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213 results on '"Hielscher T"'

1. 738P Combined ipilimumab and nivolumab in previously treated patients with cancer of unknown primary: Results of the CheCUP trial

Author

Pouyiourou, M., primary, Kraft, B., additional, Wohlfromm, T., additional, Stahl, M., additional, Kubuschok, B., additional, Löffler, H., additional, Hacker, U.T., additional, Huebner, G., additional, Westphalen, C.B., additional, Bitzer, M., additional, Ernst, T., additional, Schuett, P., additional, Hielscher, T., additional, Delorme, S., additional, Stenzinger, A., additional, Bochtler, T., additional, and Krämer, A., additional

Published
2022
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3. Phase III trial of bortezomib, cyclophosphamide and dexamethasone (VCD) versus bortezomib, doxorubicin and dexamethasone (PAd) in newly diagnosed myeloma

Author

Mai, E K, Bertsch, U, Dürig, J, Kunz, C, Haenel, M, Blau, I W, Munder, M, Jauch, A, Schurich, B, Hielscher, T, Merz, M, Huegle-Doerr, B, Seckinger, A, Hose, D, Hillengass, J, Raab, M S, Neben, K, Lindemann, H-W, Zeis, M, Gerecke, C, Schmidt-Wolf, I G H, Weisel, K, Scheid, C, Salwender, H, and Goldschmidt, H

Published
2015
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5. Integrated Molecular-Morphologic Meningioma Classification: A Multicenter Retrospective Analysis, Retrospectively and Prospectively Validated

Author

Maas, SLN, Stichel, D, Hielscher, T, Sievers, P, Berghoff, AS, Schrimpf, D, Sill, M, Euskirchen, P, Blume, C, Patel, A, Dogan, H, Reuss, D, Dohmen, H, Stein, M, Reinhardt, A, Suwala, AK, Wefers, AK, Baumgarten, P, Ricklefs, F, Rushing, EJ, Bewerunge-Hudler, M, Ketter, R, Schittenhelm, J, Jaunmuktane, Z, Leu, S, Greenway, FEA, Bridges, LR, Jones, T, Grady, C, Serrano, J, Golfinos, J, Sen, C, Mawrin, C, Jungk, C, Hänggi, D, Westphal, M, Lamszus, K, Etminan, N, Jungwirth, G, Herold-Mende, C, Unterberg, A, Harter, PN, Wirsching, H-G, Neidert, MC, Ratliff, M, Platten, M, Snuderl, M, Aldape, KD, Brandner, S, Hench, J, Frank, S, Pfister, SM, Jones, DTW, Reifenberger, G, Acker, T, Wick, W, Weller, M, Preusser, M, von Deimling, A, Sahm, F, and German Consortium on Aggressive Meningiomas (KAM)

Abstract

PURPOSE: Meningiomas are the most frequent primary intracranial tumors. Patient outcome varies widely from benign to highly aggressive, ultimately fatal courses. Reliable identification of risk of progression for individual patients is of pivotal importance. However, only biomarkers for highly aggressive tumors are established (CDKN2A/B and TERT), whereas no molecularly based stratification exists for the broad spectrum of patients with low- and intermediate-risk meningioma. METHODS: DNA methylation data and copy-number information were generated for 3,031 meningiomas (2,868 patients), and mutation data for 858 samples. DNA methylation subgroups, copy-number variations (CNVs), mutations, and WHO grading were analyzed. Prediction power for outcome was assessed in a retrospective cohort of 514 patients, validated on a retrospective cohort of 184, and on a prospective cohort of 287 multicenter cases. RESULTS: Both CNV- and methylation family-based subgrouping independently resulted in increased prediction accuracy of risk of recurrence compared with the WHO classification (c-indexes WHO 2016, CNV, and methylation family 0.699, 0.706, and 0.721, respectively). Merging all risk stratification approaches into an integrated molecular-morphologic score resulted in further substantial increase in accuracy (c-index 0.744). This integrated score consistently provided superior accuracy in all three cohorts, significantly outperforming WHO grading (c-index difference P = .005). Besides the overall stratification advantage, the integrated score separates more precisely for risk of progression at the diagnostically challenging interface of WHO grade 1 and grade 2 tumors (hazard ratio 4.34 [2.48-7.57] and 3.34 [1.28-8.72] retrospective and prospective validation cohorts, respectively). CONCLUSION: Merging these layers of histologic and molecular data into an integrated, three-tiered score significantly improves the precision in meningioma stratification. Implementation into diagnostic routine informs clinical decision making for patients with meningioma on the basis of robust outcome prediction.

Published
2021

8. P04.04 Optimizing dasatinib for glioblastoma treatment

Author

Alhalabi, O, primary, Göttmann, M, additional, Gold, M, additional, Fletcher, M, additional, Hielscher, T, additional, Iskar, M, additional, Kessler, T, additional, Wittmann, E, additional, Schlue, S, additional, Rahman, S, additional, Hai, L, additional, Hansen-Palmus, L, additional, Puccio, L, additional, Nakano, I, additional, Herold-Mende, C, additional, Baumgartner, U, additional, Day, B, additional, Wick, W, additional, Sahm, F, additional, Fraenkel, E, additional, Phillips, E, additional, and Goidts, V, additional

Published
2021
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12. IL4I1 is a metabolic immune checkpoint that activates the AHR and promotes tumor progression

Author

Sadik, A., Somarribas Patterson, L.F., Öztürk, S., Mohapatra, S.R., Panitz, V., Secker, P.F., Pfänder, P., Loth, Stefanie, Salem, H., Prentzell, M.T., Berdel, B., Iskar, M., Faessler, E., Reuter, F., Kirst, I., Kalter, V., Foerster, K.I., Jäger, E., Ramallo Guevara, C., Sobeh, M., Hielscher, T., Poschet, G., Reinhardt, A., Hassel, J.C., Zapatka, M., Hahn, U., von Deimling, A., Hopf, C., Schlichting, Rita, Escher, Beate, Burhenne, J., Haefeli, W.E., Ishaque, N., Böhme, Alexander, Schäuble, S., Thedieck, K., Trump, S., Seiffert, M., Opitz, C.A., Sadik, A., Somarribas Patterson, L.F., Öztürk, S., Mohapatra, S.R., Panitz, V., Secker, P.F., Pfänder, P., Loth, Stefanie, Salem, H., Prentzell, M.T., Berdel, B., Iskar, M., Faessler, E., Reuter, F., Kirst, I., Kalter, V., Foerster, K.I., Jäger, E., Ramallo Guevara, C., Sobeh, M., Hielscher, T., Poschet, G., Reinhardt, A., Hassel, J.C., Zapatka, M., Hahn, U., von Deimling, A., Hopf, C., Schlichting, Rita, Escher, Beate, Burhenne, J., Haefeli, W.E., Ishaque, N., Böhme, Alexander, Schäuble, S., Thedieck, K., Trump, S., Seiffert, M., and Opitz, C.A.

Abstract

Aryl hydrocarbon receptor (AHR) activation by tryptophan (Trp) catabolites enhances tumor malignancy and suppresses anti-tumor immunity. The context specificity of AHR target genes has so far impeded systematic investigation of AHR activity and its upstream enzymes across human cancers. A pan-tissue AHR signature, derived by natural language processing, revealed that across 32 tumor entities, interleukin-4-induced-1 (IL4I1) associates more frequently with AHR activity than IDO1 or TDO2, hitherto recognized as the main Trp-catabolic enzymes. IL4I1 activates the AHR through the generation of indole metabolites and kynurenic acid. It associates with reduced survival in glioma patients, promotes cancer cell motility, and suppresses adaptive immunity, thereby enhancing the progression of chronic lymphocytic leukemia (CLL) in mice. Immune checkpoint blockade (ICB) induces IDO1 and IL4I1. As IDO1 inhibitors do not block IL4I1, IL4I1 may explain the failure of clinical studies combining ICB with IDO1 inhibition. Taken together, IL4I1 blockade opens new avenues for cancer therapy.

Published
2020

14. Final results of a randomized trial comparing 1, 3, or 6 infusions of Rituximab plus 6 cycles CHOP provide valuable preliminary data towards a more cost-effective and safer treatment of advanced follicular lymphoma

Author

McClanahan, F., Hielscher, T., Rieger, M., Hensel, M., Bentz, M., Schmidt-Wolf, I., Käbisch, A., Salwender, H., Dürk, H., Staiger, H., Mandel, T., Neben, K., Hillengass, J., Leo, E., Krämer, A., Ho, A. D., and Witzens-Harig, M.

Published
2012
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15. Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMGHD-4 trial

Author

Goldschmidt, H., Lokhorst, H. M., Mai, E. K., van der Holt, B., Blau, I. W., Zweegman, S., Weisel, K. C., Vellenga, E., Pfreundschuh, M., Kersten, M. J., Scheid, C., Croockewit, S., Raymakers, R., Hose, D., Potamianou, A., Jauch, A., Hillengass, J., Stevens-Kroef, M., Raab, M. S., Broijl, A., Lindemann, H. W., Bos, G. M. J., Brossart, P., Kooy, M. van Marwijk, Ypma, P., Duehrsen, U., Schaafsma, R. M., Bertsch, U., Hielscher, T., Jarari, Le, Salwender, H. J., Sonneveld, P., Goldschmidt, H., Lokhorst, H. M., Mai, E. K., van der Holt, B., Blau, I. W., Zweegman, S., Weisel, K. C., Vellenga, E., Pfreundschuh, M., Kersten, M. J., Scheid, C., Croockewit, S., Raymakers, R., Hose, D., Potamianou, A., Jauch, A., Hillengass, J., Stevens-Kroef, M., Raab, M. S., Broijl, A., Lindemann, H. W., Bos, G. M. J., Brossart, P., Kooy, M. van Marwijk, Ypma, P., Duehrsen, U., Schaafsma, R. M., Bertsch, U., Hielscher, T., Jarari, Le, Salwender, H. J., and Sonneveld, P.

Abstract

The Dutch-Belgian Cooperative Trial Group for Hematology Oncology Group-65/German-speaking Myeloma Multicenter Group-HD4 (HOVON-65/GMMG-HD4) phase III trial compared bortezomib (BTZ) before and after high-dose melphalan and autologous stem cell transplantation (HDM, PAD arm) compared with classical cytotoxic agents prior and thalidomide after HDM (VAD arm) in multiple myeloma (MM) patients aged 18-65 years. Here, the long-term follow-up and data on second primary malignancies (SPM) are presented. After a median follow-up of 96 months, progression-free survival (censored at allogeneic transplantation, PFS) remained significantly prolonged in the PAD versus VAD arm (hazard ratio (HR) = 0.76, 95% confidence interval (95% CI) of 0.65-0.89, P = 0.001). Overall survival (OS) was similar in the PAD versus VAD arm (HR = 0.89, 95% CI: 0.74-1.08, P = 0.24). The incidence of SPM were similar between the two arms (7% each, P = 0.73). The negative prognostic effects of the cytogenetic aberration deletion 17p13 (clone size >= 10%) and renal impairment at baseline (serum creatinine > 2 mg dl(-1)) on PFS and OS remained abrogated in the PAD but not VAD arm. OS from first relapse/progression was similar between the study arms (HR = 1.02, P = 0.85). In conclusion, the survival benefit with BTZ induction/maintenance compared with classical cytotoxic agents and thalidomide maintenance is maintained without an increased risk of SPM.

Published
2018

16. MAGNETIC RESONANCE IMAGING BEFORE AND AFTER UPFRONT AUTOLOGOUS TRANSPLANTATION IDENTIFIES PATIENTS WITH ADVERSE OUTCOME BUT RESPONSE TO TREATMENT WITHIN THE PROSPECTIVE GMMG MM5 PHASE III TRIAL

Author

Merz, M., Hielscher, T., Seckinger, A., Jauch, A., Mai, E. K., Bertsch, U., Raab, M. S., Neben, K., Salwender, H., Blau, I. W., Lindemann, H. W., Duerig, J., Scheid, C., Haenel, M., Weisel, K., Delorme, S., Kauczor, H. U., Hose, D., Goldschmidt, H., Hillengass, J., Merz, M., Hielscher, T., Seckinger, A., Jauch, A., Mai, E. K., Bertsch, U., Raab, M. S., Neben, K., Salwender, H., Blau, I. W., Lindemann, H. W., Duerig, J., Scheid, C., Haenel, M., Weisel, K., Delorme, S., Kauczor, H. U., Hose, D., Goldschmidt, H., and Hillengass, J.

Published
2018

17. Bortezomib before and after high-dose therapy in myeloma : long-term results from the phase III HOVON-65/GMMG-HD4 trial

Author

Goldschmidt, H, Lokhorst, H M, Mai, E K, van der Holt, B, Blau, I W, Zweegman, S, Weisel, K C, Vellenga, E, Pfreundschuh, M, Kersten, M J, Scheid, C, Croockewit, S, Raymakers, R, Hose, D, Potamianou, A, Jauch, A, Hillengass, J, Stevens-Kroef, M, Raab, M S, Broijl, A, Lindemann, H W, Bos, G M J, Brossart, P, van Marwijk Kooy, M, Ypma, P, Duehrsen, U, Schaafsma, R M, Bertsch, U, Hielscher, T, Jarari, Le, Salwender, H J, Sonneveld, P, Goldschmidt, H, Lokhorst, H M, Mai, E K, van der Holt, B, Blau, I W, Zweegman, S, Weisel, K C, Vellenga, E, Pfreundschuh, M, Kersten, M J, Scheid, C, Croockewit, S, Raymakers, R, Hose, D, Potamianou, A, Jauch, A, Hillengass, J, Stevens-Kroef, M, Raab, M S, Broijl, A, Lindemann, H W, Bos, G M J, Brossart, P, van Marwijk Kooy, M, Ypma, P, Duehrsen, U, Schaafsma, R M, Bertsch, U, Hielscher, T, Jarari, Le, Salwender, H J, and Sonneveld, P

Published
2018

18. Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMG-HD4 trial

Author

Externen Hematologie, MS Hematologie, Infection & Immunity, Regenerative Medicine and Stem Cells, Goldschmidt, H, Lokhorst, H M, Mai, E K, van der Holt, B, Blau, I W, Zweegman, S, Weisel, K C, Vellenga, E, Pfreundschuh, M, Kersten, M J, Scheid, C, Croockewit, S, Raymakers, R, Hose, D, Potamianou, A, Jauch, A, Hillengass, J, Stevens-Kroef, M, Raab, M S, Broijl, A, Lindemann, H W, Bos, G M J, Brossart, P, van Marwijk Kooy, M, Ypma, P, Duehrsen, U, Schaafsma, R M, Bertsch, U, Hielscher, T, Jarari, Le, Salwender, H J, Sonneveld, P, Externen Hematologie, MS Hematologie, Infection & Immunity, Regenerative Medicine and Stem Cells, Goldschmidt, H, Lokhorst, H M, Mai, E K, van der Holt, B, Blau, I W, Zweegman, S, Weisel, K C, Vellenga, E, Pfreundschuh, M, Kersten, M J, Scheid, C, Croockewit, S, Raymakers, R, Hose, D, Potamianou, A, Jauch, A, Hillengass, J, Stevens-Kroef, M, Raab, M S, Broijl, A, Lindemann, H W, Bos, G M J, Brossart, P, van Marwijk Kooy, M, Ypma, P, Duehrsen, U, Schaafsma, R M, Bertsch, U, Hielscher, T, Jarari, Le, Salwender, H J, and Sonneveld, P

Published
2018

19. Whole-body computed tomography versus conventional skeletal survey in patients with multiple myeloma: A study of the International Myeloma Working Group

Author

Hillengass, J Moulopoulos, LA Delorme, S Koutoulidis, V Mosebach, J Hielscher, T Drake, M Rajkumar, SV Oestergaard, B Abildgaard, N others

Subjects
Health Sciences, otorhinolaryngologic diseases, Επιστήμες Υγείας
Abstract

For decades, conventional skeletal survey (CSS) has been the standard imaging technique for multiple myeloma (MM). However, recently whole-body computed tomography (WBCT) has been implemented into the diagnostic criteria of MM. This analysis compares sensitivity and prognostic significance of WBCT and CSS in patients with smoldering MM (SMM) and MM. Fifty-four of 212 patients (25.5%) had a negative CSS and a positive WBCT for osteolytic lesions (P

Published
2017

21. Prediction of early overall and infection-related mortality during induction therapy in transplant-eligible multiple myeloma - a pooled analysis from three GMMG phase III trials

Author

Mai, E. K., Hielscher, T., Bertsch, U., Schlenzka, J., Salwender, H. J., Munder, M., Gerecke, C., Pfreundschuh, M., Duehrsen, U., Brossart, P., Neben, K., Hillengass, J., Raab, M. S., Hose, D., Merz, M., Breitkreutz, I., Jauch, A., Martin, H., Lindemann, H. -W., Scheid, C., Weisel, K. C., Blau, I. W., Goldschmidt, H., Mai, E. K., Hielscher, T., Bertsch, U., Schlenzka, J., Salwender, H. J., Munder, M., Gerecke, C., Pfreundschuh, M., Duehrsen, U., Brossart, P., Neben, K., Hillengass, J., Raab, M. S., Hose, D., Merz, M., Breitkreutz, I., Jauch, A., Martin, H., Lindemann, H. -W., Scheid, C., Weisel, K. C., Blau, I. W., and Goldschmidt, H.

Published
2017

22. 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

23. Whole-body computed tomography versus conventional skeletal survey in patients with multiple myeloma: a study of the International Myeloma Working Group

Author

Hillengass, J, primary, Moulopoulos, L A, additional, Delorme, S, additional, Koutoulidis, V, additional, Mosebach, J, additional, Hielscher, T, additional, Drake, M, additional, Rajkumar, S V, additional, Oestergaard, B, additional, Abildgaard, N, additional, Hinge, M, additional, Plesner, T, additional, Suehara, Y, additional, Matsue, K, additional, Withofs, N, additional, Caers, J, additional, Waage, A, additional, Goldschmidt, H, additional, Dimopoulos, M A, additional, Lentzsch, S, additional, Durie, B, additional, and Terpos, E, additional

Published
2017
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24. Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMG-HD4 trial

Author

Goldschmidt, H, primary, Lokhorst, H M, additional, Mai, E K, additional, van der Holt, B, additional, Blau, I W, additional, Zweegman, S, additional, Weisel, K C, additional, Vellenga, E, additional, Pfreundschuh, M, additional, Kersten, M J, additional, Scheid, C, additional, Croockewit, S, additional, Raymakers, R, additional, Hose, D, additional, Potamianou, A, additional, Jauch, A, additional, Hillengass, J, additional, Stevens-Kroef, M, additional, Raab, M S, additional, Broijl, A, additional, Lindemann, H W, additional, Bos, G M J, additional, Brossart, P, additional, van Marwijk Kooy, M, additional, Ypma, P, additional, Duehrsen, U, additional, Schaafsma, R M, additional, Bertsch, U, additional, Hielscher, T, additional, Jarari, Le, additional, Salwender, H J, additional, and Sonneveld, P, additional

Published
2017
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26. 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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27. Peripheral neuropathy associated with subcutaneous or intravenous bortezomib in patients with newly diagnosed myeloma treated within the GMMG MM5 phase III trial

Author

Merz, M., primary, Salwender, H., additional, Haenel, M., additional, Mai, E. K., additional, Bertsch, U., additional, Kunz, C., additional, Hielscher, T., additional, Blau, I. W., additional, Scheid, C., additional, Hose, D., additional, Seckinger, A., additional, Jauch, A., additional, Hillengass, J., additional, Raab, M. S., additional, Schurich, B., additional, Munder, M., additional, Brossart, P., additional, Gerecke, C., additional, Lindemann, H.-W., additional, Zeis, M., additional, Weisel, K., additional, Duerig, J., additional, and Goldschmidt, H., additional

Published
2016
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28. Phase III trial of bortezomib, cyclophosphamide and dexamethasone (VCD) versus bortezomib, doxorubicin and dexamethasone (PAd) in newly diagnosed myeloma

Author

Mai, E. K., Bertsch, U., Duerig, J., Kunz, C., Haenel, M., Blau, I. W., Munder, M., Jauch, A., Schurich, B., Hielscher, T., Merz, M., Huegle-Doerr, B., Seckinger, A., Hose, D., Hillengass, J., Raab, M. S., Neben, K., Lindemann, H-W, Zeis, M., Gerecke, C., Schmidt-Wolf, I. G. H., Weisel, K., Scheid, C., Salwender, H., Goldschmidt, H., Mai, E. K., Bertsch, U., Duerig, J., Kunz, C., Haenel, M., Blau, I. W., Munder, M., Jauch, A., Schurich, B., Hielscher, T., Merz, M., Huegle-Doerr, B., Seckinger, A., Hose, D., Hillengass, J., Raab, M. S., Neben, K., Lindemann, H-W, Zeis, M., Gerecke, C., Schmidt-Wolf, I. G. H., Weisel, K., Scheid, C., Salwender, H., and Goldschmidt, H.

Abstract

We aimed at demonstrating non-inferiority of bortezomib/cyclophosphamide/dexamethasone (VCD) compared to bortezomib/doxorubicin/dexamethasone (PAd) induction therapy with respect to very good partial response rates or better (>= VGPR) in 504 newly diagnosed, transplant-eligible multiple myeloma patients. VCD was found to be non-inferior to PAd with respect to >= VGPR rates (37.0 versus 34.3%, P = 0.001). The rates of progressive disease (PD) were 0.4% (VCD) versus 4.8% (PAd; P = 0.003). In the PAd arm, 11 of 12 patients with PD had either renal impairment (creatinine >= 2 mg/dl) at diagnosis or the cytogenetic abnormality gain 1q21, whereas no PD was observed in these subgroups in the VCD arm. Leukocytopenia/neutropenia (>= 3 degrees) occurred more frequently in the VCD arm (35.2% versus 11.3%, P<0.001). Neuropathy rates (>= 2 degrees) were higher in the PAd group (14.9 versus 8.4%, P = 0.03). Serious adverse events, both overall and those related to thromboembolic events, were higher in the PAd group (32.7 versus 24.0%, P = 0.04 and 2.8 versus 0.4%, P = 0.04). Stem cell collection was not impeded by VCD. VCD is as effective as PAd in terms of achieving >= VGPR rates with fewer PD and has a favorable toxicity profile. Therefore, VCD is preferable to PAd as induction therapy.

Published
2015

29. Comparative assessment of myeloma response to induction treatment in the GMMG MM5 study using IMWG criteria and hevylite assay

Author

Scheid, C., Hose, D., Bertsch, U., Hielscher, T., Kunz, C., Salwender, H., Haenel, M., Merz, M., Mai, E. K., Schurich, B., Munder, M., Schmidt-Wolf, I, Gerecke, C., Lindemann, W., Zeis, M., Weisel, K., Duerig, J., Jauch, A., Peters-Regehr, T., Zorn, M., Goldschmidt, H., Scheid, C., Hose, D., Bertsch, U., Hielscher, T., Kunz, C., Salwender, H., Haenel, M., Merz, M., Mai, E. K., Schurich, B., Munder, M., Schmidt-Wolf, I, Gerecke, C., Lindemann, W., Zeis, M., Weisel, K., Duerig, J., Jauch, A., Peters-Regehr, T., Zorn, M., and Goldschmidt, H.

Published
2015

30. MYCN-amplified medulloblastomas: biological and clinical heterogeneity

Author

Korshunov, Andrey, Remke, M., Kool, M., Hielscher, T., Northcott, P.A., Wit, H., Jones, D.T.W., Ryzhova, M., Benner, A., Lichter, P., Von Deimling, A., and Pfister, S. M.

Subjects
ddc: 610, 610 Medical sciences, Medicine, neoplasms
Abstract

Amplifications of MYC define a subset of high-risk medulloblastoma patients. However, the prognostic role of MYCN oncogene amplification remains unresolved. We aimed to evaluate the prognostic value of this alteration in 67 medulloblastomas with MYCN amplification (MYCN-MB). Twenty-one tumors were examined[for full text, please go to the a.m. URL], 57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN)

Published
2012

31. Bortezomib during induction and maintenance before and after autologous transplantation improves overall survival in patients with renal impairment : subgroup analysis from the HOVON-65/GMMG-HD4 randomized trial for newly diagnosed multiple myeloma

Author

Scheid, C., Sonneveld, P., Schmidt-Wolf, I., van der Holt, B., Hielscher, T., el Jarari, L., Bertsch, U., Salwender, H., Zweegman, S., Hanel, M., Vellenga, E., Schubert, J., Blau, I. W., Jie, A., van de Velde, H., Peter, N., Schaafsma, M., Lindemann, W., Kersten, M., Dührsen, Ulrich, Delforge, M., Weisel, K., Croockewit, S., Martin, H., Wittebol, S., Schouten, H., van Marwijk-Kooy, M., Wijermans, P., Lokhorst, H., Goldschmidt, H., GMMG, and HOVON

Subjects
Medizin
Published
2011

32. Bortezomib before and after high-dose chemotherapy improves the survival in patients with newly diagnosed multiple myeloma and renal insufficiency - a subgroup analysis of the prospective randomised GMMG HD4/HOVON 65 study

Author

Scheid, C., Sonneveld, P., Schmidt-Wolf, I., van der Holt, B., Hielscher, T., el Jarari, L., Bertsch, U., Salwender, H., Zweegman, S., Hanel, M., Vellenga, E., Schubert, J., Blau, I. W., Jie, A., van de Velde, H., Peter, N., Schaafsma, M., Lindemann, W., Kersten, M. J., Dührsen, Ulrich, Delforge, M., Weisel, K., Croockewit, S., Martin, H., Wittebol, S., Schouten, H., van Marwijk-Kooy, M., Wijermans, P., Lokhorst, H. M., Goldschmidt, H., and GMMG HOVON

Subjects
Medizin
Published
2011

33. Concomitant gain of 1q21 and MYC translocation define a poor prognostic subgroup of hyperdiploid multiple myeloma

Author

Weinhold, N., primary, Kirn, D., additional, Seckinger, A., additional, Hielscher, T., additional, Granzow, M., additional, Bertsch, U., additional, Egerer, G., additional, Salwender, H., additional, Blau, I. W., additional, Weisel, K., additional, Hillengass, J., additional, Raab, M. S., additional, Hose, D., additional, Goldschmidt, H., additional, and Jauch, A., additional

Published
2015
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34. Subcutaneous versus intravenous bortezomib in two different induction therapies for newly diagnosed multiple myeloma: an interim analysis from the prospective GMMG-MM5 trial

Author

Merz, M., primary, Salwender, H., additional, Haenel, M., additional, Mai, E. K., additional, Bertsch, U., additional, Kunz, C., additional, Hielscher, T., additional, Blau, I. W., additional, Scheid, C., additional, Hose, D., additional, Seckinger, A., additional, Jauch, A., additional, Hillengass, J., additional, Raab, M. S., additional, Schurich, B., additional, Munder, M., additional, Schmidt-Wolf, I. G. H., additional, Gerecke, C., additional, Lindemann, H.-W., additional, Zeis, M., additional, Weisel, K., additional, Duerig, J., additional, and Goldschmidt, H., additional

Published
2015
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35. A magnetic resonance imaging-based prognostic scoring system to predict outcome in transplant-eligible patients with multiple myeloma

Author

Mai, E. K., primary, Hielscher, T., additional, Kloth, J. K., additional, Merz, M., additional, Shah, S., additional, Raab, M. S., additional, Hillengass, M., additional, Wagner, B., additional, Jauch, A., additional, Hose, D., additional, Weber, M.-A., additional, Delorme, S., additional, Goldschmidt, H., additional, and Hillengass, J., additional

Published
2015
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36. Bortezomib/cyclophosphamide/dexamethasone (VCD) is equally effective and has a favorable toxicity profile compared to bortezomib/doxorubicin/dexamethasone (PAd) as induction therapy in newly diagnosed, transplant-eligible myeloma patients: Results from the multicenter, phase III clinical trial GMMG-MM5

Author

Mai, E. K., Bertsch, U., Duerig, J., Kunz, C., Haenel, M., Blau, I. W., Munder, M., Jauch, A., Schurich, B., Hielscher, T., Merz, M., Huegle-Doerr, B., Seckinger, A., Hose, D., Hillengass, J., Raab, M. S., Neben, K., Lindemann, H-W, Zeis, M., Gerecke, C., Schmidt-Wolf, I. G. H., Weisel, K., Scheid, C., Salwender, H., Goldschmidt, H., Mai, E. K., Bertsch, U., Duerig, J., Kunz, C., Haenel, M., Blau, I. W., Munder, M., Jauch, A., Schurich, B., Hielscher, T., Merz, M., Huegle-Doerr, B., Seckinger, A., Hose, D., Hillengass, J., Raab, M. S., Neben, K., Lindemann, H-W, Zeis, M., Gerecke, C., Schmidt-Wolf, I. G. H., Weisel, K., Scheid, C., Salwender, H., and Goldschmidt, H.

Published
2014

37. mTOR target NDRG1 confers MGMT-dependent resistance to alkylating chemotherapy

Author

Weiler, M, Blaes, J, Pusch, S, Sahm, F, Czabanka, M, Luger, S, Bunse, L, Solecki, G, Eichwald, V, Jugold, M, Hodecker, S, Osswald, M, Meisner, C, Hielscher, T, Rübmann, P, Pfenning, P N, Ronellenfitsch, M, Kempf, T, Schnölzer, M, Abdollahi, A, Lang, F, Bendszus, M, von Deimling, A, Winkler, F, Weller, M, Vajkoczy, P, Platten, M, Wick, W, Weiler, M, Blaes, J, Pusch, S, Sahm, F, Czabanka, M, Luger, S, Bunse, L, Solecki, G, Eichwald, V, Jugold, M, Hodecker, S, Osswald, M, Meisner, C, Hielscher, T, Rübmann, P, Pfenning, P N, Ronellenfitsch, M, Kempf, T, Schnölzer, M, Abdollahi, A, Lang, F, Bendszus, M, von Deimling, A, Winkler, F, Weller, M, Vajkoczy, P, Platten, M, and Wick, W

Abstract

A hypoxic microenvironment induces resistance to alkylating agents by activating targets in the mammalian target of rapamycin (mTOR) pathway. The molecular mechanisms involved in this mTOR-mediated hypoxia-induced chemoresistance, however, are unclear. Here we identify the mTOR target N-myc downstream regulated gene 1 (NDRG1) as a key determinant of resistance toward alkylating chemotherapy, driven by hypoxia but also by therapeutic measures such as irradiation, corticosteroids, and chronic exposure to alkylating agents via distinct molecular routes involving hypoxia-inducible factor (HIF)-1alpha, p53, and the mTOR complex 2 (mTORC2)/serum glucocorticoid-induced protein kinase 1 (SGK1) pathway. Resistance toward alkylating chemotherapy but not radiotherapy was dependent on NDRG1 expression and activity. In posttreatment tumor tissue of patients with malignant gliomas, NDRG1 was induced and predictive of poor response to alkylating chemotherapy. On a molecular level, NDRG1 bound and stabilized methyltransferases, chiefly O(6)-methylguanine-DNA methyltransferase (MGMT), a key enzyme for resistance to alkylating agents in glioblastoma patients. In patients with glioblastoma, MGMT promoter methylation in tumor tissue was not more predictive for response to alkylating chemotherapy in patients who received concomitant corticosteroids.

Published
2014

38. Malignant astrocytomas of elderly patients lack favorable molecular markers: an analysis of the NOA-08 study collective

Author

Wiestler, B, Claus, R, Hartlieb, S A, Schliesser, M G, Weiss, E K, Hielscher, T, Platten, M, Dittmann, L M, Meisner, C, Felsberg, J, Happold, C, Simon, M, Nikkhah, G, Papsdorf, K, Steinbach, J P, Sabel, M, Grimm, C, Weichenhan, D, Tews, B, Reifenberger, G, Capper, D, Müller, W, Plass, C, Weller, M, Wick, W, Wiestler, B, Claus, R, Hartlieb, S A, Schliesser, M G, Weiss, E K, Hielscher, T, Platten, M, Dittmann, L M, Meisner, C, Felsberg, J, Happold, C, Simon, M, Nikkhah, G, Papsdorf, K, Steinbach, J P, Sabel, M, Grimm, C, Weichenhan, D, Tews, B, Reifenberger, G, Capper, D, Müller, W, Plass, C, Weller, M, and Wick, W

Abstract

Background The number of patients age >65 years with malignant gliomas is increasing. Prognosis of these patients is worse compared with younger patients. To determine biological differences among malignant gliomas of different age groups and help to explain the survival heterogeneity seen in the NOA-08 trial, the prevalence and impact of recently established biomarkers for outcome in younger patients were characterized in elderly patients. Methods Prevalences of mutations of isocitrate dehydrogenase 1 (IDH1) and histone H3.3 (H3F3A), the glioma cytosine-phosphate-guanine island methylator phenotype (G-CIMP), and methylation of alkylpurine DNA N-glycosylase (APNG) and peroxiredoxin 1 (PRDX1) promoters were determined in a representative biomarker subset (n = 126 patients with anaplastic astrocytoma or glioblastoma) from the NOA-08 trial. Results IDH1 mutations (R132H) were detected in only 3/126 patients, precluding determination of an association between IDH mutation and outcome. These 3 patients also displayed the G-CIMP phenotype. None of the IDH1 wild-type tumors were G-CIMP positive. Mutations in H3F3A were absent in all 103 patients sequenced for H3F3A. MassARRAY analysis of the APNG promoter revealed generally low methylation levels and failed to confirm any predictive properties for benefit from alkylating chemotherapy. Neither did PRDX1 promoter methylation show differential methylation or association with outcome in this cohort. In a 170-patient cohort from The Cancer Genome Atlas database matched for relevant prognostic factors, age ≥65 years was strongly associated with shorter survival. Conclusions Despite an age-independent stable frequency of O(6)-methylguanine-DNA methyltransferase (MGMT) promoter hypermethylation, tumors in this age group largely lack prognostically favorable markers established in younger glioblastoma patients, which likely contributes to the overall worse prognosis of elderly patients. However, the survival differences hint at fun

Published
2013

39. MYCN-amplified medulloblastomas: biological and clinical heterogeneity

Author

Korshunov, A, Remke, M, Kool, M, Hielscher, T, Northcott, PA, Wit, H, Jones, DTW, Ryzhova, M, Benner, A, Lichter, P, von Deimling, A, Pfister, SM, Korshunov, A, Remke, M, Kool, M, Hielscher, T, Northcott, PA, Wit, H, Jones, DTW, Ryzhova, M, Benner, A, Lichter, P, von Deimling, A, and Pfister, SM

Published
2012

40. OMICS AND PROGNSTIC MARKERS

Author

Adachi, K., primary, Sasaki, H., additional, Nagahisa, S., additional, Yoshida, K., additional, Hattori, N., additional, Nishiyama, Y., additional, Kawase, T., additional, Hasegawa, M., additional, Abe, M., additional, Hirose, Y., additional, Alentorn, A., additional, Marie, Y., additional, Poggioli, S., additional, Alshehhi, H., additional, Boisselier, B., additional, Carpentier, C., additional, Mokhtari, K., additional, Capelle, L., additional, Figarella-Branger, D., additional, Hoang-Xuan, K., additional, Sanson, M., additional, Delattre, J.-Y., additional, Idbaih, A., additional, Yust-Katz, S., additional, Anderson, M., additional, Olar, A., additional, Eterovic, A., additional, Ezzeddine, N., additional, Chen, K., additional, Zhao, H., additional, Fuller, G., additional, Aldape, K., additional, de Groot, J., additional, Andor, N., additional, Harness, J., additional, Lopez, S. G., additional, Fung, T. L., additional, Mewes, H. W., additional, Petritsch, C., additional, Arivazhagan, A., additional, Somasundaram, K., additional, Thennarasu, K., additional, Pandey, P., additional, Anandh, B., additional, Santosh, V., additional, Chandramouli, B., additional, Hegde, A., additional, Kondaiah, P., additional, Rao, M., additional, Bell, R., additional, Kang, R., additional, Hong, C., additional, Song, J., additional, Costello, J., additional, Nagarajan, R., additional, Zhang, B., additional, Diaz, A., additional, Wang, T., additional, Bie, L., additional, Li, Y., additional, Liu, H., additional, Luyo, W. F. C., additional, Carnero, M. H., additional, Iruegas, M. E. P., additional, Morell, A. R., additional, Figueiras, M. C., additional, Lopez, R. L., additional, Valverde, C. F., additional, Chan, A. K.-Y., additional, Pang, J. C.-S., additional, Chung, N. Y.-F., additional, Li, K. K.-W., additional, Poon, W. S., additional, Chan, D. T.-M., additional, Wang, Y., additional, Ng, H.-a. K., additional, Chaumeil, M., additional, Larson, P., additional, Yoshihara, H., additional, Vigneron, D., additional, Nelson, S., additional, Pieper, R., additional, Phillips, J., additional, Ronen, S., additional, Clark, V., additional, Omay, Z. E., additional, Serin, A., additional, Gunel, J., additional, Omay, B., additional, Grady, C., additional, Youngblood, M., additional, Bilguvar, K., additional, Baehring, J., additional, Piepmeier, J., additional, Gutin, P., additional, Vortmeyer, A., additional, Brennan, C., additional, Pamir, M. N., additional, Kilic, T., additional, Krischek, B., additional, Simon, M., additional, Yasuno, K., additional, Gunel, M., additional, Cohen, A. L., additional, Sato, M., additional, Aldape, K. D., additional, Mason, C., additional, Diefes, K., additional, Heathcock, L., additional, Abegglen, L., additional, Shrieve, D., additional, Couldwell, W., additional, Schiffman, J. D., additional, Colman, H., additional, D'Alessandris, Q. 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A., additional, Date, I., additional, Geisenberger, C., additional, Mock, A., additional, Warta, R., additional, Schwager, C., additional, Hartmann, C., additional, von Deimling, A., additional, Abdollahi, A., additional, Herold-Mende, C., additional, Gevaert, O., additional, Achrol, A., additional, Gholamin, S., additional, Mitra, S., additional, Westbroek, E., additional, Loya, J., additional, Mitchell, L., additional, Chang, S., additional, Steinberg, G., additional, Plevritis, S., additional, Cheshier, S., additional, Xu, J., additional, Napel, S., additional, Zaharchuk, G., additional, Harsh, G., additional, Gutman, D., additional, Holder, C., additional, Colen, R., additional, Dunn, W., additional, Jain, R., additional, Cooper, L., additional, Hwang, S., additional, Flanders, A., additional, Brat, D., additional, Hayes, J., additional, Droop, A., additional, Thygesen, H., additional, Boissinot, M., additional, Westhead, D., additional, Short, S., additional, Lawler, S., additional, Bady, P., additional, Kurscheid, S., additional, Delorenzi, M., additional, Hegi, M. 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M., additional, White, P., additional, Oka, T., additional, Jalbert, L., additional, Elkhaled, A., additional, Jensen, R., additional, Salzman, K., additional, Schabel, M., additional, Gillespie, D., additional, Mumert, M., additional, Johnson, B., additional, Mazor, T., additional, Barnes, M., additional, Yamamoto, S., additional, Ueda, H., additional, Tatsuno, K., additional, Aihara, K., additional, Bollen, A., additional, Hirst, M., additional, Marra, M., additional, Mukasa, A., additional, Saito, N., additional, Aburatani, H., additional, Berger, M., additional, Taylor, B., additional, Popov, S., additional, Mackay, A., additional, Ingram, W., additional, Burford, A., additional, Jury, A., additional, Vinci, M., additional, Jones, C., additional, Jones, D. T. W., additional, Hovestadt, V., additional, Picelli, S., additional, Wang, W., additional, Northcott, P. A., additional, Kool, M., additional, Reifenberger, G., additional, Pietsch, T., additional, Sultan, M., additional, Lehrach, H., additional, Yaspo, M.-L., additional, Borkhardt, A., additional, Landgraf, P., additional, Eils, R., additional, Korshunov, A., additional, Zapatka, M., additional, Radlwimmer, B., additional, Pfister, S. M., additional, Lichter, P., additional, Joy, A., additional, Smirnov, I., additional, Reiser, M., additional, Shapiro, W., additional, Kim, S., additional, Feuerstein, B., additional, Jungk, C., additional, Friauf, S., additional, Unterberg, A., additional, Juratli, T. A., additional, McElroy, J., additional, Meng, W., additional, Huebner, A., additional, Geiger, K. D., additional, Krex, D., additional, Schackert, G., additional, Chakravarti, A., additional, Lautenschlaeger, T., additional, Kim, B. Y., additional, Jiang, W., additional, Beiko, J., additional, Prabhu, S., additional, DeMonte, F., additional, Sawaya, R., additional, Cahill, D., additional, McCutcheon, I., additional, Lau, C., additional, Wang, L., additional, Terashima, K., additional, Yamaguchi, S., additional, Burstein, M., additional, Sun, J., additional, Suzuki, T., additional, Nishikawa, R., additional, Nakamura, H., additional, Natsume, A., additional, Terasaka, S., additional, Ng, H.-K., additional, Muzny, D., additional, Gibbs, R., additional, Wheeler, D., additional, Zhang, X.-q., additional, Sun, S., additional, Lam, K.-f., additional, Kiang, K. M. Y., additional, Pu, J. K. S., additional, Ho, A. S. W., additional, Leung, G. K. K., additional, Loebel, F., additional, Curry, W. T., additional, Barker, F. G., additional, Lelic, N., additional, Chi, A. S., additional, Cahill, D. P., additional, Lu, D., additional, Yin, J., additional, Teo, C., additional, McDonald, K., additional, Madhankumar, A., additional, Weston, C., additional, Slagle-Webb, B., additional, Sheehan, J., additional, Patel, A., additional, Glantz, M., additional, Connor, J., additional, Maire, C., additional, Francis, J., additional, Zhang, C.-Z., additional, Jung, J., additional, Manzo, V., additional, Adalsteinsson, V., additional, Homer, H., additional, Blumenstiel, B., additional, Pedamallu, C. S., additional, Nickerson, E., additional, Ligon, A., additional, Love, C., additional, Meyerson, M., additional, Ligon, K., additional, Jalbert, L. E., additional, Nelson, S. J., additional, Bollen, A. W., additional, Smirnov, I. V., additional, Song, J. S., additional, Olshen, A. B., additional, Berger, M. S., additional, Chang, S. M., additional, Taylor, B. S., additional, Costello, J. F., additional, Mehta, S., additional, Armstrong, B., additional, Peng, S., additional, Bapat, A., additional, Berens, M., additional, Melendez, B., additional, Mollejo, M., additional, Mur, P., additional, Hernandez-Iglesias, T., additional, Fiano, C., additional, Ruiz, J., additional, Rey, J. A., additional, Stadler, V., additional, Schulte, A., additional, Lamszus, K., additional, Schichor, C., additional, Westphal, M., additional, Tonn, J.-C., additional, Morozova, O., additional, Katzman, S., additional, Grifford, M., additional, Salama, S., additional, Haussler, D., additional, Olshen, A., additional, Fouse, S., additional, Nakamizo, S., additional, Sasayama, T., additional, Tanaka, H., additional, Tanaka, K., additional, Mizukawa, K., additional, Yoshida, M., additional, Kohmura, E., additional, Northcott, P., additional, Jones, D., additional, Pfister, S., additional, Otani, R., additional, Takayanagi, S., additional, Saito, K., additional, Tanaka, S., additional, Shin, M., additional, Ozawa, T., additional, Riester, M., additional, Cheng, Y.-K., additional, Huse, J., additional, Helmy, K., additional, Charles, N., additional, Squatrito, M., additional, Michor, F., additional, Holland, E., additional, Perrech, M., additional, Dreher, L., additional, Rohn, G., additional, Goldbrunner, R., additional, Timmer, M., additional, Pollo, B., additional, Palumbo, V., additional, Calatozzolo, C., additional, Patane, M., additional, Nunziata, R., additional, Farinotti, M., additional, Silvani, A., additional, Lodrini, S., additional, Finocchiaro, G., additional, Lopez, E., additional, Rioscovian, A., additional, Ruiz, R., additional, Siordia, G., additional, de Leon, A. P., additional, Rostomily, C., additional, Rostomily, R., additional, Silbergeld, D., additional, Kolstoe, D., additional, Chamberlain, M., additional, Silber, J., additional, Roth, P., additional, Keller, A., additional, Hoheisel, J., additional, Codo, P., additional, Bauer, A., additional, Backes, C., additional, Leidinger, P., additional, Meese, E., additional, Thiel, E., additional, Korfel, A., additional, Weller, M., additional, Nagae, G., additional, Nagane, M., additional, Sanborn, J. Z., additional, Mikkelsen, T., additional, Jhanwar, S., additional, Chin, L., additional, Nishihara, M., additional, Schliesser, M., additional, Grimm, C., additional, Weiss, E., additional, Claus, R., additional, Weichenhan, D., additional, Weiler, M., additional, Hielscher, T., additional, Sahm, F., additional, Wiestler, B., additional, Klein, A.-C., additional, Blaes, J., additional, Plass, C., additional, Wick, W., additional, Stragliotto, G., additional, Rahbar, A., additional, Soderberg-Naucler, C., additional, Won, M., additional, Ezhilarasan, R., additional, Sun, P., additional, Blumenthal, D., additional, Vogelbaum, M., additional, Jenkins, R., additional, Jeraj, R., additional, Brown, P., additional, Jaeckle, K., additional, Schiff, D., additional, Dignam, J., additional, Atkins, J., additional, Brachman, D., additional, Werner-Wasik, M., additional, Mehta, M., additional, Shen, J., additional, Luan, J., additional, Yu, A., additional, Matsutani, M., additional, Liang, Y., additional, Man, T.-K., additional, Trister, A., additional, Tokita, M., additional, Mikheeva, S., additional, Mikheev, A., additional, Friend, S., additional, van den Bent, M., additional, Erdem, L., additional, Gorlia, T., additional, Taphoorn, M., additional, Kros, J., additional, Wesseling, P., additional, Dubbink, H., additional, Ibdaih, A., additional, French, P., additional, van Thuijl, H., additional, Heimans, J., additional, Ylstra, B., additional, Reijneveld, J., additional, Prabowo, A., additional, Scheinin, I., additional, van Essen, H., additional, Spliet, W., additional, Ferrier, C., additional, van Rijen, P., additional, Veersema, T., additional, Thom, M., additional, Meeteren, A. S.-v., additional, Aronica, E., additional, Kim, H., additional, Zheng, S., additional, Brat, D. J., additional, Virk, S., additional, Amini, S., additional, Sougnez, C., additional, Barnholtz-Sloan, J., additional, Verhaak, R. G. W., additional, Watts, C., additional, Sottoriva, A., additional, Spiteri, I., additional, Piccirillo, S., additional, Touloumis, A., additional, Collins, P., additional, Marioni, J., additional, Curtis, C., additional, Tavare, S., additional, Tews, B., additional, Yeung, T. P. C., additional, Al-Khazraji, B., additional, Morrison, L., additional, Hoffman, L., additional, Jackson, D., additional, Lee, T.-Y., additional, Yartsev, S., additional, Bauman, G., additional, Fu, J., additional, Vegesna, R., additional, Mao, Y., additional, Heathcock, L. E., additional, Torres-Garcia, W., additional, Wang, S., additional, McKenna, A., additional, Brennan, C. W., additional, Yung, W. K. A., additional, Weinstein, J. N., additional, Sulman, E. P., additional, and Koul, D., additional

Published
2013
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43. EPENDYMOMA

Author

Zaghloul, M., primary, Elbeltagy, M., additional, Mousa, A., additional, Eldebawy, E., additional, Amin, A., additional, Pavelka, Z., additional, Vranova, V., additional, Valaskova, I., additional, Tomasikova, L., additional, Oltova, A., additional, Ventruba, J., additional, Mackerle, Z., additional, Kren, L., additional, Skotakova, J., additional, Zitterbart, K., additional, Sterba, J., additional, Milde, T., additional, Kleber, S., additional, Korshunov, A., additional, Witt, H., additional, Hielscher, T., additional, Koch, P., additional, Koch, H.-G., additional, Jugold, M., additional, Deubzer, H. E., additional, Oehme, I., additional, Lodrini, M., additional, Grone, H.-J., additional, Benner, A., additional, Brustle, O., additional, Gilbertson, R. J., additional, von Deimling, A., additional, Kulozik, A. E., additional, Pfister, S. M., additional, Ana, M.-V., additional, Witt, O., additional, Kool, M., additional, Mack, S. C., additional, Taylor, M. D., additional, Fouyssac, F., additional, Schmitt, E., additional, Mansuy, L., additional, Marchal, J.-C., additional, Coffinet, L., additional, Bernier, V., additional, Chastagner, P., additional, Sperl, D., additional, Zacharoulis, S., additional, Massimino, M., additional, Schiavello, E., additional, Pizer, B., additional, Piette, C., additional, Kitanovski, L., additional, von Hoff, K., additional, Quehenberger, F., additional, Rutkowski, S., additional, Benesch, M., additional, Tzaridis, T.-D., additional, Bender, S., additional, Pfaff, E., additional, Barbus, S., additional, Bageritz, J., additional, Jones, D.-T.-W., additional, Kulozik, A., additional, Lichter, P., additional, Pfister, S.-M., additional, Song, S.-H., additional, Kang, C.-W., additional, Kim, S.-H., additional, Bandopadhayay, P., additional, Ullrich, N., additional, Goumnerova, L., additional, Scott, R. M., additional, Silvera, V. M., additional, Ligon, K. L., additional, Marcus, K. J., additional, Robison, N., additional, Manley, P. E., additional, Chi, S., additional, Kieran, M. W., additional, Biassoni, V., additional, Pierani, P., additional, Cesaro, S., additional, Maura, M., additional, Mack, S., additional, Jager, N., additional, Jones, D. T. W., additional, Stutz, A., additional, Northcott, P. A., additional, Fults, D. W., additional, Gupta, N., additional, Karajannis, M., additional, Rutka, J. T., additional, Korbel, J., additional, de Rezende, A. C. P., additional, Chen, M. J., additional, da Silva, N. S., additional, Cappellano, A., additional, Cavalheiro, S., additional, Weltman, E., additional, Currle, S., additional, Thiruvenkatam, R., additional, Murugesan, M., additional, Kranenburg, T., additional, Phoenix, T., additional, Gupta, K., additional, Gilbertson, R., additional, Rogers, H., additional, Kilday, J.-P., additional, Mayne, C., additional, Ward, J., additional, Adamowicz-Brice, M., additional, Schwalbe, E., additional, Clifford, S., additional, Coyle, B., additional, Grundy, R., additional, Mitra, B., additional, Domerg, C., additional, Andreiuolo, F., additional, Osteso-Ibanez, T., additional, Mauguen, A., additional, Varlet, P., additional, Le Deley, M.-C., additional, Lowe, J., additional, Ellison, D. W., additional, Grill, J., additional, Grundy, R. G., additional, Fleischhack, G., additional, Pajtler, K., additional, Zimmermann, M., additional, Warmuth-Metz, M., additional, Kortmann, R.-D., additional, Pietsch, T., additional, Faldum, A., additional, Bode, U., additional, Gandola, L., additional, Pecori, E., additional, Scarzello, G., additional, Barra, S., additional, Mascarin, M., additional, Scoccianti, S., additional, Mussano, A., additional, Garre, M. L., additional, Jacopo, S., additional, Viscardi, E., additional, Balter, R., additional, Bertin, D., additional, Giangaspero, F., additional, Pearlman, M., additional, Khatua, S., additional, Van Meter, T., additional, Koul, D., additional, Yung, A., additional, Paulino, A., additional, Su, J., additional, Dauser, R., additional, Whitehead, W., additional, Teh, B., additional, Chintagumpala, M., additional, Perek, D., additional, Drogosiewicz, M., additional, Filipek, I., additional, Polnik, M. P., additional, Baginska, B. D., additional, Wachowiak, J., additional, Kazmierczak, B., additional, Sobol, G., additional, Musiol, K., additional, Kowalczyk, J., additional, Slusarz, H. W., additional, Peregud-Pogorzelski, J., additional, Grajkowska, W., additional, Roszkowski, M., additional, Teo, W.-Y., additional, Okcu, F., additional, Mahajan, A., additional, Adesina, A., additional, Jea, A., additional, Bollo, R., additional, Paulino, A. C., additional, Velez-Char, N., additional, Doerner, E., additional, Muehlen, A. z., additional, Vladimirova, V., additional, Kortmann, R., additional, Friedrich, C., additional, von Bueren, A. O., additional, Barszczyk, M., additional, Buczkowicz, P., additional, Morrison, A., additional, Tabori, U., additional, Hawkins, C., additional, Krajewski, K., additional, Kammler, G., additional, von Bueren, A., additional, Krauss, J., additional, Ferreira, C., additional, Dieffenbach, G., additional, Barbosa, C., additional, Cuny, P., additional, Piccinin, E., additional, Brenca, M., additional, Lorenzetto, E., additional, Sardi, I., additional, Genitori, L., additional, Pollo, B., additional, Maestro, R., additional, Modena, P., additional, MacDonald, S., additional, Ebb, D., additional, Lavally, B., additional, Yeap, B., additional, Marcus, K., additional, Tarbell, N., additional, Yock, T., additional, Schittone, S., additional, Donson, A., additional, Birks, D., additional, Amani, V., additional, Griesinger, A., additional, Handler, M., additional, Madey, M., additional, Merchant, T., additional, Foreman, N., additional, Hukin, J., additional, Ailon, T., additional, Dunham, C., additional, Carret, A.-S., additional, McNeely, P. D., additional, Zelcer, S., additional, Wilson, B., additional, Lafay-Cousin, L., additional, Johnston, D., additional, Eisenstat, D., additional, Silva, M., additional, Jabado, N., additional, Yip, S., additional, Goddard, K., additional, Fryer, C., additional, Hendson, G., additional, Dunn, S., additional, Singhal, A., additional, Lassen-Ramshad, Y., additional, Vestergaard, A., additional, Seiersen, K., additional, Schultz, H. P., additional, Hoeyer, M., additional, Petersen, J. B., additional, Moreno, L., additional, Popov, S., additional, Jury, A., additional, Al Sarraj, S., additional, Jones, C., additional, Bowers, D., additional, Gargan, L., additional, Horton, C. J., additional, Rakheja, D., additional, Margraf, L., additional, Yeung, J., additional, Hamilton, R., additional, Okada, H., additional, Jakacki, R., additional, Pollack, I., additional, Fleming, A., additional, Saint-Martin, C., additional, Freeman, C., additional, Albrecht, S., additional, and Montes, J.-L., additional

Published
2012
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45. Proliferation is a central independent prognostic factor and target for personalized and risk-adapted treatment in multiple myeloma

Author

Hose, D., primary, Reme, T., additional, Hielscher, T., additional, Moreaux, J., additional, Messner, T., additional, Seckinger, A., additional, Benner, A., additional, Shaughnessy, J. D., additional, Barlogie, B., additional, Zhou, Y., additional, Hillengass, J., additional, Bertsch, U., additional, Neben, K., additional, Mohler, T., additional, Rossi, J. F., additional, Jauch, A., additional, Klein, B., additional, and Goldschmidt, H., additional

Published
2010
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46. Combining information regarding chromosomal aberrations t(4;14) and del(17p13) with the International Staging System classification allows stratification of myeloma patients undergoing autologous stem cell transplantation

Author

Neben, K., primary, Jauch, A., additional, Bertsch, U., additional, Heiss, C., additional, Hielscher, T., additional, Seckinger, A., additional, Mors, T., additional, Muller, N. Z., additional, Hillengass, J., additional, Raab, M. S., additional, Ho, A. D., additional, Hose, D., additional, and Goldschmidt, H., additional

Published
2010
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47. Therapeutic impact of cytoreductive surgery and irradiation of posterior fossa ependymoma in the molecular era: A retrospective multicohort analysis

Author

Uri Tabori, Marta M. Alonso, Frank S. Lieberman, James T. Rutka, Xing Fan, Kevin Petrecca, Michael A. Grotzer, Lyndsey Emery, Jennifer A. Chan, Luca Massimi, Elizabeth Vera-Bolanos, Antonio Omuro, Richard Everson, Stewart Goldman, Sarah Leary, Alvaro Lassaletta, Sofia Nunes, Ralph P. Ermoian, Betty Luu, Cynthia Hawkins, Amulya A. Nageswara Rao, Jeffrey R. Leonard, Maura Massimino, Teresa Tuñón, Massimo Zollo, James M. Olson, Almos Klekner, Andrey Korshunov, Ute Bartels, Tong Lin, Roger J. Packer, Matthias A. Karajannis, David W. Ellison, Christopher Dunham, David D. Eisenstat, Jaume Mora, Martin Mynarek, Erwin G. Van Meir, Roger E. McLendon, Karel Zitterbart, Corrine Gardner, Giuseppe Cinalli, Amar Gajjar, Kenneth Aldape, Karin M. Muraszko, Vijay Ramaswamy, Thomas Hielscher, Ronald L. Hamilton, Lola B. Chambless, Michael D. Prados, David T.W. Jones, Harshad Ladha, Horacio Soto, Wiesława Grajkowska, Jason E. Cain, Felice Giangaspero, Marcel Kool, Eric S. Lipp, William H. Yong, Andrew J. Grossbach, Tibor Hortobágyi, Tarek Shalaby, Helen Wheeler, Peter Hauser, Marie Lise C. van Veelen, Kristian W. Pajtler, Dorcas Fulton, Mariarita Santi, László Bognár, Jaroslav Sterba, Jing Wu, Ji Yeoun Lee, Carlos Gilberto Carlotti, Katja von Hoff, Stefan Rutkowski, Michael D. Taylor, Daniela Pretti da Cunha Tirapelli, Phillipe Metellus, Stephen C. Mack, Thomas E. Merchant, Samer K. Elbabaa, Marc Remke, Girish Dhall, Riccardo Soffietti, Eric Bouffet, Miguel A. Guzman, Khalida Wani, Charles G. Eberhart, Terri S. Armstrong, Tom Mikkelsen, Francesca R. Buttarelli, Nada Jabado, Paul G. Fisher, Juliette Hukin, Maryam Fouladi, Sama Ahsan, Sueli Mieko Oba-Shinjo, Linda M. Liau, Satoru Osuka, Sridharan Gururangan, Peter B. Dirks, Eugene Hwang, Howard Colman, H. Ian Robins, Caterina Giannini, Suely Kazue Nagahashi Marie, Frank van Landeghem, Mark R. Gilbert, Ulrich Schüller, Florence M.G. Cavalli, David Zagzag, Ian F. Pollack, Claudia C. Faria, Stefan M. Pfister, Shin Jung, Ramaswamy, V, Hielscher, T, Mack, Sc, Lassaletta, A, Lin, T, Pajtler, Kw, Jones, Dt, Luu, B, Cavalli, Fm, Aldape, K, Remke, M, Mynarek, M, Rutkowski, S, Gururangan, S, Mclendon, Re, Lipp, E, Dunham, C, Hukin, J, Eisenstat, Dd, Fulton, D, van Landeghem, Fk, Santi, M, van Veelen, Ml, Van Meir, Eg, Osuka, S, Fan, X, Muraszko, Km, Tirapelli, Dp, Oba Shinjo, Sm, Marie, Sk, Carlotti, Cg, Lee, Jy, Rao, Aa, Giannini, C, Faria, Cc, Nunes, S, Mora, J, Hamilton, Rl, Hauser, P, Jabado, N, Petrecca, K, Jung, S, Massimi, L, Zollo, Massimo, Cinalli, G, Bognár, L, Klekner, A, Hortobágyi, T, Leary, S, Ermoian, Rp, Olson, Jm, Leonard, Jr, Gardner, C, Grajkowska, Wa, Chambless, Lb, Cain, J, Eberhart, Cg, Ahsan, S, Massimino, M, Giangaspero, F, Buttarelli, Fr, Packer, Rj, Emery, L, Yong, Wh, Soto, H, Liau, Lm, Everson, R, Grossbach, A, Shalaby, T, Grotzer, M, Karajannis, Ma, Zagzag, D, Wheeler, H, von Hoff, K, Alonso, Mm, Tuñon, T, Schüller, U, Zitterbart, K, Sterba, J, Chan, Ja, Guzman, M, Elbabaa, Sk, Colman, H, Dhall, G, Fisher, Pg, Fouladi, M, Gajjar, A, Goldman, S, Hwang, E, Kool, M, Ladha, H, Vera Bolanos, E, Wani, K, Lieberman, F, Mikkelsen, T, Omuro, Am, Pollack, If, Prados, M, Robins, Hi, Soffietti, R, Wu, J, Metellus, P, Tabori, U, Bartels, U, Bouffet, E, Hawkins, Ce, Rutka, Jt, Dirks, P, Pfister, Sm, Merchant, Te, Gilbert, Mr, Armstrong, T, Korshunov, A, Ellison, Dw, Taylor, M. d., Ramaswamy V., Hielscher T., Mack S.C., Lassaletta A., Lin T., Pajtler K.W., Jones D.T.W., Luu B., Cavalli F.M.G., Aldape K., Remke M., Mynarek M., Rutkowski S., Gururangan S., McLendon R.E., Lipp E.S., Dunham C., Hukin J., Eisenstat D.D., Fulton D., Van Landeghem F.K.H., Santi M., Van Veelen M.-L.C., Van Meir E.G., Osuka S., Fan X., Muraszko K.M., Tirapelli D.P.C., Oba-Shinjo S.M., Marie S.K.N., Carlotti C.G., Lee J.Y., Rao A.A.N., Giannini C., Faria C.C., Nunes S., Mora J., Hamilton R.L., Hauser P., Jabado N., Petrecca K., Jung S., Massimi L., Zollo M., Cinalli G., Bognar L., Klekner A., Hortobagyi T., Leary S., Ermoian R.P., Olson J.M., Leonard J.R., Gardner C., Grajkowska W.A., Chambless L.B., Cain J., Eberhart C.G., Ahsan S., Massimino M., Giangaspero F., Buttarelli F.R., Packer R.J., Emery L., Yong W.H., Soto H., Liau L.M., Everson R., Grossbach A., Shalaby T., Grotzer M., Karajannis M.A., Zagzag D., Wheeler H., Von Hoff K., Alonso M.M., Tunon T., Schuller U., Zitterbart K., Sterba J., Chan J.A., Guzman M., Elbabaa S.K., Colman H., Dhall G., Fisher P.G., Fouladi M., Gajjar A., Goldman S., Hwang E., Kool M., Ladha H., Vera-Bolanos E., Wani K., Lieberman F., Mikkelsen T., Omuro A.M., Pollack I.F., Prados M., Robins H.I., Soffietti R., Wu J., Metellus P., Tabori U., Bartels U., Bouffet E., Hawkins C.E., Rutka J.T., Dirks P., Pfister S.M., Merchant T.E., Gilbert M.R., Armstrong T.S., Korshunov A., Ellison D.W., Taylor M.D., and Neurosurgery

Subjects
Male, Ependymoma, Cancer Research, medicine.medical_treatment, cancer research, oncology, posterior fossa ependymoma, cytoreductive surgery, radiation therapy, Infratentorial Neoplasms, Cohort Studies, 0302 clinical medicine, Retrospective Studie, Medicine, Pediatric ependymoma, Child, 10. No inequality, Infratentorial Neoplasm, biology, Cytoreduction Surgical Procedures, Combined Modality Therapy, 3. Good health, Oncology, Child, Preschool, 030220 oncology & carcinogenesis, Female, Radiology, Human, Adult, medicine.medical_specialty, Adolescent, Fossa, Ependymoma, biomarkers, 03 medical and health sciences, Original Reports, Humans, Retrospective Studies, Chemotherapy, business.industry, Proportional hazards model, Infant, Retrospective cohort study, biology.organism_classification, medicine.disease, Surgery, Radiation therapy, Cohort Studie, business, 030217 neurology & neurosurgery
Abstract

Purpose Posterior fossa ependymoma comprises two distinct molecular variants termed EPN_PFA and EPN_PFB that have a distinct biology and natural history. The therapeutic value of cytoreductive surgery and radiation therapy for posterior fossa ependymoma after accounting for molecular subgroup is not known. Methods Four independent nonoverlapping retrospective cohorts of posterior fossa ependymomas (n = 820) were profiled using genome-wide methylation arrays. Risk stratification models were designed based on known clinical and newly described molecular biomarkers identified by multivariable Cox proportional hazards analyses. Results Molecular subgroup is a powerful independent predictor of outcome even when accounting for age or treatment regimen. Incompletely resected EPN_PFA ependymomas have a dismal prognosis, with a 5-year progression-free survival ranging from 26.1% to 56.8% across all four cohorts. Although first-line (adjuvant) radiation is clearly beneficial for completely resected EPN_PFA, a substantial proportion of patients with EPN_PFB can be cured with surgery alone, and patients with relapsed EPN_PFB can often be treated successfully with delayed external-beam irradiation. Conclusion The most impactful biomarker for posterior fossa ependymoma is molecular subgroup affiliation, independent of other demographic or treatment variables. However, both EPN_PFA and EPN_PFB still benefit from increased extent of resection, with the survival rates being particularly poor for subtotally resected EPN_PFA, even with adjuvant radiation therapy. Patients with EPN_PFB who undergo gross total resection are at lower risk for relapse and should be considered for inclusion in a randomized clinical trial of observation alone with radiation reserved for those who experience recurrence.

Published
2016

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

Author

Iska Moxon-Emre, Livia Garzia, Karin M. Muraszko, Thomas Hielscher, Satoru Osuka, Xing Fan, Andrew S. Moore, Toshihiro Kumabe, Betty Luu, Cynthia Hawkins, Tibor Hortobágyi, David T.W. Jones, Leos Kren, Sridharan Gururangan, Peter Hauser, Peter B. Dirks, David Shih, Jeffrey R. Leonard, Andrey Korshunov, Michael K. Cooper, Gerald A. Grant, Naoki Kagawa, Andrew R. Hallahan, Claudia C. Faria, Pim J. French, Donald J. Mabbott, Joshua B. Rubin, Jaume Mora, Sarah Leary, Michael A. Grotzer, Cécile Faure-Conter, Stefan M. Pfister, Erwin G. Van Meir, Rajeev Vibhakar, Bognár László, Shin Jung, Yoon Jae Cho, Reid C. Thompson, Nada Jabado, Alexander G. Weil, David C.Y. Low, Karel Zitterbart, Enrique López-Aguilar, Alice Carvalho, Kenneth Tou En Chang, Ho Keung Ng, Ana Nikolic, Eric M. Thompson, Jennifer A. Chan, James T. Rutka, Kay Ka Wai Li, Yu Yao, Paul A. Northcott, Vijay Ramaswamy, Roger E. McLendon, Wan Tew Seow, Wendy J. Ingram, Wiesława Grajkowska, Ronald L. Hamilton, Marcel Kool, Caterina Giannini, William A. Weiss, Luca Massimi, Ian F. Pollack, Marie Lise C. van Veelen, Jaroslav Sterba, David Lyden, Ji Yeoun Lee, Ulrich Schüller, Sébastien Perreault, Nalin Gupta, Johan M. Kros, Arman Jahangiri, Roger J. Packer, Brandyn A. Castro, Lola B. Chambless, Jeffrey J. Olson, Seung-Ki Kim, Almos Klekner, Woo Youl Jang, Uri Tabori, Michelle Fèvre-Montange, Marc Remke, Takafumi Wataya, Michael D. Taylor, Sofia Nunes, Marta Perek-Polnik, Tímea Pócza, Amulya A. Nageswara Rao, James M. Drake, Tenzin Gayden, Alexandre Vasiljevic, Eric S. Lipp, Christian Schneider, Alvaro Lassaletta, Jennifer Adamski, Tarek Shalaby, Darell D. Bigner, Teiji Tominaga, Naoya Hashimoto, Anne Jouvet, Abhaya V. Kulkarni, Noriyuki Kijima, Tomoko Shofuda, José Pimentel, Eric Bouffet, Maria Luisa Garrè, Thompson E.M., Hielscher T., Bouffet E., Remke M., Luu B., Gururangan S., McLendon R.E., Bigner D.D., Lipp E.S., Perreault S., Cho Y.-J., Grant G., Kim S.-K., Lee J.Y., Rao A.A.N., Giannini C., Li K.K.W., Ng H.-K., Yao Y., Kumabe T., Tominaga T., Grajkowska W.A., Perek-Polnik M., Low D.C.Y., Seow W.T., Chang K.T.E., Mora J., Pollack I.F., Hamilton R.L., Leary S., Moore A.S., Ingram W.J., Hallahan A.R., Jouvet A., Fevre-Montange M., Vasiljevic A., Faure-Conter C., Shofuda T., Kagawa N., Hashimoto N., Jabado N., Weil A.G., Gayden T., Wataya T., Shalaby T., Grotzer M., Zitterbart K., Sterba J., Kren L., Hortobagyi T., Klekner A., Laszlo B., Pocza T., Hauser P., Schuller U., Jung S., Jang W.-Y., French P.J., Kros J.M., van Veelen M.-L.C., Massimi L., Leonard J.R., Rubin J.B., Vibhakar R., Chambless L.B., Cooper M.K., Thompson R.C., Faria C.C., Carvalho A., Nunes S., Pimentel J., Fan X., Muraszko K.M., Lopez-Aguilar E., Lyden D., Garzia L., Shih D.J.H., Kijima N., Schneider C., Adamski J., Northcott P.A., Kool M., Jones D.T.W., Chan J.A., Nikolic A., Garre M.L., Van Meir E.G., Osuka S., Olson J.J., Jahangiri A., Castro B.A., Gupta N., Weiss W.A., Moxon-Emre I., Mabbott D.J., Lassaletta A., Hawkins C.E., Tabori U., Drake J., Kulkarni A., Dirks P., Rutka J.T., Korshunov A., Pfister S.M., Packer R.J., Ramaswamy V., Taylor M.D., Neurology, Pathology, and Neurosurgery

Subjects
Adult, Male, medicine.medical_specialty, Canada, medicine.medical_treatment, Klinikai orvostudományok, Article, Disease-Free Survival, Brain Neoplasm, 03 medical and health sciences, 0302 clinical medicine, Retrospective Studie, medicine, Humans, Child, Retrospective Studies, Medulloblastoma, Chemotherapy, Proportional hazards model, business.industry, Brain Neoplasms, Hazard ratio, Cancer, Infant, Retrospective cohort study, Orvostudományok, medicine.disease, Prognosis, Combined Modality Therapy, Magnetic Resonance Imaging, 3. Good health, Surgery, Radiation therapy, Oncology, 030220 oncology & carcinogenesis, Child, Preschool, Disease Progression, Female, business, 030217 neurology & neurosurgery, Chemoradiotherapy, Human
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 (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

49. Epigenetic Silencing of DKK3 in Medulloblastoma

Author

Sara Stigliani, Gian Paolo Tonini, Marcel Kool, Massimo Romani, André Oberthuer, Francesca Valdora, Claudio Brigati, Barbara Banelli, Marc Remke, Giuseppe Cinalli, Massimo Zollo, Simona Coco, Tiziana Servidei, Alfa H.C. Bai, Stefano Moretti, Thomas Hielscher, Stefan M. Pfister, Valdora, F, Banelli, B, Stigliani, S, Pfister, Sm, Moretti, S, Kool, M, Remke, M, Bai, Ah, Brigati, C, Hielscher, T, Romani, M, Servidei, T, Zollo, Massimo, Cinalli, G, Oberthuer, A, Tonini, Gp, Coco, S., National Cancer Research Institute, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Laboratoire d'analyse et modélisation de systèmes pour l'aide à la décision (LAMSADE), Université Paris Dauphine-PSL, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), The University of Hong Kong (HKU), Division of Pediatric Oncology, Catholic University of Rome, Ceinge, centro di Ingegneria Genetica e Biotecnologie Avanzate, Children's Hospital of Cologne, and Universita degli Studi di Padova

Subjects
Male, DKK family, lcsh:Chemistry, 0302 clinical medicine, Databases, Genetic, medulloblastoma, Wnt antagonists, DKK3 downregulation, histone deacetylase, TSA, RNA, Neoplasm, Child, lcsh:QH301-705.5, Spectroscopy, Regulation of gene expression, Genetics, 0303 health sciences, Wnt signaling pathway, General Medicine, Methylation, Middle Aged, Computer Science Applications, Neoplasm Proteins, Gene Expression Regulation, Neoplastic, 030220 oncology & carcinogenesis, Child, Preschool, Intercellular Signaling Peptides and Proteins, Female, Chemokines, medicine.drug, Adult, Adolescent, Biology, Catalysis, Article, Inorganic Chemistry, 03 medical and health sciences, Cell Line, Tumor, microRNA, medicine, Gene silencing, Humans, [INFO]Computer Science [cs], Epigenetics, Gene Silencing, RNA, Messenger, Physical and Theoretical Chemistry, Molecular Biology, 030304 developmental biology, Adaptor Proteins, Signal Transducing, Aged, Gene Expression Profiling, Organic Chemistry, Infant, Chromatin Assembly and Disassembly, Trichostatin A, lcsh:Biology (General), lcsh:QD1-999, Cancer research, Histone deacetylase
Abstract

Cet article est en libre accès.; International audience; Medulloblastoma (MB) is a malignant pediatric brain tumor arising in the cerebellum consisting of four distinct subgroups: WNT, SHH, Group 3 and Group 4, which exhibit different molecular phenotypes. We studied the expression of Dickkopf (DKK) 1–4 family genes, inhibitors of the Wnt signaling cascade, in MB by screening 355 expression profiles derived from four independent datasets. Upregulation of DKK1, DKK2 and DKK4 mRNA was observed in the WNT subgroup, whereas DKK3 was downregulated in 80% MBs across subgroups with respect to the normal cerebellum (p < 0.001). Since copy number aberrations targeting the DKK3 locus (11p15.3) are rare events, we hypothesized that epigenetic factors could play a role in DKK3 regulation. Accordingly, we studied 77 miRNAs predicting to repress DKK3; however, no significant inverse correlation between miRNA/mRNA expression was observed. Moreover, the low methylation levels in the DKK3 promoters (median: 3%, 5% and 5% for promoter 1, 2 and 3, respectively) excluded the downregulation of gene expression by methylation. On the other hand, the treatment of MB cells with Trichostatin A (TSA), a potent inhibitor of histone deacetylases (HDAC), was able to restore both DKK3 mRNA and protein. In conclusion, DKK3 downregulation across all MB subgroups may be due to epigenetic mechanisms, in particular, through chromatin condensation.

Published
2013
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50. Patterns of progression in a contemporary cohort of 447 patients with smoldering multiple myeloma.

Author

Werly A, Hampel M, Hielscher T, Zuern K, Schmidt SK, Visram A, Raab MS, Mueller-Tidow C, Goldschmidt H, and Mai EK

Subjects
Humans, Male, Female, Aged, Middle Aged, Aged, 80 and over, Adult, Cohort Studies, Multiple Myeloma diagnosis, Multiple Myeloma pathology, Multiple Myeloma therapy, Multiple Myeloma epidemiology, Smoldering Multiple Myeloma diagnosis, Disease Progression
Published
2024
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