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1. Kindliche Tumoren

Author

Milker-Zabel, S., Wannenmacher, Michael, editor, Wenz, Frederik, editor, and Debus, Jürgen, editor

Published
2013
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7. DEGRO 2004: 10. Jahreskongress der Deutschen Gesellschaft für Radioonkologie

Author

Wendt, Thomas G., Gademann, G., Pambor, C., Grießbach, I., von Specht, H., Martin, T., Baltas, D., Kurek, R., Röddiger, S., Tunn, U. W., Zamboglou, N., Eich, H. T., Staar, S., Gossmann, A., Hansemann, K., Semrau, R., Skripnitchenko, R., Diehl, V., Müller, R.-P., Sehlen, S., Willich, N., Rühl, U., Lukas, P., Dühmke, E., Engel, K., Tabbert, E., Bolck, M., Knaack, S., Annweiler, H., Krempien, R., Hoppe, H., Harms, W., Daeuber, S., Schorr, O., Treiber, M., Debus, J., Alber, M., Paulsen, F., Birkner, M., Bakai, A., Belka, C., Budach, W., Grosser, K.-H., Kramer, R., Kober, B., Reinert, M., Schneider, P., Hertel, A., Feldmann, H., Csere, P., Hoinkis, C., Rothe, G., Zahn, P., Alheit, H., Cavanaugh, S. X., Kupelian, P., Reddy, C., Pollock, B., Fuss, M., Roeddiger, S., Dannenberg, T., Rogge, B., Drechsler, D., Herrmann, T., Alberti, W., Schwarz, R., Graefen, M., Krüll, A., Rudat, V., Huland, H., Fehr, C., Baum, C., Glocker, S., Nüsslin, F., Heil, T., Lemnitzer, H., Knips, M., Baumgart, O., Thiem, W., Kloetzer, K.-H., Hoffmann, L., Neu, B., Hültenschmidt, B., Sautter-Bihl, M.-L., Micke, O., Seegenschmiedt, M. H., Köppen, D., Klautke, G., Fietkau, R., Schultze, J., Schlichting, G., Koltze, H., Kimmig, B., Glatzel, M., Fröhlich, D., Bäsecke, S., Krauß, A., Strauß, D., Buth, K.-J., Böhme, R., Oehler, W., Bottke, D., Keilholz, U., Heufelder, K., Wiegel, T., Hinkelbein, W., Rödel, C., Papadopoulos, T., Munnes, M., Wirtz, R., Sauer, R., Rödel, F., Lubgan, D., Distel, L., Grabenbauer, G. G., Sak, A., Stüben, G., Pöttgen, C., Grehl, S., Stuschke, M., Müller, K., Pfaffendorf, C., Mayerhofer, A., Köhn, F. M., Ring, J., van Beuningen, D., Meineke, V., Neubauer, S., Keller, U., Wittlinger, M., Riesenbeck, D., Greve, B., Exeler, R., Ibrahim, M., Liebscher, C., Severin, E., Ott, O., Pötter, R., Hammer, J., Hildebrandt, G., Beckmann, M. W., Strnad, V., Fehlauer, F., Tribius, S., Bajrovic, A., Höller, U., Rades, D., Warszawski, A., Baumann, R., Madry-Gevecke, B., Karstens, J. H., Grehn, C., Hensley, F., Berns, C., Wannenmacher, M., Semrau, S., Reimer, T., Gerber, B., Ketterer, P., Koepcke, E., Hänsgen, G., Strauß, H. G., Dunst, J., Füller, J., Kalb, S., Wendt, T., Weitmann, H. D., Waldhäusl, C., Knocke, T.-H., Lamprecht, U., Classen, J., Kaulich, T. W., Aydeniz, B., Bamberg, M., Wiezorek, T., Banz, N., Salz, H., Scheithauer, M., Schwedas, M., Lutterbach, J., Bartelt, S., Frommhold, H., Lambert, J., Hornung, D., Swiderski, S., Walke, M., Siefert, A., Pöllinger, B., Krimmel, K., Schaffer, M., Koelbl, O., Bratengeier, K., Vordermark, D., Flentje, M., Hero, B., Berthold, F., Combs, S. E., Gutwein, S., Schulz-Ertner, D., van Kampen, M., Thilmann, C., Kocher, M., Kunze, S., Schild, S., Ikezaki, K., Müller, B., Sieber, R., Weiß, C., Wolf, I., Wenz, F., Weber, K.-J., Schäfer, J., Engling, A., Laufs, S., Veldwijk, M. R., Milanovic, D., Fleckenstein, K., Zeller, W., Fruehauf, S., Herskind, C., Weinmann, M., Jendrossek, V., Rübe, C., Appold, S., Kusche, S., Hölscher, T., Brüchner, K., Geyer, P., Baumann, M., Kumpf, R., Zimmermann, F., Schill, S., Geinitz, H., Nieder, C., Jeremic, B., Molls, M., Liesenfeld, S., Petrat, H., Hesselmann, S., Schäfer, U., Bruns, F., Horst, E., Wilkowski, R., Assmann, G., Nolte, A., Diebold, J., Löhrs, U., Fritz, P., Hans-Jürgen, K., Mühlnickel, W., Bach, P., Wahlers, B., Kraus, H.-J., Wulf, J., Hädinger, U., Baier, K., Krieger, T., Müller, G., Hof, H., Herfarth, K., Brunner, T., Hahn, S. M., Schreiber, F. S., Rustgi, A. K., McKenna, W. G., Bernhard, E. J., Guckenberger, M., Meyer, K., Willner, J., Schmidt, M., Kolb, M., Li, M., Gong, P., Abdollahi, A., Trinh, T., Huber, P. E., Christiansen, H., Saile, B., Neubauer-Saile, K., Tippelt, S., Rave-Fränk, M., Hermann, R. M., Dudas, J., Hess, C. F., Schmidberger, H., Ramadori, G., Andratschke, N., Price, R., Ang, K.-K., Schwarz, S., Kulka, U., Busch, M., Schlenger, L., Bohsung, J., Eichwurzel, I., Matnjani, G., Sandrock, D., Richter, M., Wurm, R., Budach, V., Feussner, A., Gellermann, J., Jordan, A., Scholz, R., Gneveckow, U., Maier-Hauff, K., Ullrich, R., Wust, P., Felix, R., Waldöfner, N., Seebass, M., Ochel, H.-J., Dani, A., Varkonyi, A., Osvath, M., Szasz, A., Messer, P. M., Blumstein, N. M., Gottfried, H.-W., Schneider, E., Reske, S. N., Röttinger, E. M., Grosu, A.-L., Franz, M., Stärk, S., Weber, W., Heintz, M., Indenkämpen, F., Beyer, T., Lübcke, W., Levegrün, S., Hayen, J., Czech, N., Mbarek, B., Köster, R., Thurmann, H., Todorovic, M., Schuchert, A., Meinertz, T., Münzel, T., Grundtke, H., Hornig, B., Hehr, T., Dilcher, C., Chan, R. C., Mintz, G. S., Kotani, J.-I., Shah, V. M., Canos, D. A., Weissman, N. J., Waksman, R., Wolfram, R., Bürger, B., Schrappe, M., Timmermann, B., Lomax, A., Goitein, G., Schuck, A., Mattke, A., Int-Veen, C., Brecht, I., Bernhard, S., Treuner, J., Koscielniak, E., Heinze, F., Kuhlen, M., von Schorlemer, I., Ahrens, S., Hunold, A., Könemann, S., Winkelmann, W., Jürgens, H., Gerstein, J., Polivka, B., Sykora, K.-W., Bremer, M., Thamm, R., Höpfner, C., Gumprecht, H., Jäger, R., Leonardi, M. A., Frank, A. M., Trappe, A. E., Lumenta, C. B., Östreicher, E., Pinsker, K., Müller, A., Fauser, C., Arnold, W., Henzel, M., Groß, M. W., Engenhart-Cabillic, R., Schüller, P., Palkovic, S., Schröder, J., Wassmann, H., Block, A., Bauer, R., Keffel, F.-W., Theophil, B., Wisser, L., Rogger, M., Niewald, M., van Lengen, V., Mathias, K., Welzel, G., Bohrer, M., Steinvorth, S., Schleußner, C., Leppert, K., Röhrig, B., Strauß, B., van Oorschot, B., Köhler, N., Anselm, R., Winzer, A., Schneider, T., Koch, U., Schönekaes, K., Mücke, R., Büntzel, J., Kisters, K., Scholz, C., Keller, M., Winkler, C., Prause, N., Busch, R., Roth, S., Haas, I., Willers, R., Schultze-Mosgau, S., Wiltfang, J., Kessler, P., Neukam, F. W., Röper, B., Nüse, N., Auer, F., Melzner, W., Geiger, M., Lotter, M., Kuhnt, T., Müller, A. C., Jirsak, N., Gernhardt, C., Schaller, H.-G., Al-Nawas, B., Klein, M. O., Ludwig, C., Körholz, J., Grötz, K. A., Huppers, K., Kunkel, M., Olschewski, T., Bajor, K., Lang, B., Lang, E., Kraus-Tiefenbacher, U., Hofheinz, R., von Gerstenberg-Helldorf, B., Willeke, F., Hochhaus, A., Roebel, M., Oertel, S., Riedl, S., Buechler, M., Foitzik, T., Ludwig, K., Klar, E., Meyer, A., Meier zu Eissen, J., Schwab, D., Meyer, T., Höcht, S., Siegmann, A., Sieker, F., Pigorsch, S., Milicic, B., Acimovic, L., Milisavljevic, S., Radosavljevic-Asic, G., Presselt, N., Baum, R. P., Treutler, D., Bonnet, R., Schmücking, M., Sammour, D., Fink, T., Ficker, J., Pradier, O., Lederer, K., Weiss, E., Hille, A., Welz, S., Sepe, S., Friedel, G., Spengler, W., Susanne, E., Kölbl, O., Hoffmann, W., Wörmann, B., Günther, A., Becker-Schiebe, M., Güttler, J., Schul, C., Nitsche, M., Körner, M. K., Oppenkowski, R., Guntrum, F., Malaimare, L., Raub, M., Schöfl, C., Averbeck, T., Hacker, I., Blank, H., Böhme, C., Imhoff, D., Eberlein, K., Weidauer, S., Böttcher, H. D., Edler, L., Tatagiba, M., Molina, H., Ostertag, C., Milker-Zabel, S., Zabel, A., Schlegel, W., Hartmann, A., Wildfang, I., Kleinert, G., Hamm, K., Reuschel, W., Wehrmann, R., Kneschaurek, P., Münter, M. W., Nikoghosyan, A., Didinger, B., Nill, S., Rhein, B., Küstner, D., Schalldach, U., Eßer, D., Göbel, H., Wördehoff, H., Pachmann, S., Hollenhorst, H., Dederer, K., Evers, C., Lamprecht, J., Dastbaz, A., Schick, B., Fleckenstein, J., Plinkert, P. K., Rübe, Chr., Merz, T., Sommer, B., Mencl, A., Ghilescu, V., Astner, S., Martin, A., Momm, F., Volegova-Neher, N. J., Schulte-Mönting, J., Guttenberger, R., Buchali, A., Blank, E., Sidow, D., Huhnt, W., Gorbatov, T., Heinecke, A., Beckmann, G., Bentia, A.-M., Schmitz, H., Spahn, U., Heyl, V., Prott, P.-J., Galalae, R., Schneider, R., Voith, C., Scheda, A., Hermann, B., Bauer, L., Melchert, F., Kröger, N., Grüneisen, A., Jänicke, F., Zander, A., Zuna, I., Schlöcker, I., Wagner, K., John, E., Dörk, T., Lochhas, G., Houf, M., Lorenz, D., Link, K.-H., Prott, F.-J., Thoma, M., Schauer, R., Heinemann, V., Romano, M., Reiner, M., Quanz, A., Oppitz, U., Bahrehmand, R., Tine, M., Naszaly, A., Patonay, P., Mayer, Á., Markert, K., Mai, S.-K., Lohr, F., Dobler, B., Pinkawa, M., Fischedick, K., Treusacher, P., Cengiz, D., Mager, R., Borchers, H., Jakse, G., Eble, M. J., Asadpour, B., Krenkel, B., Holy, R., Kaplan, Y., Block, T., Czempiel, H., Haverkamp, U., Prümer, B., Christian, T., Benkel, P., Weber, C., Gruber, S., Reimann, P., Blumberg, J., Krause, K., Fischedick, A.-R., Kaube, K., Steckler, K., Henzel, B., Licht, N., Loch, T., Krystek, A., Lilienthal, A., Alfia, H., Claßen, J., Spillner, P., Knutzen, B., Souchon, R., Schulz, I., Grüschow, K., Küchenmeister, U., Vogel, H., Wolff, D., Ramm, U., Licner, J., Rudolf, F., Moog, J., Rahl, C. G., Mose, S., Vorwerk, H., Weiß, E., Engert, A., Seufert, I., Schwab, F., Dahlke, J., Zabelina, T., Krüger, W., Kabisch, H., Platz, V., Wolf, J., Pfistner, B., Stieltjes, B., Wilhelm, T., Schmuecking, M., Junker, K., Treutier, D., Schneider, C. P., Leonhardi, J., Niesen, A., Hoeffken, K., Schmidt, A., Mueller, K.-M., Schmid, I., Lehmann, K., Blumstein, C. G., Kreienberg, R., Freudenberg, L., Kühl, H., Stahl, M., Elo, B., Erichsen, P., Stattaus, H., Welzel, T., Mende, U., Heiland, S., Salter, B. J., Schmid, R., Stratakis, D., Huber, R. M., Haferanke, J., Zöller, N., Henke, M., Lorenzen, J., Grzyska, B., Kuhlmey, A., Adam, G., Hamelmann, V., Bölling, T., Job, H., Panke, J. E., Feyer, P., Püttmann, S., Siekmeyer, B., Jung, H., Gagel, B., Militz, U., Piroth, M., Schmachtenberg, A., Hoelscher, T., Verfaillie, C., Kaminski, B., Lücke, E., Mörtel, H., Eyrich, W., Fritsch, M., Georgi, J.-C., Plathow, C., Zieher, H., Kiessling, F., Peschke, P., Kauczor, H.-U., Licher, J., Schneider, O., Henschler, R., Seidel, C., Kolkmeyer, A., Nguyen, T. P., Janke, K., Michaelis, M., Bischof, M., Stoffregen, C., Lipson, K., Weber, K., Ehemann, V., Jürgen, D., Achanta, P., Thompson, K., Martinez, J. L., Körschgen, T., Pakala, R., Pinnow, E., Hellinga, D., O’Tio, F., Katzer, A., Kaffer, A., Kuechler, A., Steinkirchner, S., Dettmar, N., Cordes, N., Frick, S., Kappler, M., Taubert, H., Bartel, F., Schmidt, H., Bache, M., Frühauf, S., Wenk, T., Litzenberger, K., Erren, M., van Valen, F., Liu, L., Yang, K., Palm, J., Püsken, M., Behe, M., Behr, T. M., Marini, P., Johne, A., Claussen, U., Liehr, T., Steil, V., Moustakis, C., Griessbach, I., Oettel, A., Schaal, C., Reinhold, M., Strasssmann, G., Braun, I., Vacha, P., Richter, D., Osterham, T., Wolf, P., Guenther, G., Miemietz, M., Lazaridis, E. A., Forthuber, B., Sure, M., Klein, J., Saleske, H., Riedel, T., Hirnle, P., Horstmann, G., Schoepgens, H., Van Eck, A., Bundschuh, O., Van Oosterhut, A., Xydis, K., Theodorou, K., Kappas, C., Zurheide, J., Fridtjof, N., Ganswindt, U., Weidner, N., Buchgeister, M., Weigel, B., Müller, S. B., Glashörster, M., Weining, C., Hentschel, B., Sauer, O. A., Kleen, W., Beck, J., Lehmann, D., Ley, S., Fink, C., Puderbach, M., Hosch, W., Schmähl, A., Jung, K., Stoßberg, A., Rolf, E., Damrau, M., Oetzel, D., Maurer, U., Maurer, G., Lang, K., Zumbe, J., Hahm, D., Fees, H., Robrandt, B., Melcher, U., Niemeyer, M., Mondry, A., Kanellopoulos-Niemeyer, V., Karle, H., Jacob-Heutmann, D., Born, C., Mohr, W., Kutzner, J., Thelen, M., Schiebe, M., Pinkert, U., Piasswilm, L., Pohl, F., Garbe, S., Wolf, K., Nour, Y., Barwig, P., Trog, D., Schäfer, C., Herbst, M., Dietl, B., Cartes, M., Schroeder, F., Sigingan-Tek, G., Feierabend, R., Theden, S., Schlieck, A., Gotthardt, M., Glowalla, U., Kremp, S., Hamid, O., Riefenstahl, N., Michaelis, B., Schaal, G., Liebermeister, E., Niewöhner-Desbordes, U., Kowalski, M., Franz, N., Stahl, W., Baumbach, C., Thale, J., Wagner, W., Justus, B., Huston, A. L., Seaborn, R., Rai, P., Rha, S.-W., Sakas, G., Wesarg, S., Zogal, P., Schwald, B., Seibert, H., Berndt-Skorka, R., Seifert, G., Schoenekaes, K., Bilecen, C., Ito, W., Matschuck, G., and Isik, D.

Published
2004
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15. 2537

Author

Zabel-du Bois, A., primary, Milker-Zabel, S., additional, Huber, P., additional, Schlegel, W., additional, and Debus, J., additional

Published
2006
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16. 2538

Author

Milker-Zabel, S., primary, Zabel-du Bois, A., additional, Huber, P., additional, Schlegel, W., additional, and Debus, J., additional

Published
2006
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20. DEGRO 2004

Author

Wendt, Thomas G., primary, Gademann, G., additional, Pambor, C., additional, Grießbach, I., additional, von Specht, H., additional, Martin, T., additional, Baltas, D., additional, Kurek, R., additional, Röddiger, S., additional, Tunn, U. W., additional, Zamboglou, N., additional, Eich, H. T., additional, Staar, S., additional, Gossmann, A., additional, Hansemann, K., additional, Semrau, R., additional, Skripnitchenko, R., additional, Diehl, V., additional, Müller, R.-P., additional, Sehlen, S., additional, Willich, N., additional, Rühl, U., additional, Lukas, P., additional, Dühmke, E., additional, Engel, K., additional, Tabbert, E., additional, Bolck, M., additional, Knaack, S., additional, Annweiler, H., additional, Krempien, R., additional, Hoppe, H., additional, Harms, W., additional, Daeuber, S., additional, Schorr, O., additional, Treiber, M., additional, Debus, J., additional, Alber, M., additional, Paulsen, F., additional, Birkner, M., additional, Bakai, A., additional, Belka, C., additional, Budach, W., additional, Grosser, K.-H., additional, Kramer, R., additional, Kober, B., additional, Reinert, M., additional, Schneider, P., additional, Hertel, A., additional, Feldmann, H., additional, Csere, P., additional, Hoinkis, C., additional, Rothe, G., additional, Zahn, P., additional, Alheit, H., additional, Cavanaugh, S. X., additional, Kupelian, P., additional, Reddy, C., additional, Pollock, B., additional, Fuss, M., additional, Roeddiger, S., additional, Dannenberg, T., additional, Rogge, B., additional, Drechsler, D., additional, Herrmann, T., additional, Alberti, W., additional, Schwarz, R., additional, Graefen, M., additional, Krüll, A., additional, Rudat, V., additional, Huland, H., additional, Fehr, C., additional, Baum, C., additional, Glocker, S., additional, Nüsslin, F., additional, Heil, T., additional, Lemnitzer, H., additional, Knips, M., additional, Baumgart, O., additional, Thiem, W., additional, Kloetzer, K.-H., additional, Hoffmann, L., additional, Neu, B., additional, Hültenschmidt, B., additional, Sautter-Bihl, M.-L., additional, Micke, O., additional, Seegenschmiedt, M. H., additional, Köppen, D., additional, Klautke, G., additional, Fietkau, R., additional, Schultze, J., additional, Schlichting, G., additional, Koltze, H., additional, Kimmig, B., additional, Glatzel, M., additional, Fröhlich, D., additional, Bäsecke, S., additional, Krauß, A., additional, Strauß, D., additional, Buth, K.-J., additional, Böhme, R., additional, Oehler, W., additional, Bottke, D., additional, Keilholz, U., additional, Heufelder, K., additional, Wiegel, T., additional, Hinkelbein, W., additional, Rödel, C., additional, Papadopoulos, T., additional, Munnes, M., additional, Wirtz, R., additional, Sauer, R., additional, Rödel, F., additional, Lubgan, D., additional, Distel, L., additional, Grabenbauer, G. G., additional, Sak, A., additional, Stüben, G., additional, Pöttgen, C., additional, Grehl, S., additional, Stuschke, M., additional, Müller, K., additional, Pfaffendorf, C., additional, Mayerhofer, A., additional, Köhn, F. M., additional, Ring, J., additional, van Beuningen, D., additional, Meineke, V., additional, Neubauer, S., additional, Keller, U., additional, Wittlinger, M., additional, Riesenbeck, D., additional, Greve, B., additional, Exeler, R., additional, Ibrahim, M., additional, Liebscher, C., additional, Severin, E., additional, Ott, O., additional, Pötter, R., additional, Hammer, J., additional, Hildebrandt, G., additional, Beckmann, M. W., additional, Strnad, V., additional, Fehlauer, F., additional, Tribius, S., additional, Bajrovic, A., additional, Höller, U., additional, Rades, D., additional, Warszawski, A., additional, Baumann, R., additional, Madry-Gevecke, B., additional, Karstens, J. H., additional, Grehn, C., additional, Hensley, F., additional, Berns, C., additional, Wannenmacher, M., additional, Semrau, S., additional, Reimer, T., additional, Gerber, B., additional, Ketterer, P., additional, Koepcke, E., additional, Hänsgen, G., additional, Strauß, H. G., additional, Dunst, J., additional, Füller, J., additional, Kalb, S., additional, Wendt, T., additional, Weitmann, H. D., additional, Waldhäusl, C., additional, Knocke, T.-H., additional, Lamprecht, U., additional, Classen, J., additional, Kaulich, T. W., additional, Aydeniz, B., additional, Bamberg, M., additional, Wiezorek, T., additional, Banz, N., additional, Salz, H., additional, Scheithauer, M., additional, Schwedas, M., additional, Lutterbach, J., additional, Bartelt, S., additional, Frommhold, H., additional, Lambert, J., additional, Hornung, D., additional, Swiderski, S., additional, Walke, M., additional, Siefert, A., additional, Pöllinger, B., additional, Krimmel, K., additional, Schaffer, M., additional, Koelbl, O., additional, Bratengeier, K., additional, Vordermark, D., additional, Flentje, M., additional, Hero, B., additional, Berthold, F., additional, Combs, S. E., additional, Gutwein, S., additional, Schulz-Ertner, D., additional, van Kampen, M., additional, Thilmann, C., additional, Kocher, M., additional, Kunze, S., additional, Schild, S., additional, Ikezaki, K., additional, Müller, B., additional, Sieber, R., additional, Weiß, C., additional, Wolf, I., additional, Wenz, F., additional, Weber, K.-J., additional, Schäfer, J., additional, Engling, A., additional, Laufs, S., additional, Veldwijk, M. R., additional, Milanovic, D., additional, Fleckenstein, K., additional, Zeller, W., additional, Fruehauf, S., additional, Herskind, C., additional, Weinmann, M., additional, Jendrossek, V., additional, Rübe, C., additional, Appold, S., additional, Kusche, S., additional, Hölscher, T., additional, Brüchner, K., additional, Geyer, P., additional, Baumann, M., additional, Kumpf, R., additional, Zimmermann, F., additional, Schill, S., additional, Geinitz, H., additional, Nieder, C., additional, Jeremic, B., additional, Molls, M., additional, Liesenfeld, S., additional, Petrat, H., additional, Hesselmann, S., additional, Schäfer, U., additional, Bruns, F., additional, Horst, E., additional, Wilkowski, R., additional, Assmann, G., additional, Nolte, A., additional, Diebold, J., additional, Löhrs, U., additional, Fritz, P., additional, Hans-Jürgen, K., additional, Mühlnickel, W., additional, Bach, P., additional, Wahlers, B., additional, Kraus, H.-J., additional, Wulf, J., additional, Hädinger, U., additional, Baier, K., additional, Krieger, T., additional, Müller, G., additional, Hof, H., additional, Herfarth, K., additional, Brunner, T., additional, Hahn, S. M., additional, Schreiber, F. S., additional, Rustgi, A. K., additional, McKenna, W. G., additional, Bernhard, E. J., additional, Guckenberger, M., additional, Meyer, K., additional, Willner, J., additional, Schmidt, M., additional, Kolb, M., additional, Li, M., additional, Gong, P., additional, Abdollahi, A., additional, Trinh, T., additional, Huber, P. E., additional, Christiansen, H., additional, Saile, B., additional, Neubauer-Saile, K., additional, Tippelt, S., additional, Rave-Fränk, M., additional, Hermann, R. M., additional, Dudas, J., additional, Hess, C. F., additional, Schmidberger, H., additional, Ramadori, G., additional, Andratschke, N., additional, Price, R., additional, Ang, K.-K., additional, Schwarz, S., additional, Kulka, U., additional, Busch, M., additional, Schlenger, L., additional, Bohsung, J., additional, Eichwurzel, I., additional, Matnjani, G., additional, Sandrock, D., additional, Richter, M., additional, Wurm, R., additional, Budach, V., additional, Feussner, A., additional, Gellermann, J., additional, Jordan, A., additional, Scholz, R., additional, Gneveckow, U., additional, Maier-Hauff, K., additional, Ullrich, R., additional, Wust, P., additional, Felix, R., additional, Waldöfner, N., additional, Seebass, M., additional, Ochel, H.-J., additional, Dani, A., additional, Varkonyi, A., additional, Osvath, M., additional, Szasz, A., additional, Messer, P. M., additional, Blumstein, N. M., additional, Gottfried, H.-W., additional, Schneider, E., additional, Reske, S. N., additional, Röttinger, E. M., additional, Grosu, A.-L., additional, Franz, M., additional, Stärk, S., additional, Weber, W., additional, Heintz, M., additional, Indenkämpen, F., additional, Beyer, T., additional, Lübcke, W., additional, Levegrün, S., additional, Hayen, J., additional, Czech, N., additional, Mbarek, B., additional, Köster, R., additional, Thurmann, H., additional, Todorovic, M., additional, Schuchert, A., additional, Meinertz, T., additional, Münzel, T., additional, Grundtke, H., additional, Hornig, B., additional, Hehr, T., additional, Dilcher, C., additional, Chan, R. C., additional, Mintz, G. S., additional, Kotani, J.-I., additional, Shah, V. M., additional, Canos, D. A., additional, Weissman, N. J., additional, Waksman, R., additional, Wolfram, R., additional, Bürger, B., additional, Schrappe, M., additional, Timmermann, B., additional, Lomax, A., additional, Goitein, G., additional, Schuck, A., additional, Mattke, A., additional, Int-Veen, C., additional, Brecht, I., additional, Bernhard, S., additional, Treuner, J., additional, Koscielniak, E., additional, Heinze, F., additional, Kuhlen, M., additional, von Schorlemer, I., additional, Ahrens, S., additional, Hunold, A., additional, Könemann, S., additional, Winkelmann, W., additional, Jürgens, H., additional, Gerstein, J., additional, Polivka, B., additional, Sykora, K.-W., additional, Bremer, M., additional, Thamm, R., additional, Höpfner, C., additional, Gumprecht, H., additional, Jäger, R., additional, Leonardi, M. A., additional, Frank, A. M., additional, Trappe, A. E., additional, Lumenta, C. B., additional, Östreicher, E., additional, Pinsker, K., additional, Müller, A., additional, Fauser, C., additional, Arnold, W., additional, Henzel, M., additional, Groß, M. W., additional, Engenhart-Cabillic, R., additional, Schüller, P., additional, Palkovic, S., additional, Schröder, J., additional, Wassmann, H., additional, Block, A., additional, Bauer, R., additional, Keffel, F.-W., additional, Theophil, B., additional, Wisser, L., additional, Rogger, M., additional, Niewald, M., additional, van Lengen, V., additional, Mathias, K., additional, Welzel, G., additional, Bohrer, M., additional, Steinvorth, S., additional, Schleußner, C., additional, Leppert, K., additional, Röhrig, B., additional, Strauß, B., additional, van Oorschot, B., additional, Köhler, N., additional, Anselm, R., additional, Winzer, A., additional, Schneider, T., additional, Koch, U., additional, Schönekaes, K., additional, Mücke, R., additional, Büntzel, J., additional, Kisters, K., additional, Scholz, C., additional, Keller, M., additional, Winkler, C., additional, Prause, N., additional, Busch, R., additional, Roth, S., additional, Haas, I., additional, Willers, R., additional, Schultze-Mosgau, S., additional, Wiltfang, J., additional, Kessler, P., additional, Neukam, F. W., additional, Röper, B., additional, Nüse, N., additional, Auer, F., additional, Melzner, W., additional, Geiger, M., additional, Lotter, M., additional, Kuhnt, T., additional, Müller, A. C., additional, Jirsak, N., additional, Gernhardt, C., additional, Schaller, H.-G., additional, Al-Nawas, B., additional, Klein, M. O., additional, Ludwig, C., additional, Körholz, J., additional, Grötz, K. A., additional, Huppers, K., additional, Kunkel, M., additional, Olschewski, T., additional, Bajor, K., additional, Lang, B., additional, Lang, E., additional, Kraus-Tiefenbacher, U., additional, Hofheinz, R., additional, von Gerstenberg-Helldorf, B., additional, Willeke, F., additional, Hochhaus, A., additional, Roebel, M., additional, Oertel, S., additional, Riedl, S., additional, Buechler, M., additional, Foitzik, T., additional, Ludwig, K., additional, Klar, E., additional, Meyer, A., additional, Meier zu Eissen, J., additional, Schwab, D., additional, Meyer, T., additional, Höcht, S., additional, Siegmann, A., additional, Sieker, F., additional, Pigorsch, S., additional, Milicic, B., additional, Acimovic, L., additional, Milisavljevic, S., additional, Radosavljevic-Asic, G., additional, Presselt, N., additional, Baum, R. P., additional, Treutler, D., additional, Bonnet, R., additional, Schmücking, M., additional, Sammour, D., additional, Fink, T., additional, Ficker, J., additional, Pradier, O., additional, Lederer, K., additional, Weiss, E., additional, Hille, A., additional, Welz, S., additional, Sepe, S., additional, Friedel, G., additional, Spengler, W., additional, Susanne, E., additional, Kölbl, O., additional, Hoffmann, W., additional, Wörmann, B., additional, Günther, A., additional, Becker-Schiebe, M., additional, Güttler, J., additional, Schul, C., additional, Nitsche, M., additional, Körner, M. K., additional, Oppenkowski, R., additional, Guntrum, F., additional, Malaimare, L., additional, Raub, M., additional, Schöfl, C., additional, Averbeck, T., additional, Hacker, I., additional, Blank, H., additional, Böhme, C., additional, Imhoff, D., additional, Eberlein, K., additional, Weidauer, S., additional, Böttcher, H. D., additional, Edler, L., additional, Tatagiba, M., additional, Molina, H., additional, Ostertag, C., additional, Milker-Zabel, S., additional, Zabel, A., additional, Schlegel, W., additional, Hartmann, A., additional, Wildfang, I., additional, Kleinert, G., additional, Hamm, K., additional, Reuschel, W., additional, Wehrmann, R., additional, Kneschaurek, P., additional, Münter, M. W., additional, Nikoghosyan, A., additional, Didinger, B., additional, Nill, S., additional, Rhein, B., additional, Küstner, D., additional, Schalldach, U., additional, Eßer, D., additional, Göbel, H., additional, Wördehoff, H., additional, Pachmann, S., additional, Hollenhorst, H., additional, Dederer, K., additional, Evers, C., additional, Lamprecht, J., additional, Dastbaz, A., additional, Schick, B., additional, Fleckenstein, J., additional, Plinkert, P. K., additional, Rübe, Chr., additional, Merz, T., additional, Sommer, B., additional, Mencl, A., additional, Ghilescu, V., additional, Astner, S., additional, Martin, A., additional, Momm, F., additional, Volegova-Neher, N. J., additional, Schulte-Mönting, J., additional, Guttenberger, R., additional, Buchali, A., additional, Blank, E., additional, Sidow, D., additional, Huhnt, W., additional, Gorbatov, T., additional, Heinecke, A., additional, Beckmann, G., additional, Bentia, A.-M., additional, Schmitz, H., additional, Spahn, U., additional, Heyl, V., additional, Prott, P.-J., additional, Galalae, R., additional, Schneider, R., additional, Voith, C., additional, Scheda, A., additional, Hermann, B., additional, Bauer, L., additional, Melchert, F., additional, Kröger, N., additional, Grüneisen, A., additional, Jänicke, F., additional, Zander, A., additional, Zuna, I., additional, Schlöcker, I., additional, Wagner, K., additional, John, E., additional, Dörk, T., additional, Lochhas, G., additional, Houf, M., additional, Lorenz, D., additional, Link, K.-H., additional, Prott, F.-J., additional, Thoma, M., additional, Schauer, R., additional, Heinemann, V., additional, Romano, M., additional, Reiner, M., additional, Quanz, A., additional, Oppitz, U., additional, Bahrehmand, R., additional, Tine, M., additional, Naszaly, A., additional, Patonay, P., additional, Mayer, Á., additional, Markert, K., additional, Mai, S.-K., additional, Lohr, F., additional, Dobler, B., additional, Pinkawa, M., additional, Fischedick, K., additional, Treusacher, P., additional, Cengiz, D., additional, Mager, R., additional, Borchers, H., additional, Jakse, G., additional, Eble, M. J., additional, Asadpour, B., additional, Krenkel, B., additional, Holy, R., additional, Kaplan, Y., additional, Block, T., additional, Czempiel, H., additional, Haverkamp, U., additional, Prümer, B., additional, Christian, T., additional, Benkel, P., additional, Weber, C., additional, Gruber, S., additional, Reimann, P., additional, Blumberg, J., additional, Krause, K., additional, Fischedick, A.-R., additional, Kaube, K., additional, Steckler, K., additional, Henzel, B., additional, Licht, N., additional, Loch, T., additional, Krystek, A., additional, Lilienthal, A., additional, Alfia, H., additional, Claßen, J., additional, Spillner, P., additional, Knutzen, B., additional, Souchon, R., additional, Schulz, I., additional, Grüschow, K., additional, Küchenmeister, U., additional, Vogel, H., additional, Wolff, D., additional, Ramm, U., additional, Licner, J., additional, Rudolf, F., additional, Moog, J., additional, Rahl, C. G., additional, Mose, S., additional, Vorwerk, H., additional, Weiß, E., additional, Engert, A., additional, Seufert, I., additional, Schwab, F., additional, Dahlke, J., additional, Zabelina, T., additional, Krüger, W., additional, Kabisch, H., additional, Platz, V., additional, Wolf, J., additional, Pfistner, B., additional, Stieltjes, B., additional, Wilhelm, T., additional, Schmuecking, M., additional, Junker, K., additional, Treutier, D., additional, Schneider, C. P., additional, Leonhardi, J., additional, Niesen, A., additional, Hoeffken, K., additional, Schmidt, A., additional, Mueller, K.-M., additional, Schmid, I., additional, Lehmann, K., additional, Blumstein, C. G., additional, Kreienberg, R., additional, Freudenberg, L., additional, Kühl, H., additional, Stahl, M., additional, Elo, B., additional, Erichsen, P., additional, Stattaus, H., additional, Welzel, T., additional, Mende, U., additional, Heiland, S., additional, Salter, B. J., additional, Schmid, R., additional, Stratakis, D., additional, Huber, R. M., additional, Haferanke, J., additional, Zöller, N., additional, Henke, M., additional, Lorenzen, J., additional, Grzyska, B., additional, Kuhlmey, A., additional, Adam, G., additional, Hamelmann, V., additional, Bölling, T., additional, Job, H., additional, Panke, J. E., additional, Feyer, P., additional, Püttmann, S., additional, Siekmeyer, B., additional, Jung, H., additional, Gagel, B., additional, Militz, U., additional, Piroth, M., additional, Schmachtenberg, A., additional, Hoelscher, T., additional, Verfaillie, C., additional, Kaminski, B., additional, Lücke, E., additional, Mörtel, H., additional, Eyrich, W., additional, Fritsch, M., additional, Georgi, J.-C., additional, Plathow, C., additional, Zieher, H., additional, Kiessling, F., additional, Peschke, P., additional, Kauczor, H.-U., additional, Licher, J., additional, Schneider, O., additional, Henschler, R., additional, Seidel, C., additional, Kolkmeyer, A., additional, Nguyen, T. P., additional, Janke, K., additional, Michaelis, M., additional, Bischof, M., additional, Stoffregen, C., additional, Lipson, K., additional, Weber, K., additional, Ehemann, V., additional, Jürgen, D., additional, Achanta, P., additional, Thompson, K., additional, Martinez, J. L., additional, Körschgen, T., additional, Pakala, R., additional, Pinnow, E., additional, Hellinga, D., additional, O’Tio, F., additional, Katzer, A., additional, Kaffer, A., additional, Kuechler, A., additional, Steinkirchner, S., additional, Dettmar, N., additional, Cordes, N., additional, Frick, S., additional, Kappler, M., additional, Taubert, H., additional, Bartel, F., additional, Schmidt, H., additional, Bache, M., additional, Frühauf, S., additional, Wenk, T., additional, Litzenberger, K., additional, Erren, M., additional, van Valen, F., additional, Liu, L., additional, Yang, K., additional, Palm, J., additional, Püsken, M., additional, Behe, M., additional, Behr, T. M., additional, Marini, P., additional, Johne, A., additional, Claussen, U., additional, Liehr, T., additional, Steil, V., additional, Moustakis, C., additional, Griessbach, I., additional, Oettel, A., additional, Schaal, C., additional, Reinhold, M., additional, Strasssmann, G., additional, Braun, I., additional, Vacha, P., additional, Richter, D., additional, Osterham, T., additional, Wolf, P., additional, Guenther, G., additional, Miemietz, M., additional, Lazaridis, E. A., additional, Forthuber, B., additional, Sure, M., additional, Klein, J., additional, Saleske, H., additional, Riedel, T., additional, Hirnle, P., additional, Horstmann, G., additional, Schoepgens, H., additional, Van Eck, A., additional, Bundschuh, O., additional, Van Oosterhut, A., additional, Xydis, K., additional, Theodorou, K., additional, Kappas, C., additional, Zurheide, J., additional, Fridtjof, N., additional, Ganswindt, U., additional, Weidner, N., additional, Buchgeister, M., additional, Weigel, B., additional, Müller, S. B., additional, Glashörster, M., additional, Weining, C., additional, Hentschel, B., additional, Sauer, O. A., additional, Kleen, W., additional, Beck, J., additional, Lehmann, D., additional, Ley, S., additional, Fink, C., additional, Puderbach, M., additional, Hosch, W., additional, Schmähl, A., additional, Jung, K., additional, Stoßberg, A., additional, Rolf, E., additional, Damrau, M., additional, Oetzel, D., additional, Maurer, U., additional, Maurer, G., additional, Lang, K., additional, Zumbe, J., additional, Hahm, D., additional, Fees, H., additional, Robrandt, B., additional, Melcher, U., additional, Niemeyer, M., additional, Mondry, A., additional, Kanellopoulos-Niemeyer, V., additional, Karle, H., additional, Jacob-Heutmann, D., additional, Born, C., additional, Mohr, W., additional, Kutzner, J., additional, Thelen, M., additional, Schiebe, M., additional, Pinkert, U., additional, Piasswilm, L., additional, Pohl, F., additional, Garbe, S., additional, Wolf, K., additional, Nour, Y., additional, Barwig, P., additional, Trog, D., additional, Schäfer, C., additional, Herbst, M., additional, Dietl, B., additional, Cartes, M., additional, Schroeder, F., additional, Sigingan-Tek, G., additional, Feierabend, R., additional, Theden, S., additional, Schlieck, A., additional, Gotthardt, M., additional, Glowalla, U., additional, Kremp, S., additional, Hamid, O., additional, Riefenstahl, N., additional, Michaelis, B., additional, Schaal, G., additional, Liebermeister, E., additional, Niewöhner-Desbordes, U., additional, Kowalski, M., additional, Franz, N., additional, Stahl, W., additional, Baumbach, C., additional, Thale, J., additional, Wagner, W., additional, Justus, B., additional, Huston, A. L., additional, Seaborn, R., additional, Rai, P., additional, Rha, S.-W., additional, Sakas, G., additional, Wesarg, S., additional, Zogal, P., additional, Schwald, B., additional, Seibert, H., additional, Berndt-Skorka, R., additional, Seifert, G., additional, Schoenekaes, K., additional, Bilecen, C., additional, Ito, W., additional, Matschuck, G., additional, and Isik, D., additional

Published
2004
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35. Evaluation of time, attendance of medical staff and resources for radiotherapy in pediatric and adolescent patients. The DEGRO-QUIRO trial.

Author

Zabel-du Bois A, Milker-Zabel S, Bruns F, Christiansen H, Ernst I, Willich N, Popp W, Debus J, and Sack H

Subjects
Adolescent, Anesthesia, General, Child, Cooperative Behavior, Germany, Hospitals, University statistics & numerical data, Humans, Interdisciplinary Communication, Utilization Review statistics & numerical data, Workforce, Health Resources statistics & numerical data, Medical Staff, Hospital statistics & numerical data, National Health Programs statistics & numerical data, Radiation Oncology, Radiotherapy statistics & numerical data, Time and Motion Studies
Abstract

Background: The German Society of Radiation Oncology (DEGRO) initiated a multicenter trial to develop and evaluate adequate modules to assert core procedures in radiotherapy. The aim of this prospective evaluation was to methodical assess the required resources for radiotherapy in pediatric and adolescent patients., Material and Methods: At three radiotherapy centers of excellence (University Hospitals of Heidelberg and Münster, the Medical School of Hannover), the manpower and time required for radiotherapy in pediatric and adolescent patients was prospectively documented consistently over a 2-year period. The data were collected using specifically developed standard forms and were evaluated using specific process analysis tools., Results: A total number of 1914 data sets were documented and carefully analyzed. The personnel time requirements for all occupational groups were calculated as total time needed for a specific procedure and mean time per person. Regarding radiotherapy in general anesthesia, the required manpower was higher. The personnel time requirements in these cases were also longer, mainly due to longer room occupancy. Overall, the required resources were remarkably similar between the three different departments and may, therefore, be considered as representative., Conclusion: For the first time, the personnel time requirements of a radiotherapy department for the maintenance, protection, and optimization of operational readiness for radiotherapy in pediatric and adolescent patients with and without general anesthesia were determined methodically.

Published
2014
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36. Proposal for a new prognostic score for linac-based radiosurgery in cerebral arteriovenous malformations.

Author

Milker-Zabel S, Kopp-Schneider A, Wiesbauer H, Schlegel W, Huber P, Debus J, and Zabel-du Bois A

Subjects
Adolescent, Adult, Age Factors, Aged, Child, Child, Preschool, Female, Follow-Up Studies, Humans, Intracranial Arteriovenous Malformations classification, Intracranial Arteriovenous Malformations complications, Intracranial Arteriovenous Malformations diagnostic imaging, Intracranial Hemorrhages epidemiology, Intracranial Hemorrhages etiology, Likelihood Functions, Male, Middle Aged, Multivariate Analysis, Prognosis, Radiography, Radiosurgery adverse effects, Radiosurgery standards, Radiotherapy Dosage, Reference Values, Treatment Outcome, Young Adult, Intracranial Arteriovenous Malformations surgery, Radiosurgery methods
Abstract

Purpose: We evaluate patient-, angioma-, and treatment-specific factors for successful obliteration of cerebral arteriovenous malformations (AVM) to develop a new appropriate score to predict patient outcome after linac-based radiosurgery (RS)., Methods and Materials: This analysis in based on 293 patients with cerebral AVM. Mean age at treatment was 38.8 years (4-73 years). AVM classification according Spetzler-Martin was 55 patients Grade I (20.5%), 114 Grade II (42.5%), 79 Grade III (29.5%), 19 Grade IV (7.1%), and 1 Grade V (0.4%). Median maximum AVM diameter was 3.0 cm (range, 0.3-10 cm). Median dose prescribed to the 80% isodose was 18 Gy (range, 12-22 Gy). Eighty-five patients (29.1%) had prior partial embolization; 141 patients (51.9%) experienced intracranial hemorrhage before RS. Median follow-up was 4.2 years., Results: Age at treatment, maximum diameter, nidus volume, and applied dose were significant factors for successful obliteration. Under presumption of proportional hazard in the dose range between 12 and 22 Gy/80% isodose, an increase of obliteration rate of approximately 25% per Gy was seen. On the basis of multivariate analysis, a prediction score was calculated including AVM maximum diameter and age at treatment. The prediction error up to the time point 8 years was 0.173 for the Heidelberg score compared with the Kaplan-Meier value of 0.192. An increase of the score of 1 point results in a decrease of obliteration chance by a factor of 0.447., Conclusion: The proposed score is linac-based radiosurgery-specific and easy to handle to predict patient outcome. Further validation on an independent patient cohort is necessary., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Published
2012
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37. Repeated linac-based radiosurgery in high-grade cerebral arteriovenous-malformations (AVM) Spetzler-Martin grade III to IV previously treated with radiosurgery.

Author

Hauswald H, Milker-Zabel S, Sterzing F, Schlegel W, Debus J, and Zabel-du Bois A

Subjects
Adolescent, Adult, Child, Female, Humans, Male, Middle Aged, Radiosurgery adverse effects, Radiotherapy Dosage, Arteriovenous Fistula surgery, Intracranial Arteriovenous Malformations surgery, Radiosurgery methods
Abstract

Background: Aim was to access outcome and toxicity of repeated linac-based radiosurgery in incompletely obliterated cerebral AVM., Patients and Methods: Between 1998 and 2008, 11 patients were treated with repeated radiosurgery. The median dose to the 80%-isodose was 15 Gy (range, 12-18 Gy). During initial radiosurgery the median dose was 18 Gy (range, 9-22 Gy)., Results: The median time interval between initial radiosurgery and re-treatment was 9 years (range, 4-16 years). The median follow-up was 26 months (range, 2-115 months). Treatment response was seen in 8 patients (89%). Complete (partial) obliteration was achieved in 5 (3) patients (56%, 33%, respectively).The median time to complete obliteration was 26 months (range, 5-45 months). Pre-existing neurological symptoms improved in 2 patients (18%), were stable in 7 patients (64%) and worsened in 2 patients (18%). Prevalence of intracranial hemorrhage was 9% (1/11). Post-re-treatment intracranial hemorrhage rate was 2.7% (1/38 years at risk). During follow-up, no secondary malignancies or toxicity>grade III were observed., Conclusion: Repeated linac-based radiosurgery in incompletely obliterated cerebral AVM is an effective treatment option with a high rate of treatment response and an acceptable risk for side effects. Marginal doses above 15 Gy might further improve the rate of complete obliterations., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Published
2011
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38. Intensity modulated radiotherapy in the management of sacral chordoma in primary versus recurrent disease.

Author

Zabel-du Bois A, Nikoghosyan A, Schwahofer A, Huber P, Schlegel W, Debus J, and Milker-Zabel S

Subjects
Adult, Aged, Chordoma diagnosis, Chordoma mortality, Chordoma secondary, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neoplasm Recurrence, Local diagnosis, Neoplasm Recurrence, Local mortality, Radiotherapy Dosage, Radiotherapy Planning, Computer-Assisted, Spinal Neoplasms diagnosis, Spinal Neoplasms mortality, Spinal Neoplasms pathology, Survival Rate, Chordoma radiotherapy, Neoplasm Recurrence, Local radiotherapy, Radiotherapy, Intensity-Modulated, Sacrum, Spinal Neoplasms radiotherapy
Abstract

Purpose: To investigate treatment outcome in patients suffering from sacral chordoma after intensity modulated radiotherapy (IMRT) for primary versus recurrent disease., Material/methods: We report on 34 patients with histologically proven sacral chordoma. Seventeen patients were treated at time of initial diagnosis with post-operative IMRT (n=13) or with IMRT alone (n=4). Seventeen patients were treated in recurrent disease after surgery (n=11) or with radiotherapy alone (n=6). Median total dose to the boost volume (PTV2) was 66 Gy (range, 72-54) with 2 Gy per fraction using an integrated boost concept. Median dose to target volume (PTV1) was 54 Gy in 1.8 Gy., Results: Local control was 35% (12/34) and overall survival 74% (25/34) after a median follow-up of 4.5 years. Actuarial local control was 79%, 55% and 27% after 1, 2 and 5 years, respectively. Local control was significantly higher in patients treated for primary tumors (p<0.03) and in total doses >60 Gy (p<0.01). Actuarial overall survival was 97%, 91% and 70% after 1, 2 and 5 years, respectively., Conclusion: These data demonstrate that local control after IMRT is higher in patients treated for primary tumors and using higher radiation doses. Therefore, we recommend radiotherapy as part of initial treatment in sacral chordoma., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Published
2010
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39. Patterns of failure after stereotactic radiotherapy of intracranial meningioma.

Author

Askoxylakis V, Zabel-du Bois A, Schlegel W, Debus J, Huber P, and Milker-Zabel S

Subjects
Adolescent, Adult, Aged, Child, Female, Follow-Up Studies, Humans, Kaplan-Meier Estimate, Karnofsky Performance Status, Male, Meningeal Neoplasms mortality, Meningioma mortality, Middle Aged, Retrospective Studies, Treatment Failure, Young Adult, Meningeal Neoplasms surgery, Meningioma surgery, Radiosurgery methods
Abstract

The aim of this work is to evaluate patterns of failure in patients with recurrent meningioma after stereotactic radiotherapy. Of 411 patients with intracranial meningioma treated with radiotherapy at our institution, 22 patients with local tumor progression diagnosed by magnetic resonance imaging (MRI) after radiotherapy (RT) were identified and further investigated. The histologic grade of the meningiomas was World Health Organization (WHO) grade I in 54.5%, WHO grade II in 27.3%, and WHO grade III in 9.1% of cases. Fourteen patients had received fractionated stereotactic RT; five patients underwent intensity-modulated RT. The median total dose was 57.6 Gy at 1.8 Gy/fraction, five times weekly. Local recurrences were divided into the dosimetric categories "central" ("in-field") and "marginal" ("out-field"). Median follow-up was 59.5 months. Eleven local failures were found to be central, and 11 were marginal. Recurrence-free survival (P < 0.05) and site of local recurrence (P < 0.05) depended statistically significantly on histology. Median recurrence-free survival was 46 months for patients with benign meningioma (WHO grade I) and 31.5 months for patients with higher-grade meningioma (WHO grade II/III). In the WHO grade I group, three recurrences were central and nine were marginal, whereas in the WHO grade II/III group seven recurrences were central and one was marginal. Median time to local tumor progression and site of local recurrence significantly depended on histological grade of meningioma. Regarding site of failure, improvement of dose coverage for benign meningiomas and dose escalation for high-grade tumors might further improve therapy outcome.

Published
2010
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40. Gene expression signatures in the peripheral blood after radiosurgery of human cerebral arteriovenous malformations.

Author

Zabel-du Bois A, Wagner-Ecker M, Milker-Zabel S, Schwager C, Wirkner U, Debus J, Abdollahi A, and Huber PE

Subjects
Adult, Aged, Cyclin-Dependent Kinase 6 genetics, Down-Regulation genetics, Down-Regulation radiation effects, Female, Humans, Male, Middle Aged, Neuropilin-2 genetics, Oligonucleotide Array Sequence Analysis, Prognosis, Protein C Inhibitor genetics, RNA, Messenger genetics, RNA, Messenger radiation effects, STAT3 Transcription Factor genetics, Toll-Like Receptor 4 genetics, Treatment Outcome, Young Adult, Blood Proteins genetics, Gene Expression Profiling, Intracranial Arteriovenous Malformations genetics, Intracranial Arteriovenous Malformations surgery, Radiosurgery
Abstract

Purpose: To unravel biological mechanisms potentially resulting in the obliteration process after radiosurgery (RS) of human cerebral arteriovenous malformations (AVMs) by investigating molecular signatures on the transcriptomic level in peripheral blood of patients., Patients and Methods: Venous blood samples were obtained at definite points of time before and after RS. The samples were tested for radiation-induced changes regarding biological markers (mRNA) using cDNA and oligo-microarray technology. The corresponding expression profiles were correlated with clinical data and obliteration signs in radiologic imaging., Results: The proof of principle that RS outcome can be successfully correlated with transcriptomics of cellular blood components as disease parameter was demonstrated. The authors identified 76 differentially regulated genes (p < 0.001) after RS. Interestingly, in particular genes with known roles in anti-angiogenic and pro-coagulative pathways were identified as potentially relevant. In particularly, the authors found a significant downregulation of neuropilin-2, protein C inhibitor and cyclin-dependent kinase 6. They also found that low pretreatment blood mRNA levels of TLR4 (toll-like receptor 4) and STAT3 (signal transducer and activator of transcription 3) correlated with fast obliteration of AVMs., Conclusion: The authors report on a novel technique for molecular biological analysis of blood from patients with cerebral AVM treated with RS. Differential regulation of genes in peripheral blood was successfully correlated with RS and time to obliteration of AVMs. The identified genes indicate a potential new methodology to monitor RS, which may result in an individualized therapy and optimized follow-up.

Published
2010
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41. Multidisciplinary pain management based on a computerized clinical decision support system in cancer pain patients.

Author

Bertsche T, Askoxylakis V, Habl G, Laidig F, Kaltschmidt J, Schmitt SP, Ghaderi H, Bois AZ, Milker-Zabel S, Debus J, Bardenheuer HJ, and Haefeli WE

Subjects
Aged, Analgesics, Chi-Square Distribution, Cohort Studies, Female, Humans, Male, Middle Aged, Neoplasms complications, Outcome Assessment, Health Care, Pain etiology, Pain Measurement methods, Prospective Studies, Quality of Life, Treatment Outcome, Decision Support Systems, Clinical statistics & numerical data, Guideline Adherence, Pain Management
Abstract

A prospective controlled intervention cohort study in cancer pain patients (n=50 per group) admitted to radiation oncology wards (62 beds, 3 wards) was conducted in a 1621-bed university hospital. We investigated the effect of an intervention consisting of daily pain assessment using the numeric visual analog scale (NVAS) and pain therapy counseling to clinicians based on a computerized clinical decision support system (CDSS) to correct deviations from pain therapy guidelines. Effects on guideline adherence (primary outcome), pain relief (NVAS) at rest and during physical activity (both groups: cross-sectional assessment on day 5; intervention group: every day assessment), co-analgesic prescription, and acceptance rates of recommendations (secondary outcomes) were assessed. The number of patients with at least one deviation from guidelines at discharge was decreased by the intervention from 37 (74%) in controls to 7 (14%, p<0.001). In the intervention group, pain (NVAS) decreased during hospital stay at rest from 3.0 (Delta(0.5) (Q(75%)-Q(25%))=3.0) on admission to 1.5 (Delta(0.5)=1.0) at discharge (p<0.01) and during physical activity from 7.0 (Delta(0.5)=4.0) on admission to 2.5 (Delta(0.5)=3.8) at discharge (p<0.001). At discharge, the number of patients treated with co-analgesics increased from 23 (46%) in controls to 33 (66%) in the intervention group (p=0.04). From 279 recommendations issued in the intervention 85% were fully accepted by the physicians. Deviations from well-established guidelines are frequent in pain therapy. A multidisciplinary pain management increased adherence to pain management guidelines.

Published
2009
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42. Fractionated stereotactic radiation therapy in the management of primary optic nerve sheath meningiomas.

Author

Milker-Zabel S, Huber P, Schlegel W, Debus J, and Zabel-du Bois A

Subjects
Adolescent, Adult, Aged, Dose Fractionation, Radiation, Female, Humans, Longitudinal Studies, Magnetic Resonance Imaging methods, Male, Meningioma physiopathology, Middle Aged, Nerve Sheath Neoplasms physiopathology, Optic Nerve Neoplasms physiopathology, Visual Acuity, Visual Fields physiology, Young Adult, Meningioma radiotherapy, Nerve Sheath Neoplasms radiotherapy, Optic Nerve Neoplasms radiotherapy, Radiotherapy Planning, Computer-Assisted methods
Abstract

We analysed our long-term results after fractionated stereotactic radiotherapy (FSRT) in patients with primary optic nerve sheath (pONSM) meningioma, as a rare subtype of meningiomas. Between 01/1995 and 12/2007, 32 patients with pONSM were treated with FSRT. Fifteen patients received radiotherapy as primary treatment, four after biopsy, and six patients after surgical resection. Seven patients were irradiated for recurrent disease. Seventeen lesions were histologically proven and determined as WHO grade I pONSM. Median target volume was 15.7 cc, median total dose 54.9 Gy. Twenty-nine patients showed clinical symptoms before radiotherapy like reduced vision, unilateral loss of vision, or an exophthalmia. Median follow-up was 4.5 years. Overall local tumor control was 100%. Twenty-six patients had stable disease based on CT/MRI, while 6/32 had a partial remission of tumor volume. 97% of our patients showed stable vision or an improvement of visual acuity. Eleven patients (38%) showed an improvement of pre-existing clinical symptoms like double vision, exophthalmia and visual acuity. Only one patient showed an impairment of vision with progressive concentric decreasing of the visual field on the side of the irradiated ONSM. These data demonstrate that FSRT is an effective and safe treatment modality for local control in patients with pONSM with minimal risk of significant late toxicity.

Published
2009
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43. Influence of intravenous contrast agent on dose calculation in 3-D treatment planning for radiosurgery of cerebral arteriovenous malformations.

Author

Zabel-du Bois A, Ackermann B, Hauswald H, Schramm O, Sroka-Perez G, Huber P, Debus J, and Milker-Zabel S

Subjects
Humans, Injections, Intravenous, Radiotherapy Dosage, Reproducibility of Results, Sensitivity and Specificity, Treatment Outcome, Contrast Media administration & dosage, Intracranial Arteriovenous Malformations radiotherapy, Radiosurgery methods, Radiotherapy Planning, Computer-Assisted methods, Relative Biological Effectiveness, Tomography, X-Ray Computed methods
Abstract

Purpose: To investigate the influence of local density increase by i.v. contrast agent on dose calculation in linac-based radiosurgery (RS) of cerebral arteriovenous malformations (AVMs)., Material and Methods: RS was performed after three-dimensional (3-D) treatment planning using a total number of nine to 14 beams. Mean target volume was 5.3 cm(3) (range, 0.1-41.2 cm(3)). Mean maximum diameter was 23.2 mm (range, 8-51 mm). Dose deviation was estimated and calculated from the enhanced and unenhanced datasets of 30 patients. Dose calculation was performed using the same RS treatment plan on both datasets. Both plans were standardized to 1 Gy at isocenter with the same dose weight for all beams., Results: Mean difference of Hounsfield units (DeltaHU) between enhanced and unenhanced CT was 152 HU (range, 50-350 HU). The estimated dose deviation was

Published
2009
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44. SU11657 enhances radiosensitivity of human meningioma cells.

Author

Milker-Zabel S, Zabel-du Bois A, Ranai G, Trinh T, Unterberg A, Debus J, Lipson KE, Abdollahi A, and Huber PE

Subjects
Cell Migration Assays methods, Cell Proliferation drug effects, Cell Proliferation radiation effects, Cell Survival drug effects, Cell Survival radiation effects, Dose-Response Relationship, Drug, Drug Screening Assays, Antitumor, Humans, Meningeal Neoplasms blood supply, Meningeal Neoplasms metabolism, Meningeal Neoplasms pathology, Meningioma blood supply, Meningioma metabolism, Meningioma pathology, Neoplasm Proteins metabolism, Umbilical Veins cytology, Umbilical Veins drug effects, Vascular Endothelial Growth Factors metabolism, Meningeal Neoplasms radiotherapy, Meningioma radiotherapy, Organic Chemicals pharmacology, Radiation Tolerance drug effects, Receptor Protein-Tyrosine Kinases antagonists & inhibitors
Abstract

Purpose: To analyze the effect of the multireceptor tyrosine kinase inhibitor SU11657 (primarily vascular endothelial growth factor, platelet-derived growth factor) in combination with irradiation in freshly isolated primary human meningioma cells., Methods and Materials: Tumor specimens were obtained from meningioma patients undergoing surgery at the Department of Neurosurgery, University of Heidelberg, Germany. For the present study only cells up to passage 6 were used. Benign and atypical meningioma cells and human umbilical vein endothelial cells (HUVEC) were treated with SU11657 alone and in combination with 6-MV photons (0-10 Gy). Clonogenic survival and cell proliferation were determined alone and in coculture assays to determine direct and paracrine effects., Results: Radiation and SU11657 alone reduced cell proliferation in atypical and benign meningioma cells as well as in HUVEC in a dose-dependent manner. SU11657 alone also reduced clonogenic survival of benign and atypical meningioma cells. SU11657 increased radiosensitivity of human meningioma cells in clonogenic survival and cell number/proliferation assays. The anticlonogenic and antiproliferative effects alone and the radiosensitization effects of SU11657 were more pronounced in atypical meningioma cells compared with benign meningioma cells., Conclusion: Small-molecule tyrosine kinase inhibitors like SU11657 are capable of amplifying the growth inhibitory effects of irradiation in meningioma cells. These data provide a rationale for further clinical evaluation of this combination concept, especially in atypical and malignant meningioma patients.

Published
2008
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45. [Postoperative radiotherapy of the chest wall in patients with male breast cancer].

Author

Zabel-du Bois A, Milker-Zabel S, Wannenmacher M, and Debus J

Subjects
Actuarial Analysis, Aged, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Breast Neoplasms, Male drug therapy, Breast Neoplasms, Male mortality, Breast Neoplasms, Male surgery, Chemotherapy, Adjuvant, Combined Modality Therapy, Cyclophosphamide administration & dosage, Disease-Free Survival, Fluorouracil administration & dosage, Follow-Up Studies, Humans, Lymph Node Excision, Lymphatic Metastasis, Male, Mastectomy, Modified Radical, Mastectomy, Segmental, Methotrexate administration & dosage, Middle Aged, Neoplasm Recurrence, Local drug therapy, Neoplasm Recurrence, Local mortality, Neoplasm Recurrence, Local radiotherapy, Neoplasm Recurrence, Local surgery, Prognosis, Radioisotope Teletherapy, Radiotherapy, Adjuvant, Tamoxifen therapeutic use, Thoracic Wall radiation effects, Breast Neoplasms, Male radiotherapy
Abstract

Introduction: We analysed our long-term results with postoperative radiotherapy of the chest wall in male breast cancer patients with respect to local control and survival., Methods: Twenty-five patients with 26 histological proven carcinomas of the male breast underwent postoperative radiotherapy of the chest wall with (n = 15) or without regional lymphatics after mastectomy. Additionally 13 patients received adjuvant hormones and 3 patients adjuvant chemotherapy. Median age at treatment was 62.2 years (45.9-78.5 years). Median follow-up was 15.3 years (7.7-27.5 years)., Results: Overall survival after radiotherapy was 28 %, disease-specific survival was 64 %. Actuarial 3-, 5- and 10-year survival was 72 %, 56 % and 35 %. Median survival time was 6.1 years. Actuarial progression-free survival was 80 %, 52 % and 43 % after 3, 5 and 10 years, respectively. Local tumor control was 92 % (24 / 26). Survival was significantly affected by the presence of lymph node metastases (p < 0.01) and localisation of the tumor in the right breast (p < 0.04)., Conclusion: Postoperative radiotherapy is an important part of the management of male breast cancer to improve local control and progression-free survival. The presence of lymph node metastases significantly impairs survival.

Published
2007
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46. Risk of hemorrhage and obliteration rates of LINAC-based radiosurgery for cerebral arteriovenous malformations treated after prior partial embolization.

Author

Zabel-du Bois A, Milker-Zabel S, Huber P, Schlegel W, and Debus J

Subjects
Adolescent, Adult, Aged, Child, Child, Preschool, Embolization, Therapeutic methods, Follow-Up Studies, Humans, Intracranial Arteriovenous Malformations classification, Intracranial Arteriovenous Malformations therapy, Middle Aged, Risk Assessment, Intracranial Arteriovenous Malformations surgery, Intracranial Hemorrhages etiology, Postoperative Hemorrhage etiology, Radiosurgery adverse effects
Abstract

Purpose: We investigate patient outcome, risk of hemorrhage, and factors affecting obliteration after LINAC-based radiosurgery (RS) for cerebral arteriovenous malformations (AVM) treated after partial embolization., Methods and Materials: This analysis is based on 50 patients treated after prior embolization. According to the Spetzler-Martin criteria the AVM classification was as follows: 9 patients, Grade I (18%); 19, Grade II (38%); 18, Grade III (36%); and 4, Grade IV (8%). Median RS-based AVM score was 1.41. Median single dose was 18 Gy/ 80% isodose (range, 15-22 Gy) and median AVM volume was 4.0 cc (range, 0.2-22.6 cc). In all, 34 patients (68%) experienced hemorrhage before RS. Median follow-up was 3.1 year (range, 8.5 months to 15 years)., Results: Actuarial complete obliteration rate was 67% after 3 years and 78% after 4 years. The complete obliteration rate was significantly higher in AVM <3 cm (92% vs. 60%, p < 0.01) and in AVM Spetzler-Martin Grade I/II (90% vs. 59%, p < 0,01). Intracranial hemorrhage after RS was seen in 6 patients (12%) after 8.5 months median. Annual bleeding risk was 7.9% after 1 year and 2.2% after 2 years. It was found that AVM diameter > or =3 cm (p < 0.006), AVM volume > or =4 cc (p < 0.01), AVM score > or =1.5 (p < 0.03), and single dose <18 Gy (p < 0.03) were associated with a significant higher bleeding risk., Conclusions: The rate of obliteration after RS in AVM treated after prior partial embolization depends on size as well as Spetzler-Martin grade. The risk of intracranial hemorrhage is not increased after RS and depends on AVM score, size, and volume, as well as on applied single dose.

Published
2007
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47. Intensity-modulated radiotherapy for complex-shaped meningioma of the skull base: long-term experience of a single institution.

Author

Milker-Zabel S, Zabel-du Bois A, Huber P, Schlegel W, and Debus J

Subjects
Adolescent, Adult, Aged, Female, Germany epidemiology, Humans, Longitudinal Studies, Male, Middle Aged, Prognosis, Risk Assessment methods, Risk Factors, Survival Analysis, Survival Rate, Treatment Outcome, Meningeal Neoplasms mortality, Meningeal Neoplasms radiotherapy, Meningioma mortality, Meningioma radiotherapy, Radiotherapy, Conformal mortality, Skull Base Neoplasms mortality, Skull Base Neoplasms radiotherapy
Abstract

Purpose: We analyzed our long-term experience with intensity-modulated radiotherapy (IMRT) in patients with complex-shaped meningioma of the skull base., Patients and Methods: Between January 1998 and December 2004, 94 patients with complex-shaped meningioma were treated using IMRT at our institution. Tumor distribution was: World Health Organization (WHO) Grade 1 in 54.3%, WHO Grade 2 in 9.6%, and WHO Grade 3 in 4.2%. In 31.9% of patients, the clinical and radiologic characteristics of the tumor were consistent with the diagnosis of meningioma. Twenty-six patients received radiotherapy as primary treatment and 14 patients postoperative for residual disease. Fifty-four patients were treated after local recurrence. Median target volume was 81.4 mL, median total dose was 57.6 Gy given in 32 fractions., Results: Median follow-up was 4.4 years. Overall local control was 93.6%. Sixty-nine patients had stable disease based on computed tomography/magnetic resonance imaging (MRI), whereas 19 had a tumor volume reduction after IMRT. Six patients showed local tumor progression on MRI 22.3 months' median after IMRT. Three patients died from non-treatment-related conditions after IMRT. In 39.8% of the patients, preexisting neurologic deficits improved. Worsening of preexisting neurologic symptoms was seen in 4 patients and 2 patients developed new clinical symptoms from local tumor progression. Transient side effects such as headache were seen in 7 patients. Treatment-induced loss of vision was seen in 1 of 53 reirradiated patients with a Grade 3 meningioma 9 months after retreatment with IMRT., Conclusion: These data demonstrate that IMRT is an effective and safe treatment modality for long-term local control of complex-shaped and otherwise difficult to treat meningioma.

Published
2007
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48. Fractionated stereotactic radiation therapy in the management of benign cavernous sinus meningiomas : long-term experience and review of the literature.

Author

Milker-Zabel S, Zabel-du Bois A, Huber P, Schlegel W, and Debus J

Subjects
Follow-Up Studies, Humans, Magnetic Resonance Imaging, Meningeal Neoplasms diagnosis, Meningeal Neoplasms diagnostic imaging, Meningeal Neoplasms mortality, Meningeal Neoplasms pathology, Meningeal Neoplasms surgery, Meningioma diagnosis, Meningioma diagnostic imaging, Meningioma mortality, Meningioma pathology, Meningioma surgery, Neoplasm Recurrence, Local radiotherapy, Radiosurgery, Radiotherapy Dosage, Radiotherapy Planning, Computer-Assisted, Remission Induction, Safety, Stereotaxic Techniques, Time Factors, Tomography, X-Ray Computed, Cavernous Sinus pathology, Dose Fractionation, Radiation, Meningeal Neoplasms radiotherapy, Meningioma radiotherapy
Abstract

Purpose: To analyze own long-term results with fractionated stereotactic radiotherapy (FSRT) in patients with benign meningiomas of the cavernous sinus and to review the literature on these rare lesions., Patients and Methods: 57 patients were treated with FSRT for benign meningiomas of the cavernous sinus between 01/1990 and 12/2003 at the authors' institution. Histology was WHO grade I in 28/57 lesions, and undetermined in 29/57 lesions. 29 patients received radiotherapy as primary treatment, ten following surgery, and 18 patients were irradiated for recurrent disease. Median target volume was 35.2 cm3. Median total dose was 57.6 Gy with 1.8 Gy per fraction. 51/57 patients showed clinical symptoms before radiotherapy like reduced vision (n = 19), diplopia (n = 25), or trigeminal hyp-/dysesthesia (n = 17)., Results: Median follow-up period was 6.5 years. 50/57 patients were followed for > 36 months. Overall local tumor control was 100%. 39/57 patients had stable disease based on CT/MRI, while 18/57 had a partial remission of tumor volume. Overall survival for patients with WHO grade I meningiomas was 95.5% after 5 and 10 years. Two patients died 2.8 and 4.1 years after radiotherapy due to cardiac failure. In 11/57 patients, preexisting neurologic deficits improved. There was one patient with recurrent hyperlacrimation of one eye on the side of the irradiated meningioma. Three patients complained about subjective visual deterioration after FSRT without any objective findings in an ophthalmologic examination. No late toxicity RTOG >/= degrees III was seen., Conclusion: These data demonstrate that FSRT is an effective and safe treatment modality for local control of benign cavernous sinus meningiomas with a minimal risk of significant late toxicity.

Published
2006
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49. Pediatric cerebral arteriovenous malformations: the role of stereotactic linac-based radiosurgery.

Author

Zabel-du Bois A, Milker-Zabel S, Huber P, Schlegel W, and Debus J

Subjects
Adolescent, Child, Child, Preschool, Female, Humans, Intracranial Hemorrhages etiology, Male, Radiosurgery adverse effects, Retrospective Studies, Treatment Outcome, Intracranial Arteriovenous Malformations surgery, Radiosurgery methods
Abstract

Purpose: To evaluate retrospectively clinical outcome and obliteration rates after linac-based radiosurgery (RS) in children with cerebral arteriovenous malformations (AVM)., Methods and Materials: Between 1996 and 2002, 22 children with cerebral AVM were treated at our institution. Mean age at treatment was 11.8 years (range, 4.4-16.4 years). Classification according to Spetzler-Martin was 1 child grade I (4%), 7 grade II (32%), 12 grade III (56%), 1 grade IV (4%), and 1 grade V (4%). Median single dose was 18 Gy/80%-isodose. Median AVM volume was 4.2 mL (range, 0.4-26.5 mL). Median RS-based AVM-score was 1.07 (range, 0.61-3.55). Fifty-nine percent of children experienced intracranial hemorrhage before RS. Median follow-up was 3.1 years (range, 1.7-7.3 years)., Results: Actuarial complete obliteration rate (CO) was 54% after 3 years and 65% after 4 years, respectively. Median time interval to CO was 27.1 months. Intracranial hemorrhage after RS was seen in five children after median 13.9 months. Annual bleeding risk was 9.1% after 1 year and 13.6% after 2 years. Maximum diameter>or=3 cm and AVM-volume>or=6 mL were significant predictors for intracranial hemorrhage. Neurologic deficits were improved/completely dissolved in 58% of children and remained stable in 42%. No new onset of neurologic dysfunction was seen after RS., Conclusions: RS is safe and effective in pediatric cerebral AVM with high obliteration rates. Size and volume of AVM are significant predictors for intracranial bleeding. The same treatment guidelines as in adults should be applied. Careful long-term follow-up observation is required after RS from long life expectation.

Published
2006
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50. Human glioblastoma and carcinoma xenograft tumors treated by combined radiation and imatinib (Gleevec).

Author

Oertel S, Krempien R, Lindel K, Zabel A, Milker-Zabel S, Bischof M, Lipson KE, Peschke P, Debus J, Abdollahi A, and Huber PE

Subjects
Animals, Benzamides, Carcinoma, Squamous Cell blood supply, Carcinoma, Squamous Cell pathology, Cell Line, Tumor, Cell Proliferation drug effects, Cell Proliferation radiation effects, Chemotherapy, Adjuvant, Dose Fractionation, Radiation, Endothelial Cells drug effects, Endothelial Cells radiation effects, Glioblastoma blood supply, Glioblastoma pathology, Humans, Imatinib Mesylate, Mice, Mice, Inbred BALB C, Mice, Nude, Microcirculation drug effects, Microcirculation radiation effects, Radiotherapy, Adjuvant, Transplantation, Heterologous, Tumor Stem Cell Assay, Antineoplastic Agents therapeutic use, Carcinoma, Squamous Cell drug therapy, Carcinoma, Squamous Cell radiotherapy, Glioblastoma drug therapy, Glioblastoma radiotherapy, Piperazines therapeutic use, Protein Kinase Inhibitors therapeutic use, Pyrimidines therapeutic use, Radiation-Sensitizing Agents therapeutic use
Abstract

Background and Purpose: Imatinib (Gleevec, Glivec) is an inhibitor of alpha- and beta-platelet-derived growth factor receptors and other tyrosine kinases, that are also associated with the function of growth factors. Imatinib has been approved for the treatment of chronic myelogenous leukemia and gastrointestinal stromal tumors and is under investigation for the therapy of several other malignant tumors. Since radiotherapy is an important treatment option in many tumors, combined effects of imatinib and radiation were analyzed here., Material and Methods: In vitro, U87 cells (human glioblastoma), A431 cells (human epidermoid carcinoma), and HUVECs (human umbilical venous endothelial cells) were treated with imatinib alone and in combination with radiation. Clonogenic survival and cell proliferation were determined with and without additional radiation (0-10 Gy). In vivo, U87 and A431 cells (5 x 10(6)) were subcutaneously injected into hind limbs of balb c nu/u mice. Drug and radiation treatments started on day 0 when tumor volumes were approximately 400-500 mm(3). Tumors were treated with 5 x 5 Gy (U87) or 6 x 5 Gy (A431) on consecutive days from day 0. Imatinib was administered orally via the mouse diet starting on day 0 until the end of observation. Tumor growth and microvessel density (CD31 IHC) were analyzed., Results: In vitro, imatinib increased radiosensitivity of U87 and A431 tumor cells as well as HUVECs in both clonogenic and cell number/proliferation assays. The enhancement of radiosensitivity in HUVECs was comparable to that observed in the tumor cells. In vivo, the concurrent and continuous administration of imatinib increased tumor growth delay of fractionated radiotherapy in the carcinoma and the glioblastoma models at reduced microvessel densities. No apparent additional toxicity by the combination of radiation and imatinib versus monotherapies was observed in terms of weight, skin, or general behavior., Conclusion: Imatinib (Gleevec), a "molecular targeted" approved drug for human malignancies, can enhance the tumor growth reduction induced by fractionated radiotherapy in glioblastoma and carcinoma models. The data provides a rationale to further investigate the combination.

Published
2006
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