Imaging Biomarkers for Adult Medulloblastomas

Genetic Entities May Be Identified by Their MR Imaging Radiophenotype

V C Keil, M Warmuth-Metz, C Reh, S J Enkirch, C Reinert, D Beier, D T W Jones, T Pietsch, H H Schild, E Hattingen, P Hau

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Abstract

BACKGROUND AND PURPOSE: The occurrence of medulloblastomas in adults is rare; nevertheless, these tumors can be subdivided into genetic and histologic entities each having distinct prognoses. This study aimed to identify MR imaging biomarkers to classify these entities and to uncover differences in MR imaging biomarkers identified in pediatric medulloblastomas.

MATERIALS AND METHODS: Eligible preoperative MRIs from 28 patients (11 women; 22-53 years of age) of the Multicenter Pilot-study for the Therapy of Medulloblastoma of Adults (NOA-7) cohort were assessed by 3 experienced neuroradiologists. Lesions and perifocal edema were volumetrized and multiparametrically evaluated for classic morphologic characteristics, location, hydrocephalus, and Chang criteria. To identify MR imaging biomarkers, we correlated genetic entities sonic hedgehog (SHH) TP53 wild type, wingless (WNT), and non-WNT/non-SHH medulloblastomas (in adults, Group 4), and histologic entities were correlated with the imaging criteria. These MR imaging biomarkers were compared with corresponding data from a pediatric study.

RESULTS: There were 19 SHH TP53 wild type (69%), 4 WNT-activated (14%), and 5 Group 4 (17%) medulloblastomas. Six potential MR imaging biomarkers were identified, 3 of which, hydrocephalus (P = .03), intraventricular macrometastases (P = .02), and hemorrhage (P = .04), when combined, could identify WNT medulloblastoma with 100% sensitivity and 88.3% specificity (95% CI, 39.8%-100.0% and 62.6%-95.3%). WNT-activated nuclear β-catenin accumulating medulloblastomas were smaller than the other entities (95% CI, 5.2-22.3 cm(3) versus 35.1-47.6 cm(3); P = .03). Hemorrhage was exclusively present in non-WNT/non-SHH medulloblastomas (P = .04; n = 2/5). MR imaging biomarkers were all discordant from those identified in the pediatric cohort. Desmoplastic/nodular medulloblastomas were more rarely in contact with the fourth ventricle (4/15 versus 7/13; P = .04).

CONCLUSIONS: MR imaging biomarkers can help distinguish histologic and genetic medulloblastoma entities in adults and appear to be different from those identified in children.

Original languageEnglish
JournalAmerican Journal of Neuroradiology
Volume38
Issue number10
Pages (from-to)1892-1898
ISSN0195-6108
DOIs
Publication statusPublished - 2017

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Medulloblastoma
Pediatrics
Fourth Ventricle
Multicenter Studies

Keywords

  • Journal Article

Cite this

Keil, V C ; Warmuth-Metz, M ; Reh, C ; Enkirch, S J ; Reinert, C ; Beier, D ; Jones, D T W ; Pietsch, T ; Schild, H H ; Hattingen, E ; Hau, P. / Imaging Biomarkers for Adult Medulloblastomas : Genetic Entities May Be Identified by Their MR Imaging Radiophenotype. In: American Journal of Neuroradiology. 2017 ; Vol. 38, No. 10. pp. 1892-1898.
@article{b95ce736e7a648c7833da59636668911,
title = "Imaging Biomarkers for Adult Medulloblastomas: Genetic Entities May Be Identified by Their MR Imaging Radiophenotype",
abstract = "BACKGROUND AND PURPOSE: The occurrence of medulloblastomas in adults is rare; nevertheless, these tumors can be subdivided into genetic and histologic entities each having distinct prognoses. This study aimed to identify MR imaging biomarkers to classify these entities and to uncover differences in MR imaging biomarkers identified in pediatric medulloblastomas.MATERIALS AND METHODS: Eligible preoperative MRIs from 28 patients (11 women; 22-53 years of age) of the Multicenter Pilot-study for the Therapy of Medulloblastoma of Adults (NOA-7) cohort were assessed by 3 experienced neuroradiologists. Lesions and perifocal edema were volumetrized and multiparametrically evaluated for classic morphologic characteristics, location, hydrocephalus, and Chang criteria. To identify MR imaging biomarkers, we correlated genetic entities sonic hedgehog (SHH) TP53 wild type, wingless (WNT), and non-WNT/non-SHH medulloblastomas (in adults, Group 4), and histologic entities were correlated with the imaging criteria. These MR imaging biomarkers were compared with corresponding data from a pediatric study.RESULTS: There were 19 SHH TP53 wild type (69{\%}), 4 WNT-activated (14{\%}), and 5 Group 4 (17{\%}) medulloblastomas. Six potential MR imaging biomarkers were identified, 3 of which, hydrocephalus (P = .03), intraventricular macrometastases (P = .02), and hemorrhage (P = .04), when combined, could identify WNT medulloblastoma with 100{\%} sensitivity and 88.3{\%} specificity (95{\%} CI, 39.8{\%}-100.0{\%} and 62.6{\%}-95.3{\%}). WNT-activated nuclear β-catenin accumulating medulloblastomas were smaller than the other entities (95{\%} CI, 5.2-22.3 cm(3) versus 35.1-47.6 cm(3); P = .03). Hemorrhage was exclusively present in non-WNT/non-SHH medulloblastomas (P = .04; n = 2/5). MR imaging biomarkers were all discordant from those identified in the pediatric cohort. Desmoplastic/nodular medulloblastomas were more rarely in contact with the fourth ventricle (4/15 versus 7/13; P = .04).CONCLUSIONS: MR imaging biomarkers can help distinguish histologic and genetic medulloblastoma entities in adults and appear to be different from those identified in children.",
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Keil, VC, Warmuth-Metz, M, Reh, C, Enkirch, SJ, Reinert, C, Beier, D, Jones, DTW, Pietsch, T, Schild, HH, Hattingen, E & Hau, P 2017, 'Imaging Biomarkers for Adult Medulloblastomas: Genetic Entities May Be Identified by Their MR Imaging Radiophenotype', American Journal of Neuroradiology, vol. 38, no. 10, pp. 1892-1898. https://doi.org/10.3174/ajnr.A5313

Imaging Biomarkers for Adult Medulloblastomas : Genetic Entities May Be Identified by Their MR Imaging Radiophenotype. / Keil, V C; Warmuth-Metz, M; Reh, C; Enkirch, S J; Reinert, C; Beier, D; Jones, D T W; Pietsch, T; Schild, H H; Hattingen, E; Hau, P.

In: American Journal of Neuroradiology, Vol. 38, No. 10, 2017, p. 1892-1898.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Imaging Biomarkers for Adult Medulloblastomas

T2 - Genetic Entities May Be Identified by Their MR Imaging Radiophenotype

AU - Keil, V C

AU - Warmuth-Metz, M

AU - Reh, C

AU - Enkirch, S J

AU - Reinert, C

AU - Beier, D

AU - Jones, D T W

AU - Pietsch, T

AU - Schild, H H

AU - Hattingen, E

AU - Hau, P

N1 - © 2017 American Society of Neuroradiology.

PY - 2017

Y1 - 2017

N2 - BACKGROUND AND PURPOSE: The occurrence of medulloblastomas in adults is rare; nevertheless, these tumors can be subdivided into genetic and histologic entities each having distinct prognoses. This study aimed to identify MR imaging biomarkers to classify these entities and to uncover differences in MR imaging biomarkers identified in pediatric medulloblastomas.MATERIALS AND METHODS: Eligible preoperative MRIs from 28 patients (11 women; 22-53 years of age) of the Multicenter Pilot-study for the Therapy of Medulloblastoma of Adults (NOA-7) cohort were assessed by 3 experienced neuroradiologists. Lesions and perifocal edema were volumetrized and multiparametrically evaluated for classic morphologic characteristics, location, hydrocephalus, and Chang criteria. To identify MR imaging biomarkers, we correlated genetic entities sonic hedgehog (SHH) TP53 wild type, wingless (WNT), and non-WNT/non-SHH medulloblastomas (in adults, Group 4), and histologic entities were correlated with the imaging criteria. These MR imaging biomarkers were compared with corresponding data from a pediatric study.RESULTS: There were 19 SHH TP53 wild type (69%), 4 WNT-activated (14%), and 5 Group 4 (17%) medulloblastomas. Six potential MR imaging biomarkers were identified, 3 of which, hydrocephalus (P = .03), intraventricular macrometastases (P = .02), and hemorrhage (P = .04), when combined, could identify WNT medulloblastoma with 100% sensitivity and 88.3% specificity (95% CI, 39.8%-100.0% and 62.6%-95.3%). WNT-activated nuclear β-catenin accumulating medulloblastomas were smaller than the other entities (95% CI, 5.2-22.3 cm(3) versus 35.1-47.6 cm(3); P = .03). Hemorrhage was exclusively present in non-WNT/non-SHH medulloblastomas (P = .04; n = 2/5). MR imaging biomarkers were all discordant from those identified in the pediatric cohort. Desmoplastic/nodular medulloblastomas were more rarely in contact with the fourth ventricle (4/15 versus 7/13; P = .04).CONCLUSIONS: MR imaging biomarkers can help distinguish histologic and genetic medulloblastoma entities in adults and appear to be different from those identified in children.

AB - BACKGROUND AND PURPOSE: The occurrence of medulloblastomas in adults is rare; nevertheless, these tumors can be subdivided into genetic and histologic entities each having distinct prognoses. This study aimed to identify MR imaging biomarkers to classify these entities and to uncover differences in MR imaging biomarkers identified in pediatric medulloblastomas.MATERIALS AND METHODS: Eligible preoperative MRIs from 28 patients (11 women; 22-53 years of age) of the Multicenter Pilot-study for the Therapy of Medulloblastoma of Adults (NOA-7) cohort were assessed by 3 experienced neuroradiologists. Lesions and perifocal edema were volumetrized and multiparametrically evaluated for classic morphologic characteristics, location, hydrocephalus, and Chang criteria. To identify MR imaging biomarkers, we correlated genetic entities sonic hedgehog (SHH) TP53 wild type, wingless (WNT), and non-WNT/non-SHH medulloblastomas (in adults, Group 4), and histologic entities were correlated with the imaging criteria. These MR imaging biomarkers were compared with corresponding data from a pediatric study.RESULTS: There were 19 SHH TP53 wild type (69%), 4 WNT-activated (14%), and 5 Group 4 (17%) medulloblastomas. Six potential MR imaging biomarkers were identified, 3 of which, hydrocephalus (P = .03), intraventricular macrometastases (P = .02), and hemorrhage (P = .04), when combined, could identify WNT medulloblastoma with 100% sensitivity and 88.3% specificity (95% CI, 39.8%-100.0% and 62.6%-95.3%). WNT-activated nuclear β-catenin accumulating medulloblastomas were smaller than the other entities (95% CI, 5.2-22.3 cm(3) versus 35.1-47.6 cm(3); P = .03). Hemorrhage was exclusively present in non-WNT/non-SHH medulloblastomas (P = .04; n = 2/5). MR imaging biomarkers were all discordant from those identified in the pediatric cohort. Desmoplastic/nodular medulloblastomas were more rarely in contact with the fourth ventricle (4/15 versus 7/13; P = .04).CONCLUSIONS: MR imaging biomarkers can help distinguish histologic and genetic medulloblastoma entities in adults and appear to be different from those identified in children.

KW - Journal Article

U2 - 10.3174/ajnr.A5313

DO - 10.3174/ajnr.A5313

M3 - Journal article

VL - 38

SP - 1892

EP - 1898

JO - American Journal of Neuroradiology

JF - American Journal of Neuroradiology

SN - 0195-6108

IS - 10

ER -