Korean Journal of Radiology

The Korean Society of Radiology (대한영상의학회)
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Optimized Image-Based Surrogate Endpoints in Targeted Therapies for Glioblastoma: A Systematic Review and Meta-Analysis of Phase III Randomized Controlled Trials

  • Chong Hyun Suh (Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Ho Sung Kim (Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Seung Chai Jung (Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Choong Gon Choi (Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Sang Joon Kim (Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Kyung Won Kim (Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center)
  • Received : 2019.11.09
  • Accepted : 2019.12.19
  • Published : 2020.04.01
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Abstract

Objective: We aimed to determine the optimized image-based surrogate endpoints (IBSEs) in targeted therapies for glioblastoma through a systematic review and meta-analysis of phase III randomized controlled trials (RCTs). Materials and Methods: A systematic search of OVID-MEDLINE and EMBASE for phase III RCTs on glioblastoma was performed in December 2017. Data on overall survival (OS) and IBSEs, including progression-free survival (PFS), 6-month PFS (6moPFS), 12-month PFS (12moPFS), median PFS, and objective response rate (ORR) were extracted. Weighted linear regression analysis for the hazard ratio for OS and the hazard ratios or odds ratios for IBSEs was performed. The associations between IBSEs and OS were evaluated. Subgroup analyses according to disease stage (newly diagnosed glioblastoma versus recurrent glioblastoma), types of test treatment, and types of response assessment criteria were performed. Results: Twenty-three phase III RCTs published between 2000 and 2017, including 8387 patients, met the inclusion criteria. OS showed strong correlations with PFS (standardized β coefficient [R] = 0.719), 6moPFS (R = 0.647), and 12moPFS (R = 0.638). OS showed no correlations with median PFS and ORR. In subgroup analysis according to types of therapies, PFS showed the highest correlations with OS in targeted therapies for cell cycle pathways (R = 0.913) and growth factor receptors and their downstream pathways (R = 0.962). 12moPFS showed the highest correlation with OS in antiangiogenic therapy (R = 0.821). The response assessment in neuro-oncology criteria provided higher correlation coefficients between OS and IBSEs than the Macdonald criteria. Conclusion: Overall, PFS is an optimized IBSE in targeted therapies for glioblastoma; however, 12moPFS is optimal in antiangiogenic therapy.

Keywords

Acknowledgement

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (grant number: NRF-2017R1A2A2A05001217).

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