Early post-bevacizumab progression on contrast-enhanced MRI as a prognostic marker for overall survival in recurrent glioblastoma: results from the ACRIN 6677/RTOG 0625 Central Reader Study

Boxerman, Jerrold L.; Zhang, Zheng; Safriel, Yair; Larvie, Mykol; Snyder, Bradley S.; Jain, Rajan; Linda, T.; Sorensen, A. Gregory; Gilbert, Mark R.; Barboriak, Daniel P.

doi:10.1093/neuonc/not049

Cited by 74 publications

(62 citation statements)

References 51 publications

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“…31 In a recent phase II clinical trial, FLAIR and postcontrast T1-weighted imaging were evaluated for their ability to predict overall survival in patients with recurrent glioblastoma multiforme treated with the anti–vascular endothelial growth factor drug bevacizumab. 32 It was found that an increase in enhancement was associated with poorer survival, while FLAIR progression did not reveal a significant survival disadvantage. 32 The results of this study are promising in predicting treatment failure for those who show progression on T1-weighted imaging, yet standard imaging has still remained ineffective in determining true responders from pseudoresponders in those who have diminished enhancement.…”

Section: Discussionmentioning

confidence: 97%

Repeatability of Standardized and Normalized Relative CBV in Patients with Newly Diagnosed Glioblastoma

Prah¹,

Stufflebeam

Paulson

et al. 2015

AJNR Am J Neuroradiol

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BACKGROUND AND PURPOSE For more widespread clinical use advanced imaging methods such as relative cerebral blood volume must be both accurate and repeatable. The aim of this study was to determine the repeatability of relative CBV measurements in newly diagnosed glioblastoma multiforme by using several of the most commonly published estimation techniques. MATERIALS AND METHODS The relative CBV estimates were calculated from dynamic susceptibility contrast MR imaging in double-baseline examinations for 33 patients with treatment-naïve and pathologically proved glioblastoma multiforme (men=20; mean age=55 years). Normalized and standardized relative CBV were calculated by using 6 common postprocessing methods. The repeatability of both normalized and standardized relative CBV, in both tumor and contralateral brain, was examined for each method with metrics of repeatability, including the repeatability coefficient and within-subject coefficient of variation. The minimum sample size required to detect a parameter change of 10% or 20% was also determined for both normalized relative CBV and standardized relative CBV for each estimation method. RESULTS When ordered by the repeatability coefficient, methods using postprocessing leakage correction and ΔR2*(t) techniques offered superior repeatability. Across processing techniques, the standardized relative CBV repeatability in normal-appearing brain was comparable with that in tumor (P = .31), yet inferior in tumor for normalized relative CBV (P = .03). On the basis of the within-subject coefficient of variation, tumor standardized relative CBV estimates were less variable (13%–20%) than normalized relative CBV estimates (24%– 67%). The minimum number of participants needed to detect a change of 10% or 20% is 118–643 or 30 –161 for normalized relative CBV and 109 –215 or 28 –54 for standardized relative CBV. CONCLUSIONS The ΔR2* estimation methods that incorporate leakage correction offer the best repeatability for relative CBV, with standardized relative CBV being less variable and requiring fewer participants to detect a change compared with normalized relative CBV.

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Section: Discussionmentioning

confidence: 97%

Repeatability of Standardized and Normalized Relative CBV in Patients with Newly Diagnosed Glioblastoma

Prah¹,

Stufflebeam

Paulson

et al. 2015

AJNR Am J Neuroradiol

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“…Despite the high variability of ORRs, there is an association of OR status and OS as demonstrated in our landmark analysis for both criteria. Recently, in a study of imaging data from a phase II trial (RTOG0625) of bevacizumab with irinotecan or temozolomide in recurrent glioblastoma, Boxerman and colleagues demonstrated that early progression at 8 weeks posttreatment based on both two-dimensional and three-dimensional measurements of enhancement, rather than response, was a significant prognostic marker for OS (16). This result suggests that the association of OR and OS observed in our study could be due to including early progressors in the nonresponder group, rather than directly result from the OR status as determined by Macdonald or RANO criteria.…”

Section: Discussionmentioning

confidence: 99%

“…Of note, determination of radiographic progression relative to the gold standard provided by histopathologic confirmation has not been validated for either the Macdonald criteria or the RANO criteria in prospectively conducted clinical trials. Nonetheless, the value of adding T2/FLAIR assessment to the Macdonald criteria remains to be determined, although preliminary evidence of benefit has been suggested previously (16,17).…”

Section: Introductionmentioning

confidence: 99%

The Impact of T2/FLAIR Evaluation per RANO Criteria on Response Assessment of Recurrent Glioblastoma Patients Treated with Bevacizumab

Huang

Rahman

Ballman

et al. 2016

Clinical Cancer Research

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Purpose: The RANO criteria have not been assessed using outcome data from prospective trials. We examined the radiologic data of patients with recurrent glioblastoma from the randomized phase II trial (AVF3708g) to determine the effect of including T2/ FLAIR evaluation as per RANO criteria on measurements of objective response rates (ORRs) and progression-free survival (PFS) compared with assessment based on contrast enhancement (Macdonald criteria).Experimental Design: The ORRs and median PFS were determined using the RANO criteria and compared with those obtained using the Macdonald criteria. Landmark analyses were performed at 2, 4, and 6 months, and Cox proportional hazard models were used to determine the associations between OR and progression with subsequent survival.Results: The ORRs were 0.331 [95% confidence interval (CI), 0.260-0.409] and 0.393 (95% CI, 0.317-0.472) by RANO and Macdonald criteria, respectively (P < 0.0001). The median PFS was 4.6 months (95% CI, 4.1-5.5) using RANO criteria, compared with 6.4 months (95% CI, 5.5-7.1) as determined by Macdonald criteria (P ¼ 0.01). At 2-, 4-, and 6-month landmarks, both OR status and PFS determined by either RANO or Macdonald criteria were predictive of overall survival [OS; hazard ratios for 4-month landmark (OR HR ¼ 1.93, P ¼ 0.0012; PFS HR, 4.23, P < 0.0001)].Conclusions: The inclusion of T2/FLAIR assessment resulted in statistically significant differences in median PFS and ORRs compared with assessment of solely enhancing tumor (Macdonald criteria), although OR and PFS determined by both RANO and Macdonald criteria correlated with OS.

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“…However, no difference in OS was found in a study of HGG patients treated with the anti-angiogenic drug bevacizumab with improved versus stable contrast enhancement, raising the possibility that pseudoresponse was degrading the prognostic significance of tumor size measurements that are based on contrast-enhancing tissue. 45 This difficulty was addressed with the use of DSC, which could stratify survival in patients with improved or stable contrast enhancement, as shown in a follow-up study. 46 Although this finding has been disputed, and may depend on timing of perfusion imaging, 47 it remains a possibility that the incorporation of perfusion metrics in trials of antiangiogenic therapy could be beneficial in predicting outcome.…”

Section: Clinical Applications Of Advanced Mrimentioning

confidence: 99%

Conventional and advanced magnetic resonance imaging in patients with high-grade glioma

Pope¹,

Brandal²

2018

Q J Nucl Med Mol Imaging

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Magnetic resonance imaging is integral to the care of patients with high-grade gliomas. Anatomic detail can be acquired with conventional structural imaging, but newer approaches also add capabilities to interrogate image-derived physiologic and molecular characteristics of central nervous system neoplasms. These advanced imaging techniques are increasingly employed to generate biomarkers that better reflect tumor burden and therapy response. The following is an overview of current strategies based on advanced magnetic resonance imaging that are used in the assessment of high-grade glioma patients with an emphasis on how novel imaging biomarkers can potentially advance patient care.

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Early post-bevacizumab progression on contrast-enhanced MRI as a prognostic marker for overall survival in recurrent glioblastoma: results from the ACRIN 6677/RTOG 0625 Central Reader Study

Abstract: Early progression on 2D-T1 and 3D-T1, but not FLAIR MRI, after 8 and 16 weeks of anti-vascular endothelial growth factor therapy has highly significant prognostic value for OS in recurrent GBM.

Cited by 74 publications

References 51 publications

Repeatability of Standardized and Normalized Relative CBV in Patients with Newly Diagnosed Glioblastoma

Repeatability of Standardized and Normalized Relative CBV in Patients with Newly Diagnosed Glioblastoma

The Impact of T2/FLAIR Evaluation per RANO Criteria on Response Assessment of Recurrent Glioblastoma Patients Treated with Bevacizumab

Conventional and advanced magnetic resonance imaging in patients with high-grade glioma

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