Expression-based intrinsic glioma subtypes are prognostic in low-grade gliomas of the EORTC22033-26033 clinical trial

Y. Gao; B. Weenink; M. J. van den Bent; L. Erdem-Eraslan; J. M. Kros; P. A. E. Sillevis Smitt; K. Hoang-Xuan; A. A. Brandes; M. Vos; F. Dhermain; R. Enting; G. F. Ryan; O. Chinot; M. Ben Hassel; M. E. van Linde; W. P. Mason; J. M. M. Gijtenbeek; C. Balana; A. von Deimling; Th Gorlia; R. Stupp; M. E. Hegi; B. G. Baumert; P. J. French

doi:10.1016/j.ejca.2018.02.023

Publication

Expression-based intrinsic glioma subtypes are prognostic in low-grade gliomas of the EORTC22033-26033 clinical trial

Gao, Y., Weenink, B., van den Bent, M. J., Erdem-Eraslan, L., Kros, J. M., Smitt, P. A. E. S., Hoang-Xuan, K., Brandes, A. A., Vos, M., Dhermain, F., Enting, R., Ryan, G. F., Chinot, O., Ben Hassel, M., van Linde, M. E., Mason, W. P., Gijtenbeek, J. M. M., Balana, C., von Deimling, A., Gorlia, T., Stupp, R., Hegi, M. E., Baumert, B. G. & French, P. J., May-2018, In : European Journal of Cancer. 94, p. 168-178 11 p.

Research output: Contribution to journal › Article › Academic › peer-review

APA

Gao, Y., Weenink, B., van den Bent, M. J., Erdem-Eraslan, L., Kros, J. M., Smitt, P. A. E. S., Hoang-Xuan, K., Brandes, A. A., Vos, M., Dhermain, F., Enting, R., Ryan, G. F., Chinot, O., Ben Hassel, M., van Linde, M. E., Mason, W. P., Gijtenbeek, J. M. M., Balana, C., von Deimling, A., ... French, P. J. (2018). Expression-based intrinsic glioma subtypes are prognostic in low-grade gliomas of the EORTC22033-26033 clinical trial. European Journal of Cancer, 94, 168-178. https://doi.org/10.1016/j.ejca.2018.02.023

Author

Gao, Y. ; Weenink, B. ; van den Bent, M. J. ; Erdem-Eraslan, L. ; Kros, J. M. ; Smitt, P. A. E. Sillevis ; Hoang-Xuan, K. ; Brandes, A. A. ; Vos, M. ; Dhermain, F. ; Enting, R. ; Ryan, G. F. ; Chinot, O. ; Ben Hassel, M. ; van Linde, M. E. ; Mason, W. P. ; Gijtenbeek, J. M. M. ; Balana, C. ; von Deimling, A. ; Gorlia, Th ; Stupp, R. ; Hegi, M. E. ; Baumert, B. G. ; French, P. J. / Expression-based intrinsic glioma subtypes are prognostic in low-grade gliomas of the EORTC22033-26033 clinical trial. In: European Journal of Cancer. 2018 ; Vol. 94. pp. 168-178.

Harvard

Gao, Y, Weenink, B, van den Bent, MJ, Erdem-Eraslan, L, Kros, JM, Smitt, PAES, Hoang-Xuan, K, Brandes, AA, Vos, M, Dhermain, F, Enting, R, Ryan, GF, Chinot, O, Ben Hassel, M, van Linde, ME, Mason, WP, Gijtenbeek, JMM, Balana, C, von Deimling, A, Gorlia, T, Stupp, R, Hegi, ME, Baumert, BG & French, PJ 2018, 'Expression-based intrinsic glioma subtypes are prognostic in low-grade gliomas of the EORTC22033-26033 clinical trial', European Journal of Cancer, vol. 94, pp. 168-178. https://doi.org/10.1016/j.ejca.2018.02.023

Standard

Expression-based intrinsic glioma subtypes are prognostic in low-grade gliomas of the EORTC22033-26033 clinical trial. / Gao, Y.; Weenink, B.; van den Bent, M. J.; Erdem-Eraslan, L.; Kros, J. M.; Smitt, P. A. E. Sillevis; Hoang-Xuan, K.; Brandes, A. A.; Vos, M.; Dhermain, F.; Enting, R.; Ryan, G. F.; Chinot, O.; Ben Hassel, M.; van Linde, M. E.; Mason, W. P.; Gijtenbeek, J. M. M.; Balana, C.; von Deimling, A.; Gorlia, Th; Stupp, R.; Hegi, M. E.; Baumert, B. G.; French, P. J.

In: European Journal of Cancer, Vol. 94, 05.2018, p. 168-178.

Research output: Contribution to journal › Article › Academic › peer-review

Vancouver

Gao Y, Weenink B, van den Bent MJ, Erdem-Eraslan L, Kros JM, Smitt PAES et al. Expression-based intrinsic glioma subtypes are prognostic in low-grade gliomas of the EORTC22033-26033 clinical trial. European Journal of Cancer. 2018 May;94:168-178. https://doi.org/10.1016/j.ejca.2018.02.023

BibTeX

@article{c151c30a4dc14d0cb979e8f8e8027efd,

title = "Expression-based intrinsic glioma subtypes are prognostic in low-grade gliomas of the EORTC22033-26033 clinical trial",

abstract = "Introduction: The European Organisation for Research and Treatment of Cancer (EORTC) 22033-26033 clinical trial (NCT00182819) investigated whether initial temozolomide (TMZ) chemotherapy confers survival advantage compared with radiotherapy (RT) in low-grade glioma (LGG) patients. In this study, we performed gene expression profiling on tissues from this trial to identify markers associated with progression-free survival (PFS) and treatment response.Methods: Gene expression profiling, performed on 195 samples, was used to assign tumours to one of six intrinsic glioma subtypes (IGSs; molecularly similar tumours as previously defined using unsupervised expression analysis) and to determine the composition of immune infiltrate. DNA copy number changes were determined using OncoScan arrays.Results: We confirm that IGSs are prognostic in the EORTC22033-26033 clinical trial. Specific genetic changes segregate in distinct IGSs: most samples assigned to IGS-9 have IDH-mutations and 1p19q codeletion, samples assigned to IGS-17 have IDH-mutations without 1p19q codeletion and samples assigned to other intrinsic subtypes often are IDH-wildtype. A trend towards benefit from RT was observed for samples assigned to IGS-9 (hazard ratio [HR] for TMZ is 1.90, P = 0.065) but not for samples assigned to IGS-17 (HR 0.87, P = 0.62). We did not identify genes significantly associated with PFS within intrinsic subtypes, although followup time is limited. We also show that LGGs and glioblastomas differ in their immune infiltrate, which suggests that LGGs are less amenable to checkpoint inhibitoretype immune therapies. Gene expression analysis also allows identification of relatively rare subtypes. Indeed, one patient with a pilocytic astrocytoma was identified.Conclusion: IGSs are prognostic for PFS in EORTC22033-26033 clinical trial samples. (C) 2018 Elsevier Ltd. All rights reserved.",

keywords = "Low grade glioma, Intrinsic subtype, Pilocytic astrocytoma, Gene expression profiling, Immunophenotype, BELOB, OLIGODENDROGLIAL BRAIN-TUMORS, CENTRAL-NERVOUS-SYSTEM, PHASE-III TRIAL, RANDOMIZED-TRIAL, VINCRISTINE CHEMOTHERAPY, PILOCYTIC ASTROCYTOMAS, ADJUVANT PROCARBAZINE, RADIATION-THERAPY, EORTC 22033-26033, MGMT METHYLATION",

author = "Y. Gao and B. Weenink and {van den Bent}, {M. J.} and L. Erdem-Eraslan and Kros, {J. M.} and Smitt, {P. A. E. Sillevis} and K. Hoang-Xuan and Brandes, {A. A.} and M. Vos and F. Dhermain and R. Enting and Ryan, {G. F.} and O. Chinot and {Ben Hassel}, M. and {van Linde}, {M. E.} and Mason, {W. P.} and Gijtenbeek, {J. M. M.} and C. Balana and {von Deimling}, A. and Th Gorlia and R. Stupp and Hegi, {M. E.} and Baumert, {B. G.} and French, {P. J.}",

year = "2018",

month = may,

doi = "10.1016/j.ejca.2018.02.023",

language = "English",

volume = "94",

pages = "168--178",

journal = "European Journal of Cancer",

issn = "0959-8049",

publisher = "ELSEVIER SCI LTD",

}

RIS

TY - JOUR

T1 - Expression-based intrinsic glioma subtypes are prognostic in low-grade gliomas of the EORTC22033-26033 clinical trial

AU - Gao, Y.

AU - Weenink, B.

AU - van den Bent, M. J.

AU - Erdem-Eraslan, L.

AU - Kros, J. M.

AU - Smitt, P. A. E. Sillevis

AU - Hoang-Xuan, K.

AU - Brandes, A. A.

AU - Vos, M.

AU - Dhermain, F.

AU - Enting, R.

AU - Ryan, G. F.

AU - Chinot, O.

AU - Ben Hassel, M.

AU - van Linde, M. E.

AU - Mason, W. P.

AU - Gijtenbeek, J. M. M.

AU - Balana, C.

AU - von Deimling, A.

AU - Gorlia, Th

AU - Stupp, R.

AU - Hegi, M. E.

AU - Baumert, B. G.

AU - French, P. J.

PY - 2018/5

Y1 - 2018/5

N2 - Introduction: The European Organisation for Research and Treatment of Cancer (EORTC) 22033-26033 clinical trial (NCT00182819) investigated whether initial temozolomide (TMZ) chemotherapy confers survival advantage compared with radiotherapy (RT) in low-grade glioma (LGG) patients. In this study, we performed gene expression profiling on tissues from this trial to identify markers associated with progression-free survival (PFS) and treatment response.Methods: Gene expression profiling, performed on 195 samples, was used to assign tumours to one of six intrinsic glioma subtypes (IGSs; molecularly similar tumours as previously defined using unsupervised expression analysis) and to determine the composition of immune infiltrate. DNA copy number changes were determined using OncoScan arrays.Results: We confirm that IGSs are prognostic in the EORTC22033-26033 clinical trial. Specific genetic changes segregate in distinct IGSs: most samples assigned to IGS-9 have IDH-mutations and 1p19q codeletion, samples assigned to IGS-17 have IDH-mutations without 1p19q codeletion and samples assigned to other intrinsic subtypes often are IDH-wildtype. A trend towards benefit from RT was observed for samples assigned to IGS-9 (hazard ratio [HR] for TMZ is 1.90, P = 0.065) but not for samples assigned to IGS-17 (HR 0.87, P = 0.62). We did not identify genes significantly associated with PFS within intrinsic subtypes, although followup time is limited. We also show that LGGs and glioblastomas differ in their immune infiltrate, which suggests that LGGs are less amenable to checkpoint inhibitoretype immune therapies. Gene expression analysis also allows identification of relatively rare subtypes. Indeed, one patient with a pilocytic astrocytoma was identified.Conclusion: IGSs are prognostic for PFS in EORTC22033-26033 clinical trial samples. (C) 2018 Elsevier Ltd. All rights reserved.

AB - Introduction: The European Organisation for Research and Treatment of Cancer (EORTC) 22033-26033 clinical trial (NCT00182819) investigated whether initial temozolomide (TMZ) chemotherapy confers survival advantage compared with radiotherapy (RT) in low-grade glioma (LGG) patients. In this study, we performed gene expression profiling on tissues from this trial to identify markers associated with progression-free survival (PFS) and treatment response.Methods: Gene expression profiling, performed on 195 samples, was used to assign tumours to one of six intrinsic glioma subtypes (IGSs; molecularly similar tumours as previously defined using unsupervised expression analysis) and to determine the composition of immune infiltrate. DNA copy number changes were determined using OncoScan arrays.Results: We confirm that IGSs are prognostic in the EORTC22033-26033 clinical trial. Specific genetic changes segregate in distinct IGSs: most samples assigned to IGS-9 have IDH-mutations and 1p19q codeletion, samples assigned to IGS-17 have IDH-mutations without 1p19q codeletion and samples assigned to other intrinsic subtypes often are IDH-wildtype. A trend towards benefit from RT was observed for samples assigned to IGS-9 (hazard ratio [HR] for TMZ is 1.90, P = 0.065) but not for samples assigned to IGS-17 (HR 0.87, P = 0.62). We did not identify genes significantly associated with PFS within intrinsic subtypes, although followup time is limited. We also show that LGGs and glioblastomas differ in their immune infiltrate, which suggests that LGGs are less amenable to checkpoint inhibitoretype immune therapies. Gene expression analysis also allows identification of relatively rare subtypes. Indeed, one patient with a pilocytic astrocytoma was identified.Conclusion: IGSs are prognostic for PFS in EORTC22033-26033 clinical trial samples. (C) 2018 Elsevier Ltd. All rights reserved.

KW - Low grade glioma

KW - Intrinsic subtype

KW - Pilocytic astrocytoma

KW - Gene expression profiling

KW - Immunophenotype

KW - BELOB

KW - OLIGODENDROGLIAL BRAIN-TUMORS

KW - CENTRAL-NERVOUS-SYSTEM

KW - PHASE-III TRIAL

KW - RANDOMIZED-TRIAL

KW - VINCRISTINE CHEMOTHERAPY

KW - PILOCYTIC ASTROCYTOMAS

KW - ADJUVANT PROCARBAZINE

KW - RADIATION-THERAPY

KW - EORTC 22033-26033

KW - MGMT METHYLATION

U2 - 10.1016/j.ejca.2018.02.023

DO - 10.1016/j.ejca.2018.02.023

M3 - Article

VL - 94

SP - 168

EP - 178

JO - European Journal of Cancer

JF - European Journal of Cancer

SN - 0959-8049

ER -

ID: 65349695

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