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2. Hippocampal Sparing Radiotherapy in adults with Primary Brain Tumors: A comparative planning and dosimetric study using IMPT, IMRT and 3DCRT
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Aka, P, Taylor, R, Hugtenburg, R, Lambert, J, Powell, J, Bevolo, T, Gao, M, Gondi, V, Hartsell, W.H, Bolsi, A, Beer, J, Belosi, M.F, Siewert, D, Lomax, A.J, Weber, D.C, Huang, Y.J, Huang, C.C, Chao, P.J, Liu, C, Shang, H, Ding, X, Wang, Y, Mammar, H, Froelich, Sébastien, Alapetite, Claire, Bolle, Stéphanie, Calugaru, Valentin, Feuvret, Loic, Helfre, Sylvie, Champion, Laurence, Goudjil, Farid, Dendal, Remi, Engelholm, S.A, Munck Af Rosenschold, P, Kristensen, I, Smulders, B, Muhic, A, Alkner, S, Jacob, E, Engelholm, S, Aljabab, S, Lui, A, Wong, T, Liao, J, Laramore, G, Parvathaneni, U, Kharouta, M, Pidikiti, R, Jesseph, F, Smith, M, Dobbins, D, Mattson, D, Choi, S, Mansur, D, Machtay, M, Bhatt, A, Lütgendorf-Caucig, C, Dunavölgyi, R, Georg, P, Perpar, A, Fussl, C, Konstantinovic, R, Ulrike, M, Piero, F, Eugen, H, Vidal, M, Gerard, A, Barnel, C, Maneval, D, Herault, J, Claren, A, Doyen, J, Dendale, R, Toutee, A, Pasquie, I, Goudjil, F, Lumbroso Lerouic, L, Levy, C, Desjardins, L, Cassoux, N, Elisei, G, Pella, A, Calvi, G, Ricotti, R, Tagaste, B, Valvo, F, Ciocca, M, Via, R, Mastella, E, Baroni, G, Saotome, N, Yonai, S, Makishima, H, Hara, Y, Inaniwa, T, Sakama, M, Kanematsu, N, Tsuji, H, Furukawa, T, Shirai, T, Sauerwein, W, Finger, P.T, Gallie, B, Gavrylyuk, Y, Thariat, J, Salleron, J, Maschi, C, Fevrier, E, Caujolle, J.P, Hofverberg, P, Angellier, G, Peyrichon, M.L, Breneman, J, Esslinger, H, Pater, L, Vatner, R, Habrand, J.L, Stefan, D, Lesueur, P, Kao, W, Véla, A, Geffrelot, J, Tessonnier, T, Balosso, J, Mahé, M.A, Lim, P.S, Rompokos, V, Chang, Y.C, Royle, G, Gaze, M, Gains, J, Vennarini, S, Francesco, F, Rombi, B, Amichetti, M, Schwarz, M, Lorentini, S, Mee, T, Burnet, N.G, Crellin, A, Kirkby, N.F, Smith, E, Kirkby, K.J, Roggio, M, Buwenge, M, Melchionda, F, Ammendolia, I, Ronchi, L, Cammelli, S, Morganti, A.G, Youn, S.H, Kim, J.Y, Park, H.J, Shin, S.H, Lee, S.H, Hong, E.K, Czerska, K, Winczura, P, Wejs-Maternik, J, Blukis, A, Antonowicz-Szydlowska, M, Rucinski, A, Olko, P, Badzio, A, Kopec, R, Franceschini, D, Cozzi, L, De Rose, F, Meattini, I, Fogliata, A, Cozzi, S, Becherini, C, Tomatis, S, Livi, L, Scorsetti, M, Garda, A, Fattahi, S, Michel, A, Mutter, R, Yan, E, Park, S, Corbin, K, Giap, H, LAM, W.W, Geng, H, Tang, K.K, Lee, T.Y, Kong, C.W, Yang, B, Chiu, T.L, Cheung, K.Y, Yu, S.K, Ma, M, Gao, X, Zhao, Z, Zhao, B, Mullikin, T, Routman, D, Yu, J, Greco, K, Fagundes, M, Shan, J, Daniels, T, Rule, W, DeWees, T, Hu, Y, Bues, M, Sio, T, Liu, W, chenbin, L, yuehu, P, yuenan, W, Bai, Y, Gao, X.S, Zhao, Z.L, Ma, M.W, Ren, X.Y, Salem, A, Woolf, D, Aznar, M, Azadeh, A, Eccles, C, Charlwood, F, Faivre-Finn, C, Teoh, S, Fiorini, F, George, B, Vallis, K, Van den Heuvel, F, Huang, E.Y, Juang, P.J, Pan, S, Hawkins, M, Clarke, M, Lowe, M, Radhakrishna, G, Schaub, S, Bowen, S, Nyflot, M, Chapman, T, Apisarnthanarax, S, Vitek, P, Kubes, J, Vondracek, V, Vinakurau, S, Zamecnik, L, Vitolo, V, Barcellini, A, Brugnatelli, S, Cobianchi, L, Vanoli, A, Fossati, P, Facoetti, A, Dionigi, P, Orecchia, R, Iannalfi, A, Vischioni, B, Ronchi, S, D’Ippolito, E, Petrucci, R, Yamaguchi, H, Honda, M, Hamada, K, Todate, Y, Seto, I, Suzuki, M, Wada, H, Murakami, M, Yu, Z, Zheng, W, Lien-Chun, L, Zhengshan, H, Qing, Z, Jiade, L, Guoliang, J, Fiore, M.R, D'Ippolito, E, Fukumitsu, N, Hayakawa, T, Yamashita, T, Mima, M, Demizu, Y, Suzuki, T, Soejima, T, Hartsell, W, Collins, S, Casablanca, V, Mihalcik, S, Brennan, E, Van Nispen, A, Corbett, A, Mohammed, N, Lee, P, van Nispen, A, Liang, Y.S, Mein, S, Kopp, B, Choi, K, Haberer, T, Debus, J, Abdollahi, A, Mairani, A, Ogino, H, Iwata, H, Hashimoto, S, Nakajima, K, Hattori, Y, Nomura, K, Shibamoto, Y, Li, P, Wu, S, Deng, L, Zhang, G, Zhang, Q, Fu, S, Yang, Z, Zhang, Y, Sasaki, R, Okimoto, T, Akasaka, H, Miyawaki, D, Yoshida, K, Wang, T, Komatsu, S, Fukumoto, T, Shuang, W, Xin, C, zhengshan, H, Shen, F, Vorobyov, N, Andreev, G, Martynova, N, Lyubinsky, A, Kubasov, A, Chen, J, Ma, N, Lu, Y, Zhao, J, Shahnazi, K, Lu, J, Jiang, G, Mao, J, Walser, M, Bojaxhiu, B, Kawashiro, S, Tran, S, Pica, A, Bachtiary, B, Weber, D, Gaito, S, Abravan, A, Richardson, J, Colaco, R, Saunders, D, Brennan, B, Petersen, I, Ahmed, S, Laack, N, Mizoe, J.E, Iizumi, T, Minohara, S, Kusano, Y, Matsuzaki, Y, Tsuchida, K, Serizawa, I, Yoshida, D, Katoh, H, Sakurai, H, Tujii, H, Kim, T.H, Park, J.W, Bo Hyun, K, Hyunjung, K, Sung Ho, M, Sang Soo, K, Sang Myung, W, Young-Hwan, K, Woo Jin, L, Dae Yong, K, Hong, Z, Wang, Z, Koroulakis, A, Molitoris, J, Kaiser, A, Hanna, N, Jiang, Y, Regine, W, DeCesaris, C.M, Choi, J.I, Carr, S.R, Burrows, W.M, Regine, W.F, Simone, C.B, Aihara, T, Hiratsuka, J, Kamitani, N, Higashino, M, Kawata, R, Kumada, H, Ono, K, Chou, Y.C, Dippolito, E, Bonora, M, Alterio, D, Gandini, S, Jereczeck, B.A, Kelly, C, Dobeson, C, Iqbal, S, Chatterjee, S, Hague, C, Li, T, Lin, A, Lukens, J, Slevin, N, Thomson, D, van Herk, M, West, C, Teo, K, Jeans, E, Manzar, G, Patel, S, Ma, D, Lester, S, Foote, R, Friborg, J, Jensen, K, Hansen, C.R, Andersen, E, Andersen, M, Eriksen, J.G, Johansen, J, Overgaard, J, Grau, C, Dědečková, K, Vítek, P, Ondrová, B, Sláviková, S, Zapletalová, S, Zapletal, R, Vondráček, V, Rotnáglová, E, Kwanghyun, J, Woojin, L, Dongryul, O, Yong Chan, A, Paudel, N, Schmidt, S, Ruckman, M, Gans, S, Stauffer, M, Helenowski, I, Patel, U, Samant, S, Gentile, M, Damico, N, Yao, M, Shuja, M, Routman, D.M, Foote, R.L, Garces, Y.I, Neben-Wittich, M.A, Patel, S.H, McGee, L.A, Harmsen, W.S, Ma, D.J, Sommat, K, Tong, A.K.T, Hu, J, Ong, A.L.K, Wang, F, Sin, S.Y, Wee, T.S, Tan, W.K, Fong, K.W, Soong, Y.L, Wallace, N, Fredericks, S, Fitzgerald, T, Vernimmen, F, Petringa, G, Cirrone, P, Agosteo, S, Attili, A, Cammarata, F.P, Cuttone, G, Conte, V, La Tessa, C, Manti, L, Rosenfeld, A, Lojacono, P.A, Hennings, F, Fattori, G, Peroni, M, Lomax, A, Hrbacek, J, Nguyen, H.G, Bach Cuadra, M, Sznitman, R, Schalenbourg, A, Pflaeger, A, Weber, A, Seidel, S, Stark, R, Heufelder, J, Mailhot Vega, R, Bradley, J, Lockney, N, Macdonald, S, Liang, X, Mazal, A, Mendenhall, N, Sher, D, Korreman, S.S, Andreasen, S, Petersen, J.B, Offersen, B.V, Gergelis, K, Jethwa, K, Whitaker, T, Shiraishi, S, Shumway, D, Press, R, Shelton, J, Zhang, C, Dang, Q, Tian, S, Shu, T, Seldon, C, Jani, A, Zhou, J, McDonald, M, Gort, E, Beukema, J.C, Spijkerman-Bergsma, M.J, Both, S, Langendijk, J.A, Matysiak, W.P, Brouwer, C.L, Baba, K, Numajiri, H, Murofushi, K, Oshiro, Y, Mizumoto, M, Onishi, K, Nonaka, T, Ishikawa, H, Okumura, T, Dominietto, M, Adam, K, Ahlhelm, F.J, Safai, S, Abdul-Jabbar, L, Song, J, Tseng, Y. D, Rockhill, J, Fink, J, Chang, L, Halasz, L. M, Guntrum, F, Steinmeier, T, Nagaraja, S, Jazmati, D, Geismar, D, Timmermann, B, Plaude, S, Lynch, C, Petras, K, Chang, J, Grimm, S, Lukas, R, Kumthekar, P, Merrell, R, Kalapurakal, J, Gross, J, Hoppe, B, Simone, C, Nichols, R.C, Pham, D, Mohindra, P, Chon, B, Morris, C, Li, Z, Flampouri, S, Powell, J.R, Murray, L, Burnet, N, Fernandez, S, Lingard, Z, McParland, L, O’Hara, D, Whitfield, G, Short, S.C, Guan, X, Gao, J, Hu, W, Yang, J, Xing, X, Hu, C, Kong, L, Zou, Z, Thomas, H, Sasidharan, B.K, Rengan, R, Zeng, J, Busold, S, Heese, J, Cerello, P, Bottura, L, Felcini, E, Ferrero, V, Monaco, V, Pennazio, F, de Rijk, G, Chang, H, KyungDon, C, Byunghun, H, Gyuseong, C, Chilukuri, S, Jalali, R, Panda, P.K, Korn, G, Larosa, G, Russo, A, Schillaci, F, Scuderi, V, Margarone, D, Fredén, E, Almhagen, E, Mejaddam, Y, Siegbahn, A, Guardiola, C, Gómez, F, Prieto-Pena, J, Fleta, C, De Marzi, L, Prezado, Y, Kabolizadeh, P, Reitemeier, P, Navin, M, Hamstra, D, Anderson, J, Stevens, C, Bartolucci, L, Adrien, C, Lejars, M, Vaillant, M, Fourquet, A, Robillard, M, Costa, E, Kirova, Y, Kolano, A.M, Degiovanni, A, Farr, J.B, Kundel, S, Pinto, M, Kurichiyanil, N, Würl, M, Englbrecht, F, Hillbrand, M, Schreiber, J, Parodi, K, Kurup, A, Magliari, A, Perez, J, Masui, S, Asano, T, Owen, H, Burt, G, Apsimon, R, Pitman, S, Popovici, M.A, Vasilache, R, Safavi-Naeini, M, Chacon, A, Howell, N, Middleton, R.J, Fraser, B, Guatelli, S, Rendina, L, Matsufuji, N, Gregoire, M.C, Sikora, K, Pettingell, J, Crocker, M, Saplaouras, A, Snijders, A, Mao, J.H, Nakamura, K, Bin, J, Gonsalves, A, Mao, H.S, Steinke, S, Roach, M, Leemans, W, Blakely, E, Takayama, K, Tan, T.S, Wee, J.T.S, Tuan, J.K.L, Wang, M.L.C, Quah, J.S.H, Tay, N.C.W, Lee, J.C.L, Lim, J.K.H, Oei, A.A, Tan, J.M, Park, S.Y, Chow, W.W.L, Omar, Y.B, Chew, P.G, Taylor, P, Lee, J, Tsurudome, T, Hirabayashi, M, Tsutsui, H, Yoshida, J, Takahashi, N, Kamiguchi, N, Hashimoto, A, Tachikawa, T, Mikami, Y, Kumata, Y, Wang, M, Chua, E.T, Wee, J, Wong, F.Y, Tuan, J, Master, Z, Wong, S, Welsh, J, Hentz, C, Pankuch, M, DeJongh, F, Xia, Y, Aitkenhead, A.H, Appleby, R, Merchant, M.J, MacKay, R.I, Young, H, Hughes, V, Alsulimane, M, Barajas, C.A, Taylor, J, Casse, G, Omar, A, Burdin, S, Boon, C, Lester, J, Thomas, A.J, Khan, A, Huthart, L, Leaver, K, Snell, J, Warlow, A, Burigo, L.N, Oborn, B, Belosi, F, Fredh, A, van de Water, S, Schneider, T, Patriarca, A, Bergs, J, Hierso, E, Hirayama, R, Martínez-Rovira, I, Seksek, O, Shirato, H, Nakamura, T, Ogino, T, Akimoto, T, Tamamura, H, Nishimoto, N, Proton-Net, G, Shimizu, S, Fabiano, S, Bangert, M, Guckenberger, M, Unkelbach, J, Mcauley, G, Teran, A, Slater, J, Wroe, A, Boon, I, Clorley, J, Owen, K, Oliver, T, Cicchetti, A, Ballarini, F, Rancati, T, Carrara, M, Zaffaroni, N, Bezawy, R. El, Carante, M, Valdagni, R, Faccini, R, Forte, G.I, Dhinsey, S, Greenshaw, T, Parsons, J, Welsch, C, Stock, M, Grevillot, L, Kragl, G, Carlino, A, Martino, G, Hug, E, Arya, H, Chirayath, V.A, Jin, M, Weiss, A.H, Glass, G.A, Chi, Y, Kaplan, L.P, Perez, R.A, Vestergaard, A, Gittings, E, Stamper, J, Beltran, C, Mark, P, Furutani, K, McAuley, G, Gordon, J, Boisseau, P, Dart, A, Nett, W, Kollipara, S, Grossmann, M, Actis, O, Diete, W, Rudolf, D, Klein, H.U, Kramert, R, Meer, D, Venkataraman, C, Waterstradt, T, Hérault, J, Bergerot, J.M, Hsi, W.C, Zhou, R, Zhang, X, Yang, F, Yinxiangzi, S, Sun, J, Li, X, Zhiling, C, Yuehu, P, Mengya, G, Haiyun, K, Qi, L, Zhentang, Z, Lin, Y.H, Tan, H.Q, Tan, L.K.R, Ang, K.W, Xiufang, L, Milkowski, K, Pang, D, Jones, M, Mizota, M, Tsunashima, Y, Himukai, T, Ogata, R, Uno, T, Ouyang, L, Jia, B, Li, D, Paul, K, Pullia, M, Savazzi, S, Lante, V, Foglio, S, Donetti, M, Falbo, L, Casalegno, L, Rousseau, M, Shinomiya, K, Yazawa, T, Iseki, Y, Kanai, Y, Hirata, Y, 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Choy, H, Miyashiro, I, Bush, D, Chuong, M, Kozarek, J, Rubens, M, Larson, G, Vargas, C, Hung, S.P, Hsieh, C.E, Huang, B.S, Tsang, N.M, Smith, N, Viehman, J, Harmsen, W, Elswick, S, Boughey, J, Harless, C, Jimenez, R, Hickey, S, DePauw, N, Ho, A, Taghian, A, MacDonald, S, Meek, A, Hedrick, S, Baliga, S, Gallotto, S, Lewy, J, Patteson, B, Speroni, S, Omsberg, A, Tarbell, N, Musolino, P, Yock, T, Indelicato, D, Rotondo, R, Mailhot, R, Uezono, H, Bradfield, S, Agarwal, V, Gillies, C, Gosling, A, Casares-Magaz, O, Eskildsen, S.F, Lassen, Y, Hasle, H, Tofting-Olesen, K, Alapetite, C, Puget, S, Nauraye, C, Beccaria, K, Bolle, S, Doz, F, Sainte-Rose, C, Bouffet, E, Zerah, M, Wu, J, Qiu, X, Hua, W, Mao, Y, Frakulli, R, Kramer, P.H, Glas, M, Blase, C, Tippelt, S, Konrath, L, Gruber, N, Schallerbauer-Peter, A, Mock, U, Niyazi, M, Niemierko, A, Schapira, E, Kim, V, Oh, K.S, Hwang, W.L, Busse, P.M, Loeffler, J.S, Shih, H.A, Appel, H, Tseng, Y.D, Tsai, H, Sinesi, C, Rossi, C, Badiyan, S, Kotecha, R, Pike, L, Horick, N, Yeap, B, Franck, K, Wang, I, Loeffler, J, McKenna, M, Shih, H, Kountouri, M, Kole, A.J, Murray, F.R, Kliebsch, U, Combescure, C, iannalfi, A, Riva, G, Dougherty, J, Kruse, J, Iott, M, Brown, P, Olivier, K, Brodin, P, Kabarriti, R, Schechter, C, Kalnicki, S, Garg, M, Tomé, W, Lu, J.J, Chen, P.J, Dhanireddy, B, Severo, C, Lee, C.H, Lin, C.R, Rosier, L, Mathis, T, DeLaney, T, Lin, S, O’Meara, E, Powell, T, Hong, T, Hall, D, Liu, A, Ntentas, G, Dedeckova, K, Darby, S, Cutter, D, Zapletalova, S, Chen, Y.L, Miao, R, Lee, H, Hsiao-Ming, L, Choy, E, Cote, G, Eulitz, J, Lutz, B, Enghardt, W, Lühr, A, Mcmahon, S, Prise, K, Sung Hyun, L, Tansho, R, Mizushima, K, Warmenhoven, J.W, Hufnagl, A, Friedrich, T, Deycmar, S, Gruber, S, Dörr, W, Pruschy, M, Waissi, W, Burckel, H, Nicol, A, Noel, G, Yousef, I, Koizumi, M, Santa Cruz, G.A, González, S.J, Longhino, J, Provenzano, L, Oña, P, Rao, M, Cantarelli, M.D.L.Á, Leiras, A, Olivera, M.S, Alessandrini, P, Brollo, F, Boggio, E, Costa, H, Ventimiglia, R, Binia, S, Nievas, S.I, Langle, Y, Eijan, A.M, Colombo, L.L, Kawai, K, Nakamura, H, Natsuko, K, Masaki, H, Nakada, M, Furuse, M, Miyatake, S.I, Koivunoro, H, Kankaanranta, L, González, S, Joensuu, H, Sokol, O, Hild, S, Wiedemann, J, Köthe, A, Perry, D, Batie, M, Mascia, A, Sertorio, M, Luhr, A, Suckert, T, Müller, J, Beyreuther, E, Gotz, M, Haase, R, Schürer, M, Tillner, F, von Neubeck, C, Davis, A, Sishc, B, Saha, J, Ding, L, Story, M, Wagner, S, Kim, S.Y, Geary, S, Woodruff, T, Xu, T, Meng, Q, Gilchrist, S, Perentesis, J.P, Zheng, Y, Wells, S.I, Kong, Y, Liu, Y, Geng, Y, Knoll, M, Schwager, C, Schlegel, J, Schnölzer, M, Ding, L.H, Aroumougame, A, Chen, B, Saha, D, Pompos, A, Carter, R, Nickson, C, Thomson, J, Hill, M, Rodrigues, D, Snider, J, Sharma, A, Zakhary, M, Kara, L, Vujaskovic, Z, Dykstra, M, Best, T, Keane, F, Khandekar, M, Fintelmann, F, Willers, H, Singh, P, Eley, J, Malyapa, R, Mahmood, J, Hårdemark, B, Sandison, G.A, Wootton, L.S, Miyoaka, R.S, Laramore, G.E, Yang, P, van der Weide, H, Maduro, J, Heesters, M, Gawryszuk, A, Davila-Fajardo, R, Langendijk, H, Eckhard, M, Maxwell, A, VanNamen, K, Cashin, M, Jacovic, A, Dunn, M, kim, T, Jung, J, Kim, J, Swerdloff, S, Saunders, A, Thomas, J, Kidani, T, Okada, A, Tomida, K, Pennington, H, Xiaoqiang, L, Weigang, H, An, Q, Di, Y, Craig, S, Inga, G, Peyman, K, Xuanfeng, D, Cunningham, C, de Kock, M, Slabbert, J, Panaino, C.M, Phoenix, B, Regan, P.H, Shearman, R, Collins, S.M, Taylor, M.J, Grayson, M, Kato, K, Choi, H, Jang, J.W, Shin, W.G, Min, C.H, McMahon, S, Padilla Cabal, F, Fragoso, J.A, Resch, A.F, Katsis, A, Girdhani, S, Marshall, A, Jackson, I, Bentzen, S, Parry, R, Gantz, S, Schellhammer, S, Hoffmann, A, Delorme, R, Dos Santos, M, Salmon, R, Öden, J, Bullivant, K, Rucksdashal, R, Ferret, E, Covington, F, Rice, S, Decesaris, C, Siddiqui, O, Kowalski, E, Samanta, S, and Rothwell, B
- Subjects
Biology: Biological Differences between Carbon, Proton and Photons Poster Discussion SessionsPTC58-0642 ,Physics: Absolute and Relative DosimetryPTC58-0180 ,Biology: Biology and Clinical InterfacePTC58-0685 ,Physics: Commissioning New FacilitiesPTC58-0385 ,Physics: 4D Treatment and DeliveryPTC58-0546 ,Clinics: EyePTC58-0714 ,Biology: Biological Differences between Carbon, Proton and Photons Poster Discussion SessionsPTC58-0528 ,Physics: Quality Assurance and VerificationPTC58-0507 ,Oral AbstractsPhysics: Dose Calculation and OptimisationPTC58-0661 ,Biology: Translational and Biomarkers Poster Discussion SessionsPTC58-0221 ,Oral AbstractsPhysics: Dose Calculation and OptimisationPTC58-0531 ,Oral AbstractsPhysics: Dose Calculation and OptimisationPTC58-0653 ,Biology: Drug and Immunotherapy CombinationsPTC58-0163 ,Clinics: Sarcoma - LymphomaPTC58-0055 ,Biology: Drug and Immunotherapy CombinationsPTC58-0166 ,Clinics: CNS / Skull BasePTC58-0198 ,Physics: Treatment PlanningPTC58-0421 ,Clinics: PediatricsPTC58-0560 ,General: New HorizonsPTC58-0709 ,Physics: Treatment PlanningPTC58-0664 ,Clinics: Eye / Breast / Pelvis Poster Discussion SessionsPTC58-0286 ,Physics: Treatment PlanningPTC58-0666 ,Biology: Translational and Biomarkers Poster Discussion SessionsPTC58-0346 ,Physics: Treatment PlanningPTC58-0547 ,Physics: Treatment PlanningPTC58-0308 ,Physics: Treatment PlanningPTC58-0549 ,Physics: Beam Delivery and Nozzle Design Poster Discussion SessionsPTC58-0111 ,Physics: Absolute and Relative DosimetryPTC58-0050 ,Biology: Enhanced Biology in Treatment Planning Poster Discussion SessionsPTC58-0587 ,Biology: Biology and Clinical InterfacePTC58-0454 ,Physics: Absolute and Relative DosimetryPTC58-0052 ,Physics: Commissioning New FacilitiesPTC58-0395 ,Physics: 4D Treatment and DeliveryPTC58-0534 ,Physics: Dose Calculation and OptimisationPTC58-0072 ,Physics: 4D Treatment and DeliveryPTC58-0533 ,Physics: 4D Treatment and DeliveryPTC58-0538 ,Physics: Commissioning New Facilities Poster Discussion SessionsPTC58-0113 ,Physics: Quality Assurance and VerificationPTC58-0633 ,Physics: Treatment PlanningPTC58-0431 ,Physics: Beam Delivery and Nozzle DesignPTC58-0230 ,Biology: Mathematical Modelling SimulationPTC58-0179 ,Clinics: Head and Neck / EyePTC58-0365 ,Physics: Treatment PlanningPTC58-0319 ,Biology: Translational and Biomarkers Poster Discussion SessionsPTC58-0697 ,Biology: Biology and Clinical InterfacePTC58-0663 ,Physics: Commissioning New FacilitiesPTC58-0240 ,Physics: Adaptive TherapyPTC58-0177 ,Physics: Commissioning New FacilitiesPTC58-0363 ,Physics: Commissioning New FacilitiesPTC58-0487 ,Physics: 4D Treatment and DeliveryPTC58-0209 ,Physics: 4D Treatment and DeliveryPTC58-0206 ,Clinics: CNS / Skull BasePTC58-0294 ,Physics: Commissioning New FacilitiesPTC58-0127 ,Biology: Mathematical Modelling SimulationPTC58-0068 ,Physics: Treatment Planning Poster Discussion SessionsPTC58-0062 ,Physics: 4D Treatment and DeliveryPTC58-0692 ,Physics: Quality Assurance and VerificationPTC58-0723 ,Physics: Commissioning New Facilities Poster Discussion SessionsPTC58-0494 ,Physics: Treatment PlanningPTC58-0643 ,Physics: Treatment PlanningPTC58-0521 ,Physics: Treatment PlanningPTC58-0402 ,Physics: Treatment PlanningPTC58-0405 ,Clinics: Head and Neck / EyePTC58-0273 ,Clinics: GIPTC58-0397 ,Physics: Treatment PlanningPTC58-0648 ,Biology: Enhanced Biology in Treatment Planning Poster Discussion SessionsPTC58-0489 ,Physics: Quality Assurance and VerificationPTC58-0617 ,Physics: Quality Assurance and VerificationPTC58-0616 ,Physics: Dose Calculation and Optimisation Poster Discussion SessionsPTC58-0668 ,Clinics: CNS / Skull BasePTC58-0188 ,Oral AbstractsPhysics: Dose Calculation and OptimisationPTC58-0625 ,Physics: Treatment PlanningPTC58-0654 ,Physics: Treatment PlanningPTC58-0655 ,Biology: Drug and Immunotherapy Combinations Poster Discussion SessionsPTC58-0133 ,Clinics: PediatricsPTC58-0313 ,Physics: Treatment PlanningPTC58-0659 ,Poster AbstractsClinics: CNSPTC58-0290 ,Physics: Commissioning New FacilitiesPTC58-0064 ,Physics: Adaptive TherapyPTC58-0396 ,Physics: Dose Calculation and OptimisationPTC58-0281 ,Physics: Quality Assurance and VerificationPTC58-0427 ,Physics: Quality Assurance and VerificationPTC58-0669 ,General: New Horizons SessionPTC58-0191 ,Physics: Dose Calculation and Optimisation Poster Discussion SessionsPTC58-0217 ,Physics: Quality Assurance and VerificationPTC58-0303 ,Physics: Quality Assurance and VerificationPTC58-0665 ,Clinics: Sarcoma - LymphomaPTC58-0495 ,Physics: Dose Calculation and OptimisationPTC58-0398 ,Physics: Quality Assurance and VerificationPTC58-0667 ,Physics: Quality Assurance and VerificationPTC58-0425 ,Physics: Quality Assurance and VerificationPTC58-0541 ,Physics: Treatment PlanningPTC58-0584 ,Physics: Quality Assurance and VerificationPTC58-0540 ,Biology: Drug and Immunotherapy Combinations Poster Discussion SessionsPTC58-0163 ,Physics: Treatment PlanningPTC58-0224 ,Physics: Treatment PlanningPTC58-0229 ,Clinics: PediatricsPTC58-0249 ,Physics: Beam Delivery and Nozzle Design Poster Discussion SessionsPTC58-0555 ,Clinics: PediatricPTC58-0463 ,Physics: Commissioning New Facilities Poster Discussion SessionsPTC58-0556 ,Physics: Absolute and Relative DosimetryPTC58-0498 ,Physics: Commissioning New FacilitiesPTC58-0078 ,Physics: Dose Calculation and OptimisationPTC58-0270 ,Physics: Dose Calculation and OptimisationPTC58-0032 ,Physics: Dose Calculation and OptimisationPTC58-0274 ,Physics: 4D Treatment and DeliveryPTC58-0614 ,Physics: Dose Calculation and OptimisationPTC58-0026 ,Clinics: Head and Neck / EyePTC58-0280 ,Clinics: Eye / Breast / Pelvis Poster Discussion SessionsPTC58-0091 ,Physics: Treatment PlanningPTC58-0593 ,Biology: Drug and Immunotherapy CombinationsPTC58-0012 ,Physics: Dose Calculation and OptimisationPTC58-0025 ,Physics: Dose Calculation and OptimisationPTC58-0146 ,Clinics: Sarcoma - LymphomaPTC58-0261 ,Physics: Treatment PlanningPTC58-0110 ,Clinics: Lung / Sarcoma / LymphomaPTC58-0733 ,Physics: Quality Assurance and VerificationPTC58-0554 ,Physics: Treatment PlanningPTC58-0597 ,Physics: Dose Calculation and Optimisation Poster Discussion SessionsPTC58-0330 ,Physics: Treatment PlanningPTC58-0115 ,Physics: Treatment PlanningPTC58-0598 ,Physics: Absolute and Relative DosimetryPTC58-0040 ,Physics: Absolute and Relative DosimetryPTC58-0282 ,Biology: Enhanced Biology in Treatment Planning Poster Discussion SessionsPTC58-0399 ,Physics: Absolute and Relative DosimetryPTC58-0283 ,Physics: Commissioning New Facilities Poster Discussion SessionsPTC58-0569 ,Clinics: GUPTC58-0647 ,Biology: Biological Differences between Carbon, Proton and Photons Poster Discussion SessionsPTC58-0506 ,Physics: Commissioning New FacilitiesPTC58-0047 ,Physics: Dose Calculation and OptimisationPTC58-0067 ,Clinics: GUPTC58-0409 ,Physics: Dose Calculation and OptimisationPTC58-0065 ,Biology: BNCT Poster Discussion SessionsPTC58-0586 ,Physics: Absolute and Relative Dosimetry PTC58-0393 ,Physics: Image GuidancePTC58-0712 ,Physics: Quality Assurance and VerificationPTC58-0645 ,Physics: Treatment PlanningPTC58-0683 ,Biology: BNCT Poster Discussion SessionsPTC58-0107 ,Physics: Treatment Planning Poster Discussion SessionsPTC58-0266 ,Physics: Monitoring and Modelling MotionPTC58-0530 ,Biology: BNCT Poster Discussion SessionsPTC58-0341 ,Physics: Commissioning New FacilitiesPTC58-0172 ,Physics: Commissioning New Facilities Poster Discussion SessionsPTC58-0456 ,Physics: Dose Calculation and OptimisationPTC58-0170 ,Physics: Commissioning New Facilities Poster Discussion SessionsPTC58-0458 ,Physics: Absolute and Relative DosimetryPTC58-0034 ,Physics: Quality Assurance and VerificationPTC58-0417 ,Physics: Quality Assurance and VerificationPTC58-0413 ,Physics: Treatment Planning Poster Discussion SessionsPTC58-0492 ,Physics: Dose Calculation and OptimisationPTC58-0168 ,Clinics: GI / Sarcoma Poster Discussion SessionsPTC58-0724 ,Physics: Treatment PlanningPTC58-0694 ,Physics: Adaptive TherapyPTC58-0005 ,Physics: Treatment PlanningPTC58-0696 ,Physics: Treatment PlanningPTC58-0453 ,Physics: Adaptive TherapyPTC58-0366 ,Clinics: BreastPTC58-0197 ,Physics: Beam Delivery and Nozzle DesignPTC58-0652 ,Physics: Treatment Planning Poster Discussion SessionsPTC58-0017 ,Physics: Treatment PlanningPTC58-0338 ,Clinics: Head and Neck / EyePTC58-0539 ,General: New Horizons SessionPTC58-0390 ,Physics: Image Guidance Poster Discussion SessionsPTC58-0651 ,General: New HorizonsPTC58-0660 ,Physics: Dose Calculation and OptimisationPTC58-0360 ,Physics: Image GuidancePTC58-0297 ,Physics: 4D Treatment and DeliveryPTC58-0147 ,Scientific: RTTPTC58-0388 ,Physics: Dose Calculation and OptimisationPTC58-0484 ,General: New HorizonsPTC58-0301 ,Physics: Dose Calculation and OptimisationPTC58-0485 ,General: New HorizonsPTC58-0304 ,Physics: 4D Treatment and Delivery Poster Discussion SessionsPTC58-0532 ,Clinics: GIPTC58-0575 ,General: New HorizonsPTC58-0306 ,Physics: Quality Assurance and VerificationPTC58-0589 ,Clinics: CNS / Pediatrics / Lung Poster Discussion SessionsPTC58-0344 ,Physics: Quality Assurance and VerificationPTC58-0225 ,Physics: Treatment PlanningPTC58-0381 ,Physics: Quality Assurance and VerificationPTC58-0467 ,Clinics: CNS / Pediatrics / Lung Poster Discussion SessionsPTC58-0585 ,Physics: Commissioning New FacilitiesPTC58-0416 ,Physics: Quality Assurance and VerificationPTC58-0228 ,Physics: Quality Assurance and VerificationPTC58-0348 ,Physics: Dose Calculation and OptimisationPTC58-0234 ,Physics: Quality Assurance and VerificationPTC58-0101 ,Physics: Treatment PlanningPTC58-0386 ,Physics: Dose Calculation and OptimisationPTC58-0118 ,Physics: Treatment PlanningPTC58-0265 ,Physics: Dose Calculation and OptimisationPTC58-0119 ,Clinics: GIPTC58-0218 ,Physics: Treatment PlanningPTC58-0267 ,Physics: Treatment PlanningPTC58-0387 ,Clinics: BreastPTC58-0142 ,Physics: Treatment PlanningPTC58-0269 ,Physics: Beam Delivery and Nozzle DesignPTC58-0620 ,Clinics: PediatricsPTC58-0048 ,Physics: Quality Assurance and VerificationPTC58-0220 ,Physics: Quality Assurance and VerificationPTC58-0461 ,Physics: Treatment PlanningPTC58-0029 ,Physics: Absolute and Relative DosimetryPTC58-0571 ,Physics: Image GuidancePTC58-0046 ,Clinics: GUPTC58-0557 ,Physics: Absolute and Relative DosimetryPTC58-0211 ,Oral AbstractsPhysics: Dose Calculation and OptimisationPTC58-0131 ,Oral AbstractsPhysics: Dose Calculation and OptimisationPTC58-0373 ,General: New HorizonsPTC58-0411 ,Physics: Dose Calculation and OptimisationPTC58-0595 ,Clinics: CNS / Skull BasePTC58-0361 ,General: New HorizonsPTC58-0414 ,General: New HorizonsPTC58-0537 ,Clinics: GI / Sarcoma Poster Discussion SessionsPTC58-0628 ,Physics: Treatment PlanningPTC58-0271 ,Physics: Commissioning New FacilitiesPTC58-0307 ,Physics: Quality Assurance and VerificationPTC58-0359 ,Physics: Quality Assurance and VerificationPTC58-0354 ,General: New HorizonsPTC58-0419 ,Physics: Treatment PlanningPTC58-0035 ,Biology: BNCTPTC58-0474 ,Clinics: GIPTC58-0460 ,Biology: BNCTPTC58-0596 ,Clinics: GIPTC58-0222 ,Physics: Image GuidancePTC58-0193 ,Clinics: PediatricPTC58-0312 ,Clinics: GUPTC58-0441 ,Clinics: LungPTC58-0701 ,Clinics: EyePTC58-0536 ,Clinics: GUPTC58-0205 ,Physics: Dose Calculation and OptimisationPTC58-0140 ,Clinics: GUPTC58-0208 ,Physics: Dose Calculation and OptimisationPTC58-0020 ,Physics: Image GuidancePTC58-0195 ,Poster AbstractsClinics: CNSPTC58-0717 ,Physics: Quality Assurance and VerificationPTC58-0325 ,Physics: Dose Calculation and OptimisationPTC58-0015 ,Physics: Commissioning New FacilitiesPTC58-0634 ,General: New HorizonsPTC58-0646 ,Physics: Quality Assurance and VerificationPTC58-0566 ,Physics: Dose Calculation and OptimisationPTC58-0134 ,Physics: Dose Calculation and OptimisationPTC58-0376 ,Biology: Mathematical Modelling SimulationPTC58-0462 ,Biology: BNCTPTC58-0567 ,General: New HorizonsPTC58-0527 ,Physics: Treatment PlanningPTC58-0482 ,Clinics: GI, GU, BreastPTC58-0693 ,Physics: Commissioning New FacilitiesPTC58-0518 ,Physics: Quality Assurance and VerificationPTC58-0686 ,Physics: Quality Assurance and VerificationPTC58-0202 ,Physics: Quality Assurance and VerificationPTC58-0322 ,Physics: Quality Assurance and VerificationPTC58-0564 ,Physics: Quality Assurance and VerificationPTC58-0680 ,Physics: Treatment PlanningPTC58-0247 ,Physics: Quality Assurance and VerificationPTC58-0682 ,Physics: Quality Assurance and VerificationPTC58-0440 ,Biology: Translational and BiomarkersPTC58-0514 ,Physics: Beam Delivery and Nozzle Design Poster Discussion SessionsPTC58-0178 ,Clinics: EyePTC58-0520 ,Physics: Absolute and Relative DosimetryPTC58-0231 ,Clinics: Head and Neck / EyePTC58-0424 ,Physics: Absolute and Relative DosimetryPTC58-0471 ,Physics: Absolute and Relative DosimetryPTC58-0356 ,Physics: Dose Calculation and OptimisationPTC58-0491 ,Physics: Dose Calculation and OptimisationPTC58-0250 ,Physics: Commissioning New FacilitiesPTC58-0650 ,Biology: Biology and Clinical InterfacePTC58-0719 ,Physics: Absolute and Relative DosimetryPTC58-0232 ,Physics: Absolute and Relative DosimetryPTC58-0353 ,General: New HorizonsPTC58-0511 ,Physics: Quality Assurance and VerificationPTC58-0219 ,Physics: Absolute and Relative DosimetryPTC58-0238 ,General: New HorizonsPTC58-0512 ,Physics: 4D Treatment and Delivery Poster Discussion SessionsPTC58-0401 ,Clinics: PediatricPTC58-0688 ,Physics: Quality Assurance and VerificationPTC58-0457 ,Physics: Quality Assurance and VerificationPTC58-0214 ,Physics: Quality Assurance and VerificationPTC58-0459 ,General: New HorizonsPTC58-0516 ,Physics: Treatment PlanningPTC58-0372 ,Physics: Treatment PlanningPTC58-0011 ,Physics: Treatment PlanningPTC58-0254 ,Physics: Quality Assurance and VerificationPTC58-0332 ,Clinics: CNS / Skull BasePTC58-0468 ,Biology: Mathematical Modelling SimulationPTC58-0357 ,Clinics: GI / Sarcoma Poster Discussion SessionsPTC58-0649 ,Physics: Dose Calculation and OptimisationPTC58-0006 ,Physics: Quality Assurance and VerificationPTC58-0212 ,Physics: Image Guidance Poster Discussion SessionsPTC58-0565 ,Physics: Treatment PlanningPTC58-0018 ,Physics: Treatment PlanningPTC58-0019 ,Clinics: BreastPTC58-0576 ,Clinics: Head and Neck / EyePTC58-0335 ,Clinics: Head and Neck / EyePTC58-0577 ,General: New HorizonsPTC58-0621 ,Physics: Absolute and Relative DosimetryPTC58-0426 ,Physics: Commissioning New Facilities Poster Discussion SessionsPTC58-0268 ,Physics: Absolute and Relative DosimetryPTC58-0423 ,Physics: Treatment PlanningPTC58-0184 ,Physics: Quality Assurance and VerificationPTC58-0149 ,Clinics: GIPTC58-0378 ,Clinics: GIPTC58-0257 ,Clinics: CNS / Pediatrics / Lung Poster Discussion SessionsPTC58-0662 ,General: New HorizonsPTC58-0627 ,Physics: Treatment PlanningPTC58-0186 ,Physics: Treatment PlanningPTC58-0185 ,Physics: Quality Assurance and VerificationPTC58-0144 ,Biology: BNCT Poster Discussion SessionsPTC58-0602 ,Physics: Treatment PlanningPTC58-0189 ,Physics: Dose Calculation and OptimisationPTC58-0315 ,Clinics: Head and neckPTC58-0300 ,General: New Horizons SessionPTC58-0347 ,Physics: Image GuidancePTC58-0082 ,Clinics: BreastPTC58-0443 ,Physics: 4D Treatment and Delivery Poster Discussion SessionsPTC58-0629 ,Physics: Adaptive Therapy Poster Discussion SessionsPTC58-0007 ,Physics: Commissioning New FacilitiesPTC58-0472 ,Clinics: GI, GU, BreastPTC58-0515 ,Physics: Dose Calculation and Optimisation Poster Discussion SessionsPTC58-0606 ,Oral AbstractsPhysics: Dose Calculation and OptimisationPTC58-0450 ,Physics: Absolute and Relative DosimetryPTC58-0657 ,Physics: Dose Calculation and OptimisationPTC58-0551 ,Physics: Treatment PlanningPTC58-0192 ,Clinics: CNS / Pediatrics / Lung Poster Discussion SessionsPTC58-0675 ,Physics: Treatment PlanningPTC58-0194 ,Physics: Dose Calculation and OptimisationPTC58-0544 ,Physics: Treatment PlanningPTC58-0199 ,Physics: Quality Assurance and VerificationPTC58-0037 ,Oral AbstractsPhysics: Dose Calculation and OptimisationPTC58-0207 ,Clinics: CNS / Pediatrics / Lung Poster Discussion SessionsPTC58-0434 ,Physics: Quality Assurance and VerificationPTC58-0036 ,Physics: Quality Assurance and VerificationPTC58-0278 ,Physics: Quality Assurance and VerificationPTC58-0394 ,Physics: Quality Assurance and VerificationPTC58-0151 ,Physics: Quality Assurance and VerificationPTC58-0154 ,Physics: Dose Calculation and OptimisationPTC58-0428 ,Clinics: BreastPTC58-0116 ,Biology: Enhanced Biology in Treatment Planning Poster Discussion SessionsPTC58-0435 ,Physics: Commissioning New FacilitiesPTC58-0681 ,Physics: Absolute and Relative DosimetryPTC58-0323 ,Physics: Dose Calculation and OptimisationPTC58-0583 ,Physics: Absolute and Relative DosimetryPTC58-0448 ,Clinics: CNS / Skull BasePTC58-0251 ,General: New HorizonsPTC58-0721 ,Physics: Absolute and Relative DosimetryPTC58-0203 ,Physics: Dose Calculation and OptimisationPTC58-0455 ,Physics: 4D Treatment and DeliveryPTC58-0130 ,Physics: Commissioning New FacilitiesPTC58-0679 ,Physics: Absolute and Relative DosimetryPTC58-0329 ,General: New HorizonsPTC58-0604 ,Physics: Absolute and Relative DosimetryPTC58-0449 ,Clinics: CNS / Skull BasePTC58-0132 ,General: New HorizonsPTC58-0607 ,Physics: Quality Assurance and VerificationPTC58-0122 ,Physics: Quality Assurance and VerificationPTC58-0243 ,Physics: Treatment PlanningPTC58-0165 ,Oral AbstractsPhysics: Dose Calculation and OptimisationPTC58-0437 ,Physics: 4D Treatment and DeliveryPTC58-0377 ,Physics: Quality Assurance and VerificationPTC58-0125 ,Physics: Quality Assurance and VerificationPTC58-0245 ,Physics: Dose Calculation and OptimisationPTC58-0337 ,Clinics: GI / Sarcoma Poster Discussion SessionsPTC58-0334 ,Physics: Quality Assurance and VerificationPTC58-0121 ,General: New Horizons SessionPTC58-0563 ,General: New Horizons SessionPTC58-0321 ,Clinics: Head and Neck / EyePTC58-0477 ,Physics: Quality Assurance and VerificationPTC58-0480 ,Clinics: GUPTC58-0010 ,Clinics: EyePTC58-0684 ,Clinics: GUPTC58-0496 ,Clinics: Head and neckPTC58-0676 ,Clinics: GUPTC58-0137 ,Physics: Beam Delivery and Nozzle Design Poster Discussion SessionsPTC58-0256 ,Physics: 4D Treatment and DeliveryPTC58-0117 ,Physics: Absolute and Relative DosimetryPTC58-0552 ,Physics: Absolute and Relative DosimetryPTC58-0310 ,Physics: Absolute and Relative DosimetryPTC58-0672 ,Physics: Absolute and Relative DosimetryPTC58-0436 ,Physics: Dose Calculation and OptimisationPTC58-0452 ,Physics: Dose Calculation and OptimisationPTC58-0331 ,Physics: Commissioning New FacilitiesPTC58-0213 ,Biology: Mathematical Modelling SimulationPTC58-0272 ,Clinics: EyePTC58-0326 ,Physics: Commissioning New FacilitiesPTC58-0568 ,Physics: Dose Calculation and OptimisationPTC58-0444 ,Physics: Quality Assurance and VerificationPTC58-0379 ,Physics: Treatment Planning Poster Discussion SessionsPTC58-0095 ,Physics: Treatment PlanningPTC58-0053 ,Physics: Absolute and Relative DosimetryPTC58-0438 ,Physics: Absolute and Relative DosimetryPTC58-0317 ,Physics: Quality Assurance and VerificationPTC58-0497 ,Physics: Quality Assurance and VerificationPTC58-0375 ,Physics: Treatment PlanningPTC58-0056 ,Physics: 4D Treatment and DeliveryPTC58-0124 ,Clinics: GIPTC58-0009 ,Physics: Quality Assurance and VerificationPTC58-0014 ,Physics: Quality Assurance and VerificationPTC58-0374 ,Clinics: LungPTC58-0727 ,General: New Horizons SessionPTC58-0578 ,Clinics: GI / Sarcoma Poster Discussion SessionsPTC58-0470 ,Clinics: LungPTC58-0204 ,Clinics: Head and neckPTC58-0227 ,Clinics: LungPTC58-0446 ,Physics: Quality Assurance and VerificationPTC58-0190 ,Clinics: Eye / Breast / Pelvis Poster Discussion SessionsPTC58-0609 ,Clinics: LungPTC58-0689 ,General: New HorizonsPTC58-0021 ,General: New HorizonsPTC58-0262 ,Biology: BNCT Poster Discussion SessionsPTC58-0081 ,Clinics: GIPTC58-0726 ,General: New HorizonsPTC58-0145 ,Physics: Image GuidancePTC58-0573 ,General: New HorizonsPTC58-0027 ,General: New HorizonsPTC58-0028 ,Biology: Mathematical Modelling and SimulationPTC58-0148 ,Physics: Dose Calculation and OptimisationPTC58-0635 ,Physics: Image GuidancePTC58-0215 ,Physics: Image GuidancePTC58-0336 ,Poster AbstractsClinics: CNSPTC58-0535 ,Physics: Quality Assurance and VerificationPTC58-0187 ,Biology: BNCT Poster Discussion SessionsPTC58-0084 ,General: New Investigator SessionPTC58-0339 ,General: New Horizons SessionPTC58-0420 ,Physics: Treatment Planning Poster Discussion SessionsPTC58-0523 ,Biology: BNCT Poster Discussion SessionsPTC58-0088 ,Clinics: GI / Sarcoma Poster Discussion SessionsPTC58-0112 ,Physics: Quality Assurance and VerificationPTC58-0182 ,Clinics: Eye / Breast / Pelvis Poster Discussion SessionsPTC58-0615 ,Physics: Quality Assurance and VerificationPTC58-0080 ,Biology: BNCTPTC58-0085 ,Physics: Adaptive Therapy Poster Discussion SessionsPTC58-0722 ,General: New HorizonsPTC58-0253 ,General: New HorizonsPTC58-0255 ,Clinics: PediatricPTC58-0703 ,General: New HorizonsPTC58-0499 ,Physics: Image Guidance Poster Discussion SessionsPTC58-0380 ,General: New HorizonsPTC58-0259 ,Clinics: GI, GU, BreastPTC58-0288 ,Clinics: GI, GU, BreastPTC58-0045 ,Physics: Absolute and Relative DosimetryPTC58-0619 ,Clinics: PediatricPTC58-0707 ,Physics: Quality Assurance and VerificationPTC58-0196 ,Physics: Quality Assurance and VerificationPTC58-0074 ,Physics: Quality Assurance and VerificationPTC58-0077 ,Biology: BNCT Poster Discussion SessionsPTC58-0073 ,Biology: BNCTPTC58-0075 ,Biology: Biological Differences between Carbon, Proton and Photons Poster Discussion SessionsPTC58-0093 ,Clinics: GUPTC58-0161 ,Clinics: GI / Sarcoma Poster Discussion SessionsPTC58-0371 ,Physics: Monitoring and Modelling MotionPTC58-0181 ,General: New HorizonsPTC58-0120 ,General: New HorizonsPTC58-0362 ,General: New HorizonsPTC58-0364 ,Physics: Image GuidancePTC58-0473 ,Scientific: RTTPTC58-0641 ,Clinics: CNS / Pediatrics / Lung Poster Discussion SessionsPTC58-0296 ,General: New HorizonsPTC58-0004 ,General: New HorizonsPTC58-0128 ,Clinics: BreastPTC58-0316 ,Physics: 4D Treatment and Delivery Poster Discussion SessionsPTC58-0236 ,General: New HorizonsPTC58-0008 ,General: New Investigator SessionPTC58-0673 ,Physics: Quality Assurance and VerificationPTC58-0167 ,Physics: Quality Assurance and VerificationPTC58-0289 ,Physics: Quality Assurance and VerificationPTC58-0284 ,General: New Horizons SessionPTC58-0522 ,Physics: Quality Assurance and VerificationPTC58-0164 ,Physics: Quality Assurance and VerificationPTC58-0285 ,Clinics: Eye / Breast / Pelvis Poster Discussion SessionsPTC58-0623 ,Clinics: Eye / Breast / Pelvis Poster Discussion SessionsPTC58-0502 ,Clinics: GUPTC58-0293 ,Biology: Translational and BiomarkersPTC58-0599 ,Biology: BNCTPTC58-0063 ,Clinics: LungPTC58-0656 ,General: New HorizonsPTC58-0592 ,Biology: BNCT Poster Discussion SessionsPTC58-0092 ,Poster AbstractsClinics: CNSPTC58-0302 ,Physics: Image GuidancePTC58-0464 ,General: New HorizonsPTC58-0352 ,Physics: Image GuidancePTC58-0465 ,General: New HorizonsPTC58-0476 ,Physics: Image GuidancePTC58-0100 ,General: New HorizonsPTC58-0235 ,Biology: Mathematical Modelling and SimulationPTC58-0349 ,Physics: Treatment PlanningPTC58-0094 ,Physics: 4D Treatment and Delivery Poster Discussion SessionsPTC58-0367 ,Physics: Dose Calculation and OptimisationPTC58-0400 ,Biology: Translational and BiomarkersPTC58-0244 ,Physics: Dose Calculation and OptimisationPTC58-0640 ,Biology: Mathematical Modelling and SimulationPTC58-0355 ,General: New Investigator SessionPTC58-0320 ,Physics: Quality Assurance and VerificationPTC58-0057 ,Physics: Quality Assurance and VerificationPTC58-0174 ,Physics: Quality Assurance and VerificationPTC58-0295 ,Physics: Dose Calculation and OptimisationPTC58-0529 ,Clinics: GI / Sarcoma Poster Discussion SessionsPTC58-0123 ,Physics: Quality Assurance and VerificationPTC58-0171 ,Biology: Biological Differences between Carbon, Proton and Photons Poster Discussion SessionsPTC58-0049 ,Clinics: BreastPTC58-0731 ,General: New HorizonsPTC58-0223 ,General: New HorizonsPTC58-0102 ,General: New HorizonsPTC58-0466 ,Scientific: RTTPTC58-0503 ,Clinics: CNS / Pediatrics / Lung Poster Discussion SessionsPTC58-0389 ,General: New HorizonsPTC58-0108 ,General: New HorizonsPTC58-0109 ,Physics: Commissioning New FacilitiesPTC58-0736 ,Biology: Mathematical Modelling and SimulationPTC58-0343 ,Biology: Mathematical Modelling and SimulationPTC58-0342 ,Clinics: GI, GU, BreastPTC58-0237 ,Physics: Dose Calculation and OptimisationPTC58-0711 ,Biology: Mathematical Modelling and SimulationPTC58-0581 ,Clinics: GI, GU, BreastPTC58-0114 ,Clinics: Base of SkullPTC58-0730 ,Clinics: Head and neckPTC58-0383 ,Clinics: CNS / Skull BasePTC58-0559 ,Clinics: Base of SkullPTC58-0613 ,General: New HorizonsPTC58-0691 ,Biology: Biological Differences between Carbon, Proton and Photons Poster Discussion SessionsPTC58-0054 ,General: New HorizonsPTC58-0210 ,Clinics: BreastPTC58-0729 ,General: New HorizonsPTC58-0574 ,Clinics: GI, GU, BreastPTC58-0239 ,Scientific: RTTPTC58-0637 ,General: New HorizonsPTC58-0579 ,Clinics: Lung / Sarcoma / LymphomaPTC58-0176 ,General: New HorizonsPTC58-0699 ,Clinics: CNS / Pediatrics / Lung Poster Discussion SessionsPTC58-0156 ,Biology: Mathematical Modelling and SimulationPTC58-0333 ,Biology: Translational and BiomarkersPTC58-0345 ,Physics: Image GuidancePTC58-0369 ,Physics: Commissioning New FacilitiesPTC58-0509 ,Biology: Mathematical Modelling SimulationPTC58-0658 ,Biology: Biological Differences between Carbon, Proton and Photons Poster Discussion SessionsPTC58-0051 ,General: New Investigator SessionPTC58-0548 ,Clinics: GI, GU, BreastPTC58-0241 ,Clinics: Eye / Breast / Pelvis Poster Discussion SessionsPTC58-0412 ,Clinics: GI / Sarcoma Poster Discussion SessionsPTC58-0024 ,Clinics: LungPTC58-0226 ,Biology: Biological Differences between Carbon, Proton and Photons Poster Discussion SessionsPTC58-0069 ,General: New HorizonsPTC58-0562 ,General: New HorizonsPTC58-0561 ,General: New HorizonsPTC58-0201 ,Biology: Mathematical Modelling and SimulationPTC58-0439 ,General: New HorizonsPTC58-0445 ,General: New HorizonsPTC58-0324 ,Physics: Image GuidancePTC58-0031 ,Biology: Mathematical Modelling and SimulationPTC58-0558 ,Physics: Image GuidancePTC58-0392 ,Biology: Mathematical Modelling and SimulationPTC58-0678 ,Physics: Beam Delivery and Nozzle DesignPTC58-0090 ,General: New Investigator SessionPTC58-0630 ,Biology: Biological Differences between Carbon / Proton and Photons Carbons / Proton and PhotonPTC58-0524 ,Physics: Commissioning New FacilitiesPTC58-0713 ,Clinics: GI, GU, BreastPTC58-0139 ,Clinics: CNS / Pediatrics / Lung Poster Discussion SessionsPTC58-0248 ,Clinics: CNS / Pediatrics / Lung Poster Discussion SessionsPTC58-0368 ,Biology: Enhanced Biology in Treatment PlanningPTC58-0519 ,General: New Horizons SessionPTC58-0720 ,Physics: Quality Assurance and VerificationPTC58-0083 ,General: New HorizonsPTC58-0311 ,General: New HorizonsPTC58-0674 ,General: New HorizonsPTC58-0553 ,Physics: Image GuidancePTC58-0023 ,Scientific: RTTPTC58-0612 ,General: New HorizonsPTC58-0677 ,Biology: Mathematical Modelling and SimulationPTC58-0545 ,Physics: Dose Calculation and OptimisationPTC58-0601 ,Physics: Dose Calculation and OptimisationPTC58-0725 ,Physics: Quality Assurance and VerificationPTC58-0098 ,Physics: Dose Calculation and OptimisationPTC58-0605 ,Biology: Biological Differences between Carbon / Proton and Photons Carbons / Proton and PhotonPTC58-0517 ,Biology: Translational and Biomarkers Poster Discussion SessionsPTC58-0618 ,Physics: Monitoring and Modelling MotionPTC58-0481 ,Clinics: GI / Sarcoma Poster Discussion SessionsPTC58-0071 ,Physics: Adaptive TherapyPTC58-0351 ,Physics: 4D Treatment and DeliveryPTC58-0702 ,Physics: Image GuidancePTC58-0734 ,Physics: Image GuidancePTC58-0611 ,Physics: Treatment Planning Poster Discussion SessionsPTC58-0486 ,Physics: Absolute and Relative Dosimetry Poster Discussion SessionsPTC58-0442 ,Biology: Drug and Immunotherapy CombinationsPTC58-0327 ,Clinics: Head and Neck / EyePTC58-0096 ,Clinics: LungPTC58-0159 ,Physics: Treatment PlanningPTC58-0708 ,General: New HorizonsPTC58-0097 ,Physics: Treatment Planning Poster Discussion SessionsPTC58-0350 ,Biology: Biological Differences between Carbon / Proton and Photons Carbons / Proton and PhotonPTC58-0016 ,Physics: Adaptive TherapyPTC58-0104 ,Physics: Absolute and Relative Dosimetry Poster Discussion SessionsPTC58-0433 ,Physics: Image GuidancePTC58-0608 ,Biology: Translational and Biomarkers Poster Discussion SessionsPTC58-0610 ,Clinics: Head and neckPTC58-0058 ,Physics: Treatment PlanningPTC58-0715 ,Clinics: Head and neckPTC58-0298 ,Clinics: EyePTC58-0099 ,General: New HorizonsPTC58-0086 ,General: New HorizonsPTC58-0089 ,Clinics: Lung / Sarcoma / LymphomaPTC58-0200 ,Poster AbstractsClinics: CNSPTC58-0157 ,Clinics: LungPTC58-0141 ,Clinics: LungPTC58-0260 ,Clinics: LungPTC58-0264 ,Physics: Image GuidancePTC58-0513 ,Physics: Image GuidancePTC58-0631 ,Clinics: Eye / Breast / Pelvis Poster Discussion SessionsPTC58-0469 ,Biology: BNCT Poster Discussion SessionsPTC58-0384 ,Physics: Image GuidancePTC58-0639 ,Clinics: PediatricsPTC58-0700 ,Clinics: LungPTC58-0136 ,Clinics: BreastPTC58-0706 ,General: New HorizonsPTC58-0079 ,Biology: Drug and Immunotherapy Combinations Poster Discussion SessionsPTC58-0406 ,Clinics: Base of SkullPTC58-0382 ,Physics: Image GuidancePTC58-0624 ,Physics: Beam Delivery and Nozzle DesignPTC58-0173 ,Biology: Drug and Immunotherapy CombinationsPTC58-0358 ,Poster AbstractsClinics: CNSPTC58-0690 ,General: New HorizonsPTC58-0061 ,Clinics: Lung / Sarcoma / LymphomaPTC58-0580 ,Physics: Monitoring and Modelling MotionPTC58-0162 ,Physics: Adaptive TherapyPTC58-0550 ,Physics: Adaptive TherapyPTC58-0430 ,Clinics: Lung / Sarcoma / LymphomaPTC58-0103 ,General: New Investigator SessionPTC58-0252 ,Physics: Quality Assurance and VerificationPTC58-0704 ,Physics: Image GuidancePTC58-0418 ,Clinics: Base of SkullPTC58-0572 ,Clinics: Lung / Sarcoma / LymphomaPTC58-0106 ,Physics: Beam Delivery and Nozzle DesignPTC58-0022 ,Physics: Monitoring and Modelling MotionPTC58-0279 ,Physics: Treatment Planning Poster Discussion SessionsPTC58-0447 ,Physics: Treatment PlanningPTC58-0622 ,Clinics: PediatricsPTC58-0644 ,Biology: Biology and Clinical InterfacePTC58-0490 ,Clinics: CNS / Skull BasePTC58-0716 ,General: New HorizonsPTC58-0292 ,Biology: Biological Differences between Carbon / Proton and Photons Carbons / Proton and PhotonPTC58-0570 ,General: New HorizonsPTC58-0059 ,Physics: Quality Assurance and VerificationPTC58-0710 ,Biology: Biological Differences between Carbon / Proton and Photons Carbons / Proton and PhotonPTC58-0216 ,Physics: Image GuidancePTC58-0404 ,Physics: Image GuidancePTC58-0525 ,Physics: Image GuidancePTC58-0526 ,Poster AbstractsClinics: CNSPTC58-0328 ,Clinics: LungPTC58-0070 ,Clinics: Eye / Breast / Pelvis Poster Discussion SessionsPTC58-0135 ,Biology: BNCT Poster Discussion SessionsPTC58-0391 ,Physics: Treatment PlanningPTC58-0510 ,Physics: Treatment PlanningPTC58-0636 ,Physics: Treatment PlanningPTC58-0638 ,Physics: Image GuidancePTC58-0408 ,Physics: Absolute and Relative Dosimetry Poster Discussion SessionsPTC58-0632 ,Physics: Treatment Planning Poster Discussion SessionsPTC58-0318 ,Biology: Enhanced Biology in Treatment PlanningPTC58-0246 ,Clinics: PediatricsPTC58-0504 ,General: New HorizonsPTC58-0160 ,Physics: Image Guidance Poster Discussion SessionsPTC58-0076 ,Physics: Monitoring and Modelling MotionPTC58-0143 ,Biology: Mathematical Modelling and SimulationPTC58-0718 ,Physics: Image GuidancePTC58-0671 ,Clinics: LungPTC58-0183 ,Physics: Image GuidancePTC58-0670 ,Report ,Physics: Treatment Planning Poster Discussion SessionsPTC58-0422 ,Biology: Biological Differences between Carbon / Proton and Photons Carbons / Proton and PhotonPTC58-0129 ,Physics: Adaptive Therapy Poster Discussion SessionsPTC58-0705 ,Biology: Enhanced Biology in Treatment PlanningPTC58-0258 ,General: New HorizonsPTC58-0030 ,General: New HorizonsPTC58-0150 ,Biology: Biology and Clinical InterfacePTC58-0479 ,General: New HorizonsPTC58-0153 ,Clinics: PediatricPTC58-0087 ,General: New HorizonsPTC58-0152 ,General: New HorizonsPTC58-0155 ,General: New HorizonsPTC58-0033 ,General: New HorizonsPTC58-0158 ,Physics: Image GuidancePTC58-0429 ,Biology: Translational and BiomarkersPTC58-0287 ,Physics: Adaptive TherapyPTC58-0403 ,Physics: Image GuidancePTC58-0309 - Published
- 2020
3. FLASH Mechanisms Track (Oral Presentations) FLASH PROTON PENCIL BEAM SCANNING IRRADIATION USING A CLINICAL GANTRY DIMINISHES RADIATION INDUCED SKIN AND SOFT TISSUE TOXICITY IN MICE
- Author
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Cunningham, S., primary, Mccauley, S., additional, Speth, J., additional, Abel, E., additional, Sharma, R., additional, Perentesis, J., additional, Wells, S., additional, Mascia, A., additional, and Sertorio, M., additional
- Published
- 2022
- Full Text
- View/download PDF
4. Comparison of FLASH vs Conventional Dose Rate Proton Radiation in Endogenous Mouse Brain Tumor Model
- Author
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Rao, R., primary, Ogurek, S., additional, Sertorio, M., additional, Mascia, A.E., additional, Sengupta, D., additional, Girdhani, S., additional, Perentesis, J.P., additional, and Lu, Q.R., additional
- Published
- 2020
- Full Text
- View/download PDF
5. O086 - FLASH Mechanisms Track (Oral Presentations) FLASH PROTON PENCIL BEAM SCANNING IRRADIATION USING A CLINICAL GANTRY DIMINISHES RADIATION INDUCED SKIN AND SOFT TISSUE TOXICITY IN MICE
- Author
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Cunningham, S., Mccauley, S., Speth, J., Abel, E., Sharma, R., Perentesis, J., Wells, S., Mascia, A., and Sertorio, M.
- Published
- 2022
- Full Text
- View/download PDF
6. Combined effects of arsenic exposure and diabetes on male reproductive functions
- Author
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Souza, A. C. F., primary, Bastos, D. S. S., additional, Sertorio, M. N., additional, Santos, F. C., additional, Ervilha, L. O. G., additional, de Oliveira, L. L., additional, and Machado-Neves, M., additional
- Published
- 2019
- Full Text
- View/download PDF
7. Proton Treatment Suppresses Exosome Production in Head and Neck Squamous Cell Carcinoma.
- Author
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Chimote AA, Lehn MA, Bhati J, Mascia AE, Sertorio M, Lamba MA, Ionascu D, Tang AL, Langevin SM, Khodoun MV, Wise-Draper TM, and Conforti L
- Abstract
Proton therapy (PT) is emerging as an effective and less toxic alternative to conventional X-ray-based photon therapy (XRT) for patients with advanced head and neck squamous cell carcinomas (HNSCCs) owing to its clustered dose deposition dosimetric characteristics. For optimal efficacy, cancer therapies, including PT, must elicit a robust anti-tumor response by effector and cytotoxic immune cells in the tumor microenvironment (TME). While tumor-derived exosomes contribute to immune cell suppression in the TME, information on the effects of PT on exosomes and anti-tumor immune responses in HNSCC is not known. In this study, we generated primary HNSCC cells from tumors resected from HNSCC patients, irradiated them with 5 Gy PT or XRT, and isolated exosomes from cell culture supernatants. HNSCC cells exposed to PT produced 75% fewer exosomes than XRT- and non-irradiated HNSCC cells. This effect persisted in proton-irradiated cells for up to five days. Furthermore, we observed that exosomes from proton-irradiated cells were identical in morphology and immunosuppressive effects (suppression of IFN-γ release by peripheral blood mononuclear cells) to those of photon-irradiated cells. Our results suggest that PT limits the suppressive effect of exosomes on cancer immune surveillance by reducing the production of exosomes that can inhibit immune cell function.
- Published
- 2024
- Full Text
- View/download PDF
8. Impact of Multiple Beams on the FLASH Effect in Soft Tissue and Skin in Mice.
- Author
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Mascia A, McCauley S, Speth J, Nunez SA, Boivin G, Vilalta M, Sharma RA, Perentesis JP, and Sertorio M
- Subjects
- Female, Humans, Animals, Mice, Radiotherapy Planning, Computer-Assisted methods, Fibrosis, Radiotherapy Dosage, Protons, Proton Therapy methods
- Abstract
Purpose: FLASH proton pencil beam scanning (p-PBS) showed a reduction in mouse skin toxicity and fibrosis when delivered as a single, uninterrupted, high-dose fraction. Clinical p-PBS treatment usually requires multiple beams to achieve good conformality, and these beams are separated by minutes to allow patient and equipment repositioning. We evaluate the impact of multibeam versus single-beam proton radiation on the FLASH sparing effect on skin toxicity., Methods and Materials: The right hind leg of 10-week-old female C57Bl/6j mice was irradiated using a Varian ProBeam proton beam scanning gantry system at conventional (1 Gy/s) or FLASH (100 Gy/s) average field dose rate. We scored the skin toxicity after different doses for 7 weeks. The treatment was delivered as 1, 2, or 3 equal beams with an interruption of 2 minutes. For each beam delivery, the equipment remained in the same position so that there was a full overlap of beams administered., Results: Single-beam delivery confirmed a benefit for p-PBS FLASH in this model at 30, 35, and 40 Gy. At 30 and 35 Gy, a single beam interruption of 2 minutes (2 × 15 Gy or 2 × 17.5 Gy) reduced the FLASH sparing effect, which remained significant (P < .001). However, 2 interruptions (3 × 10 Gy or 3 × 11.6 Gy) abrogated the normal tissue sparing effect., Conclusions: Our results indicate that the FLASH sparing effect in areas of beam overlap can be compromised by interruptions in delivery time. Time gap between overlapping beams and spatial arrangement of the delivered beams are important parameters for FLASH studies. The effect of multibeam needs to be studied on different organs of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Published
- 2024
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- View/download PDF
9. Development of a Single-Neurosphere Culture to Assess Radiation Toxicity and Pre-Clinical Cancer Combination Therapy Safety.
- Author
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Pathak B, Lange TE, Lampe K, Hollander E, Oria M, Murphy KP, Salomonis N, Sertorio M, and Oria M
- Abstract
Radiation therapy (RT) is a crucial treatment modality for central nervous system (CNS) tumors but toxicity to healthy CNS tissues remains a challenge. Additionally, environmental exposure to radiation during nuclear catastrophes or space travel presents a risk of CNS toxicity. However, the underlying mechanisms of radiation-induced CNS toxicity are not fully understood. Neural progenitor cells (NPCs) are highly radiosensitive, resulting in decreased neurogenesis in the hippocampus. This study aimed to characterize a novel platform utilizing rat NPCs cultured as 3D neurospheres (NSps) to screen the safety and efficacy of experimental drugs with and without radiation exposure. The effect of radiation on NSp growth and differentiation was assessed by measuring sphere volume and the expression of neuronal differentiation markers Nestin and GFAP and proliferation marker Ki67. Radiation exposure inhibited NSp growth, decreased proliferation, and increased GFAP expression, indicating astrocytic differentiation. RNA sequencing analysis supported these findings, showing upregulation of Notch, BMP2/4, S100b, and GFAP gene expression during astrogenesis. By recapitulating radiation-induced toxicity and astrocytic differentiation, this single-NSp culture system provides a high-throughput preclinical model for assessing the effects of various radiation modalities and evaluates the safety and efficacy of potential therapeutic interventions in combination with radiation.
- Published
- 2023
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- View/download PDF
10. Varied Photon Radiation Sources Produce Differences in Cellular Response.
- Author
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Korns J, McCauley S, Lehn M, Takiar V, Sertorio M, and Lamba M
- Subjects
- Humans, Cell Line, Tumor, Radiation Dosage, Squamous Cell Carcinoma of Head and Neck pathology, Squamous Cell Carcinoma of Head and Neck radiotherapy, Cell Survival radiation effects, Apoptosis radiation effects, DNA Damage radiation effects, Radiation, Ionizing classification
- Abstract
In vitro studies allow evaluation of normal or cancer cell responses to radiation, either alone or in combination with agents used to modify these biological responses. Ionizing radiation can be produced by a variety of particles and sources, with varying energy spectra, interaction probabilities, linear energy transfer, dose uniformity, dose rates, and delivery methods. Multiple radiation sources have been used to irradiate cells in the published literature. However, the equivalence of response in cell culture models across radiation sources has not been rigorously established. Moreover, current reporting of radiation source parameters lacks consistency and rigor which may impact the reproducibility of pre-clinical data between laboratories. Relevant choices of radiation source are also of high importance due to growing interest in comparing photon versus particle radiation effect on biological responses. Therefore, this study robustly evaluates the cellular response (cell survival, apoptosis, and DNA damage) of three distinct cell lines using four unique photon generating radiation sources. We hypothesize there may be subtle differences across the radiation sources, without an appreciable difference in cellular response. The four photon irradiation energies investigated, 662 keV, 100 kVp, 220 kVp, 6 MV, did produce subtle differences in DNA damage and cell survival when treating three distinct tumor cell lines. These variations in cellular response emphasize the need to carefully consider irradiation source, energy, and dose rate depending on study goal and endpoint., (©2023 by Radiation Research Society. All rights of reproduction in any form reserved.)
- Published
- 2023
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- View/download PDF
11. FLASH Radiotherapy for the Treatment of Symptomatic Bone Metastases (FAST-01): Protocol for the First Prospective Feasibility Study.
- Author
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Daugherty EC, Mascia A, Zhang Y, Lee E, Xiao Z, Sertorio M, Woo J, McCann C, Russell K, Levine L, Sharma R, Khuntia D, Bradley J, Simone CB 2nd, Perentesis J, and Breneman J
- Abstract
Background: In preclinical studies, FLASH therapy, in which radiation delivered at ultrahigh dose rates of ≥40 Gy per second, has been shown to cause less injury to normal tissues than radiotherapy delivered at conventional dose rates. This paper describes the protocol for the first-in-human clinical investigation of proton FLASH therapy., Objective: FAST-01 is a prospective, single-center trial designed to assess the workflow feasibility, toxicity, and efficacy of FLASH therapy for the treatment of painful bone metastases in the extremities., Methods: Following informed consent, 10 subjects aged ≥18 years with up to 3 painful bone metastases in the extremities (excluding the feet, hands, and wrists) will be enrolled. A treatment field selected from a predefined library of plans with fixed field sizes (from 7.5 cm × 7.5 cm up to 7.5 cm × 20 cm) will be used for treatment. Subjects will receive 8 Gy of radiation in a single fraction-a well-established palliative regimen evaluated in prior investigations using conventional dose rate photon radiotherapy. A FLASH-enabled Varian ProBeam proton therapy unit will be used to deliver treatment to the target volume at a dose rate of ≥40 Gy per second, using the plateau (transmission) portion of the proton beam. After treatment, subjects will be assessed for pain response as well as any adverse effects of FLASH radiation. The primary end points include assessing the workflow feasibility and toxicity of FLASH treatment. The secondary end point is pain response at the treated site(s), as measured by patient-reported pain scores, the use of pain medication, and any flare in bone pain after treatment. The results will be compared to those reported historically for conventional dose rate photon radiotherapy, using the same radiation dose and fractionation., Results: FAST-01 opened to enrollment on November 3, 2020. Initial results are expected to be published in 2022., Conclusions: The results of this investigation will contribute to further developing and optimizing the FLASH-enabled ProBeam proton therapy system workflow. The pain response and toxicity data acquired in our study will provide a greater understanding of FLASH treatment effects on tumor responses and normal tissue toxicities, and they will inform future FLASH trial designs., Trial Registration: : ClinicalTrials.gov NCT04592887; http://clinicaltrials.gov/ct2/show/NCT04592887., International Registered Report Identifier (irrid): DERR1-10.2196/41812., (©Emily C Daugherty, Anthony Mascia, Yong Zhang, Eunsin Lee, Zhiyan Xiao, Mathieu Sertorio, Jennifer Woo, Claire McCann, Kenneth Russell, Lisa Levine, Ricky Sharma, Deepak Khuntia, Jeffrey Bradley, Charles B Simone II, John Perentesis, John Breneman. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 05.01.2023.)
- Published
- 2023
- Full Text
- View/download PDF
12. Proton FLASH Radiotherapy for the Treatment of Symptomatic Bone Metastases: The FAST-01 Nonrandomized Trial.
- Author
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Mascia AE, Daugherty EC, Zhang Y, Lee E, Xiao Z, Sertorio M, Woo J, Backus LR, McDonald JM, McCann C, Russell K, Levine L, Sharma RA, Khuntia D, Bradley JD, Simone CB 2nd, Perentesis JP, and Breneman JC
- Subjects
- Child, Humans, Male, Middle Aged, Adult, Aged, Aged, 80 and over, Female, Pain etiology, Palliative Care, Treatment Outcome, Protons, Bone Neoplasms radiotherapy, Bone Neoplasms secondary
- Abstract
Importance: To our knowledge, there have been no clinical trials of ultra-high-dose-rate radiotherapy delivered at more than 40 Gy/sec, known as FLASH therapy, nor first-in-human use of proton FLASH., Objectives: To assess the clinical workflow feasibility and treatment-related toxic effects of FLASH and pain relief at the treatment sites., Design, Setting, and Participants: In the FAST-01 nonrandomized trial, participants treated at Cincinnati Children's/UC Health Proton Therapy Center underwent palliative FLASH radiotherapy to extremity bone metastases. Patients 18 years and older with 1 to 3 painful extremity bone metastases and life expectancies of 2 months or more were eligible. Patients were excluded if they had foot, hand, and wrist metastases; metastases locally treated in the 2 weeks prior; metal implants in the treatment field; known enhanced tissue radiosensitivity; and implanted devices at risk of malfunction with radiotherapy. One of 11 patients who consented was excluded based on eligibility. The end points were evaluated at 3 months posttreatment, and patients were followed up through death or loss to follow-up for toxic effects and pain assessments. Of the 10 included patients, 2 died after the 2-month follow-up but before the 3-month follow-up; 8 participants completed the 3-month evaluation. Data were collected from November 3, 2020, to January 28, 2022, and analyzed from January 28, 2022, to September 1, 2022., Interventions: Bone metastases were treated on a FLASH-enabled (≥40 Gy/sec) proton radiotherapy system using a single-transmission proton beam. This is consistent with standard of care using the same prescription (8 Gy in a single fraction) but on a conventional-dose-rate (approximately 0.03 Gy/sec) photon radiotherapy system., Main Outcome and Measures: Main outcomes included patient time on the treatment couch, device-related treatment delays, adverse events related to FLASH, patient-reported pain scores, and analgesic use., Results: A total of 10 patients (age range, 27-81 years [median age, 63 years]; 5 [50%] male) underwent FLASH radiotherapy at 12 metastatic sites. There were no FLASH-related technical issues or delays. The average (range) time on the treatment couch was 18.9 (11-33) minutes per patient and 15.8 (11-22) minutes per treatment site. Median (range) follow-up was 4.8 (2.3-13.0) months. Adverse events were mild and consistent with conventional radiotherapy. Transient pain flares occurred in 4 of the 12 treated sites (33%). In 8 of the 12 sites (67%) patients reported pain relief, and in 6 of the 12 sites (50%) patients reported a complete response (no pain)., Conclusions and Relevance: In this nonrandomized trial, clinical workflow metrics, treatment efficacy, and safety data demonstrated that ultra-high-dose-rate proton FLASH radiotherapy was clinically feasible. The treatment efficacy and the profile of adverse events were comparable with those of standard-of-care radiotherapy. These findings support the further exploration of FLASH radiotherapy in patients with cancer., Trial Registration: ClinicalTrials.gov Identifier: NCT04592887.
- Published
- 2023
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13. The influence of parental high-fat high-sugar diet on the gut-brain axis in male offspring.
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César H, Nascimento Sertorio M, Santamarina A, Alves de Souza E, Valles Mennitti L, Jamar G, Jucá A, Picin Casagrande B, Estadela D, and Pellegrini Pisani L
- Subjects
- Animals, Brain-Gut Axis, Diet, High-Fat, Female, Humans, Male, Pregnancy, Rats, Rats, Wistar, Sugars, Ghrelin, Maternal Nutritional Physiological Phenomena
- Abstract
Purpose: The gut-brain axis (GBA) is implicated in the development of obesity, and its role in developmental programming needs to be explored. This study uncovers the effects of a parental high-fat, high-sugar diet (HFS) on the gut (colon) and brain (hypothalamus) GBA of male Wistar rat offspring at weaning until adulthood., Methods: For ten weeks before mating, male progenitors were fed a control diet (CD) or HFS, whereas dams were fed CD or HFS during pregnancy and lactation. Male offspring aged 21-and 90-day old were assessed for: Gene expression of toll-like receptor 4 (TLR4) pathway and zonula occludens 1 (ZO1) in the colon and hypothalamus; hypothalamic gene expression of orexigenic neuropeptides and Leptin receptor; serum levels of lipopolysaccharide (LPS), glucagon like peptide 1 (GLP-1), Ghrelin and neuropeptide Y (NPY); colonic cytokine levels; FaecalBifidobacterium spp.andLactobacillus spp. DNA., Results: Paternal HFS showed increased endotoxaemia, reduced colonic gene expression of ZO1 and reduced colonic TNF-α at weaning. In the adult offspring, paternal HFS showed increased NPY, reduced serum Ghrelin, colonic pro-inflammatory cytokines, and lower faecalBifidobacteriumspp. DNA. Maternal diet showed increased hypothalamic gene expression of myeloid differentiation primary response 88 (MYD88) at weaning. The maternal HFS diet showed increased NPY and reduced faecalBifidobacteriumspp. andLactobacillusspp. DNA in the adult offspring. The combined effect of parental diet showed increased NPY at weaning, and lowerBifidobacteriumspp. andLactobacillus spp.in the adult offspring., Conclusion: Maternal and paternal HFS diet seem to influence the programming of the gut-brain axis, leading to increased visceral adiposity and weight of male offspring at weaning, the effect that lasted until adulthood., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
- Published
- 2022
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14. Cognitive and behavioral effects of whole brain conventional or high dose rate (FLASH) proton irradiation in a neonatal Sprague Dawley rat model.
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Williams MT, Sugimoto C, Regan SL, Pitzer EM, Fritz AL, Sertorio M, Mascia AE, Vatner RE, Perentesis JP, and Vorhees CV
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- Animals, Cognition, Maze Learning, Rats, Rats, Sprague-Dawley, Brain, Protons
- Abstract
Recent studies suggest that ultra-high dose rates of proton radiation (>40 Gy/s; FLASH) confer less toxicity to exposed healthy tissue and reduce cognitive decline compared with conventional radiation dose rates (~1 Gy/s), but further preclinical data are required to demonstrate this sparing effect. In this study, postnatal day 11 (P11) rats were treated with whole brain irradiation with protons at a total dose of 0, 5, or 8 Gy, comparing a conventional dose rate of 1 Gy/s vs. a FLASH dose rate of 100 Gy/s. Beginning on P64, rats were tested for locomotor activity, acoustic and tactile startle responses (ASR, TSR) with or without prepulses, novel object recognition (NOR; 4-object version), striatal dependent egocentric learning ([configuration A] Cincinnati water maze (CWM-A)), prefrontal dependent working memory (radial water maze (RWM)), hippocampal dependent spatial learning (Morris water maze (MWM)), amygdala dependent conditioned freezing, and the mirror image CWM [configuration B (CWM-B)]. All groups had deficits in the CWM-A procedure. Weight reductions, decreased center ambulation in the open-field, increased latency on day-1 of RWM, and deficits in CWM-B were observed in all irradiated groups, except the 5 Gy FLASH group. ASR and TSR were reduced in the 8 Gy FLASH group and day-2 latencies in the RWM were increased in the FLASH groups compared with controls. There were no effects on prepulse trials of ASR or TSR, NOR, MWM, or conditioned freezing. The results suggest striatal and prefrontal cortex are sensitive regions at P11 to proton irradiation, with reduced toxicity from FLASH at 5 Gy., Competing Interests: These experiments were funded by Varian, a Siemens Healthineers company that granted the authors intellectual freedom to publish the data. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
- Published
- 2022
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15. Head and Neck Cancer Susceptibility and Metabolism in Fanconi Anemia.
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Chihanga T, Vicente-Muñoz S, Ruiz-Torres S, Pal B, Sertorio M, Andreassen PR, Khoury R, Mehta P, Davies SM, Lane AN, Romick-Rosendale LE, and Wells SI
- Abstract
Fanconi anemia (FA) is a rare inherited, generally autosomal recessive syndrome, but it displays X-linked or dominant negative inheritance for certain genes. FA is characterized by a deficiency in DNA damage repair that results in bone marrow failure, and in an increased risk for various epithelial tumors, most commonly squamous cell carcinomas of the head and neck (HNSCC) and of the esophagus, anogenital tract and skin. Individuals with FA exhibit increased human papilloma virus (HPV) prevalence. Furthermore, a subset of anogenital squamous cell carcinomas (SCCs) in FA harbor HPV sequences and FA-deficient laboratory models reveal molecular crosstalk between HPV and FA proteins. However, a definitive role for HPV in HNSCC development in the FA patient population is unproven. Cellular metabolism plays an integral role in tissue homeostasis, and metabolic deregulation is a known hallmark of cancer progression that supports uncontrolled proliferation, tumor development and metastatic dissemination. The metabolic consequences of FA deficiency in keratinocytes and associated impact on the development of SCC in the FA population is poorly understood. Herein, we review the current literature on the metabolic consequences of FA deficiency and potential effects of resulting metabolic reprogramming on FA cancer phenotypes.
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- 2022
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16. Therapeutic Advancements in Metal and Metal Oxide Nanoparticle-Based Radiosensitization for Head and Neck Cancer Therapy.
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Dubey P, Sertorio M, and Takiar V
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Although radiation therapy (RT) is one of the mainstays of head and neck cancer (HNC) treatment, innovative approaches are needed to further improve treatment outcomes. A significant challenge has been to design delivery strategies that focus high doses of radiation on the tumor tissue while minimizing damage to surrounding structures. In the last decade, there has been increasing interest in harnessing high atomic number materials (Z-elements) as nanoparticle radiosensitizers that can also be specifically directed to the tumor bed. Metallic nanoparticles typically display chemical inertness in cellular and subcellular systems but serve as significant radioenhancers for synergistic tumor cell killing in the presence of ionizing radiation. In this review, we discuss the current research and therapeutic efficacy of metal nanoparticle (MNP)-based radiosensitizers, specifically in the treatment of HNC with an emphasis on gold- (AuNPs), gadolinium- (AGdIX), and silver- (Ag) based nanoparticles together with the metallic oxide-based hafnium (Hf), zinc (ZnO) and iron (SPION) nanoparticles. Both in vitro and in vivo systems for different ionizing radiations including photons and protons were reviewed. Finally, the current status of preclinical and clinical studies using MNP-enhanced radiation therapy is discussed.
- Published
- 2022
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17. Inherited DNA Repair Defects Disrupt the Structure and Function of Human Skin.
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Ruiz-Torres S, Brusadelli MG, Witte DP, Wikenheiser-Brokamp KA, Sauter S, Nelson AS, Sertorio M, Chlon TM, Lane A, Mehta PA, Myers KC, Bedard MC, Pal B, Supp DM, Lambert PF, Komurov K, Kovacic MB, Davies SM, and Wells SI
- Subjects
- Cell Differentiation, Child, DNA Repair, Humans, Skin, Carcinoma, Squamous Cell, Fanconi Anemia genetics
- Abstract
Squamous cell carcinoma (SCC) is a global public health burden originating in epidermal stem and progenitor cells (ESPCs) of the skin and mucosa. To understand how genetic risk factors contribute to SCC, studies of ESPC biology are imperative. Children with Fanconi anemia (FA) are a paradigm for extreme SCC susceptibility caused by germline loss-of-function mutations in FA DNA repair pathway genes. To discover epidermal vulnerabilities, patient-derived pluripotent stem cells (PSCs) conditional for the FA pathway were differentiated into ESPCs and PSC-derived epidermal organotypic rafts (PSC-EORs). FA PSC-EORs harbored diminished cell-cell junctions and increased proliferation in the basal cell compartment. Furthermore, desmosome and hemidesmosome defects were identified in the skin of FA patients, and these translated into accelerated blistering following mechanically induced stress. Together, we demonstrate that a critical DNA repair pathway maintains the structure and function of human skin and provide 3D epidermal models wherein SCC prevention can now be explored., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2021
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18. FLASH Proton Pencil Beam Scanning Irradiation Minimizes Radiation-Induced Leg Contracture and Skin Toxicity in Mice.
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Cunningham S, McCauley S, Vairamani K, Speth J, Girdhani S, Abel E, Sharma RA, Perentesis JP, Wells SI, Mascia A, and Sertorio M
- Abstract
Ultra-high dose rate radiation has been reported to produce a more favorable toxicity and tumor control profile compared to conventional dose rates that are used for patient treatment. So far, the so-called FLASH effect has been validated for electron, photon and scattered proton beam, but not yet for proton pencil beam scanning (PBS). Because PBS is the state-of-the-art delivery modality for proton therapy and constitutes a wide and growing installation base, we determined the benefit of FLASH PBS on skin and soft tissue toxicity. Using a pencil beam scanning nozzle and the plateau region of a 250 MeV proton beam, a uniform physical dose of 35 Gy (toxicity study) or 15 Gy (tumor control study) was delivered to the right hind leg of mice at various dose rates: Sham, Conventional (Conv, 1 Gy/s), Flash60 (57 Gy/s) and Flash115 (115 Gy/s). Acute radiation effects were quantified by measurements of plasma and skin levels of TGF-β1 and skin toxicity scoring. Delayed irradiation response was defined by hind leg contracture as a surrogate of irradiation-induced skin and soft tissue toxicity and by plasma levels of 13 different cytokines (CXCL1, CXCL10, Eotaxin, IL1-beta, IL-6, MCP-1, Mip1alpha, TNF-alpha, TNF-beta, VEGF, G-CSF, GM-CSF and TGF- β1). Plasma and skin levels of TGF-β1, skin toxicity and leg contracture were all significantly decreased in FLASH compared to Conv groups of mice. FLASH and Conv PBS had similar efficacy with regards to growth control of MOC1 and MOC2 head and neck cancer cells transplanted into syngeneic, immunocompetent mice. These results demonstrate consistent delivery of FLASH PBS radiation from 1 to 115 Gy/s in a clinical gantry. Radiation response following delivery of 35 Gy indicates potential benefits of FLASH versus conventional PBS that are related to skin and soft tissue toxicity.
- Published
- 2021
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19. Differential transcriptome response to proton versus X-ray radiation reveals novel candidate targets for combinatorial PT therapy in lymphoma.
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Sertorio M, Nowrouzi A, Akbarpour M, Chetal K, Salomonis N, Brons S, Mascia A, Ionascu D, McCauley S, Kupneski T, Köthe A, Debus J, Perentesis JP, Abdollahi A, Zheng Y, and Wells SI
- Subjects
- Animals, Humans, Mice, Protons, Transcriptome, X-Rays, Lymphoma genetics, Proton Therapy
- Abstract
Background and Purpose: Knowledge of biological responses to proton therapy (PT) in comparison to X-ray remains in its infancy. Identification of PT specific molecular signals is an important opportunity for the discovery of biomarkers and synergistic drugs to advance clinical application. Since PT is used for the treatment of lymphoma, we report here transcriptomic responses of lymphoma cell lines to PT vs X-ray and identify potential therapeutic targets., Materials and Methods: Two lymphoma cell lines of human (BL41) and murine (J3D) origin were irradiated by X-ray and PT. Differential transcriptome regulation was quantified by RNA sequencing for each radiation type at 12 hours post irradiation. Gene-set enrichment analysis revealed deregulated molecular pathways and putative targets for lymphoma cell sensitization to PT., Results: Transcriptomic gene set enrichment analyses uncovered pathways that contribute to the unfolded protein response (UPR) and mitochondrial transport. Functional validation at multiple time points demonstrated increased UPR activation and decreased protein translation, perhaps due to increased oxidative stress and oxidative protein damage after PT. PPARgamma was identified as a potential regulator of the PT transcriptomic response. Inhibition of PPARgamma by two compounds, T0070907 and SR2595, sensitized lymphoma cells to PT., Conclusions: Proton vs X-ray radiation leads to the transcriptional regulation of a specific subset of genes in line with diminished protein translation and UPR activation that may be due to oxidative stress. This study demonstrates that different radiation qualities trigger distinct cellular responses in lymphoma cells, and identifies PPARgamma inhibition as a potential strategy for the sensitization of lymphoma to PT., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2021
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20. Whole brain proton irradiation in adult Sprague Dawley rats produces dose dependent and non-dependent cognitive, behavioral, and dopaminergic effects.
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Williams MT, Sugimoto C, Regan SL, Pitzer EM, Fritz AL, Mascia AE, Sertorio M, Vatner RE, Perentesis JP, and Vorhees CV
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- Animals, Dose-Response Relationship, Radiation, Learning radiation effects, Male, Maze Learning radiation effects, Memory radiation effects, Prepulse Inhibition radiation effects, Rats, Rats, Sprague-Dawley, Behavior, Animal radiation effects, Cognition radiation effects, Cranial Irradiation, Motor Activity radiation effects
- Abstract
Proton radiotherapy causes less off-target effects than X-rays but is not without effect. To reduce adverse effects of proton radiotherapy, a model of cognitive deficits from conventional proton exposure is needed. We developed a model emphasizing multiple cognitive outcomes. Adult male rats (10/group) received a single dose of 0, 11, 14, 17, or 20 Gy irradiation (the 20 Gy group was not used because 50% died). Rats were tested once/week for 5 weeks post-irradiation for activity, coordination, and startle. Cognitive assessment began 6-weeks post-irradiation with novel object recognition (NOR), egocentric learning, allocentric learning, reference memory, and proximal cue learning. Proton exposure had the largest effect on activity and prepulse inhibition of startle 1-week post-irradiation that dissipated each week. 6-weeks post-irradiation, there were no effects on NOR, however proton exposure impaired egocentric (Cincinnati water maze) and allocentric learning and caused reference memory deficits (Morris water maze), but did not affect proximal cue learning or swimming performance. Proton groups also had reduced striatal levels of the dopamine transporter, tyrosine hydroxylase, and the dopamine receptor D1, effects consistent with egocentric learning deficits. This new model will facilitate investigations of different proton dose rates and drugs to ameliorate the cognitive sequelae of proton radiotherapy.
- Published
- 2020
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21. DEK Expression in Breast Cancer Cells Leads to the Alternative Activation of Tumor Associated Macrophages.
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Pease NA, Shephard MS, Sertorio M, Waltz SE, and Vinnedge LMP
- Abstract
Breast cancer (BC) is the second leading cause of cancer deaths among women. DEK is a known oncoprotein that is highly expressed in over 60% of breast cancers and is an independent marker of poor prognosis. However, the molecular mechanisms by which DEK promotes tumor progression are poorly understood. To identify novel oncogenic functions of DEK, we performed RNA-Seq analysis on isogenic Dek-knockout and complemented murine BC cells. Gene ontology analyses identified gene sets associated with immune system regulation and cytokine-mediated signaling and differential cytokine and chemokine expression was confirmed across Dek-proficient versus Dek-deficient cells. By exposing murine bone marrow-derived macrophages (BMDM) to tumor cell conditioned media (TCM) to mimic a tumor microenvironment, we showed that Dek-expressing breast cancer cells produce a cytokine milieu, including up-regulated Tslp and Ccl5 and down-regulated Cxcl1, Il-6, and GM-CSF, that drives the M2 polarization of macrophages. We validated this finding in primary murine mammary tumors and show that Dek expression in vivo is also associated with increased expression of M2 macrophage markers in murine tumors. Using TCGA data, we verified that DEK expression in primary human breast cancers correlates with the expression of several genes identified by RNA-Seq in our murine model and with M2 macrophage phenotypes. Together, our data demonstrate that by regulating the production of multiple secreted factors, DEK expression in BC cells creates a potentially immune suppressed tumor microenvironment, particularly by inducing M2 tumor associated macrophage (TAM) polarization.
- Published
- 2020
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22. Cancer Cell Metabolism: Implications for X-ray and Particle Radiation Therapy.
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Sertorio M, Perentesis JP, Vatner RE, Mascia AE, Zheng Y, and Wells SI
- Abstract
Advances in radiation delivery technologies and immunotherapy have improved effective cancer treatments and long-term outcomes. Experimental and clinical trials have demonstrated the benefit of a combination of radiation therapy and immunotherapy for tumor eradication. Despite precise radiation dose delivery that is achievable by particle therapy and benefits from reactivating the antitumor immune response, resistance to both therapeutic strategies is frequently observed in patients. Understanding the biological origins of such resistance will create new opportunities for improved cancer treatment. Cancer metabolism and especially a high rate of aerobic glycolysis leading to overproduction and release of lactate is one such biological process favoring tumor progression and treatment resistance. Because of their known protumor effects, aerobic glycolysis and lactate production are potential targets for increased efficacy of radiation alone or in combination with immunotherapy. In the following review, we present an overview of the interplay of cancer cell lactate metabolism with the tumor microenvironment and immune cells. We discuss how a deeper understanding and careful modulation of lactate metabolism and radiation therapy might exploit this interplay for improved therapeutic outcome., Competing Interests: Conflicts of Interest: The authors have no conflicts to disclose., (©Copyright 2018 International Journal of Particle Therapy.)
- Published
- 2018
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23. Loss of DEK induces radioresistance of murine restricted hematopoietic progenitors.
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Serrano-Lopez J, Nattamai K, Pease NA, Shephard MS, Wellendorf AM, Sertorio M, Smith EA, Geiger H, Wells SI, Cancelas JA, and Privette Vinnedge LM
- Subjects
- Animals, Hematopoietic Stem Cells cytology, Mice, Mice, Knockout, DNA Damage, DNA-Binding Proteins deficiency, Hematopoiesis physiology, Hematopoietic Stem Cells metabolism, Oncogene Proteins deficiency, Poly-ADP-Ribose Binding Proteins deficiency, Radiation Tolerance physiology
- Abstract
Self-renewing hematopoietic stem cells and multipotent progenitor cells are responsible for maintaining hematopoiesis throughout an individual's lifetime. For overall health and survival, it is critical that the genome stability of these cells is maintained and that the cell population is not exhausted. Previous reports have indicated that the DEK protein, a chromatin structural protein that functions in numerous nuclear processes, is required for DNA damage repair in vitro and long-term engraftment of hematopoietic stem cells in vivo. Therefore, we investigated the role of DEK in normal hematopoiesis and response to DNA damaging agents in vivo. Here, we report that hematopoiesis is largely unperturbed in DEK knockout mice compared with wild-type (WT) controls. However, DEK knockout mice have fewer radioprotective units, but increased capacity to survive repeated sublethal doses of radiation exposure compared with WT mice. Furthermore, this increased survival correlated with a sustained quiescent state in which DEK knockout restricted hematopoietic progenitor cells (HPC-1) were nearly three times more likely to be quiescent following irradiation compared with WT cells and were significantly more radioresistant during the early phases of myeloid reconstitution. Together, our studies indicate that DEK functions in the normal hematopoietic stress response to recurrent radiation exposure., (Copyright © 2018 ISEH – Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
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24. In Vivo RNAi Screen Unveils PPARγ as a Regulator of Hematopoietic Stem Cell Homeostasis.
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Sertorio M, Du W, Amarachintha S, Wilson A, and Pang Q
- Subjects
- Animals, Benzamides pharmacology, Cells, Cultured, Chromans pharmacology, Fanconi Anemia genetics, Fanconi Anemia metabolism, Hematopoiesis, Humans, Mice, PPAR gamma agonists, PPAR gamma antagonists & inhibitors, PPAR gamma genetics, Pyridines pharmacology, RNA, Small Interfering genetics, Thiazolidinediones pharmacology, Troglitazone, Tumor Suppressor Protein p53 metabolism, Fanconi Anemia Complementation Group D2 Protein genetics, Hematopoietic Stem Cells metabolism, Homeostasis, PPAR gamma metabolism
- Abstract
Hematopoietic stem cell (HSC) defects can cause repopulating impairment leading to hematologic diseases. To target HSC deficiency in a disease setting, we exploited the repopulating defect of Fanconi anemia (FA) HSCs to conduct an in vivo short hairpin RNA (shRNA) screen. We exposed Fancd2
-/- HSCs to a lentiviral shRNA library targeting 947 genes. We found enrichment of shRNAs targeting genes involved in the PPARγ pathway that has not been linked to HSC homeostasis. PPARγ inhibition by shRNA or chemical compounds significantly improves the repopulating ability of Fancd2-/- HSCs. Conversely, activation of PPARγ in wild-type HSCs impaired hematopoietic repopulation. In mouse HSCs and patient-derived lymphoblasts, PPARγ activation is manifested in upregulating the p53 target p21. PPARγ and co-activators are upregulated in total bone marrow and stem/progenitor cells from FA patients. Collectively, this work illustrates the utility of RNAi technology coupled with HSC transplantation for the discovery of novel genes and pathways involved in stress hematopoiesis., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2017
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25. Loss of Fancc Impairs Antibody-Secreting Cell Differentiation in Mice through Deregulating the Wnt Signaling Pathway.
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Sertorio M, Amarachintha S, Wilson A, and Pang Q
- Subjects
- Animals, Antibody-Producing Cells immunology, B-Lymphocytes cytology, B-Lymphocytes immunology, B-Lymphocytes metabolism, Cluster Analysis, Gene Expression Profiling, Immunoglobulin Class Switching genetics, Immunoglobulin Class Switching immunology, Immunoglobulin G genetics, Immunoglobulin G immunology, Mice, Mice, Knockout, Transcriptome, Wnt Proteins metabolism, Antibody-Producing Cells cytology, Antibody-Producing Cells metabolism, Cell Differentiation genetics, Cell Differentiation immunology, Fanconi Anemia Complementation Group C Protein deficiency, Wnt Signaling Pathway
- Abstract
Fanconi anemia (FA) is characterized by a progressive bone marrow failure and an increased incidence of cancer. FA patients have high susceptibility to immune-related complications such as infection and posttransplant graft-versus-host disease. In this study, we investigated the effect of FA deficiency in B cell function using the Fancc mouse model. Fancc(-/-) B cells show a specific defect in IgG2a switch and impaired Ab-secreting cell (ASC) differentiation. Global transcriptome analysis of naive B cells by mRNA sequencing demonstrates that FA deficiency deregulates a network of genes involved in immune function. Significantly, many genes implicated in Wnt signaling were aberrantly expressed in Fancc(-/-) B cells. Consistently, Fancc(-/-) B cells accumulate high levels of β-catenin under both resting and stimulated conditions, suggesting hyperactive Wnt signaling. Using an in vivo Wnt GFP reporter assay, we verified the upregulation of Wnt signaling as a potential mechanism responsible for the impaired Fancc(-/-) B cell differentiation. Furthermore, we showed that Wnt signaling inhibits ASC differentiation possibly through repression of Blimp1 and that Fancc(-/-) B cells are hypersensitive to Wnt activation during ASC differentiation. Our findings identify Wnt signaling as a physiological regulator of ASC differentiation and establish a role for the Wnt pathway in normal B cell function and FA immune deficiency., (Copyright © 2016 by The American Association of Immunologists, Inc.)
- Published
- 2016
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26. Correction: FOXP3+ Regulatory T Cells in Hepatic Fibrosis and Splenomegaly Caused by Schistosoma japonicum: The Spleen May Be a Major Source of Tregs in Subjects with Splenomegaly.
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Romano A, Hou X, Sertorio M, Dessein H, Cabantous S, Oliveira P, Li J, Oyegue S, Arnaud V, Luo X, Daujat-Chavanieu M, Mariani O, Sastre X, Dombey AM, He H, Li Y, and Dessein A
- Published
- 2016
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27. FOXP3+ Regulatory T Cells in Hepatic Fibrosis and Splenomegaly Caused by Schistosoma japonicum: The Spleen May Be a Major Source of Tregs in Subjects with Splenomegaly.
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Romano A, Hou X, Sertorio M, Dessein H, Cabantous S, Oliveira P, Li J, Oyegue S, Arnaud V, Luo X, Daujat-Chavanieu M, Mariani O, Sastre X, Dombey AM, He H, Li Y, and Dessein A
- Subjects
- Adult, Aged, Animals, Antigens, CD analysis, China, Cohort Studies, Humans, Immunophenotyping, Liver pathology, Liver Cirrhosis complications, Male, Middle Aged, Occupational Exposure, Spleen pathology, Splenomegaly complications, T-Lymphocytes, Regulatory chemistry, Forkhead Transcription Factors analysis, Liver Cirrhosis pathology, Schistosomiasis japonica pathology, Splenomegaly pathology, T-Lymphocyte Subsets chemistry, T-Lymphocyte Subsets immunology, T-Lymphocytes, Regulatory immunology
- Abstract
Schistosoma eggs cause chronic liver inflammation and a complex disease characterized by hepatic fibrosis (HF) and splenomegaly (SplM). FOXP3+ Tregs could regulate inflammation, but it is unclear where these cells are produced and what roles they play in human schistosomiasis. We investigated blood and spleen FOXP3+ Tregs in Chinese fishermen with lifelong exposure to Schistosoma japonicum and various degrees of liver and spleen disease. FOXP3+ Tregs accounted for 4.3% of CD4+ T cells and 41.2% of FOXP3+CD4+ T cells; they could be divided into CD45RA-FOXP3hi effector (eTregs) and CD45RA+FOXP3low naive Tregs. Blood Treg levels were high in severe HF (+1.3; p = 0.004) and in SplM (+1.03, p = 0.03). Multivariate regression showed that severe HF (+0.85, p = 0.01) and SplM (+0.97; p = 0.05) were independently associated with the higher proportion of Tregs in the blood. This effect was mostly due to an increase in the proportion of eTregs in the blood of HF+++ (+0.9%; p = 0.04) and SplM (+0.9%; p = 0.04) patients. The proportion of eTregs expressing CXCR3 in the blood was lower in the HF+++ patients (37.4 +/- 5.9%) than in those with milder fibrosis (51.7 ± 2%; p = 0.009), whereas proportion were similar for cells expressing CD25hi, CCR7, and CTLA-4. Splenectomy improves symptoms and was associated with decreases in blood FOXP3+ Treg (-2.5; p<0.001) and eTreg (-1.3; p = 0.03) levels. SplM spleens contained a high proportion of eTregs with CXCR3, CCR5 and CTLA4 upregulation and CCR7 downregulation. This, and the strong expression of ligands of CXCR3 and CCR5 in the liver (n = 8) but not in the spleen suggested that spleen eTregs migrated to Th1-infiltrated liver tissues. Such migration may be attenuated in hepatosplenic patients due to lower levels of CXCR3 expression on Tregs (p = 0.009). Thus, higher blood Treg levels are associated with severe liver disease and splenomegaly. Our data are consistent with the hypothesis that the spleen is a major source of Tregs in subjects with splenomegaly. In most cases, Tregs migrate to the Th1-infiltrated liver and the lower levels of CXCR3+ Tregs in the blood of patients with severe schistosomiasis suggest that decreases in Treg migration sites of inflammation may aggravate the disease.
- Published
- 2016
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28. Reply: To PMID 25476703.
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Sertorio M, Carmo RF, Cabantous S, Vasconcelos L, Pereira LB, Moura P, and Dessein A
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- Animals, Female, Humans, Male, Hepatitis C, Chronic complications, Interleukins physiology, Liver Cirrhosis etiology, Receptors, Interleukin physiology, Schistosomiasis complications
- Published
- 2015
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29. Fanconi Anemia Mesenchymal Stromal Cells-Derived Glycerophospholipids Skew Hematopoietic Stem Cell Differentiation Through Toll-Like Receptor Signaling.
- Author
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Amarachintha S, Sertorio M, Wilson A, Li X, and Pang Q
- Subjects
- Animals, Cells, Cultured, Coculture Techniques, Fanconi Anemia genetics, Fanconi Anemia Complementation Group A Protein genetics, Fanconi Anemia Complementation Group D2 Protein genetics, Mesenchymal Stem Cells metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, Signal Transduction physiology, Cell Differentiation physiology, Fanconi Anemia Complementation Group A Protein deficiency, Fanconi Anemia Complementation Group D2 Protein deficiency, Glycerophospholipids biosynthesis, Hematopoietic Stem Cells metabolism, Toll-Like Receptor 4 metabolism
- Abstract
Fanconi anemia (FA) patients develop bone marrow (BM) failure or leukemia. One standard care for these devastating complications is hematopoietic stem cell transplantation. We identified a group of mesenchymal stromal cells (MSCs)-derived metabolites, glycerophospholipids, and their endogenous inhibitor, 5-(tetradecyloxy)-2-furoic acid (TOFA), as regulators of donor hematopoietic stem and progenitor cells. We provided two pieces of evidence that TOFA could improve hematopoiesis-supporting function of FA MSCs: (a) limiting-dilution cobblestone area-forming cell assay revealed that TOFA significantly increased cobblestone colonies in Fanca-/- or Fancd2-/- cocultures compared to untreated cocultures. (b) Competitive repopulating assay using output cells collected from cocultures showed that TOFA greatly alleviated the abnormal expansion of the donor myeloid (CD45.2+Gr1+Mac1+) compartment in both peripheral blood and BM of recipient mice transplanted with cells from Fanca-/- or Fancd2-/- cocultures. Furthermore, mechanistic studies identified Tlr4 signaling as the responsible pathway mediating the effect of glycerophospholipids. Thus, targeting glycerophospholipid biosynthesis in FA MSCs could be a therapeutic strategy to improve hematopoiesis and stem cell transplantation., (© 2015 AlphaMed Press.)
- Published
- 2015
- Full Text
- View/download PDF
30. Transcriptional profiling of Foxo3a and Fancd2 regulated genes in mouse hematopoietic stem cells.
- Author
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Li X, Zhang T, Wilson A, Amarachintha S, Sertorio M, and Pang Q
- Abstract
Functional maintenance of hematopoietic stem cells (HSCs) is constantly challenged by stresses like DNA damage and oxidative stress. Foxo factors, particularly Foxo3a, function to regulate the self-renewal of HSCs and contribute to the maintenance of the HSC pool during aging by providing resistance to oxidative stress. Fancd2 -deficient mice had multiple hematopoietic defects, including HSC loss in early development and in response to cellular stresses including oxidative stress. The cellular mechanisms underlying HSC loss in Fancd2 -deficient mice include abnormal cell cycle status, loss of quiescence, and compromised hematopoietic repopulating capacity of HSCs. To address on a genome wide level the genes and pathways that are impacted by deletion of the Fancd2 and Foxo3a , we performed microarray analysis on phenotypic HSCs (Lin
- ckit+ Sca-1+ CD150+ CD48- ) from Fancd2 single knockout, Foxo3a single knockout and Fancd2-/-Foxo3a-/- double-knockout (dKO) mice. Here we provide detailed methods and analysis on these microarray data which has been deposited in Gene Expression Omnibus (GEO): GSE64215.- Published
- 2015
- Full Text
- View/download PDF
31. IL-22 and IL-22 binding protein (IL-22BP) regulate fibrosis and cirrhosis in hepatitis C virus and schistosome infections.
- Author
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Sertorio M, Hou X, Carmo RF, Dessein H, Cabantous S, Abdelwahed M, Romano A, Albuquerque F, Vasconcelos L, Carmo T, Li J, Varoquaux A, Arnaud V, Oliveira P, Hamdoun A, He H, Adbelmaboud S, Mergani A, Zhou J, Monis A, Pereira LB, Halfon P, Bourlière M, Parana R, Dos Reis M, Gonnelli D, Moura P, Elwali NE, Argiro L, Li Y, and Dessein A
- Subjects
- Adult, Animals, Female, Humans, Male, Mice, Middle Aged, Interleukin-22, Hepatitis C, Chronic complications, Interleukins physiology, Liver Cirrhosis etiology, Receptors, Interleukin physiology, Schistosomiasis complications
- Abstract
Unlabelled: Interleukin (IL)-22 acts on epithelia, hepatocytes, and pancreatic cells and stimulates innate immunity, tissue protection, and repair. IL-22 may also cause inflammation and abnormal cell proliferation. The binding of IL-22 to its receptor is competed by IL-22 binding protein (IL-22BP), which may limit the deleterious effects of IL-22. The role of IL-22 and IL-22BP in chronic liver diseases is unknown. We addressed this question in individuals chronically infected with schistosomes or hepatitis C virus (HCV). We first demonstrate that schistosome eggs stimulate production of IL-22 transcripts and inhibit accumulation of IL22-BP transcripts in schistosome-infected mice, and that schistosome eggs selectively stimulate production of IL-22 in cultures of blood leukocytes from individuals chronically infected with Schistosoma japonicum. High IL-22 levels in cultures correlated with protection against hepatic fibrosis and portal hypertension. To test further the implication of IL-22/IL-22BP in hepatic disease, we analyzed common genetic variants of IL22RA2, which encodes IL-22BP, and found that the genotypes, AA, GG of rs6570136 (P = 0.003; odds ratio [OR] = 2), and CC, TT of rs2064501 (P = 0.01; OR = 2), were associated with severe fibrosis in Chinese infected with S. japonicum. We confirmed this result in Sudanese (rs6570136 GG [P = 0.0007; OR = 8.2], rs2064501 TT [P = 0.02; OR = 3.1]), and Brazilians (rs6570136 GG [P = 0.003; OR = 26], rs2064501 TC, TT (P = 0.03; OR = 11]) infected with S. mansoni. The aggravating genotypes were associated with high IL22RA2 transcripts levels. Furthermore, these same variants were also associated with HCV-induced fibrosis and cirrhosis (rs6570136 GG, GA [P = 0.007; OR = 1.7], rs2064501 TT, TC (P = 0.004; OR = 2.4])., Conclusions: These results provide strong evidence that IL-22 protects against and IL-22BP aggravates liver fibrosis and cirrhosis in humans with chronic liver infections. Thus, pharmacological modulation of IL-22 BP may be an effective strategy to limit cirrhosis., (© 2014 by the American Association for the Study of Liver Diseases.)
- Published
- 2015
- Full Text
- View/download PDF
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