Relevance of T2 signal changes in the assessment of progression of glioblastoma according to the Response Assessment in Neurooncology criteria

Radbruch, Alexander; Lutz, Kira; Wiestler, Benedikt; Bäumer, Philipp; Heiland, Sabine; Wick, Wolfgang; Bendszus, Martin

doi:10.1093/neuonc/nor200

Cited by 77 publications

(71 citation statements)

References 24 publications

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“…The rate of 23% found in our data is well in line with other reports [7,8,13]. Although the percentages reported by Wick et al [7] and those in our series are similar, the approach of the two studies is nevertheless different.…”

Section: Discussionsupporting

confidence: 91%

“…In some patients, gliomatosis-like changes have been noted [6]. It is reassuring that a carefully matched analysis revealed that the rate of patients with T2-only PD and/or a gliomatosis-type development was not higher with bevacizumab therapy than with any other salvage therapy [7,8]. Although FLAIR-only PD is commonly perceived as a feature associated with poor survival, the impact of the finding of FLAIR-only PD on survival has never been systematically evaluated.…”

Section: Introductionmentioning

confidence: 99%

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FLAIR-Only Progression in Bevacizumab-Treated Relapsing Glioblastoma Does Not Predict Short Survival

Schaub¹,

Greschus

Seifert

et al. 2013

Oncology

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Objectives: In this study, we analyzed the prognostic value of different MRI progression patterns for survival in patients with recurrent malignant glioma treated with the vascular endothelial growth factor antibody bevacizumab. Patients and Methods: Twenty-six adult patients with recurrent malignant glioma treated with bevacizumab or bevacizumab/irinotecan were retrospectively analyzed for the development of contrast-enhanced (T1-weighted MRI) and T2/FLAIR lesions. According to the progression pattern, patients were divided into 3 subgroups: (1) patients with primarily progressive contrast-enhanced lesions in the first MRI after initiation of therapy (‘primary PD group'); (2) patients with stable or regressive enhanced lesions but progressive FLAIR lesions (‘FLAIR-only PD group'), and (3) patients with stable or regressive contrast-enhanced T1 and FLAIR lesions (‘no PD group'). Results: Overall survival (OS) in the 6 patients in the FLAIR-only PD group was not significantly different from the 11 patients in the no PD group (median 311 vs. 254 days, respectively). In contrast, survival in the FLAIR-only PD group was significantly better (p = 0.025) than in the primary PD group. Conclusion: FLAIR-only progression is not an independent prognostic factor negatively influencing OS in recurrent glioblastoma treated with bevacizumab and should not lead to discontinuation of bevacizumab therapy.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

FLAIR-Only Progression in Bevacizumab-Treated Relapsing Glioblastoma Does Not Predict Short Survival

Schaub¹,

Greschus

Seifert

et al. 2013

Oncology

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“…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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“…Although classifying T2/FLAIR lesions based on presence of a circumscribed appearance may improve their association with patient outcome [75•], assessment of lesion morphology remains qualitative at this time. Prior attempts in direct measurement of T2/FLAIR lesions using a bi-dimensional technique in a retrospective series of recurrent GBM resulted in identification of nonenhancing progression that is predictive of subsequent enhancing tumor progression [79]. Nevertheless, among patients with recurrent GBM treated with bevacizumab, progression determined by volumetric measurements of T2/FLAIR lesions alone did not predict overall survival [80].…”

Section: Evaluation Of Non-enhancing Tumor Burdenmentioning

confidence: 99%

How Treatment Monitoring Is Influencing Treatment Decisions in Glioblastomas

Neagu

Huang

Reardon

et al. 2015

Curr Treat Options Neurol

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Glioblastoma (GBM), the most common malignant primary tumor in adults, carries a dismal prognosis with an average median survival of 14-16 months. The current standard of care for newly diagnosed GBM consists of maximal safe resection followed by fractionated radiotherapy combined with concurrent temozolomide and 6 to 12 cycles of adjuvant temozolomide. The determination of treatment response and clinical decision-making in the treatment of GBM depends on accurate radiographic assessment. Differentiating treatment response from tumor progression is challenging and combines long-term follow-up using standard MRI, with assessing clinical status and corticosteroid dependency. At progression, bevacizumab is the mainstay of treatment. Incorporation of antiangiogenic therapies leads to rapid blood-brain barrier normalization with remarkable radiographic response often not accompanied by the expected survival benefit, further complicating imaging assessment. Improved radiographic interpretation criteria, such as the Response Assessment in Neuro-Oncology (RANO) criteria, incorporate non-enhancing disease but still fall short of definitely distinguishing tumor progression, pseudoresponse, and pseudoprogression. With new evolving treatment modalities for this devastating disease, advanced imaging modalities are increasingly becoming part of routine clinical care in a field where neuroimaging has such essential role in guiding treatment decisions and defining clinical trial eligibility and efficacy.

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Relevance of T2 signal changes in the assessment of progression of glioblastoma according to the Response Assessment in Neurooncology criteria

Cited by 77 publications

References 24 publications

FLAIR-Only Progression in Bevacizumab-Treated Relapsing Glioblastoma Does Not Predict Short Survival

FLAIR-Only Progression in Bevacizumab-Treated Relapsing Glioblastoma Does Not Predict Short Survival

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

How Treatment Monitoring Is Influencing Treatment Decisions in Glioblastomas

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