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346 results on '"Bouffet, E"'

1. Use of Sodium Thiosulfate as an Otoprotectant in Patients With Cancer Treated With Platinum Compounds: A Review of the Literature

Author: Meijer, AJM, Diepstraten, FA, Ansari, M, Bouffet, E, Bleyer, A, Fresneau, B, Geller, JI, Huitema, ADR, Kogner, P, Maibach, R, O'Neill, AF, Papadakis, V, Rajput, KM, Veal, GJ, Sullivan, M, van den Heuvel-eibrink, MM, Brock, PR, Meijer, AJM, Diepstraten, FA, Ansari, M, Bouffet, E, Bleyer, A, Fresneau, B, Geller, JI, Huitema, ADR, Kogner, P, Maibach, R, O'Neill, AF, Papadakis, V, Rajput, KM, Veal, GJ, Sullivan, M, van den Heuvel-eibrink, MM, and Brock, PR
Abstract: PURPOSE: Hearing loss occurs in 50%-70% of children treated with cisplatin. Scientific efforts have led to the recent approval of a pediatric formula of intravenous sodium thiosulfate (STS) for otoprotection by the US Food and Drug Administration, the European Medicines Agency, and the Medicines and Health Regulatory Authority in the United Kingdom. To inform stakeholders regarding the clinical utility of STS, the current review summarizes available literature on the efficacy, pharmacokinetics (PK), and safety of systemic STS to minimize cisplatin-induced hearing loss (CIHL). DESIGN: A comprehensive narrative review is presented. RESULTS: Thirty-one articles were summarized. Overall, systemic STS effectively reduces CIHL in the preclinical and controlled clinical study settings, in both adults and children with cancer. The extent of CIHL reduction depends on the timing and dosing of STS in relation to cisplatin. Both preclinical and clinical data suggest that systemic STS may affect plasma platinum levels, but studies are inconclusive. Delayed systemic administration of STS, at 6 hours after the cisplatin infusion, does not affect cisplatin-induced inhibition of tumor growth or cellular cytotoxicity in the preclinical setting, nor affect cisplatin efficacy and survival in children with localized disease in the clinical setting. CONCLUSION: Systemic administration of STS effectively reduces the development and degree of CIHL in both the preclinical and clinical settings. More studies are needed on the PK of STS and cisplatin drug combinations, the efficacy and safety of STS in patients with disseminated disease, and the ability of STS to prevent further deterioration of pre-established hearing loss.
Published: 2024

2. Epigenomic alterations define lethal CIMP-positive ependymomas of infancy

Author: Mack, SC, Witt, H, Piro, RM, Gu, L, Zuyderduyn, S, Stütz, AM, Wang, X, Gallo, M, Garzia, L, Zayne, K, Zhang, X, Ramaswamy, V, Jäger, N, Jones, DTW, Sill, M, Pugh, TJ, Ryzhova, M, Wani, KM, Shih, DJH, Head, R, Remke, M, Bailey, SD, Zichner, T, Faria, CC, Barszczyk, M, Stark, S, Seker-Cin, H, Hutter, S, Johann, P, Bender, S, Hovestadt, V, Tzaridis, T, Dubuc, AM, Northcott, PA, Peacock, J, Bertrand, KC, Agnihotri, S, Cavalli, FMG, Clarke, I, Nethery-Brokx, K, Creasy, CL, Verma, SK, Koster, J, Wu, X, Yao, Y, Milde, T, Sin-Chan, P, Zuccaro, J, Lau, L, Pereira, S, Castelo-Branco, P, Hirst, M, Marra, MA, Roberts, SS, Fults, D, Massimi, L, Cho, YJ, Van Meter, T, Grajkowska, W, Lach, B, Kulozik, AE, von Deimling, A, Witt, O, Scherer, SW, Fan, X, Muraszko, KM, Kool, M, Pomeroy, SL, Gupta, N, Phillips, J, Huang, A, Tabori, U, Hawkins, C, Malkin, D, Kongkham, PN, Weiss, WA, Jabado, N, Rutka, JT, Bouffet, E, Korbel, JO, Lupien, M, Aldape, KD, Bader, GD, Eils, R, Lichter, P, Dirks, PB, Pfister, SM, Korshunov, A, and Taylor, MD
Subjects: Biological Sciences, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Genetics, Pediatric, Human Genome, Rare Diseases, Animals, Brain Neoplasms, CpG Islands, DNA Methylation, Embryonic Stem Cells, Ependymoma, Epigenesis, Genetic, Epigenomics, Female, Gene Expression Regulation, Neoplastic, Gene Silencing, Histones, Humans, Infant, Mice, Mice, Inbred NOD, Mice, SCID, Mutation, Phenotype, Polycomb Repressive Complex 2, Prognosis, Rhombencephalon, Xenograft Model Antitumor Assays, General Science & Technology
Abstract: Ependymomas are common childhood brain tumours that occur throughout the nervous system, but are most common in the paediatric hindbrain. Current standard therapy comprises surgery and radiation, but not cytotoxic chemotherapy as it does not further increase survival. Whole-genome and whole-exome sequencing of 47 hindbrain ependymomas reveals an extremely low mutation rate, and zero significant recurrent somatic single nucleotide variants. Although devoid of recurrent single nucleotide variants and focal copy number aberrations, poor-prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype. Transcriptional silencing driven by CpG methylation converges exclusively on targets of the Polycomb repressive complex 2 which represses expression of differentiation genes through trimethylation of H3K27. CpG island methylator phenotype-positive hindbrain ependymomas are responsive to clinical drugs that target either DNA or H3K27 methylation both in vitro and in vivo. We conclude that epigenetic modifiers are the first rational therapeutic candidates for this deadly malignancy, which is epigenetically deregulated but genetically bland.
Published: 2014

3. How do parents and providers trade-off between disability and survival? Preferences in the treatment of pediatric medulloblastoma

Author: Khakban A, Mohammadi T, Lynd LD, Mabbott DJ, Bouffet E, Gastonguay L, Zafari Z, Malkin D, Taylor MD, and Marra CA
Subjects: Best Worst Scaling (BWS), Preference, Medulloblastoma, Trade-off, Cancer, Medicine (General), R5-920
Abstract: Amir Khakban,1 Tima Mohammadi,2 Larry D Lynd,1 Don J Mabbott,3,4 Eric Bouffet,5,6 Louise Gastonguay,1 Zafar Zafari,7 David Malkin,5,6 Michael D Taylor,8,9 Carlo A Marra10 1Collaboration for Outcomes Research and Evaluation, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC, Canada; 2Centre for Health Evaluation and Outcome Sciences, University of British Columbia, St Paul’s Hospital, Vancouver, BC, Canada; 3Department of Psychology, University of Toronto, Toronto, ON, Canada; 4Department of Psychology, The Hospital for Sick Children, Toronto, ON, Canada; 5Department of Pediatrics, University of Toronto, Toronto, ON, Canada; 6Department of Haematology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada; 7Health Policy and Management, Mailman School of Public Health, Columbia University, New York, NY, USA; 8Departments of Surgery, Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; 9Department of Neurosurgery, The Hospital for Sick Children, Toronto, ON, Canada; 10School of Pharmacy, University of Otago, Dunedin, New Zealand Objective: The aim of this study was to determine the preferences of parents with children with medulloblastoma and clinicians who manage this condition and their trade-offs between survival and disability using a best–worst scaling (BWS) choice experiment. Methods: Mixed methods were used to develop a BWS tool. Health professionals involved in the care of medulloblastoma patients were contacted through oncology networks in Canada. Parents of children diagnosed with brain tumors were recruited via two clinics in Vancouver and Toronto. The profile case BWS was used with each participant completing 12 choice profiles with the respondent indicating the best and worst features of each profile. Surveys were stratified into good, moderate, and poor prognosis based on the probability of survival presented. Paired model conditional logit analysis was used to generate quantitative preferences. Results: Fifty-four parents (80% female) and 176 providers (36% female, 79% oncologists) participated in this study. There were many similarities in the parents’ and providers’ preferences for treatment although the parents tended to value survival higher than disability while providers seemed to value the opposite. Specifically, providers were willing to take more risk of recurrence in a child with good prognosis compared to intermediate and poor prognosis. Also, parents were less willing to take more survival risks than providers when they had to trade-off between mild disability and survival rate. Conclusion: This study provides useful insights into the preferences of parents and health care providers, the stakeholders of a collaborative decision for the treatment of pediatric medulloblastoma, and compares their values and trade-offs between different levels of survival and disability. Keywords: best–worst scaling, BWS, preference, medulloblastoma, trade-off, cancer
Published: 2018

4. Global effort to evacuate Ukrainian children with cancer and blood disorders who have been affected by war

Author: Agulnik, A, Kizyma, R, Salek, M, Wlodarski, M, Pogorelyy, M, Oszer, A, Yakimkova, T, Nogovitsyna, Y, Dutkiewicz, M, Dalle, J, Dirksen, U, Eggert, A, Fernandez-Teijeiro, A, Greiner, J, Kraal, K, Mueller, A, Sramkova, L, Zecca, M, Wise, P, Mlynarski, W, Avula, M, Adyrov, M, Berlanga, P, Blackwood, C, Bouffet, E, Czauderna, P, de Koning, L, dos Reis Farinha, N, Foster, W, Graetz, D, Gupta, S, Holter, W, Hough, R, Kliuchkivska, K, Kolenova, A, Kolodrubiec, J, Moreira, D, Mukkada, S, Mykychak, I, Raciborska, A, Salman, Z, Sopilnyak, A, Tyupa, S, Vinitsky, A, Wobst, N, Miller, B, Rasul, S, Rodriguez-Galindo, C, Alanbousi, I, Alexander, S, Apel, A, Bal, W, Balwierz, W, Basset-Salom, L, Bastardo Blanco, D, Bauer, K, Bayazitov, I, Bhakta, N, Bien, E, Bieniek, K, Blair, S, Bodak, K, Bordeianu, I, Braganca, J, Bucurenci, M, Budny, E, Budzyn, A, Bumgardner, C, Burditt, R, Burnside Clapp, V, Bykov, V, Canete, A, Carnelli, M, Cela, E, Cepowska, Z, Chaber, R, Cherner-Drieux, A, Chubata, M, Clough, H, Czernicka - Siwecka, J, Czyzewski, K, Dashchakovska, O, Dembowska-Baginska, B, Derwich, K, Dommett, R, Dorosh, O, Drabko, K, Dragomir, M, Dworzak, M, Dyma, S, Earl, J, English, M, Evseev, D, Farren, B, Fedyk, N, Ferneza, S, Fox Irwin, L, Galazkowski, R, Ganieva, G, Garanzha, V, Gelman, M, Godzinski, J, Goeres, A, Golban, R, Griksaitis, M, Hampel, M, Hastings, S, Heenen, D, Hill, M, Holiuk, I, Hutnik, L, Irga-Jaworska, N, Istomin, O, Janczar, S, Kacharian, A, Kalwak, K, Karolczyk, G, Karpenko, N, Katsubo, H, Kaznowska, B, Kentsis, A, Ketteler, P, Kienesberger, A, Kiselev, R, Kizyma, Z, Klymniuk, H, Kostiuk, Y, Kowalik, T, Kozlova, O, Kozubenko, V, Kramar, T, Krawczuk-Rybak, M, Kulemzina, I, Kurkowska, P, Kuzyk, A, Ladenstein, R, Laguna, P, Lassaletta, A, Lehmberg, K, Leontieva, O, Liashenko, S, Loizou, L, Lucchetta, S, Lupo, M, Lysytsia, L, Lysytsia, O, Machnik, K, Mainland, J, Matczak, K, Matysiak, M, Mayeur, P, Minervina, A, Mishkova, V, Mizia-Malarz, A, Morales La Madrid, A, Moreno, L, Moskvin, V, Muszynska-Roslan, K, Nelson, A, Ociepa, T, Oltolini, S, Onipko, N, Pappas, A, Patel, A, Patrahau, A, Pauley, J, Pavlenko, Y, Pavlovych, A, Peregud-Pogorzelski, J, Perek-Polnik, M, Perez, V, Perez-Martinez, A, Pikman, Y, Pitozzi, G, Portugal, R, Posternak, V, Prete, A, Pritchard-Jones, K, Radaelli, A, Reeves, T, Reinhardt, D, Reshetnyak, A, Rider, A, Rizzari, C, Rizzi, D, Rodriguez Hermosillo, K, Ronenko, O, Rostowska, A, Rudko, L, Sakaan, F, Sakhar, N, Savva, N, Scaccaglia, D, Schaeffer, E, Schneider, C, Scobie, N, Semeniuk, O, Shevchyk, R, Shuler, A, Shvets, S, Skoczen, S, Smeal, W, Sokolowski, I, Sonkin, A, Stepanjuk, A, Spota, A, Sterba, J, Styczynski, J, Svintsova, O, Synyuta, A, Szczepanski, T, Szczucinski, P, Szmyd, B, Tasso Cereceda, M, Teliuk, A, Tomanek, I, Topping, P, Torrent, M, Trelinska, J, Troyanovska, O, Trubnikova, E, Tsurkan, L, Tsymbalyuk-Voloshyn, I, Urasinski, T, Urbanek-Dadela, A, Vasilieva, N, Vasilyeva, A, Verdu-Amoros, J, Vilcu-Bajurean, N, Vinitsky, L, Volpe, G, Vorobel, O, Wachowiak, J, Wasiak, M, Wiedower, L, Wuenschel, L, Wysocki, M, Yurieva, M, Zagurska, A, Zakharenko, S, Zakharenko, A, Zapotochna, K, Zawitkowska, J, Agulnik A., Kizyma R., Salek M., Wlodarski M. W., Pogorelyy M., Oszer A., Yakimkova T., Nogovitsyna Y., Dutkiewicz M., Dalle J. -H., Dirksen U., Eggert A., Fernandez-Teijeiro A., Greiner J., Kraal K., Mueller A., Sramkova L., Zecca M., Wise P. H., Mlynarski W., Avula M., Adyrov M. V., Berlanga P., Blackwood C. A., Bouffet E., Czauderna P. S., de Koning L. A., dos Reis Farinha N. J., Foster W. B., Graetz D. E., Gupta S., Holter W., Hough R. E., Kliuchkivska K., Kolenova A., Kolodrubiec J., Moreira D. C., Mukkada S. T., Mykychak I., Raciborska A., Salman Z. S., Sopilnyak A., Tyupa S., Vinitsky A., Wobst N. M., Miller B. A., Rasul S. S., Rodriguez-Galindo C., Alanbousi I., Alexander S. W., Apel A., Bal W. A., Balwierz W. A., Basset-Salom L., Bastardo Blanco D., Bauer K. J., Bayazitov I. T., Bhakta N. H., Bien E. I., Bieniek K. A., Blair S. J., Bodak K. I., Bordeianu I. M., Braganca J. M., Bucurenci M. S., Budny E. B., Budzyn A., Bumgardner C. C., Burditt R. N., Burnside Clapp V. G., Bykov V., Canete A., Carnelli M., Cela E., Cepowska Z. P., Chaber R., Cherner-Drieux A., Chubata M., Clough H. M., Czernicka - Siwecka J., Czyzewski K., Dashchakovska O., Dembowska-Baginska B. M., Derwich K., Dommett R., Dorosh O., Drabko K. A., Dragomir M. D., Dworzak M., Dyma S., Earl J. D., English M. W., Evseev D. A., Farren B. S., Fedyk N., Ferneza S., Fox Irwin L. E., Galazkowski R. M., Ganieva G., Garanzha V., Gelman M. S., Godzinski J. K., Goeres A. F., Golban R., Griksaitis M. J., Hampel M. A., Hastings S. G., Heenen D. L., Hill M. C., Holiuk I., Hutnik L. M., Irga-Jaworska N., Istomin O., Janczar S. L., Kacharian A., Kalwak K., Karolczyk G. M., Karpenko N. M., Katsubo H., Kaznowska B. J., Kentsis A., Ketteler P., Kienesberger A., Kiselev R., Kizyma Z., Klymniuk H., Kostiuk Y., Kowalik T., Kozlova O., Kozubenko V., Kramar T., Krawczuk-Rybak M., Kulemzina I., Kurkowska P., Kuzyk A. S., Ladenstein R. L., Laguna P. J., Lassaletta A., Lehmberg K., Leontieva O., Liashenko S., Loizou L. G., Lucchetta S. A., Lupo M. W., Lysytsia L., Lysytsia O., Machnik K. A., Mainland J. A., Matczak K. E., Matysiak M. J., Mayeur P., Minervina A. A., Mishkova V., Mizia-Malarz A. J., Morales La Madrid A., Moreno L., Moskvin V. P., Muszynska-Roslan K. M., Nelson A. J., Ociepa T., Oltolini S., Onipko N., Pappas A., Patel A. B., Patrahau A., Pauley J. L., Pavlenko Y., Pavlovych A., Peregud-Pogorzelski J., Perek-Polnik M., Perez V., Perez-Martinez A., Pikman Y., Pitozzi G., Portugal R. G., Posternak V. V., Prete A., Pritchard-Jones K., Radaelli A., Reeves T., Reinhardt D., Reshetnyak A. V., Rider A. J., Rizzari C., Rizzi D., Rodriguez Hermosillo K. G., Ronenko O., Rostowska A. O., Rudko L., Sakaan F. M., Sakhar N., Savva N. N., Scaccaglia D., Schaeffer E. H., Schneider C. U., Scobie N., Semeniuk O., Shevchyk R., Shuler A. I., Shvets S., Skoczen S. P., Smeal W. J., Sokolowski I., Sonkin A. A., Stepanjuk A. I., Spota A., Sterba J., Styczynski J., Svintsova O., Synyuta A. V., Szczepanski T., Szczucinski P. K., Szmyd B. M., Tasso Cereceda M., Teliuk A., Tomanek I., Topping P., Torrent M., Trelinska J., Troyanovska O., Trubnikova E., Tsurkan L. G., Tsymbalyuk-Voloshyn I., Urasinski T. F., Urbanek-Dadela A., Vasilieva N., Vasilyeva A., Verdu-Amoros J., Vilcu-Bajurean N., Vinitsky L., Volpe G., Vorobel O., Wachowiak J. T., Wasiak M. S., Wiedower L. A., Wuenschel L. I., Wysocki M. S., Yurieva M., Zagurska A., Zakharenko S. S., Zakharenko A. V., Zapotochna K., Zawitkowska J. E., Agulnik, A, Kizyma, R, Salek, M, Wlodarski, M, Pogorelyy, M, Oszer, A, Yakimkova, T, Nogovitsyna, Y, Dutkiewicz, M, Dalle, J, Dirksen, U, Eggert, A, Fernandez-Teijeiro, A, Greiner, J, Kraal, K, Mueller, A, Sramkova, L, Zecca, M, Wise, P, Mlynarski, W, Avula, M, Adyrov, M, Berlanga, P, Blackwood, C, Bouffet, E, Czauderna, P, de Koning, L, dos Reis Farinha, N, Foster, W, Graetz, D, Gupta, S, Holter, W, Hough, R, Kliuchkivska, K, Kolenova, A, Kolodrubiec, J, Moreira, D, Mukkada, S, Mykychak, I, Raciborska, A, Salman, Z, Sopilnyak, A, Tyupa, S, Vinitsky, A, Wobst, N, Miller, B, Rasul, S, Rodriguez-Galindo, C, Alanbousi, I, Alexander, S, Apel, A, Bal, W, Balwierz, W, Basset-Salom, L, Bastardo Blanco, D, Bauer, K, Bayazitov, I, Bhakta, N, Bien, E, Bieniek, K, Blair, S, Bodak, K, Bordeianu, I, Braganca, J, Bucurenci, M, Budny, E, Budzyn, A, Bumgardner, C, Burditt, R, Burnside Clapp, V, Bykov, V, Canete, A, Carnelli, M, Cela, E, Cepowska, Z, Chaber, R, Cherner-Drieux, A, Chubata, M, Clough, H, Czernicka - Siwecka, J, Czyzewski, K, Dashchakovska, O, Dembowska-Baginska, B, Derwich, K, Dommett, R, Dorosh, O, Drabko, K, Dragomir, M, Dworzak, M, Dyma, S, Earl, J, English, M, Evseev, D, Farren, B, Fedyk, N, Ferneza, S, Fox Irwin, L, Galazkowski, R, Ganieva, G, Garanzha, V, Gelman, M, Godzinski, J, Goeres, A, Golban, R, Griksaitis, M, Hampel, M, Hastings, S, Heenen, D, Hill, M, Holiuk, I, Hutnik, L, Irga-Jaworska, N, Istomin, O, Janczar, S, Kacharian, A, Kalwak, K, Karolczyk, G, Karpenko, N, Katsubo, H, Kaznowska, B, Kentsis, A, Ketteler, P, Kienesberger, A, Kiselev, R, Kizyma, Z, Klymniuk, H, Kostiuk, Y, Kowalik, T, Kozlova, O, Kozubenko, V, Kramar, T, Krawczuk-Rybak, M, Kulemzina, I, Kurkowska, P, Kuzyk, A, Ladenstein, R, Laguna, P, Lassaletta, A, Lehmberg, K, Leontieva, O, Liashenko, S, Loizou, L, Lucchetta, S, Lupo, M, Lysytsia, L, Lysytsia, O, Machnik, K, Mainland, J, Matczak, K, Matysiak, M, Mayeur, P, Minervina, A, Mishkova, V, Mizia-Malarz, A, Morales La Madrid, A, Moreno, L, Moskvin, V, Muszynska-Roslan, K, Nelson, A, Ociepa, T, Oltolini, S, Onipko, N, Pappas, A, Patel, A, Patrahau, A, Pauley, J, Pavlenko, Y, Pavlovych, A, Peregud-Pogorzelski, J, Perek-Polnik, M, Perez, V, Perez-Martinez, A, Pikman, Y, Pitozzi, G, Portugal, R, Posternak, V, Prete, A, Pritchard-Jones, K, Radaelli, A, Reeves, T, Reinhardt, D, Reshetnyak, A, Rider, A, Rizzari, C, Rizzi, D, Rodriguez Hermosillo, K, Ronenko, O, Rostowska, A, Rudko, L, Sakaan, F, Sakhar, N, Savva, N, Scaccaglia, D, Schaeffer, E, Schneider, C, Scobie, N, Semeniuk, O, Shevchyk, R, Shuler, A, Shvets, S, Skoczen, S, Smeal, W, Sokolowski, I, Sonkin, A, Stepanjuk, A, Spota, A, Sterba, J, Styczynski, J, Svintsova, O, Synyuta, A, Szczepanski, T, Szczucinski, P, Szmyd, B, Tasso Cereceda, M, Teliuk, A, Tomanek, I, Topping, P, Torrent, M, Trelinska, J, Troyanovska, O, Trubnikova, E, Tsurkan, L, Tsymbalyuk-Voloshyn, I, Urasinski, T, Urbanek-Dadela, A, Vasilieva, N, Vasilyeva, A, Verdu-Amoros, J, Vilcu-Bajurean, N, Vinitsky, L, Volpe, G, Vorobel, O, Wachowiak, J, Wasiak, M, Wiedower, L, Wuenschel, L, Wysocki, M, Yurieva, M, Zagurska, A, Zakharenko, S, Zakharenko, A, Zapotochna, K, Zawitkowska, J, Agulnik A., Kizyma R., Salek M., Wlodarski M. W., Pogorelyy M., Oszer A., Yakimkova T., Nogovitsyna Y., Dutkiewicz M., Dalle J. -H., Dirksen U., Eggert A., Fernandez-Teijeiro A., Greiner J., Kraal K., Mueller A., Sramkova L., Zecca M., Wise P. H., Mlynarski W., Avula M., Adyrov M. V., Berlanga P., Blackwood C. A., Bouffet E., Czauderna P. S., de Koning L. A., dos Reis Farinha N. J., Foster W. B., Graetz D. E., Gupta S., Holter W., Hough R. E., Kliuchkivska K., Kolenova A., Kolodrubiec J., Moreira D. C., Mukkada S. T., Mykychak I., Raciborska A., Salman Z. S., Sopilnyak A., Tyupa S., Vinitsky A., Wobst N. M., Miller B. A., Rasul S. S., Rodriguez-Galindo C., Alanbousi I., Alexander S. W., Apel A., Bal W. A., Balwierz W. A., Basset-Salom L., Bastardo Blanco D., Bauer K. J., Bayazitov I. T., Bhakta N. H., Bien E. I., Bieniek K. A., Blair S. J., Bodak K. I., Bordeianu I. M., Braganca J. M., Bucurenci M. S., Budny E. B., Budzyn A., Bumgardner C. C., Burditt R. N., Burnside Clapp V. G., Bykov V., Canete A., Carnelli M., Cela E., Cepowska Z. P., Chaber R., Cherner-Drieux A., Chubata M., Clough H. M., Czernicka - Siwecka J., Czyzewski K., Dashchakovska O., Dembowska-Baginska B. M., Derwich K., Dommett R., Dorosh O., Drabko K. A., Dragomir M. D., Dworzak M., Dyma S., Earl J. D., English M. W., Evseev D. A., Farren B. S., Fedyk N., Ferneza S., Fox Irwin L. E., Galazkowski R. M., Ganieva G., Garanzha V., Gelman M. S., Godzinski J. K., Goeres A. F., Golban R., Griksaitis M. J., Hampel M. A., Hastings S. G., Heenen D. L., Hill M. C., Holiuk I., Hutnik L. M., Irga-Jaworska N., Istomin O., Janczar S. L., Kacharian A., Kalwak K., Karolczyk G. M., Karpenko N. M., Katsubo H., Kaznowska B. J., Kentsis A., Ketteler P., Kienesberger A., Kiselev R., Kizyma Z., Klymniuk H., Kostiuk Y., Kowalik T., Kozlova O., Kozubenko V., Kramar T., Krawczuk-Rybak M., Kulemzina I., Kurkowska P., Kuzyk A. S., Ladenstein R. L., Laguna P. J., Lassaletta A., Lehmberg K., Leontieva O., Liashenko S., Loizou L. G., Lucchetta S. A., Lupo M. W., Lysytsia L., Lysytsia O., Machnik K. A., Mainland J. A., Matczak K. E., Matysiak M. J., Mayeur P., Minervina A. A., Mishkova V., Mizia-Malarz A. J., Morales La Madrid A., Moreno L., Moskvin V. P., Muszynska-Roslan K. M., Nelson A. J., Ociepa T., Oltolini S., Onipko N., Pappas A., Patel A. B., Patrahau A., Pauley J. L., Pavlenko Y., Pavlovych A., Peregud-Pogorzelski J., Perek-Polnik M., Perez V., Perez-Martinez A., Pikman Y., Pitozzi G., Portugal R. G., Posternak V. V., Prete A., Pritchard-Jones K., Radaelli A., Reeves T., Reinhardt D., Reshetnyak A. V., Rider A. J., Rizzari C., Rizzi D., Rodriguez Hermosillo K. G., Ronenko O., Rostowska A. O., Rudko L., Sakaan F. M., Sakhar N., Savva N. N., Scaccaglia D., Schaeffer E. H., Schneider C. U., Scobie N., Semeniuk O., Shevchyk R., Shuler A. I., Shvets S., Skoczen S. P., Smeal W. J., Sokolowski I., Sonkin A. A., Stepanjuk A. I., Spota A., Sterba J., Styczynski J., Svintsova O., Synyuta A. V., Szczepanski T., Szczucinski P. K., Szmyd B. M., Tasso Cereceda M., Teliuk A., Tomanek I., Topping P., Torrent M., Trelinska J., Troyanovska O., Trubnikova E., Tsurkan L. G., Tsymbalyuk-Voloshyn I., Urasinski T. F., Urbanek-Dadela A., Vasilieva N., Vasilyeva A., Verdu-Amoros J., Vilcu-Bajurean N., Vinitsky L., Volpe G., Vorobel O., Wachowiak J. T., Wasiak M. S., Wiedower L. A., Wuenschel L. I., Wysocki M. S., Yurieva M., Zagurska A., Zakharenko S. S., Zakharenko A. V., Zapotochna K., and Zawitkowska J. E.
Published: 2022

5. SIOP PODC-adapted treatment guidelines for craniopharyngioma in low- and middle-income settings

Author: Amayiri, N, Spitaels, A, Zaghloul, M, Figaji, A, Cavalheiro, S, Muller, HL, Elhassan, M, Parkes, J, Mushtaq, N, El Beltagy, M, Yousef, YA, Esiashvili, N, Sullivan, M, da Costa, MD, Dastoli, P, Mubarak, F, Bartels, U, Chamdine, O, Davidson, A, Musharbash, A, Alcasabas, P, Bouffet, E, Bailey, S, Amayiri, N, Spitaels, A, Zaghloul, M, Figaji, A, Cavalheiro, S, Muller, HL, Elhassan, M, Parkes, J, Mushtaq, N, El Beltagy, M, Yousef, YA, Esiashvili, N, Sullivan, M, da Costa, MD, Dastoli, P, Mubarak, F, Bartels, U, Chamdine, O, Davidson, A, Musharbash, A, Alcasabas, P, Bouffet, E, and Bailey, S
Abstract: Pediatric craniopharyngioma is a rare tumor with excellent survival but significant long-term morbidities due to the loco-regional tumor growth or secondary to its treatment. Visual impairment, panhypopituitarism, hypothalamic damage, and behavioral changes are among the main challenges. This tumor should be managed under the care of a multidisciplinary team to determine the optimum treatment within the available resources. This is particularly important for low middle-income countries where resources are variable. This report provides risk-stratified management guidelines for children diagnosed with craniopharyngioma in a resource-limited setting.
Published: 2023

6. Global characteristics and outcomes of SARS-CoV-2 infection in children and adolescents with cancer (GRCCC): a cohort study

Author: Mukkada, S, Bhakta, N, Chantada, G, Chen, Y, Vedaraju, Y, Faughnan, L, Homsi, M, Muniz-Talavera, H, Ranadive, R, Metzger, M, Friedrich, P, Agulnik, A, Jeha, S, Lam, C, Dalvi, R, Hessissen, L, Moreira, D, Santana, V, Sullivan, M, Bouffet, E, Caniza, M, Devidas, M, Pritchard-Jones, K, Rodriguez-Galindo, C, Ribelles, A, Balduzzi, A, Elhaddad, A, Casanovas, A, Garcia Velazquez, A, Laptsevich, A, Chang, A, F. Sampaio A., L, Gonzalez Prieto, A, Lassaletta, A, Suarez M, A, Alcasabas, A, Colita, A, Morales La Madrid, A, Samudio, A, Tondo, A, Colombini, A, Kattamis, A, Lopez Facundo, N, Bhattacharyya, A, Alimi, A, Phulpin, A, Vakrmanova, B, Aksoy, B, Brethon, B, Kobuin, J, Nolasco Monteiro, C, Paillard, C, Vezina, C, Ceyhun, B, Hentea, C, Meazza, C, Ortiz-Morales, D, Solorzano, R, Arce Cabrera, D, Zama, D, Ghosh, D, Ramirez-Rivera, D, Calle Jara, D, Janic, D, Rey Helo, E, Gouache, E, Guerrero Quiroz, E, Lopez, E, Thebault, E, Maradiegue, E, de Berranger, E, Ebeid, F, Galaverna, F, Antillon-Klussmann, F, Espinoza Chacur, F, Negro, F, Carraro, F, Compagno, F, Barriga, F, Tamayo Pedraza, G, Sanchez Fernandez, G, Naidu, G, Tokuc, G, Alias, H, B Segocio, H, Boudiaf, H, Asetre Luna, I, Maia, I, Astigarraga, I, Maza, I, Montoya Vasquez, J, Jazbec, J, Lazic, J, Beck Dean, J, Rouger-Gaudichon, J, Contreras Gonzalez, J, Huerta Aragones, J, Fuster, J, Quintana, J, Palma, J, Svojgr, K, Quintero, K, Malic Tudor, K, Georgantzi, K, P Schultz, K, Urena Horno, L, Fraquelli, L, Meneghello, L, Shalaby, L, Macias Mora, L, A Renner, L, Nunes Silva, L, Sisinni, L, Hammad, M, Fernandez Sanmartin, M, Zubieta A, C, Drozdowski, M, Kourti, M, Palladino, M, Miranda Madrazo, M, Poiree, M, Popova, M, Melgar, M, Baragano, M, Aviles-Robles, M, Provenzi, M, Mendes Lins, M, Fatih Orhan, M, Villarroel, M, Jeronimo, M, Varas Palma, M, Rafie Raza, M, M Justin, M, Shaheen, N, Dominguez-Pinilla, N, Whipple, N, Andre, N, Hrusak, O, Velasco Puyo, P, Zacasa Vargas, P, Olate Mellado, P, Yola Gassant, P, Diaz Romero, P, De Santis, R, Kebudi, R, Boranbayeva, R, Vasquez, R, Segura, R, Rosado, R, Gomez, S, Raimbault, S, Gunasekera, S, Makkeyah, S, Buyukkapu Bay, S, M Gomez, S, Bouttefroy, S, Islam, S, Abouelnaga, S, Torres, S, Cesaro, S, Nunes, S, Rouxinol, S, Bhaumik, S, Saliyeva, S, Inostroza, T, Velasquez, T, Hnin, T, Noren-Nystrom, U, Baretta, V, Jimenez-Antolinez, Y, Perez Alonso, V, Ayer Miller, V, Gandemer, V, Lotero, V, Mishkova, V, Gomez-Garcia, W, Margaryan, Y, Syed, Y, Mukkada S., Bhakta N., Chantada G. L., Chen Y., Vedaraju Y., Faughnan L., Homsi M. R., Muniz-Talavera H., Ranadive R., Metzger M., Friedrich P., Agulnik A., Jeha S., Lam C., Dalvi R., Hessissen L., Moreira D. C., Santana V. M., Sullivan M., Bouffet E., Caniza M. A., Devidas M., Pritchard-Jones K., Rodriguez-Galindo C., Ribelles A. J., Balduzzi A., Elhaddad A., Casanovas A., Garcia Velazquez A., Laptsevich A., Chang A., F. Sampaio A. L., Gonzalez Prieto A., Lassaletta A., Suarez M A., Alcasabas A. P., Colita A., Morales La Madrid A., Samudio A., Tondo A., Colombini A., Kattamis A., Lopez Facundo N. A., Bhattacharyya A., Alimi A., Phulpin A., Vakrmanova B., Aksoy B. A., Brethon B., Kobuin J. B., Nolasco Monteiro C., Paillard C., Vezina C., Ceyhun B., Hentea C., Meazza C., Ortiz-Morales D., Solorzano R. D., Arce Cabrera D., Zama D., Ghosh D., Ramirez-Rivera D., Calle Jara D. A., Janic D., Rey Helo E., Gouache E., Guerrero Quiroz E., Lopez E., Thebault E., Maradiegue E., de Berranger E., Ebeid F. S. E., Galaverna F., Antillon-Klussmann F., Espinoza Chacur F., Negro F. D., Carraro F., Compagno F., Barriga F., Tamayo Pedraza G., Sanchez Fernandez G., Naidu G., Tokuc G., Alias H., B Segocio H. G., Boudiaf H., Asetre Luna I., Maia I., Astigarraga I., Maza I., Montoya Vasquez J. E., Jazbec J., Lazic J., Beck Dean J., Rouger-Gaudichon J., Contreras Gonzalez J. C., Huerta Aragones J., Fuster J. L., Quintana J., Palma J., Svojgr K., Quintero K., Malic Tudor K., Georgantzi K., P Schultz K. A., Urena Horno L., Fraquelli L., Meneghello L., Shalaby L., Macias Mora L. L., A Renner L., Nunes Silva L., Sisinni L., Hammad M., Fernandez Sanmartin M., Zubieta A C. M., Drozdowski M. C., Kourti M., Palladino M. M., Miranda Madrazo M. R., Poiree M., Popova M., Melgar M., Baragano M., Aviles-Robles M. J., Provenzi M., Mendes Lins M., Fatih Orhan M., Villarroel M., Jeronimo M., Varas Palma M., Rafie Raza M., M Justin M., Shaheen N., Dominguez-Pinilla N., Whipple N. S., Andre N., Hrusak O., Velasco Puyo P., Zacasa Vargas P., Olate Mellado P., Yola Gassant P., Diaz Romero P., De Santis R., Kebudi R., Boranbayeva R., Vasquez R., Segura R. A., Rosado R. E., Gomez S., Raimbault S., Gunasekera S., Makkeyah S. M., Buyukkapu Bay S., M Gomez S., Bouttefroy S., Islam S., Abouelnaga S., Torres S. F., Cesaro S., Nunes S., Rouxinol S., Bhaumik S., Saliyeva S., Inostroza T., Velasquez T., Hnin T. M., Noren-Nystrom U., Baretta V., Jimenez-Antolinez Y. V., Perez Alonso V., Ayer Miller V., Gandemer V., Lotero V., Mishkova V., Gomez-Garcia W., Margaryan Y., Syed Y., Mukkada, S, Bhakta, N, Chantada, G, Chen, Y, Vedaraju, Y, Faughnan, L, Homsi, M, Muniz-Talavera, H, Ranadive, R, Metzger, M, Friedrich, P, Agulnik, A, Jeha, S, Lam, C, Dalvi, R, Hessissen, L, Moreira, D, Santana, V, Sullivan, M, Bouffet, E, Caniza, M, Devidas, M, Pritchard-Jones, K, Rodriguez-Galindo, C, Ribelles, A, Balduzzi, A, Elhaddad, A, Casanovas, A, Garcia Velazquez, A, Laptsevich, A, Chang, A, F. Sampaio A., L, Gonzalez Prieto, A, Lassaletta, A, Suarez M, A, Alcasabas, A, Colita, A, Morales La Madrid, A, Samudio, A, Tondo, A, Colombini, A, Kattamis, A, Lopez Facundo, N, Bhattacharyya, A, Alimi, A, Phulpin, A, Vakrmanova, B, Aksoy, B, Brethon, B, Kobuin, J, Nolasco Monteiro, C, Paillard, C, Vezina, C, Ceyhun, B, Hentea, C, Meazza, C, Ortiz-Morales, D, Solorzano, R, Arce Cabrera, D, Zama, D, Ghosh, D, Ramirez-Rivera, D, Calle Jara, D, Janic, D, Rey Helo, E, Gouache, E, Guerrero Quiroz, E, Lopez, E, Thebault, E, Maradiegue, E, de Berranger, E, Ebeid, F, Galaverna, F, Antillon-Klussmann, F, Espinoza Chacur, F, Negro, F, Carraro, F, Compagno, F, Barriga, F, Tamayo Pedraza, G, Sanchez Fernandez, G, Naidu, G, Tokuc, G, Alias, H, B Segocio, H, Boudiaf, H, Asetre Luna, I, Maia, I, Astigarraga, I, Maza, I, Montoya Vasquez, J, Jazbec, J, Lazic, J, Beck Dean, J, Rouger-Gaudichon, J, Contreras Gonzalez, J, Huerta Aragones, J, Fuster, J, Quintana, J, Palma, J, Svojgr, K, Quintero, K, Malic Tudor, K, Georgantzi, K, P Schultz, K, Urena Horno, L, Fraquelli, L, Meneghello, L, Shalaby, L, Macias Mora, L, A Renner, L, Nunes Silva, L, Sisinni, L, Hammad, M, Fernandez Sanmartin, M, Zubieta A, C, Drozdowski, M, Kourti, M, Palladino, M, Miranda Madrazo, M, Poiree, M, Popova, M, Melgar, M, Baragano, M, Aviles-Robles, M, Provenzi, M, Mendes Lins, M, Fatih Orhan, M, Villarroel, M, Jeronimo, M, Varas Palma, M, Rafie Raza, M, M Justin, M, Shaheen, N, Dominguez-Pinilla, N, Whipple, N, Andre, N, Hrusak, O, Velasco Puyo, P, Zacasa Vargas, P, Olate Mellado, P, Yola Gassant, P, Diaz Romero, P, De Santis, R, Kebudi, R, Boranbayeva, R, Vasquez, R, Segura, R, Rosado, R, Gomez, S, Raimbault, S, Gunasekera, S, Makkeyah, S, Buyukkapu Bay, S, M Gomez, S, Bouttefroy, S, Islam, S, Abouelnaga, S, Torres, S, Cesaro, S, Nunes, S, Rouxinol, S, Bhaumik, S, Saliyeva, S, Inostroza, T, Velasquez, T, Hnin, T, Noren-Nystrom, U, Baretta, V, Jimenez-Antolinez, Y, Perez Alonso, V, Ayer Miller, V, Gandemer, V, Lotero, V, Mishkova, V, Gomez-Garcia, W, Margaryan, Y, Syed, Y, Mukkada S., Bhakta N., Chantada G. L., Chen Y., Vedaraju Y., Faughnan L., Homsi M. R., Muniz-Talavera H., Ranadive R., Metzger M., Friedrich P., Agulnik A., Jeha S., Lam C., Dalvi R., Hessissen L., Moreira D. C., Santana V. M., Sullivan M., Bouffet E., Caniza M. A., Devidas M., Pritchard-Jones K., Rodriguez-Galindo C., Ribelles A. J., Balduzzi A., Elhaddad A., Casanovas A., Garcia Velazquez A., Laptsevich A., Chang A., F. Sampaio A. L., Gonzalez Prieto A., Lassaletta A., Suarez M A., Alcasabas A. P., Colita A., Morales La Madrid A., Samudio A., Tondo A., Colombini A., Kattamis A., Lopez Facundo N. A., Bhattacharyya A., Alimi A., Phulpin A., Vakrmanova B., Aksoy B. A., Brethon B., Kobuin J. B., Nolasco Monteiro C., Paillard C., Vezina C., Ceyhun B., Hentea C., Meazza C., Ortiz-Morales D., Solorzano R. D., Arce Cabrera D., Zama D., Ghosh D., Ramirez-Rivera D., Calle Jara D. A., Janic D., Rey Helo E., Gouache E., Guerrero Quiroz E., Lopez E., Thebault E., Maradiegue E., de Berranger E., Ebeid F. S. E., Galaverna F., Antillon-Klussmann F., Espinoza Chacur F., Negro F. D., Carraro F., Compagno F., Barriga F., Tamayo Pedraza G., Sanchez Fernandez G., Naidu G., Tokuc G., Alias H., B Segocio H. G., Boudiaf H., Asetre Luna I., Maia I., Astigarraga I., Maza I., Montoya Vasquez J. E., Jazbec J., Lazic J., Beck Dean J., Rouger-Gaudichon J., Contreras Gonzalez J. C., Huerta Aragones J., Fuster J. L., Quintana J., Palma J., Svojgr K., Quintero K., Malic Tudor K., Georgantzi K., P Schultz K. A., Urena Horno L., Fraquelli L., Meneghello L., Shalaby L., Macias Mora L. L., A Renner L., Nunes Silva L., Sisinni L., Hammad M., Fernandez Sanmartin M., Zubieta A C. M., Drozdowski M. C., Kourti M., Palladino M. M., Miranda Madrazo M. R., Poiree M., Popova M., Melgar M., Baragano M., Aviles-Robles M. J., Provenzi M., Mendes Lins M., Fatih Orhan M., Villarroel M., Jeronimo M., Varas Palma M., Rafie Raza M., M Justin M., Shaheen N., Dominguez-Pinilla N., Whipple N. S., Andre N., Hrusak O., Velasco Puyo P., Zacasa Vargas P., Olate Mellado P., Yola Gassant P., Diaz Romero P., De Santis R., Kebudi R., Boranbayeva R., Vasquez R., Segura R. A., Rosado R. E., Gomez S., Raimbault S., Gunasekera S., Makkeyah S. M., Buyukkapu Bay S., M Gomez S., Bouttefroy S., Islam S., Abouelnaga S., Torres S. F., Cesaro S., Nunes S., Rouxinol S., Bhaumik S., Saliyeva S., Inostroza T., Velasquez T., Hnin T. M., Noren-Nystrom U., Baretta V., Jimenez-Antolinez Y. V., Perez Alonso V., Ayer Miller V., Gandemer V., Lotero V., Mishkova V., Gomez-Garcia W., Margaryan Y., and Syed Y.
Abstract: Background: Previous studies have shown that children and adolescents with COVID-19 generally have mild disease. Children and adolescents with cancer, however, can have severe disease when infected with respiratory viruses. In this study, we aimed to understand the clinical course and outcomes of SARS-CoV-2 infection in children and adolescents with cancer. Methods: We did a cohort study with data from 131 institutions in 45 countries. We created the Global Registry of COVID-19 in Childhood Cancer to capture de-identified data pertaining to laboratory-confirmed SARS-CoV-2 infections in children and adolescents (<19 years) with cancer or having received a haematopoietic stem-cell transplantation. There were no centre-specific exclusion criteria. The registry was disseminated through professional networks through email and conferences and health-care providers were invited to submit all qualifying cases. Data for demographics, oncological diagnosis, clinical course, and cancer therapy details were collected. Primary outcomes were disease severity and modification to cancer-directed therapy. The registry remains open to data collection. Findings: Of 1520 submitted episodes, 1500 patients were included in the study between April 15, 2020, and Feb 1, 2021. 1319 patients had complete 30-day follow-up. 259 (19·9%) of 1301 patients had a severe or critical infection, and 50 (3·8%) of 1319 died with the cause attributed to COVID-19 infection. Modifications to cancer-directed therapy occurred in 609 (55·8%) of 1092 patients receiving active oncological treatment. Multivariable analysis revealed several factors associated with severe or critical illness, including World Bank low-income or lower-middle-income (odds ratio [OR] 5·8 [95% CI 3·8–8·8]; p<0·0001) and upper-middle-income (1·6 [1·2–2·2]; p=0·0024) country status; age 15–18 years (1·6 [1·1–2·2]; p=0·013); absolute lymphocyte count of 300 or less cells per mm3 (2·5 [1·8–3·4]; p<0·0001), absolute neutrophil count
Published: 2021

7. Radiomics of Pediatric Low-Grade Gliomas: Toward a Pretherapeutic Differentiation of BRAF-Mutated and BRAF-Fused Tumors

Author: Wagner, M W, Hainc, N, Khalvati, F, Namdar, K, Figueiredo, L, Sheng, M, Laughlin, S, Shroff, M M, Bouffet, E, Tabori, U, Hawkins, C, Yeom, K W, Ertl-Wagner, B B, and University of Zurich
Subjects: Oncology, medicine.medical_specialty, medicine.diagnostic_test, Receiver operating characteristic, business.industry, Area under the curve, 610 Medicine & health, Retrospective cohort study, Fluid-attenuated inversion recovery, Confidence interval, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Text mining, 10043 Clinic for Neuroradiology, Internal medicine, Cohort, Biopsy, medicine, Radiology, Nuclear Medicine and imaging, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: BACKGROUND AND PURPOSE B-Raf proto-oncogene, serine/threonine kinase (BRAF) status has important implications for prognosis and therapy of pediatric low-grade gliomas. Currently, BRAF status classification relies on biopsy. Our aim was to train and validate a radiomics approach to predict BRAF fusion and BRAF V600E mutation. MATERIALS AND METHODS In this bi-institutional retrospective study, FLAIR MR imaging datasets of 115 pediatric patients with low-grade gliomas from 2 children's hospitals acquired between January 2009 and January 2016 were included and analyzed. Radiomics features were extracted from tumor segmentations, and the predictive model was tested using independent training and testing datasets, with all available tumor types. The model was selected on the basis of a grid search on the number of trees, opting for the best split for a random forest. We used the area under the receiver operating characteristic curve to evaluate model performance. RESULTS The training cohort consisted of 94 pediatric patients with low-grade gliomas (mean age, 9.4 years; 45 boys), and the external validation cohort comprised 21 pediatric patients with low-grade gliomas (mean age, 8.37 years; 12 boys). A 4-fold cross-validation scheme predicted BRAF status with an area under the curve of 0.75 (SD, 0.12) (95% confidence interval, 0.62-0.89) on the internal validation cohort. By means of the optimal hyperparameters determined by 4-fold cross-validation, the area under the curve for the external validation was 0.85. Age and tumor location were significant predictors of BRAF status (P values = .04 and
Published: 2021
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8. Pediatric pineoblastoma: A pooled outcome study of North American and Australian therapeutic data

Author: Hansford, JR, Huang, J, Endersby, R, Dodgshun, AJ, Li, BK, Hwang, E, Leary, S, Gajjar, A, Von Hoff, K, Wells, O, Wray, A, Kotecha, RS, Raleigh, DR, Stoller, S, Mueller, S, Schild, SE, Bandopadhayay, P, Fouladi, M, Bouffet, E, Huang, A, Onar-Thomas, A, Gottardo, NG, Hansford, JR, Huang, J, Endersby, R, Dodgshun, AJ, Li, BK, Hwang, E, Leary, S, Gajjar, A, Von Hoff, K, Wells, O, Wray, A, Kotecha, RS, Raleigh, DR, Stoller, S, Mueller, S, Schild, SE, Bandopadhayay, P, Fouladi, M, Bouffet, E, Huang, A, Onar-Thomas, A, and Gottardo, NG
Abstract: BACKGROUND: Pineoblastoma is a rare brain tumor usually diagnosed in children. Given its rarity, no pineoblastoma-specific trials have been conducted. Studies have included pineoblastoma accruing for other embryonal tumors over the past 30 years. These included only occasional children with pineoblastoma, making clinical features difficult to interpret and determinants of outcome difficult to ascertain. PATIENTS AND METHODS: Centrally or independently reviewed series with treatment and survival data from North American and Australian cases were pooled. To investigate associations between variables, Fisher's exact tests, Wilcoxon-Mann-Whitney tests, and Spearman correlations were used. Kaplan-Meier plots, log-rank tests, and Cox proportional hazards models were used in survival analyses. RESULTS: We describe a pooled cohort of 178 pineoblastoma cases from Children's Oncology Group (n = 82) and institutional series (n = 96) over 30 years. Children <3 years of age have significantly worse survival compared to older children, with 5-year progression-free survival (PFS) and overall survival (OS) estimates of 13.5 ± 5.1% and 16.2 ± 5.3%, respectively, compared with 60.8 ± 5.6% and 67.3 ± 5.0% for ≥3 years old (both P < .0001). Multivariable analysis showed male sex was associated with worse PFS in children <3 years of age (hazard ratio [HR] 3.93, 95% CI 1.80-8.55; P = .0006), suggestive of sex-specific risks needing future validation. For children ≥3 years of age, disseminated disease at diagnosis was significantly associated with an inferior 5-year PFS of 39.2 ± 9.7% (HR 2.88, 95% CI 1.52-5.45; P = .0012) and 5-year OS of 49.8 ± 9.1% (HR 2.87, 95% CI 1.49-5.53; P = .0016). CONCLUSION: Given the rarity of this tumor, prospective, collaborative international studies will be vital to improving the long-term survival of these patients.
Published: 2022

9. Genomic predictors of response to PD-1 inhibition in children with germline DNA replication repair deficiency

Author: Das, A, Sudhaman, S, Morgenstern, D, Coblentz, A, Chung, J, Stone, SC, Alsafwani, N, Liu, ZA, Abu Al Karsaneh, O, Soleimani, S, Ladany, H, Chen, D, Zatzman, M, Cabric, V, Nobre, L, Bianchi, V, Edwards, M, Nahum, LCS, Ercan, AB, Nabbi, A, Constantini, S, Dvir, R, Yalon-Oren, M, Campino, GA, Caspi, S, Larouche, V, Reddy, A, Osborn, M, Mason, G, Lindhorst, S, Bronsema, A, Magimairajan, V, Opocher, E, De Mola, RL, Sabel, M, Frojd, C, Sumerauer, D, Samuel, D, Cole, K, Chiaravalli, S, Massimino, M, Tomboc, P, Ziegler, DS, George, B, Van Damme, A, Hijiya, N, Gass, D, McGee, RB, Mordechai, O, Bowers, DC, Laetsch, TW, Lossos, A, Blumenthal, DT, Sarosiek, T, Yen, LY, Knipstein, J, Bendel, A, Hoffman, LM, Luna-Fineman, S, Zimmermann, S, Scheers, I, Nichols, KE, Zapotocky, M, Hansford, JR, Maris, JM, Dirks, P, Taylor, MD, Kulkarni, A, Shroff, M, Tsang, DS, Villani, A, Xu, W, Aronson, M, Durno, C, Shlien, A, Malkin, D, Getz, G, Maruvka, YE, Ohashi, PS, Hawkins, C, Pugh, TJ, Bouffet, E, Tabori, U, Das, A, Sudhaman, S, Morgenstern, D, Coblentz, A, Chung, J, Stone, SC, Alsafwani, N, Liu, ZA, Abu Al Karsaneh, O, Soleimani, S, Ladany, H, Chen, D, Zatzman, M, Cabric, V, Nobre, L, Bianchi, V, Edwards, M, Nahum, LCS, Ercan, AB, Nabbi, A, Constantini, S, Dvir, R, Yalon-Oren, M, Campino, GA, Caspi, S, Larouche, V, Reddy, A, Osborn, M, Mason, G, Lindhorst, S, Bronsema, A, Magimairajan, V, Opocher, E, De Mola, RL, Sabel, M, Frojd, C, Sumerauer, D, Samuel, D, Cole, K, Chiaravalli, S, Massimino, M, Tomboc, P, Ziegler, DS, George, B, Van Damme, A, Hijiya, N, Gass, D, McGee, RB, Mordechai, O, Bowers, DC, Laetsch, TW, Lossos, A, Blumenthal, DT, Sarosiek, T, Yen, LY, Knipstein, J, Bendel, A, Hoffman, LM, Luna-Fineman, S, Zimmermann, S, Scheers, I, Nichols, KE, Zapotocky, M, Hansford, JR, Maris, JM, Dirks, P, Taylor, MD, Kulkarni, A, Shroff, M, Tsang, DS, Villani, A, Xu, W, Aronson, M, Durno, C, Shlien, A, Malkin, D, Getz, G, Maruvka, YE, Ohashi, PS, Hawkins, C, Pugh, TJ, Bouffet, E, and Tabori, U
Abstract: Cancers arising from germline DNA mismatch repair deficiency or polymerase proofreading deficiency (MMRD and PPD) in children harbour the highest mutational and microsatellite insertion-deletion (MS-indel) burden in humans. MMRD and PPD cancers are commonly lethal due to the inherent resistance to chemo-irradiation. Although immune checkpoint inhibitors (ICIs) have failed to benefit children in previous studies, we hypothesized that hypermutation caused by MMRD and PPD will improve outcomes following ICI treatment in these patients. Using an international consortium registry study, we report on the ICI treatment of 45 progressive or recurrent tumors from 38 patients. Durable objective responses were observed in most patients, culminating in a 3 year survival of 41.4%. High mutation burden predicted response for ultra-hypermutant cancers (>100 mutations per Mb) enriched for combined MMRD + PPD, while MS-indels predicted response in MMRD tumors with lower mutation burden (10-100 mutations per Mb). Furthermore, both mechanisms were associated with increased immune infiltration even in 'immunologically cold' tumors such as gliomas, contributing to the favorable response. Pseudo-progression (flare) was common and was associated with immune activation in the tumor microenvironment and systemically. Furthermore, patients with flare who continued ICI treatment achieved durable responses. This study demonstrates improved survival for patients with tumors not previously known to respond to ICI treatment, including central nervous system and synchronous cancers, and identifies the dual roles of mutation burden and MS-indels in predicting sustained response to immunotherapy.
Published: 2022

10. MEDB-49. Relapsed SHH medulloblastomas in young children. Are there alternatives to full-dose craniospinal irradiation?

Author: Erker, C, Craig, B, Bailey, S, Massimino, M, Larouche, V, L Finlay, J, Kline, C, Michaiel, G, Margol, A, Cohen, K, Cacciotti, C, Harrods, V, Doris, K, AbdelBaki, M, Amayiri, N, Wang, Z, Hansford, J, Hukin, J, Salloum, R, Hoffman, L, Muray, J, Ginn, K, Zapotocky, Z, Baroni, L, Ramaswamy, V, Gilheens, S, Aguiera, D, Mazewski, C, Shah, S, Strother, D, Muller, S, Gajjar, A, Northcott, P, Clifford, S, Robinson, G, Bouffet, E, Lafay-Cousin, L, Erker, C, Craig, B, Bailey, S, Massimino, M, Larouche, V, L Finlay, J, Kline, C, Michaiel, G, Margol, A, Cohen, K, Cacciotti, C, Harrods, V, Doris, K, AbdelBaki, M, Amayiri, N, Wang, Z, Hansford, J, Hukin, J, Salloum, R, Hoffman, L, Muray, J, Ginn, K, Zapotocky, Z, Baroni, L, Ramaswamy, V, Gilheens, S, Aguiera, D, Mazewski, C, Shah, S, Strother, D, Muller, S, Gajjar, A, Northcott, P, Clifford, S, Robinson, G, Bouffet, E, and Lafay-Cousin, L
Abstract: BACKGROUND/RATIONAL: Following initial irradiation sparing therapy, many young children with relapsed medulloblastoma can be salvaged with craniospinal irradiation (CSI). However, the interval to relapse is short and neurocognitive sequelae remain a major concern. The contribution of molecular subgrouping may help refine indications and modalities of salvage strategies in this population. METHOD: From a cohort of 151 young children with molecularly characterized relapsed medulloblastoma, subset analysis of the SHH medulloblastoma was conducted to describe the practice of salvage radiotherapy and associated post-relapse survival (PRS). RESULTS: Sixty-seven SHH medulloblastoma patients (46 M0; 54 GTR; 11 non-ND/MBEN) received salvage therapy with curative intent. Before relapse, 54 (80.6%) received conventional chemotherapy (CC), 13 (19.4%) high-dose chemotherapy (HDC), while seven had additional focal radiotherapy (fRT). Median time to relapse was 11.1 months (range 3.8-41.0) and 43.3% were localized. Thirty patients (16 localized relapse) underwent surgery. Forty-seven (71.2%) received salvage radiotherapy (20 with CC; 10 with HDC; 15 alone, two unknown). CSI and fRT accounted for 82% and 18% respectively. CSI median dose was 36Gy (range 18-39Gy). Ten patients (eight with localized relapse) received CSI doses ≤23.4Gy. Nineteen patients (28.8%) did not receive any radiotherapy (nine HDC; 10 CC only). Radiotherapy was associated with better 3-year PRS (73.0% versus 36.1%; p=0.001). All patients treated with CSI ≤ 23.4Gy were alive at median follow-up of 69 months(24-142). Six of nine patients treated with HDC without irradiation were alive at last follow-up. Sixty-three percent of patients received reduced dose CSI(≤23.4Gy), fRT, or no radiotherapy, and their PRS did not significantly differ from those who received CSI ≥ 30.6Gy (p = 0.54). CONCLUSION: While salvage CSI provided PRS benefit in this SHH medulloblastoma cohort, we report the use of reduced salva
Published: 2022

11. Hippocampal Sparing Radiotherapy in adults with Primary Brain Tumors: A comparative planning and dosimetric study using IMPT, IMRT and 3DCRT

Author: 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, 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D, Rockhill, J, Fink, J, Chang, L, Halasz, L. 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E, Fukuo, Y, Kanemitsu, T, Fukumura, M, Kosaka, T, Hiramatsu, R, Kuroiwa, T, Miyatake, S, Kawabata, S, Kirihata, M, Goldfinger, J.A, Garabalino, M.A, Pozzi, E.C, Ramos, P, De Leo, L.N, Yu, Q, Engelbrecht, M, Sioen, S, Miles, X, Nair, S, Ndimba, R, Baeyens, A, Vandevoorde, C, Buizza, G, Meng, J, Takai, N, Ogami, M, Nakamura, S, Ohba, Y, Liu, R.F, Zhang, Q.N, Wang, X.H, Luo, H.T, Kong, Y.R, Jansen, J, Tirinato, L, Marafioti, M.G, Hanley, R, Yao, X.Q, Pagliari, F, Huang, C.Y, Wong, W.K.R, Ho, Y.W, Nam, P.H, Koryakin, S.N, Troshina, M.V, Koryakina, E.V, Potetnya, V.I, Baykuzina, R.M, Lychagin, A.A, Ulyanenko, S.E, Molinelli, S, Giuseppe, M, Tran, L, Bolst, D, James, B, Steinsberger, T, Alliger, C, Dahle, T.J, Rusten, E, Wright, P, Forsback, S, Silvoniemi, A, Minn, H, Andersson, S, Buti, G, Barragán Montero, A.M, Vasquez-Osario, E, Sabouri, P, Nkenge, K, Yi, B, Burigo, L, Greilich, S, Thomas, R, Clark, C, Lourenco, A, Oancea, C, Granja, C, Kodaira, S, Coplan, M, Graybill, J, Lutz, L, Shahi, C, Su, J.J, Thompson, A, Romano, F, Shipley, D, Hong, T.S, Labarbe, R, Wolfgang, J.A, Meyer, S, Bortfeldt, J, Lämmer, P, Schnürle, K, Peters, N, Möhler, C, Hofmann, C, Koschik, A, Bryce-Atkinson, A, Van Nugteren, J, De Rijk, G, Kirby, G, Dutoit, B, Vignati, A, Ahmadi Ganjeh, Z, Fausti, F, Giordanengo, S, Hammad Ali, O, Sacchi, R, Shakarami, Z, Cirio, R, Inoue, J, Tachibana, M, Shimizu, Y, Ochi, T, Amano, D, Miyashita, T, Cooley, J, Nyamane, S, Zwart, T, Wagner, M, Lu, M, Rosenthal, S, Hashimoto, T, Katoh, N, Tamura, H, Emert, F, Missimer, J, Eichenberger, P, Gmuer, C, Spengler, C, Kamp, F, Hofmaier, J, Reiner, M, Belka, C, Van Ooteghem, G, Dasnoy-Sumell, D, Geets, X, Chen, C.C, Galbreath, G, Shmulenson, R, Pinheiro de Almeida, I, van Elmpt, W, Vilches Freixas, G, Unipan, M, Verhaegen, F, Bosmans, G, Garcia, G, Cevallos Robalino, L, Guzman-Garcia, K, Vega-Carrillo, H.R, Gomez-Ros, J.M, Gallego, E, Hintenlang, K, Martin, M, Gupta, N, Meissner, J, Smathers, J, Ainsley, C, Yin, L, Jagt, T, Breedveld, S, van Haveren, R, Nout, R, Astreinidou, E, Staring, M, Heijmen, B, Hoogeman, M, Stokes, W, Matter, M, Nenoff, L, Toramatsu, C, Wakizaka, H, Nitta, M, Nishikido, F, Hirano, Y, Yoshida, E, Miller, J, Maris, A, Kalle, R, Franco, G, Kierkels, R.G.J, van den Hoek, J.G.M, Bijl, H.P, Dieters, M, Steenbakkers, R.J.H.M, Dejongh, F, DeJongh, E, Rykalin, V, Karonis, N, Ordonez, C, Duffin, K, Winans, J, Neph, R, Sanchez-Parcerisa, D, Lopez-Aguirre, M, Dolcet Llerena, A, Udias, J, Oxley, D, Besson, R, Meier, G, Nanz, A, Schorta, M, Fleury, E, Trnková, P, Erdal, E, Hassan, K, Beenakker, J.W, Pignol, J.P, Matysiak, W, Tian, L, Zepter, S, Winterhalter, C, Shim, S, Gouldstone, C, Trnkova, P, Vatnitsky, S, Liu, K, Li, E, Zhuangming, S, Lowenstein, J, De Wilde, O, Bossier, V, Lerot, X, Pouppez, A, Xx, X, Verburg, J, Hueso-Gonzalez, F, Ruggieri, T, Amato, C, Ghesquiere-Dierickx, L, Felix-Bautista, R, Deville, C, Barsky, A, Vapiwala, N, Mohamad, O, Tabuchi, T, Nitta, Y, Nomoto, A, Kasuya, G, 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

12. Clinical and molecular characteristics of pediatric low-grade glioma complicated with ventriculo-peritoneal shunt related ascites

Author: Solano-Páez P, Fonseca A, Baroni LV, Amayiri N, Pérez-Somarriba Moreno Marta, Freytes C, Quiroga E, Rivero M, Márquez J, Lassaletta Á, and Bouffet E
Subjects: Pediatric low grade glioma, Ascites, MAPK pathway, Ventriculo peritoneal shunt, RAS
Abstract: Introduction Ventriculo-peritoneal shunt (VPS) related ascites is a rare complication of pediatric low grade gliomas (pLGG). Physiopathology of this complication is not fully understood and there is paucity of data regarding the molecular profile of pLGG gliomas complicating with ascites and the optimal management of this unusual event. Methods International multi-institutional retrospective analysis of patients diagnosed with BRAF altered pLGG and ascites arising as a complication of VPS. Demographics, tumor characteristics, therapeutic approaches and outcomes were recorded. Results Nineteen patients were identified. Median age at diagnosis was 14 months (R: 2-144). Most patients (17; 89.4%) presented with lesions involving the optic pathway. Mean tumor standard volume was 34.8 cm(2) (R: 12.5-85.4). Pilocytic Astrocytoma was the most frequent histological diagnosis (14;7 3.7%). Eight (42.1%) tumors harbored BRAF V600-E mutation and seven (36.8%) KIAA1549 fusion. The onset of ascites was documented at a median time of 5 months following VPS insertion. Four (21%) patients were managed with paracentesis only, 7(36.8%) required both paracentesis and shunt diversion, 7(36.8%) required only a shunt diversion and 1 (5.2%) patient was managed conservatively. Chemotherapy regimen was changed in 10 patients following ascites. Eight patients received targeted therapy (4 dabrafenib/4 trametinib) and 5 were radiated. There were eleven survivors with a median OS of 69 months (R: 3-144). Conclusions Ascites is an early feature in the clinical course of young patients with midline BRAF altered pLGG, with high mortality rate observed in our cohort. The hypothesis of ascites as an adverse prognostic factor in pLGG warrants further prospective research.
Published: 2022

13. NASPGHAN Annual Meeting Abstracts

Author: Durno, C, Ercan, A, Aronson, M, Villani, A, Bouffet, E, Erdman, S, Scheers, Isabelle, Bronsema, A, Tabori, U, UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, and UCL - (SLuc) Service de gastro-entérologie et hépatologie pédiatrique
Subjects: and Child Health, Pediatrics, Perinatology and Child Health, Gastroenterology, Pediatrics, Perinatology
Abstract: Background: Constitutional mismatch repair deficiency syndrome (CMMRD) is a severe cancer predisposition syndrome causing intestinal polyposis and a high risk of early onset gastrointestinal, brain, and hematological cancers. International guidelines for surveillance exist but no study has systematically evaluated the efficacy of this protocol. Aim: Our aim was to determine if surveillance affects outcome. The primary outcome measure was overall survival. The secondary outcome measure was detection of new cancers. Methods: Patients referred to the International Replication Repair Consortium undergo genetic testing to confirm CMMRD. All individuals were diagnosed with CMMRD through diagnostic criteria by the genetic counsellor at the consortium. A surveillance protocol consisting of frequent biochemical, endoscopic and imaging studies was recommended and initiated internationally on Jan 1, 2012. Protocol included upper endoscopy, colonoscopy, video capsule endoscopy and/or magnetic resonance enterography, and brain MRI. Whole-body MRI was recommended as of Jan 1, 2018. Surveillance questionnaire was sent to the responsible physician with diagnostic fields completed by the registry coordinator as a double check of reliability. Survival analyses was completed using an as-treated approach. Results: Cancer and surveillance data was collected from 64 (50%) of 127 CMMRD individuals registered in the Consortium from 41 countries. There were 114 tumours reported in 60 patients including 55 brain, 28 gastrointestinal (GI), 17 hematological and 14 other malignancies. Surveillance data was available on 110 cancers; 16 were incidental cancers, 68 were symptomatic and 26 were discovered through surveillance. Surveillance identified 13 GI cancers, 11 brain, and 2 hematological malignancies. The gastrointestinal cancers included 5 colorectal, 7 small bowel, and one gastric. Four patients were unaffected. Five-year overall survival was 95% for tumors discovered by surveillance, compared to 43% for symptomatic tumors (p=0.001). Overall survival for gastrointestinal tumors identified by surveillance was 100% (n=13) compared to 79% (n=19) for symptomatic lesions (p=0.1). Similarly, 5-year survival was 83+/-15% and 32+/-7% for surveillance and non-surveillance of brain tumors (p=0.03). Median age at diagnosis of gastrointestinal cancer was 14.6 years (range 9.0-50.6 years). Conclusion: These data support a survival benefit in CMMRD patients undergoing a surveillance protocol.
Published: 2019
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14. Global characteristics and outcomes of SARS-CoV-2 infection in children and adolescents with cancer (GRCCC): a cohort study

Author: Mukkada S, Bhakta N, Chantada G, Chen Y, Vedaraju Y, Faughnan L, Homsi MR, Muniz-Talavera H, Ranadive R, Metzger M, Friedrich P, Agulnik A, Jeha S, Lam C, Dalvi R, Hessissen L, Moreira DC, Santana VM, Sullivan M, Bouffet E, Caniza MA, Devidas M, Pritchard-Jones K, Rodriguez-Galindo C, and Global Registry of COVID-19 in Childhood Cancer
Abstract: BACKGROUND: Previous studies have shown that children and adolescents with COVID-19 generally have mild disease. Children and adolescents with cancer, however, can have severe disease when infected with respiratory viruses. In this study, we aimed to understand the clinical course and outcomes of SARS-CoV-2 infection in children and adolescents with cancer. METHODS: We did a cohort study with data from 131 institutions in 45 countries. We created the Global Registry of COVID-19 in Childhood Cancer to capture de-identified data pertaining to laboratory-confirmed SARS-CoV-2 infections in children and adolescents (
Published: 2021

15. Title: Defining the clinical and prognostic landscape of embryonal tumors with multi-layered rosettes (ETMRs), a rare brain tumor registry (RBTC) study.

Author: Gajjar A., Leary S., Mulcahy Levy J.M., Lassaletta A., Rivas E., Reddy A., Gillespie G.Y., Gupta N., Yalon-Oren M., Amariglio L., Nakamura H., Wu K.-S., Wong T.-T., Ra Y.-S., Spina M.L., Emanuele P.V., Massimi L., Buccoliero A.M., Hansford J.R., Grundy R.G., Adamek D., Fangusaro J., Scharnhorst D., Johnston D., Lafay-Cousin L., Camelo-Piragua S., Kabbara N., Boutarbouch M., Da Costa M.J.G., Hanson D., Wood P., Al-Hussaini M., Amayiri N., Wang Y., Catchpoole D., Michaud J., Bendel A.E., Ellezam B., Gerber N., Plant A., Jeffery R., Dunham C., Moertel C., Walter A., Ziegler D., Dodgshun A., Gottardo N., Demir A., Ramanujachar R., Raabe E., Mary S., Dirks P., Taylor M., Eugene H., Lindsey H., Tihan T., Mette J., Dahl C., Low S., Smith A., Hazrati L.-N., Kresak J., Gino S., Tan E., Morales A., Santa-Maria V., Hawkins C., Bartels U., Stephens D., Nobusawa S., Dufour C., Bourdeaut F., Andre N., Bouffet E., Huang A., Khan S., Solano-Paez P., Suwal T., Al-Karmi S., Lu M., Ho B., Fouladi M., Gajjar A., Leary S., Mulcahy Levy J.M., Lassaletta A., Rivas E., Reddy A., Gillespie G.Y., Gupta N., Yalon-Oren M., Amariglio L., Nakamura H., Wu K.-S., Wong T.-T., Ra Y.-S., Spina M.L., Emanuele P.V., Massimi L., Buccoliero A.M., Hansford J.R., Grundy R.G., Adamek D., Fangusaro J., Scharnhorst D., Johnston D., Lafay-Cousin L., Camelo-Piragua S., Kabbara N., Boutarbouch M., Da Costa M.J.G., Hanson D., Wood P., Al-Hussaini M., Amayiri N., Wang Y., Catchpoole D., Michaud J., Bendel A.E., Ellezam B., Gerber N., Plant A., Jeffery R., Dunham C., Moertel C., Walter A., Ziegler D., Dodgshun A., Gottardo N., Demir A., Ramanujachar R., Raabe E., Mary S., Dirks P., Taylor M., Eugene H., Lindsey H., Tihan T., Mette J., Dahl C., Low S., Smith A., Hazrati L.-N., Kresak J., Gino S., Tan E., Morales A., Santa-Maria V., Hawkins C., Bartels U., Stephens D., Nobusawa S., Dufour C., Bourdeaut F., Andre N., Bouffet E., Huang A., Khan S., Solano-Paez P., Suwal T., Al-Karmi S., Lu M., Ho B., and Fouladi M.
Abstract: ETMR, an aggressive disease characterised by C19MC alterations, were previously categorised as various histologic diagnoses. The clinical spectrum and impact of conventional multi-modal therapy on this new WHO diagnostic category remains poorly understood as a majority of ~200 cases reported to date lack molecular confirmation. We undertook comprehensive clinico-pathologic studies of a large molecularly confirmed cohort to improve disease recognition and treatment approaches. Amongst 623 CNSPNETs patients enrolled in the RBTC registry, 159 primary ETMRs were confirmed based on a combination of FISH (125), methylation analysis (88), SNP and RNAseq (32) analyses; 91% had C19MC amplification/gains/fusions, 9% lacked C19MC alterations but had global methylation features of ETMR NOS. ETMRs arose in young patients (median age 26 months) predominantly as localized disease (M0-72%, M2-3 -18%) at multiple locations including cerebrum (60%) cerebellum (18%), midline structures (6%); notably 10% were brainstem primaries mimicking DIPG. Uni-and multivariate analyses of clinical and treatment details of curative regimens available for 110 patients identified metastatic disease (p=0.002), brainstem locations(p=0.005), extent of surgery, receipt of multi-modal therapy including high dose chemotherapy and radiation (P<0.001) as significant treatment prognosticators, while C19MC status, age and gender were nonsignificant risk factors. Analyses of events in all patients showed respective EFS at 3 and 12 months of 84%(95%CI:77-91) and 37%(95%CI:20-41) and 4yr OS of 27%(95%CI:18-37) indicating despite intensified therapies ETMR is a rapidly progressive and fatal disease. Our comprehensive data on the largest cohort of molecularly-confirmed ETMRs provides a critical framework to guide current clinical management and development of clinical trials.
Published: 2021

16. Clinical Outcomes and Patient-Matched Molecular Composition of Relapsed Medulloblastoma

Author: Kumar, R, Smith, KS, Deng, M, Terhune, C, Robinson, GW, Orr, BA, Liu, APY, Lin, T, Billups, CA, Chintagumpala, M, Bowers, DC, Hassall, TE, Hansford, JR, Khuong-Quang, DA, Crawford, JR, Bendel, AE, Gururangan, S, Schroeder, K, Bouffet, E, Bartels, U, Fisher, MJ, Cohn, R, Partap, S, Kellie, SJ, McCowage, G, Paulino, AC, Rutkowski, S, Fleischhack, G, Dhall, G, Klesse, LJ, Leary, S, Nazarian, J, Kool, M, Wesseling, P, Ryzhova, M, Zheludkova, O, Golanov, A, McLendon, RE, Packer, RJ, Dunham, C, Hukin, J, Fouladi, M, Faria, CC, Pimentel, J, Walter, AW, Jabado, N, Cho, Y-J, Perreault, S, Croul, SE, Zapotocky, M, Hawkins, C, Tabori, U, Taylor, MD, Pfister, SM, Klimo, P, Boop, FA, Ellison, DW, Merchant, TE, Onar-Thomas, A, Korshunov, A, Jones, DTW, Gajjar, A, Ramaswamy, V, Northcott, PA, Kumar, R, Smith, KS, Deng, M, Terhune, C, Robinson, GW, Orr, BA, Liu, APY, Lin, T, Billups, CA, Chintagumpala, M, Bowers, DC, Hassall, TE, Hansford, JR, Khuong-Quang, DA, Crawford, JR, Bendel, AE, Gururangan, S, Schroeder, K, Bouffet, E, Bartels, U, Fisher, MJ, Cohn, R, Partap, S, Kellie, SJ, McCowage, G, Paulino, AC, Rutkowski, S, Fleischhack, G, Dhall, G, Klesse, LJ, Leary, S, Nazarian, J, Kool, M, Wesseling, P, Ryzhova, M, Zheludkova, O, Golanov, A, McLendon, RE, Packer, RJ, Dunham, C, Hukin, J, Fouladi, M, Faria, CC, Pimentel, J, Walter, AW, Jabado, N, Cho, Y-J, Perreault, S, Croul, SE, Zapotocky, M, Hawkins, C, Tabori, U, Taylor, MD, Pfister, SM, Klimo, P, Boop, FA, Ellison, DW, Merchant, TE, Onar-Thomas, A, Korshunov, A, Jones, DTW, Gajjar, A, Ramaswamy, V, and Northcott, PA
Abstract: PURPOSE: We sought to investigate clinical outcomes of relapsed medulloblastoma and to compare molecular features between patient-matched diagnostic and relapsed tumors. METHODS: Children and infants enrolled on either SJMB03 (NCT00085202) or SJYC07 (NCT00602667) trials who experienced medulloblastoma relapse were analyzed for clinical outcomes, including anatomic and temporal patterns of relapse and postrelapse survival. A largely independent, paired molecular cohort was analyzed by DNA methylation array and next-generation sequencing. RESULTS: A total of 72 of 329 (22%) SJMB03 and 52 of 79 (66%) SJYC07 patients experienced relapse with significant representation of Group 3 and wingless tumors. Although most patients exhibited some distal disease (79%), 38% of patients with sonic hedgehog tumors experienced isolated local relapse. Time to relapse and postrelapse survival varied by molecular subgroup with longer latencies for patients with Group 4 tumors. Postrelapse radiation therapy among previously nonirradiated SJYC07 patients was associated with long-term survival. Reirradiation was only temporizing for SJMB03 patients. Among 127 patients with patient-matched tumor pairs, 9 (7%) experienced subsequent nonmedulloblastoma CNS malignancies. Subgroup (96%) and subtype (80%) stabilities were largely maintained among the remainder. Rare subgroup divergence was observed from Group 4 to Group 3 tumors, which is coincident with genetic alterations involving MYC, MYCN, and FBXW7. Subgroup-specific patterns of alteration were identified for driver genes and chromosome arms. CONCLUSION: Clinical behavior of relapsed medulloblastoma must be contextualized in terms of up-front therapies and molecular classifications. Group 4 tumors exhibit slower biological progression. Utility of radiation at relapse is dependent on patient age and prior treatments. Degree and patterns of molecular conservation at relapse vary by subgroup. Relapse tissue enables verification of molecular ta
Published: 2021

17. PINEOBLASTOMA: A POOLED OUTCOME STUDY OF NORTH AMERICAN AND AUSTRALIAN THERAPEUTIC DATA

Author: Hansford, J, Huang, J, Dodgshun, A, Li, B, Hwang, E, Leary, S, Gajjar, A, Von Hoff, K, Endersby, R, Wells, O, Wray, A, Kotecha, R, Raleigh, D, Stoller, S, Mueller, S, Schild, S, Bandopadhayay, P, Fouladi, M, Bouffet, E, Huang, A, Onar, A, Gottardo, N, Hansford, J, Huang, J, Dodgshun, A, Li, B, Hwang, E, Leary, S, Gajjar, A, Von Hoff, K, Endersby, R, Wells, O, Wray, A, Kotecha, R, Raleigh, D, Stoller, S, Mueller, S, Schild, S, Bandopadhayay, P, Fouladi, M, Bouffet, E, Huang, A, Onar, A, and Gottardo, N
Abstract: Background Pineoblastoma (PB) is a rare embryonal brain tumour most often diagnosed in young children. To date, no clinical trials have been conducted specific to pediatric PB. Collaborative studies performed over the past 30 years have included PB in studies accruing for other embryonal tumours, primarily medulloblastoma (MB), but also including the entity formerly known as CNS-PNET and atypical teratoid rhabdoid tumors. Each of these studies have included only a small number of children with PB, making clinical features difficult to interpret and determinants of outcome difficult to ascertain. Patients and Methods Published centrally reviewed series with sufficient treatment and outcome data from North American and Australian cases were pooled. To investigate associations between variables, Fisher’s exact and Wilcoxon-Mann-Whitney tests, and Spearman correlations were used as appropriate. Kaplan-Meier plots, log-rank tests, and Cox proportional hazards models were used in survival analysis. Results We describe a 30-year review of the reported clinical features of PB and a pooled centrally reviewed, cohort analysis of cases (n=178) from the Children’s Oncology Group (COG) (n=82) groups and several published, centrally reviewed institutional series (n=96). We find young children <3 years of age have a dramatically poorer outlook compared to older children (5-year OS 16.2% +/- 5.3% vs 67.3% +/- 5%) confirming new and novel approaches are needed in future clinical trials for this at risk group. Interestingly, male gender was predictive of worse outcome possibly suggestive of gender specific subgroup risks that needs validation in future studies. Assessment of radiation therapy is not possible as the vast majority of children under age three did not receive any form of radiation therapy. Conclusion Given the relative scarcity of this tumor and the emerging data on subgroups of pineoblastoma, prospective, collaborative international studies will be vital
Published: 2021

18. The threat of the COVID-19 pandemic on reversing global life-saving gains in the survival of childhood cancer: a call for collaborative action from SIOP, IPSO, PROS, WCC, CCI, St Jude Global, UICC and WHPCA

Author: Pritchard-Jones, K, Abib, SDC, Esiashvili, N, Kaspers, GJL, Rosser, J, Van Doorninck, JA, Braganca, JML, Hoffman, R, Rodriguez-Galindo, C, Adams, C, Connor, SR, Abdelhafeez, AH, Bouffet, E, Howard, SC, Challinor, JM, Hessissen, L, Dalvi, RB, Kearns, P, Chantada, GL, Frazier, LA, Sullivan, MJ, Schulte, FSM, Morrissey, LK, Kozhaeva, O, Luna-Fineman, S, Khan, MS, Pritchard-Jones, K, Abib, SDC, Esiashvili, N, Kaspers, GJL, Rosser, J, Van Doorninck, JA, Braganca, JML, Hoffman, R, Rodriguez-Galindo, C, Adams, C, Connor, SR, Abdelhafeez, AH, Bouffet, E, Howard, SC, Challinor, JM, Hessissen, L, Dalvi, RB, Kearns, P, Chantada, GL, Frazier, LA, Sullivan, MJ, Schulte, FSM, Morrissey, LK, Kozhaeva, O, Luna-Fineman, S, and Khan, MS
Abstract: The COVID-19 pandemic poses an unprecedented health crisis in all socio-economic regions across the globe. While the pandemic has had a profound impact on access to and delivery of health care by all services, it has been particularly disruptive for the care of patients with life-threatening noncommunicable diseases (NCDs) such as the treatment of children and young people with cancer. The reduction in child mortality from preventable causes over the last 50 years has seen childhood cancer emerge as a major unmet health care need. Whilst survival rates of 85% have been achieved in high income countries, this has not yet been translated into similar outcomes for children with cancer in resource-limited settings where survival averages 30%. Launched in 2018, by the World Health Organization (WHO), the Global Initiative for Childhood Cancer (GICC) is a pivotal effort by the international community to achieve at least 60% survival for children with cancer by 2030. The WHO GICC is already making an impact in many countries but the disruption of cancer care during the COVID-19 pandemic threatens to set back this global effort to improve the outcome for children with cancer, wherever they may live. As representatives of the global community committed to fostering the goals of the GICC, we applaud the WHO response to the COVID-19 pandemic, in particular we support the WHO's call to ensure the needs of patients with life threatening NCDs including cancer are not compromised during the pandemic. Here, as collaborative partners in the GICC, we highlight specific areas of focus that need to be addressed to ensure the immediate care of children and adolescents with cancer is not disrupted during the pandemic; and measures to sustain the development of cancer care so the long-term goals of the GICC are not lost during this global health crisis.
Published: 2021

19. Outcomes by Clinical and Molecular Features in Children With Medulloblastoma Treated With Risk-Adapted Therapy: Results of an International Phase III Trial (SJMB03)

Author: Gajjar, A, Robinson, GW, Smith, KS, Lin, T, Merchant, TE, Chintagumpala, M, Mahajan, A, Su, J, Bouffet, E, Bartels, U, Schechter, T, Hassall, T, Robertson, T, Nicholls, W, Gururangan, S, Schroeder, K, Sullivan, M, Wheeler, G, Hansford, JR, Kellie, SJ, McCowage, G, Cohn, R, Fisher, MJ, Krasin, MJ, Stewart, CF, Broniscer, A, Buchhalter, I, Tatevossian, RG, Orr, BA, Neale, G, Klimo, P, Boop, F, Srinivasan, A, Pfister, SM, Gilbertson, RJ, Onar-Thomas, A, Ellison, DW, Northcott, PA, Gajjar, A, Robinson, GW, Smith, KS, Lin, T, Merchant, TE, Chintagumpala, M, Mahajan, A, Su, J, Bouffet, E, Bartels, U, Schechter, T, Hassall, T, Robertson, T, Nicholls, W, Gururangan, S, Schroeder, K, Sullivan, M, Wheeler, G, Hansford, JR, Kellie, SJ, McCowage, G, Cohn, R, Fisher, MJ, Krasin, MJ, Stewart, CF, Broniscer, A, Buchhalter, I, Tatevossian, RG, Orr, BA, Neale, G, Klimo, P, Boop, F, Srinivasan, A, Pfister, SM, Gilbertson, RJ, Onar-Thomas, A, Ellison, DW, and Northcott, PA
Abstract: Purpose: SJMB03 (ClinicalTrials.gov identifier: NCT00085202) was a phase III risk-adapted trial that aimed to determine the frequency and clinical significance of biological variants and genetic alterations in medulloblastoma. Patients and Methods: Patients 3-21 years old were stratified into average-risk and high-risk treatment groups based on metastatic status and extent of resection. Medulloblastomas were molecularly classified into subgroups (Wingless [WNT], Sonic Hedgehog [SHH], group 3, and group 4) and subtypes based on DNA methylation profiles and overlaid with gene mutations from next-generation sequencing. Coprimary study end points were (1) to assess the relationship between ERBB2 protein expression in tumors and progression-free survival (PFS), and (2) to estimate the frequency of mutations associated with WNT and SHH tumors. Clinical and molecular risk factors were evaluated, and the most robust were used to model new risk-classification categories. Results: Three hundred thirty eligible patients with medulloblastoma were enrolled. Five-year PFS was 83.2% (95% CI, 78.4 to 88.2) for average-risk patients (n = 227) and 58.7% (95% CI, 49.8 to 69.1) for high-risk patients (n = 103). No association was found between ERBB2 status and PFS in the overall cohort (P = .74) or when patients were stratified by clinical risk (P = .71). Mutations in CTNNB1 (96%), DDX3X (37%), and SMARCA4 (24%) were most common in WNT tumors and PTCH1 (38%), TP53 (21%), and DDX3X (19%) in SHH tumors. Methylome profiling classified 53 WNT (17.4%), 48 SHH (15.7%), 65 group 3 (21.3%), and 139 group 4 (45.6%) tumors. A comprehensive clinicomolecular risk factor analysis identified three low-risk groups (WNT, low-risk SHH, and low-risk combined groups 3 and 4) with excellent (5-year PFS > 90%) and two very high-risk groups (high-risk SHH and high-risk combined groups 3 and 4) with poor survival (5-year PFS < 60%). CONCLUSION These results establish a new risk stratification for future medu
Published: 2021

20. Survival Benefit for Individuals With Constitutional Mismatch Repair Deficiency Undergoing Surveillance

Author: Durno, C, Ercan, AB, Bianchi, V, Edwards, M, Aronson, M, Galati, M, Atenafu, EG, Abebe-Campino, G, Al-Battashi, A, Alharbi, M, Azad, VF, Baris, HN, Basel, D, Bedgood, R, Bendel, A, Ben-Shachar, S, Blumenthal, DT, Blundell, M, Bornhorst, M, Bronsema, A, Cairney, E, Rhode, S, Caspi, S, Chamdin, A, Chiaravalli, S, Constantini, S, Crooks, B, Das, A, Dvir, R, Farah, R, Foulkes, WD, Frenkel, Z, Gallinger, B, Gardner, S, Gass, D, Ghalibafian, M, Gilpin, C, Goldberg, Y, Goudie, C, Hamid, SA, Hampel, H, Hansford, JR, Harlos, C, Hijiya, N, Hsu, S, Kamihara, J, Kebudi, R, Knipstein, J, Koschmann, C, Kratz, C, Larouche, V, Lassaletta, A, Lindhorst, S, Ling, SC, Link, MP, De Mola, RL, Luiten, R, Lurye, M, Maciaszek, JL, MagimairajanIssai, V, Maher, OM, Massimino, M, McGee, RB, Mushtaq, N, Mason, G, Newmark, M, Nicholas, G, Nichols, KE, Nicolaides, T, Opocher, E, Osborn, M, Oshrine, B, Pearlman, R, Pettee, D, Rapp, J, Rashid, M, Reddy, A, Reichman, L, Remke, M, Robbins, G, Roy, S, Sabel, M, Samuel, D, Scheers, I, Schneider, KW, Sen, S, Stearns, D, Sumerauer, D, Swallow, C, Taylor, L, Thomas, G, Toledano, H, Tomboc, P, Van Damme, A, Winer, I, Yalon, M, Yen, LY, Zapotocky, M, Zelcer, S, Ziegler, DS, Zimmermann, S, Hawkins, C, Malkin, D, Bouffet, E, Villani, A, Tabori, U, Durno, C, Ercan, AB, Bianchi, V, Edwards, M, Aronson, M, Galati, M, Atenafu, EG, Abebe-Campino, G, Al-Battashi, A, Alharbi, M, Azad, VF, Baris, HN, Basel, D, Bedgood, R, Bendel, A, Ben-Shachar, S, Blumenthal, DT, Blundell, M, Bornhorst, M, Bronsema, A, Cairney, E, Rhode, S, Caspi, S, Chamdin, A, Chiaravalli, S, Constantini, S, Crooks, B, Das, A, Dvir, R, Farah, R, Foulkes, WD, Frenkel, Z, Gallinger, B, Gardner, S, Gass, D, Ghalibafian, M, Gilpin, C, Goldberg, Y, Goudie, C, Hamid, SA, Hampel, H, Hansford, JR, Harlos, C, Hijiya, N, Hsu, S, Kamihara, J, Kebudi, R, Knipstein, J, Koschmann, C, Kratz, C, Larouche, V, Lassaletta, A, Lindhorst, S, Ling, SC, Link, MP, De Mola, RL, Luiten, R, Lurye, M, Maciaszek, JL, MagimairajanIssai, V, Maher, OM, Massimino, M, McGee, RB, Mushtaq, N, Mason, G, Newmark, M, Nicholas, G, Nichols, KE, Nicolaides, T, Opocher, E, Osborn, M, Oshrine, B, Pearlman, R, Pettee, D, Rapp, J, Rashid, M, Reddy, A, Reichman, L, Remke, M, Robbins, G, Roy, S, Sabel, M, Samuel, D, Scheers, I, Schneider, KW, Sen, S, Stearns, D, Sumerauer, D, Swallow, C, Taylor, L, Thomas, G, Toledano, H, Tomboc, P, Van Damme, A, Winer, I, Yalon, M, Yen, LY, Zapotocky, M, Zelcer, S, Ziegler, DS, Zimmermann, S, Hawkins, C, Malkin, D, Bouffet, E, Villani, A, and Tabori, U
Abstract: PURPOSE: Constitutional mismatch repair deficiency syndrome (CMMRD) is a lethal cancer predisposition syndrome characterized by early-onset synchronous and metachronous multiorgan tumors. We designed a surveillance protocol for early tumor detection in these individuals. PATIENTS AND METHODS: Data were collected from patients with confirmed CMMRD who were registered in the International Replication Repair Deficiency Consortium. Tumor spectrum, efficacy of the surveillance protocol, and malignant transformation of low-grade lesions were examined for the entire cohort. Survival outcomes were analyzed for patients followed prospectively from the time of surveillance implementation. RESULTS: A total of 193 malignant tumors in 110 patients were identified. Median age of first cancer diagnosis was 9.2 years (range: 1.7-39.5 years). For patients undergoing surveillance, all GI and other solid tumors, and 75% of brain cancers were detected asymptomatically. By contrast, only 16% of hematologic malignancies were detected asymptomatically (P < .001). Eighty-nine patients were followed prospectively and used for survival analysis. Five-year overall survival (OS) was 90% (95% CI, 78.6 to 100) and 50% (95% CI, 39.2 to 63.7) when cancer was detected asymptomatically and symptomatically, respectively (P = .001). Patient outcome measured by adherence to the surveillance protocol revealed 4-year OS of 79% (95% CI, 54.8 to 90.9) for patients undergoing full surveillance, 55% (95% CI, 28.5 to 74.5) for partial surveillance, and 15% (95% CI, 5.2 to 28.8) for those not under surveillance (P < .0001). Of the 64 low-grade tumors detected, the cumulative likelihood of transformation from low-to high-grade was 81% for GI cancers within 8 years and 100% for gliomas in 6 years. CONCLUSION: Surveillance and early cancer detection are associated with improved OS for individuals with CMMRD.
Published: 2021

21. Clinical phenotypes and prognostic features of embryonal tumours with multi-layered rosettes: a Rare Brain Tumor Registry study.

Author: Khan, S, Solano-Paez, P, Suwal, T, Lu, M, Al-Karmi, S, Ho, B, Mumal, I, Shago, M, Hoffman, LM, Dodgshun, A, Nobusawa, S, Tabori, U, Bartels, U, Ziegler, DS, Hansford, JR, Ramaswamy, V, Hawkins, C, Dufour, C, André, N, Bouffet, E, Huang, A, Rare Brain Tumor Registry, Khan, S, Solano-Paez, P, Suwal, T, Lu, M, Al-Karmi, S, Ho, B, Mumal, I, Shago, M, Hoffman, LM, Dodgshun, A, Nobusawa, S, Tabori, U, Bartels, U, Ziegler, DS, Hansford, JR, Ramaswamy, V, Hawkins, C, Dufour, C, André, N, Bouffet, E, Huang, A, and Rare Brain Tumor Registry
Abstract: BACKGROUND: Embryonal tumours with multi-layered rosettes (ETMRs) are a newly recognised, rare paediatric brain tumour with alterations of the C19MC microRNA locus. Due to varied diagnostic practices and scarce clinical data, disease features and determinants of outcomes for these tumours are poorly defined. We did an integrated clinicopathological and molecular analysis of primary ETMRs to define clinical phenotypes, and to identify prognostic factors of survival and key treatment modalities for this orphan disease. METHODS: Paediatric patients with primary ETMRs and tissue available for analyses were identified from the Rare Brain Tumor Consortium global registry. The institutional histopathological diagnoses were centrally re-reviewed as per the current WHO CNS tumour guidelines, using histopathological and molecular assays. Only patients with complete clinical, treatment, and survival data on Nov 30, 2019, were included in clinicopathological analyses. Among patients who received primary multi-modal curative regimens, event-free survival and overall survival were determined using Cox proportional hazard and log-rank analyses. Univariate and multivariable Cox proportional hazard regression was used to estimate hazard ratios (HRs) with 95% CIs for clinical, molecular, or treatment-related prognostic factors. FINDINGS: 159 patients had a confirmed molecular diagnosis of primary ETMRs (median age at diagnosis 26 months, IQR 18-36) and were included in our clinicopathological analysis. ETMRs were predominantly non-metastatic (94 [73%] of 128 patients), arising from multiple sites; 84 (55%) of 154 were cerebral tumours and 70 (45%) of 154 arose at sites characteristic of other brain tumours. Hallmark C19MC alterations were seen in 144 (91%) of 159 patients; 15 (9%) were ETMR not otherwise specified. In patients treated with curative intent, event-free survival was 57% (95% CI 47-68) at 6 months and 31% (21-42) at 2 years; overall survival was 29% (20-38) at 2 years an
Published: 2021

22. WNT-activated embryonal tumors of the pineal region: ectopic medulloblastomas or a novel pineoblastoma subgroup?

Author: Liu APY, Priesterbach-Ackley LP, Orr BA, Li BK, Gudenas B, Reddingius RE, Suñol M, Lavarino C, Gene-Olaciregui N, Santa-María López V, Fisher MJ, Hazrati LN, Bouffet E, Huang A, Robinson GW, Wesseling P, Northcott PA, and Gajjar A
Published: 2020

23. Bevacizumab for NF2-associated vestibular schwannomas of childhood and adolescence

Author: Renzi S, Michaeli O, Salvador-Hernandez H, Alderete D, Ponce NF, Zapotocky M, Hansford JR, Malalasekera VS, Toledano H, Maguire B, Bouffet E, Ramaswamy V, and Baroni LV
Subjects: bevacizumab, genetic structures, brain tumors, otorhinolaryngologic diseases, NF2, vestibular schwannomas
Abstract: Seventeen children at six institutions with neurofibromatosis type 2 (NF2)-related vestibular schwannomas received bevacizumab. Eight of the 13 patients with initial hearing loss (61%) showed objective hearing improvement within six months of treatment. No patients showed hearing deterioration during therapy; however, only two patients showed objective radiological response. Seven of eight patients had tumor progression or worsening hearing loss upon cessation of treatment. Bevacizumab was well tolerated with no patients discontinuing therapy. Bevacizumab appears to postpone hearing loss in childhood NF2-associated vestibular schwannomas, but responses are not durable, suggesting that either longer maintenance therapy or new strategies are required.
Published: 2020

24. Treatment response of CNS high-grade neuroepithelial tumors with MN1 alteration

Author: Baroni LV, Rugilo C, Lubieniecki F, Sampor C, Freytes C, Nobre L, Hansford JR, Malalasekera VS, Zapotocky M, Dodgshun A, Martinez OC, Morales-La Madrid A, Lavarino C, Suñol M, Rutkowski S, Schuller U, Bouffet E, Ramaswamy V, and Alderete D
Subjects: neuroepithelial tumor, astroblastoma, CNS HGNET-MN1, MN1, ependymoma
Abstract: Central nervous system high-grade neuroepithelial tumor with MN1 alteration (CNS HGNET-MN1) is a rare recently described entity. Fourteen CNS HGNET-MN1 patients were identified using genome-wide methylation arrays/RT-PCR across seven institutions. All patients had surgery (gross total resection: 10; subtotal resection: four) as initial management followed by observation alone in three patients, followed by radiotherapy in eight patients (focal: five; craniospinal: two; CyberKnife: one) and systemic chemotherapy in three patients. Seven patients relapsed; five local and two metastatic, despite adjuvant radiotherapy, of which three died. Treatment of CNS HGNET-MN1 remains a major treatment challenge despite aggressive surgical resections and upfront radiotherapy, warranting new approaches to this rare malignancy.
Published: 2020

25. Embryonal tumors with multi-layered rosettes: a disease of dysregulated miRNAs.

Author: Bouffet E., Huang A., Raghuram N., Khan S., Mumal I., Bouffet E., Huang A., Raghuram N., Khan S., and Mumal I.
Abstract: Introduction: ETMRs are highly lethal, pediatric embryonal brain tumors, previously classified as various histologic diagnoses including supratentorial primitive neuroectodermal tumors (sPNET) and CNS PNET. With recognition that these tumors harbor recurrent amplification of a novel oncogenic miRNA cluster on chr19, C19MC, ETMRs were designated as a distinct biological and molecular entity with a spectrum of histologic and clinical manifestations. Method(s): We reviewed published literature describing clinical presentation, the genetic and epigenetic drivers of oncogenesis, and recent therapeutic strategies adopted to combat these aggressive tumors. Result(s): As a consequence of C19MC amplification, ETMRs upregulate several oncogenic and pluripotency proteins, including LIN28A, DNMT3B and MYCN, that confer a unique epigenetic signature reminiscent of nascent embryonic stem cells. In this review, we focus on the dysregulation of miRNAs in ETMR, the major pathogenic mechanism identified in this disease. Conclusion(s): Despite the use of multi-modal therapeutic regimens, ETMR patients have dismal survival. Understanding the unique biology of these tumors has provided new insights towards novel therapeutic targets.Copyright © 2020, Springer Science+Business Media, LLC, part of Springer Nature.
Published: 2020

26. The COVID-19 pandemic: A rapid global response for children with cancer from SIOP, COG, SIOP-E, SIOP-PODC, IPSO, PROS, CCI, and St Jude Global

Author: Sullivan, M, Bouffet, E, Rodriguez-Galindo, C, Luna-Fineman, S, Khan, MS, Kearns, P, Hawkins, DS, Challinor, J, Morrissey, L, Fuchs, J, Marcus, K, Balduzzi, A, Basset-Salom, L, Caniza, M, Baker, JN, Kebudi, R, Hessissen, L, Sullivan, R, Pritchard-Jones, K, Sullivan, M, Bouffet, E, Rodriguez-Galindo, C, Luna-Fineman, S, Khan, MS, Kearns, P, Hawkins, DS, Challinor, J, Morrissey, L, Fuchs, J, Marcus, K, Balduzzi, A, Basset-Salom, L, Caniza, M, Baker, JN, Kebudi, R, Hessissen, L, Sullivan, R, and Pritchard-Jones, K
Abstract: The COVID-19 pandemic is one of the most serious global challenges to delivering affordable and equitable treatment to children with cancer we have witnessed in the last few decades. This Special Report aims to summarize general principles for continuing multidisciplinary care during the SARS-CoV-2 (COVID-19) pandemic. With contributions from the leadership of the International Society for Pediatric Oncology (SIOP), Children's Oncology Group (COG), St Jude Global program, and Childhood Cancer International, we have sought to provide a framework for healthcare teams caring for children with cancer during the pandemic. We anticipate the burden will fall particularly heavily on children, their families, and cancer services in low- and middle-income countries. Therefore, we have brought together the relevant clinical leads from SIOP Europe, COG, and SIOP-PODC (Pediatric Oncology in Developing Countries) to focus on the six most curable cancers that are part of the WHO Global Initiative in Childhood Cancer. We provide some practical advice for adapting diagnostic and treatment protocols for children with cancer during the pandemic, the measures taken to contain it (e.g., extreme social distancing), and how to prepare for the anticipated recovery period.
Published: 2020

27. LINC-10. SIOP PODC ADAPTED TREATMENT GUIDELINES FOR CRANIOPHARYNGIOMA IN LOW- AND MIDDLE-INCOME SETTINGS

Author: amayiri, N, Spitaels, A, Zaghloul, M, Figaji, A, Cavalheiro, S, Muller, HL, Elhassan, M, Parkes, J, Mushtaq, N, El Beltagy, M, Yousef, Y, Esiashvili, N, Sullivan, M, da Costa, MD, Dastoli, P, Mubarak, F, Bartels, U, Chamdine, O, Davidson, A, Musharbash, A, Alcasabas, P, Bouffet, E, Bailey, S, amayiri, N, Spitaels, A, Zaghloul, M, Figaji, A, Cavalheiro, S, Muller, HL, Elhassan, M, Parkes, J, Mushtaq, N, El Beltagy, M, Yousef, Y, Esiashvili, N, Sullivan, M, da Costa, MD, Dastoli, P, Mubarak, F, Bartels, U, Chamdine, O, Davidson, A, Musharbash, A, Alcasabas, P, Bouffet, E, and Bailey, S
Abstract: Pediatric craniopharyngioma is a rare tumor with excellent survival but significant long-term morbidities due to the loco-regional tumor growth or secondary to its treatment. Visual impairment, panhypopituitarism, hypothalamic damage and behavioral changes are amongst the main challenges. This tumor should be managed under the care of a multidisciplinary team to determine the optimum treatment within the available resources. This is particularly important for low middle-income countries (LMICs) where resources are variable. We provide a risk-stratified management guideline for children diagnosed with craniopharyngioma in a resource limited setting based on the service levels describing the facilities and personnel required for management as previously specified by the Pediatric Oncology in Developing Countries (PODC) committee of The International Society of Pediatric Oncology (SIOP). A multi-disciplinary group of neurosurgeons, radiation and pediatric oncologists, radiologists, pediatric endocrinologists and an ophthalmologist with experience in managing children with craniopharyngioma in LMIC setting was formed and carried online meetings to form a consensus guideline. The clinical characteristics (including the visual and endocrine presentations), suggestive radiological features as well as potential treatment options including surgery, radiotherapy and intra-cystic therapies were discussed in depth and in relation to available resources. In addition, hormonal management, pre- and post-operative PICU care and expected future complications related to craniopharyngioma and to follow up these children were discussed and documented in the guideline. We believe this guideline is a useful reference for health care providers in LMIC.
Published: 2020

28. Pattern of Relapse and Treatment Response in WNT-Activated Medulloblastoma

Author: Nobre, L, Zapotocky, M, Khan, S, Fukuoka, K, Fonseca, A, McKeown, T, Sumerauer, D, Vicha, A, Grajkowska, WA, Trubicka, J, Li, KKW, Ng, H-K, Massimi, L, Lee, JY, Kim, S-K, Zelcer, S, Vasiljevic, A, Faure-Conter, C, Hauser, P, Lach, B, Van Veelen-Vincent, M-L, French, PJ, Van Meir, EG, Weiss, WA, Gupta, N, Pollack, IF, Hamilton, RL, Rao, AAN, Giannini, C, Rubin, JB, Moore, AS, Chambless, LB, Vibhakar, R, Ra, YS, Massimino, M, McLendon, RE, Wheeler, H, Zollo, M, Ferruci, V, Kumabe, T, Faria, CC, Sterba, J, Jung, S, Lopez-Aguilar, E, Mora, J, Carlotti, CG, Olson, JM, Leary, S, Cain, J, Krskova, L, Zamecnik, J, Hawkins, CE, Tabori, U, Huang, A, Bartels, U, Northcott, PA, Taylor, MD, Yip, S, Hansford, JR, Bouffet, E, Ramaswamy, V, Nobre, L, Zapotocky, M, Khan, S, Fukuoka, K, Fonseca, A, McKeown, T, Sumerauer, D, Vicha, A, Grajkowska, WA, Trubicka, J, Li, KKW, Ng, H-K, Massimi, L, Lee, JY, Kim, S-K, Zelcer, S, Vasiljevic, A, Faure-Conter, C, Hauser, P, Lach, B, Van Veelen-Vincent, M-L, French, PJ, Van Meir, EG, Weiss, WA, Gupta, N, Pollack, IF, Hamilton, RL, Rao, AAN, Giannini, C, Rubin, JB, Moore, AS, Chambless, LB, Vibhakar, R, Ra, YS, Massimino, M, McLendon, RE, Wheeler, H, Zollo, M, Ferruci, V, Kumabe, T, Faria, CC, Sterba, J, Jung, S, Lopez-Aguilar, E, Mora, J, Carlotti, CG, Olson, JM, Leary, S, Cain, J, Krskova, L, Zamecnik, J, Hawkins, CE, Tabori, U, Huang, A, Bartels, U, Northcott, PA, Taylor, MD, Yip, S, Hansford, JR, Bouffet, E, and Ramaswamy, V
Abstract: Over the past decade, wingless-activated (WNT) medulloblastoma has been identified as a candidate for therapy de-escalation based on excellent survival; however, a paucity of relapses has precluded additional analyses of markers of relapse. To address this gap in knowledge, an international cohort of 93 molecularly confirmed WNT MB was assembled, where 5-year progression-free survival is 0.84 (95%, 0.763-0.925) with 15 relapsed individuals identified. Maintenance chemotherapy is identified as a strong predictor of relapse, with individuals receiving high doses of cyclophosphamide or ifosphamide having only one very late molecularly confirmed relapse (p = 0.032). The anatomical location of recurrence is metastatic in 12 of 15 relapses, with 8 of 12 metastatic relapses in the lateral ventricles. Maintenance chemotherapy, specifically cumulative cyclophosphamide doses, is a significant predictor of relapse across WNT MB. Future efforts to de-escalate therapy need to carefully consider not only the radiation dose but also the chemotherapy regimen and the propensity for metastatic relapses.
Published: 2020

29. HGG-20. DIAGNOSTIC AND BIOLOGICAL ROLE OF METHYLATION PATTERNS IN REPLICATION REPAIR DEFICIENT HIGH GRADE GLIOMAS

Author: Dodgshun, A, Fukuoka, K, Edwards, M, Bianchi, V, Sexton-Oates, A, Larouche, V, Magimairajan, V, Lindhorst, S, Yalon, M, Mason, G, Crooks, B, Constantini, S, Massimino, M, Chiaravalli, S, Ramdas, J, Mason, W, Shamvil, A, Farah, R, Van Damme, A, Opocher, E, Hamid, SA, Ziegler, D, Samuel, D, Cole, KA, Tomboc, P, Stearns, D, Thomas, G, Lossos, A, Sullivan, M, Hansford, JR, Jones, D, Mackay, A, Jones, C, Ramaswamy, V, Hawkins, C, Bouffet, E, Tabori, U, Dodgshun, A, Fukuoka, K, Edwards, M, Bianchi, V, Sexton-Oates, A, Larouche, V, Magimairajan, V, Lindhorst, S, Yalon, M, Mason, G, Crooks, B, Constantini, S, Massimino, M, Chiaravalli, S, Ramdas, J, Mason, W, Shamvil, A, Farah, R, Van Damme, A, Opocher, E, Hamid, SA, Ziegler, D, Samuel, D, Cole, KA, Tomboc, P, Stearns, D, Thomas, G, Lossos, A, Sullivan, M, Hansford, JR, Jones, D, Mackay, A, Jones, C, Ramaswamy, V, Hawkins, C, Bouffet, E, and Tabori, U
Abstract: Replication repair deficiency (RRD) is an important driving mechanism of pediatric high grade glioma (pHGG) occurring predominantly in the context of germline mutations in RRD-associated genes. Although pHGG present specific patterns of DNA methylation corresponding to driving oncogenic processes, methylation patterns have not been well studied in RRD tumors. We analyzed 52 RRD pHGG using either 450k or 850k methylation arrays. These arrays were compared with 234 PHGG driven by other genetic or epigenetic mechanisms and 10 additional pHGG samples known to be hypermutant. RRD pHGG displayed a methylation pattern corresponding to specific secondary mutations such as IDH1 and H3K27M. Strikingly, RRD pHGG lacking these known secondary mutations largely clustered together with a poorly described group previously labelled Wild type-C. Most of the hypermutant tumors clustered in a similar location suggesting undiagnosed RRD may be a driving force for tumors clustering in this location. Analysis of methylation patterns revealed that RRD pHGG displayed a unique CpG Island Demethylator Phenotype in contrast to the Methylator Phenotype described in other cancers. This effect was most concentrated at gene promotors. Prominent demethylation was observed in genes and pathways critical to cellular survival including cell cycle, gene expression, cellular metabolism and cellular organization. These data suggest that methylation profiles may provide diagnostic information for the detection of RRD pHGG. Furthermore, our findings highlight the unique natural selection pressures in these highly dysregulated, hypermutant cancers and provide novel impact of hypermutation and RRD on the cancer epigenome.
Published: 2020

30. COVD-04. CHARACTERISTICS OF SARS-COV-2 IN 64 CHILDREN WITH CNS TUMORS: A REPORT FROM THE SIOP/ST. JUDE CHILDREN’S RESEARCH HOSPITAL (SJCRH) GLOBAL COVID-19 CHILDHOOD CANCER REGISTRY

Author: Moreira, D, Bouffet, E, Bhakta, N, Chantada, G, Chen, Y, Faughnan, L, Vedaraju, Y, Avula, M, Homsi, M, Naidu, P, Pappas, A, Ranadive, R, Santana, V, Sullivan, M, Baroni, L, Caniza, M, Devidas, M, Pritchard-Jones, K, Rodriguez-Galindo, C, Mukkada, S, Moreira, D, Bouffet, E, Bhakta, N, Chantada, G, Chen, Y, Faughnan, L, Vedaraju, Y, Avula, M, Homsi, M, Naidu, P, Pappas, A, Ranadive, R, Santana, V, Sullivan, M, Baroni, L, Caniza, M, Devidas, M, Pritchard-Jones, K, Rodriguez-Galindo, C, and Mukkada, S
Abstract: BACKGROUND The GCCCR is a collaboration between SIOP and SJCRH to describe the natural history of SARS-CoV-2 in children with cancer across the world. METHODS The GCCCR is a deidentified registry of patients <19 years of age with cancer or recipients of a hematopoietic stem cell transplant and laboratory-confirmed SARS-CoV-2 infection. Demographic data, cancer diagnosis, cancer-directed therapy, and clinical characteristics of SARS-CoV-2 infection were collected. Outcomes were collected at 30-days and 60-days post infection. RESULTS As of August 10th 2020, the GCCCR included 730 cases from 35 countries, including 64 children with CNS tumors (8.8%) from 17 countries. The most frequent diagnoses were embryonal tumors (31.2%) and low-grade glioma (17.2%). Thirty-nine (60.9%) children were asymptomatic from infection, while 19 (29.7%) patients required hospital admission and 2 (6.3%) transferred to the intensive care unit. There was a significant association between infection severity and ANC <500 (p=0.04). At the time of infection, 44 (68.8%) patients were undergoing cancer-directed therapy. Thirty-two cases have follow-up data. No modification in cancer-directed therapy occurred in 11 (34.4%) patients, while chemotherapy was modified in 6 (18.8%), radiotherapy delayed in 2 (6.3%), and surgery postponed in 1 (3.1%). No patients died from SARS-CoV-2 infection, although 2 died from non-COVID-19 related causes. CONCLUSION The frequency and severity of COVID infection among children with CNS tumors appears to be proportionally lower compared to other children with cancer. Although this is the largest cohort of patients reported to date, additional insight is needed, including the effects of treatment modifications on outcomes.
Published: 2020

31. Early advice on managing children with cancer during the COVID-19 pandemic and a call for sharing experiences

Author: Bouffet, E, Challinor, J, Sullivan, M, Biondi, A, Rodriguez-Galindo, C, Pritchard-Jones, K, Bouffet, E, Challinor, J, Sullivan, M, Biondi, A, Rodriguez-Galindo, C, and Pritchard-Jones, K
Published: 2020

32. Pineoblastoma segregates into molecular sub-groups with distinct clinico-pathologic features: a Rare Brain Tumor Consortium registry study

Author: Li, BK, Vasiljevic, A, Dufour, C, Yao, F, Ho, BLB, Lu, M, Hwang, EI, Gururangan, S, Hansford, JR, Fouladi, M, Nobusawa, S, Laquerriere, A, Delisle, M-B, Fangusaro, J, Forest, F, Toledano, H, Solano-Paez, P, Leary, S, Birks, D, Hoffman, LM, Szathmari, A, Faure-Conter, C, Fan, X, Catchpoole, D, Zhou, L, Schultz, KAP, Ichimura, K, Gauchotte, G, Jabado, N, Jones, C, Loussouarn, D, Mokhtari, K, Rousseau, A, Ziegler, DS, Tanaka, S, Pomeroy, SL, Gajjar, A, Ramaswamy, V, Hawkins, C, Grundy, RG, Hill, DA, Bouffet, E, Huang, A, Jouvet, A, Li, BK, Vasiljevic, A, Dufour, C, Yao, F, Ho, BLB, Lu, M, Hwang, EI, Gururangan, S, Hansford, JR, Fouladi, M, Nobusawa, S, Laquerriere, A, Delisle, M-B, Fangusaro, J, Forest, F, Toledano, H, Solano-Paez, P, Leary, S, Birks, D, Hoffman, LM, Szathmari, A, Faure-Conter, C, Fan, X, Catchpoole, D, Zhou, L, Schultz, KAP, Ichimura, K, Gauchotte, G, Jabado, N, Jones, C, Loussouarn, D, Mokhtari, K, Rousseau, A, Ziegler, DS, Tanaka, S, Pomeroy, SL, Gajjar, A, Ramaswamy, V, Hawkins, C, Grundy, RG, Hill, DA, Bouffet, E, Huang, A, and Jouvet, A
Abstract: Pineoblastomas (PBs) are rare, aggressive pediatric brain tumors of the pineal gland with modest overall survival despite intensive therapy. We sought to define the clinical and molecular spectra of PB to inform new treatment approaches for this orphan cancer. Tumor, blood, and clinical data from 91 patients with PB or supratentorial primitive neuroectodermal tumor (sPNETs/CNS-PNETs), and 2 pineal parenchymal tumors of intermediate differentiation (PPTIDs) were collected from 29 centres in the Rare Brain Tumor Consortium. We used global DNA methylation profiling to define a core group of PB from 72/93 cases, which were delineated into five molecular sub-groups. Copy number, whole exome and targeted sequencing, and miRNA expression analyses were used to evaluate the clinico-pathologic significance of each sub-group. Tumors designated as group 1 and 2 almost exclusively exhibited deleterious homozygous loss-of-function alterations in miRNA biogenesis genes (DICER1, DROSHA, and DGCR8) in 62 and 100% of group 1 and 2 tumors, respectively. Recurrent alterations of the oncogenic MYC-miR-17/92-RB1 pathway were observed in the RB and MYC sub-group, respectively, characterized by RB1 loss with gain of miR-17/92, and recurrent gain or amplification of MYC. PB sub-groups exhibited distinct clinical features: group 1-3 arose in older children (median ages 5.2-14.0 years) and had intermediate to excellent survival (5-year OS of 68.0-100%), while Group RB and MYC PB patients were much younger (median age 1.3-1.4 years) with dismal survival (5-year OS 37.5% and 28.6%, respectively). We identified age < 3 years at diagnosis, metastatic disease, omission of upfront radiation, and chr 16q loss as significant negative prognostic factors across all PBs. Our findings demonstrate that PB exhibits substantial molecular heterogeneity with sub-group-associated clinical phenotypes and survival. In addition to revealing novel biology and therapeutics, molecular sub-grouping of PB can be explo
Published: 2020

33. Medulloblastoma has a global impact on health related quality of life: Findings from an international cohort

Author: de Medeiros, CB, Moxon-Emre, I, Scantlebury, N, Malkin, D, Ramaswamy, V, Decker, A, Law, N, Kumabe, T, Leonard, J, Rubin, J, Jung, S, Kim, SK, Gupta, N, Weiss, W, Faria, CC, Vibhakar, R, Lafay-Cousin, L, Chan, J, Kros, J.M., Janzen, L, Taylor, MD, Bouffet, E, Mabbott, DJ, de Medeiros, CB, Moxon-Emre, I, Scantlebury, N, Malkin, D, Ramaswamy, V, Decker, A, Law, N, Kumabe, T, Leonard, J, Rubin, J, Jung, S, Kim, SK, Gupta, N, Weiss, W, Faria, CC, Vibhakar, R, Lafay-Cousin, L, Chan, J, Kros, J.M., Janzen, L, Taylor, MD, Bouffet, E, and Mabbott, DJ
Published: 2020

34. NASPGHAN Annual Meeting Abstracts

Author: UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, UCL - (SLuc) Service de gastro-entérologie et hépatologie pédiatrique, Durno, C, Ercan, A, Aronson, M, Villani, A, Bouffet, E, Erdman, S, Scheers, Isabelle, Bronsema, A, Tabori, U, UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, UCL - (SLuc) Service de gastro-entérologie et hépatologie pédiatrique, Durno, C, Ercan, A, Aronson, M, Villani, A, Bouffet, E, Erdman, S, Scheers, Isabelle, Bronsema, A, and Tabori, U
Abstract: Background: Constitutional mismatch repair deficiency syndrome (CMMRD) is a severe cancer predisposition syndrome causing intestinal polyposis and a high risk of early onset gastrointestinal, brain, and hematological cancers. International guidelines for surveillance exist but no study has systematically evaluated the efficacy of this protocol. Aim: Our aim was to determine if surveillance affects outcome. The primary outcome measure was overall survival. The secondary outcome measure was detection of new cancers. Methods: Patients referred to the International Replication Repair Consortium undergo genetic testing to confirm CMMRD. All individuals were diagnosed with CMMRD through diagnostic criteria by the genetic counsellor at the consortium. A surveillance protocol consisting of frequent biochemical, endoscopic and imaging studies was recommended and initiated internationally on Jan 1, 2012. Protocol included upper endoscopy, colonoscopy, video capsule endoscopy and/or magnetic resonance enterography, and brain MRI. Whole-body MRI was recommended as of Jan 1, 2018. Surveillance questionnaire was sent to the responsible physician with diagnostic fields completed by the registry coordinator as a double check of reliability. Survival analyses was completed using an as-treated approach. Results: Cancer and surveillance data was collected from 64 (50%) of 127 CMMRD individuals registered in the Consortium from 41 countries. There were 114 tumours reported in 60 patients including 55 brain, 28 gastrointestinal (GI), 17 hematological and 14 other malignancies. Surveillance data was available on 110 cancers; 16 were incidental cancers, 68 were symptomatic and 26 were discovered through surveillance. Surveillance identified 13 GI cancers, 11 brain, and 2 hematological malignancies. The gastrointestinal cancers included 5 colorectal, 7 small bowel, and one gastric. Four patients were unaffected. Five-year overall survival was 95% for tumors discovered by surveillance, comp
Published: 2019

35. Alterations in ALK/ROS1/NTRK/MET drive a group of infantile hemispheric gliomas.

Author: Guerreiro Stucklin, AS, Ryall, S, Fukuoka, K, Zapotocky, M, Lassaletta, A, Li, C, Bridge, T, Kim, B, Arnoldo, A, Kowalski, PE, Zhong, Y, Johnson, M, Ramani, AK, Siddaway, R, Nobre, LF, de Antonellis, P, Dunham, C, Cheng, S, Boué, DR, Finlay, JL, Coven, SL, de Prada, I, Perez-Somarriba, M, Faria, CC, Grotzer, MA, Rushing, E, Sumerauer, D, Zamecnik, J, Krskova, L, Garcia Ariza, M, Cruz, O, Morales La Madrid, A, Solano, P, Terashima, K, Nakano, Y, Ichimura, K, Nagane, M, Sakamoto, H, Gil-da-Costa, MJ, Silva, R, Johnston, DL, Michaud, J, Wilson, B, van Landeghem, FKH, Oviedo, A, McNeely, PD, Crooks, B, Fried, I, Zhukova, N, Hansford, JR, Nageswararao, A, Garzia, L, Shago, M, Brudno, M, Irwin, MS, Bartels, U, Ramaswamy, V, Bouffet, E, Taylor, MD, Tabori, U, Hawkins, C, Guerreiro Stucklin, AS, Ryall, S, Fukuoka, K, Zapotocky, M, Lassaletta, A, Li, C, Bridge, T, Kim, B, Arnoldo, A, Kowalski, PE, Zhong, Y, Johnson, M, Ramani, AK, Siddaway, R, Nobre, LF, de Antonellis, P, Dunham, C, Cheng, S, Boué, DR, Finlay, JL, Coven, SL, de Prada, I, Perez-Somarriba, M, Faria, CC, Grotzer, MA, Rushing, E, Sumerauer, D, Zamecnik, J, Krskova, L, Garcia Ariza, M, Cruz, O, Morales La Madrid, A, Solano, P, Terashima, K, Nakano, Y, Ichimura, K, Nagane, M, Sakamoto, H, Gil-da-Costa, MJ, Silva, R, Johnston, DL, Michaud, J, Wilson, B, van Landeghem, FKH, Oviedo, A, McNeely, PD, Crooks, B, Fried, I, Zhukova, N, Hansford, JR, Nageswararao, A, Garzia, L, Shago, M, Brudno, M, Irwin, MS, Bartels, U, Ramaswamy, V, Bouffet, E, Taylor, MD, Tabori, U, and Hawkins, C
Abstract: Infant gliomas have paradoxical clinical behavior compared to those in children and adults: low-grade tumors have a higher mortality rate, while high-grade tumors have a better outcome. However, we have little understanding of their biology and therefore cannot explain this behavior nor what constitutes optimal clinical management. Here we report a comprehensive genetic analysis of an international cohort of clinically annotated infant gliomas, revealing 3 clinical subgroups. Group 1 tumors arise in the cerebral hemispheres and harbor alterations in the receptor tyrosine kinases ALK, ROS1, NTRK and MET. These are typically single-events and confer an intermediate outcome. Groups 2 and 3 gliomas harbor RAS/MAPK pathway mutations and arise in the hemispheres and midline, respectively. Group 2 tumors have excellent long-term survival, while group 3 tumors progress rapidly and do not respond well to chemoradiation. We conclude that infant gliomas comprise 3 subgroups, justifying the need for specialized therapeutic strategies.
Published: 2019

36. A C19MC-LIN28A-MYCN Oncogenic Circuit Driven by Hijacked Super-enhancers Is a Distinct Therapeutic Vulnerability in ETMRs: A Lethal Brain Tumor

Author: Sin-Chan, P, Mumal, I, Suwal, T, Ho, B, Fan, X, Singh, I, Du, Y, Lu, M, Patel, N, Torchia, J, Popovski, D, Fouladi, M, Guilhamon, P, Hansford, JR, Leary, S, Hoffman, LM, Mulcahy Levy, JM, Lassaletta, A, Solano-Paez, P, Rivas, E, Reddy, A, Gillespie, GY, Gupta, N, Van Meter, TE, Nakamura, H, Wong, TT, Ra, YS, Kim, SK, Massimi, L, Grundy, RG, Fangusaro, J, Johnston, D, Chan, J, Lafay-Cousin, L, Hwang, EI, Wang, Y, Catchpoole, D, Michaud, J, Ellezam, B, Ramanujachar, R, Lindsay, H, Taylor, MD, Hawkins, CE, Bouffet, E, Jabado, N, Singh, SK, Kleinman, CL, Barsyte-Lovejoy, D, Li, XN, Dirks, PB, Lin, CY, Mack, SC, Rich, JN, Huang, A, Sin-Chan, P, Mumal, I, Suwal, T, Ho, B, Fan, X, Singh, I, Du, Y, Lu, M, Patel, N, Torchia, J, Popovski, D, Fouladi, M, Guilhamon, P, Hansford, JR, Leary, S, Hoffman, LM, Mulcahy Levy, JM, Lassaletta, A, Solano-Paez, P, Rivas, E, Reddy, A, Gillespie, GY, Gupta, N, Van Meter, TE, Nakamura, H, Wong, TT, Ra, YS, Kim, SK, Massimi, L, Grundy, RG, Fangusaro, J, Johnston, D, Chan, J, Lafay-Cousin, L, Hwang, EI, Wang, Y, Catchpoole, D, Michaud, J, Ellezam, B, Ramanujachar, R, Lindsay, H, Taylor, MD, Hawkins, CE, Bouffet, E, Jabado, N, Singh, SK, Kleinman, CL, Barsyte-Lovejoy, D, Li, XN, Dirks, PB, Lin, CY, Mack, SC, Rich, JN, and Huang, A
Abstract: © 2019 Elsevier Inc. Embryonal tumors with multilayered rosettes (ETMRs) are highly lethal infant brain cancers with characteristic amplification of Chr19q13.41 miRNA cluster (C19MC) and enrichment of pluripotency factor LIN28A. Here we investigated C19MC oncogenic mechanisms and discovered a C19MC-LIN28A-MYCN circuit fueled by multiple complex regulatory loops including an MYCN core transcriptional network and super-enhancers resulting from long-range MYCN DNA interactions and C19MC gene fusions. Our data show that this powerful oncogenic circuit, which entraps an early neural lineage network, is potently abrogated by bromodomain inhibitor JQ1, leading to ETMR cell death. Sin-Chan et al. uncover a C19MC-LIN28A-MYCN super-enhancer-dependent oncogenic circuit in embryonal tumors with multilayered rosettes (ETMRs). The circuit entraps an early neural lineage network to sustain embryonic epigenetic programming and is vulnerable to bromodomain inhibition, which promotes ETMR cell death.
Published: 2019

37. A C19MC-LIN28A-MYCN Oncogenic Circuit Driven by Hijacked Super-enhancers Is a Distinct Therapeutic Vulnerability in ETMRs: A Lethal Brain Tumor

Author: Sin-Chan, P., Mumal, I., Suwal, T., Ho, B., Fan, X., Singh, I., Du, Y., Lu, M., Patel, N., Torchia, J., Popovski, D., Fouladi, M., Guilhamon, P., Hansford, J. R., Leary, S., Hoffman, L. M., Mulcahy Levy, J. M., Lassaletta, A., Solano-Paez, P., Rivas, E., Reddy, A., Gillespie, G. Y., Gupta, N., Van Meter, T. E., Nakamura, H., Wong, T. -T., Ra, Y. -S., Kim, S. -K., Massimi, Luca, Grundy, R. G., Fangusaro, J., Johnston, D., Chan, J., Lafay-Cousin, L., Hwang, E. I., Wang, Y., Catchpoole, D., Michaud, J., Ellezam, B., Ramanujachar, R., Lindsay, H., Taylor, M. D., Hawkins, C. E., Bouffet, E., Jabado, N., Singh, S. K., Kleinman, C. L., Barsyte-Lovejoy, D., Li, X. -N., Dirks, P. B., Lin, C. Y., Mack, S. C., Rich, J. N., Huang, A., Massimi L., Sin-Chan, P., Mumal, I., Suwal, T., Ho, B., Fan, X., Singh, I., Du, Y., Lu, M., Patel, N., Torchia, J., Popovski, D., Fouladi, M., Guilhamon, P., Hansford, J. R., Leary, S., Hoffman, L. M., Mulcahy Levy, J. M., Lassaletta, A., Solano-Paez, P., Rivas, E., Reddy, A., Gillespie, G. Y., Gupta, N., Van Meter, T. E., Nakamura, H., Wong, T. -T., Ra, Y. -S., Kim, S. -K., Massimi, Luca, Grundy, R. G., Fangusaro, J., Johnston, D., Chan, J., Lafay-Cousin, L., Hwang, E. I., Wang, Y., Catchpoole, D., Michaud, J., Ellezam, B., Ramanujachar, R., Lindsay, H., Taylor, M. D., Hawkins, C. E., Bouffet, E., Jabado, N., Singh, S. K., Kleinman, C. L., Barsyte-Lovejoy, D., Li, X. -N., Dirks, P. B., Lin, C. Y., Mack, S. C., Rich, J. N., Huang, A., and Massimi L.
Abstract: Embryonal tumors with multilayered rosettes (ETMRs) are highly lethal infant brain cancers with characteristic amplification of Chr19q13.41 miRNA cluster (C19MC) and enrichment of pluripotency factor LIN28A. Here we investigated C19MC oncogenic mechanisms and discovered a C19MC-LIN28A-MYCN circuit fueled by multiple complex regulatory loops including an MYCN core transcriptional network and super-enhancers resulting from long-range MYCN DNA interactions and C19MC gene fusions. Our data show that this powerful oncogenic circuit, which entraps an early neural lineage network, is potently abrogated by bromodomain inhibitor JQ1, leading to ETMR cell death. Sin-Chan et al. uncover a C19MC-LIN28A-MYCN super-enhancer-dependent oncogenic circuit in embryonal tumors with multilayered rosettes (ETMRs). The circuit entraps an early neural lineage network to sustain embryonic epigenetic programming and is vulnerable to bromodomain inhibition, which promotes ETMR cell death.
Published: 2019

38. Second re-irradiation for DIPG progression, re-considering 'old strategies' with new approaches

Author: Morales-La Madrid A, Santa-María V, Cruz-Martínez O, Mora J, Puerta Roldan P, Guillen-Quesada A, Suñol M, de Torres C, Lassaletta A, Laperriere N, Villà S, and Bouffet E
Subjects: DIPG, Second re-irradiation
Abstract: Diffuse intrinsic pontine glioma (DIPG) is an aggressive infiltrative glioma for which no curative therapy is available. Radiation therapy (RT) is the only potentially effective intervention in delaying tumor progression, but only transiently. At progression, re-irradiation is gaining popularity as an effective palliative therapy. However, at second progression, exclusive symptomatic treatment is usually offered. Here we report two patients with DIPG at second progression who were treated with a second re-irradiation course with good response. Importantly, treatment was well tolerated with no irradiation associated acute toxicity identified.
Published: 2017

39. Phase II open-label, global study evaluating dabrafenib in combination with trametinib in pediatric patients with BRAF V600–mutant high-grade glioma (HGG) or low-grade glioma (LGG)

Author: Hargrave, D., primary, Witt, O., additional, Cohen, K., additional, Packer, R., additional, Lissat, A., additional, Kordes, U., additional, Laetsch, T.W., additional, Hoffman, L., additional, Lassaletta, A., additional, Gerber, N.U., additional, Gilheeney, S., additional, Holm, S., additional, Kramm, C., additional, Sumerauer, D., additional, Reitmann, C., additional, Russo, M.W., additional, and Bouffet, E., additional
Published: 2018
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40. A multi-disciplinary consensus statement concerning surgical approaches to low-grade, high-grade astrocytomas and diffuse intrinsic pontine gliomas in childhood (CPN Paris 2011) using the Delphi method

Author: Walker, D. A., Liu, J., Kieran, M., Jabado, N., Picton, S., Packer, R., Rose, C. S. t., Van Meeteren, A. S., Carvalho, A., Van Damme, A., Depreitere, B., Gustavsson, B., Due Tonnessen, B. J., Bertozzi Salamon, A. I., Brentrup, A., Raybaud, C., Jones, C., Dufour, C., Dorfer, C., Sainte Rose, C., Malluci, C., Hargrave, D., Walker, D., Van Vuurden, D., De Carli, E., Bouffet, E., Van Calenbergh, F., Frappaz, D., Frassanito, P., Goodrich, J., Baechli, H., Grill, J., Ternier, J., Cappelen, J., Caird, J., Pereira, J., Riffaud, L., Baroncini, M., Walker, M., Ozek, M., Nysom, K., Varlet, P., Goodden, J., Bertolini, P., Perilongo, Giorgio, Mercier, P., Grundy, R., Kortmann, R. D., Pfister, S., Constantini, S., Sgouros, S., Holm, S., Czech, T., Merchant, T., Stokland, T., Ridola, V., and Vandertop, P.
Subjects: Cancer Research, medicine.medical_specialty, Consensus, medicine.medical_treatment, Neurosurgery, Glioma, Biopsy, medicine, Brain Stem Neoplasms, Humans, Neurofibromatosis, Child, medicine.diagnostic_test, business.industry, General surgery, Astrocytoma, medicine.disease, Surgery, Radiation therapy, Clinical trial, Oncology, Practice Guidelines as Topic, Basic and Translational Investigations, Neurology (clinical), Neoplasm Grading, business, Risk assessment
Abstract: Astrocytic tumors account for 42% of childhood brain tumors, arising in all anatomical regions and associated with neurofibromatosis type 1 (NF1) in 15%. Anatomical site determines the degree and risk of resectability; the more complete resection, the better the survival rates. New biological markers and modern radiotherapy techniques are altering the risk assessments of clinical decisions for tumor resection and biopsy. The increasingly distinct pediatric neuro-oncology multidisciplinary team (PNMDT) is developing a distinct evidence base. A multidisciplinary consensus conference on pediatric neurosurgery was held in February 2011, where 92 invited participants reviewed evidence for clinical management of hypothalamic chiasmatic glioma (HCLGG), diffuse intrinsic pontine glioma (DIPG), and high-grade glioma (HGG). Twenty-seven statements were drafted and subjected to online Delphi consensus voting by participants, seeking >70% agreement from >60% of respondents; where
Published: 2013
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41. SIOP PODC Adapted treatment guidelines for low grade gliomas in low and middle income settings

Author: Hessissen, L, Parkes, J, Amayiri, N, Mushtaq, N, Sirachainan, N, Anacak, Y, Mitra, D, Figaji, A, Schouten-van Meeteren, A, Sullivan, M, Burger, H, Davidson, A, Bouffet, E, Bailey, S, Hessissen, L, Parkes, J, Amayiri, N, Mushtaq, N, Sirachainan, N, Anacak, Y, Mitra, D, Figaji, A, Schouten-van Meeteren, A, Sullivan, M, Burger, H, Davidson, A, Bouffet, E, and Bailey, S
Abstract: Effective treatment of children with low grade glioma (LGG) requires a functioning multi-disciplinary team with adequate neurosurgical, neuroradiological, pathological, radiotherapy and chemotherapy facilities and personnel. In addition, the treating centre should have the capacity to manage a variety of LGG and treatment-associated complications. These requirements have made it difficult for many centers in low and middle-income countries (LMIC) to offer effective treatment and follow up. This article provides management recommendations for children with LGG according to the level of facilities available.
Published: 2017

42. The current consensus on the clinical management of intracranial ependymoma and its distinct molecular variants

Author: Pajtler, KW, Mack, SC, Ramaswamy, V, Smith, CA, Witt, H, Smith, A, Hansford, JR, von Hoff, K, Wright, KD, Hwang, E, Frappaz, D, Kanemura, Y, Massimino, M, Faure-Conter, C, Modena, P, Tabori, U, Warren, KE, Holland, EC, Ichimura, K, Giangaspero, F, Castel, D, von Deimling, A, Kool, M, Dirks, PB, Grundy, RG, Foreman, NK, Gajjar, A, Korshunov, A, Finlay, J, Gilbertson, RJ, Ellison, DW, Aldape, KD, Merchant, TE, Bouffet, E, Pfister, SM, Taylor, MD, Pajtler, KW, Mack, SC, Ramaswamy, V, Smith, CA, Witt, H, Smith, A, Hansford, JR, von Hoff, K, Wright, KD, Hwang, E, Frappaz, D, Kanemura, Y, Massimino, M, Faure-Conter, C, Modena, P, Tabori, U, Warren, KE, Holland, EC, Ichimura, K, Giangaspero, F, Castel, D, von Deimling, A, Kool, M, Dirks, PB, Grundy, RG, Foreman, NK, Gajjar, A, Korshunov, A, Finlay, J, Gilbertson, RJ, Ellison, DW, Aldape, KD, Merchant, TE, Bouffet, E, Pfister, SM, and Taylor, MD
Abstract: Multiple independent genomic profiling efforts have recently identified clinically and molecularly distinct subgroups of ependymoma arising from all three anatomic compartments of the central nervous system (supratentorial brain, posterior fossa, and spinal cord). These advances motivated a consensus meeting to discuss: (1) the utility of current histologic grading criteria, (2) the integration of molecular-based stratification schemes in future clinical trials for patients with ependymoma and (3) current therapy in the context of molecular subgroups. Discussion at the meeting generated a series of consensus statements and recommendations from the attendees, which comment on the prognostic evaluation and treatment decisions of patients with intracranial ependymoma (WHO Grade II/III) based on the knowledge of its molecular subgroups. The major consensus among attendees was reached that treatment decisions for ependymoma (outside of clinical trials) should not be based on grading (II vs III). Supratentorial and posterior fossa ependymomas are distinct diseases, although the impact on therapy is still evolving. Molecular subgrouping should be part of all clinical trials henceforth.
Published: 2017

43. Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup: a retrospective integrated clinical and molecular analysis

Author: Thompson, EM, Hielscher, T, Bouffet, E, Remke, M, Luu, B, Gururangan, S, McLendon, RE, Bigner, DD, Lipp, ES, Perreault, S, Cho, YJ, Grant, G, Kim, SK, Lee, JY, Rao, AAN, Giannini, C, Li, KKW, Ng, HK, Yao, Y, Kumabe, T, Tominaga, T, Grajkowska, WA, Perek-Polnik, M, Low, DCY, Seow, WT, Chang, KTE, Mora, J, Pollack, IF, Hamilton, RL, Leary, S, Moore, AS, Ingram, WJ, Hallahan, AR, Jouvet, A, Fèvre-Montange, M, Vasiljevic, A, Faure-Conter, C, Shofuda, T, Kagawa, N, Hashimoto, N, Jabado, N, Weil, AG, Gayden, T, Wataya, T, Shalaby, T, Grotzer, M, Zitterbart, K, Sterba, J, Kren, L, Hortobágyi, T, Klekner, A, László, B, Pócza, T, Hauser, P, Schüller, U, Jung, S, Jang, WY, French, PJ, Kros, JM, van Veelen, MLC, Massimi, L, Leonard, JR, Rubin, JB, Vibhakar, R, Chambless, LB, Cooper, MK, Thompson, RC, Faria, CC, Carvalho, A, Nunes, S, Pimentel, J, Fan, X, Muraszko, KM, López-Aguilar, E, Lyden, D, Garzia, L, Shih, DJH, Kijima, N, Schneider, C, Adamski, J, Northcott, PA, Kool, M, Jones, DTW, Chan, JA, Nikolic, A, Garre, ML, Van Meir, EG, Osuka, S, Olson, JJ, Jahangiri, A, and Castro, BA
Subjects: Adult, Male, Canada, Brain Neoplasms, Infant, Prognosis, Magnetic Resonance Imaging, Combined Modality Therapy, Disease-Free Survival, Child, Preschool, Disease Progression, Humans, Female, Child, Medulloblastoma, Retrospective Studies
Abstract: © 2016 Elsevier Ltd Background Patients with incomplete surgical resection of medulloblastoma are controversially regarded as having a marker of high-risk disease, which leads to patients undergoing aggressive surgical resections, so-called second-look surgeries, and intensified chemoradiotherapy. All previous studies assessing the clinical importance of extent of resection have not accounted for molecular subgroup. We analysed the prognostic value of extent of resection in a subgroup-specific manner. Methods We retrospectively identified patients who had a histological diagnosis of medulloblastoma and complete data about extent of resection and survival from centres participating in the Medulloblastoma Advanced Genomics International Consortium. We collected from resections done between April, 1997, and February, 2013, at 35 international institutions. We established medulloblastoma subgroup affiliation by gene expression profiling on frozen or formalin-fixed paraffin-embedded tissues. We classified extent of resection on the basis of postoperative imaging as gross total resection (no residual tumour), near-total resection (30 Gy vs no craniospinal irradiation). The primary analysis outcome was the effect of extent of resection by molecular subgroup and the effects of other clinical variables on overall and progression-free survival. Findings We included 787 patients with medulloblastoma (86 with WNT tumours, 242 with SHH tumours, 163 with group 3 tumours, and 296 with group 4 tumours) in our multivariable Cox models of progression-free and overall survival. We found that the prognostic benefit of increased extent of resection for patients with medulloblastoma is attenuated after molecular subgroup affiliation is taken into account. We identified a progression-free survival benefit for gross total resection over sub-total resection (hazard ratio [HR] 1·45, 95% CI 1·07–1·96, p=0·16) but no overall survival benefit (HR 1·23, 0·87–1·72, p=0·24). We saw no progression-free survival or overall survival benefit for gross total resection compared with near-total resection (HR 1·05, 0·71–1·53, p=0·8158 for progression-free survival and HR 1·14, 0·75–1·72, p=0·55 for overall survival). No significant survival benefit existed for greater extent of resection for patients with WNT, SHH, or group 3 tumours (HR 1·03, 0·67–1·58, p=0·89 for sub-total resection vs gross total resection). For patients with group 4 tumours, gross total resection conferred a benefit to progression-free survival compared with sub-total resection (HR 1·97, 1·22–3·17, p=0·0056), especially for those with metastatic disease (HR 2·22, 1·00–4·93, p=0·050). However, gross total resection had no effect on overall survival compared with sub-total resection in patients with group 4 tumours (HR 1·67, 0·93–2·99, p=0·084). Interpretation The prognostic benefit of increased extent of resection for patients with medulloblastoma is attenuated after molecular subgroup affiliation is taken into account. Although maximum safe surgical resection should remain the standard of care, surgical removal of small residual portions of medulloblastoma is not recommended when the likelihood of neurological morbidity is high because there is no definitive benefit to gross total resection compared with near-total resection. Funding Canadian Cancer Society Research Institute, Terry Fox Research Institute, Canadian Institutes of Health Research, National Institutes of Health, Pediatric Brain Tumor Foundation, and the Garron Family Chair in Childhood Cancer Research.
Published: 2016
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44. MB-35VERY ENCOURAGING LONG-TERM SURVIVAL AND NEUROCOGNITIVE OUTCOME OF YOUNG CHILDREN TREATED FOR MEDULLOBLASTOMA WITH SEQUENTIAL HIGH DOSE CHEMOTHERAPY

Author: Lafay-Cousin L, Chi S, Smith A, Wells E, Madden J, Margol A, Ramaswamy V, Owen E, Strother D, Dhall G, Nicholas Foreman, Packer R, and Bouffet E
Subjects: Cancer Research, Oncology, Neurology (clinical), Abstracts from the 3rd Biennial Conference on Pediatric Neuro-Oncology Basic and Translational Research
Published: 2015

45. Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup: A retrospective integrated clinical and molecular analysis

Author: Thompson, E.M. (Eric M.), Hielscher, T. (Thomas), Bouffet, E. (Eric), Remke, M. (Marc), Luu, P. (Phan), Gururangan, S. (Sridharan), McLendon, R.E. (Roger E.), Bigner, D.D. (Darell), Lipp, E.S. (Eric S.), Perreault, S. (Sebastien), Cho, Y.-J. (Yoon-Jae), Grant, G. (Gerald), Kim, S.-K. (Seung-Ki), Lee, J.Y. (Ji Yeoun), Rao, A.A.N. (Amulya A. Nageswara), Giannini, C. (Caterina), Li, K.K.W. (Kay Ka Wai), Ng, H.-K. (Ho-Keung), Yao, Y. (Yu), Kumabe, T. (Toshihiro), Tominaga, T. (Teiji), Grajkowska, W.A. (Wieslawa), Perek-Polnik, M. (Marta), Low, D.C.Y. (David C.Y.), Seow, W.T. (Wan Tew), Chang, K.T.E. (Kenneth T.E.), Mora, J. (Jaume), Pollack, A. (Aaron), Hamilton, R.L. (Ronald L.), Leary, S. (Sarah), Moore, A.S. (Andrew S.), Ingram, W.J. (Wendy J.), Hallahan, A.R. (Andrew R.), Jouvet, A. (Anne), Fèvre-Montange, M. (Michelle), Vasiljevic, A. (Alexandre), Faure-Conter, C. (Cecile), Shofuda, T. (Tomoko), Kagawa, N. (Naoki), Hashimoto, N. (Naoya), Jabado, N. (Nada), Weil, A.G. (Alexander G.), Gayden, T. (Tenzin), Wataya, T. (Takafumi), Shalaby, T. (Tarek), Grotzer, M. (Michael), Zitterbart, K. (Karel), Sterba, J., Kren, L. (Leos), Hortobágyi, T. (Tibor), Klekner, A. (Almos), Bognár, L. (László), Pócza, T. (Tímea), Hauser, P. (Peter), Schüller, U. (Ulrich), Jung, S. (Shin), Jang, W.-Y. (Woo-Youl), French, P.J. (Pim), Kros, J.M. (Johan), Veelen-Vincent, M.L.C. (Marie-Lise) van, Massimi, L. (Luca), Leonard, J.R. (Jeffrey), Rubin, J.B. (Joshua), Vibhakar, R. (Rajeev), Chambless, L.B. (Lola B.), Cooper, M.K. (Michael), Thompson, R.C. (Reid), Faria, R. (Rui), Carvalho, A. (Alice), Nunes, S. (Sofia), Pimentel, J., Fan, X. (Xing), Muraszko, K.M. (Karin), López-Aguilar, E. (Enrique), Lyden, D. (David), Garzia, L. (Livia), Shih, D.J.H. (David J.), Kijima, N. (Noriyuki), Schneider, C. (Christian), Adamski, J. (Jennifer), Northcott, P.A. (Paul A.), Kool, M. (Marcel), Jones, D. (David), Chan, J.A. (Jennifer A.), Nikolic, A. (Ana), Garre, M.L. (Maria Luisa), Van Meir, E.G. (Erwin G.), Osuka, S. (Satoru), Olson, J.J. (Jeffrey J.), Jahangiri, A. (Arman), Castro, B.A. (Brandyn A.), Gupta, N. (Nalin), Weiss, W.A. (William A.), Moxon-Emre, I. (Iska), Mabbott, D.J. (Donald J.), Lassaletta, A. (Alvaro), Hawkins, C.E. (Cynthia), Tabori, U. (Uri), Drake, J. (James), Kulkarni, A. (Abhaya), Dirks, M. (Maaike), Rutka, J.T. (James), Korshunov, A. (Andrey), Pfister, S.M. (Stefan), Packer, R.J. (Roger J.), Ramaswamy, E.A., Taylor, M.D. (Michael), Thompson, E.M. (Eric M.), Hielscher, T. (Thomas), Bouffet, E. (Eric), Remke, M. (Marc), Luu, P. (Phan), Gururangan, S. (Sridharan), McLendon, R.E. (Roger E.), Bigner, D.D. (Darell), Lipp, E.S. (Eric S.), Perreault, S. (Sebastien), Cho, Y.-J. (Yoon-Jae), Grant, G. (Gerald), Kim, S.-K. (Seung-Ki), Lee, J.Y. (Ji Yeoun), Rao, A.A.N. (Amulya A. Nageswara), Giannini, C. (Caterina), Li, K.K.W. (Kay Ka Wai), Ng, H.-K. (Ho-Keung), Yao, Y. (Yu), Kumabe, T. (Toshihiro), Tominaga, T. (Teiji), Grajkowska, W.A. (Wieslawa), Perek-Polnik, M. (Marta), Low, D.C.Y. (David C.Y.), Seow, W.T. (Wan Tew), Chang, K.T.E. (Kenneth T.E.), Mora, J. (Jaume), Pollack, A. (Aaron), Hamilton, R.L. (Ronald L.), Leary, S. (Sarah), Moore, A.S. (Andrew S.), Ingram, W.J. (Wendy J.), Hallahan, A.R. (Andrew R.), Jouvet, A. (Anne), Fèvre-Montange, M. (Michelle), Vasiljevic, A. (Alexandre), Faure-Conter, C. (Cecile), Shofuda, T. (Tomoko), Kagawa, N. (Naoki), Hashimoto, N. (Naoya), Jabado, N. (Nada), Weil, A.G. (Alexander G.), Gayden, T. (Tenzin), Wataya, T. (Takafumi), Shalaby, T. (Tarek), Grotzer, M. (Michael), Zitterbart, K. (Karel), Sterba, J., Kren, L. (Leos), Hortobágyi, T. (Tibor), Klekner, A. (Almos), Bognár, L. (László), Pócza, T. (Tímea), Hauser, P. (Peter), Schüller, U. (Ulrich), Jung, S. (Shin), Jang, W.-Y. (Woo-Youl), French, P.J. (Pim), Kros, J.M. (Johan), Veelen-Vincent, M.L.C. (Marie-Lise) van, Massimi, L. (Luca), Leonard, J.R. (Jeffrey), Rubin, J.B. (Joshua), Vibhakar, R. (Rajeev), Chambless, L.B. (Lola B.), Cooper, M.K. (Michael), Thompson, R.C. (Reid), Faria, R. (Rui), Carvalho, A. (Alice), Nunes, S. (Sofia), Pimentel, J., Fan, X. (Xing), Muraszko, K.M. (Karin), López-Aguilar, E. (Enrique), Lyden, D. (David), Garzia, L. (Livia), Shih, D.J.H. (David J.), Kijima, N. (Noriyuki), Schneider, C. (Christian), Adamski, J. (Jennifer), Northcott, P.A. (Paul A.), Kool, M. (Marcel), Jones, D. (David), Chan, J.A. (Jennifer A.), Nikolic, A. (Ana), Garre, M.L. (Maria Luisa), Van Meir, E.G. (Erwin G.), Osuka, S. (Satoru), Olson, J.J. (Jeffrey J.), Jahangiri, A. (Arman), Castro, B.A. (Brandyn A.), Gupta, N. (Nalin), Weiss, W.A. (William A.), Moxon-Emre, I. (Iska), Mabbott, D.J. (Donald J.), Lassaletta, A. (Alvaro), Hawkins, C.E. (Cynthia), Tabori, U. (Uri), Drake, J. (James), Kulkarni, A. (Abhaya), Dirks, M. (Maaike), Rutka, J.T. (James), Korshunov, A. (Andrey), Pfister, S.M. (Stefan), Packer, R.J. (Roger J.), Ramaswamy, E.A., and Taylor, M.D. (Michael)
Abstract: Background: Patients with incomplete surgical resection of medulloblastoma are controversially regarded as having a marker of high-risk disease, which leads to patients undergoing aggressive surgical resections, so-called second-look surgeries, and intensified chemoradiotherapy. All previous studies assessing the clinical importance of extent of resection have not accounted for molecular subgroup. We analysed the prognostic value of extent of resection in a subgroup-specific manner. Methods: We retrospectively identified patients who had a histological diagnosis of medulloblastoma and complete data about extent of resection and survival from centres participating in the Medulloblastoma Advanced Genomics International Consortium. We collected from resections done between April, 1997, and February, 2013, at 35 international institutions. We established medulloblastoma subgroup affiliation by gene expression profiling on frozen or formalin-fixed paraffin-embedded tissues. We classified extent of resection on the basis of postoperative imaging as gross total resection (no residual tumour), near-total resection (<1·5 cm2 tumour remaining), or sub-total resection (≥1·5 cm2 tumour remaining). We did multivariable analyses of overall survival and progression-free survival using the variables molecular subgroup (WNT, SHH, group 4, and group 3), age (<3 vs ≥3 years old), metastatic status (metastases vs no metastases), geographical location of therapy (North America/Australia vs rest of the world), receipt of chemotherapy (yes vs no) and receipt of craniospinal irradiation (<30 Gy or >30 Gy vs no craniospinal irradiation). The primary analysis outcome was the effect of extent of resection by molecular subgroup and the effects of other clinical variables on overall and progression-free survival. Findings: We included 787 patients with medulloblastoma (86 with WNT tumours, 242 with SHH tumours, 163 with group 3 tumours, and 296 with group 4 tumours) in our multivariable Cox mod
Published: 2016
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46. Integrated (epi)-Genomic Analyses Identify Subgroup-Specific Therapeutic Targets in CNS Rhabdoid Tumors.

Author: Torchia, J, Golbourn, B, Feng, S, Ho, KC, Sin-Chan, P, Vasiljevic, A, Norman, JD, Guilhamon, P, Garzia, L, Agamez, NR, Lu, M, Chan, TS, Picard, D, de Antonellis, P, Khuong-Quang, D-A, Planello, AC, Zeller, C, Barsyte-Lovejoy, D, Lafay-Cousin, L, Letourneau, L, Bourgey, M, Yu, M, Gendoo, DMA, Dzamba, M, Barszczyk, M, Medina, T, Riemenschneider, AN, Morrissy, AS, Ra, Y-S, Ramaswamy, V, Remke, M, Dunham, CP, Yip, S, Ng, H-K, Lu, J-Q, Mehta, V, Albrecht, S, Pimentel, J, Chan, JA, Somers, GR, Faria, CC, Roque, L, Fouladi, M, Hoffman, LM, Moore, AS, Wang, Y, Choi, SA, Hansford, JR, Catchpoole, D, Birks, DK, Foreman, NK, Strother, D, Klekner, A, Bognár, L, Garami, M, Hauser, P, Hortobágyi, T, Wilson, B, Hukin, J, Carret, A-S, Van Meter, TE, Hwang, EI, Gajjar, A, Chiou, S-H, Nakamura, H, Toledano, H, Fried, I, Fults, D, Wataya, T, Fryer, C, Eisenstat, DD, Scheinemann, K, Fleming, AJ, Johnston, DL, Michaud, J, Zelcer, S, Hammond, R, Afzal, S, Ramsay, DA, Sirachainan, N, Hongeng, S, Larbcharoensub, N, Grundy, RG, Lulla, RR, Fangusaro, JR, Druker, H, Bartels, U, Grant, R, Malkin, D, McGlade, CJ, Nicolaides, T, Tihan, T, Phillips, J, Majewski, J, Montpetit, A, Bourque, G, Bader, GD, Reddy, AT, Gillespie, GY, Warmuth-Metz, M, Rutkowski, S, Tabori, U, Lupien, M, Brudno, M, Schüller, U, Pietsch, T, Judkins, AR, Hawkins, CE, Bouffet, E, Kim, S-K, Dirks, PB, Taylor, MD, Erdreich-Epstein, A, Arrowsmith, CH, De Carvalho, DD, Rutka, JT, Jabado, N, Huang, A, Torchia, J, Golbourn, B, Feng, S, Ho, KC, Sin-Chan, P, Vasiljevic, A, Norman, JD, Guilhamon, P, Garzia, L, Agamez, NR, Lu, M, Chan, TS, Picard, D, de Antonellis, P, Khuong-Quang, D-A, Planello, AC, Zeller, C, Barsyte-Lovejoy, D, Lafay-Cousin, L, Letourneau, L, Bourgey, M, Yu, M, Gendoo, DMA, Dzamba, M, Barszczyk, M, Medina, T, Riemenschneider, AN, Morrissy, AS, Ra, Y-S, Ramaswamy, V, Remke, M, Dunham, CP, Yip, S, Ng, H-K, Lu, J-Q, Mehta, V, Albrecht, S, Pimentel, J, Chan, JA, Somers, GR, Faria, CC, Roque, L, Fouladi, M, Hoffman, LM, Moore, AS, Wang, Y, Choi, SA, Hansford, JR, Catchpoole, D, Birks, DK, Foreman, NK, Strother, D, Klekner, A, Bognár, L, Garami, M, Hauser, P, Hortobágyi, T, Wilson, B, Hukin, J, Carret, A-S, Van Meter, TE, Hwang, EI, Gajjar, A, Chiou, S-H, Nakamura, H, Toledano, H, Fried, I, Fults, D, Wataya, T, Fryer, C, Eisenstat, DD, Scheinemann, K, Fleming, AJ, Johnston, DL, Michaud, J, Zelcer, S, Hammond, R, Afzal, S, Ramsay, DA, Sirachainan, N, Hongeng, S, Larbcharoensub, N, Grundy, RG, Lulla, RR, Fangusaro, JR, Druker, H, Bartels, U, Grant, R, Malkin, D, McGlade, CJ, Nicolaides, T, Tihan, T, Phillips, J, Majewski, J, Montpetit, A, Bourque, G, Bader, GD, Reddy, AT, Gillespie, GY, Warmuth-Metz, M, Rutkowski, S, Tabori, U, Lupien, M, Brudno, M, Schüller, U, Pietsch, T, Judkins, AR, Hawkins, CE, Bouffet, E, Kim, S-K, Dirks, PB, Taylor, MD, Erdreich-Epstein, A, Arrowsmith, CH, De Carvalho, DD, Rutka, JT, Jabado, N, and Huang, A
Abstract: We recently reported that atypical teratoid rhabdoid tumors (ATRTs) comprise at least two transcriptional subtypes with different clinical outcomes; however, the mechanisms underlying therapeutic heterogeneity remained unclear. In this study, we analyzed 191 primary ATRTs and 10 ATRT cell lines to define the genomic and epigenomic landscape of ATRTs and identify subgroup-specific therapeutic targets. We found ATRTs segregated into three epigenetic subgroups with distinct genomic profiles, SMARCB1 genotypes, and chromatin landscape that correlated with differential cellular responses to a panel of signaling and epigenetic inhibitors. Significantly, we discovered that differential methylation of a PDGFRB-associated enhancer confers specific sensitivity of group 2 ATRT cells to dasatinib and nilotinib, and suggest that these are promising therapies for this highly lethal ATRT subtype.
Published: 2016

47. CNS tumours The first study of dabrafenib in pediatric patients with BRAF V600–mutant relapsed or refractory low-grade gliomas

Author: Kieran, M.W., primary, Bouffet, E., additional, Tabori, U., additional, Broniscer, A., additional, Cohen, K., additional, Hansford, J., additional, Geoerger, B., additional, Hingorani, P., additional, Dunkel, I., additional, Russo, M., additional, Tseng, L., additional, Liu, Q., additional, Nebot, N., additional, Whitlock, J., additional, and Hargrave, D., additional
Published: 2016
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48. 407TiP - Phase II open-label, global study evaluating dabrafenib in combination with trametinib in pediatric patients with BRAF V600–mutant high-grade glioma (HGG) or low-grade glioma (LGG)

Author: Hargrave, D., Witt, O., Cohen, K., Packer, R., Lissat, A., Kordes, U., Laetsch, T.W., Hoffman, L., Lassaletta, A., Gerber, N.U., Gilheeney, S., Holm, S., Kramm, C., Sumerauer, D., Reitmann, C., Russo, M.W., and Bouffet, E.
Published: 2018
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49. HG-14 * CLINICAL, RADIOGRAPHIC, AND HISTOLOGIC CHARACTERISTICS OF LONG-TERM SURVIVORS OF DIFFUSE INTRINSIC PONTINE GLIOMA: A REPORT FROM THE INTERNATIONAL DIPG REGISTRY

Author: Hoffman, L. M., primary, Bartels, U., additional, Miles, L., additional, Hawkins, C., additional, Goldman, S., additional, Leary, S., additional, Hassal, T., additional, Minturn, J., additional, Packer, R., additional, Foreman, N., additional, Warren, K., additional, Broniscer, A., additional, Broxon, E., additional, Shih, C.-S., additional, Leach, J., additional, Jones, B., additional, Baugh, J., additional, Hacker, B., additional, Lerme, B., additional, Jones, C., additional, Savage, S., additional, Kirkendall, J., additional, Doughman, R., additional, Wollman, M., additional, Millett, L., additional, O'Keefe, R., additional, Bouffet, E., additional, van Vuurden, D. G., additional, and Fouladi, M., additional
Published: 2015
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50. GE-09 * COMBINED HEREDITARY AND SOMATIC MUTATIONS OF REPLICATION ERROR REPAIR GENES RESULT IN RAPID ONSET OF ULTRA-HYPERMUTATED MALIGNANT BRAIN TUMORS IN CHILDREN

Author: Shlien, A., primary, Campbell, B. B., additional, de Borja, R., additional, Alexandrov, L. B., additional, Merino, D. M., additional, Remke, M., additional, Bakry, D., additional, Dirks, P., additional, Huang, A., additional, Grundy, R. G., additional, Durno, C., additional, Aronson, M., additional, Taylor, M. D., additional, Pursell, Z. F., additional, Pearson, C. E., additional, Malkin, D., additional, Bouffet, E., additional, Hawkins, C., additional, Campbell, P. J., additional, and Tabori, U., additional
Published: 2015
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