title: Association of Diffusion and Anatomic Imaging Parameters with Survival for Patients with Newly Diagnosed Glioblastoma Participating in Two Different Clinical Trials.
abstract: OBJECTIVE
  To evaluate the time course and association with survival of anatomic lesion volumes and diffusion imaging parameters for patients with newly diagnosed glioblastoma who were treated with radiation and concurrently with either temozolomide and enzastaurin (TMZ+enza cohort) or temozolomide, erlotonib, and bevaciumab (TMZ+erl+bev cohort).
  
  
  METHODS
  Regions of interest corresponding to the contrast-enhancing and hyperintense lesions on T2-weighted images were generated. Diffusion-weighted images were processed to provide maps of apparent diffusion coefficient, fractional anisotropy, and longitudinal and radial eigenvalues. Histograms of diffusion values were generated and summary statistics calculated. Cox proportional hazards models were employed to assess the association of representative imaging parameters with survival with adjustments for age, Karnofsky performance status, and extent of resection.
  
  
  RESULTS
  Although progression-free survival was significantly longer for the TMZ+erl+bev cohort (12.8 vs 7.3 months), there was no significant difference in overall survival between the two populations (17.0 vs 17.8 months). The median contrast-enhancing lesion volumes decreased from 6.3 to 1.9 cm(3) from baseline to the postradiotherapy scan for patients in the TMZ+enza cohort and from 2.8 to 0.9cm(3) for the TMZ+erl+bev cohort. Changes in the T2 lesion volumes were only significant for the latter cohort (26.5 to 11.9 cm(3)). The median apparent diffusion coefficient and related diffusion parameters were significantly increased for the TMZ+enza cohort (1054 to 1225 μm(2)/s). More of the anatomic parameters were associated with survival for the TMZ+enza cohort, whereas more diffusion parameters were associated with survival for the TMZ+erl+bev cohort.
  
  
  CONCLUSIONS
  The early changes in anatomic and diffusion imaging parameters and their association with survival reflected differences in the mechanisms of action of the treatments that were being given. This suggests that integrating diffusion metrics and anatomic lesion volumes into the Response Assessment in Neuro-Oncology criteria would assist in interpreting treatment-induced changes and predicting outcome in patients with newly diagnosed glioblastoma who are receiving such combination treatments.
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA United States; UCSF/UCB Joint Graduate Group in Bioengineering, University of California, San Francisco, San Francisco, CA United States.
authors.forename: Qiuting
authors.initials: Q
authors.lastname: Wen
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA United States.
authors.forename: Laleh
authors.initials: L
authors.lastname: Jalilian
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA United States.
authors.forename: Janine M
authors.initials: JM
authors.lastname: Lupo
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA United States.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA United States; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA United States.
authors.forename: Ritu
authors.initials: R
authors.lastname: Roy
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA United States; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA United States.
authors.forename: Annette M
authors.initials: AM
authors.lastname: Molinaro
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA United States.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Chang
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Prados
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA United States.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Butowski
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA United States.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Clarke
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA United States; UCSF/UCB Joint Graduate Group in Bioengineering, University of California, San Francisco, San Francisco, CA United States; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA United States. Electronic address: sarah.nelson@ucsf.edu.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Nelson