Association of pre-radiotherapy tumour burden and overall survival in newly diagnosed glioblastoma adjusted for MGMT promoter methylation status

A. Alafandi; K. A. van Garderen; S. Klein; S. R. van der Voort; D. Rizopoulos; L. Nabors; R. Stupp; M. Weller; T. Gorlia; J. C. Tonn; M. Smits

doi:10.1016/j.ejca.2023.04.021

Association of pre-radiotherapy tumour burden and overall survival in newly diagnosed glioblastoma adjusted for MGMT promoter methylation status

A. Alafandi, K. A. van Garderen, S. Klein, S. R. van der Voort, D. Rizopoulos, L. Nabors, R. Stupp, M. Weller, T. Gorlia, J. C. Tonn, M. Smits^*

^*Corresponding author for this work

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

Abstract

Purpose: We retrospectively evaluated the association between postoperative pre-radiotherapy tumour burden and overall survival (OS) adjusted for the prognostic value of O⁶-methylguanine DNA methyltransferase (MGMT) promoter methylation in patients with newly diagnosed glioblastoma treated with radio-/chemotherapy with temozolomide. Materials and methods: Patients were included from the CENTRIC (EORTC 26071-22072) and CORE trials if postoperative magnetic resonance imaging scans were available within a timeframe of up to 4 weeks before radiotherapy, including both pre- and post-contrast T1w images and at least one T2w sequence (T2w or T2w-FLAIR). Postoperative (residual) pre-radiotherapy contrast-enhanced tumour (CET) volumes and non-enhanced T2w abnormalities (NT2A) tissue volumes were obtained by three-dimensional segmentation. Cox proportional hazard models and Kaplan Meier estimates were used to assess the association of pre-radiotherapy CET/NT2A volume with OS adjusted for known prognostic factors (age, performance status, MGMT status). Results: 408 tumour (of which 270 MGMT methylated) segmentations were included. Median OS in patients with MGMT methylated tumours was 117 weeks versus 61 weeks in MGMT unmethylated tumours (p < 0.001). When stratified for MGMT methylation status, higher CET volume (HR 1.020; 95% confidence interval CI [1.013–1.027]; p < 0.001) and older age (HR 1.664; 95% CI [1.214–2.281]; p = 0.002) were significantly associated with shorter OS while NT2A volume and performance status were not. Conclusion: Pre-radiotherapy CET volume was strongly associated with OS in patients receiving radio-/chemotherapy for newly diagnosed glioblastoma stratified by MGMT promoter methylation status.

Original language	English
Pages (from-to)	122-130
Number of pages	9
Journal	European Journal of Cancer
Volume	188
DOIs	https://doi.org/10.1016/j.ejca.2023.04.021
Publication status	Published - Jul 2023

Bibliographical note

Funding Information:
This study was funded by Medical Delta , KWF-EMCR-2017-11026 , Hestia -VidW-1154-20-025 . The funding source had no involvement in this study.

Publisher Copyright: © 2023 The Authors

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Alafandi, A., van Garderen, K. A., Klein, S., van der Voort, S. R., Rizopoulos, D., Nabors, L., Stupp, R., Weller, M., Gorlia, T., Tonn, J. C., & Smits, M. (2023). Association of pre-radiotherapy tumour burden and overall survival in newly diagnosed glioblastoma adjusted for MGMT promoter methylation status. European Journal of Cancer, 188, 122-130. https://doi.org/10.1016/j.ejca.2023.04.021

@article{2a2410f952d642ccbec112aefff5a491,

title = "Association of pre-radiotherapy tumour burden and overall survival in newly diagnosed glioblastoma adjusted for MGMT promoter methylation status",

abstract = "Purpose: We retrospectively evaluated the association between postoperative pre-radiotherapy tumour burden and overall survival (OS) adjusted for the prognostic value of O6-methylguanine DNA methyltransferase (MGMT) promoter methylation in patients with newly diagnosed glioblastoma treated with radio-/chemotherapy with temozolomide. Materials and methods: Patients were included from the CENTRIC (EORTC 26071-22072) and CORE trials if postoperative magnetic resonance imaging scans were available within a timeframe of up to 4 weeks before radiotherapy, including both pre- and post-contrast T1w images and at least one T2w sequence (T2w or T2w-FLAIR). Postoperative (residual) pre-radiotherapy contrast-enhanced tumour (CET) volumes and non-enhanced T2w abnormalities (NT2A) tissue volumes were obtained by three-dimensional segmentation. Cox proportional hazard models and Kaplan Meier estimates were used to assess the association of pre-radiotherapy CET/NT2A volume with OS adjusted for known prognostic factors (age, performance status, MGMT status). Results: 408 tumour (of which 270 MGMT methylated) segmentations were included. Median OS in patients with MGMT methylated tumours was 117 weeks versus 61 weeks in MGMT unmethylated tumours (p < 0.001). When stratified for MGMT methylation status, higher CET volume (HR 1.020; 95% confidence interval CI [1.013–1.027]; p < 0.001) and older age (HR 1.664; 95% CI [1.214–2.281]; p = 0.002) were significantly associated with shorter OS while NT2A volume and performance status were not. Conclusion: Pre-radiotherapy CET volume was strongly associated with OS in patients receiving radio-/chemotherapy for newly diagnosed glioblastoma stratified by MGMT promoter methylation status.",

author = "A. Alafandi and {van Garderen}, {K. A.} and S. Klein and {van der Voort}, {S. R.} and D. Rizopoulos and L. Nabors and R. Stupp and M. Weller and T. Gorlia and Tonn, {J. C.} and M. Smits",

note = "Funding Information: This study was funded by Medical Delta , KWF-EMCR-2017-11026 , Hestia -VidW-1154-20-025 . The funding source had no involvement in this study. Publisher Copyright: {\textcopyright} 2023 The Authors",

year = "2023",

month = jul,

doi = "10.1016/j.ejca.2023.04.021",

language = "English",

volume = "188",

pages = "122--130",

journal = "European Journal of Cancer",

issn = "0959-8049",

publisher = "Elsevier Ltd.",

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Alafandi, A , van Garderen, KA , Klein, S , van der Voort, SR , Rizopoulos, D, Nabors, L, Stupp, R, Weller, M, Gorlia, T, Tonn, JC & Smits, M 2023, 'Association of pre-radiotherapy tumour burden and overall survival in newly diagnosed glioblastoma adjusted for MGMT promoter methylation status', European Journal of Cancer, vol. 188, pp. 122-130. https://doi.org/10.1016/j.ejca.2023.04.021

TY - JOUR

T1 - Association of pre-radiotherapy tumour burden and overall survival in newly diagnosed glioblastoma adjusted for MGMT promoter methylation status

AU - Alafandi, A.

AU - van Garderen, K. A.

AU - Klein, S.

AU - van der Voort, S. R.

AU - Rizopoulos, D.

AU - Nabors, L.

AU - Stupp, R.

AU - Weller, M.

AU - Gorlia, T.

AU - Tonn, J. C.

AU - Smits, M.

N1 - Funding Information: This study was funded by Medical Delta , KWF-EMCR-2017-11026 , Hestia -VidW-1154-20-025 . The funding source had no involvement in this study. Publisher Copyright: © 2023 The Authors

PY - 2023/7

Y1 - 2023/7

N2 - Purpose: We retrospectively evaluated the association between postoperative pre-radiotherapy tumour burden and overall survival (OS) adjusted for the prognostic value of O6-methylguanine DNA methyltransferase (MGMT) promoter methylation in patients with newly diagnosed glioblastoma treated with radio-/chemotherapy with temozolomide. Materials and methods: Patients were included from the CENTRIC (EORTC 26071-22072) and CORE trials if postoperative magnetic resonance imaging scans were available within a timeframe of up to 4 weeks before radiotherapy, including both pre- and post-contrast T1w images and at least one T2w sequence (T2w or T2w-FLAIR). Postoperative (residual) pre-radiotherapy contrast-enhanced tumour (CET) volumes and non-enhanced T2w abnormalities (NT2A) tissue volumes were obtained by three-dimensional segmentation. Cox proportional hazard models and Kaplan Meier estimates were used to assess the association of pre-radiotherapy CET/NT2A volume with OS adjusted for known prognostic factors (age, performance status, MGMT status). Results: 408 tumour (of which 270 MGMT methylated) segmentations were included. Median OS in patients with MGMT methylated tumours was 117 weeks versus 61 weeks in MGMT unmethylated tumours (p < 0.001). When stratified for MGMT methylation status, higher CET volume (HR 1.020; 95% confidence interval CI [1.013–1.027]; p < 0.001) and older age (HR 1.664; 95% CI [1.214–2.281]; p = 0.002) were significantly associated with shorter OS while NT2A volume and performance status were not. Conclusion: Pre-radiotherapy CET volume was strongly associated with OS in patients receiving radio-/chemotherapy for newly diagnosed glioblastoma stratified by MGMT promoter methylation status.

AB - Purpose: We retrospectively evaluated the association between postoperative pre-radiotherapy tumour burden and overall survival (OS) adjusted for the prognostic value of O6-methylguanine DNA methyltransferase (MGMT) promoter methylation in patients with newly diagnosed glioblastoma treated with radio-/chemotherapy with temozolomide. Materials and methods: Patients were included from the CENTRIC (EORTC 26071-22072) and CORE trials if postoperative magnetic resonance imaging scans were available within a timeframe of up to 4 weeks before radiotherapy, including both pre- and post-contrast T1w images and at least one T2w sequence (T2w or T2w-FLAIR). Postoperative (residual) pre-radiotherapy contrast-enhanced tumour (CET) volumes and non-enhanced T2w abnormalities (NT2A) tissue volumes were obtained by three-dimensional segmentation. Cox proportional hazard models and Kaplan Meier estimates were used to assess the association of pre-radiotherapy CET/NT2A volume with OS adjusted for known prognostic factors (age, performance status, MGMT status). Results: 408 tumour (of which 270 MGMT methylated) segmentations were included. Median OS in patients with MGMT methylated tumours was 117 weeks versus 61 weeks in MGMT unmethylated tumours (p < 0.001). When stratified for MGMT methylation status, higher CET volume (HR 1.020; 95% confidence interval CI [1.013–1.027]; p < 0.001) and older age (HR 1.664; 95% CI [1.214–2.281]; p = 0.002) were significantly associated with shorter OS while NT2A volume and performance status were not. Conclusion: Pre-radiotherapy CET volume was strongly associated with OS in patients receiving radio-/chemotherapy for newly diagnosed glioblastoma stratified by MGMT promoter methylation status.

UR - http://www.scopus.com/inward/record.url?scp=85159809153&partnerID=8YFLogxK

U2 - 10.1016/j.ejca.2023.04.021

DO - 10.1016/j.ejca.2023.04.021

M3 - Article

AN - SCOPUS:85159809153

SN - 0959-8049

VL - 188

SP - 122

EP - 130

JO - European Journal of Cancer

JF - European Journal of Cancer

ER -

Association of pre-radiotherapy tumour burden and overall survival in newly diagnosed glioblastoma adjusted for MGMT promoter methylation status

Abstract

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