Validation of postoperative residual contrast-enhancing tumor volume as an independent prognostic factor for overall survival in newly diagnosed glioblastoma

Benjamin M. Ellingson, Lauren E. Abrey, Sarah J. Nelson, Timothy J Kaufmann, Josep Garcia, Olivier Chinot, Frank Saran, Ryo Nishikawa, Roger Henriksson, Warren P. Mason, Wolfgang Wick, Nicholas Butowski, Keith L. Ligon, Elizabeth R. Gerstner, Howard Colman, John De Groot, Susan Chang, Ingo Mellinghoff, Robert J. Young, Brian M. AlexanderRivka Colen, Jennie W. Taylor, Isabel Arrillaga-Romany, Arnav Mehta, Raymond Y. Huang, Whitney B. Pope, David Reardon, Tracy Batchelor, Michael Prados, Evanthia Galanis, Patrick Y. Wen, Timothy F. Cloughesy

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background. In the current study, we pooled imaging data in newly diagnosed glioblastoma (GBM) patients from international multicenter clinical trials, single institution databases, and multicenter clinical trial con-sortiums to identify the relationship between postoperative residual enhancing tumor volume and overall survival (OS). Methods. Data from 1511 newly diagnosed GBM patients from 5 data sources were included in the current study: (i) a single institution database from UCLA (N = 398; Discovery); (ii) patients from the Ben and Cathy Ivy Foundation for Early Phase Clinical Trials Network Radiogenomics Database (N = 262 from 8 centers; Confirmation); (iii) the chemoradiation placebo arm from an international phase III trial (AVAglio; N = 394 from 120 locations in 23 countries; Validation); (iv) the experimental arm from AVAglio examining chemoradiation plus bevacizumab (N = 404 from 120 locations in 23 countries; Exploratory Set 1); and (v) an Alliance (N0874) phase I/II trial of vorinostat plus chemoradiation (N = 53; Exploratory Set 2). Postsurgical, residual enhancing disease was quantified using T1 subtraction maps. Multivariate Cox regression models were used to determine influence of clinical variables, O6-methylguanine-DNA methyltransferase (MGMT) status, and residual tumor volume on OS. Results. A log-linear relationship was observed between postoperative, residual enhancing tumor volume and OS in newly diagnosed GBM treated with standard chemoradiation. Postoperative tumor volume is a prognostic factor for OS (P < 0.01), regardless of therapy, age, and MGMT promoter methylation status. Conclusion. Postsurgical, residual contrast-enhancing disease significantly negatively influences survival in patients with newly diagnosed GBM treated with chemoradiation with or without concomitant experimental therapy.

Original languageEnglish (US)
Pages (from-to)1240-1250
Number of pages11
JournalNeuro-Oncology
Volume20
Issue number9
DOIs
StatePublished - Jan 1 2018

Fingerprint

Glioblastoma
Tumor Burden
Residual Neoplasm
Survival
Methyltransferases
Clinical Trials
Databases
Multicenter Studies
Investigational Therapies
Residual Volume
Information Storage and Retrieval
DNA
Proportional Hazards Models
Methylation
Placebos
Therapeutics

Keywords

  • Bevacizumab
  • Clinical trials
  • Contrast-enhancing tumor volume
  • GBM
  • New glioblastoma
  • Prognosis
  • T1 subtraction

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research

Cite this

Validation of postoperative residual contrast-enhancing tumor volume as an independent prognostic factor for overall survival in newly diagnosed glioblastoma. / Ellingson, Benjamin M.; Abrey, Lauren E.; Nelson, Sarah J.; Kaufmann, Timothy J; Garcia, Josep; Chinot, Olivier; Saran, Frank; Nishikawa, Ryo; Henriksson, Roger; Mason, Warren P.; Wick, Wolfgang; Butowski, Nicholas; Ligon, Keith L.; Gerstner, Elizabeth R.; Colman, Howard; De Groot, John; Chang, Susan; Mellinghoff, Ingo; Young, Robert J.; Alexander, Brian M.; Colen, Rivka; Taylor, Jennie W.; Arrillaga-Romany, Isabel; Mehta, Arnav; Huang, Raymond Y.; Pope, Whitney B.; Reardon, David; Batchelor, Tracy; Prados, Michael; Galanis, Evanthia; Wen, Patrick Y.; Cloughesy, Timothy F.

In: Neuro-Oncology, Vol. 20, No. 9, 01.01.2018, p. 1240-1250.

Research output: Contribution to journalArticle

Ellingson, BM, Abrey, LE, Nelson, SJ, Kaufmann, TJ, Garcia, J, Chinot, O, Saran, F, Nishikawa, R, Henriksson, R, Mason, WP, Wick, W, Butowski, N, Ligon, KL, Gerstner, ER, Colman, H, De Groot, J, Chang, S, Mellinghoff, I, Young, RJ, Alexander, BM, Colen, R, Taylor, JW, Arrillaga-Romany, I, Mehta, A, Huang, RY, Pope, WB, Reardon, D, Batchelor, T, Prados, M, Galanis, E, Wen, PY & Cloughesy, TF 2018, 'Validation of postoperative residual contrast-enhancing tumor volume as an independent prognostic factor for overall survival in newly diagnosed glioblastoma', Neuro-Oncology, vol. 20, no. 9, pp. 1240-1250. https://doi.org/10.1093/neuonc/noy053
Ellingson, Benjamin M. ; Abrey, Lauren E. ; Nelson, Sarah J. ; Kaufmann, Timothy J ; Garcia, Josep ; Chinot, Olivier ; Saran, Frank ; Nishikawa, Ryo ; Henriksson, Roger ; Mason, Warren P. ; Wick, Wolfgang ; Butowski, Nicholas ; Ligon, Keith L. ; Gerstner, Elizabeth R. ; Colman, Howard ; De Groot, John ; Chang, Susan ; Mellinghoff, Ingo ; Young, Robert J. ; Alexander, Brian M. ; Colen, Rivka ; Taylor, Jennie W. ; Arrillaga-Romany, Isabel ; Mehta, Arnav ; Huang, Raymond Y. ; Pope, Whitney B. ; Reardon, David ; Batchelor, Tracy ; Prados, Michael ; Galanis, Evanthia ; Wen, Patrick Y. ; Cloughesy, Timothy F. / Validation of postoperative residual contrast-enhancing tumor volume as an independent prognostic factor for overall survival in newly diagnosed glioblastoma. In: Neuro-Oncology. 2018 ; Vol. 20, No. 9. pp. 1240-1250.
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T1 - Validation of postoperative residual contrast-enhancing tumor volume as an independent prognostic factor for overall survival in newly diagnosed glioblastoma

AU - Ellingson, Benjamin M.

AU - Abrey, Lauren E.

AU - Nelson, Sarah J.

AU - Kaufmann, Timothy J

AU - Garcia, Josep

AU - Chinot, Olivier

AU - Saran, Frank

AU - Nishikawa, Ryo

AU - Henriksson, Roger

AU - Mason, Warren P.

AU - Wick, Wolfgang

AU - Butowski, Nicholas

AU - Ligon, Keith L.

AU - Gerstner, Elizabeth R.

AU - Colman, Howard

AU - De Groot, John

AU - Chang, Susan

AU - Mellinghoff, Ingo

AU - Young, Robert J.

AU - Alexander, Brian M.

AU - Colen, Rivka

AU - Taylor, Jennie W.

AU - Arrillaga-Romany, Isabel

AU - Mehta, Arnav

AU - Huang, Raymond Y.

AU - Pope, Whitney B.

AU - Reardon, David

AU - Batchelor, Tracy

AU - Prados, Michael

AU - Galanis, Evanthia

AU - Wen, Patrick Y.

AU - Cloughesy, Timothy F.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background. In the current study, we pooled imaging data in newly diagnosed glioblastoma (GBM) patients from international multicenter clinical trials, single institution databases, and multicenter clinical trial con-sortiums to identify the relationship between postoperative residual enhancing tumor volume and overall survival (OS). Methods. Data from 1511 newly diagnosed GBM patients from 5 data sources were included in the current study: (i) a single institution database from UCLA (N = 398; Discovery); (ii) patients from the Ben and Cathy Ivy Foundation for Early Phase Clinical Trials Network Radiogenomics Database (N = 262 from 8 centers; Confirmation); (iii) the chemoradiation placebo arm from an international phase III trial (AVAglio; N = 394 from 120 locations in 23 countries; Validation); (iv) the experimental arm from AVAglio examining chemoradiation plus bevacizumab (N = 404 from 120 locations in 23 countries; Exploratory Set 1); and (v) an Alliance (N0874) phase I/II trial of vorinostat plus chemoradiation (N = 53; Exploratory Set 2). Postsurgical, residual enhancing disease was quantified using T1 subtraction maps. Multivariate Cox regression models were used to determine influence of clinical variables, O6-methylguanine-DNA methyltransferase (MGMT) status, and residual tumor volume on OS. Results. A log-linear relationship was observed between postoperative, residual enhancing tumor volume and OS in newly diagnosed GBM treated with standard chemoradiation. Postoperative tumor volume is a prognostic factor for OS (P < 0.01), regardless of therapy, age, and MGMT promoter methylation status. Conclusion. Postsurgical, residual contrast-enhancing disease significantly negatively influences survival in patients with newly diagnosed GBM treated with chemoradiation with or without concomitant experimental therapy.

AB - Background. In the current study, we pooled imaging data in newly diagnosed glioblastoma (GBM) patients from international multicenter clinical trials, single institution databases, and multicenter clinical trial con-sortiums to identify the relationship between postoperative residual enhancing tumor volume and overall survival (OS). Methods. Data from 1511 newly diagnosed GBM patients from 5 data sources were included in the current study: (i) a single institution database from UCLA (N = 398; Discovery); (ii) patients from the Ben and Cathy Ivy Foundation for Early Phase Clinical Trials Network Radiogenomics Database (N = 262 from 8 centers; Confirmation); (iii) the chemoradiation placebo arm from an international phase III trial (AVAglio; N = 394 from 120 locations in 23 countries; Validation); (iv) the experimental arm from AVAglio examining chemoradiation plus bevacizumab (N = 404 from 120 locations in 23 countries; Exploratory Set 1); and (v) an Alliance (N0874) phase I/II trial of vorinostat plus chemoradiation (N = 53; Exploratory Set 2). Postsurgical, residual enhancing disease was quantified using T1 subtraction maps. Multivariate Cox regression models were used to determine influence of clinical variables, O6-methylguanine-DNA methyltransferase (MGMT) status, and residual tumor volume on OS. Results. A log-linear relationship was observed between postoperative, residual enhancing tumor volume and OS in newly diagnosed GBM treated with standard chemoradiation. Postoperative tumor volume is a prognostic factor for OS (P < 0.01), regardless of therapy, age, and MGMT promoter methylation status. Conclusion. Postsurgical, residual contrast-enhancing disease significantly negatively influences survival in patients with newly diagnosed GBM treated with chemoradiation with or without concomitant experimental therapy.

KW - Bevacizumab

KW - Clinical trials

KW - Contrast-enhancing tumor volume

KW - GBM

KW - New glioblastoma

KW - Prognosis

KW - T1 subtraction

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