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Baseline pretreatment contrast enhancing tumor volume including central necrosis is a prognostic factor in recurrent glioblastoma: evidence from single and multicenter trials.

ABSTRACT: The prognostic significance of baseline contrast enhancing tumor prior to second- or third-line therapy in recurrent glioblastoma (GBM) for overall survival (OS) remains controversial, particularly in the context of repeated surgical resection and/or use of anti-angiogenic therapy. In the current study, we examined recurrent GBM patients from both single and multicenter clinical trials to test whether baseline enhancing tumor volume, including central necrosis, is a significant prognostic factor for OS in recurrent GBM.Included were 497 patients with recurrent GBM from 4 data sources: 2 single-center sites (University of Toronto, University of California Los Angeles) and 2 phase II multicenter trials (AVF3708G, Bevacizumab ± Irinotecan, NCT00345163; XL184-201, Cabozantinib, NCT00704288). T1 subtraction maps were used to define volume of contrast enhancing tumor, including central necrosis. Cox multivariable and univariate analyses were used to evaluate the relationship between tumor volume prior to second- or third-line therapy and OS.Both continuous measures of baseline tumor volume and tumors dichotomized into large (?15cc) and small (<15cc) tumors were significant predictors of OS (P<.0001), independently of age and treatment. Univariate analysis demonstrated significant OS differences (P<.05) between large (?15cc) and small (<15cc) tumors in patients under all therapeutic scenarios. Only patients treated with cabozantinib who previously failed anti-angiogenic therapy did not show an OS dependence on baseline tumor volume.Baseline tumor volume is a significant prognostic factor in recurrent GBM. Clinical trial treatment arms must have a balanced distribution of tumor size, and tumor size should be considered when interpreting therapeutic efficacy.

SUBMITTER: Ellingson BM

PROVIDER: S-EPMC5193027 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Baseline pretreatment contrast enhancing tumor volume including central necrosis is a prognostic factor in recurrent glioblastoma: evidence from single and multicenter trials.

Ellingson Benjamin M BM Harris Robert J RJ Woodworth Davis C DC Leu Kevin K Zaw Okkar O Mason Warren P WP Sahebjam Solmaz S Abrey Lauren E LE Aftab Dana T DT Schwab Gisela M GM Hessel Colin C Lai Albert A Nghiemphu Phioanh L PL Pope Whitney B WB Wen Patrick Y PY Cloughesy Timothy F TF

Neuro-oncology 20160831 1

<h4>Background</h4>The prognostic significance of baseline contrast enhancing tumor prior to second- or third-line therapy in recurrent glioblastoma (GBM) for overall survival (OS) remains controversial, particularly in the context of repeated surgical resection and/or use of anti-angiogenic therapy. In the current study, we examined recurrent GBM patients from both single and multicenter clinical trials to test whether baseline enhancing tumor volume, including central necrosis, is a significan ...[more]

PMID: 27580889

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Project description:Purpose To evaluate factors contributing to interreader variation (IRV) in parameters measured at dynamic contrast material-enhanced (DCE) MRI in patients with glioblastoma who were participating in a multicenter trial. Materials and Methods A total of 18 patients (mean age, 57 years ± 13 [standard deviation]; 10 men) who volunteered for the advanced imaging arm of ACRIN 6677, a substudy of the RTOG 0625 clinical trial for recurrent glioblastoma treatment, underwent analyzable DCE MRI at one of four centers. The 78 imaging studies were analyzed centrally to derive the volume transfer constant (Ktrans) for gadolinium between blood plasma and tissue extravascular extracellular space, fractional volume of the extracellular extravascular space (ve), and initial area under the gadolinium concentration curve (IAUGC). Two independently trained teams consisting of a neuroradiologist and a technologist segmented the enhancing tumor on three-dimensional spoiled gradient-recalled acquisition in the steady-state images. Mean and median parameter values in the enhancing tumor were extracted after registering segmentations to parameter maps. The effect of imaging time relative to treatment, map quality, imager magnet and sequence, average tumor volume, and reader variability in tumor volume on IRV was studied by using intraclass correlation coefficients (ICCs) and linear mixed models. Results Mean interreader variations (± standard deviation) (difference as a percentage of the mean) for mean and median IAUGC, mean and median Ktrans, and median ve were 18% ± 24, 17% ± 23, 27% ± 34, 16% ± 27, and 27% ± 34, respectively. ICCs for these metrics ranged from 0.90 to 1.0 for baseline and from 0.48 to 0.76 for posttreatment examinations. Variability in reader-derived tumor volume was significantly related to IRV for all parameters. Conclusion Differences in reader tumor segmentations are a significant source of interreader variation for all dynamic contrast-enhanced MRI parameters. © RSNA, 2018 Online supplemental material is available for this article. See also the editorial by Wolf in this issue.

Project description:PurposeTo compare the capability to aid prediction of clinical outcome measures, including progression-free survival (PFS) and overall survival (OS), between volumetric estimates from contrast material-enhanced (CE) T1-weighted subtraction maps and traditional segmentation in a randomized multicenter clinical trial of recurrent glioblastoma (GBM) patients treated with bevacizumab.Materials and methodsAll patients participating in this study signed institutional review board-approved informed consent at their respective institutions prior to enrolling in the multicenter clinical trial. One-hundred sixty patients with recurrent GBM enrolled as part of a HIPAA-compliant, multicenter clinical trial (AVF3708 g, BRAIN trial). Contrast-enhancing tumor volumes and change in volumes as a response to therapy were quantified by using either conventional segmentation or CE T1-weighted subtraction maps created by voxel-by-voxel subtraction of intensity-normalized nonenhanced T1-weighted images from CE T1-weighted images. These volumes were then tested as predictors of PFS and OS by using log-rank univariate analysis, the multivariate Cox proportional hazards regression model, and receiver operating characteristic analysis.ResultsUse of CE T1-weighted subtraction maps qualitatively improved visualization and improved quantification of tumor volume after bevacizumab treatment. Significant trends between the volume of tumor and change in tumor volume after therapy on CE T1-weighted subtraction maps were found for both PFS and OS (pretreatment volume < 15 cm(3), P < .003; posttreatment volume < 7.5 cm(3), P < .05; percentage change in volume > 25%, P = .004 for PFS and P = .053 for OS). CE T1-weighted subtraction maps were significantly better at aiding prediction of 6-month PFS and 12-month OS compared with conventional segmentation by using receiver operating characteristic analysis (P < .05).ConclusionUse of CE T1-weighted subtraction maps improved visualization and aided better prediction of patient survival in recurrent GBM treated with bevacizumab compared with conventional segmentation of CE T1-weighted images. Clinical trial registration no. NCT00345163. Online supplemental material is available for this article.

Dataset Information

Baseline pretreatment contrast enhancing tumor volume including central necrosis is a prognostic factor in recurrent glioblastoma: evidence from single and multicenter trials.

Publications

Baseline pretreatment contrast enhancing tumor volume including central necrosis is a prognostic factor in recurrent glioblastoma: evidence from single and multicenter trials.

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