Prognostic value of contrast enhancement and FLAIR for survival in newly diagnosed glioblastoma treated with and without bevacizumab: results from ACRIN 6686
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Background: ACRIN 6686/RTOG 0825 was a phase III trial of conventional chemoradiation plus adjuvant temozolomide with bevacizumab or without (placebo) in newly diagnosed glioblastoma. This study investigated whether changes in contrast-enhancing and fluid attenuated inversion recovery (FLAIR)-hyperintense tumor assessed by central reading prognosticate overall survival (OS). Methods: Two hundred eighty-four patients (171 men; median age 57 y, range 19-79; 159 on bevacizumab) had MRI at post-op (baseline) and pre-cycle 4 of adjuvant temozolomide (22 wk post chemoradiation initiation). Four central readers measured bidimensional lesion enhancement (2D-T1) and FLAIR hyperintensity at both time points. Changes from baseline to pre-cycle 4 for both markers were dichotomized (increasing vs non-increasing). Cox proportional hazards model and Kaplan-Meier survival estimates were used for inference. Results: Adjusting for treatment, increasing 2D-T1 (n = 262, hazard ratio [HR] = 2.07, 95% CI: 1.48-2.91, P < 0.0001) and FLAIR (n = 273, HR = 1.75, 95% CI: 1.26-2.41, P = 0.0008) significantly predicted worse OS. Median OS (days) was significantly shorter for patients with increasing versus non-increasing 2D-T1 for both bevacizumab (443 vs 535, P = 0.004) and placebo (526 vs 887, P = 0.001). Median OS was significantly shorter for patients with increasing versus non-increasing FLAIR for placebo (595 vs 872, P = 0.001), and trended similarly for bevacizumab (499 vs 535, P = 0.0935). Adjusting for 2D-T1 and treatment, increasing FLAIR represented significantly higher risk for death (HR = 1.59 [1.11-2.26], P = 0.01). Conclusion: Increased 2D-T1 significantly predicts worse OS in both treatment groups, implying absence of a substantial proportion of pseudoprogression 22 weeks after initiation of standard therapy. FLAIR adds value beyond 2D-T1 in predicting OS, potentially addressing the pseudoresponse effect by substratifying bevacizumab-treated patients with non-increasing 2D-T1.
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One of the 6 out-of-sample sites (Site 11) contributed aggregated a priori data from a multi-site randomized clinical trial for newly diagnosed glioblastoma.
“One of these 6 out-of-sample sites (Site 11) contributed aggregated a priori data from a multi-site randomized clinical trial for newly diagnosed glioblastoma (ClinicalTrials.gov Identifier: NCT00884741, RTOG082572,73, ACRIN668674,75), with inherent diversity benefiting the intended generalizability validation purpose.”
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- Authors
- Boxerman, J. L., Zhang, Z., Safriel, Y., Rogg, J. M., Wolf, R. L., Mohan, S., Marques, H., Sorensen, A. G., Gilbert, M. R., & Barboriak, D. P.
- Affiliations
- Brown University (US)
- University of South Florida (US)
- University of Pennsylvania (US)
- Massachusetts General Hospital (US)
- National Institutes of Health (US)
- Duke Medical Center (US)
- Corresponding author
- Boxerman, Jerrold L
- ORCID
- Venue
- Neuro-Oncology
- Publisher
- Oxford University Press (OUP)
- Published
- 2018-03-26
- Volume
- 20
- Issue
- 10
- Pages
- 1400-1410
- ISSN
- 1522-8517 (ISSN-L)
- 1523-5866
- PMC
- PMC6120359
- OpenAlex
- W2792671843
- Cited by
- 35
- References
- 46
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 1 · 2023: 8 · 2022: 3 · 2021: 4 · 2020: 9 · 2019: 5
- FWCI
- 2.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Neuro-Oncology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (CA021661, CA079778, CA080098, CA180794, CA180820, CA180822, CA180868)
- Biomarker, Imaging and Quality of Life Studies Funding Program (BIQSFP)
- Topics
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiomics and Machine Learning in Medical Imaging
- Life Sciences › Neuroscience › Neurology › Brain Tumor Detection and Classification
- Keywords
- glioblastoma, bevacizumab, contrast enhancement, FLAIR hyperintensity, prognostic imaging biomarkers, overall survival, adjuvant temozolomide, chemoradiotherapy, treatment response monitoring, anti-angiogenic therapy
- MeSH terms
- Bevacizumab, Temozolomide, Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Brain Neoplasms, Contrast Media, Double-Blind Method, Female, Follow-Up Studies, Glioblastoma, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Prognosis, Prospective Studies, Radiographic Image Enhancement, Retrospective Studies, Survival Rate, Young Adult
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