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Days Gained Response Discriminates Treatment Response in Patients with Recurrent Glioblastoma Receiving Bevacizumab-based Therapies

View ORCID ProfileKyle W. Singleton, Alyx B. Porter, Leland S. Hu, Sandra K Johnston, Kamila M. Bond, Cassandra R. Rickertsen, Gustavo De Leon, Scott A. Whitmire, Kamala R. Clark-Swanson, Maciej M. Mrugala, Kristin R. Swanson
doi: https://doi.org/10.1101/752402
Kyle W. Singleton
Mathematical NeuroOncology Lab, Precision Neurotherapeutics Innovation Program, Mayo Clinic, Phoenix, AZ, USA
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  • ORCID record for Kyle W. Singleton
  • For correspondence: singleton.kyle@mayo.edu
Alyx B. Porter
Division of Neuro-Oncology, Department of Neurology, Mayo Clinic, Phoenix, AZ, USA
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Leland S. Hu
Department of Radiology, Mayo Clinic, Phoenix, AZ, USA
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Sandra K Johnston
Mathematical NeuroOncology Lab, Precision Neurotherapeutics Innovation Program, Mayo Clinic, Phoenix, AZ, USADepartment of Radiology, University of Washington, Seattle, WA, USA
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Kamila M. Bond
Mathematical NeuroOncology Lab, Precision Neurotherapeutics Innovation Program, Mayo Clinic, Phoenix, AZ, USAMayo Clinic Alix School of Medicine, Mayo Clinic, Rochester, MN, USA
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Cassandra R. Rickertsen
Mathematical NeuroOncology Lab, Precision Neurotherapeutics Innovation Program, Mayo Clinic, Phoenix, AZ, USA
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Gustavo De Leon
Mathematical NeuroOncology Lab, Precision Neurotherapeutics Innovation Program, Mayo Clinic, Phoenix, AZ, USA
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Scott A. Whitmire
Mathematical NeuroOncology Lab, Precision Neurotherapeutics Innovation Program, Mayo Clinic, Phoenix, AZ, USA
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Kamala R. Clark-Swanson
Mathematical NeuroOncology Lab, Precision Neurotherapeutics Innovation Program, Mayo Clinic, Phoenix, AZ, USA
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Maciej M. Mrugala
Division of Neuro-Oncology, Department of Neurology, Mayo Clinic, Phoenix, AZ, USA
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Kristin R. Swanson
Mathematical NeuroOncology Lab, Precision Neurotherapeutics Innovation Program, Mayo Clinic, Phoenix, AZ, USADepartment of Neurosurgery, Mayo Clinic, Phoenix, AZ, USA
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Abstract

Purpose Accurate assessments of patient response to therapy are a critical component of personalized medicine. In glioblastoma multiforme (GBM), the most aggressive form of brain cancer, tumor growth dynamics are heterogenous across patients, complicating assessment of treatment response. This study aimed to analyze Days Gained (DG), a burgeoning model-based dynamic metric, for response assessment in patients with recurrent GBM who received bevacizumab-based therapies.

Experimental Design Days Gained response scores were calculated using volumetric tumor segmentations for patients receiving bevacizumab with and without concurrent cytotoxic therapy (N=62). Kaplan-Meier and Cox proportional hazards analyses were implemented to examine DG prognostic relationship to overall (OS) and progression-free survival (PFS) from the onset of treatment for recurrent GBM.

Results In patients receiving concurrent bevacizumab and cytotoxic therapy, Kaplan-Meier analysis showed significant differences in OS and PFS at previously identified DG cutoffs consistent with previous DG analyses using gadolinium-enhanced T1 weighted MR imaging. DG scores for bevacizumab monotherapy only approached significance for PFS. Cox regression showed that increases of 25 DG were significantly associated with a 12.5% reduction in OS hazard for concurrent therapy patients and a 4.4% reduction in PFS hazard for bevacizumab monotherapy.

Conclusion Days Gained has significant meaning in recurrent therapy as a metric of treatment response, even in the context of anti-angiogenic therapies. This provides further evidence supporting the use of DG as an adjunct response metric that quantitatively connects treatment response and clinical outcomes.

Footnotes

  • Funding: Ben and Catherine Ivy Foundation, James T. McDonnell Foundation Grant (220020400TT), NIH Grants U54 CA210180, U54 CA143970, U01 CA220378, and R01 NS060752

  • Conflicts of Interest: The authors declare no potential conflicts of interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted August 30, 2019.
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Days Gained Response Discriminates Treatment Response in Patients with Recurrent Glioblastoma Receiving Bevacizumab-based Therapies
Kyle W. Singleton, Alyx B. Porter, Leland S. Hu, Sandra K Johnston, Kamila M. Bond, Cassandra R. Rickertsen, Gustavo De Leon, Scott A. Whitmire, Kamala R. Clark-Swanson, Maciej M. Mrugala, Kristin R. Swanson
bioRxiv 752402; doi: https://doi.org/10.1101/752402
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Days Gained Response Discriminates Treatment Response in Patients with Recurrent Glioblastoma Receiving Bevacizumab-based Therapies
Kyle W. Singleton, Alyx B. Porter, Leland S. Hu, Sandra K Johnston, Kamila M. Bond, Cassandra R. Rickertsen, Gustavo De Leon, Scott A. Whitmire, Kamala R. Clark-Swanson, Maciej M. Mrugala, Kristin R. Swanson
bioRxiv 752402; doi: https://doi.org/10.1101/752402

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