40!! ! Volume!de!l’organe!en!question!recevant!une!dose!totale!≥!40!Gy!
V45! ! Volume!de!l’organe!en!question!recevant!une!dose!totale!≥!45!Gy!
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I.!Epidémiologie!du!cancer!du!sein!...................................................................................!1!
II.!Radiothérapie!du!cancer!du!sein!...................................................................................!1!
1.!Carcinome!invasif!......................................................................................................!1!
2.!Limites!de!la!radiothérapie!........................................................................................!2!
III.!La!Radiothérapie!Conformationnelle!Tridimensionnelle!..............................................!2!
1.!Principe!......................................................................................................................!2!
2.!Limites!.......................................................................................................................!3!
IV.!La!Radiothérapie!Conformationnelle!par!Modulation!d’Intensité!............................!3!
1.!Principes!généraux!....................................................................................................!3!
2.!Tomothérapie!............................................................................................................!4!
3.!RCMI!et!cancer!du!sein!..............................................................................................!5!
V.!Objectif!de!l’étude!.........................................................................................................!7!
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I.!Critères!d’éligibilité!.......................................................................................................!8!
1.!Critères!d’inclusion!....................................................................................................!8!
2.!Critères!d’exclusion!...................................................................................................!8!
II.!Critères!d’évaluation!.....................................................................................................!8!
1.!Critère!principal!.........................................................................................................!8!
2.!Critères!secondaires!..................................................................................................!9!
III.!Mise!en!œuvre!et!déroulement!du!traitement!.............................................................!9!
1.!Scanner!de!centrage!..................................................................................................!9!
2.!Délinéation!des!volumes!d’intérêt!............................................................................!9!
3.!Prescription!.............................................................................................................!10!
4.!Traitement!et!surveillance!......................................................................................!10!
IV.!Constitution!du!recueil!de!données!........................................................................!11!
1.!Paramètres!étudiés!.................................................................................................!11!
2.!Recueil!des!données!cliniques!.................................................................................!11!
3.!Recueil!des!données!dosimétriques!........................................................................!11!
V.!Analyse!statistique!......................................................................................................!12!
1.!Détermination!du!nombre!de!sujets!nécessaires!....................................................!12!
2.!Data!Management!...................................................................................................!12!
3.!Corrélation!entre!données!cliniques,!dosimétriques!et!toxicités!............................!12!
4.!Qualité!de!vie!..........................................................................................................!13!
VI.!Aspects!règlementaires!...........................................................................................!13!
1.!Information!des!patientes!.......................................................................................!14!
2.!Confidentialité!des!données!recueillies!...................................................................!14!
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I.!Statistique!descriptive!.................................................................................................!15!

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1.!Données!démographiques!......................................................................................!15!
2.!Suivi!des!patientes!...................................................................................................!17!
3.!Données!dosimétriques!...........................................................................................!17!
II.!Donnés!de!toxicités!.....................................................................................................!18!
III.!Recherche!de!facteurs!pronostiques!de!toxicité!aiguë!cutanée!et!œsophagienne!....!20!
1.!Facteurs!pronostiques!de!toxicité!cutanée!aiguë!de!grade!≥!2!...............................!20!
2.!Facteurs!pronostiques!de!toxicité!œsophagienne!aiguë!de!grade!≥!2!....................!23!
IV.!Recherche!de!facteurs!pronostiques!de!toxicité!tardive!cutanée!et!œsophagienne!..!
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1.!Facteurs!pronostiques!de!toxicité!cutanée!tardive!de!grade!≥!1!............................!23!
2.!Facteurs!pronostiques!de!toxicité!œsophagienne!tardive!de!grade!≥!2!.................!24!
V.!Qualité!de!vie!..............................................................................................................!24!
1.!Principes!..................................................................................................................!24!
2.!Résultats!..................................................................................................................!25!
VI.!Synthèse!des!résultats!.............................................................................................!27!
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I.!Comparaison!de!la!toxicité!avec!les!données!de!la!littérature!....................................!28!
II.!Comparaison!des!facteurs!associés!à!la!toxicité!avec!les!données!de!la!littérature!...!30!
III.!Comparaison!des!résultats!de!qualité!de!vie!..............................................................!31!
IV.!Risque!de!second!cancer!.........................................................................................!31!
V.!Limites!de!notre!étude!................................................................................................!32!
VI.!Conclusion!...............................................................................................................!32!
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Annexe!1!:!Protocole!de!sénologie!pour!la!TDM!de!centrage!.............................................!38!
Annexe!2!:!contraintes!de!doses!aux!OAR!...........................................................................!39!
Annexe!3!:!classification!du!cancer!du!sein!TNM!2009!et!AJCC!2010!.................................!40!
Annexe!4!:!principales!toxicités!de!la!radiothérapie!adjuvante!mammaire!selon!le!NCI-
CTCAE!v4.0!..........................................................................................................................!42!
Annexe!5!:!Questionnaires!de!qualité!de!vie!.......................................................................!43!
Annexe!6!:!CALENDRIER!DE!SUIVI!........................................................................................!47!
Annexe!7!:!Incidences!cumulées!de!toxicité!tardive!...........................................................!48!
Annexe!8!:!Curriculum!vitae!................................................................................................!49!
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