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Aspects pratiques de l‘emploi de Gliolan pour la résection des gliomes
Dr MANZO NORBERT* et Dr. Ulf NESTLER**Département de Neurochirurgie
CHU FORT DE FRANCE NEUROCHIRURGIE 6 B*.
Université Justus Liebig, Giessen, Allemagne**
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nécrose tumour solide zone d‘infiltration
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méthodes pour achever une résection complèteméthodes pour achever une résection complète
• ultrasonographie intraopérative
• navigation neuronale
• expérience du chirurgien
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ultrasonographie intraopérative
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navigation neuronale
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biosynthèse d’ héme
Accumulation de fluorescence Accumulation de fluorescence dans un gliome après administration de 5-ALAdans un gliome après administration de 5-ALA
acide laevuline 5-amino
COOCOO --
NHNH 33 ++CHCH 22CC
CHCH 22
CHCH 22
OO
illumination conventionelle
protoporphyrine IX
HCHC
NN
NHNH
VVMM
MM
PP
MMPP
VV
MM
CHCH
NN
CHCH
NHNH
HCHC
illumination d‘excitation
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fluorophores biologiques
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fluorescence
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modifications techniques du microscope
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vue intraopérative
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application de Gliolan
• 2 heures avant l‘ anesthésie• boire quelques ml de solution en eau• 20 mg / kg du poids• 30mg / ml solution 5-Ala
• 24h au dehors de lumière solaire directe
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étude clinique phase III 5-Ala
• groupe allemande à la recherche du gliome
• 1998-2003
• auprès des autorités européennes
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Munich
Regensburg
Frankfurt
Halle
Berlin
Aachen
Bielefeld
Augsburg
Lübeck
FuldaDresden
Essen
Hamburg
Kiel
Giessen
Dusiburg
Düsseldorf
groupe gliome 5-Ala
Principal Investigators: HJ Reulen, MunichMunich, W Stummer, DüsseldorfDüsseldorf
Sponsor: Medac GmbH, WedelWedel, CRO: Clinstud GmbH, HamburgHamburg
Investigators:F. Oppel, A. Brune, BielefeldBielefeldW. Lanksch, Virchow-Klinikum, BerlinBerlinM. Brock, J. Vesper, Benjamin Franklin, BerlinBerlinH.J. Reulen, J.-C. Tonn, C. Goetz, MunichMunichJ.M. Gilsbach, L. Mayfrank, AachenAachenV. Seifert, F.E. Zanella K. Franz, Frankfurt a. MFrankfurt a. M.G. Schackert, T. Pinzer, DresdenDresdenW. Hassler, A. Bani, DuisburgDuisburgH.-J. Meisel, B.C. Kern, HalleHalle H.M. Mehdorn, A. Nabavi, KielKielA. Brawanski, O.W. Ullrich, RegensburgRegensburgD.K. Böker, M. Winking, GiessenGiessenF. Weber, U. Langenbach, SaarbrückenSaarbrückenM. Westphal, U. Kähler, Hamburg-EppendorfHamburg-EppendorfH. Arnold, U. Knopp, LübeckLübeckT. Grumme, T. Stretz, AugsburgAugsburgD. Stolke, H. Wiedemayer, EssenEssenW. Stummer, B. Turowski, DüsseldorfDüsseldorfO.D. Wiestler, T. Pietsch, BonnBonn
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n (%)n (%) 139 (100)139 (100) 131 (100) 131 (100)
≤ ≤ 55 ans (%)55 ans (%) 45 (32)45 (32) 43 (33) 43 (33)> 55 ans (%)> 55 ans (%) 94 (68)94 (68) 88 (67) 88 (67)median (ans)median (ans) 6060 5959
““basbas”” [ 70, 80 ] (%) [ 70, 80 ] (%) 28 (20)28 (20) 31 (24) 31 (24) ““hauthaut”” [ 90, 100 ] (%) [ 90, 100 ] (%) 111 (80)111 (80) 100 (76)100 (76)
non (%)non (%) 65 (47)65 (47) 54 (41)54 (41)oui (%)oui (%) 74 (53)74 (53) 77 (59)77 (59)
WHO III° (%)WHO III° (%) 4 (3)4 (3) 5 (4)5 (4)WHO IV° (%)WHO IV° (%) 135 (97)135 (97) 126 (96)126 (96)
ALAALA blancheblanche
characteristiques démographiques (intent to treat)characteristiques démographiques (intent to treat)
ageage
KPSKPS
““éloquentéloquent””
histologiehistologie
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résections complètes en IRM postopérativerésections complètes en IRM postopérative
0
25
50
75
100
pou
rcen
t
ALA blanche
35%47/131
p < 0.0001chi2
65%90/139
volume résidual:median: 0.7 ccm
volume résidual:median: 0 ccm
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est-ce qu’il y avait du tumour résidual en IRM postopérative ?
temps de survivretemps de survivre
N 123oui non
128median [mois]95% CILog rankHazard Ratio95% CI
12.0[10.6;14.0]
17.2[14.3;19.4]p < 0.00010.55[0.42;0.73]
Patients at risk:123128
98110
62 91
22 49
5 20
3 10
1 4
1 1
dis
trib
uti
on
cu
mu
lati
ve
0 .0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
temps, mois0 6 12 18 24 30 36 42
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paramètre valeur multivariate p
tumour résidual non / oui 0.0006
KPS ≤ 80 / >80 0.0055
age ≤ 55 / > 55 0.0132
aréal éloquent non / oui 0.2144
Median tumor vol. 1.5 ccm 0 ccm
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139 104 59 28 168
131 85 28 13 75
temps sans progréssion oncologiquetemps sans progréssion oncologique
Stummer et al. Lancet Oncol. 2006;7:392-401.
po
urc
ent
de
pat
ien
ts (
%)
100
90
80
70
60
50
40
30
20
10
0
Log rankp = 0.0078
5-Ala
blanche
temps (mois)0 3 6 9 12 15
nombres
5-aminolevulinic acid
blanche
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risques
• thrombose
• convulsions épiléptiques
• résection des parties cérébrales éloquentes
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précautions
• application de Gliolan seulement:
• a) résection complète possible sans endommager des structures éloquentes
• b) après administration de dexamethasone disparition complète des déficits neurologiques
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résumé
• Gliolan (5-Ala) améliore l‘ampleur de la résection
• le moins le tumour résidual, le plus long le temps sans progréssion
• le risque d‘aggraver les symptômes préexistants