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Prognostic value of contrast enhancement and FLAIR for survival in newly diagnosed glioblastoma treated with and without bevacizumab: results from ACRIN 6686.

Publication ,  Journal Article
Boxerman, JL; Zhang, Z; Safriel, Y; Rogg, JM; Wolf, RL; Mohan, S; Marques, H; Sorensen, AG; Gilbert, MR; Barboriak, DP
Published in: Neuro Oncol
September 3, 2018

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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Published In

Neuro Oncol

DOI

EISSN

1523-5866

Publication Date

September 3, 2018

Volume

20

Issue

10

Start / End Page

1400 / 1410

Location

England

Related Subject Headings

  • Young Adult
  • Temozolomide
  • Survival Rate
  • Retrospective Studies
  • Radiographic Image Enhancement
  • Prospective Studies
  • Prognosis
  • Oncology & Carcinogenesis
  • Middle Aged
  • Male
 

Citation

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Boxerman, J. L., Zhang, Z., Safriel, Y., Rogg, J. M., Wolf, R. L., Mohan, S., … Barboriak, D. P. (2018). Prognostic value of contrast enhancement and FLAIR for survival in newly diagnosed glioblastoma treated with and without bevacizumab: results from ACRIN 6686. Neuro Oncol, 20(10), 1400–1410. https://doi.org/10.1093/neuonc/noy049
Boxerman, Jerrold L., Zheng Zhang, Yair Safriel, Jeffrey M. Rogg, Ronald L. Wolf, Suyash Mohan, Helga Marques, A Gregory Sorensen, Mark R. Gilbert, and Daniel P. Barboriak. “Prognostic value of contrast enhancement and FLAIR for survival in newly diagnosed glioblastoma treated with and without bevacizumab: results from ACRIN 6686.Neuro Oncol 20, no. 10 (September 3, 2018): 1400–1410. https://doi.org/10.1093/neuonc/noy049.
Boxerman JL, Zhang Z, Safriel Y, Rogg JM, Wolf RL, Mohan S, et al. Prognostic value of contrast enhancement and FLAIR for survival in newly diagnosed glioblastoma treated with and without bevacizumab: results from ACRIN 6686. Neuro Oncol. 2018 Sep 3;20(10):1400–10.
Boxerman, Jerrold L., et al. “Prognostic value of contrast enhancement and FLAIR for survival in newly diagnosed glioblastoma treated with and without bevacizumab: results from ACRIN 6686.Neuro Oncol, vol. 20, no. 10, Sept. 2018, pp. 1400–10. Pubmed, doi:10.1093/neuonc/noy049.
Boxerman JL, Zhang Z, Safriel Y, Rogg JM, Wolf RL, Mohan S, Marques H, Sorensen AG, Gilbert MR, Barboriak DP. Prognostic value of contrast enhancement and FLAIR for survival in newly diagnosed glioblastoma treated with and without bevacizumab: results from ACRIN 6686. Neuro Oncol. 2018 Sep 3;20(10):1400–1410.
Journal cover image

Published In

Neuro Oncol

DOI

EISSN

1523-5866

Publication Date

September 3, 2018

Volume

20

Issue

10

Start / End Page

1400 / 1410

Location

England

Related Subject Headings

  • Young Adult
  • Temozolomide
  • Survival Rate
  • Retrospective Studies
  • Radiographic Image Enhancement
  • Prospective Studies
  • Prognosis
  • Oncology & Carcinogenesis
  • Middle Aged
  • Male