Research ExplorerPublicationsNonmetastatic Medulloblastoma of Early Childhood: Results Fr...

Nonmetastatic Medulloblastoma of Early Childhood: Results From the Prospective Clinical Trial HIT-2000 and An Extended Validation Cohort

Standard

Nonmetastatic Medulloblastoma of Early Childhood: Results From the Prospective Clinical Trial HIT-2000 and An Extended Validation Cohort. / Mynarek, Martin; von Hoff, Katja; Pietsch, Torsten; Ottensmeier, Holger; Warmuth-Metz, Monika; Bison, Brigitte; Pfister, Stefan; Korshunov, Andrey; Sharma, Tanvi; Jaeger, Natalie; Ryzhova, Marina; Zheludkova, Olga; Golanov, Andrey; Rushing, Elisabeth Jane; Hasselblatt, Martin; Koch, Arend; Schüller, Ulrich; von Deimling, Andreas; Sahm, Felix; Sill, Martin; Riemenschneider, Markus J; Dohmen, Hildegard; Monoranu, Camelia Maria; Sommer, Clemens; Staszewski, Ori; Mawrin, Christian; Schittenhelm, Jens; Brück, Wolfgang; Filipski, Katharina; Hartmann, Christian; Meinhardt, Matthias; Pietschmann, Klaus; Haberler, Christine; Slavc, Irene; Gerber, Nicolas U; Grotzer, Michael; Benesch, Martin; Schlegel, Paul Gerhardt; Deinlein, Frank; von Bueren, André O; Friedrich, Carsten; Juhnke, Björn-Ole; Obrecht, Denise; Fleischhack, Gudrun; Kwiecien, Robert; Faldum, Andreas; Kortmann, Rolf Dieter; Kool, Marcel; Rutkowski, Stefan.

In: J CLIN ONCOL, Vol. 38, No. 18, 20.06.2020, p. 2028-2040.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Mynarek, M, von Hoff, K, Pietsch, T, Ottensmeier, H, Warmuth-Metz, M, Bison, B, Pfister, S, Korshunov, A, Sharma, T, Jaeger, N, Ryzhova, M, Zheludkova, O, Golanov, A, Rushing, EJ, Hasselblatt, M, Koch, A, Schüller, U, von Deimling, A, Sahm, F, Sill, M, Riemenschneider, MJ, Dohmen, H, Monoranu, CM, Sommer, C, Staszewski, O, Mawrin, C, Schittenhelm, J, Brück, W, Filipski, K, Hartmann, C, Meinhardt, M, Pietschmann, K, Haberler, C, Slavc, I, Gerber, NU, Grotzer, M, Benesch, M, Schlegel, PG, Deinlein, F, von Bueren, AO, Friedrich, C, Juhnke, B-O, Obrecht, D, Fleischhack, G, Kwiecien, R, Faldum, A, Kortmann, RD, Kool, M & Rutkowski, S 2020, 'Nonmetastatic Medulloblastoma of Early Childhood: Results From the Prospective Clinical Trial HIT-2000 and An Extended Validation Cohort', J CLIN ONCOL, vol. 38, no. 18, pp. 2028-2040. https://doi.org/10.1200/JCO.19.03057

APA

Mynarek, M., von Hoff, K., Pietsch, T., Ottensmeier, H., Warmuth-Metz, M., Bison, B., Pfister, S., Korshunov, A., Sharma, T., Jaeger, N., Ryzhova, M., Zheludkova, O., Golanov, A., Rushing, E. J., Hasselblatt, M., Koch, A., Schüller, U., von Deimling, A., Sahm, F., ... Rutkowski, S. (2020). Nonmetastatic Medulloblastoma of Early Childhood: Results From the Prospective Clinical Trial HIT-2000 and An Extended Validation Cohort. J CLIN ONCOL, 38(18), 2028-2040. https://doi.org/10.1200/JCO.19.03057

Vancouver

Mynarek M, von Hoff K, Pietsch T, Ottensmeier H, Warmuth-Metz M, Bison B et al. Nonmetastatic Medulloblastoma of Early Childhood: Results From the Prospective Clinical Trial HIT-2000 and An Extended Validation Cohort. J CLIN ONCOL. 2020 Jun 20;38(18):2028-2040. https://doi.org/10.1200/JCO.19.03057

Bibtex

@article{6d909d8336474fc48934409278a7b1ff,
title = "Nonmetastatic Medulloblastoma of Early Childhood: Results From the Prospective Clinical Trial HIT-2000 and An Extended Validation Cohort",
abstract = "PURPOSE: The 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 METHODS: From 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.RESULTS: Five 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).CONCLUSION: Systemic 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.",
author = "Martin Mynarek and {von Hoff}, Katja and Torsten Pietsch and Holger Ottensmeier and Monika Warmuth-Metz and Brigitte Bison and Stefan Pfister and Andrey Korshunov and Tanvi Sharma and Natalie Jaeger and Marina Ryzhova and Olga Zheludkova and Andrey Golanov and Rushing, {Elisabeth Jane} and Martin Hasselblatt and Arend Koch and Ulrich Sch{\"u}ller and {von Deimling}, Andreas and Felix Sahm and Martin Sill and Riemenschneider, {Markus J} and Hildegard Dohmen and Monoranu, {Camelia Maria} and Clemens Sommer and Ori Staszewski and Christian Mawrin and Jens Schittenhelm and Wolfgang Br{\"u}ck and Katharina Filipski and Christian Hartmann and Matthias Meinhardt and Klaus Pietschmann and Christine Haberler and Irene Slavc and Gerber, {Nicolas U} and Michael Grotzer and Martin Benesch and Schlegel, {Paul Gerhardt} and Frank Deinlein and {von Bueren}, {Andr{\'e} O} and Carsten Friedrich and Bj{\"o}rn-Ole Juhnke and Denise Obrecht and Gudrun Fleischhack and Robert Kwiecien and Andreas Faldum and Kortmann, {Rolf Dieter} and Marcel Kool and Stefan Rutkowski",
year = "2020",
month = jun,
day = "20",
doi = "10.1200/JCO.19.03057",
language = "English",
volume = "38",
pages = "2028--2040",
journal = "J CLIN ONCOL",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "18",

}

RIS

TY - JOUR

T1 - Nonmetastatic Medulloblastoma of Early Childhood: Results From the Prospective Clinical Trial HIT-2000 and An Extended Validation Cohort

AU - Mynarek, Martin

AU - von Hoff, Katja

AU - Pietsch, Torsten

AU - Ottensmeier, Holger

AU - Warmuth-Metz, Monika

AU - Bison, Brigitte

AU - Pfister, Stefan

AU - Korshunov, Andrey

AU - Sharma, Tanvi

AU - Jaeger, Natalie

AU - Ryzhova, Marina

AU - Zheludkova, Olga

AU - Golanov, Andrey

AU - Rushing, Elisabeth Jane

AU - Hasselblatt, Martin

AU - Koch, Arend

AU - Schüller, Ulrich

AU - von Deimling, Andreas

AU - Sahm, Felix

AU - Sill, Martin

AU - Riemenschneider, Markus J

AU - Dohmen, Hildegard

AU - Monoranu, Camelia Maria

AU - Sommer, Clemens

AU - Staszewski, Ori

AU - Mawrin, Christian

AU - Schittenhelm, Jens

AU - Brück, Wolfgang

AU - Filipski, Katharina

AU - Hartmann, Christian

AU - Meinhardt, Matthias

AU - Pietschmann, Klaus

AU - Haberler, Christine

AU - Slavc, Irene

AU - Gerber, Nicolas U

AU - Grotzer, Michael

AU - Benesch, Martin

AU - Schlegel, Paul Gerhardt

AU - Deinlein, Frank

AU - von Bueren, André O

AU - Friedrich, Carsten

AU - Juhnke, Björn-Ole

AU - Obrecht, Denise

AU - Fleischhack, Gudrun

AU - Kwiecien, Robert

AU - Faldum, Andreas

AU - Kortmann, Rolf Dieter

AU - Kool, Marcel

AU - Rutkowski, Stefan

PY - 2020/6/20

Y1 - 2020/6/20

N2 - PURPOSE: The 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 METHODS: From 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.RESULTS: Five 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).CONCLUSION: Systemic 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.

AB - PURPOSE: The 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 METHODS: From 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.RESULTS: Five 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).CONCLUSION: Systemic 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.

U2 - 10.1200/JCO.19.03057

DO - 10.1200/JCO.19.03057

M3 - SCORING: Journal article

C2 - 32330099

VL - 38

SP - 2028

EP - 2040

JO - J CLIN ONCOL

JF - J CLIN ONCOL

SN - 0732-183X

IS - 18

ER -