Prognostic value of contrast enhancement and FLAIR for survival in newly diagnosed glioblastoma treated with and without bevacizumab: results from ACRIN 6686
Year: 2018
Type: article
Abstract: 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.
Source: Neuro-Oncology
Institutions: Brown University, Rhode Island Hospital, University of South Florida, University of Pennsylvania, Massachusetts General Hospital, Athinoula A. Martinos Center for Biomedical Imaging, IMRIS (United States), National Institutes of Health, The University of Texas MD Anderson Cancer Center, National Cancer Institute, Duke Medical Center
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: Biostatistics Data Management Center for ACRIN, ECOG-ACRIN Network Group Operations Center, G2179140131, American College of Radiology Imaging Network, G2934786030, American College of Radiology Imaging Network, NRG Oncology Network Group Operations Center, ECOG-ACRIN NCORP Research Base, Biostatistics Data Management Center for ACRIN, G5643875679, G595549979, Radiation Therapy Oncology Group, ECOG-ACRIN Network Group Statistics and Data Management Center, G7454439745, NRG Oncology - Statistical and Data Management Center
OpenAlex ID: W2792671843