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1. Prophetisch begabt und zur Gemeindeleitung beauftragt. Marta und Maria in Joh 11–12

Author

Josef Pichler

Subjects
The Bible, BS1-2970
Abstract

Die beiden Schwestern Marta und Maria, die aus Lk 10,38–42 bekannt sind, werden in Joh 11–12 als prophetisch begabt und für die johanneische Gemeinde verantwortlich gezeichnet. Marta erscheint zunächst als die bestimmende Person, sie bekennt ihren Glauben und erweist sich als hochbegabte Schülerin Jesu. Durch die Salbung des Messias, die im Aufbau deutlich an die Fußwaschung Jesu als gegenkulturelle Praxis erinnert, wird Maria als Prophetin dargestellt, die mit Hingabe und Liebe die Grundbotschaft Jesu lebt und versteht. Indem Maria Jesus die Füße salbt, legt sie durch ihre Tat ein Glaubensbekenntnis ab, das jenem der Marta um nichts nachsteht.

Published
2023

2. Federated learning enables big data for rare cancer boundary detection

Author

Sarthak Pati, Ujjwal Baid, Brandon Edwards, Micah Sheller, Shih-Han Wang, G. Anthony Reina, Patrick Foley, Alexey Gruzdev, Deepthi Karkada, Christos Davatzikos, Chiharu Sako, Satyam Ghodasara, Michel Bilello, Suyash Mohan, Philipp Vollmuth, Gianluca Brugnara, Chandrakanth J. Preetha, Felix Sahm, Klaus Maier-Hein, Maximilian Zenk, Martin Bendszus, Wolfgang Wick, Evan Calabrese, Jeffrey Rudie, Javier Villanueva-Meyer, Soonmee Cha, Madhura Ingalhalikar, Manali Jadhav, Umang Pandey, Jitender Saini, John Garrett, Matthew Larson, Robert Jeraj, Stuart Currie, Russell Frood, Kavi Fatania, Raymond Y. Huang, Ken Chang, Carmen Balaña Quintero, Jaume Capellades, Josep Puig, Johannes Trenkler, Josef Pichler, Georg Necker, Andreas Haunschmidt, Stephan Meckel, Gaurav Shukla, Spencer Liem, Gregory S. Alexander, Joseph Lombardo, Joshua D. Palmer, Adam E. Flanders, Adam P. Dicker, Haris I. Sair, Craig K. Jones, Archana Venkataraman, Meirui Jiang, Tiffany Y. So, Cheng Chen, Pheng Ann Heng, Qi Dou, Michal Kozubek, Filip Lux, Jan Michálek, Petr Matula, Miloš Keřkovský, Tereza Kopřivová, Marek Dostál, Václav Vybíhal, Michael A. Vogelbaum, J. Ross Mitchell, Joaquim Farinhas, Joseph A. Maldjian, Chandan Ganesh Bangalore Yogananda, Marco C. Pinho, Divya Reddy, James Holcomb, Benjamin C. Wagner, Benjamin M. Ellingson, Timothy F. Cloughesy, Catalina Raymond, Talia Oughourlian, Akifumi Hagiwara, Chencai Wang, Minh-Son To, Sargam Bhardwaj, Chee Chong, Marc Agzarian, Alexandre Xavier Falcão, Samuel B. Martins, Bernardo C. A. Teixeira, Flávia Sprenger, David Menotti, Diego R. Lucio, Pamela LaMontagne, Daniel Marcus, Benedikt Wiestler, Florian Kofler, Ivan Ezhov, Marie Metz, Rajan Jain, Matthew Lee, Yvonne W. Lui, Richard McKinley, Johannes Slotboom, Piotr Radojewski, Raphael Meier, Roland Wiest, Derrick Murcia, Eric Fu, Rourke Haas, John Thompson, David Ryan Ormond, Chaitra Badve, Andrew E. Sloan, Vachan Vadmal, Kristin Waite, Rivka R. Colen, Linmin Pei, Murat Ak, Ashok Srinivasan, J. Rajiv Bapuraj, Arvind Rao, Nicholas Wang, Ota Yoshiaki, Toshio Moritani, Sevcan Turk, Joonsang Lee, Snehal Prabhudesai, Fanny Morón, Jacob Mandel, Konstantinos Kamnitsas, Ben Glocker, Luke V. M. Dixon, Matthew Williams, Peter Zampakis, Vasileios Panagiotopoulos, Panagiotis Tsiganos, Sotiris Alexiou, Ilias Haliassos, Evangelia I. Zacharaki, Konstantinos Moustakas, Christina Kalogeropoulou, Dimitrios M. Kardamakis, Yoon Seong Choi, Seung-Koo Lee, Jong Hee Chang, Sung Soo Ahn, Bing Luo, Laila Poisson, Ning Wen, Pallavi Tiwari, Ruchika Verma, Rohan Bareja, Ipsa Yadav, Jonathan Chen, Neeraj Kumar, Marion Smits, Sebastian R. van der Voort, Ahmed Alafandi, Fatih Incekara, Maarten M. J. Wijnenga, Georgios Kapsas, Renske Gahrmann, Joost W. Schouten, Hendrikus J. Dubbink, Arnaud J. P. E. Vincent, Martin J. van den Bent, Pim J. French, Stefan Klein, Yading Yuan, Sonam Sharma, Tzu-Chi Tseng, Saba Adabi, Simone P. Niclou, Olivier Keunen, Ann-Christin Hau, Martin Vallières, David Fortin, Martin Lepage, Bennett Landman, Karthik Ramadass, Kaiwen Xu, Silky Chotai, Lola B. Chambless, Akshitkumar Mistry, Reid C. Thompson, Yuriy Gusev, Krithika Bhuvaneshwar, Anousheh Sayah, Camelia Bencheqroun, Anas Belouali, Subha Madhavan, Thomas C. Booth, Alysha Chelliah, Marc Modat, Haris Shuaib, Carmen Dragos, Aly Abayazeed, Kenneth Kolodziej, Michael Hill, Ahmed Abbassy, Shady Gamal, Mahmoud Mekhaimar, Mohamed Qayati, Mauricio Reyes, Ji Eun Park, Jihye Yun, Ho Sung Kim, Abhishek Mahajan, Mark Muzi, Sean Benson, Regina G. H. Beets-Tan, Jonas Teuwen, Alejandro Herrera-Trujillo, Maria Trujillo, William Escobar, Ana Abello, Jose Bernal, Jhon Gómez, Joseph Choi, Stephen Baek, Yusung Kim, Heba Ismael, Bryan Allen, John M. Buatti, Aikaterini Kotrotsou, Hongwei Li, Tobias Weiss, Michael Weller, Andrea Bink, Bertrand Pouymayou, Hassan F. Shaykh, Joel Saltz, Prateek Prasanna, Sampurna Shrestha, Kartik M. Mani, David Payne, Tahsin Kurc, Enrique Pelaez, Heydy Franco-Maldonado, Francis Loayza, Sebastian Quevedo, Pamela Guevara, Esteban Torche, Cristobal Mendoza, Franco Vera, Elvis Ríos, Eduardo López, Sergio A. Velastin, Godwin Ogbole, Mayowa Soneye, Dotun Oyekunle, Olubunmi Odafe-Oyibotha, Babatunde Osobu, Mustapha Shu’aibu, Adeleye Dorcas, Farouk Dako, Amber L. Simpson, Mohammad Hamghalam, Jacob J. Peoples, Ricky Hu, Anh Tran, Danielle Cutler, Fabio Y. Moraes, Michael A. Boss, James Gimpel, Deepak Kattil Veettil, Kendall Schmidt, Brian Bialecki, Sailaja Marella, Cynthia Price, Lisa Cimino, Charles Apgar, Prashant Shah, Bjoern Menze, Jill S. Barnholtz-Sloan, Jason Martin, and Spyridon Bakas

Subjects
Science
Abstract

Federated ML (FL) provides an alternative to train accurate and generalizable ML models, by only sharing numerical model updates. Here, the authors present the largest FL study to-date to generate an automatic tumor boundary detector for glioblastoma.

Published
2022
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3. Frequency and characteristics of bacterial and viral low-grade infections of the intervertebral discs: a prospective, observational study

Author

Wolfgang Senker, Stefan Aspalter, Christian Radl, Josef Pichler, Stefan Doppler, Serge Weis, Christine Webersinke, Helga Wagner, Philipp Hermann, Martin Aichholzer, Kathrin Aufschnaiter-Hießböck, Wolfgang Thomae, Nico Stroh, Thomas Hauser, and Andreas Gruber

Subjects
Low back pain, Bacterial colonization, Intervertebral discs, Low-grade infection, Modic changes, Cutibacterium acnes, Orthopedic surgery, RD701-811
Abstract

Abstract Study design Monocentric, prospective, observational study. Objective The clinical relevance of bacterial colonization of intervertebral discs is controversial. This study aimed to determine a possible relationship between bacterial and viral colonization and low-grade infection of the discs. Methods We investigated 447 disc samples from 392 patients. Microbiological culture was used to examine the samples for bacterial growth, polymerase chain reaction (PCR) was used for detection of herpes simplex virus types 1 and 2 (HSV-1, HSV-2) and Cytomegalovirus (CMV), and histopathological analysis was used to detect signs of inflammation. The results were compared between subgroups organized according to gender, age, location of the samples, surgical approach, preoperative C-reactive protein (CRP), preoperative and 6 months postoperative Oswestry Disability Index (ODI) and Neck Disability Index (NDI), and Modic changes (MC) of the corresponding endplates. Also, we assessed the occurrence of postoperative infections within 6 months. Results Microbiological culture was positive in 38.78% of the analyzed intervertebral discs. Altogether, 180 bacteria were isolated. Coagulase-negative staphylococci (CONS) (23.41%) and Cutibacterium acnes (18.05%) were the most frequently detected microorganisms. None of HSV-1, HSV-2, or CMV were detected. Male patients (p = 0.00036) and cervical segments (p = 0.00001) showed higher rates of positive culture results. Ventral surgical approaches ( p

Published
2022
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4. Effect of different dietary fibre sources on the zootechnical performance, feeding behaviour and intestinal physiology of growing and finishing pigs

Author

Josef Pichler, Florian Hemetsberger, Melanie Buchberger, Christiane Schwarz, and Karl Schedle

Subjects
fattening pig, dietary fibre sources, behaviour, gut physiology, Animal culture, SF1-1100
Abstract

The aim of this study was to determine the effect of different sources of fibre in the diets of fattening pigs on performance, feeding behaviour and intestinal physiology. A total of 60 barrows and gilts (initial body weight 28.4 ± 0.4 kg) were allotted to four dietary treatments: control (CON), lignocellulose (LC), mycelium (MYC) and corn gluten feed (CGF). Diets were calculated to provide balanced available nutrient contents. Including MYC in the diet resulted in an increased average daily gain (P < 0.05) compared to CON and CGF, and improved gain to feed ratio (P < 0.05) compared to LC. Pigs in CON (P < 0.05) ate the fewest but largest meals, whereas treatment CGF (P < 0.05) showed the opposite effect, resulting in the same daily feeder occupation time. Regarding intestinal physiology, in ileum, no differences were observed between the contents of short chain fatty acids (SCFA), lactic acid and biogenic amines. In the colon, MYC showed an increased concentration of acetic acid (P < 0.05) as well as the total content of SCFA (P < 0.05), compared to LC and CGF. Distinct fermentation profiles of ammonia were recorded in ileal and colonic digesta, although contents remained below harmful concentrations. Morphometrical measurements showed differences between the fibre sources LC and MYC, as well as LC and the CON in all investigated gut sections. These results provide evidence that the inclusion of specific dietary fibre sources/contents can positively influence the gut morphology and performance of pigs. However, further studies are needed regarding the mode of action and physico-chemical characteristics of the different fibre sources as a precondition for their successful application in pig diets.

Published
2022
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5. Author Correction: Federated learning enables big data for rare cancer boundary detection

Author

Sarthak Pati, Ujjwal Baid, Brandon Edwards, Micah Sheller, Shih-Han Wang, G. Anthony Reina, Patrick Foley, Alexey Gruzdev, Deepthi Karkada, Christos Davatzikos, Chiharu Sako, Satyam Ghodasara, Michel Bilello, Suyash Mohan, Philipp Vollmuth, Gianluca Brugnara, Chandrakanth J. Preetha, Felix Sahm, Klaus Maier-Hein, Maximilian Zenk, Martin Bendszus, Wolfgang Wick, Evan Calabrese, Jeffrey Rudie, Javier Villanueva-Meyer, Soonmee Cha, Madhura Ingalhalikar, Manali Jadhav, Umang Pandey, Jitender Saini, John Garrett, Matthew Larson, Robert Jeraj, Stuart Currie, Russell Frood, Kavi Fatania, Raymond Y. Huang, Ken Chang, Carmen Balaña, Jaume Capellades, Josep Puig, Johannes Trenkler, Josef Pichler, Georg Necker, Andreas Haunschmidt, Stephan Meckel, Gaurav Shukla, Spencer Liem, Gregory S. Alexander, Joseph Lombardo, Joshua D. Palmer, Adam E. Flanders, Adam P. Dicker, Haris I. Sair, Craig K. Jones, Archana Venkataraman, Meirui Jiang, Tiffany Y. So, Cheng Chen, Pheng Ann Heng, Qi Dou, Michal Kozubek, Filip Lux, Jan Michálek, Petr Matula, Miloš Keřkovský, Tereza Kopřivová, Marek Dostál, Václav Vybíhal, Michael A. Vogelbaum, J. Ross Mitchell, Joaquim Farinhas, Joseph A. Maldjian, Chandan Ganesh Bangalore Yogananda, Marco C. Pinho, Divya Reddy, James Holcomb, Benjamin C. Wagner, Benjamin M. Ellingson, Timothy F. Cloughesy, Catalina Raymond, Talia Oughourlian, Akifumi Hagiwara, Chencai Wang, Minh-Son To, Sargam Bhardwaj, Chee Chong, Marc Agzarian, Alexandre Xavier Falcão, Samuel B. Martins, Bernardo C. A. Teixeira, Flávia Sprenger, David Menotti, Diego R. Lucio, Pamela LaMontagne, Daniel Marcus, Benedikt Wiestler, Florian Kofler, Ivan Ezhov, Marie Metz, Rajan Jain, Matthew Lee, Yvonne W. Lui, Richard McKinley, Johannes Slotboom, Piotr Radojewski, Raphael Meier, Roland Wiest, Derrick Murcia, Eric Fu, Rourke Haas, John Thompson, David Ryan Ormond, Chaitra Badve, Andrew E. Sloan, Vachan Vadmal, Kristin Waite, Rivka R. Colen, Linmin Pei, Murat Ak, Ashok Srinivasan, J. Rajiv Bapuraj, Arvind Rao, Nicholas Wang, Ota Yoshiaki, Toshio Moritani, Sevcan Turk, Joonsang Lee, Snehal Prabhudesai, Fanny Morón, Jacob Mandel, Konstantinos Kamnitsas, Ben Glocker, Luke V. M. Dixon, Matthew Williams, Peter Zampakis, Vasileios Panagiotopoulos, Panagiotis Tsiganos, Sotiris Alexiou, Ilias Haliassos, Evangelia I. Zacharaki, Konstantinos Moustakas, Christina Kalogeropoulou, Dimitrios M. Kardamakis, Yoon Seong Choi, Seung-Koo Lee, Jong Hee Chang, Sung Soo Ahn, Bing Luo, Laila Poisson, Ning Wen, Pallavi Tiwari, Ruchika Verma, Rohan Bareja, Ipsa Yadav, Jonathan Chen, Neeraj Kumar, Marion Smits, Sebastian R. van der Voort, Ahmed Alafandi, Fatih Incekara, Maarten M. J. Wijnenga, Georgios Kapsas, Renske Gahrmann, Joost W. Schouten, Hendrikus J. Dubbink, Arnaud J. P. E. Vincent, Martin J. van den Bent, Pim J. French, Stefan Klein, Yading Yuan, Sonam Sharma, Tzu-Chi Tseng, Saba Adabi, Simone P. Niclou, Olivier Keunen, Ann-Christin Hau, Martin Vallières, David Fortin, Martin Lepage, Bennett Landman, Karthik Ramadass, Kaiwen Xu, Silky Chotai, Lola B. Chambless, Akshitkumar Mistry, Reid C. Thompson, Yuriy Gusev, Krithika Bhuvaneshwar, Anousheh Sayah, Camelia Bencheqroun, Anas Belouali, Subha Madhavan, Thomas C. Booth, Alysha Chelliah, Marc Modat, Haris Shuaib, Carmen Dragos, Aly Abayazeed, Kenneth Kolodziej, Michael Hill, Ahmed Abbassy, Shady Gamal, Mahmoud Mekhaimar, Mohamed Qayati, Mauricio Reyes, Ji Eun Park, Jihye Yun, Ho Sung Kim, Abhishek Mahajan, Mark Muzi, Sean Benson, Regina G. H. Beets-Tan, Jonas Teuwen, Alejandro Herrera-Trujillo, Maria Trujillo, William Escobar, Ana Abello, Jose Bernal, Jhon Gómez, Joseph Choi, Stephen Baek, Yusung Kim, Heba Ismael, Bryan Allen, John M. Buatti, Aikaterini Kotrotsou, Hongwei Li, Tobias Weiss, Michael Weller, Andrea Bink, Bertrand Pouymayou, Hassan F. Shaykh, Joel Saltz, Prateek Prasanna, Sampurna Shrestha, Kartik M. Mani, David Payne, Tahsin Kurc, Enrique Pelaez, Heydy Franco-Maldonado, Francis Loayza, Sebastian Quevedo, Pamela Guevara, Esteban Torche, Cristobal Mendoza, Franco Vera, Elvis Ríos, Eduardo López, Sergio A. Velastin, Godwin Ogbole, Mayowa Soneye, Dotun Oyekunle, Olubunmi Odafe-Oyibotha, Babatunde Osobu, Mustapha Shu’aibu, Adeleye Dorcas, Farouk Dako, Amber L. Simpson, Mohammad Hamghalam, Jacob J. Peoples, Ricky Hu, Anh Tran, Danielle Cutler, Fabio Y. Moraes, Michael A. Boss, James Gimpel, Deepak Kattil Veettil, Kendall Schmidt, Brian Bialecki, Sailaja Marella, Cynthia Price, Lisa Cimino, Charles Apgar, Prashant Shah, Bjoern Menze, Jill S. Barnholtz-Sloan, Jason Martin, and Spyridon Bakas

Subjects
Science
Published
2023
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6. Choice feeding in fattening pigs: Effect of diets differing in nutrient density on feeding behaviour and fattening performance

Author

Josef Pichler, Christiane Schwarz, Martin Gierus, and Karl Schedle

Subjects
dietary fibre, energy demand, nutrient self-supply, Animal culture, SF1-1100
Abstract

The aim of this study was to determine the proportion of feed consumed by pigs when they had the choice to meet their nutrient requirements offering a low (LND) or a high (HND) nutrient dense diet on animal performance and feeding behaviour. In total 120 barrows and gilts were allotted to three dietary treatments (LND, HND and a feed choice group, FC). Diets were calculated to keep a constant ratio of megajoule net energy (MJ NE) to nutrient standardised ileal digestible (SID) lysine, SID methionine and cysteine, SID threonine, SID tryptophan, Ca, available P and Na. Pigs of the feed choice treatment that could choose between LND and HND chose an energy content between 13.3 and 13.6 MJ ME or rather 10.1 and 10.4 MJ NE. The ratio between LND and HND changed during the growing period to a higher percentage of HND (26.2% : 73.8% in the starter, 22.0% : 78.0% in the grower and 20.0% : 80.0% in the finisher phase). No differences between barrows and gilts were detected regarding the selected diet. As a result, similar zootechnical performance data were observed for HND and FC, whereas LND led to a declined (P < 0.05) performance. Regarding the feeding behaviour no differences in the parameters meal size and daily feeder visits between LND and HND (P > 0.1) were observed. However, within the FC treatment more and greater meals were consumed (P < 0.05) at the HND feeder compared to the LND feeder. Pigs of modern genetics still have the ability to cover their nutrient requirements choosing between diets differing in nutrient density without impairing performance. Furthermore, the results give no indication for the necessity of different energy levels in diets for sexed pigs.

Published
2020
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7. MRI Response Assessment in Glioblastoma Patients Treated with Dendritic-Cell-Based Immunotherapy

Author

Johanna Heugenhauser, Malik Galijasevic, Stephanie Mangesius, Georg Goebel, Johanna Buchroithner, Friedrich Erhart, Josef Pichler, Georg Widhalm, Günther Stockhammer, Sarah Iglseder, Christian F. Freyschlag, Stefan Oberndorfer, Karin Bordihn, Gord von Campe, Thomas Czech, Birgit Surböck, Tadeja Urbanic Purkart, Christine Marosi, Thomas Felzmann, and Martha Nowosielski

Subjects
radiologic response criteria, immunotherapy, glioblastoma, iRANO, mRANO, volumetric measurements, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Introduction: In this post hoc analysis we compared various response-assessment criteria in newly diagnosed glioblastoma (GB) patients treated with tumor lysate-charged autologous dendritic cells (Audencel) and determined the differences in prediction of progression-free survival (PFS) and overall survival (OS). Methods: 76 patients enrolled in a multicenter phase II trial receiving standard of care (SOC, n = 40) or SOC + Audencel vaccine (n = 36) were included. MRI scans were evaluated using MacDonald, RANO, Vol-RANO, mRANO, Vol-mRANO and iRANO criteria. Tumor volumes (T1 contrast-enhancing as well as T2/FLAIR volumes) were calculated by semiautomatic segmentation. The Kruskal-Wallis-test was used to detect differences in PFS among the assessment criteria; for correlation analysis the Spearman test was used. Results: There was a significant difference in median PFS between mRANO (8.6 months) and Vol-mRANO (8.6 months) compared to MacDonald (4.0 months), RANO (4.2 months) and Vol-RANO (5.4 months). For the vaccination arm, median PFS by iRANO was 6.2 months. There was no difference in PFS between SOC and SOC + Audencel. The best correlation between PFS/OS was detected for mRANO (r = 0.65) and Vol-mRANO (r = 0.69, each p < 0.001). A total of 16/76 patients developed a pure T2/FLAIR progressing disease, and 4/36 patients treated with Audencel developed pseudoprogression. Conclusion: When comparing different response-assessment criteria in GB patients treated with dendritic cell-based immunotherapy, the best correlation between PFS and OS was observed for mRANO and Vol-mRANO. Interestingly, iRANO was not superior for predicting OS in patients treated with Audencel.

Published
2022
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8. Rezension

Author

Josef Pichler

Subjects
The Bible, BS1-2970
Abstract

Mira Stare, Durch ihn leben. Die Lebensthematik in Joh 6 (NTA 49), Münster: Aschendorff Verlag 2004. VIII, 366 S. ISBN 3-402-04797-7

Published
2016

9. Audencel Immunotherapy Based on Dendritic Cells Has No Effect on Overall and Progression-Free Survival in Newly Diagnosed Glioblastoma: A Phase II Randomized Trial

Author

Johanna Buchroithner, Friedrich Erhart, Josef Pichler, Georg Widhalm, Matthias Preusser, Günther Stockhammer, Martha Nowosielski, Sarah Iglseder, Christian F. Freyschlag, Stefan Oberndorfer, Karin Bordihn, Gord von Campe, Markus Hoffermann, Reinhard Ruckser, Karl Rössler, Sabine Spiegl-Kreinecker, Michael B. Fischer, Thomas Czech, Carmen Visus, Günther Krumpl, Thomas Felzmann, and Christine Marosi

Subjects
glioblastoma, active immunotherapy, dendritic cells, tumor vaccine, phase II, randomized, clinical trial, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Dendritic cells (DCs) are antigen-presenting cells that are capable of priming anti-tumor immune responses, thus serving as attractive tools to generate tumor vaccines. In this multicentric randomized open-label phase II study, we investigated the efficacy of vaccination with tumor lysate-charged autologous DCs (Audencel) in newly diagnosed glioblastoma multiforme (GBM). Patients aged 18 to 70 years with histologically proven primary GBM and resection of at least 70% were randomized 1:1 to standard of care (SOC) or SOC plus vaccination (weekly intranodal application in weeks seven to 10, followed by monthly intervals). The primary endpoint was progression-free survival at 12 months. Secondary endpoints were overall survival, safety, and toxicity. Seventy-six adult patients were analyzed in this study. Vaccinations were given for seven (3–20) months on average. No severe toxicity was attributable to vaccination. Seven patients showed flu-like symptoms, and six patients developed local skin reactions. Progression-free survival at 12 months did not differ significantly between the control and vaccine groups (28.4% versus 24.5%, p = 0.9975). Median overall survival was similar with 18.3 months (vaccine: 564 days, 95% CI: 436–671 versus control: 568 days, 95% CI: 349–680; p = 0.89, harzard ratio (HR) 0.99). Hence, in this trial, the clinical outcomes of patients with primary GBM could not be improved by the addition of Audencel to SOC.

Published
2018
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34. Early Postoperative Treatment versus Initial Observation in CNS WHO Grade 2 and 3 Oligodendroglioma: Clinical Outcomes and DNA Methylation Patterns

Author

Maximilian J. Mair, Annette Leibetseder, Gerwin Heller, Rainer Puhr, Erwin Tomasich, Sebastian Goldberger, Teresa Hatziioannou, Adelheid Wöhrer, Georg Widhalm, Karin Dieckmann, Martin Aichholzer, Serge Weis, Tim von Oertzen, Julia Furtner, Josef Pichler, Matthias Preusser, and Anna S. Berghoff

Subjects
Adult, Cancer Research, Brain Neoplasms, Oligodendroglioma, Methyltransferases, DNA Methylation, World Health Organization, Isocitrate Dehydrogenase, Oncology, Lomustine, Vincristine, Procarbazine, Temozolomide, Humans, Prospective Studies, Retrospective Studies
Abstract

Purpose: The treatment of oligodendroglioma consists of tumor resection and radiochemotherapy. The timing of radiochemotherapy remains unclear, and predictive biomarkers are limited. Experimental Design: Adult patients diagnosed with isocitrate dehydrogenase (IDH)-mutated, 1p/19q-codeleted CNS WHO grade 2 and 3 oligodendroglioma at the Medical University of Vienna and the Kepler University Hospital Linz (Austria) in 1992 to 2019 were included. Progression-free (PFS) and overall survival (OS) between early postoperative treatment and initial observation were compared using propensity score–weighted Cox regression models. DNA methylation analysis of tumor tissue was performed using Illumina MethylationEPIC 850k microarrays. Results: One hundred thirty-one out of 201 (65.2%) patients with CNS WHO grade 2 and 70 of 201 (34.8%) with grade 3 oligodendroglioma were identified. Eighty-three of 201 (41.3%) patients underwent early postoperative treatment, of whom 56 of 83 (67.5%) received radiochemotherapy, 15 of 84 (18.1%) radiotherapy (RT) only and 12 of 83 (14.5%) chemotherapy only. Temozolomide-based treatment was administered to 64 of 68 (94.1%) patients, whereas RT + procarbazine, lomustine (CCNU), and vincristine (PCV) were applied in 2 of 69 (3.5%) patients. Early treatment was not associated with PFS [adjusted hazard ratio (HR) 0.74; 95% CI, 0.33–1.65, P = 0.459] or OS (adjusted HR: 2.07; 95% CI, 0.52–8.21, P = 0.302) improvement. Unsupervised clustering analysis of DNA methylation profiles from patients receiving early treatment revealed two methylation clusters correlating with PFS, whereas no association of clustering with O6-methylguanine methyltransferase (MGMT) promoter methylation, CNS WHO grade, extent of resection, and treating center could be observed. Conclusions: In this retrospective study, early postoperative treatment was not associated with improved PFS/OS in oligodendroglioma. The potentially predictive value of whole-genome methylation profiling should be validated in prospective trials.

Published
2022

38. Data from Early Postoperative Treatment versus Initial Observation in CNS WHO Grade 2 and 3 Oligodendroglioma: Clinical Outcomes and DNA Methylation Patterns

Author

Anna S. Berghoff, Matthias Preusser, Josef Pichler, Julia Furtner, Tim von Oertzen, Serge Weis, Martin Aichholzer, Karin Dieckmann, Georg Widhalm, Adelheid Wöhrer, Teresa Hatziioannou, Sebastian Goldberger, Erwin Tomasich, Rainer Puhr, Gerwin Heller, Annette Leibetseder, and Maximilian J. Mair

Abstract

Purpose:The treatment of oligodendroglioma consists of tumor resection and radiochemotherapy. The timing of radiochemotherapy remains unclear, and predictive biomarkers are limited.Experimental Design:Adult patients diagnosed with isocitrate dehydrogenase (IDH)-mutated, 1p/19q-codeleted CNS WHO grade 2 and 3 oligodendroglioma at the Medical University of Vienna and the Kepler University Hospital Linz (Austria) in 1992 to 2019 were included. Progression-free (PFS) and overall survival (OS) between early postoperative treatment and initial observation were compared using propensity score–weighted Cox regression models. DNA methylation analysis of tumor tissue was performed using Illumina MethylationEPIC 850k microarrays.Results:One hundred thirty-one out of 201 (65.2%) patients with CNS WHO grade 2 and 70 of 201 (34.8%) with grade 3 oligodendroglioma were identified. Eighty-three of 201 (41.3%) patients underwent early postoperative treatment, of whom 56 of 83 (67.5%) received radiochemotherapy, 15 of 84 (18.1%) radiotherapy (RT) only and 12 of 83 (14.5%) chemotherapy only. Temozolomide-based treatment was administered to 64 of 68 (94.1%) patients, whereas RT + procarbazine, lomustine (CCNU), and vincristine (PCV) were applied in 2 of 69 (3.5%) patients. Early treatment was not associated with PFS [adjusted hazard ratio (HR) 0.74; 95% CI, 0.33–1.65, P = 0.459] or OS (adjusted HR: 2.07; 95% CI, 0.52–8.21, P = 0.302) improvement. Unsupervised clustering analysis of DNA methylation profiles from patients receiving early treatment revealed two methylation clusters correlating with PFS, whereas no association of clustering with O6-methylguanine methyltransferase (MGMT) promoter methylation, CNS WHO grade, extent of resection, and treating center could be observed.Conclusions:In this retrospective study, early postoperative treatment was not associated with improved PFS/OS in oligodendroglioma. The potentially predictive value of whole-genome methylation profiling should be validated in prospective trials.

Published
2023

39. Data from MGMT Promoter Methylation Is a Strong Prognostic Biomarker for Benefit from Dose-Intensified Temozolomide Rechallenge in Progressive Glioblastoma: The DIRECTOR Trial

Author

Wolfgang Wick, Guido Reifenberger, Johannes Hüsing, Spyros Kollias, Peter Vajkoczy, Jürgen Meixensberger, Guido Nikkhah, Josef Pichler, Krisztian Homicsko, Roger Stupp, Roland Goldbrunner, Christine Marosi, Uwe Schlegel, Jörg C. Tonn, Michael Platten, Oliver Bähr, Ralf Ketter, Hans-Georg Wirsching, Michael C. Sabel, Ulrich Herrlinger, Peter Hau, Oliver Schnell, Antje Wick, Joachim P. Steinbach, Jörg Felsberg, Bärbel Kästner, Ghazaleh Tabatabai, and Michael Weller

Abstract

Purpose: Rechallenge with temozolomide (TMZ) at first progression of glioblastoma after temozolomide chemoradiotherapy (TMZ/RT→TMZ) has been studied in retrospective and single-arm prospective studies, applying temozolomide continuously or using 7/14 or 21/28 days schedules. The DIRECTOR trial sought to show superiority of the 7/14 regimen.Experimental Design: Patients with glioblastoma at first progression after TMZ/RT→TMZ and at least two maintenance temozolomide cycles were randomized to Arm A [one week on (120 mg/m2 per day)/one week off] or Arm B [3 weeks on (80 mg/m2 per day)/one week off]. The primary endpoint was median time-to-treatment failure (TTF) defined as progression, premature temozolomide discontinuation for toxicity, or death from any cause. O6-methylguanine DNA methyltransferase (MGMT) promoter methylation was prospectively assessed by methylation-specific PCR.Results: Because of withdrawal of support, the trial was prematurely closed to accrual after 105 patients. There was a similar outcome in both arms for median TTF [A: 1.8 months; 95% confidence intervals (CI), 1.8–3.2 vs. B: 2.0 months; 95% CI, 1.8–3.5] and overall survival [A: 9.8 months (95% CI, 6.7–13.0) vs. B: 10.6 months (95% CI, 8.1–11.6)]. Median TTF in patients with MGMT-methylated tumors was 3.2 months (95% CI, 1.8–7.4) versus 1.8 months (95% CI, 1.8–2) in MGMT-unmethylated glioblastoma. Progression-free survival rates at 6 months (PFS-6) were 39.7% with versus 6.9% without MGMT promoter methylation.Conclusions: Temozolomide rechallenge is a treatment option for MGMT promoter-methylated recurrent glioblastoma. Alternative strategies need to be considered for patients with progressive glioblastoma without MGMT promoter methylation. Clin Cancer Res; 21(9); 2057–64. ©2015 AACR.

Published
2023

40. Data from A Phase II, Randomized, Study of Weekly APG101+Reirradiation versus Reirradiation in Progressive Glioblastoma

Author

Stephanie E. Combs, Martin Bendszus, Michael Platten, Claudia Kunz, Christian Hartmann, Jürgen Debus, Inga Harting, Elena Vetlova, Josef Pichler, Andreas von Deimling, Maximilian G. Schliesser, Benedikt Wiestler, Oliver Heese, Tobias Martens, Grigory Kobyakov, Klaus Junge, Harald Fricke, and Wolfgang Wick

Abstract

Purpose: Preclinical data indicate anti-invasive activity of APG101, a CD95 ligand (CD95L)–binding fusion protein, in glioblastoma.Experimental Design: Patients (N = 91) with glioblastoma at first or second progression were randomized 1:2 between second radiotherapy (rRT; 36 Gy; five times 2 Gy per week) or rRT+APG101 (400 mg weekly i.v.). Patient characteristics [N = 84 (26 patients rRT, 58 patients rRT+APG101)] were balanced.Results: Progression-free survival at 6 months (PFS-6) rates were 3.8% [95% confidence interval (CI), 0.1–19.6] for rRT and 20.7% (95% CI, 11.2–33.4) for rRT+APG101 (P = 0.048). Median PFS was 2.5 (95% CI, 2.3–3.8) months and 4.5 (95% CI, 3.7–5.4) months with a hazard ratio (HR) of 0.49 (95% CI, 0.27–0.88; P = 0.0162) adjusted for tumor size. Cox regression analysis adjusted for tumor size revealed a HR of 0.60 (95% CI, 0.36–1.01; P = 0.0559) for rRT+APG101 for death of any cause. Lower methylation levels at CpG2 in the CD95L promoter in the tumor conferred a stronger risk reduction (HR, 0.19; 95% CI, 0.06–0.58) for treatment with APG101, suggesting a potential biomarker.Conclusions: CD95 pathway inhibition in combination with rRT is an innovative concept with clinical efficacy. It warrants further clinical development. CD95L promoter methylation in the tumor may be developed as a biomarker. Clin Cancer Res; 20(24); 6304–13. ©2014 AACR.

Published
2023

41. Supplementary Figure 1 from MGMT Promoter Methylation Is a Strong Prognostic Biomarker for Benefit from Dose-Intensified Temozolomide Rechallenge in Progressive Glioblastoma: The DIRECTOR Trial

Author

Wolfgang Wick, Guido Reifenberger, Johannes Hüsing, Spyros Kollias, Peter Vajkoczy, Jürgen Meixensberger, Guido Nikkhah, Josef Pichler, Krisztian Homicsko, Roger Stupp, Roland Goldbrunner, Christine Marosi, Uwe Schlegel, Jörg C. Tonn, Michael Platten, Oliver Bähr, Ralf Ketter, Hans-Georg Wirsching, Michael C. Sabel, Ulrich Herrlinger, Peter Hau, Oliver Schnell, Antje Wick, Joachim P. Steinbach, Jörg Felsberg, Bärbel Kästner, Ghazaleh Tabatabai, and Michael Weller

Abstract

Supplementary Figure 1. MMSE assessment at study entry, during treatment, and at follow-up

Published
2023

42. Acknowledgement from A Phase II, Randomized, Study of Weekly APG101+Reirradiation versus Reirradiation in Progressive Glioblastoma

Author

Stephanie E. Combs, Martin Bendszus, Michael Platten, Claudia Kunz, Christian Hartmann, Jürgen Debus, Inga Harting, Elena Vetlova, Josef Pichler, Andreas von Deimling, Maximilian G. Schliesser, Benedikt Wiestler, Oliver Heese, Tobias Martens, Grigory Kobyakov, Klaus Junge, Harald Fricke, and Wolfgang Wick

Abstract

Acknowledgement. List of investigators and other study stuff at the individual sites.

Published
2023

44. Suppl Figures from A Phase II, Randomized, Study of Weekly APG101+Reirradiation versus Reirradiation in Progressive Glioblastoma

Author

Stephanie E. Combs, Martin Bendszus, Michael Platten, Claudia Kunz, Christian Hartmann, Jürgen Debus, Inga Harting, Elena Vetlova, Josef Pichler, Andreas von Deimling, Maximilian G. Schliesser, Benedikt Wiestler, Oliver Heese, Tobias Martens, Grigory Kobyakov, Klaus Junge, Harald Fricke, and Wolfgang Wick

Abstract

Suppl Figures S1-S4. S1: Genomic Localization of the CpG2 in the CD95 L promoter. S2: Survival probability according to CpG2 methylation status. S3: Survival probability according to CD95L expression as detected by IHC. S4 a and b: Cox regression data for CpG1 and 2 in the CD95L promoter.

Published
2023

45. Supplementary Tables 1-7 from MGMT Promoter Methylation Is a Strong Prognostic Biomarker for Benefit from Dose-Intensified Temozolomide Rechallenge in Progressive Glioblastoma: The DIRECTOR Trial

Author

Wolfgang Wick, Guido Reifenberger, Johannes Hüsing, Spyros Kollias, Peter Vajkoczy, Jürgen Meixensberger, Guido Nikkhah, Josef Pichler, Krisztian Homicsko, Roger Stupp, Roland Goldbrunner, Christine Marosi, Uwe Schlegel, Jörg C. Tonn, Michael Platten, Oliver Bähr, Ralf Ketter, Hans-Georg Wirsching, Michael C. Sabel, Ulrich Herrlinger, Peter Hau, Oliver Schnell, Antje Wick, Joachim P. Steinbach, Jörg Felsberg, Bärbel Kästner, Ghazaleh Tabatabai, and Michael Weller

Abstract

Supplementary Tables 1-7. Supplementary Table 1. Safety and tolerability. Supplementary Table 2. Outcome by MGMT promoter methylation status and treatment arm. Supplementary Table 3. Outcome by interval from last TMZ administration and MGMT promoter methylation status. Supplementary Table 4. Adherence to Mini Mental Status data collection over the course of the study. Supplementary Table 5. Treatment effect (Arm B versus Arm A) on EORTC-QLQ-C30 and -BN20 scales evaluated at timepoint 90 days Supplementary Table 6. Absolute changes of (0-100) score points of quality of life (as assessed by the EORTC-QLQ-C30 and -BN20 scales) within one treatment cycle of 28 days in Arms A and B, along with local p-values for difference in slopes. Supplementary Table 7. Adherence to EORTC-QLQ-BN20 and -C30 data collection over the course of the study.

Published
2023

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