Nonmetastatic medulloblastoma of early childhood : results from the prospective clinical trial HIT-2000 and an extended validation cohort
PURPOSEThe HIT-2000-BIS4 trial aimed to avoid highly detrimental craniospinal irradiation (CSI) in children < 4 years of age with nonmetastatic medulloblastoma by systemic chemotherapy, intraventricular methotrexate, and risk-adapted local radiotherapy.PATIENTS AND METHODSFrom 2001-2011, 87 patie...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Mynarek, Martin - 1980- [verfasserIn] Hoff, Katja von [verfasserIn] Pietsch, Torsten [verfasserIn] Ottensmeier, Holger [verfasserIn] Warmuth-Metz, Monika [verfasserIn] Bison, Brigitte - 1964- [verfasserIn] Pfister, Stefan - 1974- [verfasserIn] Korshunov, Andrey [verfasserIn] Sharma, Tanvi - 1993- [verfasserIn] Jäger, Natalie [verfasserIn] Ryzhova, Marina [verfasserIn] Zheludkova, Olga [verfasserIn] Golanov, Andrey [verfasserIn] Rushing, Elisabeth Jane [verfasserIn] Hasselblatt, Martin - 1969- [verfasserIn] Koch, Arend Wolfgang - 1972- [verfasserIn] Schüller, Ulrich - 1976- [verfasserIn] Deimling, Andreas von - 1959- [verfasserIn] Sahm, Felix - 1984- [verfasserIn] Sill, Martin - 1982- [verfasserIn] Riemenschneider, Markus Johannes - 1974- [verfasserIn] Dohmen, Hildegard [verfasserIn] Monoranu, Camelia Maria - 1966- [verfasserIn] Sommer, Clemens - 1964- [verfasserIn] Staszewski, Ori - 1979- [verfasserIn] Mawrin, Christian - 1972- [verfasserIn] Schittenhelm, Jens Florian - 1975- [verfasserIn] Brück, Wolfgang [verfasserIn] Filipski, Katharina Johanna [verfasserIn] Hartmann, Christian [verfasserIn] Meinhardt, Matthias [verfasserIn] Pietschmann, Klaus [verfasserIn] Haberler, Christine [verfasserIn] Slavc, Irene [verfasserIn] Gerber, Nicolas U. [verfasserIn] Grotzer, Michael - 1964- [verfasserIn] Benesch, Martin [verfasserIn] Schlegel, Paul-Gerhardt - 1958- [verfasserIn] Deinlein, Frank - 1964- [verfasserIn] Bueren, André von [verfasserIn] Friedrich, Carsten - 1978- [verfasserIn] Juhnke, Björn-Ole [verfasserIn] Obrecht, Denise [verfasserIn] Fleischhack, Gudrun [verfasserIn] Kwiecien, Robert [verfasserIn] Faldum, Andreas - 1961- [verfasserIn] Kortmann, Rolf-Dieter [verfasserIn] Kool, Marcel [verfasserIn] Rutkowski, Stefan - 1965- [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
April 24, 2020 |
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| Anmerkung: |
Gesehen am 23.09.2020 |
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| Umfang: |
13 |
| Übergeordnetes Werk: |
Enthalten in: Journal of clinical oncology - Alexandria, Va. : American Society of Clinical Oncology, 1983, 38(2020), 18, Seite 2028-2040 |
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| Übergeordnetes Werk: |
volume:38 ; year:2020 ; number:18 ; pages:2028-2040 ; extent:13 |
| Links: |
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| DOI / URN: |
10.1200/JCO.19.03057 |
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| Katalog-ID: |
1733648607 |
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| 245 | 1 | 0 | |a Nonmetastatic medulloblastoma of early childhood |b results from the prospective clinical trial HIT-2000 and an extended validation cohort |c Martin Mynarek, MD; Katja von Hoff, MD; Torsten Pietsch, MD; Holger Ottensmeier, PhD; Monika Warmuth-Metz, MD; Brigitte Bison, MD; Stefan Pfister, MD; Andrey Korshunov, MD, PhD; Tanvi Sharma, MSc; Natalie Jaeger, PhD;Marina Ryzhova, MD, PhD; Olga Zheludkova, PhD, MD; Andrey Golanov, PhD, MD; Elisabeth Jane Rushing, MD;Martin Hasselblatt, MD; Arend Koch, MD; Ulrich Schüller, MD; Andreas von Deimling, MD; Felix Sahm, MD; Martin Sill, PhD; Markus J. Riemenschneider, MD; Hildegard Dohmen, MD; Camelia Maria Monoranu, MD; Clemens Sommer, MD;Ori Staszewski, MD; Christian Mawrin, MD; Jens Schittenhelm, MD; Wolfgang Brück, MD; Katharina Filipski, MD;Christian Hartmann, MD; Matthias Meinhardt, MD; Klaus Pietschmann, MD; Christine Haberler, MD; Irene Slavc, MD; Nicolas U. Gerber, MD; Michael Grotzer, MD; Martin Benesch, MD; Paul Gerhardt Schlegel, MD; Frank Deinlein, MD; André O. von Bueren, MD, PhD; Carsten Friedrich, MD; Björn-Ole Juhnke, MD; Denise Obrecht, MD; Gudrun Fleischhack, MD; Robert Kwiecien, PhD; Andreas Faldum, PhD; Rolf Dieter Kortmann, MD; Marcel Kool, PhD; and Stefan Rutkowski, MD |
| 264 | 1 | |c April 24, 2020 | |
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| 520 | |a PURPOSEThe HIT-2000-BIS4 trial aimed to avoid highly detrimental craniospinal irradiation (CSI) in children < 4 years of age with nonmetastatic medulloblastoma by systemic chemotherapy, intraventricular methotrexate, and risk-adapted local radiotherapy.PATIENTS AND METHODSFrom 2001-2011, 87 patients received systemic chemotherapy and intraventricular methotrexate. Until 2006, CSI was reserved for nonresponse or progression. After 2006, local radiotherapy was introduced for nonresponders or patients with classic medulloblastoma (CMB) or large-cell/anaplastic medulloblastoma (LCA). DNA methylation profiles of infantile sonic hedgehog-activated medulloblastoma (SHH-INF) were subdivided into iSHH-I and iSHH-II subtypes in the HIT-2000-BIS4 cohort and a validation cohort (n = 71) from the HIT group and Russia.RESULTSFive years after diagnosis, patients with desmoplastic medulloblastoma (DMB) or medulloblastoma with extensive nodularity (MBEN; n = 42) had 93% progression-free survival (5y-PFS), 100% overall survival (5y-OS), and 93% CSI-free (5y-CSI-free) survival. Patients with CMB/LCA (n = 45) had 37% 5y-PFS, 62% 5y-OS, and 39% 5y-CSI-free survival. Local radiotherapy did not improve survival in patients with CMB/LCA. All DMB/MBEN assessed by DNA methylation profiling belonged to the SHH-INF subgroup. Group 3 patients (5y-PFS, 36%; n = 14) relapsed more frequently than the SHH-INF group (5y-PFS, 93%; n = 28) or group 4 patients (5y-PFS, 83%; n = 6; P < .001). SHH-INF split into iSHH-I and iSHH-II subtypes in HIT-2000-BIS4 and the validation cohort, without prognostic impact (5y-PFS: iSHH-I, 73%, v iSHH-II, 83%; P = .25; n = 99). Intelligence quotient (IQ) was significantly lower in patients after CSI (mean IQ, 90 [no radiotherapy], v 74 [CSI]; P = .012).CONCLUSIONSystemic chemotherapy and intraventricular methotrexate led to favorable survival in both iSHH subtypes of SHH-activated DMB/MBEN with acceptable neurotoxicity. Survival in patients with non-wingless (WNT)/non-SHH disease with CMB/LCA was not improved by local radiotherapy. Patients with group 4 disease had more favorable survival rates than those with group 3 medulloblastoma. | ||
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10.1200/JCO.19.03057 doi (DE-627)1733648607 (DE-599)KXP1733648607 (OCoLC)1341361399 DE-627 ger DE-627 rda eng Mynarek, Martin 1980- verfasserin (DE-588)139768912 (DE-627)613094255 (DE-576)313038295 aut Nonmetastatic medulloblastoma of early childhood results from the prospective clinical trial HIT-2000 and an extended validation cohort Martin Mynarek, MD; Katja von Hoff, MD; Torsten Pietsch, MD; Holger Ottensmeier, PhD; Monika Warmuth-Metz, MD; Brigitte Bison, MD; Stefan Pfister, MD; Andrey Korshunov, MD, PhD; Tanvi Sharma, MSc; Natalie Jaeger, PhD;Marina Ryzhova, MD, PhD; Olga Zheludkova, PhD, MD; Andrey Golanov, PhD, MD; Elisabeth Jane Rushing, MD;Martin Hasselblatt, MD; Arend Koch, MD; Ulrich Schüller, MD; Andreas von Deimling, MD; Felix Sahm, MD; Martin Sill, PhD; Markus J. Riemenschneider, MD; Hildegard Dohmen, MD; Camelia Maria Monoranu, MD; Clemens Sommer, MD;Ori Staszewski, MD; Christian Mawrin, MD; Jens Schittenhelm, MD; Wolfgang Brück, MD; Katharina Filipski, MD;Christian Hartmann, MD; Matthias Meinhardt, MD; Klaus Pietschmann, MD; Christine Haberler, MD; Irene Slavc, MD; Nicolas U. Gerber, MD; Michael Grotzer, MD; Martin Benesch, MD; Paul Gerhardt Schlegel, MD; Frank Deinlein, MD; André O. von Bueren, MD, PhD; Carsten Friedrich, MD; Björn-Ole Juhnke, MD; Denise Obrecht, MD; Gudrun Fleischhack, MD; Robert Kwiecien, PhD; Andreas Faldum, PhD; Rolf Dieter Kortmann, MD; Marcel Kool, PhD; and Stefan Rutkowski, MD April 24, 2020 13 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Gesehen am 23.09.2020 PURPOSEThe HIT-2000-BIS4 trial aimed to avoid highly detrimental craniospinal irradiation (CSI) in children < 4 years of age with nonmetastatic medulloblastoma by systemic chemotherapy, intraventricular methotrexate, and risk-adapted local radiotherapy.PATIENTS AND METHODSFrom 2001-2011, 87 patients received systemic chemotherapy and intraventricular methotrexate. Until 2006, CSI was reserved for nonresponse or progression. After 2006, local radiotherapy was introduced for nonresponders or patients with classic medulloblastoma (CMB) or large-cell/anaplastic medulloblastoma (LCA). DNA methylation profiles of infantile sonic hedgehog-activated medulloblastoma (SHH-INF) were subdivided into iSHH-I and iSHH-II subtypes in the HIT-2000-BIS4 cohort and a validation cohort (n = 71) from the HIT group and Russia.RESULTSFive years after diagnosis, patients with desmoplastic medulloblastoma (DMB) or medulloblastoma with extensive nodularity (MBEN; n = 42) had 93% progression-free survival (5y-PFS), 100% overall survival (5y-OS), and 93% CSI-free (5y-CSI-free) survival. Patients with CMB/LCA (n = 45) had 37% 5y-PFS, 62% 5y-OS, and 39% 5y-CSI-free survival. Local radiotherapy did not improve survival in patients with CMB/LCA. All DMB/MBEN assessed by DNA methylation profiling belonged to the SHH-INF subgroup. Group 3 patients (5y-PFS, 36%; n = 14) relapsed more frequently than the SHH-INF group (5y-PFS, 93%; n = 28) or group 4 patients (5y-PFS, 83%; n = 6; P < .001). SHH-INF split into iSHH-I and iSHH-II subtypes in HIT-2000-BIS4 and the validation cohort, without prognostic impact (5y-PFS: iSHH-I, 73%, v iSHH-II, 83%; P = .25; n = 99). Intelligence quotient (IQ) was significantly lower in patients after CSI (mean IQ, 90 [no radiotherapy], v 74 [CSI]; P = .012).CONCLUSIONSystemic chemotherapy and intraventricular methotrexate led to favorable survival in both iSHH subtypes of SHH-activated DMB/MBEN with acceptable neurotoxicity. Survival in patients with non-wingless (WNT)/non-SHH disease with CMB/LCA was not improved by local radiotherapy. Patients with group 4 disease had more favorable survival rates than those with group 3 medulloblastoma. Hoff, Katja von verfasserin (DE-588)1027430309 (DE-627)729136205 (DE-576)373215975 aut Pietsch, Torsten verfasserin aut Ottensmeier, Holger verfasserin aut Warmuth-Metz, Monika verfasserin (DE-588)1158886195 (DE-627)102109854X (DE-576)504508334 aut Bison, Brigitte 1964- verfasserin (DE-588)120166445 (DE-627)696438410 (DE-576)292074913 aut Pfister, Stefan 1974- verfasserin (DE-588)123850215 (DE-627)706450930 (DE-576)293908400 aut Korshunov, Andrey verfasserin (DE-588)1043235361 (DE-627)770439365 (DE-576)394592093 aut Sharma, Tanvi 1993- verfasserin (DE-588)1203560273 (DE-627)1688534954 aut Jäger, Natalie verfasserin (DE-588)1057941662 (DE-627)795556195 (DE-576)413944638 aut Ryzhova, Marina verfasserin (DE-588)1211521982 (DE-627)169981130X aut Zheludkova, Olga verfasserin aut Golanov, Andrey verfasserin aut Rushing, Elisabeth Jane verfasserin (DE-588)1195088582 (DE-627)1677273801 aut Hasselblatt, Martin 1969- verfasserin (DE-588)123559014 (DE-627)082628998 (DE-576)293765537 aut Koch, Arend Wolfgang 1972- verfasserin (DE-588)122734432 (DE-627)082122393 (DE-576)293398879 aut Schüller, Ulrich 1976- verfasserin (DE-588)124391257 (DE-627)363315063 (DE-576)294150757 aut Deimling, Andreas von 1959- verfasserin (DE-588)103034115X (DE-627)735093946 (DE-576)378138065 aut Sahm, Felix 1984- verfasserin (DE-588)1022852132 (DE-627)717318478 (DE-576)366075020 aut Sill, Martin 1982- verfasserin (DE-588)102037330X (DE-627)691197369 (DE-576)359253377 aut Riemenschneider, Markus Johannes 1974- verfasserin (DE-588)124903118 (DE-627)367771543 (DE-576)294560459 aut Dohmen, Hildegard verfasserin (DE-588)1153028131 (DE-627)101440150X (DE-576)50001129X aut Monoranu, Camelia Maria 1966- verfasserin (DE-588)132563290 (DE-627)523949766 (DE-576)299227332 aut Sommer, Clemens 1964- verfasserin (DE-588)1070862185 (DE-627)824644514 (DE-576)432763996 aut Staszewski, Ori 1979- verfasserin (DE-588)132624729 (DE-627)524703043 (DE-576)299264432 aut Mawrin, Christian 1972- verfasserin (DE-588)122598504 (DE-627)082040826 (DE-576)293342687 aut Schittenhelm, Jens Florian 1975- verfasserin (DE-588)13081721X (DE-627)506013375 (DE-576)250548720 aut Brück, Wolfgang verfasserin (DE-588)1165098040 (DE-627)1029638497 (DE-576)510249396 aut Filipski, Katharina Johanna verfasserin (DE-588)1148666974 (DE-627)1008928518 (DE-576)496375377 aut Hartmann, Christian verfasserin (DE-588)1030180539 (DE-627)734895240 (DE-576)377991465 aut Meinhardt, Matthias verfasserin (DE-588)1176168908 (DE-627)1047301040 (DE-576)516562894 aut Pietschmann, Klaus verfasserin aut Haberler, Christine verfasserin aut Slavc, Irene verfasserin aut Gerber, Nicolas U. verfasserin aut Grotzer, Michael 1964- verfasserin (DE-588)130081922 (DE-627)490289452 (DE-576)29798702X aut Benesch, Martin verfasserin (DE-588)1199019070 (DE-627)1681391929 aut Schlegel, Paul-Gerhardt 1958- verfasserin (DE-588)1145636764 (DE-627)100683527X (DE-576)166078581 aut Deinlein, Frank 1964- verfasserin (DE-588)122378725 (DE-627)08190908X (DE-576)293245010 aut Bueren, André von verfasserin (DE-588)1027425445 (DE-627)729125017 (DE-576)373208502 aut Friedrich, Carsten 1978- verfasserin (DE-588)1205319778 (DE-627)1690893877 aut Juhnke, Björn-Ole verfasserin (DE-588)1138729248 (DE-627)896284042 (DE-576)492671389 aut Obrecht, Denise verfasserin aut Fleischhack, Gudrun verfasserin aut Kwiecien, Robert verfasserin aut Faldum, Andreas 1961- verfasserin (DE-588)11545991X (DE-627)07726567X (DE-576)289895367 aut Kortmann, Rolf-Dieter verfasserin (DE-588)119965437X (DE-627)1681979071 aut Kool, Marcel verfasserin (DE-588)1058669753 (DE-627)797393560 (DE-576)414823842 aut Rutkowski, Stefan 1965- verfasserin (DE-588)114616108 (DE-627)527107506 (DE-576)289803004 aut Enthalten in Journal of clinical oncology Alexandria, Va. : American Society of Clinical Oncology, 1983 38(2020), 18, Seite 2028-2040 Online-Ressource (DE-627)313116962 (DE-600)2005181-5 (DE-576)090887018 1527-7755 nnns volume:38 year:2020 number:18 pages:2028-2040 extent:13 https://doi.org/10.1200/JCO.19.03057 Verlag Resolving-System lizenzpflichtig Volltext https://ascopubs.org/doi/10.1200/JCO.19.03057 Verlag lizenzpflichtig Volltext GBV_USEFLAG_U GBV_ILN_120 ISIL_DE-715 SYSFLAG_1 GBV_KXP SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2021 GBV_ILN_2414 GBV_ILN_2424 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 GBV_ILN_178 GBV_ILN_2013 GBV_ILN_178 GBV_ILN_2013 ISIL_DE-16-250 AR 38 2020 18 2028-2040 13 120 01 0715 3889300006 ob at z 16-03-21 120 02 0715 3889972055 00 --%%-- --%%-- g --%%-- alma ob at z 17-03-21 178 01 3178 3765066699 x 02-10-20 2013 01 DE-16-250 3760637906 00 --%%-- --%%-- --%%-- --%%-- l01 23-09-20 120 02 0715 http://49gbv-uob-primo.hosted.exlibrisgroup.com/openurl/49GBV_UOB/UOB_services_page?u.ignore_date_coverage=true&rft.mms_id=991015113666903501 178 00 3178 00 (DE-627)50426415X Institut für Neuropathologie <Magdeburg> 178 00 3178 01 Mawrin, Christian / INPA 178 00 3178 02 (DE-627)719906830 begutachteter Zeitschriftenartikel (peer reviewed) 2013 01 DE-16-250 00 s hd2020 2013 01 DE-16-250 01 s (DE-627)1410508463 wissenschaftlicher Artikel (Zeitschrift) 2013 01 DE-16-250 02 s per_49 2013 01 DE-16-250 03 s s_13 2013 01 DE-16-250 04 p (DE-627)1464593051 Pfister, Stefan 2013 01 DE-16-250 04 k (DE-627)1416740988 Zentrum für Kinder- und Jugendmedizin 2013 01 DE-16-250 04 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 04 s pos_7 2013 01 DE-16-250 05 p (DE-627)1464592632 Korshunov, Andrey 2013 01 DE-16-250 05 k (DE-627)1416740686 Klinikum der Universität Heidelberg 2013 01 DE-16-250 05 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 05 s pos_8 2013 01 DE-16-250 06 p (DE-627)1688535756 Sharma, Tanvi 2013 01 DE-16-250 06 k (DE-627)1416535500 Fakultät für Biowissenschaften 2013 01 DE-16-250 06 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 06 s pos_9 2013 01 DE-16-250 07 p (DE-627)1688536353 Jäger, Natalie 2013 01 DE-16-250 07 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 07 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 07 s pos_10 2013 01 DE-16-250 08 p (DE-627)1448137985 Deimling, Andreas von 2013 01 DE-16-250 08 k (DE-627)1416741658 Pathologisches Institut 2013 01 DE-16-250 08 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 08 s pos_18 2013 01 DE-16-250 09 p (DE-627)143607634X Sahm, Felix 2013 01 DE-16-250 09 k (DE-627)1416741658 Pathologisches Institut 2013 01 DE-16-250 09 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 09 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 09 s pos_19 2013 01 DE-16-250 10 p (DE-627)1447991362 Hartmann, Christian 2013 01 DE-16-250 10 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 10 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 10 s pos_30 2013 01 DE-16-250 11 p (DE-627)1484823788 Kool, Marcel 2013 01 DE-16-250 11 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 11 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 11 s pos_48 178 00 3178 00 Impact factor: 32.956 178 01 3178 99 j2020 120 02 0715 alma |
| spelling |
10.1200/JCO.19.03057 doi (DE-627)1733648607 (DE-599)KXP1733648607 (OCoLC)1341361399 DE-627 ger DE-627 rda eng Mynarek, Martin 1980- verfasserin (DE-588)139768912 (DE-627)613094255 (DE-576)313038295 aut Nonmetastatic medulloblastoma of early childhood results from the prospective clinical trial HIT-2000 and an extended validation cohort Martin Mynarek, MD; Katja von Hoff, MD; Torsten Pietsch, MD; Holger Ottensmeier, PhD; Monika Warmuth-Metz, MD; Brigitte Bison, MD; Stefan Pfister, MD; Andrey Korshunov, MD, PhD; Tanvi Sharma, MSc; Natalie Jaeger, PhD;Marina Ryzhova, MD, PhD; Olga Zheludkova, PhD, MD; Andrey Golanov, PhD, MD; Elisabeth Jane Rushing, MD;Martin Hasselblatt, MD; Arend Koch, MD; Ulrich Schüller, MD; Andreas von Deimling, MD; Felix Sahm, MD; Martin Sill, PhD; Markus J. Riemenschneider, MD; Hildegard Dohmen, MD; Camelia Maria Monoranu, MD; Clemens Sommer, MD;Ori Staszewski, MD; Christian Mawrin, MD; Jens Schittenhelm, MD; Wolfgang Brück, MD; Katharina Filipski, MD;Christian Hartmann, MD; Matthias Meinhardt, MD; Klaus Pietschmann, MD; Christine Haberler, MD; Irene Slavc, MD; Nicolas U. Gerber, MD; Michael Grotzer, MD; Martin Benesch, MD; Paul Gerhardt Schlegel, MD; Frank Deinlein, MD; André O. von Bueren, MD, PhD; Carsten Friedrich, MD; Björn-Ole Juhnke, MD; Denise Obrecht, MD; Gudrun Fleischhack, MD; Robert Kwiecien, PhD; Andreas Faldum, PhD; Rolf Dieter Kortmann, MD; Marcel Kool, PhD; and Stefan Rutkowski, MD April 24, 2020 13 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Gesehen am 23.09.2020 PURPOSEThe HIT-2000-BIS4 trial aimed to avoid highly detrimental craniospinal irradiation (CSI) in children < 4 years of age with nonmetastatic medulloblastoma by systemic chemotherapy, intraventricular methotrexate, and risk-adapted local radiotherapy.PATIENTS AND METHODSFrom 2001-2011, 87 patients received systemic chemotherapy and intraventricular methotrexate. Until 2006, CSI was reserved for nonresponse or progression. After 2006, local radiotherapy was introduced for nonresponders or patients with classic medulloblastoma (CMB) or large-cell/anaplastic medulloblastoma (LCA). DNA methylation profiles of infantile sonic hedgehog-activated medulloblastoma (SHH-INF) were subdivided into iSHH-I and iSHH-II subtypes in the HIT-2000-BIS4 cohort and a validation cohort (n = 71) from the HIT group and Russia.RESULTSFive years after diagnosis, patients with desmoplastic medulloblastoma (DMB) or medulloblastoma with extensive nodularity (MBEN; n = 42) had 93% progression-free survival (5y-PFS), 100% overall survival (5y-OS), and 93% CSI-free (5y-CSI-free) survival. Patients with CMB/LCA (n = 45) had 37% 5y-PFS, 62% 5y-OS, and 39% 5y-CSI-free survival. Local radiotherapy did not improve survival in patients with CMB/LCA. All DMB/MBEN assessed by DNA methylation profiling belonged to the SHH-INF subgroup. Group 3 patients (5y-PFS, 36%; n = 14) relapsed more frequently than the SHH-INF group (5y-PFS, 93%; n = 28) or group 4 patients (5y-PFS, 83%; n = 6; P < .001). SHH-INF split into iSHH-I and iSHH-II subtypes in HIT-2000-BIS4 and the validation cohort, without prognostic impact (5y-PFS: iSHH-I, 73%, v iSHH-II, 83%; P = .25; n = 99). Intelligence quotient (IQ) was significantly lower in patients after CSI (mean IQ, 90 [no radiotherapy], v 74 [CSI]; P = .012).CONCLUSIONSystemic chemotherapy and intraventricular methotrexate led to favorable survival in both iSHH subtypes of SHH-activated DMB/MBEN with acceptable neurotoxicity. Survival in patients with non-wingless (WNT)/non-SHH disease with CMB/LCA was not improved by local radiotherapy. Patients with group 4 disease had more favorable survival rates than those with group 3 medulloblastoma. Hoff, Katja von verfasserin (DE-588)1027430309 (DE-627)729136205 (DE-576)373215975 aut Pietsch, Torsten verfasserin aut Ottensmeier, Holger verfasserin aut Warmuth-Metz, Monika verfasserin (DE-588)1158886195 (DE-627)102109854X (DE-576)504508334 aut Bison, Brigitte 1964- verfasserin (DE-588)120166445 (DE-627)696438410 (DE-576)292074913 aut Pfister, Stefan 1974- verfasserin (DE-588)123850215 (DE-627)706450930 (DE-576)293908400 aut Korshunov, Andrey verfasserin (DE-588)1043235361 (DE-627)770439365 (DE-576)394592093 aut Sharma, Tanvi 1993- verfasserin (DE-588)1203560273 (DE-627)1688534954 aut Jäger, Natalie verfasserin (DE-588)1057941662 (DE-627)795556195 (DE-576)413944638 aut Ryzhova, Marina verfasserin (DE-588)1211521982 (DE-627)169981130X aut Zheludkova, Olga verfasserin aut Golanov, Andrey verfasserin aut Rushing, Elisabeth Jane verfasserin (DE-588)1195088582 (DE-627)1677273801 aut Hasselblatt, Martin 1969- verfasserin (DE-588)123559014 (DE-627)082628998 (DE-576)293765537 aut Koch, Arend Wolfgang 1972- verfasserin (DE-588)122734432 (DE-627)082122393 (DE-576)293398879 aut Schüller, Ulrich 1976- verfasserin (DE-588)124391257 (DE-627)363315063 (DE-576)294150757 aut Deimling, Andreas von 1959- verfasserin (DE-588)103034115X (DE-627)735093946 (DE-576)378138065 aut Sahm, Felix 1984- verfasserin (DE-588)1022852132 (DE-627)717318478 (DE-576)366075020 aut Sill, Martin 1982- verfasserin (DE-588)102037330X (DE-627)691197369 (DE-576)359253377 aut Riemenschneider, Markus Johannes 1974- verfasserin (DE-588)124903118 (DE-627)367771543 (DE-576)294560459 aut Dohmen, Hildegard verfasserin (DE-588)1153028131 (DE-627)101440150X (DE-576)50001129X aut Monoranu, Camelia Maria 1966- verfasserin (DE-588)132563290 (DE-627)523949766 (DE-576)299227332 aut Sommer, Clemens 1964- verfasserin (DE-588)1070862185 (DE-627)824644514 (DE-576)432763996 aut Staszewski, Ori 1979- verfasserin (DE-588)132624729 (DE-627)524703043 (DE-576)299264432 aut Mawrin, Christian 1972- verfasserin (DE-588)122598504 (DE-627)082040826 (DE-576)293342687 aut Schittenhelm, Jens Florian 1975- verfasserin (DE-588)13081721X (DE-627)506013375 (DE-576)250548720 aut Brück, Wolfgang verfasserin (DE-588)1165098040 (DE-627)1029638497 (DE-576)510249396 aut Filipski, Katharina Johanna verfasserin (DE-588)1148666974 (DE-627)1008928518 (DE-576)496375377 aut Hartmann, Christian verfasserin (DE-588)1030180539 (DE-627)734895240 (DE-576)377991465 aut Meinhardt, Matthias verfasserin (DE-588)1176168908 (DE-627)1047301040 (DE-576)516562894 aut Pietschmann, Klaus verfasserin aut Haberler, Christine verfasserin aut Slavc, Irene verfasserin aut Gerber, Nicolas U. verfasserin aut Grotzer, Michael 1964- verfasserin (DE-588)130081922 (DE-627)490289452 (DE-576)29798702X aut Benesch, Martin verfasserin (DE-588)1199019070 (DE-627)1681391929 aut Schlegel, Paul-Gerhardt 1958- verfasserin (DE-588)1145636764 (DE-627)100683527X (DE-576)166078581 aut Deinlein, Frank 1964- verfasserin (DE-588)122378725 (DE-627)08190908X (DE-576)293245010 aut Bueren, André von verfasserin (DE-588)1027425445 (DE-627)729125017 (DE-576)373208502 aut Friedrich, Carsten 1978- verfasserin (DE-588)1205319778 (DE-627)1690893877 aut Juhnke, Björn-Ole verfasserin (DE-588)1138729248 (DE-627)896284042 (DE-576)492671389 aut Obrecht, Denise verfasserin aut Fleischhack, Gudrun verfasserin aut Kwiecien, Robert verfasserin aut Faldum, Andreas 1961- verfasserin (DE-588)11545991X (DE-627)07726567X (DE-576)289895367 aut Kortmann, Rolf-Dieter verfasserin (DE-588)119965437X (DE-627)1681979071 aut Kool, Marcel verfasserin (DE-588)1058669753 (DE-627)797393560 (DE-576)414823842 aut Rutkowski, Stefan 1965- verfasserin (DE-588)114616108 (DE-627)527107506 (DE-576)289803004 aut Enthalten in Journal of clinical oncology Alexandria, Va. : American Society of Clinical Oncology, 1983 38(2020), 18, Seite 2028-2040 Online-Ressource (DE-627)313116962 (DE-600)2005181-5 (DE-576)090887018 1527-7755 nnns volume:38 year:2020 number:18 pages:2028-2040 extent:13 https://doi.org/10.1200/JCO.19.03057 Verlag Resolving-System lizenzpflichtig Volltext https://ascopubs.org/doi/10.1200/JCO.19.03057 Verlag lizenzpflichtig Volltext GBV_USEFLAG_U GBV_ILN_120 ISIL_DE-715 SYSFLAG_1 GBV_KXP SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2021 GBV_ILN_2414 GBV_ILN_2424 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 GBV_ILN_178 GBV_ILN_2013 GBV_ILN_178 GBV_ILN_2013 ISIL_DE-16-250 AR 38 2020 18 2028-2040 13 120 01 0715 3889300006 ob at z 16-03-21 120 02 0715 3889972055 00 --%%-- --%%-- g --%%-- alma ob at z 17-03-21 178 01 3178 3765066699 x 02-10-20 2013 01 DE-16-250 3760637906 00 --%%-- --%%-- --%%-- --%%-- l01 23-09-20 120 02 0715 http://49gbv-uob-primo.hosted.exlibrisgroup.com/openurl/49GBV_UOB/UOB_services_page?u.ignore_date_coverage=true&rft.mms_id=991015113666903501 178 00 3178 00 (DE-627)50426415X Institut für Neuropathologie <Magdeburg> 178 00 3178 01 Mawrin, Christian / INPA 178 00 3178 02 (DE-627)719906830 begutachteter Zeitschriftenartikel (peer reviewed) 2013 01 DE-16-250 00 s hd2020 2013 01 DE-16-250 01 s (DE-627)1410508463 wissenschaftlicher Artikel (Zeitschrift) 2013 01 DE-16-250 02 s per_49 2013 01 DE-16-250 03 s s_13 2013 01 DE-16-250 04 p (DE-627)1464593051 Pfister, Stefan 2013 01 DE-16-250 04 k (DE-627)1416740988 Zentrum für Kinder- und Jugendmedizin 2013 01 DE-16-250 04 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 04 s pos_7 2013 01 DE-16-250 05 p (DE-627)1464592632 Korshunov, Andrey 2013 01 DE-16-250 05 k (DE-627)1416740686 Klinikum der Universität Heidelberg 2013 01 DE-16-250 05 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 05 s pos_8 2013 01 DE-16-250 06 p (DE-627)1688535756 Sharma, Tanvi 2013 01 DE-16-250 06 k (DE-627)1416535500 Fakultät für Biowissenschaften 2013 01 DE-16-250 06 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 06 s pos_9 2013 01 DE-16-250 07 p (DE-627)1688536353 Jäger, Natalie 2013 01 DE-16-250 07 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 07 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 07 s pos_10 2013 01 DE-16-250 08 p (DE-627)1448137985 Deimling, Andreas von 2013 01 DE-16-250 08 k (DE-627)1416741658 Pathologisches Institut 2013 01 DE-16-250 08 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 08 s pos_18 2013 01 DE-16-250 09 p (DE-627)143607634X Sahm, Felix 2013 01 DE-16-250 09 k (DE-627)1416741658 Pathologisches Institut 2013 01 DE-16-250 09 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 09 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 09 s pos_19 2013 01 DE-16-250 10 p (DE-627)1447991362 Hartmann, Christian 2013 01 DE-16-250 10 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 10 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 10 s pos_30 2013 01 DE-16-250 11 p (DE-627)1484823788 Kool, Marcel 2013 01 DE-16-250 11 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 11 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 11 s pos_48 178 00 3178 00 Impact factor: 32.956 178 01 3178 99 j2020 120 02 0715 alma |
| allfields_unstemmed |
10.1200/JCO.19.03057 doi (DE-627)1733648607 (DE-599)KXP1733648607 (OCoLC)1341361399 DE-627 ger DE-627 rda eng Mynarek, Martin 1980- verfasserin (DE-588)139768912 (DE-627)613094255 (DE-576)313038295 aut Nonmetastatic medulloblastoma of early childhood results from the prospective clinical trial HIT-2000 and an extended validation cohort Martin Mynarek, MD; Katja von Hoff, MD; Torsten Pietsch, MD; Holger Ottensmeier, PhD; Monika Warmuth-Metz, MD; Brigitte Bison, MD; Stefan Pfister, MD; Andrey Korshunov, MD, PhD; Tanvi Sharma, MSc; Natalie Jaeger, PhD;Marina Ryzhova, MD, PhD; Olga Zheludkova, PhD, MD; Andrey Golanov, PhD, MD; Elisabeth Jane Rushing, MD;Martin Hasselblatt, MD; Arend Koch, MD; Ulrich Schüller, MD; Andreas von Deimling, MD; Felix Sahm, MD; Martin Sill, PhD; Markus J. Riemenschneider, MD; Hildegard Dohmen, MD; Camelia Maria Monoranu, MD; Clemens Sommer, MD;Ori Staszewski, MD; Christian Mawrin, MD; Jens Schittenhelm, MD; Wolfgang Brück, MD; Katharina Filipski, MD;Christian Hartmann, MD; Matthias Meinhardt, MD; Klaus Pietschmann, MD; Christine Haberler, MD; Irene Slavc, MD; Nicolas U. Gerber, MD; Michael Grotzer, MD; Martin Benesch, MD; Paul Gerhardt Schlegel, MD; Frank Deinlein, MD; André O. von Bueren, MD, PhD; Carsten Friedrich, MD; Björn-Ole Juhnke, MD; Denise Obrecht, MD; Gudrun Fleischhack, MD; Robert Kwiecien, PhD; Andreas Faldum, PhD; Rolf Dieter Kortmann, MD; Marcel Kool, PhD; and Stefan Rutkowski, MD April 24, 2020 13 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Gesehen am 23.09.2020 PURPOSEThe HIT-2000-BIS4 trial aimed to avoid highly detrimental craniospinal irradiation (CSI) in children < 4 years of age with nonmetastatic medulloblastoma by systemic chemotherapy, intraventricular methotrexate, and risk-adapted local radiotherapy.PATIENTS AND METHODSFrom 2001-2011, 87 patients received systemic chemotherapy and intraventricular methotrexate. Until 2006, CSI was reserved for nonresponse or progression. After 2006, local radiotherapy was introduced for nonresponders or patients with classic medulloblastoma (CMB) or large-cell/anaplastic medulloblastoma (LCA). DNA methylation profiles of infantile sonic hedgehog-activated medulloblastoma (SHH-INF) were subdivided into iSHH-I and iSHH-II subtypes in the HIT-2000-BIS4 cohort and a validation cohort (n = 71) from the HIT group and Russia.RESULTSFive years after diagnosis, patients with desmoplastic medulloblastoma (DMB) or medulloblastoma with extensive nodularity (MBEN; n = 42) had 93% progression-free survival (5y-PFS), 100% overall survival (5y-OS), and 93% CSI-free (5y-CSI-free) survival. Patients with CMB/LCA (n = 45) had 37% 5y-PFS, 62% 5y-OS, and 39% 5y-CSI-free survival. Local radiotherapy did not improve survival in patients with CMB/LCA. All DMB/MBEN assessed by DNA methylation profiling belonged to the SHH-INF subgroup. Group 3 patients (5y-PFS, 36%; n = 14) relapsed more frequently than the SHH-INF group (5y-PFS, 93%; n = 28) or group 4 patients (5y-PFS, 83%; n = 6; P < .001). SHH-INF split into iSHH-I and iSHH-II subtypes in HIT-2000-BIS4 and the validation cohort, without prognostic impact (5y-PFS: iSHH-I, 73%, v iSHH-II, 83%; P = .25; n = 99). Intelligence quotient (IQ) was significantly lower in patients after CSI (mean IQ, 90 [no radiotherapy], v 74 [CSI]; P = .012).CONCLUSIONSystemic chemotherapy and intraventricular methotrexate led to favorable survival in both iSHH subtypes of SHH-activated DMB/MBEN with acceptable neurotoxicity. Survival in patients with non-wingless (WNT)/non-SHH disease with CMB/LCA was not improved by local radiotherapy. Patients with group 4 disease had more favorable survival rates than those with group 3 medulloblastoma. Hoff, Katja von verfasserin (DE-588)1027430309 (DE-627)729136205 (DE-576)373215975 aut Pietsch, Torsten verfasserin aut Ottensmeier, Holger verfasserin aut Warmuth-Metz, Monika verfasserin (DE-588)1158886195 (DE-627)102109854X (DE-576)504508334 aut Bison, Brigitte 1964- verfasserin (DE-588)120166445 (DE-627)696438410 (DE-576)292074913 aut Pfister, Stefan 1974- verfasserin (DE-588)123850215 (DE-627)706450930 (DE-576)293908400 aut Korshunov, Andrey verfasserin (DE-588)1043235361 (DE-627)770439365 (DE-576)394592093 aut Sharma, Tanvi 1993- verfasserin (DE-588)1203560273 (DE-627)1688534954 aut Jäger, Natalie verfasserin (DE-588)1057941662 (DE-627)795556195 (DE-576)413944638 aut Ryzhova, Marina verfasserin (DE-588)1211521982 (DE-627)169981130X aut Zheludkova, Olga verfasserin aut Golanov, Andrey verfasserin aut Rushing, Elisabeth Jane verfasserin (DE-588)1195088582 (DE-627)1677273801 aut Hasselblatt, Martin 1969- verfasserin (DE-588)123559014 (DE-627)082628998 (DE-576)293765537 aut Koch, Arend Wolfgang 1972- verfasserin (DE-588)122734432 (DE-627)082122393 (DE-576)293398879 aut Schüller, Ulrich 1976- verfasserin (DE-588)124391257 (DE-627)363315063 (DE-576)294150757 aut Deimling, Andreas von 1959- verfasserin (DE-588)103034115X (DE-627)735093946 (DE-576)378138065 aut Sahm, Felix 1984- verfasserin (DE-588)1022852132 (DE-627)717318478 (DE-576)366075020 aut Sill, Martin 1982- verfasserin (DE-588)102037330X (DE-627)691197369 (DE-576)359253377 aut Riemenschneider, Markus Johannes 1974- verfasserin (DE-588)124903118 (DE-627)367771543 (DE-576)294560459 aut Dohmen, Hildegard verfasserin (DE-588)1153028131 (DE-627)101440150X (DE-576)50001129X aut Monoranu, Camelia Maria 1966- verfasserin (DE-588)132563290 (DE-627)523949766 (DE-576)299227332 aut Sommer, Clemens 1964- verfasserin (DE-588)1070862185 (DE-627)824644514 (DE-576)432763996 aut Staszewski, Ori 1979- verfasserin (DE-588)132624729 (DE-627)524703043 (DE-576)299264432 aut Mawrin, Christian 1972- verfasserin (DE-588)122598504 (DE-627)082040826 (DE-576)293342687 aut Schittenhelm, Jens Florian 1975- verfasserin (DE-588)13081721X (DE-627)506013375 (DE-576)250548720 aut Brück, Wolfgang verfasserin (DE-588)1165098040 (DE-627)1029638497 (DE-576)510249396 aut Filipski, Katharina Johanna verfasserin (DE-588)1148666974 (DE-627)1008928518 (DE-576)496375377 aut Hartmann, Christian verfasserin (DE-588)1030180539 (DE-627)734895240 (DE-576)377991465 aut Meinhardt, Matthias verfasserin (DE-588)1176168908 (DE-627)1047301040 (DE-576)516562894 aut Pietschmann, Klaus verfasserin aut Haberler, Christine verfasserin aut Slavc, Irene verfasserin aut Gerber, Nicolas U. verfasserin aut Grotzer, Michael 1964- verfasserin (DE-588)130081922 (DE-627)490289452 (DE-576)29798702X aut Benesch, Martin verfasserin (DE-588)1199019070 (DE-627)1681391929 aut Schlegel, Paul-Gerhardt 1958- verfasserin (DE-588)1145636764 (DE-627)100683527X (DE-576)166078581 aut Deinlein, Frank 1964- verfasserin (DE-588)122378725 (DE-627)08190908X (DE-576)293245010 aut Bueren, André von verfasserin (DE-588)1027425445 (DE-627)729125017 (DE-576)373208502 aut Friedrich, Carsten 1978- verfasserin (DE-588)1205319778 (DE-627)1690893877 aut Juhnke, Björn-Ole verfasserin (DE-588)1138729248 (DE-627)896284042 (DE-576)492671389 aut Obrecht, Denise verfasserin aut Fleischhack, Gudrun verfasserin aut Kwiecien, Robert verfasserin aut Faldum, Andreas 1961- verfasserin (DE-588)11545991X (DE-627)07726567X (DE-576)289895367 aut Kortmann, Rolf-Dieter verfasserin (DE-588)119965437X (DE-627)1681979071 aut Kool, Marcel verfasserin (DE-588)1058669753 (DE-627)797393560 (DE-576)414823842 aut Rutkowski, Stefan 1965- verfasserin (DE-588)114616108 (DE-627)527107506 (DE-576)289803004 aut Enthalten in Journal of clinical oncology Alexandria, Va. : American Society of Clinical Oncology, 1983 38(2020), 18, Seite 2028-2040 Online-Ressource (DE-627)313116962 (DE-600)2005181-5 (DE-576)090887018 1527-7755 nnns volume:38 year:2020 number:18 pages:2028-2040 extent:13 https://doi.org/10.1200/JCO.19.03057 Verlag Resolving-System lizenzpflichtig Volltext https://ascopubs.org/doi/10.1200/JCO.19.03057 Verlag lizenzpflichtig Volltext GBV_USEFLAG_U GBV_ILN_120 ISIL_DE-715 SYSFLAG_1 GBV_KXP SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2021 GBV_ILN_2414 GBV_ILN_2424 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 GBV_ILN_178 GBV_ILN_2013 GBV_ILN_178 GBV_ILN_2013 ISIL_DE-16-250 AR 38 2020 18 2028-2040 13 120 01 0715 3889300006 ob at z 16-03-21 120 02 0715 3889972055 00 --%%-- --%%-- g --%%-- alma ob at z 17-03-21 178 01 3178 3765066699 x 02-10-20 2013 01 DE-16-250 3760637906 00 --%%-- --%%-- --%%-- --%%-- l01 23-09-20 120 02 0715 http://49gbv-uob-primo.hosted.exlibrisgroup.com/openurl/49GBV_UOB/UOB_services_page?u.ignore_date_coverage=true&rft.mms_id=991015113666903501 178 00 3178 00 (DE-627)50426415X Institut für Neuropathologie <Magdeburg> 178 00 3178 01 Mawrin, Christian / INPA 178 00 3178 02 (DE-627)719906830 begutachteter Zeitschriftenartikel (peer reviewed) 2013 01 DE-16-250 00 s hd2020 2013 01 DE-16-250 01 s (DE-627)1410508463 wissenschaftlicher Artikel (Zeitschrift) 2013 01 DE-16-250 02 s per_49 2013 01 DE-16-250 03 s s_13 2013 01 DE-16-250 04 p (DE-627)1464593051 Pfister, Stefan 2013 01 DE-16-250 04 k (DE-627)1416740988 Zentrum für Kinder- und Jugendmedizin 2013 01 DE-16-250 04 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 04 s pos_7 2013 01 DE-16-250 05 p (DE-627)1464592632 Korshunov, Andrey 2013 01 DE-16-250 05 k (DE-627)1416740686 Klinikum der Universität Heidelberg 2013 01 DE-16-250 05 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 05 s pos_8 2013 01 DE-16-250 06 p (DE-627)1688535756 Sharma, Tanvi 2013 01 DE-16-250 06 k (DE-627)1416535500 Fakultät für Biowissenschaften 2013 01 DE-16-250 06 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 06 s pos_9 2013 01 DE-16-250 07 p (DE-627)1688536353 Jäger, Natalie 2013 01 DE-16-250 07 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 07 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 07 s pos_10 2013 01 DE-16-250 08 p (DE-627)1448137985 Deimling, Andreas von 2013 01 DE-16-250 08 k (DE-627)1416741658 Pathologisches Institut 2013 01 DE-16-250 08 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 08 s pos_18 2013 01 DE-16-250 09 p (DE-627)143607634X Sahm, Felix 2013 01 DE-16-250 09 k (DE-627)1416741658 Pathologisches Institut 2013 01 DE-16-250 09 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 09 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 09 s pos_19 2013 01 DE-16-250 10 p (DE-627)1447991362 Hartmann, Christian 2013 01 DE-16-250 10 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 10 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 10 s pos_30 2013 01 DE-16-250 11 p (DE-627)1484823788 Kool, Marcel 2013 01 DE-16-250 11 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 11 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 11 s pos_48 178 00 3178 00 Impact factor: 32.956 178 01 3178 99 j2020 120 02 0715 alma |
| allfieldsGer |
10.1200/JCO.19.03057 doi (DE-627)1733648607 (DE-599)KXP1733648607 (OCoLC)1341361399 DE-627 ger DE-627 rda eng Mynarek, Martin 1980- verfasserin (DE-588)139768912 (DE-627)613094255 (DE-576)313038295 aut Nonmetastatic medulloblastoma of early childhood results from the prospective clinical trial HIT-2000 and an extended validation cohort Martin Mynarek, MD; Katja von Hoff, MD; Torsten Pietsch, MD; Holger Ottensmeier, PhD; Monika Warmuth-Metz, MD; Brigitte Bison, MD; Stefan Pfister, MD; Andrey Korshunov, MD, PhD; Tanvi Sharma, MSc; Natalie Jaeger, PhD;Marina Ryzhova, MD, PhD; Olga Zheludkova, PhD, MD; Andrey Golanov, PhD, MD; Elisabeth Jane Rushing, MD;Martin Hasselblatt, MD; Arend Koch, MD; Ulrich Schüller, MD; Andreas von Deimling, MD; Felix Sahm, MD; Martin Sill, PhD; Markus J. Riemenschneider, MD; Hildegard Dohmen, MD; Camelia Maria Monoranu, MD; Clemens Sommer, MD;Ori Staszewski, MD; Christian Mawrin, MD; Jens Schittenhelm, MD; Wolfgang Brück, MD; Katharina Filipski, MD;Christian Hartmann, MD; Matthias Meinhardt, MD; Klaus Pietschmann, MD; Christine Haberler, MD; Irene Slavc, MD; Nicolas U. Gerber, MD; Michael Grotzer, MD; Martin Benesch, MD; Paul Gerhardt Schlegel, MD; Frank Deinlein, MD; André O. von Bueren, MD, PhD; Carsten Friedrich, MD; Björn-Ole Juhnke, MD; Denise Obrecht, MD; Gudrun Fleischhack, MD; Robert Kwiecien, PhD; Andreas Faldum, PhD; Rolf Dieter Kortmann, MD; Marcel Kool, PhD; and Stefan Rutkowski, MD April 24, 2020 13 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Gesehen am 23.09.2020 PURPOSEThe HIT-2000-BIS4 trial aimed to avoid highly detrimental craniospinal irradiation (CSI) in children < 4 years of age with nonmetastatic medulloblastoma by systemic chemotherapy, intraventricular methotrexate, and risk-adapted local radiotherapy.PATIENTS AND METHODSFrom 2001-2011, 87 patients received systemic chemotherapy and intraventricular methotrexate. Until 2006, CSI was reserved for nonresponse or progression. After 2006, local radiotherapy was introduced for nonresponders or patients with classic medulloblastoma (CMB) or large-cell/anaplastic medulloblastoma (LCA). DNA methylation profiles of infantile sonic hedgehog-activated medulloblastoma (SHH-INF) were subdivided into iSHH-I and iSHH-II subtypes in the HIT-2000-BIS4 cohort and a validation cohort (n = 71) from the HIT group and Russia.RESULTSFive years after diagnosis, patients with desmoplastic medulloblastoma (DMB) or medulloblastoma with extensive nodularity (MBEN; n = 42) had 93% progression-free survival (5y-PFS), 100% overall survival (5y-OS), and 93% CSI-free (5y-CSI-free) survival. Patients with CMB/LCA (n = 45) had 37% 5y-PFS, 62% 5y-OS, and 39% 5y-CSI-free survival. Local radiotherapy did not improve survival in patients with CMB/LCA. All DMB/MBEN assessed by DNA methylation profiling belonged to the SHH-INF subgroup. Group 3 patients (5y-PFS, 36%; n = 14) relapsed more frequently than the SHH-INF group (5y-PFS, 93%; n = 28) or group 4 patients (5y-PFS, 83%; n = 6; P < .001). SHH-INF split into iSHH-I and iSHH-II subtypes in HIT-2000-BIS4 and the validation cohort, without prognostic impact (5y-PFS: iSHH-I, 73%, v iSHH-II, 83%; P = .25; n = 99). Intelligence quotient (IQ) was significantly lower in patients after CSI (mean IQ, 90 [no radiotherapy], v 74 [CSI]; P = .012).CONCLUSIONSystemic chemotherapy and intraventricular methotrexate led to favorable survival in both iSHH subtypes of SHH-activated DMB/MBEN with acceptable neurotoxicity. Survival in patients with non-wingless (WNT)/non-SHH disease with CMB/LCA was not improved by local radiotherapy. Patients with group 4 disease had more favorable survival rates than those with group 3 medulloblastoma. Hoff, Katja von verfasserin (DE-588)1027430309 (DE-627)729136205 (DE-576)373215975 aut Pietsch, Torsten verfasserin aut Ottensmeier, Holger verfasserin aut Warmuth-Metz, Monika verfasserin (DE-588)1158886195 (DE-627)102109854X (DE-576)504508334 aut Bison, Brigitte 1964- verfasserin (DE-588)120166445 (DE-627)696438410 (DE-576)292074913 aut Pfister, Stefan 1974- verfasserin (DE-588)123850215 (DE-627)706450930 (DE-576)293908400 aut Korshunov, Andrey verfasserin (DE-588)1043235361 (DE-627)770439365 (DE-576)394592093 aut Sharma, Tanvi 1993- verfasserin (DE-588)1203560273 (DE-627)1688534954 aut Jäger, Natalie verfasserin (DE-588)1057941662 (DE-627)795556195 (DE-576)413944638 aut Ryzhova, Marina verfasserin (DE-588)1211521982 (DE-627)169981130X aut Zheludkova, Olga verfasserin aut Golanov, Andrey verfasserin aut Rushing, Elisabeth Jane verfasserin (DE-588)1195088582 (DE-627)1677273801 aut Hasselblatt, Martin 1969- verfasserin (DE-588)123559014 (DE-627)082628998 (DE-576)293765537 aut Koch, Arend Wolfgang 1972- verfasserin (DE-588)122734432 (DE-627)082122393 (DE-576)293398879 aut Schüller, Ulrich 1976- verfasserin (DE-588)124391257 (DE-627)363315063 (DE-576)294150757 aut Deimling, Andreas von 1959- verfasserin (DE-588)103034115X (DE-627)735093946 (DE-576)378138065 aut Sahm, Felix 1984- verfasserin (DE-588)1022852132 (DE-627)717318478 (DE-576)366075020 aut Sill, Martin 1982- verfasserin (DE-588)102037330X (DE-627)691197369 (DE-576)359253377 aut Riemenschneider, Markus Johannes 1974- verfasserin (DE-588)124903118 (DE-627)367771543 (DE-576)294560459 aut Dohmen, Hildegard verfasserin (DE-588)1153028131 (DE-627)101440150X (DE-576)50001129X aut Monoranu, Camelia Maria 1966- verfasserin (DE-588)132563290 (DE-627)523949766 (DE-576)299227332 aut Sommer, Clemens 1964- verfasserin (DE-588)1070862185 (DE-627)824644514 (DE-576)432763996 aut Staszewski, Ori 1979- verfasserin (DE-588)132624729 (DE-627)524703043 (DE-576)299264432 aut Mawrin, Christian 1972- verfasserin (DE-588)122598504 (DE-627)082040826 (DE-576)293342687 aut Schittenhelm, Jens Florian 1975- verfasserin (DE-588)13081721X (DE-627)506013375 (DE-576)250548720 aut Brück, Wolfgang verfasserin (DE-588)1165098040 (DE-627)1029638497 (DE-576)510249396 aut Filipski, Katharina Johanna verfasserin (DE-588)1148666974 (DE-627)1008928518 (DE-576)496375377 aut Hartmann, Christian verfasserin (DE-588)1030180539 (DE-627)734895240 (DE-576)377991465 aut Meinhardt, Matthias verfasserin (DE-588)1176168908 (DE-627)1047301040 (DE-576)516562894 aut Pietschmann, Klaus verfasserin aut Haberler, Christine verfasserin aut Slavc, Irene verfasserin aut Gerber, Nicolas U. verfasserin aut Grotzer, Michael 1964- verfasserin (DE-588)130081922 (DE-627)490289452 (DE-576)29798702X aut Benesch, Martin verfasserin (DE-588)1199019070 (DE-627)1681391929 aut Schlegel, Paul-Gerhardt 1958- verfasserin (DE-588)1145636764 (DE-627)100683527X (DE-576)166078581 aut Deinlein, Frank 1964- verfasserin (DE-588)122378725 (DE-627)08190908X (DE-576)293245010 aut Bueren, André von verfasserin (DE-588)1027425445 (DE-627)729125017 (DE-576)373208502 aut Friedrich, Carsten 1978- verfasserin (DE-588)1205319778 (DE-627)1690893877 aut Juhnke, Björn-Ole verfasserin (DE-588)1138729248 (DE-627)896284042 (DE-576)492671389 aut Obrecht, Denise verfasserin aut Fleischhack, Gudrun verfasserin aut Kwiecien, Robert verfasserin aut Faldum, Andreas 1961- verfasserin (DE-588)11545991X (DE-627)07726567X (DE-576)289895367 aut Kortmann, Rolf-Dieter verfasserin (DE-588)119965437X (DE-627)1681979071 aut Kool, Marcel verfasserin (DE-588)1058669753 (DE-627)797393560 (DE-576)414823842 aut Rutkowski, Stefan 1965- verfasserin (DE-588)114616108 (DE-627)527107506 (DE-576)289803004 aut Enthalten in Journal of clinical oncology Alexandria, Va. : American Society of Clinical Oncology, 1983 38(2020), 18, Seite 2028-2040 Online-Ressource (DE-627)313116962 (DE-600)2005181-5 (DE-576)090887018 1527-7755 nnns volume:38 year:2020 number:18 pages:2028-2040 extent:13 https://doi.org/10.1200/JCO.19.03057 Verlag Resolving-System lizenzpflichtig Volltext https://ascopubs.org/doi/10.1200/JCO.19.03057 Verlag lizenzpflichtig Volltext GBV_USEFLAG_U GBV_ILN_120 ISIL_DE-715 SYSFLAG_1 GBV_KXP SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2021 GBV_ILN_2414 GBV_ILN_2424 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 GBV_ILN_178 GBV_ILN_2013 GBV_ILN_178 GBV_ILN_2013 ISIL_DE-16-250 AR 38 2020 18 2028-2040 13 120 01 0715 3889300006 ob at z 16-03-21 120 02 0715 3889972055 00 --%%-- --%%-- g --%%-- alma ob at z 17-03-21 178 01 3178 3765066699 x 02-10-20 2013 01 DE-16-250 3760637906 00 --%%-- --%%-- --%%-- --%%-- l01 23-09-20 120 02 0715 http://49gbv-uob-primo.hosted.exlibrisgroup.com/openurl/49GBV_UOB/UOB_services_page?u.ignore_date_coverage=true&rft.mms_id=991015113666903501 178 00 3178 00 (DE-627)50426415X Institut für Neuropathologie <Magdeburg> 178 00 3178 01 Mawrin, Christian / INPA 178 00 3178 02 (DE-627)719906830 begutachteter Zeitschriftenartikel (peer reviewed) 2013 01 DE-16-250 00 s hd2020 2013 01 DE-16-250 01 s (DE-627)1410508463 wissenschaftlicher Artikel (Zeitschrift) 2013 01 DE-16-250 02 s per_49 2013 01 DE-16-250 03 s s_13 2013 01 DE-16-250 04 p (DE-627)1464593051 Pfister, Stefan 2013 01 DE-16-250 04 k (DE-627)1416740988 Zentrum für Kinder- und Jugendmedizin 2013 01 DE-16-250 04 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 04 s pos_7 2013 01 DE-16-250 05 p (DE-627)1464592632 Korshunov, Andrey 2013 01 DE-16-250 05 k (DE-627)1416740686 Klinikum der Universität Heidelberg 2013 01 DE-16-250 05 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 05 s pos_8 2013 01 DE-16-250 06 p (DE-627)1688535756 Sharma, Tanvi 2013 01 DE-16-250 06 k (DE-627)1416535500 Fakultät für Biowissenschaften 2013 01 DE-16-250 06 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 06 s pos_9 2013 01 DE-16-250 07 p (DE-627)1688536353 Jäger, Natalie 2013 01 DE-16-250 07 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 07 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 07 s pos_10 2013 01 DE-16-250 08 p (DE-627)1448137985 Deimling, Andreas von 2013 01 DE-16-250 08 k (DE-627)1416741658 Pathologisches Institut 2013 01 DE-16-250 08 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 08 s pos_18 2013 01 DE-16-250 09 p (DE-627)143607634X Sahm, Felix 2013 01 DE-16-250 09 k (DE-627)1416741658 Pathologisches Institut 2013 01 DE-16-250 09 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 09 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 09 s pos_19 2013 01 DE-16-250 10 p (DE-627)1447991362 Hartmann, Christian 2013 01 DE-16-250 10 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 10 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 10 s pos_30 2013 01 DE-16-250 11 p (DE-627)1484823788 Kool, Marcel 2013 01 DE-16-250 11 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 11 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 11 s pos_48 178 00 3178 00 Impact factor: 32.956 178 01 3178 99 j2020 120 02 0715 alma |
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10.1200/JCO.19.03057 doi (DE-627)1733648607 (DE-599)KXP1733648607 (OCoLC)1341361399 DE-627 ger DE-627 rda eng Mynarek, Martin 1980- verfasserin (DE-588)139768912 (DE-627)613094255 (DE-576)313038295 aut Nonmetastatic medulloblastoma of early childhood results from the prospective clinical trial HIT-2000 and an extended validation cohort Martin Mynarek, MD; Katja von Hoff, MD; Torsten Pietsch, MD; Holger Ottensmeier, PhD; Monika Warmuth-Metz, MD; Brigitte Bison, MD; Stefan Pfister, MD; Andrey Korshunov, MD, PhD; Tanvi Sharma, MSc; Natalie Jaeger, PhD;Marina Ryzhova, MD, PhD; Olga Zheludkova, PhD, MD; Andrey Golanov, PhD, MD; Elisabeth Jane Rushing, MD;Martin Hasselblatt, MD; Arend Koch, MD; Ulrich Schüller, MD; Andreas von Deimling, MD; Felix Sahm, MD; Martin Sill, PhD; Markus J. Riemenschneider, MD; Hildegard Dohmen, MD; Camelia Maria Monoranu, MD; Clemens Sommer, MD;Ori Staszewski, MD; Christian Mawrin, MD; Jens Schittenhelm, MD; Wolfgang Brück, MD; Katharina Filipski, MD;Christian Hartmann, MD; Matthias Meinhardt, MD; Klaus Pietschmann, MD; Christine Haberler, MD; Irene Slavc, MD; Nicolas U. Gerber, MD; Michael Grotzer, MD; Martin Benesch, MD; Paul Gerhardt Schlegel, MD; Frank Deinlein, MD; André O. von Bueren, MD, PhD; Carsten Friedrich, MD; Björn-Ole Juhnke, MD; Denise Obrecht, MD; Gudrun Fleischhack, MD; Robert Kwiecien, PhD; Andreas Faldum, PhD; Rolf Dieter Kortmann, MD; Marcel Kool, PhD; and Stefan Rutkowski, MD April 24, 2020 13 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Gesehen am 23.09.2020 PURPOSEThe HIT-2000-BIS4 trial aimed to avoid highly detrimental craniospinal irradiation (CSI) in children < 4 years of age with nonmetastatic medulloblastoma by systemic chemotherapy, intraventricular methotrexate, and risk-adapted local radiotherapy.PATIENTS AND METHODSFrom 2001-2011, 87 patients received systemic chemotherapy and intraventricular methotrexate. Until 2006, CSI was reserved for nonresponse or progression. After 2006, local radiotherapy was introduced for nonresponders or patients with classic medulloblastoma (CMB) or large-cell/anaplastic medulloblastoma (LCA). DNA methylation profiles of infantile sonic hedgehog-activated medulloblastoma (SHH-INF) were subdivided into iSHH-I and iSHH-II subtypes in the HIT-2000-BIS4 cohort and a validation cohort (n = 71) from the HIT group and Russia.RESULTSFive years after diagnosis, patients with desmoplastic medulloblastoma (DMB) or medulloblastoma with extensive nodularity (MBEN; n = 42) had 93% progression-free survival (5y-PFS), 100% overall survival (5y-OS), and 93% CSI-free (5y-CSI-free) survival. Patients with CMB/LCA (n = 45) had 37% 5y-PFS, 62% 5y-OS, and 39% 5y-CSI-free survival. Local radiotherapy did not improve survival in patients with CMB/LCA. All DMB/MBEN assessed by DNA methylation profiling belonged to the SHH-INF subgroup. Group 3 patients (5y-PFS, 36%; n = 14) relapsed more frequently than the SHH-INF group (5y-PFS, 93%; n = 28) or group 4 patients (5y-PFS, 83%; n = 6; P < .001). SHH-INF split into iSHH-I and iSHH-II subtypes in HIT-2000-BIS4 and the validation cohort, without prognostic impact (5y-PFS: iSHH-I, 73%, v iSHH-II, 83%; P = .25; n = 99). Intelligence quotient (IQ) was significantly lower in patients after CSI (mean IQ, 90 [no radiotherapy], v 74 [CSI]; P = .012).CONCLUSIONSystemic chemotherapy and intraventricular methotrexate led to favorable survival in both iSHH subtypes of SHH-activated DMB/MBEN with acceptable neurotoxicity. Survival in patients with non-wingless (WNT)/non-SHH disease with CMB/LCA was not improved by local radiotherapy. Patients with group 4 disease had more favorable survival rates than those with group 3 medulloblastoma. Hoff, Katja von verfasserin (DE-588)1027430309 (DE-627)729136205 (DE-576)373215975 aut Pietsch, Torsten verfasserin aut Ottensmeier, Holger verfasserin aut Warmuth-Metz, Monika verfasserin (DE-588)1158886195 (DE-627)102109854X (DE-576)504508334 aut Bison, Brigitte 1964- verfasserin (DE-588)120166445 (DE-627)696438410 (DE-576)292074913 aut Pfister, Stefan 1974- verfasserin (DE-588)123850215 (DE-627)706450930 (DE-576)293908400 aut Korshunov, Andrey verfasserin (DE-588)1043235361 (DE-627)770439365 (DE-576)394592093 aut Sharma, Tanvi 1993- verfasserin (DE-588)1203560273 (DE-627)1688534954 aut Jäger, Natalie verfasserin (DE-588)1057941662 (DE-627)795556195 (DE-576)413944638 aut Ryzhova, Marina verfasserin (DE-588)1211521982 (DE-627)169981130X aut Zheludkova, Olga verfasserin aut Golanov, Andrey verfasserin aut Rushing, Elisabeth Jane verfasserin (DE-588)1195088582 (DE-627)1677273801 aut Hasselblatt, Martin 1969- verfasserin (DE-588)123559014 (DE-627)082628998 (DE-576)293765537 aut Koch, Arend Wolfgang 1972- verfasserin (DE-588)122734432 (DE-627)082122393 (DE-576)293398879 aut Schüller, Ulrich 1976- verfasserin (DE-588)124391257 (DE-627)363315063 (DE-576)294150757 aut Deimling, Andreas von 1959- verfasserin (DE-588)103034115X (DE-627)735093946 (DE-576)378138065 aut Sahm, Felix 1984- verfasserin (DE-588)1022852132 (DE-627)717318478 (DE-576)366075020 aut Sill, Martin 1982- verfasserin (DE-588)102037330X (DE-627)691197369 (DE-576)359253377 aut Riemenschneider, Markus Johannes 1974- verfasserin (DE-588)124903118 (DE-627)367771543 (DE-576)294560459 aut Dohmen, Hildegard verfasserin (DE-588)1153028131 (DE-627)101440150X (DE-576)50001129X aut Monoranu, Camelia Maria 1966- verfasserin (DE-588)132563290 (DE-627)523949766 (DE-576)299227332 aut Sommer, Clemens 1964- verfasserin (DE-588)1070862185 (DE-627)824644514 (DE-576)432763996 aut Staszewski, Ori 1979- verfasserin (DE-588)132624729 (DE-627)524703043 (DE-576)299264432 aut Mawrin, Christian 1972- verfasserin (DE-588)122598504 (DE-627)082040826 (DE-576)293342687 aut Schittenhelm, Jens Florian 1975- verfasserin (DE-588)13081721X (DE-627)506013375 (DE-576)250548720 aut Brück, Wolfgang verfasserin (DE-588)1165098040 (DE-627)1029638497 (DE-576)510249396 aut Filipski, Katharina Johanna verfasserin (DE-588)1148666974 (DE-627)1008928518 (DE-576)496375377 aut Hartmann, Christian verfasserin (DE-588)1030180539 (DE-627)734895240 (DE-576)377991465 aut Meinhardt, Matthias verfasserin (DE-588)1176168908 (DE-627)1047301040 (DE-576)516562894 aut Pietschmann, Klaus verfasserin aut Haberler, Christine verfasserin aut Slavc, Irene verfasserin aut Gerber, Nicolas U. verfasserin aut Grotzer, Michael 1964- verfasserin (DE-588)130081922 (DE-627)490289452 (DE-576)29798702X aut Benesch, Martin verfasserin (DE-588)1199019070 (DE-627)1681391929 aut Schlegel, Paul-Gerhardt 1958- verfasserin (DE-588)1145636764 (DE-627)100683527X (DE-576)166078581 aut Deinlein, Frank 1964- verfasserin (DE-588)122378725 (DE-627)08190908X (DE-576)293245010 aut Bueren, André von verfasserin (DE-588)1027425445 (DE-627)729125017 (DE-576)373208502 aut Friedrich, Carsten 1978- verfasserin (DE-588)1205319778 (DE-627)1690893877 aut Juhnke, Björn-Ole verfasserin (DE-588)1138729248 (DE-627)896284042 (DE-576)492671389 aut Obrecht, Denise verfasserin aut Fleischhack, Gudrun verfasserin aut Kwiecien, Robert verfasserin aut Faldum, Andreas 1961- verfasserin (DE-588)11545991X (DE-627)07726567X (DE-576)289895367 aut Kortmann, Rolf-Dieter verfasserin (DE-588)119965437X (DE-627)1681979071 aut Kool, Marcel verfasserin (DE-588)1058669753 (DE-627)797393560 (DE-576)414823842 aut Rutkowski, Stefan 1965- verfasserin (DE-588)114616108 (DE-627)527107506 (DE-576)289803004 aut Enthalten in Journal of clinical oncology Alexandria, Va. : American Society of Clinical Oncology, 1983 38(2020), 18, Seite 2028-2040 Online-Ressource (DE-627)313116962 (DE-600)2005181-5 (DE-576)090887018 1527-7755 nnns volume:38 year:2020 number:18 pages:2028-2040 extent:13 https://doi.org/10.1200/JCO.19.03057 Verlag Resolving-System lizenzpflichtig Volltext https://ascopubs.org/doi/10.1200/JCO.19.03057 Verlag lizenzpflichtig Volltext GBV_USEFLAG_U GBV_ILN_120 ISIL_DE-715 SYSFLAG_1 GBV_KXP SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2021 GBV_ILN_2414 GBV_ILN_2424 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 GBV_ILN_178 GBV_ILN_2013 GBV_ILN_178 GBV_ILN_2013 ISIL_DE-16-250 AR 38 2020 18 2028-2040 13 120 01 0715 3889300006 ob at z 16-03-21 120 02 0715 3889972055 00 --%%-- --%%-- g --%%-- alma ob at z 17-03-21 178 01 3178 3765066699 x 02-10-20 2013 01 DE-16-250 3760637906 00 --%%-- --%%-- --%%-- --%%-- l01 23-09-20 120 02 0715 http://49gbv-uob-primo.hosted.exlibrisgroup.com/openurl/49GBV_UOB/UOB_services_page?u.ignore_date_coverage=true&rft.mms_id=991015113666903501 178 00 3178 00 (DE-627)50426415X Institut für Neuropathologie <Magdeburg> 178 00 3178 01 Mawrin, Christian / INPA 178 00 3178 02 (DE-627)719906830 begutachteter Zeitschriftenartikel (peer reviewed) 2013 01 DE-16-250 00 s hd2020 2013 01 DE-16-250 01 s (DE-627)1410508463 wissenschaftlicher Artikel (Zeitschrift) 2013 01 DE-16-250 02 s per_49 2013 01 DE-16-250 03 s s_13 2013 01 DE-16-250 04 p (DE-627)1464593051 Pfister, Stefan 2013 01 DE-16-250 04 k (DE-627)1416740988 Zentrum für Kinder- und Jugendmedizin 2013 01 DE-16-250 04 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 04 s pos_7 2013 01 DE-16-250 05 p (DE-627)1464592632 Korshunov, Andrey 2013 01 DE-16-250 05 k (DE-627)1416740686 Klinikum der Universität Heidelberg 2013 01 DE-16-250 05 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 05 s pos_8 2013 01 DE-16-250 06 p (DE-627)1688535756 Sharma, Tanvi 2013 01 DE-16-250 06 k (DE-627)1416535500 Fakultät für Biowissenschaften 2013 01 DE-16-250 06 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 06 s pos_9 2013 01 DE-16-250 07 p (DE-627)1688536353 Jäger, Natalie 2013 01 DE-16-250 07 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 07 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 07 s pos_10 2013 01 DE-16-250 08 p (DE-627)1448137985 Deimling, Andreas von 2013 01 DE-16-250 08 k (DE-627)1416741658 Pathologisches Institut 2013 01 DE-16-250 08 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 08 s pos_18 2013 01 DE-16-250 09 p (DE-627)143607634X Sahm, Felix 2013 01 DE-16-250 09 k (DE-627)1416741658 Pathologisches Institut 2013 01 DE-16-250 09 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 09 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 09 s pos_19 2013 01 DE-16-250 10 p (DE-627)1447991362 Hartmann, Christian 2013 01 DE-16-250 10 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 10 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 10 s pos_30 2013 01 DE-16-250 11 p (DE-627)1484823788 Kool, Marcel 2013 01 DE-16-250 11 k (DE-627)1416466967 Medizinische Fakultät Heidelberg 2013 01 DE-16-250 11 s (DE-627)1410501914 Verfasser 2013 01 DE-16-250 11 s pos_48 178 00 3178 00 Impact factor: 32.956 178 01 3178 99 j2020 120 02 0715 alma |
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English |
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Enthalten in Journal of clinical oncology 38(2020), 18, Seite 2028-2040 volume:38 year:2020 number:18 pages:2028-2040 extent:13 |
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Enthalten in Journal of clinical oncology 38(2020), 18, Seite 2028-2040 volume:38 year:2020 number:18 pages:2028-2040 extent:13 |
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178:Institut für Neuropathologie <Magdeburg> 3178:Institut für Neuropathologie <Magdeburg> 178:Mawrin, Christian / INPA 3178:Mawrin, Christian / INPA 178:begutachteter Zeitschriftenartikel (peer reviewed) 3178:begutachteter Zeitschriftenartikel (peer reviewed) 2013:hd2020 DE-16-250:hd2020 2013:wissenschaftlicher Artikel (Zeitschrift) DE-16-250:wissenschaftlicher Artikel (Zeitschrift) 2013:per_49 DE-16-250:per_49 2013:s_13 DE-16-250:s_13 2013:Pfister, Stefan DE-16-250:Pfister, Stefan 2013:Zentrum für Kinder- und Jugendmedizin DE-16-250:Zentrum für Kinder- und Jugendmedizin 2013:Verfasser DE-16-250:Verfasser 2013:pos_7 DE-16-250:pos_7 2013:Korshunov, Andrey DE-16-250:Korshunov, Andrey 2013:Klinikum der Universität Heidelberg DE-16-250:Klinikum der Universität Heidelberg 2013:pos_8 DE-16-250:pos_8 2013:Sharma, Tanvi DE-16-250:Sharma, Tanvi 2013:Fakultät für Biowissenschaften DE-16-250:Fakultät für Biowissenschaften 2013:pos_9 DE-16-250:pos_9 2013:Jäger, Natalie DE-16-250:Jäger, Natalie 2013:Medizinische Fakultät Heidelberg DE-16-250:Medizinische Fakultät Heidelberg 2013:pos_10 DE-16-250:pos_10 2013:Deimling, Andreas von DE-16-250:Deimling, Andreas von 2013:Pathologisches Institut DE-16-250:Pathologisches Institut 2013:pos_18 DE-16-250:pos_18 2013:Sahm, Felix DE-16-250:Sahm, Felix 2013:pos_19 DE-16-250:pos_19 2013:Hartmann, Christian DE-16-250:Hartmann, Christian 2013:pos_30 DE-16-250:pos_30 2013:Kool, Marcel DE-16-250:Kool, Marcel 2013:pos_48 DE-16-250:pos_48 |
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Mynarek, Martin @@aut@@ Hoff, Katja von @@aut@@ Pietsch, Torsten @@aut@@ Ottensmeier, Holger @@aut@@ Warmuth-Metz, Monika @@aut@@ Bison, Brigitte @@aut@@ Pfister, Stefan @@aut@@ Korshunov, Andrey @@aut@@ Sharma, Tanvi @@aut@@ Jäger, Natalie @@aut@@ Ryzhova, Marina @@aut@@ Zheludkova, Olga @@aut@@ Golanov, Andrey @@aut@@ Rushing, Elisabeth Jane @@aut@@ Hasselblatt, Martin @@aut@@ Koch, Arend Wolfgang @@aut@@ Schüller, Ulrich @@aut@@ Deimling, Andreas von @@aut@@ Sahm, Felix @@aut@@ Sill, Martin @@aut@@ Riemenschneider, Markus Johannes @@aut@@ Dohmen, Hildegard @@aut@@ Monoranu, Camelia Maria @@aut@@ Sommer, Clemens @@aut@@ Staszewski, Ori @@aut@@ Mawrin, Christian @@aut@@ Schittenhelm, Jens Florian @@aut@@ Brück, Wolfgang @@aut@@ Filipski, Katharina Johanna @@aut@@ Hartmann, Christian @@aut@@ Meinhardt, Matthias @@aut@@ Pietschmann, Klaus @@aut@@ Haberler, Christine @@aut@@ Slavc, Irene @@aut@@ Gerber, Nicolas U. @@aut@@ Grotzer, Michael @@aut@@ Benesch, Martin @@aut@@ Schlegel, Paul-Gerhardt @@aut@@ Deinlein, Frank @@aut@@ Bueren, André von @@aut@@ Friedrich, Carsten @@aut@@ Juhnke, Björn-Ole @@aut@@ Obrecht, Denise @@aut@@ Fleischhack, Gudrun @@aut@@ Kwiecien, Robert @@aut@@ Faldum, Andreas @@aut@@ Kortmann, Rolf-Dieter @@aut@@ Kool, Marcel @@aut@@ Rutkowski, Stefan @@aut@@ |
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<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a2200265 4500</leader><controlfield tag="001">1733648607</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230426163441.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">200923s2020 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1200/JCO.19.03057</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)1733648607</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)KXP1733648607</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(OCoLC)1341361399</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rda</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Mynarek, Martin</subfield><subfield code="d">1980-</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(DE-588)139768912</subfield><subfield code="0">(DE-627)613094255</subfield><subfield code="0">(DE-576)313038295</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Nonmetastatic medulloblastoma of early childhood</subfield><subfield code="b">results from the prospective clinical trial HIT-2000 and an extended validation cohort</subfield><subfield code="c">Martin Mynarek, MD; Katja von Hoff, MD; Torsten Pietsch, MD; Holger Ottensmeier, PhD; Monika Warmuth-Metz, MD; Brigitte Bison, MD; Stefan Pfister, MD; Andrey Korshunov, MD, PhD; Tanvi Sharma, MSc; Natalie Jaeger, PhD;Marina Ryzhova, MD, PhD; Olga Zheludkova, PhD, MD; Andrey Golanov, PhD, MD; Elisabeth Jane Rushing, MD;Martin Hasselblatt, MD; Arend Koch, MD; Ulrich Schüller, MD; Andreas von Deimling, MD; Felix Sahm, MD; Martin Sill, PhD; Markus J. Riemenschneider, MD; Hildegard Dohmen, MD; Camelia Maria Monoranu, MD; Clemens Sommer, MD;Ori Staszewski, MD; Christian Mawrin, MD; Jens Schittenhelm, MD; Wolfgang Brück, MD; Katharina Filipski, MD;Christian Hartmann, MD; Matthias Meinhardt, MD; Klaus Pietschmann, MD; Christine Haberler, MD; Irene Slavc, MD; Nicolas U. Gerber, MD; Michael Grotzer, MD; Martin Benesch, MD; Paul Gerhardt Schlegel, MD; Frank Deinlein, MD; André O. von Bueren, MD, PhD; Carsten Friedrich, MD; Björn-Ole Juhnke, MD; Denise Obrecht, MD; Gudrun Fleischhack, MD; Robert Kwiecien, PhD; Andreas Faldum, PhD; Rolf Dieter Kortmann, MD; Marcel Kool, PhD; and Stefan Rutkowski, MD</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">April 24, 2020</subfield></datafield><datafield tag="300" ind1=" " ind2=" "><subfield code="a">13</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="500" ind1=" " ind2=" "><subfield code="a">Gesehen am 23.09.2020</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">PURPOSEThe HIT-2000-BIS4 trial aimed to avoid highly detrimental craniospinal irradiation (CSI) in children < 4 years of age with nonmetastatic medulloblastoma by systemic chemotherapy, intraventricular methotrexate, and risk-adapted local radiotherapy.PATIENTS AND METHODSFrom 2001-2011, 87 patients received systemic chemotherapy and intraventricular methotrexate. Until 2006, CSI was reserved for nonresponse or progression. After 2006, local radiotherapy was introduced for nonresponders or patients with classic medulloblastoma (CMB) or large-cell/anaplastic medulloblastoma (LCA). DNA methylation profiles of infantile sonic hedgehog-activated medulloblastoma (SHH-INF) were subdivided into iSHH-I and iSHH-II subtypes in the HIT-2000-BIS4 cohort and a validation cohort (n = 71) from the HIT group and Russia.RESULTSFive years after diagnosis, patients with desmoplastic medulloblastoma (DMB) or medulloblastoma with extensive nodularity (MBEN; n = 42) had 93% progression-free survival (5y-PFS), 100% overall survival (5y-OS), and 93% CSI-free (5y-CSI-free) survival. Patients with CMB/LCA (n = 45) had 37% 5y-PFS, 62% 5y-OS, and 39% 5y-CSI-free survival. Local radiotherapy did not improve survival in patients with CMB/LCA. All DMB/MBEN assessed by DNA methylation profiling belonged to the SHH-INF subgroup. Group 3 patients (5y-PFS, 36%; n = 14) relapsed more frequently than the SHH-INF group (5y-PFS, 93%; n = 28) or group 4 patients (5y-PFS, 83%; n = 6; P < .001). SHH-INF split into iSHH-I and iSHH-II subtypes in HIT-2000-BIS4 and the validation cohort, without prognostic impact (5y-PFS: iSHH-I, 73%, v iSHH-II, 83%; P = .25; n = 99). Intelligence quotient (IQ) was significantly lower in patients after CSI (mean IQ, 90 [no radiotherapy], v 74 [CSI]; P = .012).CONCLUSIONSystemic chemotherapy and intraventricular methotrexate led to favorable survival in both iSHH subtypes of SHH-activated DMB/MBEN with acceptable neurotoxicity. Survival in patients with non-wingless (WNT)/non-SHH disease with CMB/LCA was not improved by local radiotherapy. 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Mynarek, Martin Hoff, Katja von Pietsch, Torsten Ottensmeier, Holger Warmuth-Metz, Monika Bison, Brigitte Pfister, Stefan Korshunov, Andrey Sharma, Tanvi Jäger, Natalie Ryzhova, Marina Zheludkova, Olga Golanov, Andrey Rushing, Elisabeth Jane Hasselblatt, Martin Koch, Arend Wolfgang Schüller, Ulrich Deimling, Andreas von Sahm, Felix Sill, Martin Riemenschneider, Markus Johannes Dohmen, Hildegard Monoranu, Camelia Maria Sommer, Clemens Staszewski, Ori Mawrin, Christian Schittenhelm, Jens Florian Brück, Wolfgang Filipski, Katharina Johanna Hartmann, Christian Meinhardt, Matthias Pietschmann, Klaus Haberler, Christine Slavc, Irene Gerber, Nicolas U. Grotzer, Michael Benesch, Martin Schlegel, Paul-Gerhardt Deinlein, Frank Bueren, André von Friedrich, Carsten Juhnke, Björn-Ole Obrecht, Denise Fleischhack, Gudrun Kwiecien, Robert Faldum, Andreas Kortmann, Rolf-Dieter Kool, Marcel Rutkowski, Stefan |
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Mynarek, Martin |
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results from the prospective clinical trial HIT-2000 and an extended validation cohort |
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nonmetastatic medulloblastoma of early childhoodresults from the prospective clinical trial hit-2000 and an extended validation cohort |
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Nonmetastatic medulloblastoma of early childhood results from the prospective clinical trial HIT-2000 and an extended validation cohort |
| abstract |
PURPOSEThe HIT-2000-BIS4 trial aimed to avoid highly detrimental craniospinal irradiation (CSI) in children < 4 years of age with nonmetastatic medulloblastoma by systemic chemotherapy, intraventricular methotrexate, and risk-adapted local radiotherapy.PATIENTS AND METHODSFrom 2001-2011, 87 patients received systemic chemotherapy and intraventricular methotrexate. Until 2006, CSI was reserved for nonresponse or progression. After 2006, local radiotherapy was introduced for nonresponders or patients with classic medulloblastoma (CMB) or large-cell/anaplastic medulloblastoma (LCA). DNA methylation profiles of infantile sonic hedgehog-activated medulloblastoma (SHH-INF) were subdivided into iSHH-I and iSHH-II subtypes in the HIT-2000-BIS4 cohort and a validation cohort (n = 71) from the HIT group and Russia.RESULTSFive years after diagnosis, patients with desmoplastic medulloblastoma (DMB) or medulloblastoma with extensive nodularity (MBEN; n = 42) had 93% progression-free survival (5y-PFS), 100% overall survival (5y-OS), and 93% CSI-free (5y-CSI-free) survival. Patients with CMB/LCA (n = 45) had 37% 5y-PFS, 62% 5y-OS, and 39% 5y-CSI-free survival. Local radiotherapy did not improve survival in patients with CMB/LCA. All DMB/MBEN assessed by DNA methylation profiling belonged to the SHH-INF subgroup. Group 3 patients (5y-PFS, 36%; n = 14) relapsed more frequently than the SHH-INF group (5y-PFS, 93%; n = 28) or group 4 patients (5y-PFS, 83%; n = 6; P < .001). SHH-INF split into iSHH-I and iSHH-II subtypes in HIT-2000-BIS4 and the validation cohort, without prognostic impact (5y-PFS: iSHH-I, 73%, v iSHH-II, 83%; P = .25; n = 99). Intelligence quotient (IQ) was significantly lower in patients after CSI (mean IQ, 90 [no radiotherapy], v 74 [CSI]; P = .012).CONCLUSIONSystemic chemotherapy and intraventricular methotrexate led to favorable survival in both iSHH subtypes of SHH-activated DMB/MBEN with acceptable neurotoxicity. Survival in patients with non-wingless (WNT)/non-SHH disease with CMB/LCA was not improved by local radiotherapy. Patients with group 4 disease had more favorable survival rates than those with group 3 medulloblastoma. Gesehen am 23.09.2020 |
| abstractGer |
PURPOSEThe HIT-2000-BIS4 trial aimed to avoid highly detrimental craniospinal irradiation (CSI) in children < 4 years of age with nonmetastatic medulloblastoma by systemic chemotherapy, intraventricular methotrexate, and risk-adapted local radiotherapy.PATIENTS AND METHODSFrom 2001-2011, 87 patients received systemic chemotherapy and intraventricular methotrexate. Until 2006, CSI was reserved for nonresponse or progression. After 2006, local radiotherapy was introduced for nonresponders or patients with classic medulloblastoma (CMB) or large-cell/anaplastic medulloblastoma (LCA). DNA methylation profiles of infantile sonic hedgehog-activated medulloblastoma (SHH-INF) were subdivided into iSHH-I and iSHH-II subtypes in the HIT-2000-BIS4 cohort and a validation cohort (n = 71) from the HIT group and Russia.RESULTSFive years after diagnosis, patients with desmoplastic medulloblastoma (DMB) or medulloblastoma with extensive nodularity (MBEN; n = 42) had 93% progression-free survival (5y-PFS), 100% overall survival (5y-OS), and 93% CSI-free (5y-CSI-free) survival. Patients with CMB/LCA (n = 45) had 37% 5y-PFS, 62% 5y-OS, and 39% 5y-CSI-free survival. Local radiotherapy did not improve survival in patients with CMB/LCA. All DMB/MBEN assessed by DNA methylation profiling belonged to the SHH-INF subgroup. Group 3 patients (5y-PFS, 36%; n = 14) relapsed more frequently than the SHH-INF group (5y-PFS, 93%; n = 28) or group 4 patients (5y-PFS, 83%; n = 6; P < .001). SHH-INF split into iSHH-I and iSHH-II subtypes in HIT-2000-BIS4 and the validation cohort, without prognostic impact (5y-PFS: iSHH-I, 73%, v iSHH-II, 83%; P = .25; n = 99). Intelligence quotient (IQ) was significantly lower in patients after CSI (mean IQ, 90 [no radiotherapy], v 74 [CSI]; P = .012).CONCLUSIONSystemic chemotherapy and intraventricular methotrexate led to favorable survival in both iSHH subtypes of SHH-activated DMB/MBEN with acceptable neurotoxicity. Survival in patients with non-wingless (WNT)/non-SHH disease with CMB/LCA was not improved by local radiotherapy. Patients with group 4 disease had more favorable survival rates than those with group 3 medulloblastoma. Gesehen am 23.09.2020 |
| abstract_unstemmed |
PURPOSEThe HIT-2000-BIS4 trial aimed to avoid highly detrimental craniospinal irradiation (CSI) in children < 4 years of age with nonmetastatic medulloblastoma by systemic chemotherapy, intraventricular methotrexate, and risk-adapted local radiotherapy.PATIENTS AND METHODSFrom 2001-2011, 87 patients received systemic chemotherapy and intraventricular methotrexate. Until 2006, CSI was reserved for nonresponse or progression. After 2006, local radiotherapy was introduced for nonresponders or patients with classic medulloblastoma (CMB) or large-cell/anaplastic medulloblastoma (LCA). DNA methylation profiles of infantile sonic hedgehog-activated medulloblastoma (SHH-INF) were subdivided into iSHH-I and iSHH-II subtypes in the HIT-2000-BIS4 cohort and a validation cohort (n = 71) from the HIT group and Russia.RESULTSFive years after diagnosis, patients with desmoplastic medulloblastoma (DMB) or medulloblastoma with extensive nodularity (MBEN; n = 42) had 93% progression-free survival (5y-PFS), 100% overall survival (5y-OS), and 93% CSI-free (5y-CSI-free) survival. Patients with CMB/LCA (n = 45) had 37% 5y-PFS, 62% 5y-OS, and 39% 5y-CSI-free survival. Local radiotherapy did not improve survival in patients with CMB/LCA. All DMB/MBEN assessed by DNA methylation profiling belonged to the SHH-INF subgroup. Group 3 patients (5y-PFS, 36%; n = 14) relapsed more frequently than the SHH-INF group (5y-PFS, 93%; n = 28) or group 4 patients (5y-PFS, 83%; n = 6; P < .001). SHH-INF split into iSHH-I and iSHH-II subtypes in HIT-2000-BIS4 and the validation cohort, without prognostic impact (5y-PFS: iSHH-I, 73%, v iSHH-II, 83%; P = .25; n = 99). Intelligence quotient (IQ) was significantly lower in patients after CSI (mean IQ, 90 [no radiotherapy], v 74 [CSI]; P = .012).CONCLUSIONSystemic chemotherapy and intraventricular methotrexate led to favorable survival in both iSHH subtypes of SHH-activated DMB/MBEN with acceptable neurotoxicity. Survival in patients with non-wingless (WNT)/non-SHH disease with CMB/LCA was not improved by local radiotherapy. Patients with group 4 disease had more favorable survival rates than those with group 3 medulloblastoma. Gesehen am 23.09.2020 |
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<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a2200265 4500</leader><controlfield tag="001">1733648607</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230426163441.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">200923s2020 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1200/JCO.19.03057</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)1733648607</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)KXP1733648607</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(OCoLC)1341361399</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rda</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Mynarek, Martin</subfield><subfield code="d">1980-</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(DE-588)139768912</subfield><subfield code="0">(DE-627)613094255</subfield><subfield code="0">(DE-576)313038295</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Nonmetastatic medulloblastoma of early childhood</subfield><subfield code="b">results from the prospective clinical trial HIT-2000 and an extended validation cohort</subfield><subfield code="c">Martin Mynarek, MD; Katja von Hoff, MD; Torsten Pietsch, MD; Holger Ottensmeier, PhD; Monika Warmuth-Metz, MD; Brigitte Bison, MD; Stefan Pfister, MD; Andrey Korshunov, MD, PhD; Tanvi Sharma, MSc; Natalie Jaeger, PhD;Marina Ryzhova, MD, PhD; Olga Zheludkova, PhD, MD; Andrey Golanov, PhD, MD; Elisabeth Jane Rushing, MD;Martin Hasselblatt, MD; Arend Koch, MD; Ulrich Schüller, MD; Andreas von Deimling, MD; Felix Sahm, MD; Martin Sill, PhD; Markus J. Riemenschneider, MD; Hildegard Dohmen, MD; Camelia Maria Monoranu, MD; Clemens Sommer, MD;Ori Staszewski, MD; Christian Mawrin, MD; Jens Schittenhelm, MD; Wolfgang Brück, MD; Katharina Filipski, MD;Christian Hartmann, MD; Matthias Meinhardt, MD; Klaus Pietschmann, MD; Christine Haberler, MD; Irene Slavc, MD; Nicolas U. Gerber, MD; Michael Grotzer, MD; Martin Benesch, MD; Paul Gerhardt Schlegel, MD; Frank Deinlein, MD; André O. von Bueren, MD, PhD; Carsten Friedrich, MD; Björn-Ole Juhnke, MD; Denise Obrecht, MD; Gudrun Fleischhack, MD; Robert Kwiecien, PhD; Andreas Faldum, PhD; Rolf Dieter Kortmann, MD; Marcel Kool, PhD; and Stefan Rutkowski, MD</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">April 24, 2020</subfield></datafield><datafield tag="300" ind1=" " ind2=" "><subfield code="a">13</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="500" ind1=" " ind2=" "><subfield code="a">Gesehen am 23.09.2020</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">PURPOSEThe HIT-2000-BIS4 trial aimed to avoid highly detrimental craniospinal irradiation (CSI) in children < 4 years of age with nonmetastatic medulloblastoma by systemic chemotherapy, intraventricular methotrexate, and risk-adapted local radiotherapy.PATIENTS AND METHODSFrom 2001-2011, 87 patients received systemic chemotherapy and intraventricular methotrexate. Until 2006, CSI was reserved for nonresponse or progression. After 2006, local radiotherapy was introduced for nonresponders or patients with classic medulloblastoma (CMB) or large-cell/anaplastic medulloblastoma (LCA). DNA methylation profiles of infantile sonic hedgehog-activated medulloblastoma (SHH-INF) were subdivided into iSHH-I and iSHH-II subtypes in the HIT-2000-BIS4 cohort and a validation cohort (n = 71) from the HIT group and Russia.RESULTSFive years after diagnosis, patients with desmoplastic medulloblastoma (DMB) or medulloblastoma with extensive nodularity (MBEN; n = 42) had 93% progression-free survival (5y-PFS), 100% overall survival (5y-OS), and 93% CSI-free (5y-CSI-free) survival. Patients with CMB/LCA (n = 45) had 37% 5y-PFS, 62% 5y-OS, and 39% 5y-CSI-free survival. Local radiotherapy did not improve survival in patients with CMB/LCA. All DMB/MBEN assessed by DNA methylation profiling belonged to the SHH-INF subgroup. Group 3 patients (5y-PFS, 36%; n = 14) relapsed more frequently than the SHH-INF group (5y-PFS, 93%; n = 28) or group 4 patients (5y-PFS, 83%; n = 6; P < .001). SHH-INF split into iSHH-I and iSHH-II subtypes in HIT-2000-BIS4 and the validation cohort, without prognostic impact (5y-PFS: iSHH-I, 73%, v iSHH-II, 83%; P = .25; n = 99). Intelligence quotient (IQ) was significantly lower in patients after CSI (mean IQ, 90 [no radiotherapy], v 74 [CSI]; P = .012).CONCLUSIONSystemic chemotherapy and intraventricular methotrexate led to favorable survival in both iSHH subtypes of SHH-activated DMB/MBEN with acceptable neurotoxicity. Survival in patients with non-wingless (WNT)/non-SHH disease with CMB/LCA was not improved by local radiotherapy. Patients with group 4 disease had more favorable survival rates than those with group 3 medulloblastoma.</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Hoff, Katja von</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(DE-588)1027430309</subfield><subfield code="0">(DE-627)729136205</subfield><subfield code="0">(DE-576)373215975</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Pietsch, Torsten</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Ottensmeier, Holger</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Warmuth-Metz, Monika</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(DE-588)1158886195</subfield><subfield code="0">(DE-627)102109854X</subfield><subfield code="0">(DE-576)504508334</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Bison, Brigitte</subfield><subfield code="d">1964-</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(DE-588)120166445</subfield><subfield code="0">(DE-627)696438410</subfield><subfield code="0">(DE-576)292074913</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Pfister, Stefan</subfield><subfield code="d">1974-</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(DE-588)123850215</subfield><subfield code="0">(DE-627)706450930</subfield><subfield code="0">(DE-576)293908400</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Korshunov, Andrey</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(DE-588)1043235361</subfield><subfield code="0">(DE-627)770439365</subfield><subfield code="0">(DE-576)394592093</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Sharma, Tanvi</subfield><subfield code="d">1993-</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(DE-588)1203560273</subfield><subfield code="0">(DE-627)1688534954</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Jäger, Natalie</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(DE-588)1057941662</subfield><subfield code="0">(DE-627)795556195</subfield><subfield code="0">(DE-576)413944638</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Ryzhova, Marina</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(DE-588)1211521982</subfield><subfield code="0">(DE-627)169981130X</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Zheludkova, Olga</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Golanov, Andrey</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Rushing, Elisabeth Jane</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(DE-588)1195088582</subfield><subfield code="0">(DE-627)1677273801</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Hasselblatt, Martin</subfield><subfield code="d">1969-</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(DE-588)123559014</subfield><subfield code="0">(DE-627)082628998</subfield><subfield code="0">(DE-576)293765537</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Koch, Arend Wolfgang</subfield><subfield code="d">1972-</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(DE-588)122734432</subfield><subfield code="0">(DE-627)082122393</subfield><subfield code="0">(DE-576)293398879</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Schüller, Ulrich</subfield><subfield code="d">1976-</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(DE-588)124391257</subfield><subfield code="0">(DE-627)363315063</subfield><subfield code="0">(DE-576)294150757</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Deimling, Andreas von</subfield><subfield code="d">1959-</subfield><subfield code="e">verfasserin</subfield><subfield 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Clemens</subfield><subfield code="d">1964-</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(DE-588)1070862185</subfield><subfield code="0">(DE-627)824644514</subfield><subfield code="0">(DE-576)432763996</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Staszewski, Ori</subfield><subfield code="d">1979-</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(DE-588)132624729</subfield><subfield code="0">(DE-627)524703043</subfield><subfield code="0">(DE-576)299264432</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Mawrin, Christian</subfield><subfield code="d">1972-</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(DE-588)122598504</subfield><subfield code="0">(DE-627)082040826</subfield><subfield code="0">(DE-576)293342687</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" 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Paul-Gerhardt</subfield><subfield code="d">1958-</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(DE-588)1145636764</subfield><subfield code="0">(DE-627)100683527X</subfield><subfield code="0">(DE-576)166078581</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Deinlein, Frank</subfield><subfield code="d">1964-</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(DE-588)122378725</subfield><subfield code="0">(DE-627)08190908X</subfield><subfield code="0">(DE-576)293245010</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Bueren, André von</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(DE-588)1027425445</subfield><subfield code="0">(DE-627)729125017</subfield><subfield code="0">(DE-576)373208502</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield 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