Post-chemoradiation volumetric response predicts survival in newly diagnosed glioblastoma treated with radiation, temozolomide, and bevacizumab or placebo

Author:

Ellingson Benjamin M12345ORCID,Abrey Lauren E6,Garcia Josep6,Chinot Olivier7,Wick Wolfgang8,Saran Frank9,Nishikawa Ryo10,Henriksson Roger11,Mason Warren P12,Harris Robert J12313,Leu Kevin124,Woodworth Davis C123,Mehta Arnav114,Raymond Catalina12,Chakhoyan Ararat12,Pope Whitney B2,Cloughesy Timothy F151617

Affiliation:

1. UCLA Brain Tumor Imaging Laboratory, Center for Computer Vision and Imaging Biomarkers, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA

2. Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA

3. Department of Physics and Biology in Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA

4. Department of Bioengineering, Henry Samueli School of Engineering and Applied Science, University of California Los Angeles, Los Angeles, California, USA

5. Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA

6. F. Hoffman-La Roche, Ltd

7. Aix-Marseille University, AP-HM, Service de Neuro-Oncologie, CHU Timone, Marseille, France

8. Clinical Cooperation Unit Neuro-oncology, German Cancer Consortium, German Cancer Research Center, Heidelberg, Germany

9. The Royal Marsden NHS Foundation Trust, Sutton, UK

10. Saitama Medical University, Saitama, Japan

11. Regional Cancer Center Stockholm, Stockholm, Sweden and Umeå University, Umeå, Sweden

12. Princess Margaret Hospital, Toronto, Ontario, Canada

13. MedQIA, LLC, Los Angeles, California, USA

14. Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA

15. UCLA Brain Research Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA

16. UCLA Neuro-Oncology Program, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA

17. Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA

Abstract

Abstract Background In the current study we used contrast-enhanced T1 subtraction maps to test whether early changes in enhancing tumor volume are prognostic for overall survival (OS) in newly diagnosed glioblastoma (GBM) patients treated with chemoradiation with or without bevacizumab (BV). Methods Seven hundred ninety-eight patients (404 BV and 394 placebo) with newly diagnosed GBM in the AVAglio trial (NCT00943826) had baseline MRI scans available, while 337 BV-treated and 269 placebo-treated patients had >4 MRI scans for response evaluation. The volume of contrast-enhancing tumor was quantified and used for subsequent analyses. Results A decrease in tumor volume during chemoradiation was associated with a longer OS in the placebo group (hazard ratio [HR] = 1.578, P < 0.0001) but not BV-treated group (HR = 1.135, P = 0.4889). Results showed a higher OS in patients on the placebo arm with a sustained decrease in tumor volume using a post-chemoradiation baseline (HR = 1.692, P = 0.0005), and a trend toward longer OS was seen in BV-treated patients (HR = 1.264, P = 0.0724). Multivariable Cox regression confirmed that sustained response or stable disease was prognostic for OS (HR = 0.7509, P = 0.0127) when accounting for age (P = 0.0002), KPS (P = 0.1516), postsurgical tumor volume (P < 0.0001), O6-methylguanine-DNA methyltransferase status (P < 0.0001), and treatment type (P = 0.7637) using the post-chemoradiation baseline. Conclusions The post-chemoradiation timepoint is a better baseline for evaluating efficacy in newly diagnosed GBM. Early progression during the maintenance phase is consequential in predicting OS, supporting the use of progression-free survival rates as a meaningful surrogate for GBM.

Funder

National Brain Tumor Society

American Cancer Society

National Institutes of Health

National Cancer Institute

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,Clinical Neurology,Oncology

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