Prognostic value of contrast enhancement and FLAIR for survival in newly diagnosed glioblastoma treated with and without bevacizumab: results from ACRIN 6686. Issue 10 (26th March 2018)

• Record Type: Journal Article
• Authors: Boxerman, Jerrold L; Zhang, Zheng; Safriel, Yair; Rogg, Jeffrey M; Wolf, Ronald L; Mohan, Suyash; Marques, Helga; Sorensen, A Gregory; Gilbert, Mark R; Barboriak, Daniel P
• Is Part Of: Neuro-oncology. Volume 20:Issue 10(2018)
• Page Start: 1400
• Page End: 1410
• Publication Date: 2018-03-26
• Subjects: contrast-enhanced MRI -- fluid-attenuated inversion recovery (FLAIR) -- glioblastoma -- pseudoprogression -- pseudoresponse; Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noy049
• Languages: English
• ISSNs: 1522-8517

Abstract

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.