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3. Rindopepimut with temozolomide for patients with newly diagnosed, EGFRvIII-expressing glioblastoma (ACT IV): a randomised, double-blind, international phase 3 trial

Author

Weller, M, Butowski, N, Tran, DD, Recht, LD, Lim, M, Hirte, H, Ashby, L, Mechtler, L, Goldlust, SA, Iwamoto, F, Drappatz, J, O'Rourke, DM, Wong, M, Hamilton, MG, Finocchiaro, G, Perry, J, Wick, W, Green, J, He, Y, Turner, CD, Yellin, MJ, Keler, T, Davis, TA, Stupp, R, Sampson, JH, Campian, J, Recht, L, Goldlust, S, Becker, K, Barnett, G, Nicholas, G, Desjardins, A, Benkers, T, Wagle, N, Groves, M, Kesari, S, Horvath, Z, Merrell, R, Curry, R, O'Rourke, J, Schuster, D, Mrugala, M, Jensen, R, Trusheim, J, Lesser, G, Belanger, K, Sloan, A, Purow, B, Fink, K, Raizer, J, Schulder, M, Nair, S, Peak, S, Brandes, A, Mohile, N, Landolfi, J, Olson, J, Jennens, R, DeSouza, P, Robinson, B, Crittenden, M, Shih, K, Flowers, A, Ong, S, Connelly, J, Hadjipanayis, C, Giglio, P, Mott, F, Mathieu, D, Lessard, N, Sepulveda, SJ, Lövey, J, Wheeler, H, Inglis, PL, Hardie, C, Bota, D, Lesniak, M, Portnow, J, Frankel, B, Junck, L, Thompson, R, Berk, L, McGhie, J, Macdonald, D, Saran, F, Soffietti, R, Blumenthal, D, André de, SBCM, and Nowak, A

Abstract

© 2017 Elsevier Ltd Background Rindopepimut (also known as CDX-110), a vaccine targeting the EGFR deletion mutation EGFRvIII, consists of an EGFRvIII-specific peptide conjugated to keyhole limpet haemocyanin. In the ACT IV study, we aimed to assess whether or not the addition of rindopepimut to standard chemotherapy is able to improve survival in patients with EGFRvIII-positive glioblastoma. Methods In this randomised, double-blind, phase 3 trial, we recruited patients aged 18 years and older with glioblastoma from 165 hospitals in 22 countries. Eligible patients had newly diagnosed glioblastoma confirmed to express EGFRvIII by central analysis, and had undergone maximal surgical resection and completion of standard chemoradiation without progression. Patients were stratified by European Organisation for Research and Treatment of Cancer recursive partitioning analysis class, MGMT promoter methylation, and geographical region, and randomly assigned (1:1) with a prespecified randomisation sequence (block size of four) to receive rindopepimut (500 μg admixed with 150 μg GM-CSF) or control (100 μg keyhole limpet haemocyanin) via monthly intradermal injection until progression or intolerance, concurrent with standard oral temozolomide (150–200 mg/m2for 5 of 28 days) for 6–12 cycles or longer. Patients, investigators, and the trial funder were masked to treatment allocation. The primary endpoint was overall survival in patients with minimal residual disease (MRD; enhancing tumour

Published
2017

4. Size and composition control of core-shell structured iron/iron-oxide nanoparticles.

Author

Khurshid, H., Tzitzios, V., Wanfeng Li, Hadjipanayis, C. G., and Hadjipanayis, G. C.

Subjects
NANOPARTICLES, IRON, SURFACE active agents, IRON oxides, TEMPERATURE
Abstract

Metallic iron nanoparticles with a crystalline iron oxide shell were synthesized by the thermal decomposition of iron pentacarbonyl [Fe(CO)5] in octadecene in the presence of oleic acid and oleylamine. The effect of different synthetic parameters was investigated in details including the refluxing time and temperature, the injection temperature of iron precursor and the surfactant concentrations. The particles size can be tuned by controlling the injection temperature of iron precursor. Particle composition was adjusted by controlling the refluxing time. Both XRD diffraction and magnetic measurements indicated that these particles are very stable against oxidation which was further evidenced by microstructure analysis. [ABSTRACT FROM AUTHOR]

Published
2010
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7. STEM CELLS

Author

Cheng, L., primary, Huang, Z., additional, Zhou, W., additional, Wu, Q., additional, Rich, J., additional, Bao, S., additional, Baxter, P., additional, Mao, H., additional, Zhao, X., additional, Liu, Z., additional, Huang, Y., additional, Voicu, H., additional, Gurusiddappa, S., additional, Su, J. M., additional, Perlaky, L., additional, Dauser, R., additional, Leung, H.-c. E., additional, Muraszko, K. M., additional, Heth, J. A., additional, Fan, X., additional, Lau, C. C., additional, Man, T.-K., additional, Chintagumpala, M., additional, Li, X.-N., additional, Clark, P., additional, Zorniak, M., additional, Cho, Y., additional, Zhang, X., additional, Walden, D., additional, Shusta, E., additional, Kuo, J., additional, Sengupta, S., additional, Goel-Bhattacharya, S., additional, Kulkarni, S., additional, Cochran, B., additional, Cusulin, C., additional, Luchman, A., additional, Weiss, S., additional, Wu, M., additional, Fernandez, N., additional, Agnihotri, S., additional, Diaz, R., additional, Rutka, J., additional, Bredel, M., additional, Karamchandani, J., additional, Das, S., additional, Day, B., additional, Stringer, B., additional, Al-Ejeh, F., additional, Ting, M., additional, Wilson, J., additional, Ensbey, K., additional, Jamieson, P., additional, Bruce, Z., additional, Lim, Y. C., additional, Offenhauser, C., additional, Charmsaz, S., additional, Cooper, L., additional, Ellacott, J., additional, Harding, A., additional, Lickliter, J., additional, Inglis, P., additional, Reynolds, B., additional, Walker, D., additional, Lackmann, M., additional, Boyd, A., additional, Berezovsky, A., additional, Poisson, L., additional, Hasselbach, L., additional, Irtenkauf, S., additional, Transou, A., additional, Mikkelsen, T., additional, deCarvalho, A. C., additional, Emlet, D., additional, Del Vecchio, C., additional, Gupta, P., additional, Li, G., additional, Skirboll, S., additional, Wong, A., additional, Figueroa, J., additional, Shahar, T., additional, Hossain, A., additional, Lang, F., additional, Fouse, S., additional, Nakamura, J., additional, James, C. D., additional, Chang, S., additional, Costello, J., additional, Frerich, J. M., additional, Rahimpour, S., additional, Zhuang, Z., additional, Heiss, J. D., additional, Golebiewska, A., additional, Stieber, D., additional, Evers, L., additional, Lenkiewicz, E., additional, Brons, N. H. C., additional, Nicot, N., additional, Oudin, A., additional, Bougnaud, S., additional, Hertel, F., additional, Bjerkvig, R., additional, Barrett, M., additional, Vallar, L., additional, Niclou, S. P., additional, Hao, X., additional, Rahn, J., additional, Ujack, E., additional, Lun, X., additional, Cairncross, G., additional, Senger, D., additional, Robbins, S., additional, Harness, J., additional, Lerner, R., additional, Ihara, Y., additional, Santos, R., additional, Torre, J. D. L., additional, Lu, A., additional, Ozawa, T., additional, Nicolaides, T., additional, James, D., additional, Petritsch, C., additional, Higgins, D., additional, Schroeder, M., additional, Ball, B., additional, Milligan, B., additional, Meyer, F., additional, Sarkaria, J., additional, Henley, J., additional, Flavahan, W., additional, Hitomi, M., additional, Rahim, N., additional, Kim, Y., additional, Sloan, A., additional, Weil, R., additional, Nakano, I., additional, Li, M., additional, Lathia, J., additional, Hjelmeland, A., additional, Kaluzova, M., additional, Platt, S., additional, Kent, M., additional, Bouras, A., additional, Machaidze, R., additional, Hadjipanayis, C., additional, Kang, S.-G., additional, Kim, S.-H., additional, Huh, Y.-M., additional, Kim, E.-H., additional, Park, E.-K., additional, Chang, J. H., additional, Kim, S. H., additional, Hong, Y. K., additional, Kim, D. S., additional, Lee, S.-J., additional, Kim, E. H., additional, Kang, S. G., additional, Deleyrolle, L., additional, Sinyuk, M., additional, Goan, W., additional, Otvos, B., additional, Rohaus, M., additional, Oli, M., additional, Vedam-Mai, V., additional, Schonberg, D., additional, Lee, S.-T., additional, Chu, K., additional, Lee, S. K., additional, Kim, M., additional, Roh, J.-K., additional, Griveau, A., additional, Reichholf, B., additional, McMahon, M., additional, Rowitch, D., additional, Nitta, R., additional, Mitra, S., additional, Agarwal, M., additional, Bui, T., additional, Lin, J., additional, Adamson, C., additional, Martinez-Quintanilla, J., additional, Choi, S.-H., additional, Bhere, D., additional, Heidari, P., additional, He, D., additional, Mahmood, U., additional, Shah, K., additional, Gholamin, S., additional, Feroze, A., additional, Achrol, A., additional, Kahn, S., additional, Weissman, I., additional, Cheshier, S., additional, Sulman, E. P., additional, Wang, Q., additional, Mostovenko, E., additional, Liu, H., additional, Lichti, C. F., additional, Shavkunov, A., additional, Kroes, R. A., additional, Moskal, J. R., additional, Conrad, C. A., additional, Lang, F. F., additional, Emmett, M. R., additional, Nilsson, C. L., additional, Osuka, S., additional, Sampetrean, O., additional, Shimizu, T., additional, Saga, I., additional, Onishi, N., additional, Sugihara, E., additional, Okubo, J., additional, Fujita, S., additional, Takano, S., additional, Matsumura, A., additional, Saya, H., additional, Saito, N., additional, Fu, J., additional, Wang, S., additional, Yung, W. K. A., additional, Koul, D., additional, Schmid, R. S., additional, Irvin, D. M., additional, Vitucci, M., additional, Bash, R. E., additional, Werneke, A. M., additional, Miller, C. R., additional, Shinojima, N., additional, Takezaki, T., additional, Fueyo, J., additional, Gumin, J., additional, Gao, F., additional, Nwajei, F., additional, Marini, F. C., additional, Andreeff, M., additional, Kuratsu, J.-I., additional, Singh, S., additional, Burrell, K., additional, Koch, E., additional, Jalali, S., additional, Vartanian, A., additional, Sulman, E., additional, Wouters, B., additional, Zadeh, G., additional, Spelat, R., additional, Singer, E., additional, Matlaf, L., additional, McAllister, S., additional, Soroceanu, L., additional, Spiegl-Kreinecker, S., additional, Loetsch, D., additional, Laaber, M., additional, Schrangl, C., additional, Wohrer, A., additional, Hainfellner, J., additional, Marosi, C., additional, Pichler, J., additional, Weis, S., additional, Wurm, G., additional, Widhalm, G., additional, Knosp, E., additional, Berger, W., additional, Kuratsu, J.-i., additional, Tam, Q., additional, Tanaka, S., additional, Nakada, M., additional, Yamada, D., additional, Todo, T., additional, Hayashi, Y., additional, Hamada, J.-i., additional, Hirao, A., additional, Tilghman, J., additional, Ying, M., additional, Laterra, J., additional, Venere, M., additional, Chang, C., additional, Summers, M., additional, Rosenfeld, S., additional, Luk, S., additional, Iafrate, J., additional, Cahill, D., additional, Martuza, R., additional, Rabkin, S., additional, Chi, A., additional, Wakimoto, H., additional, Wirsching, H.-G., additional, Krishnan, S., additional, Frei, K., additional, Krayenbuhl, N., additional, Reifenberger, G., additional, Weller, M., additional, Tabatabai, G., additional, Man, J., additional, Shoemake, J., additional, and Yu, J., additional

Published
2013
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10. LAB-OMICS AND PROGNOSTIC MARKERS

Author

Jensen, R. L., primary, Abraham, S., additional, Hu, N., additional, Jensen, R. L., additional, Boulay, J.-L., additional, Leu, S., additional, Frank, S., additional, Vassella, E., additional, Vajtai, I., additional, von Felten, S., additional, Taylor, E., additional, Schulz, M., additional, Hutter, G., additional, Sailer, M., additional, Hench, J., additional, Mariani, L., additional, van Thuijl, H. F., additional, Scheinin, I., additional, van Essen, D. F., additional, Heimans, J. J., additional, Wesseling, P., additional, Ylstra, B., additional, Reijneveld, J. C., additional, Borges, A. R., additional, Larrubia, P. L., additional, Marques, J. M. B., additional, Cerdan, S. G., additional, Brastianos, P., additional, Horowitz, P., additional, Santagata, S., additional, Jones, R. T., additional, McKenna, A., additional, Getz, G., additional, Ligon, K., additional, Palescandolo, E., additional, Van Hummelen, P., additional, Stemmer-Rachamimov, A., additional, Louis, D., additional, Hahn, W. C., additional, Dunn, I., additional, Beroukhim, R., additional, Guan, X., additional, Vengoechea, J., additional, Zheng, S., additional, Sloan, A., additional, Chen, Y., additional, Brat, D., additional, O'Neill, B. P., additional, Cohen, M., additional, Aldape, K., additional, Rosenfeld, S., additional, Noushmehr, H., additional, Verhaak, R. G., additional, Barnholtz-Sloan, J., additional, Bahassi, E. M., additional, Li, Y.-Q., additional, Cross, E., additional, Li, W., additional, Vijg, J., additional, McPherson, C., additional, Warnick, R., additional, Stambrook, P., additional, Rixe, O., additional, Manterola, L., additional, Tejada-Solis, S., additional, Diez-Valle, R., additional, Gonzalez, M., additional, Jauregui, P., additional, Sampron, N., additional, Barrena, C., additional, Ruiz, I., additional, Gallego, J., additional, Delattre, J.-Y., additional, de Munain, A. L., additional, Mlonso, M. M., additional, Saito, K., additional, Mukasa, A., additional, Nagae, G., additional, Aihara, K., additional, Takayanagi, S., additional, Aburatani, H., additional, Saito, N., additional, Kong, X.-T., additional, Fu, B. D., additional, Du, S., additional, Hasso, A. N., additional, Linskey, M. E., additional, Bota, D., additional, Li, C., additional, Chen, Y.-S., additional, Chen, Z.-p., additional, Kim, C. H., additional, Cheong, J. H., additional, Kim, J. M., additional, Yelon, N. P., additional, Jacoby, E., additional, Cohen, Z. R., additional, Ishida, J., additional, Kurozumi, K., additional, Ichikawa, T., additional, Onishi, M., additional, Fujii, K., additional, Shimazu, Y., additional, Date, I., additional, Narayanan, R., additional, Ho, Q. H., additional, Levin, B. S., additional, Maeder, M. L., additional, Joung, J. K., additional, Nutt, C. L., additional, Louis, D. N., additional, Thorsteinsdottir, J., additional, Fu, P., additional, Gehrmann, M., additional, Multhoff, G., additional, Tonn, J.-C., additional, Schichor, C., additional, Thirumoorthy, K., additional, Gordon, N., additional, Walston, S., additional, Patel, D., additional, Okamoto, M., additional, Chakravarti, A., additional, Palanichamy, K., additional, French, P., additional, Erdem, L., additional, Gravendeel, L., additional, de Rooi, J., additional, Eilers, P., additional, Idbaih, A., additional, Spliet, W., additional, den Dunnen, W., additional, Teepen, J., additional, Smitt, P. S., additional, Kros, J. M., additional, Gorlia, T., additional, van den Bent, M., additional, McCarthy, D., additional, Cook, R. W., additional, Oelschlager, K., additional, Maetzold, D., additional, Hanna, M., additional, Wick, W., additional, Meisner, C., additional, Hentschel, B., additional, Platten, M., additional, Sabel, M. C., additional, Koeppen, S., additional, Ketter, R., additional, Weiler, M., additional, Tabatabai, G., additional, Schilling, A., additional, von Deimling, A., additional, Gramatzki, D., additional, Westphal, M., additional, Schackert, G., additional, Loeffler, M., additional, Simon, M., additional, Reifenberger, G., additional, Weller, M., additional, Moren, L., additional, Johansson, M., additional, Bergenheim, T., additional, Antti, H., additional, Sulman, E. P., additional, Goodman, L. D., additional, Wani, K. M., additional, DeMonte, F., additional, Aldape, K. D., additional, Krischek, B., additional, Gugel, I., additional, Aref, D., additional, Marshall, C., additional, Croul, S., additional, Zadeh, G., additional, Nilsson, C. L., additional, Sulman, E., additional, Liu, H., additional, Wild, C., additional, Lichti, C. F., additional, Emmett, M. R., additional, Lang, F. F., additional, Conrad, C., additional, Alentorn, A., additional, Marie, Y., additional, Boisselier, B., additional, Carpetier, C., additional, Mokhtari, K., additional, Hoang-Xuan, K., additional, Capelle, L., additional, Lautenschlaeger, T., additional, Huebner, A., additional, McIntyre, J. B., additional, Magliocco, T., additional, Hamilton, M., additional, Easaw, J., additional, Pollo, B., additional, Calatozzolo, C., additional, Vuono, R., additional, Guzzetti, S., additional, Eoli, M., additional, Silvani, A., additional, Di Meco, F., additional, Filippini, G., additional, Finocchiaro, G., additional, Joy, A., additional, Ramesh, A., additional, Smirnov, I., additional, Reiser, M., additional, Shapiro, W., additional, Mills, G., additional, Kim, S., additional, Feuerstein, B., additional, Gonda, D. D., additional, Li, J., additional, McCabe, N., additional, Walker, S., additional, Goffard, N., additional, Wikstrom, K., additional, McLean, E., additional, Greenan, C., additional, Delaney, T., additional, McCarthy, M., additional, McDyer, F., additional, Keating, K. E., additional, James, I. F., additional, Harrison, T., additional, Mullan, P., additional, Harkin, D. P., additional, Carter, B. S., additional, Kennedy, R. D., additional, Chen, C. C., additional, Patel, A. S., additional, Allen, J. E., additional, Dicker, D. T., additional, Rizzo, K., additional, Sheehan, J. M., additional, Glantz, M. J., additional, El-Deiry, W. S., additional, Salhia, B., additional, Ross, J. T., additional, Kiefer, J., additional, Van Cott, C., additional, Metpally, R., additional, Baker, A., additional, Sibenaller, Z., additional, Nasser, S., additional, Ryken, T., additional, Ramanathan, R., additional, Berens, M. E., additional, Carpten, J., additional, Tran, N. L., additional, Bi, Y., additional, Pal, S., additional, Zhang, Z., additional, Gupta, R., additional, Macyszyn, L., additional, Fetting, H., additional, O'Rourke, D., additional, Davuluri, R. V., additional, Ezrin, A. M., additional, Moore, K., additional, Stummer, W., additional, Hadjipanayis, C. G., additional, Cahill, D. P., additional, Beiko, J., additional, Suki, D., additional, Prabhu, S., additional, Weinberg, J., additional, Lang, F., additional, Sawaya, R., additional, Rao, G., additional, McCutcheon, I., additional, Barker, F. G., additional, Trister, A. D., additional, Bot, B., additional, Fontes, K., additional, Bridge, C., additional, Baldock, A. L., additional, Rockhill, J. K., additional, Mrugala, M. M., additional, Rockne, R. R., additional, Huang, E., additional, Swanson, K. R., additional, Underhill, H. R., additional, Zhang, J., additional, Shi, M., additional, Lin, X., additional, Mikheev, A., additional, Rostomily, R. C., additional, Scheck, A. C., additional, Stafford, P., additional, Hughes, A., additional, Cichacz, Z., additional, Coons, S. W., additional, Johnston, S. A., additional, Mainwaring, L., additional, Craig, J., additional, Garcia, D., additional, Bergthold, G., additional, Burns, M., additional, Rich, B., additional, Ramkissoon, S., additional, Eberhart, C., additional, Ligon, A., additional, Goumnerova, L., additional, Stiles, C., additional, Kieran, M., additional, Hahn, W., additional, Olausson, K. H., additional, Correia, J., additional, Gafni, E., additional, Theisen, M., additional, Hayashi, M., additional, Haidar, S., additional, Maire, C., additional, Mainwaring, L. A., additional, Norden, A., additional, Wen, P., additional, Kung, A., additional, Alexander, B., additional, Tonellato, P., additional, and Ligon, K. L., additional

Published
2012
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11. STEM CELLS

Author

Joshi, K., primary, Gupta, S., additional, Mazumder, S., additional, Okemoto, Y., additional, Angenieux, B., additional, Kornblum, H., additional, Nakano, I., additional, Synowitz, M., additional, Kumar, J., additional, Petrosino, S., additional, Imperatore, R., additional, Smith, E., additional, Wendt, P., additional, Erdmann, B., additional, Nuber, U., additional, Matiash, V., additional, Chirasani, S., additional, Cristino, L., additional, DiMarzo, V., additional, Kettenmann, H., additional, Glass, R., additional, Soroceanu, L., additional, Matlaf, L., additional, Cobbs, C., additional, Kim, Y.-W., additional, Kim, S. H., additional, Kwon, C., additional, Han, D.-y., additional, Kim, E. H., additional, Chang, J. H., additional, Liu, J.-L., additional, Kim, Y. H., additional, Kim, S., additional, Long, P. M., additional, Viapiano, M. S., additional, Jaworski, D. M., additional, Kanemura, Y., additional, Shofuda, T., additional, Kanematsu, D., additional, Matsumoto, Y., additional, Yamamoto, A., additional, Nonaka, M., additional, Moriuchi, S., additional, Nakajima, S., additional, Suemizu, H., additional, Nakamura, M., additional, Okada, Y., additional, Okano, H., additional, Yamasaki, M., additional, Price, R. L., additional, Song, J., additional, Bingmer, K., additional, Zimmerman, P., additional, Rivera, A., additional, Yi, J.-Y., additional, Cook, C., additional, Chiocca, E. A., additional, Kwon, C.-H., additional, Kang, S.-G., additional, Shin, H.-D., additional, Mok, H.-S., additional, Park, N.-R., additional, Sim, J. K., additional, Shin, H. J., additional, Park, Y. K., additional, Jeun, S. S., additional, Hong, Y.-K., additional, Lang, F. F., additional, McKenzie, B. A., additional, Zemp, F. J., additional, Lun, X., additional, Narendran, A., additional, McFadden, G., additional, Kurz, E., additional, Forsyth, P., additional, Talsma, C. E., additional, Flack, C. G., additional, Zhu, T., additional, He, X., additional, Soules, M., additional, Heth, J. A., additional, Muraszko, K., additional, Fan, X., additional, Chen, L., additional, Guerrero-Cazares, H., additional, Noiman, L., additional, Smith, C., additional, Beltran, N., additional, Levchenko, A., additional, Quinones-Hinojosa, A., additional, Peruzzi, P., additional, Godlewski, J., additional, Lawler, S. E., additional, Sarkar, S., additional, Doring, A., additional, Wang, X., additional, Kelly, J., additional, Hader, W., additional, Dunn, J. F., additional, Kinniburgh, D., additional, Robbins, S., additional, Cairncross, G., additional, Weiss, S., additional, Yong, V. W., additional, Vollmann-Zwerenz, A., additional, Velez-Char, N., additional, Jachnik, B., additional, Ramm, P., additional, Leukel, P., additional, Bogdahn, U., additional, Hau, P., additional, Kim, S.-H., additional, Lee, M. K., additional, Chwae, Y.-J., additional, Yoo, B. C., additional, Kim, K.-H., additional, Kristoffersen, K., additional, Stockhausen, M.- T., additional, Poulsen, H. S., additional, Kaluzova, M., additional, Machaidze, R., additional, Wankhede, M., additional, Hadjipanayis, C. G., additional, Romane, A. M., additional, Sim, F. J., additional, Wang, S., additional, Chandler-Militello, D., additional, Li, X., additional, Al Fanek, Y., additional, Walter, K., additional, Johnson, M., additional, Achanta, P., additional, Goldman, S. A., additional, Shinojima, N., additional, Hossain, A., additional, Takezaki, T., additional, Gumin, J., additional, Gao, F., additional, Nwajei, F., additional, Cheung, V., additional, Figueroa, J., additional, Pellegatta, S., additional, Orzan, F., additional, Anghileri, E., additional, Guzzetti, S., additional, Porrati, P., additional, Eoli, M., additional, Finocchiaro, G., additional, Fu, J., additional, Koul, D., additional, Yao, J., additional, Gumin, J. G., additional, Sulman, E., additional, Lang, F., additional, Aldape, K. K., additional, Colman, H., additional, Yung, A. W., additional, Aldape, K., additional, Alonso, M. M., additional, Manterola, L., additional, urquiza, L., additional, Cortes-Santiago, N., additional, Diez-Valle, R., additional, Tejada-Solis, S., additional, Garcia-foncillas, J., additional, Fueyo, J., additional, Gomez-Manzano, C., additional, Nguyen, S., additional, Stechishin, O., additional, Luchman, A., additional, Lathia, J. D., additional, Gallagher, J., additional, Li, M., additional, Myers, J., additional, Hjelmeland, A., additional, Huang, A., additional, Rich, J., additional, Bhat, K., additional, Vaillant, B., additional, Balasubramaniyan, V., additional, Ezhilarasan, R., additional, Hitomi, M., additional, Gadani, S., additional, Adkins, J., additional, Vasanji, A., additional, Wu, Q., additional, Soeda, A., additional, McLendon, R., additional, Chenn, A., additional, Park, D., additional, Weinstein, J. N., additional, Alfred Yung, W. K., additional, Zagzag, D., additional, Esencay, M., additional, Klopsis, D., additional, Liu, M., additional, Narayana, A., additional, Parker, E., additional, Golfinos, J., additional, Clark, P. A., additional, Kandela, I. K., additional, Weichert, J. P., additional, Kuo, J. S., additional, Fouse, S. D., additional, Nagarajan, R. P., additional, Nakamura, J., additional, James, C. D., additional, Chang, S., additional, Costello, J. F., additional, Gong, X., additional, Kankar, G., additional, Di, K., additional, Reeves, A., additional, Linskey, M., additional, Bota, D. A., additional, Schmid, R. S., additional, Bash, R. E., additional, Vitucci, M., additional, Werneke, A. M., additional, Miller, C. R., additional, Kim, E., additional, Kim, M., additional, Kim, K., additional, Lee, J., additional, Du, F., additional, Li, P., additional, Wechsler-Reya, R., additional, and Yang, Z.-j., additional

Published
2011
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12. SURGICAL THERAPIES

Author

Chambless, L. B., primary, Parker, S. L., additional, Hassam-Malani, L., additional, McGirt, M. J., additional, Thompson, R. C., additional, Zhou, T., additional, Meng, X., additional, Xu, B., additional, Wei, S., additional, Chen, X., additional, De Witt Hamer, P. C., additional, Robles, S. G., additional, Zwinderman, A. H., additional, Duffau, H., additional, Berger, M. S., additional, Gonzalez, J. D. S. R., additional, Alberto, O. V., additional, Patricia, H. M., additional, Chaichana, K., additional, Pendleton, C., additional, Chambless, L., additional, Nathan, J., additional, Camara-Quintana, J., additional, Li, G., additional, Harsh, G., additional, Thompson, R., additional, Lim, M., additional, Quinones-Hinojosa, A., additional, Oppenlander, M. E., additional, Wolf, A., additional, Porter, R., additional, Nakaji, P., additional, Smith, K. A., additional, Spetzler, R. F., additional, Sanai, N., additional, Kim, J. H., additional, Clark, A. J., additional, Jahangiri, A., additional, Sughrue, M. E., additional, McDermott, M. W., additional, Aghi, M. K., additional, Chen, C., additional, Kasper, E., additional, Warnke, P., additional, Park, C.-K., additional, Lee, S.-H., additional, Song, S. W., additional, Kim, J. W., additional, Kim, T. M., additional, Yamaguchi, F., additional, Omura, T., additional, Ten, H., additional, Ishii, Y., additional, Kojima, T., additional, Takahashi, H., additional, Teramoto, A., additional, Pereira, E. A., additional, Livermore, J., additional, Ansorge, O., additional, Bojanic, S., additional, Tong, H., additional, Yu, X., additional, Zhou, D., additional, Hou, Y., additional, Zhou, Z., additional, Zhang, J., additional, Fabiano, A. J., additional, Rigual, N., additional, Munich, S., additional, Fenstermaker, R. A., additional, Wang, F., additional, Zhao, Y., additional, Xu, B.-n., additional, Kim, E. H., additional, Oh, M. C., additional, Lee, E. J., additional, Kim, S. H., additional, Kim, Y.-H., additional, Kim, C.-Y., additional, Kim, Y. H., additional, Han, J. H., additional, Kim, S.-K., additional, Paek, S. H., additional, Wang, K.-C., additional, Kim, D. G., additional, Jung, H.-W., additional, Krex, D., additional, Lindner, C., additional, Juratli, T., additional, Raue, C., additional, Schackert, G., additional, Valdes, P. A., additional, Kim, A., additional, Leblond, F., additional, Conde, O. M., additional, Harris, B. T., additional, Paulsen, K. D., additional, Wilson, B. C., additional, Roberts, D. W., additional, Occhiogrosso, G., additional, Cascardi, P., additional, Blagia, M., additional, De Tommasi, A., additional, Gelinas-Phaneuf, N., additional, Choudhury, N., additional, Al-Habib, A., additional, Cabral, A., additional, Nadeau, E., additional, Vincent, M., additional, Pazos, V., additional, Debergue, P., additional, DiRaddo, R., additional, Del Maestro, R. F., additional, Guha-Thakurta, N., additional, Prabhu, S. S., additional, Schulder, M., additional, Zavarella, S., additional, Nardi, D., additional, Schaffer, S., additional, Ruge, M. I., additional, Grau, S., additional, Fuetsch, M., additional, Kickingereder, P., additional, Hamisch, C., additional, Treuer, H., additional, Voges, J., additional, Sturm, V., additional, Choy, W., additional, Yew, A., additional, Spasic, M., additional, Nagasawa, D., additional, Kim, W., additional, Yang, I., additional, Quigley, M. R., additional, Hobbs, J., additional, Bhatia, S., additional, Cohen, Z. R., additional, Shimon, I., additional, Hadani, M., additional, Carapella, C. M., additional, Oppido, P. A., additional, Vidiri, A., additional, Telera, S., additional, Pompili, A., additional, Villani, V., additional, Fabi, A., additional, Pace, A., additional, Cahill, D., additional, Wang, M., additional, Won, M., additional, Aldape, K., additional, Maywald, R., additional, Hegi, M., additional, Mehta, M., additional, Gilbert, M., additional, Sulman, E., additional, Vogelbaum, M., additional, Narayana, A., additional, Kunnakkat, S. D., additional, Parker, E., additional, Gruber, D., additional, Gruber, M., additional, Knopp, E., additional, Zagzag, D., additional, Golfinos, J., additional, Dziurzynski, K., additional, Blas-Boria, D., additional, Suki, D., additional, Prabhu, S., additional, Puduvalli, V., additional, Levine, N., additional, Bloch, O., additional, Han, S. J., additional, Kaur, G., additional, Parsa, A. T., additional, Fukui, O., additional, Chew, B., additional, DePowell, J. J., additional, Sanders-Taylor, C., additional, Guarnaschelli, J., additional, McPherson, C., additional, Sheth, S. A., additional, Snuderl, M., additional, Kwon, C.-S., additional, Wirth, D., additional, Yaroslavsky, A., additional, Curry, W. T., additional, Vogelbaum, M. A., additional, Hadjipanayis, C. G., additional, Mehta, M. P., additional, Gilbert, M. R., additional, Megyesi, J. F., additional, Macdonald, D., additional, Wang, B., additional, Pierre, G. H.-S., additional, Hoover, J. M., additional, Goerss, S. J., additional, Kaufmann, T. J., additional, Meyer, F. B., additional, Parney, I. F., additional, Guthikonda, B., additional, Thakur, J., additional, Khan, I., additional, Ahmed, O., additional, Shorter, C., additional, Wilson, J., additional, Welsh, J., additional, Cuellar, H., additional, and Jeroudi, M., additional

Published
2011
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13. CELL BIOLOGY AND SIGNALING

Author

Furnari, F., primary, Fenton, T., additional, Nathanson, D., additional, de Alberquerque, C. P., additional, Kuga, D., additional, Wanami, A., additional, Dang, J., additional, Yang, H., additional, Tanaka, K., additional, Gao, L., additional, Oba-Shinjo, S., additional, Uno, M., additional, Inda, M.-d.-M., additional, Bachoo, R., additional, James, C. D., additional, DePinho, R., additional, Vandenberg, S., additional, Zhou, H., additional, Marie, S., additional, Mischel, P., additional, Cavenee, W., additional, Szerlip, N., additional, Pedraza, A., additional, Huse, J., additional, Mikkelsen, T., additional, Brennan, C., additional, Castellani, R. J., additional, Ivanova, S., additional, Gerzanich, V. V., additional, Simard, J. M., additional, Ito, M., additional, See, W., additional, Mukherjee, J., additional, Ohba, S., additional, Tan, I.-L., additional, Pieper, R. O., additional, Lukiw, W. J., additional, Culicchia, F., additional, Pogue, A., additional, Bhattacharjee, S., additional, Zhao, Y., additional, Proescholdt, M. A., additional, Merrill, M., additional, Storr, E. M., additional, Lohmeier, A., additional, Brawanski, A., additional, Abraham, S., additional, Jensen, R., additional, Khatua, S., additional, Gopal, U., additional, Du, J., additional, He, F., additional, Golub, T., additional, Isaacs, J. S., additional, Dietrich, J., additional, Kalogirou-Valtis, Y., additional, Ly, I., additional, Scadden, D., additional, Proschel, C., additional, Mayer-Proschel, M., additional, Rempel, S. A., additional, Schultz, C. R., additional, Golembieski, W., additional, Brodie, C., additional, Mathew, L. K., additional, Skuli, N., additional, Mucaj, V., additional, Imtiyaz, H. Z., additional, Venneti, S., additional, Lal, P., additional, Zhang, Z., additional, Davuluri, R. V., additional, Koch, C., additional, Evans, S., additional, Simon, M. C., additional, Ranganathan, P., additional, Clark, P., additional, Salamat, S., additional, Kuo, J. S., additional, Kalejta, R. F., additional, Bhattacharjee, B., additional, Renzette, N., additional, Moser, R. P., additional, Kowalik, T. F., additional, McFarland, B. C., additional, Ma, J.-Y., additional, Langford, C. P., additional, Gillespie, G. Y., additional, Yu, H., additional, Zheng, Y., additional, Nozell, S. E., additional, Huszar, D., additional, Benveniste, E. N., additional, Lawrence, J. E., additional, Cook, N. J., additional, Rovin, R. A., additional, Winn, R. J., additional, Godlewski, J. A., additional, Ogawa, D., additional, Bronisz, A., additional, Lawler, S., additional, Chiocca, E. A., additional, Lee, S. X., additional, Wong, E. T., additional, Swanson, K. D., additional, Liu, K.-w., additional, Feng, H., additional, Kazlauskas, A., additional, Smith, E. M., additional, Symes, K., additional, Hamilton, R. L., additional, Nagane, M., additional, Nishikawa, R., additional, Hu, B., additional, Cheng, S.-Y., additional, Silber, J., additional, Jacobsen, A., additional, Ozawa, T., additional, Harinath, G., additional, Brennan, C. W., additional, Holland, E. C., additional, Sander, C., additional, Huse, J. T., additional, Sengupta, R., additional, Dubuc, A., additional, Ward, S., additional, Yang, L., additional, Northcott, P., additional, Kroll, K., additional, Taylor, M., additional, Wechsler-Reya, R., additional, Rubin, J., additional, Chu, W.-T., additional, Lee, H.-T., additional, Huang, F.-J., additional, Aldape, K., additional, Yao, J., additional, Steeg, P. S., additional, Lu, Z., additional, Xie, K., additional, Huang, S., additional, Sim, H., additional, Agudelo-Garcia, P. A., additional, Viapiano, M. S., additional, Saldivar, J., additional, Dolan, C., additional, Mora, M., additional, Nuovo, G., additional, Cole, S., additional, Stegh, A. H., additional, Ryu, M.-J., additional, Liu, Y., additional, Zhong, X., additional, Marwaha, S., additional, Li, H., additional, Wang, J., additional, Chang, Q., additional, Zhang, J., additional, Ng, H.-K., additional, Poon, W. S., additional, Zhou, L., additional, Pang, J. C., additional, Chan, A., additional, Didier, S., additional, Kwiatkowska, A., additional, Ennis, M., additional, Fortin, S., additional, Rushing, E., additional, Eschbacher, J., additional, Tran, N., additional, Symons, M., additional, Roldan, G., additional, McIntyre, J. B., additional, Easaw, J., additional, Magliocco, A., additional, Wykosky, J., additional, Furnari, F., additional, Lu, D., additional, Mreich, E., additional, Chung, S., additional, Teo, C., additional, Wheeler, H., additional, McDonald, K. L., additional, Lawn, S., additional, Forsyth, P., additional, Sonabend, A. M., additional, Lei, L., additional, Kennedy, B., additional, Soderquist, C., additional, Guarnieri, P., additional, Leung, R., additional, Yun, J., additional, Sisti, J., additional, Castelli, M., additional, Bruce, S., additional, Bruce, R., additional, Ludwig, T., additional, Rosenfeld, S., additional, Bruce, J. N., additional, Canoll, P., additional, Lamszus, K., additional, Schulte, A., additional, Gunther, H. S., additional, Riethdorf, S., additional, Phillips, H. S., additional, Westphal, M., additional, Siegal, T., additional, Zrihan, D., additional, Granit, A., additional, Lavon, I., additional, Singh, M., additional, Chandra, J., additional, Nakashima, H., additional, Godlewski, J., additional, Chiocca, A. E., additional, Kapoor, G. S., additional, Poptani, H., additional, Ittyerah, R., additional, O'Rourke, D. M., additional, Sadraei, N. H., additional, Burgett, M., additional, Ahluwalia, M., additional, Tipps, R., additional, Khosla, D., additional, Weil, R., additional, Nowacki, A., additional, Prayson, R., additional, Shi, T., additional, Gladson, C., additional, Moeckel, S., additional, Meyer, K., additional, Bosserhoff, A., additional, Spang, R., additional, Leukel, P., additional, Vollmann, A., additional, Jachnick, B., additional, Stangl, C., additional, Proescholdt, M., additional, Bogdahn, U., additional, Hau, P., additional, Kaur, G., additional, Sun, M., additional, Kaur, R., additional, Bloch, O., additional, Jian, B., additional, Parsa, A. T., additional, Hossain, A., additional, Shinojima, N., additional, Gumin, J., additional, Feng, G., additional, Lang, F. F., additional, Li, L., additional, Yang, C.-R., additional, Chakraborty, S., additional, Hatanpaa, K., additional, Chauncey, S., additional, Jiwani, A., additional, Habib, A., additional, Nguyen, T., additional, Munson, J., additional, Machaidze, R., additional, Kaluzova, M., additional, Bellamkonda, R., additional, Hadjipanayis, C. G., additional, Zhang, Y., additional, McFarland, B., additional, Bredel, M., additional, Lee, S.-H., additional, Zerrouqi, A., additional, Khwaja, F., additional, Devi, N. S., additional, Van Meir, E. G., additional, Haseley, A., additional, Boone, S., additional, Wojton, J., additional, Yu, L., additional, Kaur, B., additional, Wojton, J. A., additional, Naduparambil, J., additional, Denton, N., additional, Chakravarti, A., additional, Conrad, C. A., additional, Wang, X., additional, Sheng, X., additional, Nilsson, C., additional, Marshall, A. G., additional, Emmett, M. R., additional, Hu, Y., additional, Mark, L., additional, Zhou, Y.-H. Z., additional, Dhruv, H., additional, McDonough, W., additional, Armstrong, B., additional, Tuncali, S., additional, Kislin, K., additional, Berens, M., additional, Plas, D., additional, Gallo, C., additional, Stringer, K., additional, Kendler, A., additional, McPherson, C., additional, Castelli, M. A., additional, Ellis, J. A., additional, Assanah, M., additional, Ogden, A., additional, Liang, J., additional, Piao, Y., additional, deGroot, J. F., additional, Gordon, N., additional, Patel, D., additional, Palanichamy, K., additional, Hervey-Jumper, S., additional, Wang, A., additional, He, X., additional, Zhu, T., additional, Heth, J., additional, Muraszko, K., additional, Fan, X., additional, Liu, W. M., additional, Huang, P., additional, Rani, S., additional, Stettner, M. R., additional, Jerry, S., additional, Dai, Q., additional, Kappes, J., additional, Gladson, C. L., additional, Chakravarty, D., additional, Koul, D., additional, Alfred Yung, W. K., additional, Jensen, S. A., additional, Luciano, J., additional, Calvert, A., additional, Nagpal, V., additional, Stegh, A., additional, Kang, S.-H., additional, Yu, M. O., additional, Lee, M.-G., additional, Chi, S.-G., additional, Chung, Y.-G., additional, Cooper, M. K., additional, Valadez, J. G., additional, Grover, V. K., additional, Kouri, F. M., additional, Chin, L., additional, Ahluwalia, M. S., additional, Weil, R. J., additional, McGraw, M., additional, Barnett, G. H., additional, Kang, C., additional, Zou, J., additional, Lan, F., additional, Yue, X., additional, Shi, Z., additional, Zhang, K., additional, Han, L., additional, Pu, P., additional, Seaman, B. F., additional, Tran, N. D., additional, Battiste, J. D., additional, Sirasanagandla, S., additional, Maher, E. A., additional, Sugiarto, S., additional, Persson, A., additional, Munoz, E. G., additional, Waldhuber, M., additional, Stallcup, W., additional, Philips, J., additional, Berger, M. S., additional, Bergers, G., additional, Weiss, W. A., additional, and Petritsch, C., additional

Published
2011
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17. Stem Cells

Author

He, H., primary, Emmett, M. R., additional, Marshall, A. G., additional, Ji, Y., additional, Conrad, C. A., additional, Priebe, W., additional, Colman, H., additional, Lang, F. F., additional, Madden, T. L., additional, Kristoffersen, K., additional, Stockhausen, M.-T., additional, Poulsen, H. S., additional, Binder, Z. A., additional, Orr, B., additional, Lim, M., additional, Weingart, J. D., additional, Brem, H., additional, Olivi, A., additional, Riggins, G. J., additional, Gallia, G. L., additional, Litofsky, N. S., additional, Miller, D. C., additional, Rath, P., additional, Anthony, D. C., additional, Feng, Q., additional, Franklin, C., additional, Pei, L., additional, Free, A., additional, Kirk, M. D., additional, Shi, H., additional, Timmer, M., additional, Theiss, H., additional, Juerchott, K., additional, Ries, C., additional, Paron, I., additional, Franz, W., additional, Selbig, J., additional, Guo, K., additional, Tonn, J. C., additional, Schichor, C., additional, Zhou, Y.-H., additional, Hu, Y., additional, Pioli, P. D., additional, Rajneesh, K., additional, Limoli, C. L., additional, Yu, L., additional, Hess, K. R., additional, Linskey, M. E., additional, Faber, F., additional, Jaeger, D., additional, Thorsteinsdottir, J., additional, Albrecht, V., additional, Tonn, J.-C., additional, Price, R., additional, Song, J., additional, Zimmerman, P., additional, Duale, H., additional, Rivera, A., additional, Kaur, B., additional, Parada, L., additional, Cook, C., additional, Chiocca, E. A., additional, Kwon, C.-H., additional, Munoz, D. M., additional, Guha, A., additional, Estrada-Bernal, A., additional, Van Brocklyn, J. R., additional, Gu, C., additional, Mahasenan, K. V., additional, Joshi, K., additional, Gupta, S., additional, Mattson, A., additional, Li, C., additional, Nakano, I., additional, Chi, A. S., additional, Rheinbay, E., additional, Wakimoto, H., additional, Gillespie, S., additional, Kasif, S., additional, Rabkin, S. D., additional, Martuza, R. L., additional, Bernstein, B. E., additional, Skirboll, S. L., additional, Wurdak, H., additional, Zhu, S., additional, Romero, A., additional, Lorger, M., additional, Watson, J., additional, Chiang, C.-y., additional, Zhang, J., additional, Natu, V. S., additional, Lairson, L. L., additional, Walker, J. R., additional, Trussell, C. M., additional, Harsh, G. R., additional, Vogel, H., additional, Felding-Habermann, B., additional, Orth, A. P., additional, Miraglia, L. J., additional, Rines, D. R., additional, Schultz, P. G., additional, Hide, T., additional, Takezaki, T., additional, Nakamura, H., additional, Makino, K., additional, Kuratsu, J.-i., additional, Kondo, T., additional, Yao, J., additional, Kim, Y.-W., additional, Koul, D., additional, Almeida, J. S., additional, Weinstein, J. N., additional, Alfred Yung, W. K., additional, Miyazaki, T., additional, Chaudhury, A. R., additional, Wong, A. J., additional, Del Vecchio, C., additional, Mitra, S., additional, Han, S.-Y., additional, Holgado-Madruga, M., additional, Gupta, P., additional, Golebiewska, A., additional, Brons, N. H., additional, Bjerkvig, R., additional, Niclou, S. P., additional, Ramm, P., additional, Vollmann-Zwerenz, A., additional, Beier, C., additional, Aigner, L., additional, Bogdahn, U., additional, Kalbitzer, H. R., additional, Hau, P., additional, Sanzey, M., additional, Vallar, L., additional, Tamura, K., additional, Aoyagi, M., additional, Ando, N., additional, Ogishima, T., additional, Yamamoto, M., additional, Ohno, K., additional, Perin, A., additional, Fung, K. H., additional, Longatti, P., additional, Guiot, M.-C., additional, Del Maestro, R. F., additional, Rossi, S., additional, Stechishin, O., additional, Weiss, S., additional, Stifani, S., additional, Goodman, L., additional, Gao, F., additional, Gumin, J., additional, Ezhilarasan, R., additional, Love, P., additional, George, A., additional, Lang, F., additional, Aldape, K., additional, Sulman, E. P., additional, Soeda, A., additional, Lee, D.-H., additional, Shaffrey, M. E., additional, Oldfield, E. H., additional, Park, D. M., additional, Dietrich, J., additional, Han, R., additional, Noble, M., additional, Yang, M. Y., additional, Liu, X., additional, Madhankumar, A. B., additional, Sheehan, J., additional, Slagle-Webb, B., additional, Connor, J. R., additional, Fu, J., additional, Shen, R.-J., additional, Kaluzova, M., additional, Machaidze, R., additional, Nduom, E. N. K., additional, Burden, C. T., additional, Hadjipanayis, C. G., additional, Lei, L., additional, Sonabend, A., additional, Guarnieri, P., additional, Ludwig, T., additional, Rosenfeld, S., additional, Bruce, J., additional, Canoll, P., additional, Vaillant, B. D., additional, Bhat, K., additional, Balasubramaniyam, V., additional, Wang, S., additional, Sulman, E., additional, Goodman, L. D., additional, Love, P. N., additional, Soules, M., additional, Zhu, T., additional, Flack, C., additional, Talsma, C., additional, Hamm, L., additional, Muraszko, K., additional, Fan, X., additional, Matsuoka, Y., additional, Kawano, Y., additional, Kobayashi, D., additional, Kumagai, J., additional, Frank, R. T., additional, Najbauer, J., additional, Aboody, K. S., additional, Metz, M., additional, Garcia, E., additional, Aramburo, S., additional, Valenzuela, V., additional, Gutova, M., additional, Annala, A. J., additional, Barish, M., additional, Danks, M., additional, Kim, S. U., additional, Portnow, J., additional, Hofstetter, C., additional, Gursel, D., additional, Mubita, L., additional, Holland, E., additional, Boockvar, J., additional, Monje, M., additional, Freret, M., additional, Masek, M., additional, Edwards, M. S., additional, Fisher, P. G., additional, and Beachy, P., additional

Published
2010
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18. Pre-clinical Experimental Therapeutics and Pharmacology

Author

Jensen, R. L., primary, Gilliespie, D., additional, Ajewung, N., additional, Faure, R., additional, Kamnasaran, D., additional, Poirier, D., additional, Tamura, K., additional, Wakimoto, H., additional, Rabkin, S. D., additional, Martuza, R. L., additional, Shah, K., additional, Hashizume, R., additional, Aoki, Y., additional, Serwer, L. P., additional, Drummond, D., additional, Noble, C., additional, Park, J., additional, Bankiewicz, K., additional, James, D. C., additional, Gupta, N., additional, Agerholm-Larsen, B., additional, Iversen, H. K., additional, Jensen, K. S., additional, Moller, J., additional, Ibsen, P., additional, Mahmood, F., additional, Gehl, J., additional, Corem, E., additional, Ram, Z., additional, Daniels, D., additional, Last, D., additional, Shneor, R., additional, Salomon, S., additional, Perlstein, B., additional, Margel, S., additional, Mardor, Y., additional, Charest, G., additional, Fortin, D., additional, Mathieu, D., additional, Sanche, L., additional, Paquette, B., additional, Li, H.-F., additional, Hariono, S., additional, Dasgupta, T., additional, Kim, J.-S., additional, Haas-Kogan, D., additional, Weiss, W. A., additional, James, C. D., additional, Waldman, T., additional, Nicolaides, T., additional, Ozawa, T., additional, Rao, S., additional, Sun, H., additional, Ng, C., additional, De La Torre, J., additional, Santos, R., additional, Prados, M., additional, Butowski, N., additional, Michaud, K., additional, Solomon, D. A., additional, Prados, M. D., additional, Pandya, H., additional, Gibo, D., additional, Debinski, W., additional, Vinchon-Petit, S., additional, Jarnet, D., additional, Jadaud, E., additional, Feuvret, L., additional, Garcion, E., additional, Menei, P., additional, Chen, R., additional, Yu, J.-C., additional, Liu, C., additional, Jaffer, Z. M., additional, Chabala, J. C., additional, Winssinger, N., additional, Rubenstein, A. E., additional, Emdad, L., additional, Kothari, H., additional, Qadeer, Z., additional, Binello, E., additional, Germano, I., additional, Hirschberg, H., additional, Baek, S.-K., additional, Kwon, Y. J., additional, Sun, C. H., additional, Li, S. C., additional, Madsen, S., additional, Liu, T., additional, Wang, S.-W., additional, Gibo, D. M., additional, Fan, Q.-W., additional, Cheng, C., additional, Hackett, C., additional, Feldman, M., additional, Houseman, B. T., additional, Oakes, S. A., additional, Debnath, J., additional, Shokat, K. M., additional, Sai, K., additional, Chen, F., additional, Qiu, Z., additional, Mou, Y., additional, Zhang, X., additional, Yang, Q., additional, Chen, Z., additional, Patel, T. R., additional, Zhou, J., additional, Piepmeier, J. M., additional, Saltzman, W. M., additional, Banerjee, S., additional, Kaul, A., additional, Gianino, S. M., additional, Christians, U., additional, Gutmann, D. H., additional, Wu, J., additional, Shen, R., additional, Puduvalli, V., additional, Koul, D., additional, Alfred Yung, W. K., additional, Yun, J., additional, Sonabend, A., additional, Stuart, M., additional, Yanagihara, T., additional, Dashnaw, S., additional, Brown, T., additional, McCormick, P., additional, Romanov, A., additional, Sebastian, M., additional, Canoll, P., additional, Bruce, J. N., additional, Piao, L., additional, Joshi, K., additional, Lee, R. J., additional, Nakano, I., additional, Madsen, S. J., additional, Chou, C. C., additional, Blickenstaff, J. W., additional, Sun, C.-H., additional, Zhou, Y.-H., additional, Tome, C. M. L., additional, Wykosky, J., additional, Palma, E., additional, Nduom, E., additional, Machaidze, R., additional, Kaluzova, M., additional, Wang, Y., additional, Nie, S., additional, Hadjipanayis, C., additional, Saito, R., additional, Nakamura, T., additional, Sonoda, Y., additional, Kumabe, T., additional, Tominaga, T., additional, Lun, X., additional, Zemp, F., additional, Zhou, H., additional, Stechishin, O., additional, Kelly, J. J., additional, Weiss, S., additional, Hamilton, M. G., additional, Cairncross, G., additional, Rabinovich, B. A., additional, Bell, J., additional, McFadden, G., additional, Senger, D. L., additional, Forsyth, P. A., additional, Kang, P., additional, Jane, E. P., additional, Premkumar, D. R., additional, Pollack, I. F., additional, Yoo, J. Y., additional, Haseley, A., additional, Bratasz, A., additional, Powell, K., additional, Chiocca, E. A., additional, Kaur, B., additional, Johns, T. G., additional, Ferruzzi, P., additional, Mennillo, F., additional, De Rosa, A., additional, Rossi, M., additional, Giordano, C., additional, Magrini, R., additional, Benedetti, G., additional, Pericot, G. l., additional, Magnoni, L., additional, Mori, E., additional, Thomas, R., additional, Tunici, P., additional, Bakker, A., additional, Pradarelli, J., additional, Kaka, A., additional, Alvarez-Breckenridge, C., additional, Pan, Q., additional, Teknos, T., additional, Cen, L., additional, Ostrem, J. L., additional, Schroeder, M. A., additional, Mladek, A. C., additional, Fink, S. R., additional, Jenkins, R. B., additional, Sarkaria, J. N., additional, Madhankumar, A. B., additional, Slagle-Webb, B., additional, Park, A., additional, Pang, M., additional, Klinger, M., additional, Harbaugh, K. S., additional, Sheehan, J. M., additional, Connor, J. R., additional, Chen, T. C., additional, Wang, W., additional, Hofman, F. M., additional, Drummond, D. C., additional, Noble, C. O., additional, Park, J. W., additional, Zhou, Y., additional, Marks, J. D., additional, Alonso, M. M., additional, Gomez-Manzano, C., additional, Cortes-Santiago, N., additional, Roche, F. P., additional, Fueyo, J., additional, Johannessen, T.-C. A., additional, Grudic, A., additional, Tysnes, B. B., additional, Nigro, J., additional, Bjerkvig, R., additional, Joshi, A. D., additional, Parsons, W., additional, Velculescu, V. E., additional, Riggins, G. J., additional, Bindra, R. S., additional, Jasin, M., additional, Powell, S. N., additional, Fu, J., additional, Shen, R.-J., additional, Colman, H., additional, Lang, F. F., additional, Jensen, M. R., additional, Friedman, G. K., additional, Haas, M., additional, Cassady, K. A., additional, Gillespie, G. Y., additional, Nguyen, V., additional, Murphy, L. T., additional, Beauchamp, A. S., additional, Hollingsworth, C. K., additional, Mintz, A., additional, Garg, S., additional, Kridel, S., additional, Conrad, C. A., additional, Madden, T., additional, Ji, Y., additional, Priebe, W., additional, Seleverstov, O., additional, Purow, B. W., additional, Grant, G. A., additional, Wilson, C., additional, Campbell, M., additional, Humphries, P., additional, Li, S., additional, Li, J., additional, Johnson, A., additional, Bigner, D., additional, Dewhirst, M., additional, Pokorny, J. L., additional, Kitange, G. J., additional, Carlson, B. L., additional, Suphangul, M., additional, Petro, B., additional, Mukhtar, L., additional, Baig, M. S., additional, Villano, J., additional, Mahmud, N., additional, Keir, S. T., additional, Reardon, D. A., additional, Watson, M., additional, Shore, G. C., additional, Bigner, D. D., additional, Friedman, H. S., additional, and Gururangan, S., additional

Published
2010
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24. Hearing preservation outcomes using direct cranial nerve eight and auditory brainstem response neuromonitoring in the resection of vestibular schwannomas.

Author

Sloane DC, Nuru M, Pecoraro NC, Hand R, Strelko O, Shin WY, Russ A, Rajasekhar R, Jusue-Torres I, Hadjipanayis C, Leonetti JP, and Anderson DE

Subjects
Humans, Female, Male, Middle Aged, Retrospective Studies, Adult, Treatment Outcome, Aged, Intraoperative Neurophysiological Monitoring methods, Hearing physiology, Hearing Loss prevention & control, Hearing Loss etiology, Cohort Studies, Neurosurgical Procedures methods, Monitoring, Intraoperative methods, Neuroma, Acoustic surgery, Evoked Potentials, Auditory, Brain Stem physiology
Abstract

Objective: Advancements in microsurgical technique and technology continue to improve outcomes in patients with skull base tumor. The primary cranial nerve eight monitoring systems used in hearing preservation surgery for vestibular schwannomas (VSs) are direct cranial nerve eight monitoring (DCNEM) and auditory brainstem response (ABR), although current guidelines are unable to definitively recommend one over the other due to limited literature on the topic. Thus, further research is needed to determine the utility of DCNEM and ABR. The authors performed a retrospective cohort study and created an interactive model that compares hearing preservation outcomes based on tumor size in patients receiving ABR+DCNEM and ABR-only monitoring., Methods: Twenty-eight patients received ABR+DCNEM and 72 patients received ABR-only monitoring during VS hearing preservation surgery at a single tertiary academic medical center between January 2008 and November 2022. Inclusion criteria consisted of adult patients with a preoperative American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) hearing classification of A or B. Tumor size was measured as the maximal medial to lateral length, including the internal auditory canal component., Results: Overall hearing preservation (word recognition score [WRS] > 0%) was achieved in 31 patients with ABR-only monitoring (43.1%) and in 18 patients with ABR+DCNEM (64.3%). Serviceable hearing preservation (AAO-HNS class A or B) was attained in 19 patients with ABR-only monitoring (26.4%) and in 11 patients with ABR+DCNEM (39.3%). There was no difference in overall hearing preservation between the two groups (p = 0.13). Change in tumor size was not associated with the odds of serviceable hearing preservation for the ABR-only group (p = 0.89); however, for ABR+DCNEM, there was some indication of an interaction between tumor size and the association of ABR+DCNEM versus ABR-only monitoring, with the odds of serviceable hearing preservation at p = 0.089. Furthermore, with ABR+DCNEM, every 0.5-cm increase in tumor size was associated with a decreased odds of serviceable hearing preservation on multivariable analysis (p = 0.05). For both overall and serviceable hearing preservation, a worse preoperative AAO-HNS classification was associated with a decreased odds of preservation (OR 0.43, 95% CI 0.19-0.97, p = 0.042; OR 0.17, 95% CI 0.053-0.55, p = 0.0031, respectively)., Conclusions: The result of this interactive model study proposes that there may be a higher chance of hearing preservation when using ABR+DCNEM rather than ABR alone for smaller tumors, with that relationship reversing as tumor size increases.

Published
2024
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25. In situ brain tumor detection using a Raman spectroscopy system-results of a multicenter study.

Author

Ember K, Dallaire F, Plante A, Sheehy G, Guiot MC, Agarwal R, Yadav R, Douet A, Selb J, Tremblay JP, Dupuis A, Marple E, Urmey K, Rizea C, Harb A, McCarthy L, Schupper A, Umphlett M, Tsankova N, Leblond F, Hadjipanayis C, and Petrecca K

Subjects
Humans, Male, Female, Middle Aged, Aged, Meningioma diagnosis, Meningioma pathology, Glioblastoma pathology, Glioblastoma diagnosis, Glioblastoma surgery, Adult, Machine Learning, Brain pathology, Brain diagnostic imaging, Brain Neoplasms diagnosis, Brain Neoplasms pathology, Brain Neoplasms surgery, Spectrum Analysis, Raman methods
Abstract

Safe and effective brain tumor surgery aims to remove tumor tissue, not non-tumoral brain. This is a challenge since tumor cells are often not visually distinguishable from peritumoral brain during surgery. To address this, we conducted a multicenter study testing whether the Sentry System could distinguish the three most common types of brain tumors from brain tissue in a label-free manner. The Sentry System is a new real time, in situ brain tumor detection device that merges Raman spectroscopy with machine learning tissue classifiers. Nine hundred and seventy-six in situ spectroscopy measurements and colocalized tissue specimens were acquired from 67 patients undergoing surgery for glioblastoma, brain metastases, or meningioma to assess tumor classification. The device achieved diagnostic accuracies of 91% for glioblastoma, 97% for brain metastases, and 96% for meningiomas. These data show that the Sentry System discriminated tumor containing tissue from non-tumoral brain in real time and prior to resection., (© 2024. The Author(s).)

Published
2024
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26. Recent Developments in Magnetic Hyperthermia Therapy (MHT) and Magnetic Particle Imaging (MPI) in the Brain Tumor Field: A Scoping Review and Meta-Analysis.

Author

Rentzeperis F, Rivera D, Zhang JY, Brown C, Young T, Rodriguez B, Schupper A, Price G, Gomberg J, Williams T, Bouras A, and Hadjipanayis C

Abstract

Magnetic hyperthermia therapy (MHT) is a promising treatment modality for brain tumors using magnetic nanoparticles (MNPs) locally delivered to the tumor and activated with an external alternating magnetic field (AMF) to generate antitumor effects through localized heating. Magnetic particle imaging (MPI) is an emerging technology offering strong signal-to-noise for nanoparticle localization. A scoping review was performed by systematically querying Pubmed, Scopus, and Embase. In total, 251 articles were returned, 12 included. Articles were analyzed for nanoparticle type used, MHT parameters, and MPI applications. Preliminary results show that MHT is an exciting treatment modality with unique advantages over current heat-based therapies for brain cancer. Effective application relies on the further development of unique magnetic nanoparticle constructs and imaging modalities, such as MPI, that can enable real-time MNP imaging for improved therapeutic outcomes.

Published
2024
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27. 5-Aminolevulinic Acid Fluorescence-Guided Surgery in Head and Neck Squamous Cell Carcinoma.

Author

Filip P, Lerner DK, Kominsky E, Schupper A, Liu K, Khan NM, Roof S, Hadjipanayis C, Genden E, and Iloreta AMC

Subjects
Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Aminolevulinic Acid, Margins of Excision, Prospective Studies, Squamous Cell Carcinoma of Head and Neck surgery, Pilot Projects, Brain Neoplasms pathology, Head and Neck Neoplasms surgery, Surgery, Computer-Assisted
Abstract

Objectives: To determine the utility of 5-aminolevulinic acid (5-ALA) fluorescence for resection of head and neck carcinoma., Methods: In this prospective pilot trial, 5-ALA was administered as an oral suspension 3-5 h prior to induction of anesthesia for resection of head and neck squamous cell carcinoma (HNSCC). Following resection, 405 nm blue light was applied, and fluorescence of the tumor as well as the surgical bed was recorded. Specimen fluorescence intensity was graded categorically as none (score = 0), mild (1), moderate (2), or robust (3) by the operating surgeon intraoperatively and corroborated with final pathologic diagnosis., Results: Seven patients underwent resection with 5-ALA. Five (83%) were male with an age range of 33-82 years (mean = 60). Sites included nasal cavity (n = 3), oral cavity (n = 3), and the larynx (n = 1). All specimens demonstrated robust fluorescence when 5-ALA was administered 3-5 h preoperatively. 5-ALA fluorescence predicted the presence of perineural invasion, a positive margin, and metastatic lymphadenopathy. Two patients had acute photosensitivity reactions, and one patient had a temporary elevation of hepatic enzymes., Conclusions: 5-ALA induces robust intraoperative fluorescence of HNSCC, capable of demonstrating a positive margin, perineural invasion, and metastatic nodal disease. Although no conclusions are there about the safety of this drug in the head and neck cancer population, our study parallels the extensive safety data in the neurosurgical literature. Future applications may include intraoperative assessment of margin status, diagnostic accuracy, and impacts on survival., Level of Evidence: 4 Laryngoscope, 134:741-748, 2024., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Published
2024
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28. Exoscopic resection of a parasagittal atypical meningioma.

Author

Carrasquilla A, Zgurov A, Salih M, Le C, Matsoukas S, Feng R, Schupper AJ, and Hadjipanayis C

Abstract

This video demonstrates use of the Synaptive 3D exoscope to enhance complex meningioma resection. The patient was a 58-year-old female who presented with new-onset seizures. Workup revealed a parasagittal meningioma over the bilateral cortices. She was started on 750 mg of Keppra twice daily and tapered dexamethasone and discharged. MR venography demonstrated segmental occlusion of the superior sagittal sinus. She then underwent a diagnostic angiogram and tumor Onyx embolization of the bilateral middle meningeal artery feeders. She then underwent a craniotomy for meningioma resection using 3D exoscope guidance. She awoke with a stable examination in the intensive care unit and worked with physical therapy on postoperative day 1. The video can be found here: https://stream.cadmore.media/r10.3171/2023.10.FOCVID23164., Competing Interests: Disclosures Dr. Hadjipanayis reported personal fees from Hemerion Therapeutics, Stryker Corp., Synaptive Medical, and Integra outside the submitted work.Dr. Hadjipanayis reported personal fees from Hemerion Therapeutics, Stryker Corp., Synaptive Medical, and Integra outside the submitted work., (© 2024, The Authors.)

Published
2024
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29. A Novel Port to Facilitate Magnetic Hyperthermia Therapy for Glioma.

Author

Rodriguez B, Campbell P, Borrello J, Odland I, Williams T, Hrabarchuk EI, Young T, Sharma A, Schupper AJ, Rapoport B, Ivkov R, and Hadjipanayis C

Subjects
Animals, Brain, Magnetic Phenomena, Hyperthermia, Induced, Glioma therapy, Brain Neoplasms therapy
Abstract

High-grade gliomas (HGG) are the most common primary brain malignancy and continue to be associated with a dismal prognosis (median survival rate of 15-18 months) with standard of care therapy. Magnetic hyperthermia therapy (MHT) is an emerging intervention that leverages the ferromagnetic properties of magnetic iron-oxide nanoparticles (MIONPs) to target cancer cells that are otherwise left behind after resection. We report a novel port device to facilitate localization, delivery, and temperature measurement of MIONPs within a target lesion for MHT therapy. We conducted an in-depth literature and intellectual property review to define specifications of the conceived port device. After setting the design parameters, a thorough collaboration with neurological surgeons guided the iterative modeling process. A prototype was developed using Fusion 360 (Autodesk, San Rafael, CA) and printed on a Form 3 printer (Formlabs, Medford, MA) in Durable resin. The prototype was then tested in a phantom skull printed on a Pro-Jet 660Pro 3D printer (3D Systems, Rock Hill, SC) and a brain model based on mechanical and electrochemical properties of native brain tissue. This phantom underwent MHT heating tests using an alternating magnetic field (AMF) sequence based on current MHT workflow. Successful localization, delivery, and temperature measurement were demonstrated. The purpose of this study was twofold: first, to create and validate the procedural framework for a novel device, providing the groundwork for an upcoming comprehensive animal trial and second, to elucidate a cooperative approach between engineers and clinicians that propels advancements in medical innovation., (Copyright © 2024 by ASME.)

Published
2024
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30. Application of the Robotic-Assisted Digital Exoscope for Resection of Posterior Fossa Tumors in Adults: A Series of 45 Cases.

Author

Price G, Schupper A, Kalagara R, Chennareddy S, He C, Zhang JY, Sudhir S, Rentzeperis F, Wanna G, and Hadjipanayis C

Subjects
Humans, Adult, Male, Middle Aged, Neurosurgical Procedures, Retrospective Studies, Robotic Surgical Procedures, Brain Neoplasms surgery, Infratentorial Neoplasms diagnostic imaging, Infratentorial Neoplasms surgery
Abstract

Background and Objectives: Complete safe resection is the goal when pursuing surgical treatment for posterior fossa (PF) tumors. Efforts have led to the development of the exoscope that delineates tumors from non-neoplastic brain. This investigation aims to assess patient outcomes where PF tumor resection is performed with the exoscope by a retromastoid or suboccipital approach., Methods: A retrospective analysis was conducted for patients with PF tumors who underwent exoscope resection from 2017 to 2022. Patient demographics, clinical, operative, and outcome findings were collected. Extent of resection studies were also performed. Associations between perioperative data, discharge disposition, progression-free survival (PFS), and overall survival (OS) were evaluated., Results: A total of 45 patients (22 male patients) with a median age of 57 years were assessed. Eighteen (40%) and 27 patients (60%) were diagnosed with malignant and benign tumors, respectively. Tumor neurovascular involvement was found in 28 patients (62%). Twenty-four (53%) and 20 (44%) tumors formed in the cerebellum and cerebellopontine angle cistern, respectively. One tumor (2%) was found in the cervicomedullary junction. The mean extent of resection was 96.7% for benign and malignant tumors. The PFS and OS rate at 6 months (PFS6, OS6) was 89.7% and 95.5%, respectively. Neurological complications included sensory loss and motor deficit, with 11 patients reporting no postoperative symptoms. Of the neurological complications, 14 were temporary and 9 were permanent., Conclusion: The exoscope is an effective intraoperative visualization tool for delineating PF tumors. In our series, we achieved low postoperative tumor volumes and a high gross total resection rate., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Published
2023
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31. Trends in Immunotherapy Clinical Trials to Treat Glioblastoma: A Look at Progress and Challenges.

Author

Price G, Rossitto CP, Price H, Hadjipanayis C, and Martini M

Subjects
Humans, United States, Immunotherapy, Research Design, Registries, China, Glioblastoma therapy
Abstract

Purpose: We aimed to catalog past and present clinical trials on immunotherapy treatments for glioblastoma (GBM) and discover relevant trends in this field., Methods: Former and ongoing clinical trials involving the use of immunotherapy to treat GBM were queried in July 2022 within the clinicaltrials.gov registry (https://clinicaltrials.gov/). Pertinent trials were categorized by variables including immunotherapy classification, tumor type (newly diagnosed versus recurrent), country of origin, start date, clinical phase, study completion status, estimated subject enrollment, design, publication status, and funding source., Results: A list of 173 trials was identified in total. The number of immunotherapy clinical trials to treat GBM has increased over time. The largest proportion of trials were gene therapies (97 studies; 56.1%) and viral therapies (37 studies; 21.4%). Studies were designated as a biologic (45.1%), drug (43.9%), genetic (2.3%), or procedure (1.2%). Trials spanned 19 countries; China, the second largest contributor (5.8%) after the United States (70.0%), has increased clinical trial development in the past years. The average time to completion was 52.3 months. Trials were primarily funded by academic centers; however, one-fourth of the trials were funded by industry and 2 were funded by foundations. One-t of the trials were active and over one-third were linked to publications., Conclusions: Our findings provide a comprehensive summary of the state of immunotherapy clinical trials for GBM, highlighting the evolving nature and growing scope of this field., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Published
2023
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32. Development of a Treatment Planning Framework for Laser Interstitial Thermal Therapy (LITT).

Author

Lad Y, Jangam A, Carlton H, Abu-Ayyad M, Hadjipanayis C, Ivkov R, Zacharia BE, and Attaluri A

Abstract

Purpose: Develop a treatment planning framework for neurosurgeons treating high-grade gliomas with LITT to minimize the learning curve and improve tumor thermal dose coverage., Methods: Deidentified patient images were segmented using the image segmentation software Materialize MIMICS©. Segmented images were imported into the commercial finite element analysis (FEA) software COMSOL Multiphysics© to perform bioheat transfer simulations. The laser probe was modeled as a cylindrical object with radius 0.7 mm and length 100 mm, with a constant beam diameter. A modeled laser probe was placed in the tumor in accordance with patient specific patient magnetic resonance temperature imaging (MRTi) data. The laser energy was modeled as a deposited beam heat source in the FEA software. Penne's bioheat equation was used to model heat transfer in brain tissue. The cerebrospinal fluid (CSF) was modeled as a solid with convectively enhanced conductivity to capture heat sink effects. In this study, thermal damage-dependent blood perfusion was assessed. Pulsed laser heating was modeled based on patient treatment logs. The stationary heat source and pullback heat source techniques were modeled to compare the calculated tissue damage. The developed bioheat transfer model was compared to MRTi data obtained from a laser log during LITT procedures. The application builder module in COMSOL Multiphysics© was utilized to create a Graphical User Interface (GUI) for the treatment planning framework., Results: Simulations predicted increased thermal damage (10-15%) in the tumor for the pullback heat source approach compared with the stationary heat source. The model-predicted temperature profiles followed trends similar to those of the MRTi data. Simulations predicted partial tissue ablation in tumors proximal to the CSF ventricle., Conclusion: A mobile platform-based GUI for bioheat transfer simulation was developed to aid neurosurgeons in conveniently varying the simulation parameters according to a patient-specific treatment plan. The convective effects of the CSF should be modeled with heat sink effects for accurate LITT treatment planning.

Published
2023
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33. Association of circulating markers with cognitive decline after radiation therapy for brain metastasis.

Author

Huntoon K, Anderson SK, Ballman KV, Twohy E, Dooley K, Jiang W, An Y, Li J, von Roemeling C, Qie Y, Ross OA, Cerhan JH, Whitton AC, Greenspoon JN, Parney IF, Ashman JB, Bahary JP, Hadjipanayis C, Urbanic JJ, Farace E, Khuntia D, Laack NN, Brown PD, Roberge D, and Kim BYS

Subjects
Humans, Retrospective Studies, Amyloid beta-Peptides, Cranial Irradiation adverse effects, Cranial Irradiation methods, Brain Neoplasms secondary, Radiosurgery adverse effects, Radiosurgery methods, Cognitive Dysfunction etiology
Abstract

Background: A recent phase III trial (NCT01372774) comparing use of stereotactic radiosurgery [SRS] versus whole-brain radiation therapy [WBRT] after surgical resection of a single brain metastasis revealed that declines in cognitive function were more common with WBRT than with SRS. A secondary endpoint in that trial, and the primary objective in this secondary analysis, was to identify baseline biomarkers associated with cognitive impairment after either form of radiotherapy for brain metastasis. Here we report our findings on APOE genotype and serum levels of associated proteins and their association with radiation-induced neurocognitive decline., Methods: In this retrospective analysis of prospectively collected samples from a completed randomized clinical trial, patients provided blood samples every 3 months that were tested by genotyping and enzyme-linked immunosorbent assay, and results were analyzed in association with cognitive impairment., Results: The APOE genotype was not associated with neurocognitive impairment at 3 months. However, low serum levels of ApoJ, ApoE, or ApoA protein (all P < .01) and higher amyloid beta (Aβ 1-42) levels (P = .048) at baseline indicated a greater likelihood of neurocognitive decline at 3 months after SRS, whereas lower ApoJ levels were associated with decline after WBRT (P = .014)., Conclusions: Patients with these pretreatment serum markers should be counseled about radiation-related neurocognitive decline., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Published
2023
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34. Efficacy of laser interstitial thermal therapy for biopsy-proven radiation necrosis in radiographically recurrent brain metastases.

Author

Chan M, Tatter S, Chiang V, Fecci P, Strowd R, Prabhu S, Hadjipanayis C, Kirkpatrick J, Sun D, Sinicrope K, Mohammadi AM, Sevak P, Abram S, Kim AH, Leuthardt E, Chao S, Phillips J, Lacroix M, Williams B, Placantonakis D, Silverman J, Baumgartner J, Piccioni D, and Laxton A

Abstract

Background: Laser interstitial thermal therapy (LITT) in the setting of post-SRS radiation necrosis (RN) for patients with brain metastases has growing evidence for efficacy. However, questions remain regarding hospitalization, local control, symptom control, and concurrent use of therapies., Methods: Demographics, intraprocedural data, safety, Karnofsky performance status (KPS), and survival data were prospectively collected and then analyzed on patients who consented between 2016-2020 and who were undergoing LITT for biopsy-proven RN at one of 14 US centers. Data were monitored for accuracy. Statistical analysis included individual variable summaries, multivariable Fine and Gray analysis, and Kaplan-Meier estimated survival., Results: Ninety patients met the inclusion criteria. Four patients underwent 2 ablations on the same day. Median hospitalization time was 32.5 hours. The median time to corticosteroid cessation after LITT was 13.0 days (0.0, 1229.0) and cumulative incidence of lesional progression was 19% at 1 year. Median post-procedure overall survival was 2.55 years [1.66, infinity] and 77.1% at one year as estimated by KaplanMeier. Median KPS remained at 80 through 2-year follow-up. Seizure prevalence was 12% within 1-month post-LITT and 7.9% at 3 months; down from 34.4% within 60-day prior to procedure., Conclusions: LITT for RN was not only again found to be safe with low patient morbidity but was also a highly effective treatment for RN for both local control and symptom management (including seizures). In addition to averting expected neurological death, LITT facilitates ongoing systemic therapy (in particular immunotherapy) by enabling the rapid cessation of steroids, thereby facilitating maximal possible survival for these patients., Competing Interests: We declare that the company Monteris, which funded the trial, is also paying the publication fees for this manuscript. This may create a conflict of interest, as the company has a financial interest in the outcome of the study. However, we confirm that the study was conducted independently and that the results were not influenced by the funding source. We have disclosed all potential conflicts of interest to the journal and are committed to maintaining the integrity and objectivity of our research., (© The Author(s) 2023. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Published
2023
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35. Validation of a Temperature-Feedback Controlled Automated Magnetic Hyperthermia Therapy Device.

Author

Sharma A, Jangam A, Shen JLY, Ahmad A, Arepally N, Rodriguez B, Borrello J, Bouras A, Kleinberg L, Ding K, Hadjipanayis C, Kraitchman DL, Ivkov R, and Attaluri A

Abstract

We present in vivo validation of an automated magnetic hyperthermia therapy (MHT) device that uses real-time temperature input measured at the target to control tissue heating. MHT is a thermal therapy that uses heat generated by magnetic materials exposed to an alternating magnetic field. For temperature monitoring, we integrated a commercial fiber optic temperature probe containing four gallium arsenide (GaAs) temperature sensors. The controller device used temperature from the sensors as input to manage power to the magnetic field applicator. We developed a robust, multi-objective, proportional-integral-derivative (PID) algorithm to control the target thermal dose by modulating power delivered to the magnetic field applicator. The magnetic field applicator was a 20 cm diameter Maxwell-type induction coil powered by a 120 kW induction heating power supply operating at 160 kHz. Finite element (FE) simulations were performed to determine values of the PID gain factors prior to verification and validation trials. Ex vivo verification and validation were conducted in gel phantoms and sectioned bovine liver, respectively. In vivo validation of the controller was achieved in a canine research subject following infusion of magnetic nanoparticles (MNPs) into the brain. In all cases, performance matched controller design criteria, while also achieving a thermal dose measured as cumulative equivalent minutes at 43 °C (CEM43) 60 ± 5 min within 30 min.

Published
2023
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36. Application of 7T MRS to High-Grade Gliomas.

Author

McCarthy L, Verma G, Hangel G, Neal A, Moffat BA, Stockmann JP, Andronesi OC, Balchandani P, and Hadjipanayis CG

Subjects
Humans, Isocitrate Dehydrogenase, Magnetic Resonance Spectroscopy methods, Magnetic Resonance Imaging methods, Brain Neoplasms pathology, Glioma pathology
Abstract

MRS, including single-voxel spectroscopy and MR spectroscopic imaging, captures metabolites in high-grade gliomas. Emerging evidence indicates that 7T MRS may be more sensitive to aberrant metabolic activity than lower-field strength MRS. However, the literature on the use of 7T MRS to visualize high-grade gliomas has not been summarized. We aimed to identify metabolic information provided by 7T MRS, optimal spectroscopic sequences, and areas for improvement in and new applications for 7T MRS. Literature was found on PubMed using "high-grade glioma," "malignant glioma," "glioblastoma," "anaplastic astrocytoma," "7T," "MR spectroscopy," and "MR spectroscopic imaging." 7T MRS offers higher SNR, modestly improved spatial resolution, and better resolution of overlapping resonances. 7T MRS also yields reduced Cramér-Rao lower bound values. These features help to quantify D-2-hydroxyglutarate in isocitrate dehydrogenase 1 and 2 gliomas and to isolate variable glutamate, increased glutamine, and increased glycine with higher sensitivity and specificity. 7T MRS may better characterize tumor infiltration and treatment effect in high-grade gliomas, though further study is necessary. 7T MRS will benefit from increased sample size; reductions in field inhomogeneity, specific absorption rate, and acquisition time; and advanced editing techniques. These findings suggest that 7T MRS may advance understanding of high-grade glioma metabolism, with reduced Cramér-Rao lower bound values and better measurement of smaller metabolite signals. Nevertheless, 7T is not widely used clinically, and technical improvements are necessary. 7T MRS isolates metabolites that may be valuable therapeutic targets in high-grade gliomas, potentially resulting in wider ranging neuro-oncologic applications., (© 2022 by American Journal of Neuroradiology.)

Published
2022
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37. LAPONITE® nanodisk-"decorated" Fe 3 O 4 nanoparticles: a biocompatible nano-hybrid with ultrafast magnetic hyperthermia and MRI contrast agent ability.

Author

Basina G, Diamantopoulos G, Devlin E, Psycharis V, Alhassan SM, Pissas M, Hadjipanayis G, Tomou A, Bouras A, Hadjipanayis C, and Tzitzios V

Subjects
Clay, Contrast Media chemistry, Ferric Compounds chemistry, Magnetic Resonance Imaging methods, Silicates, Water chemistry, Hyperthermia, Induced, Nanoparticles chemistry
Abstract

Magnetic Fe 3 O 4 nanoparticles "decorated" by LAPONITE® nanodisks have been materialized utilizing the Schikorr reaction following a facile approach and tested as mediators of heat for localized magnetic hyperthermia (MH) and as magnetic resonance imaging (MRI) agents. The synthetic protocol involves the interaction between two layered inorganic compounds, ferrous hydroxide, Fe(OH) 2 , and the synthetic smectite LAPONITE® clay Na 0.7 + [(Si 8 Mg 5.5 Li 0.3 )O 20 (OH) 4 ] 0.7 - , towards the formation of superparamagnetic Fe 3 O 4 nanoparticles, which are well decorated by the diamagnetic clay nanodisks. The latter imparts high negative ζ -potential values (up to -34.1 mV) to the particles, which provide stability against flocculation and precipitation, resulting in stable water dispersions. The obtained LAPONITE®-"decorated" Fe 3 O 4 nanohybrids were characterized by powder X-ray diffraction (XRD), transmission electron microscopy (TEM), Mössbauer spectroscopy, dynamic light scattering (DLS) and vibrating sample magnetometry (VSM) at room temperature, revealing superior magnetic hyperthermia performance with specific absorption rate (SAR) values reaching 540 W g Fe -1 (28 kA m -1 , 150 kHz) for the hybrid material with a magnetic loading of 50 wt% Fe 3 O 4 /LAPONITE®. Toxicity studies were also performed with human glioblastoma (GBM) cells and human foreskin fibroblasts (HFF), which show negligible to no toxicity. Furthermore, T 2 -weighted MR imaging of rodent brain shows that the LAPONITE®-"decorated" Fe 3 O 4 nanohybrids predominantly affected the transverse T 2 relaxation time of tissue water, which resulted in a signal drop on the MRI T 2 -weighted imaging, allowing for imaging of the magnetic nanoparticles.

Published
2022
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38. Efficacy of laser interstitial thermal therapy (LITT) for newly diagnosed and recurrent IDH wild-type glioblastoma.

Author

de Groot JF, Kim AH, Prabhu S, Rao G, Laxton AW, Fecci PE, O'Brien BJ, Sloan A, Chiang V, Tatter SB, Mohammadi AM, Placantonakis DG, Strowd RE, Chen C, Hadjipanayis C, Khasraw M, Sun D, Piccioni D, Sinicrope KD, Campian JL, Kurz SC, Williams B, Smith K, Tovar-Spinoza Z, and Leuthardt EC

Abstract

Background: Treatment options for unresectable new and recurrent glioblastoma remain limited. Laser ablation has demonstrated safety as a surgical approach to treating primary brain tumors. The LAANTERN prospective multicenter registry (NCT02392078) data were analyzed to determine clinical outcomes for patients with new and recurrent IDH wild-type glioblastoma., Methods: Demographics, intraprocedural data, adverse events, KPS, health economics, and survival data were prospectively collected and then analyzed on IDH wild-type newly diagnosed and recurrent glioblastoma patients who were treated with laser ablation at 14 US centers between January 2016 and May 2019. Data were monitored for accuracy. Statistical analysis included individual variable summaries, multivariable differences in survival, and median survival numbers., Results: A total of 29 new and 60 recurrent IDH wild-type WHO grade 4 glioblastoma patients were treated. Positive MGMT promoter methylation status was present in 5/29 of new and 23/60 of recurrent patients. Median physician-estimated extent of ablation was 91%-99%. Median overall survival (OS) was 9.73 months (95% confidence interval: 5.16, 15.91) for newly diagnosed patients and median post-procedure survival was 8.97 months (6.94, 12.36) for recurrent patients. Median OS for newly diagnosed patients receiving post-LITT chemo/radiation was 16.14 months (6.11, not reached). Factors associated with improved survival were MGMT promoter methylation, adjuvant chemotherapy within 12 weeks, and tumor volume <3 cc., Conclusions: Laser ablation is a viable option for patients with new and recurrent glioblastoma. Median OS for IDH wild-type newly diagnosed glioblastoma is comparable to outcomes observed in other tumor resection studies when those patients undergo radiation and chemotherapy following LITT., (© The Author(s) 2022. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Published
2022
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39. Orbital invasion by Esthesioneuroblastoma: a comparative case series and review of literature.

Author

Wu K, Avila SA, Bhuyan R, Matloob A, Del Signore AG, Hadjipanayis C, and Chelnis J

Subjects
Adult, Female, Humans, Male, Nasal Cavity pathology, Neoplasm Staging, Retrospective Studies, Esthesioneuroblastoma, Olfactory therapy, Nose Neoplasms pathology, Nose Neoplasms therapy
Abstract

Purpose: To review the current literature on esthesioneuroblastoma (ENB) as it pertains to clinical features, grading systems, treatment options, and survival., Methods: A literature search in PubMed was performed to include all articles published in English with orbit involving ENB. Only articles that included each patient's demographics, tumor stage, treatment, or survival were included. A total of 22 articles with 104 patients were considered for this literature review. We also present five cases of ENB, all encountered in our health system, between 2010 and 2020., Results: The median age of diagnosis of orbit involving ENB was 44.5 years. Males were more likely affected than females at 72.9%. Common presenting ocular symptoms were visual change (38.1%), periorbital pain (33.3%), and diplopia (14.3%). Common clinical exam findings were proptosis (47.6%), extraocular movement deficit (23.8%), and periorbital edema (19.0%). Twenty-seven patients (77.1%) received surgery, 22 patients (62.9%) received chemotherapy, and 30 patients (85.7%) received radiation therapy as part of their treatment. Median duration of survival was 124.0 months and 5-year overall survival (OS) was 67.1%. Hyams, Kadish, and Dulguerov T-staging showed inconsistent survival prognosis while orbital invasion and lymph node metastasis had worse outcomes. Our five cases exhibited the spectrum of disease processes evidenced above, with four involving the orbit., Conclusions: ENB is a rare sinonasal tumor that can invade the orbit. Because of its rarity, no single staging system appears superior. Resection with radiation therapy has superior survival results while the benefits of chemotherapy are currently unknown.

Published
2022
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40. 3D Exoscope Navigation-Guided Approach to Middle Cranial Fossa.

Author

Kaul VF, Fan CJ, Perez E, Schwam ZG, Hadjipanayis C, and Wanna GB

Subjects
Cadaver, Humans, Petrous Bone anatomy & histology, Semicircular Canals, Tomography, X-Ray Computed, Cranial Fossa, Middle diagnostic imaging, Cranial Fossa, Middle surgery, Temporal Bone anatomy & histology, Temporal Bone diagnostic imaging, Temporal Bone surgery
Abstract

Objective: To test the feasibility and efficacy of a 3D exoscope navigation-guided middle cranial fossa (MCF) approach to the internal auditory canal (IAC); to potentially obviate the need to use dissection landmarks and instead, use the navigation probe as a guide to find structures and drill down to the IAC., Patients: Cadaveric dissection of six temporal bones., Intervention: Computed tomography temporal bone was performed with fiducials on each specimen before the dissection to employ the navigation system. Using a 3D exoscope with navigation by Synaptive (Toronto, Ontario, Canada), the MCF approach was performed., Main Outcome Measures: Navigation accuracy, ability to identify critical structures, and ability to drill out the IAC successfully., Results: All six specimens had the IAC successfully drilled out using the 3D exoscope. All dissections were performed with navigation and did not require dissecting out the greater superficial petrosal nerve and superior semicircular canal. One specimen used landmark dissection to confirm the IAC after navigation had been used to locate the IAC first. Navigation accuracy mean was 1.86 mm (range, 1.56-2.05 mm)., Conclusion: A 3D exoscope navigation-guided MCF approach to the IAC is feasible without landmark dissection., Competing Interests: Funding and conflicts of interest. The rest of the authors have no funding, financial relationships, or conflicts of interest to disclose., (Copyright © 2021, Otology & Neurotology, Inc.)

Published
2021
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41. Student Survey Results of a Virtual Medical Student Course Developed as a Platform for Neurosurgical Education During the Coronavirus Disease 2019 Pandemic.

Author

Martini ML, Yaeger KA, Kellner CP, Hadjipanayis C, Shrivastava R, Mocco J, and Morgenstern PF

Subjects
Curriculum statistics & numerical data, Education, Medical, Undergraduate methods, Educational Status, Humans, SARS-CoV-2 pathogenicity, COVID-19 complications, Education, Medical, Undergraduate statistics & numerical data, Neurosurgery education, Students, Medical statistics & numerical data, Surveys and Questionnaires
Abstract

Background: Before the coronavirus disease 2019 (COVID-19) pandemic, medical students training in neurosurgery relied on external subinternships at institutions nationwide for immersive educational experiences and to increase their odds of matching. However, external rotations for the 2020-2021 cycle were suspended given concerns of spreading COVID-19. Our objective was to provide foundational neurosurgical knowledge expected of interns, bootcamp-style instruction in basic procedures, and preinterview networking opportunities for students in an accessible, virtual format., Methods: The virtual neurosurgery course consisted of 16 biweekly 1-hour seminars over a 2-month period. Participants completed comprehensive precourse and postcourse surveys assessing their backgrounds, confidence in diverse neurosurgical concepts, and opinions of the qualities of the seminars. Responses from students completing both precourse and postcourse surveys were included., Results: An average of 82 students participated live in each weekly lecture (range, 41-150). Thirty-two participants completed both surveys. On a 1-10 scale self-assessing baseline confidence in neurosurgical concepts, participants were most confident in neuroendocrinology (6.79 ± 0.31) and least confident in spine oncology (4.24 ± 0.44), with an average of 5.05 ± 0.32 across all topics. Quality ratings for all seminars were favorable. The mean postcourse confidence was 7.79 ± 0.19, representing an improvement of 3.13 ± 0.38 (P < 0.0001)., Conclusions: Feedback on seminar quality and improvements in confidence in neurosurgical topics suggest that an interactive virtual course may be an effective means of improving students' foundational neurosurgical knowledge and providing networking opportunities before application cycles. Comparison with in-person rotations when these are reestablished may help define roles for these tools., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Published
2021
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42. Intraoperative molecular imaging clinical trials: a review of 2020 conference proceedings.

Author

Azari F, Kennedy G, Bernstein E, Hadjipanayis C, Vahrmeijer A, Smith B, Rosenthal E, Sumer B, Tian J, Henderson E, Lee A, Nguyen Q, Gibbs S, Pogue B, Orringer D, Charalampaki C, Martin L, Tanyi J, Lee M, Lee JY, and Singhal S

Subjects
Aminolevulinic Acid, Humans, Margins of Excision, Molecular Imaging, Neoplasms diagnostic imaging, Neoplasms surgery
Abstract

Significance: Surgery is often paramount in the management of many solid organ malignancies because optimal resection is a major factor in disease-specific survival. Cancer surgery has multiple challenges including localizing small lesions, ensuring negative surgical margins around a tumor, adequately staging patients by discriminating positive lymph nodes, and identifying potential synchronous cancers. Intraoperative molecular imaging (IMI) is an emerging potential tool proposed to address these issues. IMI is the process of injecting patients with fluorescent-targeted contrast agents that highlight cancer cells prior to surgery. Over the last 5 to 7 years, enormous progress has been achieved in tracer development, near-infrared camera approvals, and clinical trials. Therefore, a second biennial conference was organized at the University of Pennsylvania to gather surgical oncologists, scientists, and experts to discuss new investigative findings in the field. Our review summarizes the discussions from the conference and highlights findings in various clinical and scientific trials., Aim: Recent advances in IMI were presented, and the importance of each clinical trial for surgical oncology was critically assessed. A major focus was to elaborate on the clinical endpoints that were being utilized in IMI trials to advance the respective surgical subspecialties., Approach: Principal investigators presenting at the Perelman School of Medicine Abramson Cancer Center's second clinical trials update on IMI were selected to discuss their clinical trials and endpoints., Results: Multiple phase III, II, and I trials were discussed during the conference. Since the approval of 5-ALA for commercial use in neurosurgical malignancies, multiple tracers and devices have been developed to address common challenges faced by cancer surgeons across numerous specialties. Discussants also presented tracers that are being developed for delineation of normal anatomic structures that can serve as an adjunct during surgical procedures., Conclusions: IMI is increasingly being recognized as an improvement to standard oncologic surgical resections and will likely advance the art of cancer surgery in the coming years. The endpoints in each individual surgical subspecialty are varied depending on how IMI helps each specialty solve their clinical challenges.

Published
2021
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43. Medical Student Publications in Neurosurgery: At Which U.S. Academic Institutions Do Medical Students Publish Most?

Author

Price G, Lakomkin N, Kamat S, Baron RB, Scherschinski L, and Hadjipanayis C

Subjects
Humans, Neurosurgery education, United States, Faculty, Medical statistics & numerical data, Neurosurgery statistics & numerical data, Publishing statistics & numerical data, Students, Medical statistics & numerical data
Abstract

Background: The neurosurgery residency match is a competitive process. While medical research offers esteemed learning opportunities, productivity is closely evaluated by residency programs. Accordingly, students work diligently to make contributions on projects within their neurosurgery departments. The present study evaluated medical student research productivity for each of the 118 U.S. neurosurgery residency programs., Methods: A retrospective review of publications for 118 neurosurgery programs from January 1, 2015, to April 1, 2020, was performed. The primary outcome was any publication with a medical student as the first author. Secondary outcomes included number of faculty in each department, department region, and medical school ranking. The number of student first author publications was compared among programs, regions, and medical schools., Results: Mean numbers of medical student first author publications and faculty members per institution were 16.27 and 14.46, respectively. The top 3 neurosurgery departments with the greatest number of student first author publications were Johns Hopkins University, Brigham and Women's Hospital, and University of California, San Francisco. Salient findings included a positive correlation between the number of medical student first author publications from a neurosurgery department and the number of departmental faculty (P < 0.001, R = 0.69). Additionally, the mean number of first author medical student publications at the top 30 programs was higher than the mean for the remaining programs (P < 0.0001)., Conclusions: This study is the first to evaluate neurosurgery medical student productivity in North America. By systematizing first authorships, incoming students who desire to pursue neurosurgery can be informed of institutions with student involvement, and departments that use medical student expertise can be recognized., (Published by Elsevier Inc.)

Published
2021
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44. Use of Intraoperative Fluorophores.

Author

Schupper AJ and Hadjipanayis C

Subjects
Humans, Neurosurgical Procedures methods, Brain Neoplasms diagnostic imaging, Brain Neoplasms surgery, Fluorescent Dyes administration & dosage, Glioma diagnostic imaging, Glioma surgery, Neuronavigation methods
Abstract

Fluorescence-guided surgery provides surgeons with improved visualization of tumor tissue in the operating room to allow for maximal safe resection of brain tumors. Multiple fluorescent agents have been studied for fluorescence-guided surgery. Both nontargeted and targeted fluorescent agents are currently being used for glioblastoma multiforme visualization and resection. Fluorescence detection in the visible light or near infrared spectrum is possible. Visualization device advancements have permitted greater detection of fluorescence down to the cellular level, which may provide even greater ability for the neurosurgeon to resect tumors., Competing Interests: Disclosure C. Hadjipanayis is a consultant for NXDC and Synaptive Medical Inc. He receives royalties from NXDC. He has also received speaker fees by Carl Zeiss and Leica. A.J. Schupper has nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Published
2021
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45. Multiparametric MRI for early identification of therapeutic response in recurrent glioblastoma treated with immune checkpoint inhibitors.

Author

Song J, Kadaba P, Kravitz A, Hormigo A, Friedman J, Belani P, Hadjipanayis C, Ellingson BM, and Nael K

Subjects
Female, Humans, Immune Checkpoint Inhibitors, Magnetic Resonance Imaging, Male, Middle Aged, Multiparametric Magnetic Resonance Imaging, Retrospective Studies, Brain Neoplasms diagnostic imaging, Brain Neoplasms drug therapy, Glioblastoma diagnostic imaging, Glioblastoma drug therapy
Abstract

Background: Physiologic changes quantified by diffusion and perfusion MRI have shown utility in predicting treatment response in glioblastoma (GBM) patients treated with cytotoxic therapies. We aimed to investigate whether quantitative changes in diffusion and perfusion after treatment by immune checkpoint inhibitors (ICIs) would determine 6-month progression-free survival (PFS6) in patients with recurrent GBM., Methods: Inclusion criteria for this retrospective study were: (i) diagnosis of recurrent GBM treated with ICIs and (ii) availability of diffusion and perfusion in pre and post ICI MRI (iii) at ≥6 months follow-up from treatment. After co-registration, mean values of the relative apparent diffusion coefficient (rADC), Ktrans (volume transfer constant), Ve (extravascular extracellular space volume) and Vp (plasma volume), and relative cerebral blood volume (rCBV) were calculated from a volume-of-interest of the enhancing tumor. Final assignment of stable/improved versus progressive disease was determined on 6-month follow-up using modified Response Assessment in Neuro-Oncology criteria., Results: Out of 19 patients who met inclusion criteria and follow-up (mean ± SD: 7.8 ± 1.4 mo), 12 were determined to have tumor progression, while 7 had treatment response after 6 months of ICI treatment. Only interval change of rADC was suggestive of treatment response. Patients with treatment response (6/7: 86%) had interval increased rADC, while 11/12 (92%) with tumor progression had decreased rADC (P = 0.001). Interval change in rCBV, Ktrans, Vp, and Ve were not indicative of treatment response within 6 months., Conclusions: In patients with recurrent GBM, interval change in rADC is promising in assessing treatment response versus progression within the first 6 months following ICI treatment., Key Points: • In recurrent GBM treated with ICIs, interval change in rADC suggests early treatment response.• Interval change in rADC can be used as an imaging biomarker to determine PFS6.• Interval change in MR perfusion and permeability measures do not suggest ICI treatment response., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Published
2020
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46. Akaluc bioluminescence offers superior sensitivity to track in vivo glioma expansion.

Author

Bozec D, Sattiraju A, Bouras A, Jesu Raj JG, Rivera D, Huang Y, Junqueira Alves C, Tejero R, Tsankova NM, Zou H, Hadjipanayis C, and Friedel RH

Abstract

Background: Longitudinal tracking of tumor growth using noninvasive bioluminescence imaging (BLI) is a key approach for studies of in vivo cancer models, with particular relevance for investigations of malignant gliomas in rodent intracranial transplant paradigms. Akaluciferase (Akaluc) is a new BLI system with higher signal strength than standard firefly luciferase (Fluc). Here, we establish Akaluc BLI as a sensitive method for in vivo tracking of glioma expansion., Methods: We engineered a lentiviral vector for expression of Akaluc in high-grade glioma cell lines, including patient-derived glioma stem cell (GSC) lines. Akaluc-expressing glioma cells were compared to matching cells expressing Fluc in both in vitro and in vivo BLI assays. We also conducted proof-of-principle BLI studies with intracranial transplant cohorts receiving chemoradiation therapy., Results: Akaluc-expressing glioma cells produced more than 10 times higher BLI signals than Fluc-expressing counterparts when examined in vitro, and more than 100-fold higher signals when compared to Fluc-expressing counterparts in intracranial transplant models in vivo. The high sensitivity of Akaluc permitted detection of intracranial glioma transplants starting as early as 4 h after implantation and with as little as 5000 transplanted cells. The sensitivity of the system allowed us to follow engraftment and expansion of intracranial transplants of GSC lines. Akaluc was also robust for sensitive detection of in vivo tumor regression after therapy and subsequent relapse., Conclusion: Akaluc BLI offers superior sensitivity for in vivo tracking of glioma in the intracranial transplant paradigm, facilitating sensitive approaches for the study of glioma growth and response to therapy., (© The Author(s) 2020. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Published
2020
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47. Laser Ablation of Abnormal Neurological Tissue Using Robotic NeuroBlate System (LAANTERN): 12-Month Outcomes and Quality of Life After Brain Tumor Ablation.

Author

Kim AH, Tatter S, Rao G, Prabhu S, Chen C, Fecci P, Chiang V, Smith K, Williams BJ, Mohammadi AM, Judy K, Sloan A, Tovar-Spinoza Z, Baumgartner J, Hadjipanayis C, and Leuthardt EC

Subjects
Adult, Aged, Brain Neoplasms mortality, Female, Humans, Karnofsky Performance Status, Laser Therapy mortality, Male, Middle Aged, Prospective Studies, Registries, Robotic Surgical Procedures mortality, Survival Rate, Treatment Outcome, Brain Neoplasms surgery, Laser Therapy methods, Quality of Life, Robotic Surgical Procedures methods
Abstract

Background: Laser Ablation of Abnormal Neurological Tissue using Robotic NeuroBlate System (LAANTERN) is an ongoing multicenter prospective NeuroBlate (Monteris Medical) LITT (laser interstitial thermal therapy) registry collecting real-world outcomes and quality-of-life (QoL) data., Objective: To compare 12-mo outcomes from all subjects undergoing LITT for intracranial tumors/neoplasms., Methods: Demographics, intraprocedural data, adverse events, QoL, hospitalizations, health economics, and survival data are collected; standard data management and monitoring occur., Results: A total of 14 centers enrolled 223 subjects; the median follow-up was 223 d. There were 119 (53.4%) females and 104 (46.6%) males. The median age was 54.3 yr (range 3-86) and 72.6% had at least 1 baseline comorbidity. The median baseline Karnofsky Performance Score (KPS) was 90. Of the ablated tumors, 131 were primary and 92 were metastatic. Most patients with primary tumors had high-grade gliomas (80.9%). Patients with metastatic cancer had recurrence (50.6%) or radiation necrosis (40%). The median postprocedure hospital stay was 33.4 h (12.7-733.4). The 1-yr estimated survival rate was 73%, and this was not impacted by disease etiology. Patient-reported QoL as assessed by the Functional Assessment of Cancer Therapy-Brain was stabilized postprocedure. KPS declined by an average of 5.7 to 10.5 points postprocedure; however, 50.5% had stabilized/improved KPS at 6 mo. There were no significant differences in KPS or QoL between patients with metastatic vs primary tumors., Conclusion: Results from the ongoing LAANTERN registry demonstrate that LITT stabilizes and improves QoL from baseline levels in a malignant brain tumor patient population with high rates of comorbidities. Overall survival was better than anticipated for a real-world registry and comparative to published literature., (© Congress of Neurological Surgeons 2020.)

Published
2020
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48. Repair of a Temporal Bone Encephalocele With the Surgical Exoscope.

Author

Garneau JC, Laitman BM, Cosetti MK, Hadjipanayis C, and Wanna GB

Subjects
Aged, Craniotomy, Humans, Male, Neurosurgical Procedures, Skull Base surgery, Encephalocele diagnostic imaging, Encephalocele surgery, Temporal Bone diagnostic imaging, Temporal Bone surgery
Abstract

Objective: We describe our experience using the extracorporeal video microscope, the "exoscope" for repair of a temporal bone encephalocele., Method: The patient is a 69-year-old male with a right temporal lobe encephalocele herniating through a tegmen defect. He underwent definitive tegmen defect repair and bipolar cauterization of the encephalocele. The authors elected for a combined transmastoid and transtemporal approach in order to isolate the tegmen defect and provide watertight repair. The Synaptive robotic BrightMatter (Toronto, ON) drive video exoscope monitor system was used for the entirety of the case including both the transmastoid approach and transtemporal craniotomy., Results: No intraoperative complications were encountered during either the transmastoid (mastoidectomy) or transtemporal craniotomy. The authors were able to complete the entire case without abandonment of the exoscope in favor of the traditional binocular microscope. Advantages of this technology in clinical practice includes high-resolution three-dimensional visualization, increased degrees of freedom for exoscope adjustment, and reduced surgeon fatigue in a fixed, unnatural posture. Limitations include decreased depth perception and increased operative time., Conclusion: The exoscope system is a safe and effective alternative or adjunct to the existing binocular operating microscope for lateral skull based procedures. The exoscope provides the surgeon with a comfortable, high-resolution visualization without compromising surgical exposure and patient safety.SDC video link: http://links.lww.com/MAO/A837.

Published
2020
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49. Patents and Innovation Among Neurosurgeons from the American Association of Neurological Surgeons.

Author

Baron RB, Kessler RA, Bhammar A, Boulis N, Adler JR Jr, Kohli K, and Hadjipanayis C

Abstract

Objective Neurosurgeons have taken on the role of innovators, continuing to move the field forward over the centuries. More recently, innovation has taken the form of new technological devices and therapeutics, which require patenting. The aim of this study is to identify major areas of innovation in the field of neurosurgery by evaluating patent records. Methods This study quantifies the number of patents the American Association of Neurological Surgeons (AANS) neurosurgeons hold across different subspecialties. The United States Patent and Trademark Office (USPTO) patent database was queried using the names of 7,293 AANS members who filed patents between 1976 and 2019. Results A total of 346 (4.7%) AANS neurosurgeons hold a total of 1,025 patents. The number of patents held by each neurosurgeon ranged from one to 109. The areas that patents were filed under include cellular and genetic science (40), drug delivery (45), image guidance (82), neuromodulation (52), pain (7), peripheral nerve stimulation (24), spine (398), surgical devices (148), trauma (16), tumor (78), vascular (67), and other (68). No patents were filed under pediatrics (0). The fields with the greatest number of filed patents are spine, instruments/devices, and image guidance. Conclusion Given the technical nature of the field of neurosurgery, instruments and devices that improve localization, visualization, targeting, and spinal reconstruction are often in demand. Furthermore, since the rates of spinal procedures and implants continue to increase, higher patenting may be motivated by the opportunity to develop new products that can result in royalty payments to neurosurgeons. The advent of new technologies undoubtedly continues to push the field of neurosurgery forward., Competing Interests: John Adler is the Founder and CEO of both Cureus.com and Zap Surgical and named inventor on more than 20 patents, some of which are included in this publication (i.e., Gamma Knife, Cyberknife). Nicholas Boulis has patented the use of a stimulus to white matter. Constantinos Hadjipanayis owns patents on the use of nanoparticles for targeted therapy.. John A. Adler, founder of Cureus Inc., contributed to our work by providing direction and overview., (Copyright © 2020, Baron et al.)

Published
2020
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50. Clinical impact of intraoperative hyperlactatemia during craniotomy.

Author

Romano D, Deiner S, Cherukuri A, Boateng B, Shrivastava R, Mocco J, Hadjipanayis C, Yong R, Kellner C, Yaeger K, Lin HM, and Brallier J

Subjects
Cohort Studies, Female, Humans, Male, Middle Aged, Nervous System Diseases blood, Risk Factors, Craniotomy methods, Hyperlactatemia complications, Intraoperative Complications, Lactic Acid blood, Length of Stay statistics & numerical data, Nervous System Diseases etiology
Abstract

Object: Patients often develop markedly elevated serum lactate levels during craniotomy although the reason for this is not entirely understood. Elevated lactate levels have been associated with poor outcomes in critically ill septic shock patients, as well as patients undergoing abdominal and cardiac surgeries. We investigated whether elevated lactate in craniotomy patients is associated with neurologic complications (new neurological deficits) as well as systemic complications., Methods: We performed a cohort study of elective craniotomy patients. Demographic and intraoperative data were collected, as well as three timed intraoperative arterial lactate values. Additional lactate, creatinine and troponin values were collected immediately postoperatively as well as 12 and 24 hours postoperatively. Assessment for neurologic deficit was performed at 6 hours and 2 weeks postoperatively. Hospital length-of-stay and 30-day mortality were collected., Results: Interim analysis of 81 patients showed that no patient had postoperative myocardial infarction, renal failure, or mortality within 30 days of surgery. There was no difference in the incidence of new neurologic deficit in patients with or without elevated lactate (10/26, 38.5% vs. 15/55 27.3%, p = 0.31). Median length of stay was significantly longer in patients with elevated lactate (6.5 vs. 3 days, p = 0.003). Study enrollment was terminated early due to futility (futility index 0.16)., Conclusion: Elevated intraoperative serum lactate was not associated with new postoperative neurologic deficits, other end organ events, or 30 day mortality. Serum lactate was related to longer hospital stay., Competing Interests: The authors have declared that no competing interests exist.

Published
2019
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