Radiomic features define risk and are linked to DNA methylation attributes in primary CNS lymphoma

被引：6

作者：

Nenning, Karl-Heinz ^{[1
,2
]}

Gesperger, Johanna ^{[3
,4
]}

Furtner, Julia ^{[5
,6
]}

Nemc, Amelie ^{[7
]}

Roetzer-Pejrimovsky, Thomas ^{[3
,4
]}

Choi, Seung-Won ^{[8
]}

Mitter, Christian ^{[5
]}

Leber, Stefan L. ^{[9
]}

Hofmanninger, Johannes ^{[1
,16
,17
]}

Klughammer, Johanna ^{[7
,10
]}

Erguener, Bekir ^{[7
]}

Bauer, Marlies ^{[11
]}

Brada, Martina ^{[13
]}

Chong, Kyuha ^{[8
]}

Brandner-Kokalj, Tanisa ^{[14
]}

Freyschlag, Christian F. ^{[11
]}

Grams, Astrid ^{[15
]}

Haybaeck, Johannes

Hoenigschnabl, Selma ^{[18
]}

Hoffermann, Markus ^{[19
]}

Iglseder, Sarah ^{[20
]}

Kiesel, Barbara ^{[21
]}

Kitzwoegerer, Melitta ^{[22
]}

Kleindienst, Waltraud ^{[23
]}

Marhold, Franz ^{[24
]}

Moser, Patrizia ^{[11
,12
]}

Oberndorfer, Stefan ^{[25
]}

Pinggera, Daniel ^{[11
]}

Scheichel, Florian ^{[24
]}

Sherif, Camillo ^{[24
]}

Stockhammer, Guenther ^{[20
]}

Stultschnig, Martin ^{[26
]}

Thome, Claudius ^{[11
]}

Trenkler, Johannes ^{[27
]}

Urbanic-Purkart, Tadeja ^{[28
,29
]}

Weis, Serge ^{[30
]}

Widhalm, Georg ^{[21
]}

Wuertz, Franz ^{[14
]}

Preusser, Matthias ^{[31
]}

Baumann, Bernhard ^{[32
]}

Simonitsch-Klupp, Ingrid ^{[33
]}

Nam, Do-Hyun ^{[8
]}

Bock, Christoph ^{[7
,34
]}

Langs, Georg ^{[1
,35
]}

Woehrer, Adelheid ^{[3
,4
]}

机构：

[1] Med Univ Vienna, Dept Biomed Imaging & Image Guided Therapy, Computat Imaging Res Lab, Vienna, Austria

[2] Nathan S Kline Inst Psychiat Res, Ctr Biomed Imaging & Neuromodulat, Orangeburg, NY USA

[3] Med Univ Vienna, Dept Neurol, Div Neuropathol & Neurochem, Spitalgasse 23, A-1090 Vienna, Austria

[4] Med Univ Vienna, Comprehens Ctr Clin Neurosci & Mental Hlth, Vienna, Austria

[5] Med Univ Vienna, Dept Biomed Imaging & Image Guided Therapy, Div Neuroradiol, Vienna, Austria

[6] Danube Private Univ, Fac Med & Dent, Res Ctr Med Image Anal & Artificial Intelligence, Krems, Austria

[7] Austrian Acad Sci, CeMM Res Ctr Mol Med, Vienna, Austria

[8] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Neurosurg, Seoul, South Korea

[9] Med Univ Graz, Dept Radiol, Div Neuroradiol Vasc & Intervent Radiol, Graz, Austria

[10] Ludwig Maximilians Univ Munchen, Gene Ctr, Dept Biochem, Munich, Germany

[11] Med Univ Innsbruck, Dept Neurosurg, Innsbruck, Austria

[12] Tirolkliniken, Dept Pathol, Innpath, Innsbruck, Austria

[13] Klin Landstr, Dept Pathol, Vienna, Austria

[14] State Hosp Klagenfurt, Inst Pathol, Klagenfurt, Austria

[15] Med Univ Innsbruck, Dept Neuroradiol, Innsbruck, Austria

[16] Med Univ Innsbruck, Inst Pathol Neuropathol & Mol Pathol, Innsbruck, Austria

[17] Med Univ Graz, Inst Pathol, Ctr Mol Biomed, Graz, Austria

[18] Donauspital Vienna, Dept Pathol, Vienna, Austria

[19] State Hosp Feldkirch, Dept Neurosurg, Feldkirch, Austria

[20] Med Univ Innsbruck, Dept Neurol, Innsbruck, Austria

[21] Med Univ Vienna, Dept Neurosurg, Vienna, Austria

[22] Karl Landsteiner Univ Hlth Sci, Dept Pathol, Univ Hosp St Poelten, St Polten, Austria

[23] Paracelsus Med Univ Salzburg, Dept Neurol, Salzburg, Austria

[24] Karl Landsteiner Univ Hlth Sci, Dept Neurosurg, Univ Hosp St Poelten, St Polten, Austria

[25] Karl Landsteiner Univ Hlth Sci, Dept Neurol, Univ Hosp St Poelten, St Polten, Austria

[26] State Hosp Klagenfurt, Dept Neurol, Klagenfurt, Austria

[27] Johannes Kepler Univ Linz, Kepler Univ Hosp, Inst Neuroradiol, Neuromed Campus, Linz, Austria

[28] Med Univ Graz, Dept Neurol, Graz, Austria

[29] Med Univ Graz, Div Neuroradiol Vasc & Intervent Radiol, Graz, Austria

[30] Johannes Kepler Univ Linz, Kepler Univ Hosp, Div Neuropathol, Linz, Austria

[31] Med Univ Vienna, Dept Internal Med 1, Div Oncol, Vienna, Austria

[32] Med Univ Vienna, Ctr Med Phys & Biomed Engn, Vienna, Austria

[33] Med Univ Vienna, Dept Pathol, Vienna, Austria

[34] Med Univ Vienna, Inst Artificial Intelligence, Ctr Med Data Sci, Vienna, Austria

[35] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA USA

来源：

NEURO-ONCOLOGY ADVANCES | 2023年 / 5卷 / 01期

基金：

奥地利科学基金会;

关键词：

DNA methylation; primary CNS lymphoma; radiomics; risk score; survival; CENTRAL-NERVOUS-SYSTEM; B-CELL LYMPHOMA;

D O I：

10.1093/noajnl/vdad136

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background. The prognostic roles of clinical and laboratory markers have been exploited to model risk in patients with primary CNS lymphoma, but these approaches do not fully explain the observed variation in outcome. To date, neuroimaging or molecular information is not used. The aim of this study was to determine the utility of radiomic features to capture clinically relevant phenotypes, and to link those to molecular profiles for enhanced risk stratification. Methods. In this retrospective study, we investigated 133 patients across 9 sites in Austria (2005-2018) and an external validation site in South Korea (44 patients, 2013-2016). We used T1-weighted contrast-enhanced MRI and an L1-norm regularized Cox proportional hazard model to derive a radiomic risk score. We integrated radiomic features with DNA methylation profiles using machine learning-based prediction, and validated the most relevant biological associations in tissues and cell lines. Results. The radiomic risk score, consisting of 20 mostly textural features, was a strong and independent predictor of survival (multivariate hazard ratio = 6.56 [3.64-11.81]) that remained valid in the external validation cohort. Radiomic features captured gene regulatory differences such as in BCL6 binding activity, which was put forth as testable treatment target for a subset of patients. Conclusions. The radiomic risk score was a robust and complementary predictor of survival and reflected characteristics in underlying DNA methylation patterns. Leveraging imaging phenotypes to assess risk and inform epigenetic treatment targets provides a concept on which to advance prognostic modeling and precision therapy for this aggressive cancer.

引用

页数：12

共 46 条

[31] Increasing use of immunotherapy and prolonged survival among younger patients with primary CNS lymphoma: a population-based study [J].

Neuhauser, Magdalena ;

Roetzer, Thomas ;

Oberndorfer, Stefan ;

Kitzwoegerer, Melitta ;

Payer, Franz ;

Unterluggauer, Julia J. ;

Haybaeck, Johannes ;

Stockhammer, Guenther ;

Iglseder, Sarah ;

Moser, Patrizia ;

Thome, Claudius ;

Stultschnig, Martin ;

Wuertz, Franz ;

Brandner-Kokalj, Tanisa ;

Weis, Serge ;

Bandke, Dave ;

Pichler, Josef ;

Hutterer, Markus ;

Krenosz, Karl J. ;

Boehm, Alexandra ;

Mayrbaeurl, Beate ;

Hager-Seifert, Andrea ;

Kaufmann, Hannes ;

Dumser, Martina ;

Reiner-Concin, Angelika ;

Hoenigschnabl, Selma ;

Kleindienst, Waltraud ;

Hoffermann, Markus ;

Dieckmann, Karin ;

Kiesel, Barbara ;

Widhalm, Georg ;

Marosi, Christine ;

Jaeger, Ulrich ;

Hainfellner, Andreas ;

Hackl, Monika ;

Hainfellner, Johannes A. ;

Preusser, Matthias ;

Woehrer, Adelheid .

ACTA ONCOLOGICA, 2019, 58 (07) :967-976

[32] Discovery of Candidate DNA Methylation Cancer Driver Genes [J].

Pan, Heng ;

Renaud, Loic ;

Chaligne, Ronan ;

Bloehdorn, Johannes ;

Tausch, Eugen ;

Mertens, Daniel ;

Fink, Anna Maria ;

Fischer, Kirsten ;

Zhang, Chao ;

Betel, Doron ;

Gnirkell, Andreas ;

Imielinski, Marcin ;

Moreaux, Jerome ;

Hallek, Michael ;

Meissner, Alexander ;

Stilgenbauer, Stephan ;

Wu, Catherine J. ;

Elemento, Olivier ;

Landau, Dan A. .

CANCER DISCOVERY, 2021, 11 (09) :2266-2281

[33] Epigenomic evolution in diffuse large B-cell lymphomas [J].

Pan, Heng ;

Jiang, Yanwen ;

Boi, Michela ;

Tabbo, Fabrizio ;

Redmond, David ;

Nie, Kui ;

Ladetto, Marco ;

Chiappella, Annalisa ;

Cerchietti, Leandro ;

Shaknovich, Rita ;

Melnick, Ari M. ;

Inghirami, Giorgio G. ;

Tam, Wayne ;

Elemento, Olivier .

NATURE COMMUNICATIONS, 2015, 6

[34] Glioblastoma and primary central nervous system lymphoma: differentiation using MRI derived first-order texture analysis - a machine learning study [J].

Priya, Sarv ;

Ward, Caitlin ;

Locke, Thomas ;

Soni, Neetu ;

Maheshwarappa, Ravishankar Pillenahalli ;

Monga, Varun ;

Agarwal, Amit ;

Bathla, Girish .

NEURORADIOLOGY JOURNAL, 2021, 34 (04) :320-328

[35]

Radke J., 2022, NAT COMMUN, V13, P1

[36] Array-based DNA methylation profiling of primary lymphomas of the central nervous system [J].

Richter, Julia ;

Ammerpohl, Ole ;

Martin-Subero, Jose I. ;

Montesinos-Rongen, Manuel ;

Bibikova, Marina ;

Wickham-Garcia, Eliza ;

Wiestler, Otmar D. ;

Deckert, Martina ;

Siebert, Reiner .

BMC CANCER, 2009, 9

[37] Sex-Specific Differences in Primary CNS Lymphoma [J].

Roetzer, Thomas ;

Furtner, Julia ;

Gesperger, Johanna ;

Seebrecht, Lukas ;

Bandke, Dave ;

Brada, Martina ;

Brandner-Kokalj, Tanisa ;

Grams, Astrid ;

Haybaeck, Johannes ;

Kitzwoegerer, Melitta ;

Leber, Stefan L. ;

Marhold, Franz ;

Moser, Patrizia ;

Sherif, Camillo ;

Trenkler, Johannes ;

Unterluggauer, Julia ;

Weis, Serge ;

Wuertz, Franz ;

Hainfellner, Johannes A. ;

Langs, Georg ;

Nenning, Karl-Heinz ;

Woehrer, Adelheid .

CANCERS, 2020, 12 (06) :1-15

[38] Genetics and Pathogenesis of Diffuse Large B-Cell Lymphoma [J].

Schmitz, R. ;

Wright, G. W. ;

Huang, D. W. ;

Johnson, C. A. ;

Phelan, J. D. ;

Wang, J. Q. ;

Roulland, S. ;

Kasbekar, M. ;

Young, R. M. ;

Shaffer, A. L. ;

Hodson, D. J. ;

Xiao, W. ;

Yu, X. ;

Yang, Y. ;

Zhao, H. ;

Xu, W. ;

Liu, X. ;

Zhou, B. ;

Du, W. ;

Chan, W. C. ;

Jaffe, E. S. ;

Gascoyne, R. D. ;

Connors, J. M. ;

Campo, E. ;

Lopez-Guillermo, A. ;

Rosenwald, A. ;

Ott, G. ;

Delabie, J. ;

Rimsza, L. M. ;

Wei, K. Tay Kuang ;

Zelenetz, A. D. ;

Leonard, J. P. ;

Bartlett, N. L. ;

Tran, B. ;

Shetty, J. ;

Zhao, Y. ;

Soppet, D. R. ;

Pittaluga, S. ;

Wilson, W. H. ;

Staudt, L. M. .

NEW ENGLAND JOURNAL OF MEDICINE, 2018, 378 (15) :1396-1407

[39] DNA methylation signatures define molecular subtypes of diffuse large B-cell lymphoma [J].

Shaknovich, Rita ;

Geng, Huimin ;

Johnson, Nathalie A. ;

Tsikitas, Lucas ;

Cerchietti, Leandro ;

Greally, John M. ;

Gascoyne, Randy D. ;

Elemento, Olivier ;

Melnick, Ari .

BLOOD, 2010, 116 (20) :E81-E89

[40] LOLA: enrichment analysis for genomic region sets and regulatory elements in R and Bioconductor [J].

Sheffield, Nathan C. ;

Bock, Christoph .

BIOINFORMATICS, 2016, 32 (04) :587-589

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