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153. Diffuse glioneuronal tumour with oligodendroglioma‐like features and nuclear clusters (DGONC) – a molecularly defined glioneuronal CNS tumour class displaying recurrent monosomy 14

Author

Deng, M. Y., primary, Sill, M., additional, Sturm, D., additional, Stichel, D., additional, Witt, H., additional, Ecker, J., additional, Wittmann, A., additional, Schittenhelm, J., additional, Ebinger, M., additional, Schuhmann, M. U., additional, Figarella‐Branger, D., additional, Aronica, E., additional, Staszewski, O., additional, Preusser, M., additional, Haberler, C., additional, Lauten, M., additional, Schüller, U., additional, Hartmann, C., additional, Snuderl, M., additional, Dunham, C., additional, Jabado, N., additional, Wesseling, P., additional, Deckert, M., additional, Keyvani, K., additional, Gottardo, N., additional, Giangaspero, F., additional, Hoff, K., additional, Ellison, D. W., additional, Pietsch, T., additional, Herold-Mende, C., additional, Milde, T., additional, Witt, O., additional, Kool, M., additional, Korshunov, A., additional, Wick, W., additional, Deimling, A., additional, Pfister, S. M., additional, Jones, D. T. W., additional, and Sahm, F., additional

Published
2020
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154. DNA methylation, transcriptome and genetic copy number signatures of diffuse cerebral WHO grade II/III gliomas resolve cancer heterogeneity and development

Author

Binder, H., Willscher, E., Loeffler-Wirth, H., Hopp, L., Jones, D. T. W., Pfister, S. M., Kreuz, M., Gramatzki, D., Fortenbacher, E., Hentschel, B., Tatagiba, M., Herrlinger, U., Vatter, H., Matschke, J., Westphal, M., Krex, D., Schackert, G., Tonn, J. C., Schlegel, U., Steiger, H.-J., Wick, W., Weber, R. G., Weller, M., and Loeffler, M.

Subjects
ddc
Published
2018

155. OS7.4 Calculating the net clinical benefit in brain tumor clinical trials by combining survival and health-related quality of life data using two methods: quality adjusted survival effect sizes (QASES) and joint modelling (JM)

Author

Coomans, M, Dirven, L, Bottomley, A, van den Bent, M, Sloan, J, Stupp, R, Weller, M, Reijneveld, J C, Taphoorn, M, Aaronson, N, Baumert, B G, Brandes, A A, Chinot, O, Coens, C, Gorlia, T, Herrlinger, U, Keime-Guibert, F, Malmström, A, Martinelli, F, Talacchi, A, and Wick, W

Subjects
Cancer Research, Oncology, Oral Presentations, Neurology (clinical), humanities
Abstract

BACKGROUND The impact of treatment on both the quality and the quantity of life, i.e. the ‘net clinical benefit’, should be considered to inform glioma patients and facilitate shared decision making. We applied two methods (i.e. Quality Adjusted Effect Sizes (QASES) and Joint Modelling (JM)) that combine survival and health-related quality of life (HRQoL) data into one outcome, to gain insight in the net clinical benefit of a treatment strategy. In addition, we assessed if both methods result in similar interpretations. MATERIAL AND METHODS We calculated the net clinical benefit in one randomized controlled trial, EORTC 26951 comparing radiotherapy (RT) + PCV chemotherapy versus RT alone, as a proof of concept for other trials. With the QASES method, effect sizes for differences in survival and HRQoL between treatment arms were calculated. Next, the combined effect size can be determined by weighing the emphasis put on survival or HRQoL (e.g. survival more important). JM allows simultaneous modeling of a longitudinal outcome (HRQoL), and a time-to event outcome (survival). HRQoL scales/items that were selected for primary analysis in the main study were also selected for this analysis: fatigue, global health, social functioning, communication deficit, seizures, physical functioning, and nausea/vomiting. RESULTS 288/386 patients completed baseline HRQoL forms and were included in the analysis. Overall survival (OS) was significantly longer with combined treatment (difference of 10.8 months). In contrast, the percentage of patients who experienced a clinically relevant deterioration (≥10 points) in nausea/vomiting, fatigue, social functioning and global health up to one year after treatment compared to baseline was larger in the RT+PCV arm. The QASES corresponded to a reduction in the median OS difference from 10.8 months to 6.8 months when adjusted for the HRQoL scales/items, when given equal weights to OS and HRQoL. JM analyses resulted in a theoretical loss of treatment effect in OS of 2–6% when adjusting for HRQoL. CONCLUSION Both methods showed that adjusting for the impact of treatment on a relevant HRQoL parameter reduced the survival benefit in the experimental treatment arm compared to standard treatment arm. Applying these methods may facilitate communicating the impact of treatment to patients in clinical practice.

Published
2019
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156. Safety, efficacy, PK and PD biomarker results of the first-in-human study of mutant isocitrate dehydrogenase 1 (mIDH1) inhibitor BAY 1436032 in patients (pts) with mIDH1 advanced solid tumours

Author

Wick, W., primary, Tabatabai, G., additional, Schuler, M., additional, Rorhberg, K., additional, Chawla, S.P., additional, Janku, F., additional, Schiff, D., additional, Heinemann, V., additional, Narita, Y., additional, Ando, Y., additional, Lenz, H.J., additional, Ikeda, M., additional, Genvresse, I., additional, Rentzsch, C., additional, Reschke, S., additional, Cyris, C., additional, Cai, C., additional, Jeffers, M., additional, Peña, C., additional, and Bähr, O., additional

Published
2019
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157. OS7.2 Measuring change in health-related quality of life: the added value of analysis on the individual patient level in glioma patients in clinical decision making

Author

Coomans, M, primary, Taphoorn, M J B, additional, Aaronson, N, additional, Baumert, B G, additional, van den Bent, M, additional, Bottomley, A, additional, Brandes, A A, additional, Chinot, O, additional, Coens, C, additional, Gorlia, T, additional, Herrlinger, U, additional, Keime-Guibert, F, additional, Malmström, A, additional, Martinelli, F, additional, Stupp, R, additional, Talacchi, A, additional, Weller, M, additional, Wick, W, additional, Reijneveld, J C, additional, and Dirven, L, additional

Published
2019
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158. PL3.2 Trabectedin for recurrent WHO grade II or III meningioma: a randomized phase II study of the EORTC Brain Tumor Group (EORTC-1320-BTG)

Author

Preusser, M, primary, Silvani, A, additional, Le Rhun, E, additional, Soffietti, R, additional, Lombardi, G, additional, Sepulveda, J, additional, Brandal, P, additional, Beaney, R, additional, Bonneville-Levard, A, additional, Lorgis, V, additional, Bromberg, J, additional, Erridge, S, additional, Cameron, A, additional, Marosi, C, additional, Golfinopoulos, V, additional, Gorlia, T, additional, Weller, M, additional, and Wick, W, additional

Published
2019
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159. PL3.3 Second interim and first molecular analysis of the EORTC randomized phase III intergroup CATNON trial on concurrent and adjuvant temozolomide in anaplastic glioma without 1p/19q codeletion

Author

van den Bent, M J, primary, Erridge, S, additional, Vogelbaum, M A, additional, Nowak, A K, additional, Sanson, M, additional, Brandes, A A, additional, Wick, W, additional, Clement, P M, additional, Baurain, J F, additional, Mason, W, additional, Wheeler, H, additional, Weller, M, additional, Aldape, K, additional, Wesseling, P, additional, Kros, J M, additional, Tesileanu, C M S, additional, Golfinopoulos, V, additional, Gorlia, T, additional, Baumert, B G, additional, and French, P J, additional

Published
2019
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163. P11.07 LAPTM5 functions as a tumor suppressor via CD40 - NFêB pathway inhibition and represents a potential biomarker for temozolomide sensitivity in CD40 proficient glioblastoma

Author

Berberich, A, primary, Bartels, F, additional, Tang, Z, additional, Pusch, S, additional, Hucke, N, additional, Kessler, T, additional, Dong, Z, additional, Wiestler, B, additional, Winkler, F, additional, Platten, M, additional, Wick, W, additional, Abdollahi, A, additional, and Lemke, D, additional

Published
2019
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164. P14.108 Bevacizumab versus alkylating chemotherapy in recurrent glioblastoma

Author

Seystahl, K, primary, Hentschel, B, additional, Loew, S, additional, Gramatzki, D, additional, Felsberg, J, additional, Herrlinger, U, additional, Westphal, M, additional, Schackert, G, additional, Thon, N, additional, Schlegel, U, additional, Tatagiba, M, additional, Pietsch, T, additional, Reifenberger, G, additional, Löffler, M, additional, Wick, W, additional, and Weller, M, additional

Published
2019
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165. Relaxation-compensated amide proton transfer (APT) MRI is a predictor of survival and progression in high-grade glioma patients

Author

Paech, D, additional, Dreher, C, additional, Regnery, S, additional, Meissner, J, additional, Goerke, S, additional, Windschuh, J, additional, Deike-Hofmann, K, additional, Bickelhaupt, S, additional, Radburch, A, additional, Zaiss, M, additional, Unterberg, A, additional, Wick, W, additional, Bendszus, M, additional, Bachert, P, additional, Ladd, M, additional, and Schlemmer, H, additional

Published
2019
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167. A Phase Ib/II, open-label, multicenter study of INC280 (capmatinib) alone and in combination with buparlisib (BKM120) in adult patients with recurrent glioblastoma

Author

Bent, M.J. (Martin) van den, Azaro, A. (Analia), Vos, F. (Filip) de, Sepulveda, J. (Juan), Yung, W.K.A. (W. K. Alfred), Wen, P.Y. (Patrick), Lassman, A.B. (Andrew B.), Joerger, M., Tabatabai, G. (Ghazaleh), Rodon, J. (Jordi), Tiedt, R. (Ralph), Zhao, S. (Sylvia), Kirsilae, T. (Tiina), Cheng, Y. (Yi), Vicente, S. (Sergio), Balbin, O.A. (O. Alejandro), Zhang, H. (Hefei), Wick, W. (Wolfgang), Bent, M.J. (Martin) van den, Azaro, A. (Analia), Vos, F. (Filip) de, Sepulveda, J. (Juan), Yung, W.K.A. (W. K. Alfred), Wen, P.Y. (Patrick), Lassman, A.B. (Andrew B.), Joerger, M., Tabatabai, G. (Ghazaleh), Rodon, J. (Jordi), Tiedt, R. (Ralph), Zhao, S. (Sylvia), Kirsilae, T. (Tiina), Cheng, Y. (Yi), Vicente, S. (Sergio), Balbin, O.A. (O. Alejandro), Zhang, H. (Hefei), and Wick, W. (Wolfgang)

Abstract

Purpose: To estimate the maximum tolerated dose (MTD) and/or identify the recommended Phase II dose (RP2D) for combined INC280 and buparlisib in patients with recurrent glioblastoma with homozygous phosphatase and tensin homolog (PTEN) deletion, mutation or protein loss. Methods: This multicenter, open-label, Phase Ib/II study included adult patients with glioblastoma with mesenchymal-epithelial transcription factor (c-Met) amplification. In Phase Ib, patients received INC280 as capsules or tablets in combination with buparlisib. In Phase II, patients received INC280 only. Response was assessed centrally using Response Assessment in Neuro-Oncology response criteria for high-grade gliomas. All adverse events (AEs) were recorded and graded. Results: 33 patients entered Phase Ib, 32 with altered PTEN. RP2D was not declared due to potential drug–drug interactions, which may have resulted in lack of efficacy; thus, Phase II, including 10 patients, was continued with INC280 monotherapy only. Best response was stable disease in 30% of patients. In the selected patient population, enrollment was halted due to limited activity with INC280 monotherapy. In Phase Ib, the most common treatment-related AEs were fatigue (36.4%), nausea (30.3%) and increased alanine aminotransferase (30.3%). MTD was identified at INC280 Tab 300 mg twice daily + buparlisib 80 mg once daily. In Phase II, the most common AEs were headache (40.0%), constipation (30.0%), fatigue (30.0%) and increased lipase (30.0%). Conclusion: The combination of INC280/buparlisib resulted in no clear activity in patients with recurrent PTEN-deficient glioblastoma. More stringent molecular selection strategies might produce better outcomes. Trial registration: NCT01870726.

Published
2019
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168. Symptom clusters in newly diagnosed glioma patients: which symptom clusters are independently associated with functioning and global health status?

Author

Coomans, M.B., Dirven, L, Aaronson, N.K. (Neil), Baumert, B.G. (Brigitta), Bent, M.J. (Martin) van den, Bottomley, A. (Andrew), Brandes, A. (Alba), Chinot, O, Coens, C. (Corneel), Gorlia, T.S. (Thierry), Herrlinger, U, Keime-Guibert, F., Malmstrom, A, Martinelli, F, Stupp, R. (Roger), Talacchi, A., Weller, M. (Michael), Wick, W. (Wolfgang), Reijneveld, J.C., Taphoorn, MJ, Coomans, M.B., Dirven, L, Aaronson, N.K. (Neil), Baumert, B.G. (Brigitta), Bent, M.J. (Martin) van den, Bottomley, A. (Andrew), Brandes, A. (Alba), Chinot, O, Coens, C. (Corneel), Gorlia, T.S. (Thierry), Herrlinger, U, Keime-Guibert, F., Malmstrom, A, Martinelli, F, Stupp, R. (Roger), Talacchi, A., Weller, M. (Michael), Wick, W. (Wolfgang), Reijneveld, J.C., and Taphoorn, MJ

Abstract

Background. Symptom management in glioma patients remains challenging, as patients suffer from various concurrently occurring symptoms. This study aimed to identify symptom clusters and examine the association between these symptom clusters and patients’ functioning. Methods. Data of the CODAGLIO project was used, including individual patient data from previously published international randomized controlled trials (RCTs) in glioma patients. Symptom prevalence and level of functioning were assessed with European Organisation for Research and Treatment of Cancer (EORTC) quality of life QLQC30 and QLQ-BN20 self-report questionnaires. Associations between symptoms were examined with Spearman correlation coefficients and partial correlation networks. Hierarchical cluster analyses were performed to identify symptom clusters. Multivariable regression analyses were performed to determine independent associations between the symptom clusters and functioning, adjusted for possible confounders. Results. Included in the analysis were 4307 newly diagnosed glioma patients from 11 RCTs who completed the EORTC questionnaires before randomization. Many patients (44%) suffered from 5–10 symptoms simultaneously. Four symptom clusters were identified: a motor cluster, a fatigue cluster, a pain cluster, and a gastrointestinal/seizures/bladder control cluster. Having symptoms in the motor cluster was associated with decreased (≥10 points difference) physical, role, and

Published
2019
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169. Automated quantitative tumour response assessment of MRI in neuro-oncology with artificial neural networks: a multicentre, retrospective study

Author

Kickingereder, P., Isensee, F., Tursunova, I., Petersen, J. (Jørgen), Neuberger, U., Bonekamp, D., Brugnara, G., Schell, M., Kessler, T.A. (Torsten), Foltyn, M., Harting, I., Sahm, F., Prager, M., Nowosielski, M., Wick, W. (Wolfgang), Nolden, M., Radbruch, A., Debus, J., Schlemmer, H.P., Heiland, S., Platten, M. (Michael), Deimling, A. (Andreas) von, Bent, M.J. (Martin) van den, Gorlia, T.S. (Thierry), Bendszus, M, Maier-Hein, K.H., Kickingereder, P., Isensee, F., Tursunova, I., Petersen, J. (Jørgen), Neuberger, U., Bonekamp, D., Brugnara, G., Schell, M., Kessler, T.A. (Torsten), Foltyn, M., Harting, I., Sahm, F., Prager, M., Nowosielski, M., Wick, W. (Wolfgang), Nolden, M., Radbruch, A., Debus, J., Schlemmer, H.P., Heiland, S., Platten, M. (Michael), Deimling, A. (Andreas) von, Bent, M.J. (Martin) van den, Gorlia, T.S. (Thierry), Bendszus, M, and Maier-Hein, K.H.

Abstract

Background The Response Assessment in Neuro-Oncology (RANO) criteria and requirements for a uniform protocol have been introduced to standardise assessment of MRI scans in both clinical trials and clinical practice. However

Published
2019
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170. Symptom clusters in newly diagnosed glioma patients: which symptom clusters are independently associated with functioning and global health status?

Author

Coomans, MB, Dirven, L, Aaronson, NK, Baumert, BG, van den Bent, Martin, Bottomley, A, Brandes, AA, Chinot, O, Coens, C, Gorlia, T, Herrlinger, U, Keime-Guibert, F, Malmstrom, A, Martinelli, F, Stupp, R, Talacchi, A, Weller, M, Wick, W, Reijneveld, JC, Taphoorn, MJ, Coomans, MB, Dirven, L, Aaronson, NK, Baumert, BG, van den Bent, Martin, Bottomley, A, Brandes, AA, Chinot, O, Coens, C, Gorlia, T, Herrlinger, U, Keime-Guibert, F, Malmstrom, A, Martinelli, F, Stupp, R, Talacchi, A, Weller, M, Wick, W, Reijneveld, JC, and Taphoorn, MJ

Published
2019

171. Automated quantitative tumour response assessment of MRI in neuro-oncology with artificial neural networks: a multicentre, retrospective study

Author

Kickingereder, P, Isensee, F, Tursunova, I, Petersen, J, Neuberger, U, Bonekamp, D, Brugnara, G, Schell, M, Kessler, T, Foltyn, M, Harting, I, Sahm, F, Prager, M, Nowosielski, M, Wick, A, Nolden, M, Radbruch, A, Debus, J, Schlemmer, HP, Heiland, S, Platten, M, von Deimling, A, van den Bent, Martin, Gorlia, T, Wick, W, Bendszus, M, Maier-Hein, KH, Kickingereder, P, Isensee, F, Tursunova, I, Petersen, J, Neuberger, U, Bonekamp, D, Brugnara, G, Schell, M, Kessler, T, Foltyn, M, Harting, I, Sahm, F, Prager, M, Nowosielski, M, Wick, A, Nolden, M, Radbruch, A, Debus, J, Schlemmer, HP, Heiland, S, Platten, M, von Deimling, A, van den Bent, Martin, Gorlia, T, Wick, W, Bendszus, M, and Maier-Hein, KH

Published
2019

174. A first-in-man multicenter phase I clinical trial of the German Neurooncology Working Group evaluating a mutation-specific peptide vaccine targeting IDH1R132H in patients with newly diagnosed malignant astrocytomas

Author

Platten, M, Schilling, D, Bunse, L, Wick, A, Bunse, T, Riehl, D, Green, E, Sanghvi, K, Karapanagiotou-Schenkel, I, Harting, I, Sahm, F, Steinbach, J, Weyerbrock, A, Hense, Jörg, Misch, M, Krex, D, Setvanovic, S, Tabatabai, G, von Deimling, A, Schmitt, M, and Wick, W

Subjects
Medizin
Published
2018

175. THE ADDED VALUE OF HEALTH-RELATED QUALITY OF LIFE (HRQoL) AS A PROGNOSTIC INDICATOR OF OVERALL SURVIVAL AND PROGRESSION FREE SURVIVAL IN GLIOMA PATIENTS: A META-ANALYSIS BASED ON INDIVIDUAL PATIENT DATA FROM RANDOMIZED CONTROLLED TRIALS

Author

Coomans, M., Dirven, L., Aaronson, N., Baumert, B.G., Bent, M. van den, Bottomley, A., Brandes, A., Chinot, O., Coens, C., Gorlia, T., Herrlinger, U., Keime-Guibert, F., Malmstrom, A., Martinelli, F., Stupp, R., Talacchi, A., Wick, W., Reijneveld, J.C., and Taphoorn, M.J.B.

Published
2017

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

Author

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

Abstract

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

Published
2017
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177. Evidence-based management of adult patients with diffuse glioma

Author

Weller, M., Bent, M. van den, Tonn, J.C., Stupp, R., Preusser, M., Cohen-Jonathan-Moyal, E., Henriksson, R., Rhun, E. le, Balana, C., Chinot, O., Bendszus, M., Reijneveld, J.C., Dhermain, F., French, P., Marosi, C., Watts, C., Oberg, I., Pilkington, G., Baumert, B.G., Taphoorn, M.J.B., Hegi, M., Westphal, M., Reifenberger, G., Soffietti, R., Wick, W., and European Assoc Neuro-Oncology EANO

Published
2017

178. Neuroonkologie

Author

Wick, W, Weller, M, University of Zurich, and Wick, W

Subjects
2738 Psychiatry and Mental Health, 2728 Neurology (clinical), 2808 Neurology, 610 Medicine & health, 10040 Clinic for Neurology
Published
2015

179. Magnetization transfer ratio: a quantitative imaging biomarker for 5q spinal muscular atrophy.

Author

Kollmer, J., Kessler, T., Sam, G., Hayes, J. M., Lentz, S. I., Heiland, S., Bendszus, M., Wick, W., and Weiler, M.

Subjects
SPINAL muscular atrophy, MAGNETIZATION transfer, BIOMARKERS, SCIATIC nerve, PERIPHERAL nervous system
Abstract

Background and purpose: We quantified peripheral nerve lesions in adults with 5q‐linked spinal muscular atrophy (SMA) type 3 by analysing the magnetization transfer ratio (MTR) of the sciatic nerve, and tested its potential as a novel biomarker for macromolecular changes. Methods: Eighteen adults with SMA 3 (50% SMA 3a, 50% SMA 3b) and 18 age‐/sex‐matched healthy controls prospectively underwent magnetization transfer contrast imaging in a 3‐Tesla magnetic resonance scanner. Two axial three‐dimensional gradient echo sequences, with and without an off‐resonance saturation rapid frequency pulse, were performed at the right distal thigh. Sciatic nerve regions of interest were manually traced on 10 consecutive axial slices in the images generated without off‐resonance saturation, and then transferred to corresponding slices generated by the sequence with the off‐resonance saturation pulse. Subsequently, MTR and cross‐sectional areas (CSAs) of the sciatic nerve were analysed. In addition, detailed neurologic, physiotherapeutic and electrophysiologic examinations were conducted in all patients. Results: Sciatic nerve MTR and CSA reliably differentiated between healthy controls and SMA 3, 3a or 3b. MTR was lower in the SMA 3 (P < 0.0001), SMA 3a (P < 0.0001) and SMA 3b groups (P = 0.0020) than in respective controls. In patients with SMA 3, MTR correlated with all clinical scores, and arm nerve compound motor action potentials (CMAPs). CSA was lower in the SMA 3 (P < 0.0001), SMA 3a (P < 0.0001) and SMA 3b groups (P = 0.0006) than in controls, but did not correlate with clinical scores or electrophysiologic results. Conclusions: Magnetization transfer ratio is a novel imaging marker that quantifies macromolecular nerve changes in SMA 3, and positively correlates with clinical scores and CMAPs. [ABSTRACT FROM AUTHOR]

Published
2021
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180. Patient‐centredness in acute stroke care – a qualitative study from the perspectives of patients, relatives and staff.

Author

Busetto, L., Stang, C., Hoffmann, J., Amiri, H., Seker, F., Purrucker, J., Ringleb, P. A., Nagel, S., Bendszus, M., Wick, W., and Gumbinger, C.

Subjects
NEUROLOGICAL disorders, STROKE, QUALITATIVE research, INTENSIVE care units, STROKE units
Abstract

Background and purpose: Although patient‐centredness is considered a key component of high‐quality neurological care, it is unclear to what extent it can or should be implemented during the acute phase. Using acute stroke as an example, the aim was to identify critical junctures for patient‐centredness along the acute care pathway from the perspectives of patients, relatives and staff. Methods: A qualitative multi‐method study was conducted including 27 non‐participant observations and 37 semi‐structured interviews with patients, relatives and staff. Junctures were defined as critical when mentioned (as problematic) in two or three information sources (i.e. observations, staff interviews, or patient and relative interviews), as potentially critical when mentioned in one, and as uncritical when not mentioned. Results: Post‐procedure communication after thrombectomy, patients' stay at the stroke unit and decision‐making around transfer, discharge and rehabilitation were identified as critical junctures for patient‐centredness. Arrival at the emergency department and the (thrombectomy) treatment itself were identified as uncritical junctures, whilst history‐taking and treatment preparation, the treatment decision and patients' stay at the intensive care unit were identified as potentially critical junctures. Conclusions: In acute stroke care, patients, relatives and staff prioritize fast over patient‐centred decision‐making in the most time‐critical phases, especially before and during treatment. This is reversed after the procedure, when difficulties arise implementing a patient‐centred approach in clinical practice. To improve patient‐centredness where it is most needed, clear guidelines and accessible resources are recommended. Future research should investigate whether insights from acute phases of stroke care are applicable to other neurological conditions as well. [ABSTRACT FROM AUTHOR]

Published
2020
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181. Integrated molecular characterization of IDH -mutant glioblastomas

Author

Korshunov, A., primary, Casalini, B., additional, Chavez, L., additional, Hielscher, T., additional, Sill, M., additional, Ryzhova, M., additional, Sharma, T., additional, Schrimpf, D., additional, Stichel, D., additional, Capper, D., additional, Reuss, D. E., additional, Sturm, D., additional, Absalyamova, O., additional, Golanov, A., additional, Lambo, S., additional, Bewerunge-Hudler, M., additional, Lichter, P., additional, Herold-Mende, C., additional, Wick, W., additional, Pfister, S. M., additional, Kool, M., additional, Jones, D. T. W., additional, von Deimling, A., additional, and Sahm, F., additional

Published
2018
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186. OS6.4 NOA-16: A first-in-man multicenter phase I clinical trial of the German Neurooncology Working Group evaluating a mutation-specific peptide vaccine targeting IDH1R132H in patients with newly diagnosed malignant astrocytomas

Author

Platten, M, primary, Schilling, D, additional, Bunse, L, additional, Wick, A, additional, Bunse, T, additional, Riehl, D, additional, Green, E, additional, Sanghvi, K, additional, Karapanagiotou-Schenkel, I, additional, Harting, I, additional, Sahm, F, additional, Steinbach, J, additional, Weyerbrock, A, additional, Hense, J, additional, Misch, M, additional, Krex, D, additional, Setvanovic, S, additional, Tabatabai, G, additional, von Deimling, A, additional, Schmitt, M, additional, and Wick, W, additional

Published
2018
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189. P01.031 VXM01 phase I study in patients with progressive glioblastoma - final results

Author

Wick, W, primary, Wick, A, additional, Sahm, F, additional, Riehl, D, additional, von Deimling, A, additional, Bendszus, M, additional, Mickingereder, P, additional, Beckhove, P, additional, Schmitz Winnenthal, F, additional, Jungk, C, additional, Wieckoswski, S, additional, Keller, A, additional, Podola, L, additional, Herold-Mende, C, additional, Lubenau, H, additional, Unterberg, A, additional, and Platten, M J, additional

Published
2018
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193. T1ρ-gewichtete dynamische Glukose-verstärkte Magnetresonanztomografie bei Glioblastompatienten

Author

Paech, D, additional, Schuenke, P, additional, Koehler, C, additional, Windschuh, J, additional, Mundiyanapurath, S, additional, Bickelhaupt, S, additional, Bonekamp, D, additional, Bäumer, P, additional, Bachert, P, additional, Ladd, M, additional, Bendszus, M, additional, Wick, W, additional, Unterberg, A, additional, Schlemmer, H, additional, Zaiss, M, additional, and Radbruch, A, additional

Published
2018
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195. The DNA methylome of DDR genes and benefit from RT or TMZ in IDH mutant low-grade glioma treated in EORTC 22033

Author

Bady, P. (Pierre), Kurscheid, S. (Sebastian), Delorenzi, M. (Mauro), Gorlia, T.S. (Thierry), Bent, M.J. (Martin) van den, Hoang-Xuan, K. (Khê), Vauléon, É. (Élodie), Gijtenbeek, A., Enting, R. (Roelien), Thiessen, B. (Brian), Chinot, O., Dhermain, F.G. (Frederic), Brandes, A. (Alba), Reijneveld, J.C., Marosi, C. (Christine), Taphoorn, M.J. (Martin), Wick, W. (Wolfgang), Deimling, A. (Andreas) von, French, P.J. (Pim), Stupp, R. (Roger), Baumert, B.G. (Brigitta), Hegi, M.E. (Monika), Bady, P. (Pierre), Kurscheid, S. (Sebastian), Delorenzi, M. (Mauro), Gorlia, T.S. (Thierry), Bent, M.J. (Martin) van den, Hoang-Xuan, K. (Khê), Vauléon, É. (Élodie), Gijtenbeek, A., Enting, R. (Roelien), Thiessen, B. (Brian), Chinot, O., Dhermain, F.G. (Frederic), Brandes, A. (Alba), Reijneveld, J.C., Marosi, C. (Christine), Taphoorn, M.J. (Martin), Wick, W. (Wolfgang), Deimling, A. (Andreas) von, French, P.J. (Pim), Stupp, R. (Roger), Baumert, B.G. (Brigitta), and Hegi, M.E. (Monika)

Abstract

The optimal treatment for patients with low-grade glioma (LGG) WHO grade II remains controversial. Overall survival ranges from 2 to over 15 years depending on molecular and clinical factors. Hence, risk-adjusted treatments are required for optimizing outcome and quality of life. We aim at identifying mechanisms and associated molecular markers predictive for benefit from radiotherapy (RT) or temozolomide (TMZ) in LGG patients treated in the randomized phase III trial EORTC 22033. As candidate biomarkers for these genotoxic treatments, we considered the DNA methylome of 410 DNA damage response (DDR) genes. We first identified 62 functionally relevant CpG sites located in the promoters of 24 DDR genes, using the LGG data from The Cancer Genome Atlas. Then we tested their association with outcome [progression-free survival (PFS)] depending on treatment in 120 LGG patients of EORTC 22033, whose tumors were mutant for isocitrate dehydrogenase 1 or 2 (IDHmt), the molecular hallmark of LGG. The results suggested that seven CpGs of four DDR genes may be predictive for longer PFS in one of the treatment arms that comprised MGMT, MLH3, RAD21, and SMC4. Most interestingly, the two CpGs identified for MGMT are the same, previously selected for the MGMT-STP27 score that is used to determine the methylation status of the MGMT gene. This score was higher in the LGG with 1p/19q codeletion, in this and other independent LGG datasets. It was predictive for PFS in the TMZ, but not in the RT arm of EORTC 22033. The results support the hypothesis that a high score predicts benefit from TMZ treatment for patients with IDHmt LGG, regardless of the 1p/19q status. This MGMT methylation score may identify patients who benefit from first-line treatment with TMZ, to defer RT for long-term preservation of cognitive function and quality of life.

Published
2018
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196. DNA methylation-based classification of central nervous system tumours

Author

Capper, D, Jones, DTW, Sill, M, Hovestadt, V, Schrimpf, D, Sturm, D, Koelsche, C, Sahm, F, Chavez, L, Reuss, DE, Kratz, A, Wefers, AK, Huang, K, Pajtler, KW, Schweizer, L, Stichel, D, Olar, A, Engel, NW, Lindenberg, K, Harter, PN, Braczynski, AK, Plate, KH, Dohmen, H, Garvalov, BK, Coras, R, Hoelsken, A, Hewer, E, Bewerunge-Hudler, M, Schick, M, Fischer, R, Beschorner, R, Schittenhelm, J, Staszewski, O, Wani, K, Varlet, P, Pages, M, Temming, P, Lohmann, D, Selt, F, Witt, H, Milde, T, Witt, O, Aronica, E, Giangaspero, F, Rushing, E, Scheurlen, W, Geisenberger, C, Rodriguez, FJ, Becker, A, Preusser, M, Haberler, C, Bjerkvig, R, Cryan, J, Farrell, M, Deckert, M, Hench, J, Frank, S, Serrano, J, Kannan, K, Tsirigos, A, Brueck, W, Hofer, S, Brehmer, S, Seiz-Rosenhagen, M, Haenggi, D, Hans, V, Rozsnoki, S, Hansford, JR, Kohlhof, P, Kristensen, BW, Lechner, M, Lopes, B, Mawrin, C, Ketter, R, Kulozik, A, Khatib, Z, Heppner, F, Koch, A, Jouvet, A, Keohane, C, Muehleisen, H, Mueller, W, Pohl, U, Prinz, M, Benner, A, Zapatka, M, Gottardo, NG, Driever, PH, Kramm, CM, Mueller, HL, Rutkowski, S, von Hoff, K, Fruehwald, MC, Gnekow, A, Fleischhack, G, Tippelt, S, Calaminus, G, Monoranu, C-M, Perry, A, Jones, C, Jacques, TS, Radlwimmer, B, Gessi, M, Pietsch, T, Schramm, J, Schackert, G, Westphal, M, Reifenberger, G, Wesseling, P, Weller, M, Collins, VP, Bluemcke, I, Bendszus, M, Debus, J, Huang, A, Jabado, N, Northcott, PA, Paulus, W, Gajjar, A, Robinson, GW, Taylor, MD, Jaunmuktane, Z, Ryzhova, M, Platten, M, Unterberg, A, Wick, W, Karajannis, MA, Mittelbronn, M, Acker, T, Hartmann, C, Aldape, K, Schueller, U, Buslei, R, Lichter, P, Kool, M, Herold-Mende, C, Ellison, DW, Hasselblatt, M, Snuderl, M, Brandner, S, Korshunov, A, von Deimling, A, Pfister, SM, Capper, D, Jones, DTW, Sill, M, Hovestadt, V, Schrimpf, D, Sturm, D, Koelsche, C, Sahm, F, Chavez, L, Reuss, DE, Kratz, A, Wefers, AK, Huang, K, Pajtler, KW, Schweizer, L, Stichel, D, Olar, A, Engel, NW, Lindenberg, K, Harter, PN, Braczynski, AK, Plate, KH, Dohmen, H, Garvalov, BK, Coras, R, Hoelsken, A, Hewer, E, Bewerunge-Hudler, M, Schick, M, Fischer, R, Beschorner, R, Schittenhelm, J, Staszewski, O, Wani, K, Varlet, P, Pages, M, Temming, P, Lohmann, D, Selt, F, Witt, H, Milde, T, Witt, O, Aronica, E, Giangaspero, F, Rushing, E, Scheurlen, W, Geisenberger, C, Rodriguez, FJ, Becker, A, Preusser, M, Haberler, C, Bjerkvig, R, Cryan, J, Farrell, M, Deckert, M, Hench, J, Frank, S, Serrano, J, Kannan, K, Tsirigos, A, Brueck, W, Hofer, S, Brehmer, S, Seiz-Rosenhagen, M, Haenggi, D, Hans, V, Rozsnoki, S, Hansford, JR, Kohlhof, P, Kristensen, BW, Lechner, M, Lopes, B, Mawrin, C, Ketter, R, Kulozik, A, Khatib, Z, Heppner, F, Koch, A, Jouvet, A, Keohane, C, Muehleisen, H, Mueller, W, Pohl, U, Prinz, M, Benner, A, Zapatka, M, Gottardo, NG, Driever, PH, Kramm, CM, Mueller, HL, Rutkowski, S, von Hoff, K, Fruehwald, MC, Gnekow, A, Fleischhack, G, Tippelt, S, Calaminus, G, Monoranu, C-M, Perry, A, Jones, C, Jacques, TS, Radlwimmer, B, Gessi, M, Pietsch, T, Schramm, J, Schackert, G, Westphal, M, Reifenberger, G, Wesseling, P, Weller, M, Collins, VP, Bluemcke, I, Bendszus, M, Debus, J, Huang, A, Jabado, N, Northcott, PA, Paulus, W, Gajjar, A, Robinson, GW, Taylor, MD, Jaunmuktane, Z, Ryzhova, M, Platten, M, Unterberg, A, Wick, W, Karajannis, MA, Mittelbronn, M, Acker, T, Hartmann, C, Aldape, K, Schueller, U, Buslei, R, Lichter, P, Kool, M, Herold-Mende, C, Ellison, DW, Hasselblatt, M, Snuderl, M, Brandner, S, Korshunov, A, von Deimling, A, and Pfister, SM

Abstract

Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging-with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology.

Published
2018

197. The DNA methylome of DDR genes and benefit from RT or TMZ in IDH mutant low-grade glioma treated in EORTC 22033

Author

Bady, P, Kurscheid, S, Delorenzi, M, Gorlia, T, van den Bent, Martin, Hoang-Xuan, K, Vauleon, E, Gijtenbeek, A, Enting, R, Thiessen, B, Chinot, O, Dhermain, F, Brandes, AA, Reijneveld, JC, Marosi, C, Taphoorn, MJB, Wick, W, von Deimling, A, French, Pim, Stupp, R, Baumert, BG, Hegi, ME, Bady, P, Kurscheid, S, Delorenzi, M, Gorlia, T, van den Bent, Martin, Hoang-Xuan, K, Vauleon, E, Gijtenbeek, A, Enting, R, Thiessen, B, Chinot, O, Dhermain, F, Brandes, AA, Reijneveld, JC, Marosi, C, Taphoorn, MJB, Wick, W, von Deimling, A, French, Pim, Stupp, R, Baumert, BG, and Hegi, ME

Published
2018

198. Hirnmetastasen

Author

Wick, W, Winkler, F, Westphal, M, Weller, Michael, University of Zurich, Diener, H C, Gerloff, C, and Dietrich, M

Subjects
610 Medicine & health, 10040 Clinic for Neurology
Published
2017

199. Gliomatosis cerebri: molecular pathology and clinical course

Author

Herrlinger, U, Felsberg, J, Küker, W, Bornemann, A, Plasswilm, L, Knobbe, CB, Strik, H, Wick, W, Meyermann, R, Dichgans, J, Bamberg, M, Reifenberger, G, and Weller, M

Subjects
neoplasms
Abstract

Gliomatosis cerebri is a rare, diffusely growing neuroepithelial tumor characterized by extensive brain infiltration involving more than two cerebral lobes. Among 13 patients with gliomatosis cerebri (median age, 46 years), biopsies showed features of diffuse astrocytoma (n = 4), oligoastrocytoma (n = 1), anaplastic astrocytoma (n = 5), anaplastic oligoastrocytoma (n = 1), or glioblastoma (n = 2). Molecular genetic investigation showed TP53 mutations in three of seven tumors and both PTEN mutation and epidermal growth factor receptor overexpression in one tumor. Amplification of CDK4 or MDM2 or homozygous deletion of CDKN2A was not detected. Three of 10 patients receiving radiotherapy showed a partial response (one patient) or had stable disease (two patients) lasting for more than 1 year. Four of six patients treated with procarbazine, carmustine, vincristine chemotherapy demonstrated partial remission (one patient), minor response (two patients), or stable disease (one patient). Median survival time from diagnosis was 14 months (range, 4-91+ months). Infratentorial involvement was associated with shorter survival. We conclude that (1) the molecular genetic alterations in gliomatosis cerebri resemble those in diffuse astrocytomas; (2) the prognosis of gliomatosis cerebri is variable but for at least 50% of patients as poor as for glioblastoma; and (3) some patients respond to radiotherapy and/or procarbazine, carmustine, vincristine chemotherapy.

Published
2016
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