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1. In vivo mapping of pharmacologically induced functional reorganization onto the human brain’s neurotransmitter landscape

Author

Luppi, Andrea I, Hansen, Justine Y, Adapa, Ram, Carhart-Harris, Robin L, Roseman, Leor, Timmermann, Christopher, Golkowski, Daniel, Ranft, Andreas, Ilg, Rüdiger, Jordan, Denis, Bonhomme, Vincent, Vanhaudenhuyse, Audrey, Demertzi, Athena, Jaquet, Oceane, Bahri, Mohamed Ali, Alnagger, Naji LN, Cardone, Paolo, Peattie, Alexander RD, Manktelow, Anne E, de Araujo, Draulio B, Sensi, Stefano L, Owen, Adrian M, Naci, Lorina, Menon, David K, Misic, Bratislav, and Stamatakis, Emmanuel A

Subjects
Neurosciences, Biomedical Imaging, Brain Disorders, Underpinning research, 1.1 Normal biological development and functioning, Neurological, Good Health and Well Being, Humans, Brain, Ketamine, Membrane Transport Proteins, Methylphenidate, Modafinil
Abstract

To understand how pharmacological interventions can exert their powerful effects on brain function, we need to understand how they engage the brain's rich neurotransmitter landscape. Here, we bridge microscale molecular chemoarchitecture and pharmacologically induced macroscale functional reorganization, by relating the regional distribution of 19 neurotransmitter receptors and transporters obtained from positron emission tomography, and the regional changes in functional magnetic resonance imaging connectivity induced by 10 different mind-altering drugs: propofol, sevoflurane, ketamine, lysergic acid diethylamide (LSD), psilocybin, N,N-Dimethyltryptamine (DMT), ayahuasca, 3,4-methylenedioxymethamphetamine (MDMA), modafinil, and methylphenidate. Our results reveal a many-to-many mapping between psychoactive drugs' effects on brain function and multiple neurotransmitter systems. The effects of both anesthetics and psychedelics on brain function are organized along hierarchical gradients of brain structure and function. Last, we show that regional co-susceptibility to pharmacological interventions recapitulates co-susceptibility to disorder-induced structural alterations. Collectively, these results highlight rich statistical patterns relating molecular chemoarchitecture and drug-induced reorganization of the brain's functional architecture.

Published
2023

4. Impact of age on safety of Busulfan-Melphalan followed by autologous hematopoietic stem-cell transplantation versus standard chemotherapy in the patients of the EURO-E.W.I.N.G. 99 and Ewing 2008 clinical trials

Author

Choderlos de Laclos, Xavier, Risbourg, Séverine, Brennan, Bernadette, Bertucci, François, Gaspar, Nathalie, Gelderblom, Hans, Hawkins, Douglas S., Janeway, Katherine, Juergens, Heribert, Kasper, Bernd, Krailo, Mark D., Cécile Le Deley, Marie, Marec-Bérard, Perrine, McCabe, Martin G., Metzler, Markus, Ranft, Andreas, Strauss, Sandra, Tabone, Marie-Dominique, Windsor, Rachael, Dirksen, Uta, and Gandemer, Virginie

Published
2024
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5. Interindividual variation in ovarian reserve after gonadotoxic treatment in female childhood cancer survivors – a genome-wide association study: results from PanCareLIFE

Author

van der Perk, M.E. Madeleine, Broer, Linda, Yasui, Yutaka, Laven, Joop S.E., Robison, Leslie L., Tissing, Wim J.E., Versluys, Birgitta, Bresters, Dorine, Kaspers, Gertjan J.L., Lambalk, Cornelis B., Overbeek, Annelies, Loonen, Jacqueline J., Beerendonk, Catharina C.M., Byrne, Julianne, Berger, Claire, Clemens, Eva, van Dulmen-den Broeder, Eline, Dirksen, Uta, van der Pal, Helena J., de Vries, Andrica C.H., Winther, Jeanette Falck, Ranft, Andreas, Fosså, Sophie D., Grabow, Desiree, Muraca, Monica, Kaiser, Melanie, Kepák, Tomáš, Kruseova, Jarmila, Modan-Moses, Dalit, Spix, Claudia, Zolk, Oliver, Kaatsch, Peter, Kremer, Leontien C.M., Brooke, Russell J., Wang, Fan, Baedke, Jessica L., Uitterlinden, André G., Bos, Annelies M.E., van Leeuwen, Flora E., Ness, Kirsten K., Hudson, Melissa M., van der Kooi, Anne-Lotte L.F., and van den Heuvel-Eibrink, Marry M.

Published
2024
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6. Association between local treatment modalities and event-free survival, overall survival, and local recurrence in patients with localised Ewing Sarcoma. Report from the Ewing 2008 trial

Author

Heesen, Philip, Ranft, Andreas, Bhadri, Vivek, Brichard, Benedicte, Collaud, Stephane, Cyprova, Sona, Eich, Hans, Ek, Torben, Gelderblom, Hans, Hardes, Jendrik, Haveman, Lianne, Jabar, Susanne, Hartmann, Wolfgang, Andreou, Dimosthenis, Hauser, Peter, Kersting, Josephine, Juergens, Heribert, Kanerva, Jukka, Kühne, Thomas, Raciborska, Anna, Rascon, Jelena, Streitbürger, Arne, Timmermann, Beate, Uhlenbruch, Yasmin, and Dirksen, Uta

Published
2023
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7. Effect of Radiotherapy Dose on Outcome in Nonmetastatic Ewing Sarcoma

Author

Kersting, Josephine, Ranft, Andreas, Bhadri, Vivek, Brichard, Bénédicte, Collaud, Stéphane, Cyprová, Sona, Eich, Hans, Ek, Torben, Gelderblom, Hans, Hardes, Jendrik, Haveman, Lianne, Hartmann, Wolfgang, Hauser, Peter, Heesen, Philip, Jürgens, Heribert, Kanerva, Jukka, Kühne, Thomas, Raciborska, Anna, Rascon, Jelena, Rechl, Victor, Streitbürger, Arne, Timmermann, Beate, Uhlenbruch, Yasmine, and Dirksen, Uta

Published
2023
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8. High-Dose Chemotherapy Compared With Standard Chemotherapy and Lung Radiation in Ewing Sarcoma With Pulmonary Metastases: Results of the European Ewing Tumour Working Initiative of National Groups, 99 Trial and EWING 2008.

Author

Dirksen, Uta, Brennan, Bernadette, Le Deley, Marie-Cécile, Cozic, Nathalie, van den Berg, Henk, Bhadri, Vivek, Brichard, Bénédicte, Claude, Line, Craft, Alan, Amler, Susanne, Gaspar, Natalie, Gelderblom, Hans, Goldsby, Robert, Gorlick, Richard, Grier, Holcombe E, Guinbretiere, Jean-Marc, Hauser, Peter, Hjorth, Lars, Janeway, Katherine, Juergens, Heribert, Judson, Ian, Krailo, Mark, Kruseova, Jarmila, Kuehne, Thomas, Ladenstein, Ruth, Lervat, Cyril, Lessnick, Stephen L, Lewis, Ian, Linassier, Claude, Marec-Berard, Perrine, Marina, Neyssa, Morland, Bruce, Pacquement, Hélène, Paulussen, Michael, Randall, R Lor, Ranft, Andreas, Le Teuff, Gwénaël, Wheatley, Keith, Whelan, Jeremy, Womer, Richard, Oberlin, Odile, Hawkins, Douglas S, and Euro-E.W.I.N.G. 99 and Ewing 2008 Investigators

Subjects
Euro-E.W.I.N.G. 99 and Ewing 2008 Investigators, Humans, Bone Neoplasms, Lung Neoplasms, Neoplasm Recurrence, Local, Disease Progression, Antineoplastic Combined Chemotherapy Protocols, Neoadjuvant Therapy, Radiotherapy, Adjuvant, Pneumonectomy, Hematopoietic Stem Cell Transplantation, Transplantation, Autologous, Risk Assessment, Risk Factors, Time Factors, Adolescent, Adult, Middle Aged, Child, Child, Preschool, Infant, Europe, Female, Male, Young Adult, Sarcoma, Ewing, Progression-Free Survival, Lung, Stem Cell Research, Cancer, Pediatric, Rare Diseases, Clinical Research, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Clinical Sciences, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

PurposeThe R2Pulm trial was conducted to evaluate the effect of busulfan-melphalan high-dose chemotherapy with autologous stem-cell rescue (BuMel) without whole-lung irradiation (WLI) on event-free survival (main end point) and overall survival, compared with standard chemotherapy with WLI in Ewing sarcoma (ES) presenting with pulmonary and/or pleural metastases.MethodsFrom 2000 to 2015, we enrolled patients younger than 50 years of age with newly diagnosed ES and with only pulmonary or pleural metastases. Patients received chemotherapy with six courses of vincristine, ifosfamide, doxorubicin, and etoposide (VIDE) and one course of vincristine, dactinomycin, and ifosfamide (VAI) before either BuMel or seven courses of VAI and WLI (VAI plus WLI) by randomized assignment. The analysis was conducted as intention to treat. The estimates of the hazard ratio (HR), 95% CI, and P value were corrected for the three previous interim analyses by the inverse normal method.ResultsOf 543 potentially eligible patients, 287 were randomly assigned to VAI plus WLI (n = 143) or BuMel (n = 144). Selected patients requiring radiotherapy to an axial primary site were excluded from randomization to avoid excess organ toxicity from interaction between radiotherapy and busulfan. Median follow-up was 8.1 years. We did not observe any significant difference in survival outcomes between treatment groups. Event-free survival was 50.6% versus 56.6% at 3 years and 43.1% versus 52.9% at 8 years, for VAI plus WLI and BuMel patients, respectively, resulting in an HR of 0.79 (95% CI, 0.56 to 1.10; P = .16). For overall survival, the HR was 1.00 (95% CI, 0.70 to 1.44; P = .99). Four patients died as a result of BuMel-related toxicity, and none died after VAI plus WLI. Significantly more patients in the BuMel arm experienced severe acute toxicities than in the VAI plus WLI arm.ConclusionIn ES with pulmonary or pleural metastases, there is no clear benefit from BuMel compared with conventional VAI plus WLI.

Published
2019

9. Primary Mediastinal Ewing's Sarcoma: Post Hoc Analysis from Two International Multicenter Prospective Randomized Trials.

Author

Stork, Theresa, Ranft, Andreas, Aigner, Clemens, Jurgens, Heribert, Ladenstein, Ruth L., Timmermann, Beate, Van den Berg, Henk, Dirksen, Uta, and Collaud, Stéphane

Subjects
*MEDIASTINUM, *RESEARCH funding, *DATA analysis, *RARE diseases, *TREATMENT effectiveness, *DESCRIPTIVE statistics, *LONGITUDINAL method, *COMBINED modality therapy, *RESEARCH, *STATISTICS, *EWING'S sarcoma, *OVERALL survival
Abstract

Simple Summary: Ewing sarcomas are rare, aggressive tumors, occurring mostly in children and adolescents. They usually derive from the bone; however, extraskeletal Ewing sarcomas develop in the soft tissue. Ewing sarcoma of the mediastinum is extremely rare; there are only a few cases reported in the literature. The outcome is usually poor with about 30% 5-year survival. We retrieved data from two international, multicenter, prospective, clinical trials investigating the optimal treatment for patients with Ewing sarcoma. We then analyzed the patient and treatment characteristics to gain a better understanding of this rare tumor entity. This study is the first to describe the prevalence of mediastinal Ewing sarcoma in a homogeneously treated patient cohort. Objective: Ewing sarcoma (EWS) of the mediastinum is extremely rare, with only a few cases reported in the literature. We aimed to gain a better understanding of primary mediastinal EWS, describing patients treated within two international, multicenter, prospective, randomized EWS trials. Methods: Data from patients with primary mediastinal EWS were retrieved from the database of the EURO-E.W.I.N.G.99 (ClinicalTrials.gov identifier: NCT00020566) and EWING 2008 (ClinicalTrials.gov identifier: NCT00987636) trials. Patient and treatment characteristics were analyzed. Results: Out of 2969 patients with EWS, 9 (0.3%) had primary mediastinal EWS. The median age at diagnosis was 30.5 years (4 to 49). At the time of diagnosis, n = 3 (33%) patients had synchronous metastases. All patients underwent multiagent chemotherapy. Local therapy for non-metastatic patients was surgery (n = 2, 22%), surgery and radiotherapy (n = 2, 22%) or radiotherapy alone (n = 2, 22%). Surgery consisted of extended resections in most patients (n = 3, 33%). Five-year survival for the whole cohort was 64%. Apart from one patient who was lost to follow-up, all patients (n = 4) who had undergone surgery were alive at the end of follow-up. Conclusions: Primary mediastinal ES is extremely rare, with a prevalence of 0.3% among EWS. Five-year survival was favorable compared to primary mediastinal sarcoma of all histologies and in line with EWS of different origin. [ABSTRACT FROM AUTHOR]

Published
2025
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10. Sonstige Therapieformen – Hämotherapie – Ernährung – apparativ – onkologisch – alternativ – perspektivisch

Author

Thiele, Thomas, Selleng, Kathleen, Ranft, Andreas, Kochs, Eberhard Friedrich, Waldfahrer, Frank, Leuwer, Rudolf, Klein, Martin, Appold, Steffen, Folprecht, Gunnar, Schuler, Patrick, Dörr, Wolfgang, Dörr, Elke, Grötz, Knut A., Riesenbeck, Dorothea, Friese, Karl-Heinz, Plath, Michaela, Zaoui, Karim, and Reiß, Michael, editor

Published
2021
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11. Chirurgische Therapie

Author

Reiß, Michael, Reiß, Gilfe, Weber, Rainer, Leuwer, Rudolf, Müller, Andreas, Ranft, Andreas, Kochs, Eberhard Friedrich, Waldfahrer, Frank, Schraven, Sebastian, Lippert, Burkard M., Bulut, Cem O., Iro, Heinrich, Möckelmann, Nikolaus, Münscher, Adrian, Siegert, Ralf, Preyer, Serana, Jungehülsing, Markus, Tasman, Abel Jan, Hosemann, Werner, Mattheis, Stefan, Verse, Thomas, Zenk, Johannes, Koscielny, Sven, Gutjahr, Kathleen, Mir-Salim, Parwis, and Reiß, Michael, editor

Published
2021
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12. HNO-Heilkunde in Klinik und Praxis

Author

Reiß, Michael, Reiß, Gilfe, Guntinas-Lichius, Orlando, Plontke, Stefan K., Müller, Andreas, Ranft, Andreas, Kochs, Eberhard Friedrich, Send, Thorsten, Michel, Olaf, Weber, Rainer, Müller, Rainer, Schönweiler, Rainer, Schönweiler, Bettina, Waldfahrer, Frank, Ebner, Winfried, Schaefer, Christof, and Reiß, Michael, editor

Published
2021
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14. Communication and ethical considerations for fertility preservation for patients with childhood, adolescent, and young adult cancer: recommendations from the PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group

Author

Anderson, Richard A, Barnbrock, Anke, Beck, Joern D, Bos, Annelies M E, Calaminus, Gabriele, Constine, Louis S, Demeestere, Isabelle, Denzer, Christian, Grabow, Desiree, di Iorgi, Natascia, Hoefgen, Holly R, Jahnukainen, Kirsi, Kaatsch, Peter, Kebudi, Rejin, Lambalk, Cornelis, Langer, Thorsten, Loonen, Jacqueline, Lorenzo, Armando, Meacham, Lillian R, Meissner, Andreas, Mitchell, Rod T, Nahata, Leena, Ranft, Andreas, Dinkelman-Smit, Marij, Stern, Catharyn, Stutz-Grunder, Eveline, Tournaye, Herman, van Dorp, Wendy, van Pelt, Ans M M, de Vries, Andrica, Yu, Richard, Mulder, Renée L, Font-Gonzalez, Anna, van Dulmen-den Broeder, Eline, Quinn, Gwendolyn P, Ginsberg, Jill P, Loeffen, Erik A H, Hudson, Melissa M, Burns, Karen C, van Santen, Hanneke M, Berger, Claire, Diesch, Tamara, Dirksen, Uta, Giwercman, Aleksander, Gracia, Clarisa, Hunter, Sarah E, Kelvin, Joanne F, Klosky, James L, Laven, Joop S E, Lockart, Barbara A, Neggers, Sebastian J C M M, Peate, Michelle, Phillips, Bob, Reed, Damon R, Tinner, Eva Maria E, Byrne, Julianne, Veening, Margreet, van de Berg, Marleen, Verhaak, Chris M, Anazodo, Antoinette, Rodriguez-Wallberg, Kenny, van den Heuvel-Eibrink, Marry M, Asogwa, Ogechukwu A, Brownsdon, Alexandra, Wallace, W Hamish, Green, Daniel M, Skinner, Roderick, Haupt, Riccardo, Kenney, Lisa B, Levine, Jennifer, van de Wetering, Marianne D, Tissing, Wim J E, Paul, Norbert W, Kremer, Leontien C M, and Inthorn, Julia

Published
2021
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15. Factors Influencing the Outcome of Patients with Primary Ewing Sarcoma of the Sacrum

Author

Rechl, Victor, primary, Ranft, Andreas, additional, Bhadri, Vivek, additional, Brichard, Benedicte, additional, Collaud, Stephane, additional, Cyprova, Sona, additional, Eich, Hans, additional, Ek, Torben, additional, Gelderblom, Hans, additional, Hardes, Jendrik, additional, Haveman, Lianne M., additional, Hartmann, Wolfgang, additional, Hauser, Peter, additional, Heesen, Philip, additional, Jürgens, Heribert, additional, Kanerva, Jukka, additional, Kühne, Thomas, additional, Raciborska, Anna, additional, Rascon, Jelena, additional, Streitbürger, Arne, additional, Uhlenbruch, Yasmin, additional, Timmermann, Beate, additional, Kersting, Josephine, additional, Pham, Minh Thanh, additional, and Dirksen, Uta, additional

Published
2024
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16. Interindividual variation in ovarian reserve after gonadotoxic treatment in female childhood cancer survivors - a genome-wide association study: results from PanCareLIFE

Author

MS VPG/Gynaecologie, Cancer, Speerpunt, Zorg en O&O, Child Health, van der Perk, M E Madeleine, Broer, Linda, Yasui, Yutaka, Laven, Joop S E, Robison, Leslie L, Tissing, Wim J E, Versluys, Birgitta, Bresters, Dorine, Kaspers, Gertjan J L, Lambalk, Cornelis B, Overbeek, Annelies, Loonen, Jacqueline J, Beerendonk, Catharina C M, Byrne, Julianne, Berger, Claire, Clemens, Eva, van Dulmen-den Broeder, Eline, Dirksen, Uta, van der Pal, Helena J, de Vries, Andrica C H, Winther, Jeanette Falck, Ranft, Andreas, Fosså, Sophie D, Grabow, Desiree, Muraca, Monica, Kaiser, Melanie, Kepák, Tomáš, Kruseova, Jarmila, Modan-Moses, Dalit, Spix, Claudia, Zolk, Oliver, Kaatsch, Peter, Kremer, Leontien C M, Brooke, Russell J, Wang, Fan, Baedke, Jessica L, Uitterlinden, André G, Bos, Annelies M E, van Leeuwen, Flora E, Ness, Kirsten K, Hudson, Melissa M, van der Kooi, Anne-Lotte L F, van den Heuvel-Eibrink, Marry M, PanCareLIFE Consortium, MS VPG/Gynaecologie, Cancer, Speerpunt, Zorg en O&O, Child Health, van der Perk, M E Madeleine, Broer, Linda, Yasui, Yutaka, Laven, Joop S E, Robison, Leslie L, Tissing, Wim J E, Versluys, Birgitta, Bresters, Dorine, Kaspers, Gertjan J L, Lambalk, Cornelis B, Overbeek, Annelies, Loonen, Jacqueline J, Beerendonk, Catharina C M, Byrne, Julianne, Berger, Claire, Clemens, Eva, van Dulmen-den Broeder, Eline, Dirksen, Uta, van der Pal, Helena J, de Vries, Andrica C H, Winther, Jeanette Falck, Ranft, Andreas, Fosså, Sophie D, Grabow, Desiree, Muraca, Monica, Kaiser, Melanie, Kepák, Tomáš, Kruseova, Jarmila, Modan-Moses, Dalit, Spix, Claudia, Zolk, Oliver, Kaatsch, Peter, Kremer, Leontien C M, Brooke, Russell J, Wang, Fan, Baedke, Jessica L, Uitterlinden, André G, Bos, Annelies M E, van Leeuwen, Flora E, Ness, Kirsten K, Hudson, Melissa M, van der Kooi, Anne-Lotte L F, van den Heuvel-Eibrink, Marry M, and PanCareLIFE Consortium

Published
2024

17. Interindividual variation in ovarian reserve after gonadotoxic treatment in female childhood cancer survivors – a genome-wide association study:results from PanCareLIFE

Author

van der Perk, M. E.Madeleine, Broer, Linda, Yasui, Yutaka, Laven, Joop S.E., Robison, Leslie L., Tissing, Wim J.E., Versluys, Birgitta, Bresters, Dorine, Kaspers, Gertjan J.L., Lambalk, Cornelis B., Overbeek, Annelies, Loonen, Jacqueline J., Beerendonk, Catharina C.M., Byrne, Julianne, Berger, Claire, Clemens, Eva, van Dulmen-den Broeder, Eline, Dirksen, Uta, van der Pal, Helena J., de Vries, Andrica C.H., Winther, Jeanette Falck, Ranft, Andreas, Fosså, Sophie D., Grabow, Desiree, Muraca, Monica, Kaiser, Melanie, Kepák, Tomáš, Kruseova, Jarmila, Modan-Moses, Dalit, Spix, Claudia, Zolk, Oliver, Kaatsch, Peter, Kremer, Leontien C.M., Brooke, Russell J., Wang, Fan, Baedke, Jessica L., Uitterlinden, André G., Bos, Annelies M.E., van Leeuwen, Flora E., Ness, Kirsten K., Hudson, Melissa M., van der Kooi, Anne Lotte L.F., van den Heuvel-Eibrink, Marry M., van der Perk, M. E.Madeleine, Broer, Linda, Yasui, Yutaka, Laven, Joop S.E., Robison, Leslie L., Tissing, Wim J.E., Versluys, Birgitta, Bresters, Dorine, Kaspers, Gertjan J.L., Lambalk, Cornelis B., Overbeek, Annelies, Loonen, Jacqueline J., Beerendonk, Catharina C.M., Byrne, Julianne, Berger, Claire, Clemens, Eva, van Dulmen-den Broeder, Eline, Dirksen, Uta, van der Pal, Helena J., de Vries, Andrica C.H., Winther, Jeanette Falck, Ranft, Andreas, Fosså, Sophie D., Grabow, Desiree, Muraca, Monica, Kaiser, Melanie, Kepák, Tomáš, Kruseova, Jarmila, Modan-Moses, Dalit, Spix, Claudia, Zolk, Oliver, Kaatsch, Peter, Kremer, Leontien C.M., Brooke, Russell J., Wang, Fan, Baedke, Jessica L., Uitterlinden, André G., Bos, Annelies M.E., van Leeuwen, Flora E., Ness, Kirsten K., Hudson, Melissa M., van der Kooi, Anne Lotte L.F., and van den Heuvel-Eibrink, Marry M.

Abstract

Objective: To discover new variants associated with low ovarian reserve after gonadotoxic treatment among adult female childhood cancer survivors using a genome-wide association study approach. Design: Genome-wide association study. Setting: Not applicable. Patients: A discovery cohort of adult female childhood cancer survivors from the pan-European PanCareLIFE cohort (n = 743; median age: 25.8 years), excluding those who received bilateral ovarian irradiation, bilateral oophorectomy, central nervous system or total body irradiation, or stem cell transplantation. Replication was attempted in the US-based St. Jude Lifetime Cohort (n = 391; median age: 31.3 years). Exposure: Female childhood cancer survivors are at risk of therapy-related gonadal impairment. Alkylating agents are well-established risk factors, and the interindividual variability in gonadotoxicity may be explained by genetic polymorphisms. Data were collected in real-life conditions, and cyclophosphamide equivalent doses were used to quantify alkylation agent exposure. Main Outcome Measure: Anti-Müllerian hormone (AMH) levels served as a proxy for ovarian function, and the findings were combined in a meta-analysis. Results: Three genome-wide significant (<5.0 × 10−8) and 16 genome-wide suggestive (<5.0 × 10−6) loci were associated with log-transformed AMH levels, adjusted for cyclophosphamide equivalent dose of alkylating agents, age at diagnosis, and age at study in the PanCareLIFE cohort. On the basis of the effect allele frequency (EAF) (>0.01 if not genome-wide significant), and biologic relevance, 15 single nucleotide polymorphisms were selected for replication. None of the single nucleotide polymorphisms were statistically significantly associated with AMH levels. A meta-analysis indicated that rs78861946 was associated with borderline genome-wide statistical significance (reference/effect allele: C/T; effect allele frequency: 0.04, beta (SE): −0.484 (0.091). Con

Published
2024

19. Therapeutic targeting of the PLK1-PRC1-axis triggers cell death in genomically silent childhood cancer

Author

Li, Jing, Ohmura, Shunya, Marchetto, Aruna, Orth, Martin F., Imle, Roland, Dallmayer, Marlene, Musa, Julian, Knott, Maximilian M. L., Hölting, Tilman L. B., Stein, Stefanie, Funk, Cornelius M., Sastre, Ana, Alonso, Javier, Bestvater, Felix, Kasan, Merve, Romero-Pérez, Laura, Hartmann, Wolfgang, Ranft, Andreas, Banito, Ana, Dirksen, Uta, Kirchner, Thomas, Cidre-Aranaz, Florencia, and Grünewald, Thomas G. P.

Published
2021
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20. Translational evidence for RRM2 as a prognostic biomarker and therapeutic target in Ewing sarcoma

Author

Ohmura, Shunya, Marchetto, Aruna, Orth, Martin F., Li, Jing, Jabar, Susanne, Ranft, Andreas, Vinca, Endrit, Ceranski, Katharina, Carreño-Gonzalez, Martha J., Romero-Pérez, Laura, Wehweck, Fabienne S., Musa, Julian, Bestvater, Felix, Knott, Maximilian M. L., Hölting, Tilman L. B., Hartmann, Wolfgang, Dirksen, Uta, Kirchner, Thomas, Cidre-Aranaz, Florencia, and Grünewald, Thomas G. P.

Published
2021
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21. Gene expression and immunohistochemical analyses identify SOX2 as major risk factor for overall survival and relapse in Ewing sarcoma patients

Author

Sannino, Giuseppina, Marchetto, Aruna, Ranft, Andreas, Jabar, Susanne, Zacherl, Constanze, Alba-Rubio, Rebeca, Stein, Stefanie, Wehweck, Fabienne S., Kiran, Merve M., Hölting, Tilman L.B., Musa, Julian, Romero-Pérez, Laura, Cidre-Aranaz, Florencia, Knott, Maximilian M.L., Li, Jing, Jürgens, Heribert, Sastre, Ana, Alonso, Javier, Da Silveira, Willian, Hardiman, Gary, Gerke, Julia S., Orth, Martin F., Hartmann, Wolfgang, Kirchner, Thomas, Ohmura, Shunya, Dirksen, Uta, and Grünewald, Thomas G.P.

Published
2019
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22. Supplementary Figure S2 from Zoledronic Acid Add-on Therapy for Standard-Risk Ewing Sarcoma Patients in the Ewing 2008R1 Trial

Author

Koch, Raphael, primary, Haveman, Lianne, primary, Ladenstein, Ruth, primary, Brichard, Benedicte, primary, Jürgens, Heribert, primary, Cyprova, Sona, primary, van den Berg, Henk, primary, Hassenpflug, Wolf, primary, Raciborska, Anna, primary, Ek, Torben, primary, Baumhoer, Daniel, primary, Egerer, Gerlinde, primary, Kager, Leo, primary, Renard, Marleen, primary, Hauser, Peter, primary, Burdach, Stefan, primary, Bovee, Judith V.M.G., primary, Hong, Angela M., primary, Reichardt, Peter, primary, Kruseova, Jarmila, primary, Streitbürger, Arne, primary, Kühne, Thomas, primary, Kessler, Torsten, primary, Bernkopf, Marie, primary, Butterfaß-Bahloul, Trude, primary, Dhooge, Catharina, primary, Bauer, Sebastian, primary, Kiss, János, primary, Paulussen, Michael, primary, Bonar, Fiona, primary, Ranft, Andreas, primary, Timmermann, Beate, primary, Rascon, Jelena, primary, Vieth, Volker, primary, Kanerva, Jukka, primary, Faldum, Andreas, primary, Hartmann, Wolfgang, primary, Hjorth, Lars, primary, Bhadri, Vivek A., primary, Metzler, Markus, primary, Gelderblom, Hans, primary, and Dirksen, Uta, primary

Published
2023
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23. Supplementary Data S2 from Zoledronic Acid Add-on Therapy for Standard-Risk Ewing Sarcoma Patients in the Ewing 2008R1 Trial

Author

Koch, Raphael, primary, Haveman, Lianne, primary, Ladenstein, Ruth, primary, Brichard, Benedicte, primary, Jürgens, Heribert, primary, Cyprova, Sona, primary, van den Berg, Henk, primary, Hassenpflug, Wolf, primary, Raciborska, Anna, primary, Ek, Torben, primary, Baumhoer, Daniel, primary, Egerer, Gerlinde, primary, Kager, Leo, primary, Renard, Marleen, primary, Hauser, Peter, primary, Burdach, Stefan, primary, Bovee, Judith V.M.G., primary, Hong, Angela M., primary, Reichardt, Peter, primary, Kruseova, Jarmila, primary, Streitbürger, Arne, primary, Kühne, Thomas, primary, Kessler, Torsten, primary, Bernkopf, Marie, primary, Butterfaß-Bahloul, Trude, primary, Dhooge, Catharina, primary, Bauer, Sebastian, primary, Kiss, János, primary, Paulussen, Michael, primary, Bonar, Fiona, primary, Ranft, Andreas, primary, Timmermann, Beate, primary, Rascon, Jelena, primary, Vieth, Volker, primary, Kanerva, Jukka, primary, Faldum, Andreas, primary, Hartmann, Wolfgang, primary, Hjorth, Lars, primary, Bhadri, Vivek A., primary, Metzler, Markus, primary, Gelderblom, Hans, primary, and Dirksen, Uta, primary

Published
2023
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24. Supplementary Table S5 from Zoledronic Acid Add-on Therapy for Standard-Risk Ewing Sarcoma Patients in the Ewing 2008R1 Trial

Author

Koch, Raphael, primary, Haveman, Lianne, primary, Ladenstein, Ruth, primary, Brichard, Benedicte, primary, Jürgens, Heribert, primary, Cyprova, Sona, primary, van den Berg, Henk, primary, Hassenpflug, Wolf, primary, Raciborska, Anna, primary, Ek, Torben, primary, Baumhoer, Daniel, primary, Egerer, Gerlinde, primary, Kager, Leo, primary, Renard, Marleen, primary, Hauser, Peter, primary, Burdach, Stefan, primary, Bovee, Judith V.M.G., primary, Hong, Angela M., primary, Reichardt, Peter, primary, Kruseova, Jarmila, primary, Streitbürger, Arne, primary, Kühne, Thomas, primary, Kessler, Torsten, primary, Bernkopf, Marie, primary, Butterfaß-Bahloul, Trude, primary, Dhooge, Catharina, primary, Bauer, Sebastian, primary, Kiss, János, primary, Paulussen, Michael, primary, Bonar, Fiona, primary, Ranft, Andreas, primary, Timmermann, Beate, primary, Rascon, Jelena, primary, Vieth, Volker, primary, Kanerva, Jukka, primary, Faldum, Andreas, primary, Hartmann, Wolfgang, primary, Hjorth, Lars, primary, Bhadri, Vivek A., primary, Metzler, Markus, primary, Gelderblom, Hans, primary, and Dirksen, Uta, primary

Published
2023
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25. Study Protocol S1 from Zoledronic Acid Add-on Therapy for Standard-Risk Ewing Sarcoma Patients in the Ewing 2008R1 Trial

Author

Koch, Raphael, primary, Haveman, Lianne, primary, Ladenstein, Ruth, primary, Brichard, Benedicte, primary, Jürgens, Heribert, primary, Cyprova, Sona, primary, van den Berg, Henk, primary, Hassenpflug, Wolf, primary, Raciborska, Anna, primary, Ek, Torben, primary, Baumhoer, Daniel, primary, Egerer, Gerlinde, primary, Kager, Leo, primary, Renard, Marleen, primary, Hauser, Peter, primary, Burdach, Stefan, primary, Bovee, Judith V.M.G., primary, Hong, Angela M., primary, Reichardt, Peter, primary, Kruseova, Jarmila, primary, Streitbürger, Arne, primary, Kühne, Thomas, primary, Kessler, Torsten, primary, Bernkopf, Marie, primary, Butterfaß-Bahloul, Trude, primary, Dhooge, Catharina, primary, Bauer, Sebastian, primary, Kiss, János, primary, Paulussen, Michael, primary, Bonar, Fiona, primary, Ranft, Andreas, primary, Timmermann, Beate, primary, Rascon, Jelena, primary, Vieth, Volker, primary, Kanerva, Jukka, primary, Faldum, Andreas, primary, Hartmann, Wolfgang, primary, Hjorth, Lars, primary, Bhadri, Vivek A., primary, Metzler, Markus, primary, Gelderblom, Hans, primary, and Dirksen, Uta, primary

Published
2023
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26. An energy costly architecture of neuromodulators for human brain evolution and cognition

Author

Castrillon, Gabriel, primary, Epp, Samira, additional, Bose, Antonia, additional, Fraticelli, Laura, additional, Hechler, André, additional, Belenya, Roman, additional, Ranft, Andreas, additional, Yakushev, Igor, additional, Utz, Lukas, additional, Sundar, Lalith, additional, Rauschecker, Josef P, additional, Preibisch, Christine, additional, Kurcyus, Katarzyna, additional, and Riedl, Valentin, additional

Published
2023
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27. PanCareLIFE: The scientific basis for a European project to improve long-term care regarding fertility, ototoxicity and health-related quality of life after cancer occurring among children and adolescents

Author

Kaatsch, P., Grabow, D., Byrne, J., Campbell, H., Clissmann, C., O'Brien, K., Kremer, L.C.M., Langer, T., van Dulmen-den Broeder, E., van den Berg, Dr. MH., van den Heuvel-Eibrink, M.M., Borgmann-Staudt, A., am Zehnhoff-Dinnesen, A., Kuehni, C.E., Haupt, R., Kepak, T., Berger, C., Winther, J.F., Kruseova, J., Calaminus, G., Baust, K., Dirksen, U., van Leeuwen, F., Schilling, R., Strauss, G., Ranft, A., Garré, M.-L., Fosså, S., Leiper, A., Lackner, H., Panasiuk, A., Krawczuk-Rybak, Dr. M., Kunstreich, M., Cario, H., Zolk, O., Bielack, S., Stefanowicz, J., Grandage, V., Modan, D., Paul, Norbert W., Knudsen, Lisbeth E., Byrne, Julianne, Grabow, Desiree, Campbell, Helen, O'Brien, Kylie, Bielack, Stefan, am Zehnhoff-Dinnesen, Antoinette, Calaminus, Gabriele, Kremer, Leontien, Langer, Thorsten, van den Heuvel-Eibrink, Marry M., van Dulmen-den Broeder, Eline, Baust, Katja, Bautz, Andrea, Beck, Jörn D., Berger, Claire, Binder, Harald, Borgmann-Staudt, Anja, Broer, Linda, Cario, Holger, Casagranda, Leonie, Clemens, Eva, Deuster, Dirk, de Vries, Andrica, Dirksen, Uta, Winther, Jeanette Falck, Fosså, Sophie, Font-Gonzalez, Anna, Grandage, Victoria, Haupt, Riccardo, Hecker-Nolting, Stefanie, Hjorth, Lars, Kaiser, Melanie, Kenborg, Line, Kepak, Tomas, Kepáková, Kateřina, Krawczuk-Rybak, Maryna, Kruseova, Jarmila, Kuehni, Claudia E., Kunstreich, Marina, Kuonen, Rahel, Lackner, Herwig, Leiper, Alison, Loeffen, Erik A.H., Luks, Ales, Modan-Moses, Dalit, Mulder, Renee, Parfitt, Ross, Ranft, Andreas, Ruud, Ellen, Schilling, Ralph, Spix, Claudia, Stefanowicz, Joanna, Strauβ, Gabriele, Uitterlinden, Andre G., van den Berg, Marleen, van der Kooi, Anne-Lotte, van Dijk, Marloes, van Leeuwen, Flora, Zolk, Oliver, Zöller, Daniela, and Kaatsch, Peter

Published
2018
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28. Array-based DNA-methylation profiling in sarcomas with small blue round cell histology provides valuable diagnostic information

Author

Koelsche, Christian, Hartmann, Wolfgang, Schrimpf, Daniel, Stichel, Damian, Jabar, Susanne, Ranft, Andreas, Reuss, David E., Sahm, Felix, Jones, David T.W., Bewerunge-Hudler, Melanie, Trautmann, Marcel, Klingebiel, Thomas, Vokuhl, Christian, Gessler, Manfred, Wardelmann, Eva, Petersen, Iver, Baumhoer, Daniel, Flucke, Uta, Antonescu, Cristina, Esteller, Manel, Fröhling, Stefan, Kool, Marcel, Pfister, Stefan M., Mechtersheimer, Gunhild, Dirksen, Uta, and von Deimling, Andreas

Published
2018
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30. Zoledronic acid add-on therapy for standard-risk Ewing sarcoma patients in the Ewing 2008R1 trial

Author

Koch, Raphael, primary, Haveman, Lianne, additional, Ladenstein, Ruth, additional, BRICHARD, Bénédicte, additional, Juergens, Heribert, additional, Cyprová, Soňa, additional, van den Berg, Henk, additional, Hassenpflug, Wolf, additional, Raciborska, Anna, additional, Ek, Torben, additional, Baumhoer, Daniel, additional, Egerer, Gerlinde, additional, Kager, Leo, additional, Renard, Marleen, additional, Hauser, Peter, additional, Burdach, Stefan, additional, Bovee, Judith V.M.G., additional, Hong, Angela M., additional, Reichardt, Peter, additional, Kruseova, Jarmila, additional, Streitbürger, Arne, additional, Kühne, Thomas, additional, Kessler, Torsten, additional, Bernkopf, Marie, additional, Butterfaß-Bahloul, Trude, additional, Dhooge, Catharina, additional, Bauer, Sebastian, additional, Kiss, János, additional, Paulussen, Michael, additional, Bonar, Fiona, additional, Ranft, Andreas, additional, Timmermann, Beate, additional, Rascon, Jelena, additional, Vieth, Volker, additional, Kanerva, Jukka, additional, Faldum, Andreas, additional, Hartmann, Wolfgang, additional, Hjorth, Lars, additional, Bhadri, Vivek A., additional, Metzler, Markus, additional, Gelderblom, Hans, additional, and Dirksen, Uta, additional

Published
2023
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31. Which Factors Are Associated with Local Control and Survival of Patients with Localized Pelvic Ewing’s Sarcoma? A Retrospective Analysis of Data from the Euro-EWING99 Trial

Author

Andreou, Dimosthenis, Ranft, Andreas, Gosheger, Georg, Timmermann, Beate, Ladenstein, Ruth, Hartmann, Wolfgang, Bauer, Sebastian, Baumhoer, Daniel, van den Berg, Henk, Dijkstra, P.D. Sander, Dürr, Hans Roland, Gelderblom, Hans, Hardes, Jendrik, Hjorth, Lars, Kreyer, Justus, Kruseova, Jarmila, Leithner, Andreas, Scobioala, Sergiu, Streitbürger, Arne, Tunn, Per-Ulf, Wardelmann, Eva, Windhager, Reinhard, Jürgens, Heribert, and Dirksen, Uta

Published
2020
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33. Global neuronal activity drives cerebrospinal fluid motion mediated by brain blood volume changes in humans

Author

Zimmermann, Juliana, primary, Boudriot, Clara, additional, Eipert, Christiane, additional, Hoffmann, Gabriel, additional, Nuttall, Rachel, additional, Schneider, Sebastian, additional, Schmitzer, Lena, additional, Kufer, Jan, additional, Kaczmarz, Stephan, additional, Hedderich, Dennis M, additional, Ranft, Andreas, additional, Golkowski, Daniel, additional, Priller, Josef, additional, Zimmer, Claus, additional, Ilg, Rüdiger, additional, Schneider, Gerhard, additional, Preibisch, Christine, additional, Sorg, Christian, additional, and Zott, Benedikt, additional

Published
2023
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34. Figure S3 from Quantification of Translocation-Specific ctDNA Provides an Integrating Parameter for Early Assessment of Treatment Response and Risk Stratification in Ewing Sarcoma

Author

Krumbholz, Manuela, primary, Eiblwieser, Johanna, primary, Ranft, Andreas, primary, Zierk, Jakob, primary, Schmidkonz, Christian, primary, Stütz, Adrian M, primary, Peneder, Peter, primary, Tomazou, Eleni M., primary, Agaimy, Abbas, primary, Bäuerle, Tobias, primary, Hartmann, Wolfgang, primary, Dirksen, Uta, primary, and Metzler, Markus, primary

Published
2023
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39. Genetic variation in gonadal impairment in female survivors of childhood cancer: a PanCareLIFE study protocol

Author

van der Kooi, Anne-Lotte L. F., Clemens, Eva, Broer, Linda, Zolk, Oliver, Byrne, Julianne, Campbell, Helen, van den Berg, Marleen, Berger, Claire, Calaminus, Gabriele, Dirksen, Uta, Winther, Jeanette Falck, Fosså, Sophie D, Grabow, Desiree, Haupt, Riccardo, Kaiser, Melanie, Kepak, Tomas, Kremer, Leontien, Kruseova, Jarmila, Modan-Moses, Dalit, Ranft, Andreas, Spix, Claudia, Kaatsch, Peter, Laven, Joop S. E., van Dulmen-den Broeder, Eline, Uitterlinden, André G., van den Heuvel-Eibrink, Marry M., and on behalf of the PanCareLIFE Consortium

Published
2018
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41. Relevance of Abnormal KCNN1 Expression and Osmotic Hypersensitivity in Ewing Sarcoma

Author

Fuest, Sebastian, Post, Christoph, Balbach, Sebastian T., Jabar, Susanne, Neumann, Ilka, Schimmelpfennig, Sandra, Sargin, Sarah, Nass, Elke, Budde, Thomas, Kailayangiri, Sareetha, Altvater, Bianca, Ranft, Andreas, Hartmann, Wolfgang, Dirksen, Uta, Rössig, Claudia, Schwab, Albrecht, and Pethő, Zoltán

Subjects
610 Medicine and health, Medizin
Abstract

Ewing sarcoma (EwS) is a rare and highly malignant bone tumor occurring mainly in childhood and adolescence. Physiologically, the bone is a central hub for Ca2+ homeostasis, which is severely disturbed by osteolytic processes in EwS. Therefore, we aimed to investigate how ion transport proteins involved in Ca2+ homeostasis affect EwS pathophysiology. We characterized the expression of 22 candidate genes of Ca2+-permeable or Ca2+-regulated ion channels in three EwS cell lines and found the Ca2+-activated K+ channel KCa2.1 (KCNN1) to be exceptionally highly expressed. We revealed that 'KCNN1' expression is directly regulated by the disease-driving oncoprotein EWSR1-FL1. Due to its consistent overexpression in EwS, 'KCNN1' mRNA could be a prognostic marker in EwS. In a large cohort of EwS patients, however, 'KCNN1' mRNA quantity does not correlate with clinical parameters. Several functional studies including patch clamp electrophysiology revealed no evidence for KCa2.1 function in EwS cells. Thus, elevated KCNN1 expression is not translated to KCa2.1 channel activity in EwS cells. However, we found that the low K+ conductance of EwS cells renders them susceptible to hypoosmotic solutions. The absence of a relevant K+ conductance in EwS thereby provides an opportunity for hypoosmotic therapy that can be exploited during tumor surgery., Finanziert durch den Open-Access-Publikationsfonds der Westfälischen Wilhelms-Universität Münster (WWU Münster).

Published
2022
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43. Ewing Sarcoma as Secondary Malignant Neoplasm—Epidemiological and Clinical Analysis of an International Trial Registry

Author

Zöllner, Stefan K., primary, Kauertz, Katja L., additional, Kaiser, Isabelle, additional, Kerkhoff, Maximilian, additional, Schaefer, Christiane, additional, Tassius, Madita, additional, Jabar, Susanne, additional, Jürgens, Heribert, additional, Ladenstein, Ruth, additional, Kühne, Thomas, additional, Haveman, Lianne M., additional, Paulussen, Michael, additional, Ranft, Andreas, additional, and Dirksen, Uta, additional

Published
2022
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44. Relevance of Abnormal KCNN1 Expression and Osmotic Hypersensitivity in Ewing Sarcoma

Author

Fuest, Sebastian, primary, Post, Christoph, additional, Balbach, Sebastian T., additional, Jabar, Susanne, additional, Neumann, Ilka, additional, Schimmelpfennig, Sandra, additional, Sargin, Sarah, additional, Nass, Elke, additional, Budde, Thomas, additional, Kailayangiri, Sareetha, additional, Altvater, Bianca, additional, Ranft, Andreas, additional, Hartmann, Wolfgang, additional, Dirksen, Uta, additional, Rössig, Claudia, additional, Schwab, Albrecht, additional, and Pethő, Zoltán, additional

Published
2022
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46. High-Dose Treosulfan and Melphalan as Consolidation Therapy Versus Standard Therapy for High-Risk (Metastatic) Ewing Sarcoma

Author

Koch, Raphael, primary, Gelderblom, Hans, additional, Haveman, Lianne, additional, Brichard, Benedicte, additional, Jürgens, Heribert, additional, Cyprova, Sona, additional, van den Berg, Henk, additional, Hassenpflug, Wolf, additional, Raciborska, Anna, additional, Ek, Torben, additional, Baumhoer, Daniel, additional, Egerer, Gerlinde, additional, Eich, Hans Theodor, additional, Renard, Marleen, additional, Hauser, Peter, additional, Burdach, Stefan, additional, Bovee, Judith, additional, Bonar, Fiona, additional, Reichardt, Peter, additional, Kruseova, Jarmila, additional, Hardes, Jendrik, additional, Kühne, Thomas, additional, Kessler, Torsten, additional, Collaud, Stephane, additional, Bernkopf, Marie, additional, Butterfaß-Bahloul, Trude, additional, Dhooge, Catharina, additional, Bauer, Sebastian, additional, Kiss, János, additional, Paulussen, Michael, additional, Hong, Angela, additional, Ranft, Andreas, additional, Timmermann, Beate, additional, Rascon, Jelena, additional, Vieth, Volker, additional, Kanerva, Jukka, additional, Faldum, Andreas, additional, Metzler, Markus, additional, Hartmann, Wolfgang, additional, Hjorth, Lars, additional, Bhadri, Vivek, additional, and Dirksen, Uta, additional

Published
2022
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47. Mapping Pharmacologically-induced Functional Reorganisation onto the Brain’s Neurotransmitter Landscape

Author

Luppi, Andrea I., primary, Hansen, Justine Y., additional, Adapa, Ram, additional, Carhart-Harris, Robin L., additional, Roseman, Leor, additional, Timmermann, Christopher, additional, Golkowski, Daniel, additional, Ranft, Andreas, additional, Ilg, Rüdiger, additional, Jordan, Denis, additional, Bonhomme, Vincent, additional, Vanhaudenhuyse, Audrey, additional, Demertzi, Athena, additional, Jaquet, Oceane, additional, Bahri, Mohamed Ali, additional, Alnagger, Naji L.N., additional, Cardone, Paolo, additional, Peattie, Alexander R. D., additional, Manktelow, Anne E., additional, de Araujo, Draulio B., additional, Sensi, Stefano L., additional, Owen, Adrian M., additional, Naci, Lorina, additional, Menon, David K., additional, Misic, Bratislav, additional, and Stamatakis, Emmanuel A., additional

Published
2022
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48. Value of adjuvant radiotherapy in patients with localized Ewing sarcoma at the extremities: Report from the Ewing 2008 trial.

Author

Heesen, Philip, primary, Ranft, Andreas, additional, Bhadri, Vivek, additional, Brichard, Bénédicte, additional, Collaud, Stephane, additional, Cyprova, Sona, additional, Eich, Hans-Theodor, additional, Ek, Torben, additional, Gelderblom, Hans, additional, Havemann, Lianne, additional, Hauser, Peter, additional, Juergens, Heribert, additional, Kanerva, Jukka, additional, Kuehne, Thomas, additional, Raciborska, Anna, additional, Rascon, Jelena, additional, Streitbuerger, Arne, additional, Timmermann, Beate, additional, Uhlenbruch, Yasmine, additional, and Dirksen, Uta, additional

Published
2022
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49. High-Dose Treosulfan and Melphalan as Consolidation Therapy Versus Standard Therapy for High-Risk (Metastatic) Ewing Sarcoma.

Author

UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, UCL - (SLuc) Service d'hématologie et d'oncologie pédiatrique, Koch, Raphael, Gelderblom, Hans, Haveman, Lianne, Brichard, Benedicte, Jürgens, Heribert, Cyprova, Sona, van den Berg, Henk, Hassenpflug, Wolf, Raciborska, Anna, Ek, Torben, Baumhoer, Daniel, Egerer, Gerlinde, Eich, Hans Theodor, Renard, Marleen, Hauser, Peter, Burdach, Stefan, Bovee, Judith, Bonar, Fiona, Reichardt, Peter, Kruseova, Jarmila, Hardes, Jendrik, Kühne, Thomas, Kessler, Torsten, Collaud, Stephane, Bernkopf, Marie, Butterfaß-Bahloul, Trude, Dhooge, Catharina, Bauer, Sebastian, Kiss, János, Paulussen, Michael, Hong, Angela, Ranft, Andreas, Timmermann, Beate, Rascon, Jelena, Vieth, Volker, Kanerva, Jukka, Faldum, Andreas, Metzler, Markus, Hartmann, Wolfgang, Hjorth, Lars, Bhadri, Vivek, Dirksen, Uta, UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, UCL - (SLuc) Service d'hématologie et d'oncologie pédiatrique, Koch, Raphael, Gelderblom, Hans, Haveman, Lianne, Brichard, Benedicte, Jürgens, Heribert, Cyprova, Sona, van den Berg, Henk, Hassenpflug, Wolf, Raciborska, Anna, Ek, Torben, Baumhoer, Daniel, Egerer, Gerlinde, Eich, Hans Theodor, Renard, Marleen, Hauser, Peter, Burdach, Stefan, Bovee, Judith, Bonar, Fiona, Reichardt, Peter, Kruseova, Jarmila, Hardes, Jendrik, Kühne, Thomas, Kessler, Torsten, Collaud, Stephane, Bernkopf, Marie, Butterfaß-Bahloul, Trude, Dhooge, Catharina, Bauer, Sebastian, Kiss, János, Paulussen, Michael, Hong, Angela, Ranft, Andreas, Timmermann, Beate, Rascon, Jelena, Vieth, Volker, Kanerva, Jukka, Faldum, Andreas, Metzler, Markus, Hartmann, Wolfgang, Hjorth, Lars, Bhadri, Vivek, and Dirksen, Uta

Abstract

Ewing 2008R3 was conducted in 12 countries and evaluated the effect of treosulfan and melphalan high-dose chemotherapy (TreoMel-HDT) followed by reinfusion of autologous hematopoietic stem cells on event-free survival (EFS) and overall survival in high-risk Ewing sarcoma (EWS). Phase III, open-label, prospective, multicenter, randomized controlled clinical trial. Eligible patients had disseminated EWS with metastases to bone and/or other sites, excluding patients with only pulmonary metastases. Patients received six cycles of vincristine, ifosfamide, doxorubicin, and etoposide induction and eight cycles of vincristine, actinomycin D, and cyclophosphamide consolidation therapy. Patients were randomly assigned to receive additional TreoMel-HDT or no further treatment (control). The random assignment was stratified by number of bone metastases (1, 2-5, and > 5). The one-sided adaptive-inverse-normal-4-stage-design was changed after the first interim analysis via Müller-Schäfer method. Between 2009 and 2018, 109 patients were randomly assigned, and 55 received TreoMel-HDT. With a median follow-up of 3.3 years, there was no significant difference in EFS between TreoMel-HDT and control in the adaptive design (hazard ratio [HR] 0.85; 95% CI, 0.55 to 1.32, intention-to-treat). Three-year EFS was 20.9% (95% CI, 11.5 to 37.9) in TreoMel-HDT and 19.2% (95% CI, 10.8 to 34.4) in control patients. The results were similar in the per-protocol collective. Males treated with TreoMel-HDT had better EFS compared with controls: median 1.0 years (95% CI, 0.8 to 2.2) versus 0.6 years (95% CI, 0.5 to 0.9); = .035; HR 0.52 (0.28 to 0.97). Patients age < 14 years benefited from TreoMel-HDT with a 3-years EFS of 39.3% (95% CI, 20.4 to 75.8%) versus 9% (95% CI, 2.4 to 34); = .016; HR 0.40 (0.19 to 0.87). These effects were similar in the per-protocol collective. This observation is supported by comparable results from the nonrandomized trial EE99R3. In patients with very high-risk EWS, additi

Published
2022

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