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Journal of Neuro-Oncology

, Volume 135, Issue 1, pp 75–81 | Cite as

Radiographic patterns of progression with associated outcomes after bevacizumab therapy in glioblastoma patients

  • David Cachia
  • Nabil A. Elshafeey
  • Carlos Kamiya-Matsuoka
  • Masumeh Hatami
  • Kristin D. Alfaro-Munoz
  • Jacob J. Mandel
  • Rivka Colen
  • John F. DeGroot
Clinical Study

Abstract

Treatment response and survival after bevacizumab failure remains poor in patients with glioblastoma. Several recent publications examining glioblastoma patients treated with bevacizumab have described specific radiographic patterns of disease progression as correlating with outcome. This study aims to scrutinize these previously reported radiographic prognostic models in an independent data set to inspect their reproducibility and potential for clinical utility. Sixty four patients treated at MD Anderson matched predetermined inclusion criteria. Patients were categorized based on previously published data by: (1) Nowosielski et al. into: T2-diffuse, cT1 Flare-up, non-responders and T2 circumscribed groups (2) Modified Pope et al. criteria into: local, diffuse and distant groups and (3) Bahr et al. into groups with or without new diffusion-restricted and/or pre-contrast T1-hyperintense lesions. When classified according to Nowosielski et al. criteria, the cT1 Flare-up group had the longest overall survival (OS) from bevacizumab initiation, with non-responders having the worst outcomes. The T2 diffuse group had the longest progression free survival (PFS) from start of bevacizumab. When classified by modified Pope at al. criteria, most patients did not experience a shift in tumor pattern from the pattern at baseline, while the PFS and OS in patients with local-to-local and local-to-diffuse/distant patterns of progression were similar. Patients developing restricted diffusion on bevacizumab had worse OS. Diffuse patterns of progression in patients treated with bevacizumab are rare and not associated with worse outcomes compared to other radiographic subgroups. Emergence of restricted diffusion during bevacizumab treatment was a radiographic marker of worse OS.

Keywords

Bevacizumab Glioblastoma MRI Patterns of progression 

Notes

Acknowledgements

Funding

This work was supported in part by the Sheikh Khalifa Al Nahyan Ben Zayed Institute for Personalized Cancer Therapy, and the MD Anderson Cancer Center Support Grant (P30 CA016672).

Compliance with ethical standards

Conflict of interest

Dr. JF DeGroot receives grant or research support from Sanofi-Aventis, Astrazeneca, EMD-Serano, Eli Lilly, Novartis and Deciphers Pharmaceuticals. He is a paid consultant for Celldex and Deciphera Pharmaceuticals. He is also on the DSMB for VBL Therapeutics and on the advisory board for Genentech, Novartis, Celldex and Foundation Medicine, Inc. Dr Cachia, Elshafeey, Kamiya-Matsuoka, Hatami, Mandel and Colen report no disclosures. Ms Alfaro-Munoz reports no disclosures.

Supplementary material

11060_2017_2550_MOESM1_ESM.tif (12.2 mb)
Figure e1. (A) T2 diffuse. A decrease in the contrast enhancement on T1 weighted images is noted at first follow up (b). Similarly there is a corresponding decrease in T2 signal (e). At the time of progression, a diffuse increase in T2 hyperintensity is noted (f), with no corresponding increase in contrast enhancement (c). (B) cT1 Flare-up. On post contrast sequences, there is an initial decrease in contrast enhancement (b) with subsequent increase at the time of progression (c) (C) Non-responder. After start bevacizumab, an increase in the contrast enhancement is noted at first follow-up (b). T2 signal is stable or increases (d) (D) T2 circumscribed. At the time of progression there is either a complete decrease of contrast enhancement or only a few speckled areas of contrast enhancement on post contrast T1 weighted sequences (c). At progression there is evidence of a T2 hyperintense inhomogenous mass with well defined sharp borders (arrow) (f) corresponding to the hypointense signal noted on T1 weighted images (c). (TIF 12515 KB)
11060_2017_2550_MOESM2_ESM.tif (2.8 mb)
Figure e2. (A) An area of restricted diffusion develops after starting treatment with bevacizumab that becomes more prominent on second follow-up (c). The high DWI signal corresponds to a low signal on ADC maps (e,f). (B) Emergence of a T1 hyperintense signal seen on pre-contrast T1 weighted image (c) during bevacizumab treatment (TIF 2879 KB)
11060_2017_2550_MOESM3_ESM.tif (2 mb)
Figure e3. (A) Local: Evidence of recurrent tumor around surgical cavity on post contrast T1 weighted sequence (B) Diffuse: Recurrent tumor that extends more than 3cm from surgical cavity with poorly defined margins (C) Distant: Tumor recurrence capping the left occipital horn of the lateral ventricle (b), distant from the original tumor site within the anterior pole of the left temporal lobe (a) (TIF 2085 KB)
11060_2017_2550_MOESM4_ESM.jpg (2 mb)
Figure e4. Diagram showing different time points used in this study (JPEG 2005 KB)

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Department of NeurosurgeryMedical University of South CarolinaCharlestonUSA
  2. 2.Department of Neuro-RadiologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  3. 3.Department of Neuro-OncologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  4. 4.Department of NeurologyBaylor College of MedicineHoustonUSA

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