Abstracts for the Eighth Congress of the European Association for Neuro-Oncology (EANO) : September 12–14, 2008 Barcelona, Spain
Название и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Strik H, Buhk J, Bock C, Nitsche M, Hoffmann A, Wrede A, Marosi C, Kaiser U, Christmann M, Kaina B, Perry J, Mason W, Belanger K, Kavan P, Fulton D, Easaw J, Kirby S, Macdonald D, Shields C, Pouliot J, Ewelt C, Schroeteler J, Stummer W, Felsberg J, Steiger H, Sabel M, Brandes A, Tosoni A, Franceschi E, Mazza E, Santoro A, Faedi M, Labianca R, Bertorelle R, Perrone T, Pesenti E, Bello L, Castellano A, Bertani G, Gambini A, Casarotti A, Falini A, Stummer W, Pichlmeier U, Schackert G, Grauer O, Molling J, Sutmuller R, Nierkens S, Adema G, Lamszus K, Martens T, Laabs Y, Günther H, Witte L, Westphal M, Campos B, Wan F, Zeppernick F, Ahmadi R, Farhadi M, Roth W, Beckhove P, Unterberg A, Radlwimmer B, Herold-Mende C, Bello L, Verpelli C, Bertani G, Casaceli G, Lucini V, Galli R, Sala C, Bexell D, Gunnarsson S, Tormin A, Gisselsson D, Scheding S, Bengzon J, Thon N, Leske H, Schichor C, Tonn J, Goldbrunner R, Baiker A, Neyns B, Sadones J, Joosens E, Bouttens F, Verbeke L, Baurain J, Dhondt L, Strauven T, Chaskis C, Michotte A, Wick W, Puduvalli V, Chamberlain M, Carpentier A, Cher L, Mason W, Van den Bent M, Hong S, Thornton D, Fine H, Bogdahn U, Mahapatra A, Oliushine V, Mouli C, Parfenov V, Stockhammer G, Ludwig S, Wuerth G, Heinrichs H, Schlingensiepen K, Frappaz D, Dussart S, Pierga J, Bay J, Fabbro M, Djafari L, Sunyach M, Pfister S, Janzarik W, Remke M, Ernst A, Gnekow A, Reifenberger G, Scheurlen W, Omran H, Kulozik A, Lichter P, Trevisan E, Laguzzi E, Guarneri D, Bomprezzi C, Caroli M, Leoncini B, Soffietti R, Rudà R, Rees J, Winston J, Jager R, Benton C, Caseiras G, Tofts P, Altmann D, Tozer D, Waldman A, Rudà R, Laguzzi E, Pace A, Carapella C, Riva M, Salvati M, Silvani A, Fariselli L, Caroli M, Soffietti R, Kraemer D, Angelov L, Doolittle N, Siegal T, Peereboom D, Jahnke K, Shalom E, Barnett G, McGregor J, Neuwelt E, Omuro A, Taillandier L, Chinot O, Carnin C, Barrié M, Soussain C, Tanguy M, Sierra Del Rio M, Leblond V, Hoang-Xuan K, Pels H, Juergens A, Schirgens I, Glasmacher A, Schulz H, Engert A, Diehl V, Linnebank M, Schackert G, Reichmann H, Kroschinsky F, Vogt-Schaden M, Egerer G, Bode U, Deckert M, Fimmers R, Fliessbach K, Klockgether T, Schmidt-Wolf I, Schlegel U, Villà S, Miller R, Krengli M, Abusaris H, Baumert B, Servagi-Vernat S, Igdem S, Lucas A, Boluda S, Mirimanoff R, Dufour C, Micheli J, Fourcade A, Laplanche A, Kalifa C, Couanet D, Grill J, Woehrer A, Waldhoer T, Azizi A, Leisser I, Czech T, Budka H, Hainfellner J, Slavc I, Haberler C, W A, Demopoulos A, Napolitano B, Chalif D, Black K, van den Bent M, Stupp R, Hildebrand J, Brandes A, Mirimanoff R, Mason W, Weller M, Cairncross J, Delattre J, Lacombe D, Gorlia T, D’Abbiero N, Pisanello A, De Berti G, Iotti C, Palmieri T, Ramundo D, Galeandro M, Ruggieri M, Riccardi S, Lambertini D, Bizzocchi N, Ghadirpour R, Armaroli L, Marcello N, Frenay M, Simon J, Benboubker L, Taillandier L, Castera D, Campone M, Busson A, Berger F, Lebrun C, Butowski N, Lamborn K, Chang S, Page M, Parvataneni R, Chang S, Liepa A, Nicol S, Thornton D, Prados M, Weiler M, Hartmann C, Wiewrodt D, Herrlinger U, Bamberg M, von Deimling A, Weller M, Wick W, Glas M, Ley B, Leinhaas A, Eisenreich R, Steinfarz B, Schramm J, Simon M, Herrlinger U, Brüstle O, Scheffler B, Ruano Y, Ribalta T, Rodríguez de Lope A, Fiaño C, Pérez-Magán E, Hernández-Moneo J, Campos-Martín Y, García J, Mollejo M, Meléndez B, Dufour C, Cadusseau J, Varlet P, Auger N, Daudigeos E, Rodier P, Dias-Morais A, Vassal G, Chneiweiss H, Junier M, Sminia P, van Nifterik K, van den Berg J, Ameziane N, Hulsebos T, Leenstra S, Wedekind L, Lafleur M, Stalpers L, Slotman B, Beier D, Röhrl S, Pillai D, Schwarz S, Kunz-Schughart L, Proescholdt M, Brawanski A, Bogdahn U, Wischhusen J, Reifenberger G, Hau P, Beier C, Dorresteijn L, De Bruin M, van ’t Veer M, Noordijk E, van den Berg H, Aleman B, Kappelle A, Boogerd W, van Leeuwen F, Sherman J, Aregawi D, Lai A, Rosenfeld S, Fathallah-Shaykh H, Larner J, Newman S, Schiff D, Devriendt D, De Smedt F, David P, Massager N, Suki D, Patel A, Hatiboglu M, Abou-Assi H, Sawaya R, Peereboom D, Conlin A, Seidman A, Brewer C, Eroes C, Thon N, Grasbon-Frodl E, Poepperl G, Tonn J, Kreth F, Thon N, Erös C, Pöpperl G, Herms J, Tonn J, Kreth F, Henriksson R, Capala J, Michanek A, Lindahl S, Salford L, Franzén L, Blomquist E, Westlin J, Bergenheim T, Nonoguchi N, Kawabata S, Miyatake S, Iida K, Miyata S, Yokoyama K, Kuroiwa T, Kirihata M, Imahori Y, Ono K, Sabel M, Rapp M, Özcan Z, Fischer J, Rox J, Sorg R, Judy K, Lustig R, Lopinto J, Shen S, Fiveash J, Shan J, Park C, Lee S, Kim C, Kim D, Paek S, Kim D, Heo D, Kim I, Jung H, Mariani L, Andereggen L, Arnold M, Vajtai I, Vassella E, Spiegl-Kreinecker S, Pirker C, Filipits M, Lötsch D, Buchroithner J, Pichler J, Silye R, Micksche M, Fischer J, Berger W, Preusser M, Janzer R, Felsberg J, Reifenberger G, Stupp R, Gorlia T, Marosi C, Heinzl H, Hainfellner J, Hegi M, Aaberg-Jessen C, Christensen K, Schrøder H, Offenberg H, Brünner N, Kristensen B, Tortosa A, Bruna J, Roerig P, Martínez F, Riemenschneider M, Boluda S, Giménez-Bonafé P, Reifenberger G, Gehring K, Aaronson N, Sitskoorn M, Klein M, Postma T, van den Bent M, Beute G, Enting R, Kappelle A, Boogerd W, Veninga T, Twijnstra A, Boerman D, Taphoorn M, Elandt K, Kurz C, Hassler M, Dieckmann U, Rottenfusser A, Marosi C, Rooney A, Carson A, Whittle I, Erridge S, Grant R, Beltran S, El Rawas M, Sunyach M, Berlier P, Conter C, Borson-Chazot F, Frappaz D, Waagemans M, Dijkstra M, van Nieuwenhuizen D, Wumkes M, Dirven C, Reijneveld J, Klein M, Stalpers L, Taylor R, Boota N, Bujkiewicz S, Lucas J, Robinson K, Robson K, Saran F, Michalski A, Pizer B, Dufour C, Couanet D, Figarella-Branger D, Carrie C, Doz F, Sainte-Rose C, Raquin M, Laplanche A, Grill J, Kalifa C, Dragomir M, Gruber E, Anghel R, Rosca C, Ciurea A, Tascu I, Radu C, Ollero A, Marquez-Rivas J, Ramirez G, Quiroga E, Gimenez-Pando J, Segovia-Vergel C, Slavc I, Czech T, Gruber-Olipitz M, Peyrl A, Minichmayr E, Dietrich W, Juergens A, Pels H, Rogowski S, Schulz H, Reichmann H, Vogt-Schaden M, Schmidt-Wolf I, Schlegel U, Mut M, Oǧuz K, Ayhan S, Söylemezoǧlu F, Berker M, Laguzzi E, Rudà R, Trevisan E, Guarneri D, Pedersini R, Boccaletti R, Soffietti R, Taillandier L, Pallud J, Razak R, Barbarino-Monnier P, Baron M, Bauchet L, Bernier V, Capelle L, Carnin C, Fontaine D, Gatignol P, Guillet-May F, Leroy M, Mandonnet E, Peruzzi P, Duffau H, Herold-Mende C, Lemke B, Yousef M, Ahmadi R, Dictus C, Harting I, Hartmann C, Schnitzler P, Unterberg A, Michotte A, Chaskis C, Neyns B, Tyberghien A, Declerck M, Origer I, Sadones J, Veld P, Naydenov E, Tzekov C, Minkin K, Kalev O, Toncheva D, Mirchev N, Bussarsky V, Salvati M, Brogna C, d’Elia A, Melone A, Lenzi J, Frati A, Raco A, Santoro A, Giangaspero F, Delfini R, Fariselli L, Milanesi I, Possanzini M, Brait L, Bianchi L, Tzekov C, Naydenov E, Cherninkova S, Mirchev N, Minkin K, Enchev Y, Florian S, Abrudan C, Oslobanu A, Andrasoni Z, Pompili A, Giovannetti M, Telera S, Vidiri A, Occhipinti E, Pompili A, Caroli F, Cattani F, Giovannetti M, Raus L, Telera S, Vidiri A, Occhipinti E, Oikawa M, Ito T, Sato K, Maruyama T, Muragaki Y, Iseki H, Hori T, Nakamura H, Stummer W, Meinel T, Sabel M, Schackert G, Signorelli F, De Geronimo L, Guyotat J, Gallo P, Cecchi P, Ghimenton C, Schiavo N, Pinna G, Mazza C, Gerosa M, Turazzi S, Nakasu S, Nakasu Y, Fukami T, Jito J, Caroli M, Cardia A, Menghetti C, Borsa S, De Santis A, Fornari M, Gaini S, Kozler P, Benes V, Netuka D, Kramar F, Charvat F, Heesters M, Pruim J, Wester G, Bijl H, Bolt R, van Dijk J, Mooij J, Langendijk J, Glas M, Hundsberger T, Stuplich M, Wiewrodt D, Kurzwelly D, Nguyen-Huu B, Rasch K, Herrlinger U, Martinez Garcia M, Reynes G, Balaña C, Fernandez Chacon C, Benavides M, Perez Segura P, Herrero A, Garcia Velasco A, Perez Martin X, Gil Gil M, Pichler J, Buchroithner J, Nöbauer S, Wurm G, Wies W, Wimmer S, Trenkler J, Fischer J, Preusser M, Gelpi E, Rottenfusser A, Dieckmann K, Widhalm G, Dietrich W, Bertalanffy A, Prayer D, Hainfellner J, Marosi C, Dresemann G, Hosius C, Nikolova Z, Schleyer E, Wick A, Pascher C, Wick W, Weller M, Bogdahn U, Hau P, Dictus C, Chatziaslanidou D, Becker N, Lichter P, Herold-Mende C, Wirtz C, Unterberg A, Ahmadi R, Aoki T, Nojima K, Mizutani T, Takasu A, Milanesi I, De Santis M, Bergantin A, Fumagalli M, Bianchi L, Silvani A, Fariselli L, Miyatake S, Kawabata S, Nonoguchi N, Iida K, Miyata S, Yokoyama K, Kuroiwa T, Michiue H, Kirihata M, Ono K, Beldì D, Masini L, Loi G, Stecco A, Littera A, Carriero A, Krengli M, Schroeteler J, Rapp M, Ringelstein A, Stoffels G, Langen K, Stummer W, Steiger H, Ewelt C, Sabel M, Galeano I, Prat R, Lucas A, Martínez J, Martín M, Conde R, Amador R, Bataller L, Reynes G, Bertolini F, Bagni B, Valentini A, Depenni R, Cobelli M, Casolo A, Fontana A, Falasca A, Giacobazzi P, Pinna G, Pica A, Prior J, Maeder P, Paschoud M, Stupp R, Mirimanoff R, Delaloye A, Allenbach G, Coope D, Eggers C, Vollmar S, Heiss W, Herholz K, Payer F, Wurm W, Weiss S, Zechner B, Fazekas F, Miwa K, Takenaka S, Shinoda J, Matsuo M, Ueda T, Yokoyama K, Yamada J, Yano H, Iwama T, Rutten I, Baumert B, Withofs N, Hustinx R, Heesters M, van Dijk J, Pruim J, Bijl H, Bolt R, Groen R, Langendijk J, Mooij J, Monleon D, Morales J, Gonzalez-Darder J, Talamantes F, López-Ginés C, Celda B, Cerda-Nicolas M, Cuellar S, Morales J, Calvar J, Martinetto H, Celda B, Cerda-Nicolas M, Monleon D, Bienfait H, van den Brink W, Reynes G, Parada A, Martínez-Sales V, Vila V, Martín M, Reganon E, Galeano I, Prat R, Peris M, Cárdenas E, Kaloshi G, Martin-Duverneil N, Guillevin R, Laigle-Donadey F, Marie Y, Taillibert S, Mokhtari K, Hoang-Xuan K, Delattre J, Sanson M, Andersson U, Osterman P, Sjöström S, Johansen C, Henriksson R, Brännström T, Broholm H, Christensen H, Ahlbom A, Auvinen A, Feychting M, Lönn S, Kiuru A, Swerdlow A, Schoemaker M, Roos G, Malmer B, Schnell O, Krebs B, Beer A, Romagna A, Wagner E, Kretzschmar H, Tonn J, Goldbrunner R, Pérez-Magán E, Fiaño C, Ribalta T, García J, García-Claver A, Campos-Martín Y, Ruano Y, Hernández-Moneo J, Mollejo M, Meléndez B, Jaksch H, Bresgen N, Golaszewski S, Kleindienst W, Strasser P, Bordihn K, Al-Schameri R, Spiegl-Kreinecker S, Richling B, Ladurner G, Bello L, Verpelli C, Lucini V, Bertani G, Sala C, Yoshida Y, Nakada M, Harada T, Sugimoto N, Hayashi Y, Kita D, Uchiyama N, Hayashi Y, Hamada J, Gunnarsson S, Bexell D, Visse E, Salford L, Siesjö P, Bengzon J, Darabi A, Rebetz J, Tian D, Persson A, Widegren B, Salford L, Englund E, Gisselsson D, Fan X, Yoshida K, Kosaka H, Ichikawa T, kambara H, Inoue S, Maruo T, Kurozumi K, Nakamura K, Hamada H, Date I, Avril T, Gapihan G, Saikali S, Vauleon E, Hamlat A, Diabira S, Quillien V, Ogawa D, Okada Y, Okada M, Ohkubo S, Miyake K, Kanemura Y, Ito M, Tamiya T, Nagao S, Okano H, Corno D, Cipelletti B, Pala M, Politi L, Bulfone A, Galli R, van der Meulen A, Gao P, Kakkar V, Reijnhoudt J, Biber K, Boddeke H, Mooij J, Wibom C, Sandström M, Henriksson R, Johansson M, Antti H, Bergenheim T, Bleeker F, Lamba S, Zanon C, Troost D, Hulsebos T, Vandertop W, Leenstra S, Van Tilborg A, Bardelli A, Persson O, Brynnel U, Levander F, Widegren B, Krogh M, Salford L, Carrabba G, Agnithori S, Munoz D, Ehsani S, Mukhopadhyay D, Croul S, Guha A, Lavon I, Zrihan D, Cohen M, Reubinoff B, Einstein O, Ben-Hur T, Smith Y, Siegal T, Thon N, Leske H, Restle F, Grau S, Baiker A, Tonn J, Goldbrunner R, Avci C, Oktar N, Dalbasti T, Yilmaz S, Dodurga Y, Dogan Z, Numanoglu S, Akalin T, Gunduz C, Tabatabai G, Moehle R, Mittelbronn M, Weller M, Wick W, Gramatzki D, Weller M, Capper D, Mittelbronn M, Wick W, Tritschler I, Jones T, Johns C, Barnes J, Duntsch C, Sarissky M, Pilatova M, Perjesi P, Mojzis J, Sulla I, Cohen-Jonathan-Moyal E, Skuli N, Monferran S, Delmas C, Favre G, Bonnet J, Toulas C, Lefranc F, Mijatovic T, Kiss R, Alexandru O, Carapancea M, Fetea A, Dragutescu L, Castro J, Georgescu A, Backlund M, Dricu A, Tabatabaie P, Bergström P, Henriksson R, Bergenheim T, Santandreu F, Couce M, Brell M, Gene A, Oliver J, Roca P, Bruna J, González L, Miró J, Velasco R, Gil M, Tortosa A, Le Rhun E, Baranzelli M, Perret M, Dubois F, Bonneterre J, Hoffmann A, Buhk J, Nitsche M, Strik H, Takenaka S, Miwa K, Shinoda J, Matsuo M, Ueda T, Yokoyama K, Yamada J, Yano H, Iwama T, Devriendt D, De Smedt F, David P, Massager N, Salvati M, Brogna C, D‘elia A, Melone A, Lenzi J, Bastianello S, Raco A, Santoro A, Giangaspero F, Delfini R, Muñoz S, Cuadrado V, Arruga J, Castillo L, Prat R, Galeano I, Todolí J, Amador R, Bataller L, Martín M, Reynes G, Happold C, Ernemann U, Roth P, Wick W, Weller M, Schmidt F, Ros T, Rebersek M, Boc M, Ocvirk J, Jereb S, Groselj L, Knific J, Graus F, Saiz A, Lai M, Bruna J, López F, Sabater L, Blanco Y, Rey M, Ribalta T, Dalmau J, Cordera S, Bottacchi E, Alvaro M, Joossens E, Neyns B, Mrugala M, Johnston S, Chamberlain M, San J, Rockhill J, Haug J, Spence A, Hilverda K, Heimans J, Bosma I, Postma T, Vandertop P, Slotman B, Reijneveld J, Klein M, Bellver-Pérez A, Muntaner G, Tort B, Ureste M, Salcedo J, Heese O, Schmidt M, Nickel S, Westphal M, Dijkstra M, van Nieuwenhuizen D, Stalpers L, Waagemans M, Vandertop W, Heimans J, Leenstra S, Dirven C, Reijneveld J, Klein M, Pamucka M, Czopkiewicz L, Jawien̓ W, Kosniewski W, Tokar P, Polednia-Jabłon̓ska K, Detert N, Blesing C, Warner N, Russell V, Matijasevic M, Arsenijevic J, Milosevic S, Ždrale Z, Tomasevic Z, Spetz A, Henriksson R, Salander P, La Rocca R, Vitaz T, Villanueva W, Hodes J, Cervera A, New P, Litofsky N, Litofsky N, Salvati M, Brogna C, d‘Elia A, Melone A, Lenzi J, Frati A, Rojas M, Santoro A, Giangaspero F, Delfini R, Goeppert M, Felsberg J, Stummer W, Reifenberger G, Steiger H, Sabel M, Bock H, Hinz J, Kantelhardt S, Rohde V, Giese A, Caroli M, Campanella R, Menghetti C, Zella S, Borsa S, Costa F, De Santis A, Fornari M, Gaini S, Beauchesne P, Carnin C, Bernier V, Taillandier L, Grimm S, Marymont M, Chandler J, Muro K, Newman S, Levy R, Rice L, Burns K, Cabreza C, Raizer J, Weber F, Floeth F, Asher A, Westphal M, Merchant N, Harutyunyan L, Galstyan H, Matosyan V, Jamakochyan G, Cordier D, Forrer F, Kneifel S, Müller-Brand J, Mäcke H, Merlo A, Okada M, Hatakeyama T, Ogawa D, Ookubo S, Miyake K, Kawai N, Tamiya T, Yamamoto Y, Nishiyama Y, Widhalm G, Wolfsberger S, Preusser M, Wöhrer A, Kotter M, Czech T, Marosi C, Knosp E, Garcia M, Tortosa A, Maldonado X, Gonzalez S, Balaña C, Gallego O, Verger E, Fuentes R, Navarro V, Gil M, Nakasu Y, Mitsuya K, Horiguchi S, Watanabe R, Nakasu S, Sanz C, Ramirez J, Ruiz-Xivillé N, Carrato C, Granada I, Millá F, Ariza A, Villá S, Rosell R, Balaña C, Mellai M, Chiò A, Lanotte M, Cassoni P, Caldera V, Annovazzi L, Finocchiaro G, Schiffer D, Wemmert S, Ketter R, Bettscheider M, Alt S, Kammers K, Rahnenführer J, Steudel W, Urbschat S, Sadones J, Michotte A, Veld P, Chaskis C, Menten J, Joosens E, Strauven T, Califice S, De Greve J, Neyns B, Lee C, Kim M, Kang Y, Joo M, Park S, Fontaine D, Vandenbos F, Lebrun C, Paquis V, Frenay M, Ferrer-Luna R, Martinetto H, Mata M, Nuñez L, Arias E, Dasi F, Calvar J, Piquer J, Sevlever G, Celda B, Hülper P, Kugler W, Lakomek M, Erdlenbruch B, Hong Y, Kim C, Chung D, Jung C, Kim T, Salford L, Persson O, Carlsson A, Widegren B, Siesjö P, Skagerberg G, Ingvarsson J, Wingren C, Borrebaeck C, Ketter R, Rahnenführer J, Henn W, Feiden W, Steudel W, Wemmert S, Urbschat S, Mata M, López-Ginés C, Gil-Benso R, Cortes O, Gonzalez-Darder J, Celda B, Cerdá-Nicolás M, Miwa T, Hirose Y, Sasaki H, Yoshida K, Kawase T, López-Ginés C, Faus C, Gil-Benso R, Monleon D, Mata M, Morales J, Leon J, Gonzalez-Darder J, Celda B, Cerdá-Nicolás M, Martinez R, Basten O, Ropero S, Hofmann E, Giese A, Behr R, Esteller M, Celda B, Monleon D, Piquer J, Llacer J, Revert A, Molla E, Martinez-Bisbal M, Entz-Werle N, Guerin E, Legrain M, Neuville A, Maitrot D, Lutz P, Kehrli P, Gaub M, Bauchet L, Rigau V, Mathieu-Daudé H, Branger D, Fabbro P, Taillandier L, Marcos-Gragera R, Raspall R, Vilardell L, Barraza G, Joly C, Garcia-Gil M, Lee H, Gilbert A, MacArthur R, Fabbro M, Maran A, Rigau V, Bauchet L, Duffau H, Peray P, Costes V, Erridge S, Kerr G, Hart M, McNamara S, Smith C, Grant R, Whittle I, Gregor A, de Campos J, Kusak M, Klein C, Ayerbe J, del Villar A, Sarasa J, de Campos J, Kusak M, Vallejo L, Sarasa J, del Villar A, Menei P, Metellus P, Loiseau H, Capelle L, Jacquet G, Guyotat J, Salvati M, Brogna C, d‘Elia A, Melone A, Lenzi J, Frati A, Santoro A, Esposito V, Giangaspero F, Delfini R, Salvati M, Brogna C, Melone A, D‘elia A, Donato V, Esposito V, Santoro A, Giangaspero F, Delfini R, Cantore G, Dresemann G, Sorenson G, Reardon D, Hosius C, Parker R, Nikolova Z, Molina-Garrido M, Guillen-Ponce C, Guirado-Risueño M, Mora A, Molina M, Molina M, Carrato A, Molnár P, Barla S, Nagy D, Nagy G, Berényi E, Dobai J, Linhares P, Martinho O, Lopes J, Vaz R, Reis R, Hwang J, Sohn Y, Hwang S, Martinez R, Hofmann E, Behr R, Basten O, Ropero S, Esteller M, Lefranc F, Ingrassia L, Van Quaquebeke E, Darro F, Kiss R, Onishi M, Ichikawa T, Inoue S, Maruo T, Kosaka H, Yoshida K, Kurozumi K, Kambara H, Chiocca E, Date I, Lefranc F, Spiegl-Kreinecker S, Haibe-Kains B, Bontempi G, Decaestecker C, Berger W, Kiss R, Oellers P, Senner V, Paulus W, Thanos S, Maruo T, Ichikawa T, Kanzaki H, Onishi M, Inoue S, Yoshida K, Kambara H, Ouchida M, Shimizu K, Date I, Jung S, Ryu H, Pei J, Jin S, Jung T, Moon K, Kim I, Kang S, Kugler W, Hülper P, Lakomek M, Gavish M, Veenman L, Short S, Martindale C, Worku M, Bourne S, Roth P, Schmidt F, Herrmann C, Kissel M, Leban J, Weller M, Kanno H, Kobayashi N, Yoshida T, Lefranc F, Mijatovic T, De Neve N, Gaussin J, Van Quaquebeke E, Van Vynckt F, Darro F, Kiss R, Mardor Y, Last D, Merchant N, Denmeade S, Daniels D, Ram Z, Chen H, Kwan A, Chen Z, Allerstorfer S, Pirker C, Spiegl-Kreinecker S, Pichler J, Buchroithner J, Grusch M, Silye R, Fischer J, Micksche M, Berger W, Toering S, Boer K, Heimans J, Aronica E, Reijneveld J, Niclou S, Danzeisen C, Brons N, Eikesdal H, Enger P, Bjerkvig R, Patil S, Burzynski S, Chittur S, Mrowczynski E, Grela K, Valle-Argos B, Gómez-Nicola D, Nieto-Sampedro M, Inda M, Bonavia R, Tan P, Hadwiger P, Mukasa A, Narita Y, Sah D, Furnari F, Cavenee W, Schichor C, von Luettichau I, Krebs B, Grau S, Herms J, Tonn J, Nelson P, Goldbrunner R
Аннотация
Background: Standard treatment consisting of surgery, irradiation plus concomitant and following T is established in GBM with median survival of 15.6 months, indicating the need for further effective treatment. In several phase II studies B plus I showed impressive objective response rates (>50%) in pre-treated GBM pts with low toxicity rate, duration of response, however, was moderate. Therefore, B plus I might be an effective induction regimen for T resistant GBM patients as basis for further treatments. In colo-rectal cancer a lower dose of B plus I was effective, therefore B and I dose was reduced. Methods: From December 2006 to October 2007, 44 pts with progressive GBM resistant to T were treated with B 4 mg/kg body weight intravenously (iv) followed by I 80 mg/m2 iv repeated every 2 weeks. ECOG performance status (PF) was 0–2 in 43 pts, 3 in 1 patient. MRI scans were required at baseline (no hemorrhage was allowed) after 4 weeks and afterward every 6 weeks. Treatment was given until progressive disease (PD) or intolerable toxicity occurred. Results: All 44 pts were eligible for toxicity and efficacy; median follow-up was 7 months; 33 pts were male, 11 female; median age was 45 years (21–79); 32 pts had primary GBM; and 12 pts secondary GBM. All pts had prior irradiation (56–60 Gy); 4 pts had 4 prior chemotherapy regimens, 11 pts 3, 22 pts 2, and 7 pts T only. The only patient with PF 3 died of clostridium sepsis during grade IV leucopenia after the first treatment; 1 patient developed grade III leucopenia; 2 pts grade III thrombopenia; 1 patient grade III pneumonia; 2 pts asymptomatic intracerebral bleeds requiring treatment delay; and 1 patient grade III fatigue. In 22 pts a partial response (PR) was achieved; in 15 pts disease stabilization for at least 2 months; and 7 pts showed primary PD. Median duration of PR was 3 months (2–8); best MRI response was acchieved after 4 to 8 weeks of treatment. Data will be updated. Conclusion: B plus I seems to be the most effective regimen for induction of objective response in multiple pretreated GBM pts with excellent toxicity profile. Efficacy of the low dose regimen was comparable to other published regimen. In targeted therapy the principle of maximum tolerated dose (MTD) is not necessarily identical with the optimal treatment dose (OTD) which might be much lower. Confirmation is required. A following maintenance treatment should be considered. Background: Tumor stem cells (TSCs) are responsible for tumor initiation and therapy resistance in a variety of cancers, including leukemia, carcinomas of the breast and colon as well as several types of brain tumors. Differentiation of TSCs has been discussed as a possible approach to eradicate the tumor-driving cell population disrooting the actively proliferating tumor bulk. Since all-trans retinoic acid (ATRA) is known as a modulator of differentiation and proliferation, we sought to elucidate whether ATRA induces differentiation of glioblastoma-derived TSCs, so-called brain tumor stem cells (BTSCs), and if tumor-relevant properties of these cells are affected by differentiation. Methods: BTSC lines (n = 3) with high CD133 content (68%–93%) were treated with ATRA-containing medium. Change in proliferation and CD133 content was monitored by BrDU incorporation assay and FACS analysis, respectively. Impact of differentiation on the angiogenic capacity of BTSCs was measured by quantification of angiogenic cytokines and assessed in a HUVEC-based tube formation assay. Potential effects on BTSC invasiveness were studied in a 3D-collagen invasion model. Finally, we studied whether in vitro effects could be confirmed in vivo using a NOD/SCID-mouse xenograft model. Results: We present evidence that BTSCs exposed to ATRA increase their proliferative activity and simultaneously lower the expression of stem cell–related antigen CD133 by up to 75% in favor of incremented linage markers GFAP, MBP, and beta3-tubulin. Furthermore, we report on significantly reduced VEGF and bFGF secretion by 70%–82% and 95%–99%, respectively, as well as significantly lowered tube formation by up to 55% following differentiation. Additionally, we show that differentiation elicits strong anti-invasive effects reducing collagen invasion by up to 46% and that these effects are associated with a marked downregulation of invasion-related MMP2 protein (up to sevenfold). Finally, we report that xenografted tumors of differentiated BTSCs are significantly smaller (only 15% of BTSC tumor volume) and less invasive than undifferentiated BTSC tumor xenografts. Correspondingly, animals bearing differentiated cells show both significantly better PFS and OS than mice with BTSC xenografts (pConclusion: Altogether, these results highlight the potential of differentiation treatment to target the tumor-driving compartment in glioblastoma and point out a potential therapeutic value in the eradication of TSCs. Introduction: Astrocytomas are the most frequent brain tumors in children, mainly low-grade neoplasias, but represent a very heterogeneous group of tumors. Aim: To review the clinical experience with low-grade astrocytomas (LGA), their histopathological and clinical features, therapeutic approach, and prognostic features. Patients and Methods: A retrospective study of children (0–18 y), diagnosed with LGA within a 30-year period (1974–2004) was performed. Histology variables included histological pattern, tumor classification (edited WHO version), and immunohistochemistry (IHC) in a tissue microarray for GFAP, WT1, p53, and ki67 expression. Results: A total of 143 patients managed at our institution for LGA were included. Average age at diagnosis was 7.4 y (SD 4.3). Seventy-three (51%) patients were male. Neurofibromatosis was documented in 11 cases (8.1%). Initial symptoms were headache (35.8%), seizures (20.9%), motor deficit (16.4%), visual (10.4%), and ataxia (9.7%). 84 tumors (58.7%) were infratentorial. Primary sites were cerebellum (41.2%), hemispheres (21.3), optic pathway (14%), brainstem (14%), spinal tumors (6.6), or mesencephalic (2.9%). Fifty tumors (39.7%) sited at midline and 30% each were right and left. Hydrocephalus was present in 61 patients (42.7%) and a mixed solid-cystic pattern was seen in 80% of cases. Only 4 patients had metastases (2.9%). Surgery was complete in 60 patients (45.1%). 27 patients had two or more resections (18.9%). A derivative procedure for hydrocephalus was required in 37 patients (27.4%), 31 of them currently device-dependent (23.1%). Pathological review classified 93 tumors as WHO grade-9 (73.8%), and 33 as grade II tumors (13 as fibrillary and 3 as pleomorhic xantoastrocytomas). IHQ for p53 was negative, save for 5 patients, all grade II tumors; Ki67 expression was >5% in 92.6% of cases, and WT1 (nuclear) 59.7%. No significative differences in survival were found among histological subtypes or IHQ pattern, but a trend for higher mortality in WT1 positive tumors was appreciated. Neurological complications were the most frequent in the immediate postoperative period (41 [31.3%]). Adjuvant therapy was given in 53 (37%) cases: radiation therapy in 36 patients (25%) and chemotherapy in 22 patients (15.3%). Currently, 15 (11.3%) patients have died of disease, 67 (50.4%) patients are alive with no evidence of disease, and 51 (38.3%) patients are alive with disease (median follow-up of 200 months). An age younger than 12 months was a prognosis factor, as 4 of 5 infants have died. Long-term secondary effects have been documented in 54 (37.8%) patients, 17 with more than one sequel. Forty-nine (35.5%) cases are lost to follow-up when discharged to adult care. Conclusions: LGA in infants have an unfavorable prognosis. We are not aware of the current status of the eldest patients; long-term follow-up is necessary, but unfeasible in the actual health setting. Imaging changes in malignant brain tumor patients may represent treatment effects rather than progression of disease [deWit MC 2004]. Pathological material from such patients generally reveals regions of bland acellular necrosis, admixed with a minority of active tumor. Such changes have been called early treatment related necrosis (ETRN) by some investigators [Chamberlain MC 2007]. ETRN has important ramifications for patient care and clinical trial design. When ETRN occurs, effective regimens may be discontinued, investigative agents may appear more effective than they are, and clinical trials designed around progression free survival endpoints may prematurely terminate. ETRN’s association with overall survival is unknown. We report a retrospective chart review of 65 newly diagnosed, high-grade gliomas treated at a single institution with concurrent radiotherapy and temozolomide. We identify eight patients with ETRN, defined as pathological findings inconsistent with tumor growth (n = 6) and >25% radiographic improvement despite therapy discontinuation (n = 1) or no therapy change (n = 1). ETRN occurred in all eight patients within six months of completing radiotherapy. We compared ETRN overall survivals with the entire cohort (n = 57); those who progressed within six months of completing radiation therapy (n = 23), but did not meet the definition of ETRN; and patients who progressed during radiation therapy (n = 7). Patients who progressed during radiotherapy had the shortest median overall survival (OS) (n = 7, OS = 4.6 months, 95%CI = 3.0–8.8) when compared with all other patients (n = 58, OS = 20.1 months, 95%CI = 15.1–23.9). This result was highly statistically significant (log-rank pIntroduction: Brain metastases from breast cancer (BCBM) have become more prevalent with improved systemic therapies for this malignancy. As a result, recurrent brain metastases after whole brain radiation therapy (WBRT) are becoming more common. Patupilone is an epothilone which crosses the blood brain barrier and is many-fold more potent than paclitaxel or docetaxel. This agent has activity against systemic breast cancer as well as brain metastases from non–small cell lung cancer. This trial evaluates patupilone in patients with BCBM. Methods: This multicenter, phase II study will enroll 45 pts with progressive, measurable BCBM after WBRT with an exploratory group of 10 additional pts with leptomeningeal disease or asymptomatic, unirradiated brain metastases. Patients may continue trastuzumab and hormonal therapy but no other chemotherapy. Patients must be at least 4 weeks past WBRT, 3 weeks past cytotoxic therapy (6 weeks for nitrosoureas), 2 weeks past noncytotoxic agents, and on a stable dose of steroids. Exclusions are prior treatment with epothilones and NCI CTC grade > 1 diarrhea or neuropathy. Patients receive patupilone 10 mg/m2 i.v. over 20 minutes every 3 weeks with MRI brain and CT chest/abdomen every 6 weeks. The primary endpoint is 3-month central nervous system (CNS) progression free survival (PFS). Secondary endpoints include toxicity, systemic disease response rate, and overall survival. Results: 18 pts have enrolled since February 2007 including 14 in the primary study group. The median age is 55 (43–68 yrs). All have had prior chemotherapy: 94% taxanes and 71% anthracyclines. Baseline KPS is 60–70 in 28% (5 pts) and 80–100 in 72% (13 pts). Toxicity data are available for 17 pts. The most common toxicity has been diarrhea—grade 1: 8 pts (47%); grade 2: 4 pts (24%) and grade 3: 5 pts (29%). Four grade 4 events (hypokalemia [2], upper GI bleeding, and anemia) have occurred. Three pts have had 25% dose reductions (myalgia, diarrhea/hypokalemia, and GI ulcer). Three patients have died, 1 possibly related to therapy. To date, best responses have been 3 partial responses (1 confirmed), 3 stable disease, 9 progressive disease, and 1 too early. One pt withdrew before assessment, and 1 pt died before assessment. The 3-month PFS in the CNS is 3/18 (17%). One pt suspected of radiographic progression on MRI underwent resection and had only necrotic tissue without viable tumor. Conclusions: Patupilone has activity against recurrent breast cancer brain metastases. The three-month CNS progression-free survival is 17%. Toxicity is acceptable in this heavily pretreated patient population. The finding of necrosis in one patient with apparent radiographic progression suggests the need for careful evaluation of previously irradiated lesions in patients treated with chemotherapy for BCBM. The role for agents like patupilone will be come more important as the ability to control systemic disease improves Introduction: Prognosis of disseminated medulloblastomas (DMB) is poor and treatment remains a major challenge in young children because of the late toxicity of standard dose craniospinal irradiation (CSI). We developed therefore a new strategy based on sequential high-dose chemotherapy (HDC) followed by autologous stem cell transplantation (ASCT) and reduced dose CSI. Patients and Methods: Thirty-four children were enrolled in this phase II study. Median age at diagnosis was 3.2 years (range, 0.8 to 7). Chang stages were M1 (6 pts) and M3 (28 pts). After initial surgery, children received two courses of carboplatin-etoposide; then peripheral blood stem cells were harvested. In absence of disease progression, five sequential courses of chemotherapy followed by ASCT were performed: melphalan (100 mg/m2) at day 43, cisplatin (100 mg/m2) at day 64, melphalan at day 85, cisplatin at day 106 and thiotepa (720 mg/m2) at day 127. Children with resectable tumor residue were operated at the end of chemotherapy. Treatment was completed by age-adapted CSI. Results: At the end of the chemotherapy 11 pts were in CR, 7 in PR. Out of the 19 pts who completed the treatment, 13 children are alive in CR1 (median follow-up, 26 months). Delivered doses of CSI were 50 Gy to the posterior fossa and 18 Gy to the brain and spinal canal in 3 pts, 50 Gy and 24 Gy in 6, and 50 Gy and 35 Gy in 1. The overall survival is 50% at 30 months. The haematological toxicity was high but manageable; no toxic death was observed. Conclusion: This chemotherapy regimen combined with reduced dose CSI produced a survival that compares favorably with published data. A longer follow-up is necessary to assess long-term quality of life. Introduction: Clinical outcomes of patients with intramedullary tumors seem to depend on histology and extent of surgical resection. The aim of our study was to assess surgical results and the neurological outcome of these patients. Material and Methods: A total of 43 tumor resections was performed in 38 patients (27 ependymoma, 7 astrocytoma WHO °I, 4 astrocytoma WHO °II) between 1/2002 and 5/2006 under intraoperative electrophysiological monitoring, 29 in the ependymoma, and 14 in the astrocytoma group. For ependymomas mean tumor extension was 2.9 levels (range 1–10), and in astrocytomas was 3.7 levels (range 1–9). In case of multilevel approaches, we performed a laminoplasty with refixation of the incised lamina(e). Routine intraoperative ultrasound and postoperative MRT was done to evaluate complete tumor removal. Clinical outcome using the McCormick scale (McC 0, no deficit −5, completely dependent) was assessed before operation, one week and 6 months after surgery. Results: Complete tumor removal was achieved in 22/29 ependymomas and in 6/14 astocytomas, 76% and 43%, respectively. Recurrent tumor growth during follow-up (range 6–40 months) was noted in 2 astrocytoma patients and no ependymoma patients. Ependymoma patients showed an improvement of neurological function during follow-up: Median McC improved from 2 (95%CI: 0.29) to 1 (0.38) after 1 week and 1 (0.40) after 6 months. In astrocytomas, in only 4/14 cases patients (McC 1–2) improved slightly. However, McC scores remained unchanged: 2 (0.36) preoperatively, 2 (0.39), and 2 (0.43) postoperatively. No neurological deterioration was seen in these patients. Conclusion: In contrast to generally high resection rates and encouraging outcomes in ependymomas, favorable neurological outcomes in astrocytomas are achieved only by (1) using cautious intraoperatibe strategies and (2) in patients with good preoperative McC. Therefore, early admission for surgery instead of watchful waiting should be the strategy in these patients. Introduction: Invasive skull base meningiomas are challenging from the surgical point of view. Although benign, meningiomas of the skull base are locally invasive and have a high recurrence rate. Materials and Methods: A total of 136 patients (82 females and 54 males) with intra- and extracranial meningiomas aged 11–72 years (median age = 49 years) were operated on by different variants of bifrontal and orbito-zygomatic approaches between 1998 and 2005. Tumor locations include anterior cranial fossa with or without extension to cribriform plate, ethmoid sinus, sphenoid sinus, orbit, subtemporal fossa, and nasal cavity. Most patients had benign meningiomas. Skull base reconstruction was usually performed with a pericranial flap, and/or abdominal fat. A temporal muscle flap was also used in some patients. The clinical outcomes were graded as follows: good (complete recovery), moderate (improvement), and poor (unchanged or severely disabled). Results: Total tumor resections were achieved in 67 cases, subtotal or large resections in 56 cases, and partial resection in 13 cases. Of 136 treated patients, good and moderate outcomes were observed in 81 and 44 patients, respectively, while 11 patients had poor outcome and 2 patients died postoperatively from pulmonary embolism within 10–15 days after surgery. Postoperative complications included CSF leakage (8 cases), infection (4 cases), transient impaired vision (9 cases), oculomotor deficit (18 cases), anosmia (12 cases). Conclusions: Total tumor removal at an early stage is the recommended therapy for the most patients but is not always feasible because of vital structures involvement at the skull base. Extensive tumor resections with intraoperative damage of cranial nerves lead to significant neurology deficiency, thus the optimal treatment of invasive skull base meningiomas is subtotal resection with subsequent radiotherapy. Background: The purpose of this report was to investigate the potential role of positrone emission tomography using 18F-fluoroetyltyrosine (FET-PET) in early detection of disease relapse or progression in high-grade gliomas. Methods: FET-PET (Advance, General Electric Medical System, Milwaukee, WI) was performed in 7 patients (pts) with high-grade gliomas after a neuroradiological suspicious of relapse/progression. Ninety minutes after the intravenous injection of approximately 185 MBq of FET, late images of the brain were obtained. FET uptake in the lesion was semiquantitatively evaluated by measuring the maximal standardized uptake value (SUVmax) and compared with the results of MRI/spectroscopy or histological specimen after surgery. Results: In the last year (November 2006–2007) 7 pts (6 men and 1 woman; median age, 47; range: 21–69) followed at our institution underwent FET-PET after the evidence of lesion enhancement on MRI. Three had a diagnosis of glioblastoma multiforme (all radically operated) and four anaplastic astrocytoma/oligoastrocytoma (2 partial and 2 complete exeresis). Four pts received radiotherapy (60 Gy in 30 fractions) and concomitant temozolomide (75 mg/msq/daily) and three only radiotherapy. Median time from the end of post-surgical therapy and neuroradiological doubt of relapse/progression was 6.3 months. In 5 pts FET-PET demonstrated an increase of FET uptake (median SUVmax values = 2.9; range: 1.7–3.4) in enhancing lesions on MRI. One patient presented a doubtful uptake in the site of the lesion, while another one presented a “circle pattern” uptake in the site of surgery. Spectroscopy was performed in 5 of 7 pts: in 4 cases it was suggestive of relapse/progression and in 1 case of radionecrosis. One patient underwent surgery for relapse: the histological sample demonstrated an active glioblastoma (KI67 = 15%). After a median follow-up of 26.1 months, 5 patients died for disease progression and 2 patients are still alive with no clear evidence of disease relapse/progression. Concordance between FET-PET and MRI/spectroscopy or histological specimen was showed in 6 of 7 patients (85%). Conclusions: FET-PET can be useful in the management of high-grade gliomas to detect relapse or tumor progression early after post-surgical treatment (chemo and/or radiotherapy). A longer follow-up and more cases are necessary to confirm this observation. Objective: The integrin alpha v beta 3 (αvβ3) has been appointed a key player in the angiogenesis of malignant gliomas. However, there is still a controversy about the expression and distribution of αvβ3 integrin due to malignancy. The aim of our study was to assess the extent and pattern of αvβ3 integrin expression within primary glioblastomas and low-grade gliomas. Methods: Immunohistochemical stainings from tumor samples (GBM: n = 12; LGG: n = 4) for detection of αvβ3 integrin (clone LM609) were performed simultaneously and automatically to reach a maximum of accuracy. Staining was quantified by a special imaging software, which was calibrated for this purpose to xenotransplanted human melanoma cells (M21) expressing αvβ3. Within a selected area, it measured (1) the mean intensity of the desired immunohistochemical staining and (2) the immunohistochemically positive fraction at a desired immunohistochemical staining intensity. To further analyze the distribution of the integrin subunits αv and β3, Western blot analysis from corresponding histological sections (GBM: n = 20; LGG: n = 5) was performed. The microvascular distribution to αvβ3 expression in these tumors was determined by costaining with endothelial cell specific markers (CD31). Results: The expression of αvβ3 was found to be significantly higher in glioblastomas than in low-grade gliomas, whereby focal strong reactivity was restricted to glioblastomas only. Different glioblastomas show a very heterogeneous expression of αvβ3 integrin which ranges from slightly to very strong integrin expression similar to high expressing non-CNS tumors. Subsequent analysis revealed that not only endothelial cells contribute to the overall amount of αvβ3 integrin in the tumors. In malignant gliomas, more than three quarters of the overall integrin expression (about 85 %) derived from glial tumor cells. Moreover, Western blot analysis demonstrated a significant difference in the expression of the β3-integrin subunit between glioblastomas and low-grade gliomas. Conclusion: The presented data lead to new insights in the pattern of αvβ3 integrin in gliomas. Since antiangiogenic therapy with integrin αvβ3-antagonists has reached clinical trials for patients with malignant gliomas minute detection and quantification of αvβ3 integrin expression could be a prerequisite for selection of patients suitable for this kind of additional therapy. High-grade gliomas are the most common primary brain tumors and associated with poor survival. Deleted in malignant brain tumor-1 (DMBT-1), is a candidate tumor suppressor gene that is located at chromosome 10q 25.3–26.1. In brain, lung, and gastrointestinal tumors, homozygous deletions and lack of mRNA expression DMBT1 are frequently observed. Phosphatase and tensin homology deleted on chromosome 10 (PTEN) expression potently suppressed the growth and tumorigenicity of human glioblastoma cells. Expression of PTEN in cancer cells devoid of a functional gene product has been shown to inhibit cellular growth and the tumorigenic capabilities of cells. Genetic alterations occurs at high frequency in a variety of human tumors is loss of heterozygosity (LOH) at 10q23. Oncogenes are generally mutated form of protooncogenes that cause the transformation of normal cells into a cancerous tumor cells. They stimulate cell growth and over-expression of these genes cause growing out of control. Human oligodendrocyte lineage transcription factors 2 (OLIG2) gene is an oncogene that is expressed strongly in oligodendroglioma. Neoplastic cells of oligodendroglioma resemble oligodendrocytes or their progenitor cells and may derive from cells of this lineage. In this study we aimed to identify the roles of these genes and correlation between their expression profiles in malignant disease progression. Human brain tumor samples were obtained from patients who underwent primary therapeutic subtotal or total tumor resection performed under surgical operation. All cases signed a written informed constant statement approved by local ethics committee. Explant cell cultures were performed from brain tumor tissues of 21 (9 females, 12 males; average age 50.24±16.10) cases. Malignant lesions have been described in the medical history of all cases: GBM WHO grade IV (21 cases). Total RNA was isolated from tumor cells. RNA of the tumor samples were reverse-transcribed with oligo dT primers and quantified by real-time reverse transcription polymerase chain reaction performed with the LightCycler instrument. U87MG glioblastoma cell line was used as positive control. Gene expression levels higher than U87MG gene expression were accepted as positive. The mean relative ratios of DMBT1, PTEN, and OLIG2 genes were found; 0.546, 203.691, and 0.661, respectively. When we compare the gene expression levels with U87-MG cells, we found that DMBT1 gene expression was significantly decreased (pBackground: We present a male patient aged 17 at diagnosis of an alveolar rhabdomyosarcoma (T4/pN2c/M0) of the paranasal sinuses with a tumor cyst (76 m³) extending per continuitatem into the left frontal cerebral lobe with no contact to the cerebrospinal fluid (CSF) system. Additionally to the systemic sarcoma chemotherapy, we locally treated the tumor cyst with repeated intraluminal liposomal cytarabine (DepoCyt) injections. DepoCyt is composed of the pyrimidine analog cytarabine which is encapsulated in multivesicular, lipid-based particles. After a single intrathecal injection these particles cause a sustained release of cytarabine, maintainig cytotoxic concentrations in the CSF up to 14 days. Procedure: At day 3 of the i.v. sarcoma chemotherapy (CHT; CWS 2002) the intracranial tumor cyst volume increased, causing symptoms of elevated intracranial pressure. Serial punctures via an implanted Rickham reservoir decreased the cyst volume and improved the symptoms. The cystic fluid showed a massive amount of tumor cells. Because of the recurrent increase in cyst volume we started an intraluminal CHT by injection of DepoCyt via the Rickham reservoir. The injections were given at day 24 (1 mg), 28 (5 mg), 35 (5 mg), and 49 (5 mg) after initiation of the i.v. sarcoma CHT. DepoCyt trough concentrations of the cystic fluid were determined prior to the injections. Meanwhile, the i.v. sarcoma CHT was continued, including an interposed local irradiation of all primary tumor sites. Results: After 4 intraluminal DepoCyt injections and concomitant i.v. sarcoma CHT, a partial shrinkage of the cyst was observed by MRI/sonography prior to the local irradiation. After the third DepoCyt injection no more cystic tumor cells were microscopically seen. The tumor cyst completely collapsed at day 53 of the i.v. sarcoma CHT and DepoCyt injections were terminated. The lowest DepoCyt concentration was 2.1 mg/l at day 5 after the first injection (1 mg). The highest concentration was 7.0 mg/l at day 8 after the second injection (5 mg). These concentrations are in the range of the ventricular CSF after an intraventricular injection of 75 mg DepoCyt in adults. The patient received 4 DepoCyt injections without side effects. Two months after termination of the primary CHT the patient experienced a multifocal relapse, but a residual of the tumor cyst was not observed. Conclusion: We conclude that the intraluminal liposomal cytarabine contributed to the disappearance of the intracranial tumor cyst and that inoperable or CHT resistent intracranial malignant cysts could locally be treated with the described strategy Introduction: Medulloblastoma is a very rare disease in adult population. Standard treatment include craniospinal irradiation (usually 36 Gy). In children risk-adapted radiation dose is employed to reduce the neurotoxicity. Toxicity of cranio-spinal irradiation is not evaluated in adults population. Material and Methods: The records of all patients with medulloblatoma who were irradiated in Centre Léon Bérard from 1978 to 2000 were retrospectively reviewed. Only patient who were free of disease more than 7 years after treatment were included in this study. The regular follow-ups were performed by the neuro-oncology team of Centre Léon Bérard. Twelve patients received serial neurocognitive testing. Results: Thirty-two patients were free of disease 7 years or more after radiotherapy (RT). At last follow-up 5 patients are working with no modification of employement. Three more patients have part-time jobs. Eight patients who were working after RT lost their jobs (5–20 years after RT) because of neurocognitive sequelae, and 2 of them were unable to take care of them at last follow-up. Severe hearing loss occurred in 15/32 patients. Three had second cancer. Among 12 patients who received serial neurocognitive testing median IQ (WAISS III) is 77. Conclusion: High incidence of toxicity suggested that current protocols may require modifications for adults with medulloblastoma. Over the past years aberrant DNA methylation was shown to be a common molecular lesion in human tumors which had also impact on patient prognosis and treatment response. In glioblastoma patients, epigenetic silencing of the promotor gene region of the O6-methylguanine-DNA methyltransferase MGMT is shown to be predictive of response to temozolomide treatment. The aim of our current study was to investigate the methylation status of MGMT and, additionally to our previous findings, p15, p16, 14ARF and correlate these results with the clinical data. DNA was isolated from fresh frozen GBM biopsies (n = 27) and modified by sodium bisulfite. Promotor methylation of p15, p16, p14ARF and MGMT was analyzed by MS-PCR. Only patients with a KPS >70, radiation and TMZ-chemotherapy after radical tumor resection were included. We observed promotor hypermethylation of MGMT in 56%, and of p15 in 37% of the tumors, whereas hypermethylation of p16 and p14arf were rare. Our previous study showed that temozolomide increases the median survival time of patients with tumors harboring deletions on 9p within the region for p15 and p16 and deletions on 10q within the region for MGMT. Interestingly, also hypermethylation of p15 emerged as a significant predictor of a shorter overall survival (16.9 vs. 23.8 months, P = 0.025; log-rank test), whereas MGMT hypermethylation had no effect on median overall survival (22.5 vs. 22.1 months, P = 0.49; log-rank test). In the presence of other clinically relevant factors (age, KPS, sex, MGMT), p15 hypermethylation remains the only significant predictor in the investigated tumors (P = 0.021; Cox regression). Although these results need to be confirmed in larger series, our retrospective study suggests that p15 hypermethylation can act as an additional important prognostic factor for survival (and treatment response) in glioblastomas. Introduction: There is an increasing interest for deeper biochemical knowledge of brain tumors for improving their diagnosis and for monitoring the treatment response. Proton magnetic resonance spectroscopy (1H MRS) is the only non-invasive technique able to investigate brain tumor molecular profiles and to provide molecular images. In addition, there are new molecular techniques that can provide detailed biochemical information in tumor biopsies: high resolution MR at magic angle (HR-MAS) and DNA microarrays. The aim of this communication is to verify the complementarity among in vivo 1H MRS and ex vivo metabolomics (HR MAS) and transcriptomics (DNA microarrays) data for improving the diagnosis and prognosis of brain tumor using multicenter protocols of a European project (eTUMOUR). Material and Methods: In vivo 1H MRS and ex vivo HR MAS and DNA microarrays were applied in 50 patients with histological diagnosis of: GBM, astrocytoma, meningioma, oligodendroglioma, oligoastrocytoma and metastasis. The range of tumor biopsy used was 16–35 mg. MRI studies were acquired in a clinical 1.5T instrument (Philips). 1H MRS protocols enclose SV (TE 31 and 136 ms) localized in the lesion, with TR = 2,000 ms. The SV was adjusted to the largest cellularity region of the lesion by using spectroscopy imaging (CSI) (TE 272 ms). HR MAS studies were done at 0C and 4 KHz spinning in 11 and 14T instruments (Bruker). Standard methods of biopsies RNA extraction were applied in the 50 patients. The quality was verified through spectrometric analysis using Agilent bio-analyzer. The expression alterations were analyzed by using pangenomic Genechip Human-Genome U133Plus2.0. Results: In vivo (1H MRS) and ex vivo (HR MAS) metabolic profiles have allowed differentiating among different brain tumors through a particular set of metabolites (lipids, choline, mio-Inositol, alanine, among others). Likewise, the alterations in transcription processes (EGFR, PTK, etc.) has also allowed a molecular differentiation among brain tumors. Conclusions: The combined use of 1H MRS, HR MAS, and DNA microarrays multicenter protocols has provided a set of biomarkers for a molecular classification of brain tumors, allowing the identification of tumor subtypes (as in GBM and meningiomas) and correlation with survival. This set of biomarkers can be used for improving the diagnosis and prognosis and for helping in a better selection and control of the therapy of brain tumors. Background: MacDonald et al. (1990) combined review of tumor imagery (e.g., MRI/CT scans), with neurological and steroid information for tumor assessment of patients with GBM in clinical trials. Completion of a randomized phase III clinical trial comparing Imatinib (I) plus Hydroxyurea (HU) vs. HU alone, as well as interim reviews of other GBM trials, demonstrated key differences between investigator and central independent review (CIR) results, and the impact of steroids within the assessment. The inclusion of a CIR team in clinical trials is ensuring consistent, high quality data when CIR teams and investigators follow and interpret assessments in a similar manner. Discussion: When using the MacDonald criteria, sensitivity analyses of progression free - (PFS) and overall survival (OS) highlighted strong similarity between the site assessment and the CIR data excluding steroids. When the same review was conducted including steroid information, site and CIR response data were markedly different. CIR review adopted a strict algorithmic approach, which was closely matched when reproducing the results programmatically. Where possible, the same methodologies as outlined in other key clinical trials were adopted, but evidently, different emphasis was placed on different aspects: MRI frequency, and the impact of steroid and neurological information varied. The discrepancy between sensitivity and specificity of neurological and/or steroid dose assessment for determination of progressive disease (PD) especially within the first 2 months after starting a new treatment is well known. Alignment and appropriate consideration of practicalities is required to permit uniform assessment across different therapies in the treatment of GBM. This will be of use to regulators, physicians, and the pharmaceutical industry as a whole. Recurrent GBM remains an unmet medical need. A comprehensive review of the impact of different ways of handling steroid, MRI, and neurological assessments was performed in relation to assessment of recurrent GBM using the MacDonald criteria. Modifications to the existing criteria are suggested to increase the specificity of assessments performed. Conclusions: Evaluation of neurological, steroid, and MRI assessments should be conducted within the same time window—initially at 4 weekly (at least first 3 months), later on at 8 weekly intervals. These intervals can be easily mapped onto each other for comparison purposes and provide a good compromise for fluctuation around the world of different timeframes in standard of care treatments. Neurological and steroid assessments should be used as preliminary-factor in determination of PD during the first 2 months of assessment to be confirmed or corrected by following clinical/neurological, steroid, and MRI assessment. Especially the influence of dexamethasone on ventral upper leg muscles must be taken into consideration. Background: Free platinum formulation: cisplatin, carboplatin and oxaliplatin as well as their liposomal formulation (Lipoplatin for cisplatin and Lipoxal for oxaliplatin) are largely used as cytotoxic agents in the treatment of many tumor types. However, free platinum formulation are known to cause severe adverse reactions including renal toxicity, gastrointestinal toxicity, peripheral neuropathy, asthenia and ototoxicity. On the other hand, radiotherapy potentially can cause the appearance of new cancers and may enhance invasion of existing cancer. To reduce side effects of these therapies and maintain an efficient antineoplasic effect, one may consider lowering the dose of individual therapeutic treatments and combining both therapies to obtain a synergistic superadditive effect. In treatment against glioblastoma multiform, the development of an aggressive but selective therapy is needed. In this project, we tested different platinum compounds to identify which one shows the best synergy with radiation. Material and Methods: The cytotoxicity of platinum compounds against F98 glioma cell line in-vitro was assessed by colony formation assay. Cell uptake of platinum in this cell line and platinum was measured by Induced coupled plasma mass spectrometer. After four hours exposure to platinum, cells were irradiated (2.21 Gy) with a 60Co source. Results: The relative cytotoxcicity induced by the five platinum formulations was oxaliplatin > Lipoxal > cisplatin > Lipoplatin > carboplatin. On the other hand, when F98 cell line incubated with platinum were irradiated, the combination index calculated and the relative potency were Lipoplatin > carboplatin > oxaliplatin > Lipoxal > cisplatin. Cell uptake of platinum were Lipoplatin > Lipoxal > oxaliplatin > cisplatin > carboplatin. Conclusions: In the present work, Lipoplatin shows the best cytotoxic combination with radiation to treat F98 cell line in vitro and shown the best cellular uptake. These results establish the efficiency of platinum compounds for radio-chemotherapy in vitro to treat F98 provide clues to manage in vivo experiments. They indicate new avenues to improve the treatment of brain cancer and increase the survival rate of GBM patients.