Benjamin M Ellingson1,2, Lauren E Abrey3, Sarah J Nelson4, Timothy J Kaufmann5, Josep Garcia3, Olivier Chinot6, Frank Saran7, Ryo Nishikawa8, Roger Henriksson9, Warren P Mason10, Wolfgang Wick11, Nicholas Butowski12, Keith L Ligon13, Elizabeth R Gerstner14, Howard Colman15, John de Groot16, Susan Chang12, Ingo Mellinghoff17, Robert J Young17, Brian M Alexander18, Rivka Colen19, Jennie W Taylor12, Isabel Arrillaga-Romany14, Arnav Mehta1,2, Raymond Y Huang20, Whitney B Pope2, David Reardon21, Tracy Batchelor14, Michael Prados12, Evanthia Galanis22,23, Patrick Y Wen21, Timothy F Cloughesy24. 1. UCLA Brain Tumor Imaging Laboratory, Center for Computer Vision and Imaging Biomarkers, David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, California, USA. 2. Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA. 3. F. Hoffman-La Roche, Ltd, Basel, Switzerland. 4. Department of Radiology and Biomedical Imaging, University of California San Francisco (UCSF), San Francisco, California, USA. 5. Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA. 6. Aix-Marseille University, AP-HM, Service de Neuro-Oncologie, CHU Timone, Marseille, France. 7. The Royal Marsden NHS Foundation Trust, Sutton, UK. 8. Saitama Medical University, Saitama, Japan. 9. Regional Cancer Center Stockholm, Stockholm, Sweden and Umeå University, Umeå, Sweden. 10. Princess Margaret Hospital, Toronto, Ontario, Canada. 11. Clinical Cooperation Unit Neurooncology, German Cancer Consortium, German Cancer Research Center, Heidelberg, Germany. 12. Department of Neurosurgery, University of California San Francisco, San Francisco, California, USA. 13. Department of Oncologic Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA. 14. Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA. 15. Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA. 16. Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 17. Memorial Sloan Kettering Cancer Center, New York, New York, USA. 18. Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA. 19. Department of Neuroradiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 20. Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts, USA. 21. Center for Neuro-Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA. 22. Department of Molecular Medicine, Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota, USA. 23. Department of Oncology, Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota, USA. 24. UCLA Neuro-Oncology Program, Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
Abstract
Background: In the current study, we pooled imaging data in newly diagnosed glioblastoma (GBM) patients from international multicenter clinical trials, single institution databases, and multicenter clinical trial consortiums to identify the relationship between postoperative residual enhancing tumor volume and overall survival (OS). Methods: Data from 1511 newly diagnosed GBM patients from 5 data sources were included in the current study: (i) a single institution database from UCLA (N = 398; Discovery); (ii) patients from the Ben and Cathy Ivy Foundation for Early Phase Clinical Trials Network Radiogenomics Database (N = 262 from 8 centers; Confirmation); (iii) the chemoradiation placebo arm from an international phase III trial (AVAglio; N = 394 from 120 locations in 23 countries; Validation); (iv) the experimental arm from AVAglio examining chemoradiation plus bevacizumab (N = 404 from 120 locations in 23 countries; Exploratory Set 1); and (v) an Alliance (N0874) phase I/II trial of vorinostat plus chemoradiation (N = 53; Exploratory Set 2). Postsurgical, residual enhancing disease was quantified using T1 subtraction maps. Multivariate Cox regression models were used to determine influence of clinical variables, O6-methylguanine-DNA methyltransferase (MGMT) status, and residual tumor volume on OS. Results: A log-linear relationship was observed between postoperative, residual enhancing tumor volume and OS in newly diagnosed GBM treated with standard chemoradiation. Postoperative tumor volume is a prognostic factor for OS (P < 0.01), regardless of therapy, age, and MGMT promoter methylation status. Conclusion: Postsurgical, residual contrast-enhancing disease significantly negatively influences survival in patients with newly diagnosed GBM treated with chemoradiation with or without concomitant experimental therapy.
Background: In the current study, we pooled imaging data in newly diagnosed glioblastoma (GBM) patients from international multicenter clinical trials, single institution databases, and multicenter clinical trial consortiums to identify the relationship between postoperative residual enhancing tumor volume and overall survival (OS). Methods: Data from 1511 newly diagnosed GBM patients from 5 data sources were included in the current study: (i) a single institution database from UCLA (N = 398; Discovery); (ii) patients from the Ben and Cathy Ivy Foundation for Early Phase Clinical Trials Network Radiogenomics Database (N = 262 from 8 centers; Confirmation); (iii) the chemoradiation placebo arm from an international phase III trial (AVAglio; N = 394 from 120 locations in 23 countries; Validation); (iv) the experimental arm from AVAglio examining chemoradiation plus bevacizumab (N = 404 from 120 locations in 23 countries; Exploratory Set 1); and (v) an Alliance (N0874) phase I/II trial of vorinostat plus chemoradiation (N = 53; Exploratory Set 2). Postsurgical, residual enhancing disease was quantified using T1 subtraction maps. Multivariate Cox regression models were used to determine influence of clinical variables, O6-methylguanine-DNA methyltransferase (MGMT) status, and residual tumor volume on OS. Results: A log-linear relationship was observed between postoperative, residual enhancing tumor volume and OS in newly diagnosed GBM treated with standard chemoradiation. Postoperative tumor volume is a prognostic factor for OS (P < 0.01), regardless of therapy, age, and MGMT promoter methylation status. Conclusion: Postsurgical, residual contrast-enhancing disease significantly negatively influences survival in patients with newly diagnosed GBM treated with chemoradiation with or without concomitant experimental therapy.
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