TY - JOUR
T1 - Days gained response discriminates treatment response in patients with recurrent glioblastoma receiving bevacizumab-based therapies
AU - Singleton, Kyle W.
AU - Porter Umphrey, Alyx B
AU - Hu, Leland S
AU - Johnston, Sandra K.
AU - Bond, Kamila M.
AU - Rickertsen, Cassandra R.
AU - De Leon, Gustavo
AU - Whitmire, Scott A.
AU - Clark-Swanson, Kamala R.
AU - Mrugala, Maciej M.
AU - Swanson, Kristin
N1 - Publisher Copyright:
© 2020 The Author(s) 2020. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - Background: Accurate assessments of patient response to therapy are a critical component of personalized medicine. In glioblastoma (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. Methods: DG 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 DG cutoffs consistent with previously identified values from newly diagnosed GBM using T1-weighted gadolinium-enhanced magnetic resonance imaging (T1Gd). DG scores for bevacizumab monotherapy patients only approached significance for PFS. Cox regression showed that increases of 25 DG on T1Gd imaging 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 patients. Conclusion: DG 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.
AB - Background: Accurate assessments of patient response to therapy are a critical component of personalized medicine. In glioblastoma (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. Methods: DG 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 DG cutoffs consistent with previously identified values from newly diagnosed GBM using T1-weighted gadolinium-enhanced magnetic resonance imaging (T1Gd). DG scores for bevacizumab monotherapy patients only approached significance for PFS. Cox regression showed that increases of 25 DG on T1Gd imaging 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 patients. Conclusion: DG 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.
KW - bevacizumab
KW - combination chemotherapy
KW - glioblastoma
KW - personalized medicine
KW - response evaluation
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U2 - 10.1093/noajnl/vdaa085
DO - 10.1093/noajnl/vdaa085
M3 - Article
AN - SCOPUS:85126564464
VL - 2
JO - Neuro-Oncology Advances
JF - Neuro-Oncology Advances
SN - 2632-2498
IS - 1
M1 - vdaa085
ER -