title: Large-volume low apparent diffusion coefficient lesions predict poor survival in bevacizumab-treated glioblastoma patients.
abstract: Glioblastomas treated with bevacizumab may develop low-signal apparent diffusion coefficient (low-ADC) lesions, which may reflect increased tumor cellularity or atypical necrosis. The purpose of this study was to examine the relationship between low-ADC lesions and overall survival (OS). We hypothesized that growing low-ADC lesions would be associated with shorter OS.
  
  
  
  We retrospectively identified 52 patients treated with bevacizumab for the first (n = 42, 81%) or later recurrence of primary glioblastoma, who had low-ADC lesions and 2 post-bevacizumab scans ≤90 days apart. Low-ADC lesion volumes were measured, and normalized 5th percentile histogram low-ADC values were recorded. Using OS as the primary endpoint, semiparametric Cox models were fitted to ascertain univariate and multivariate hazard ratios (HRs) with significance at P = .05.
  
  
  
  Median OS was 9.1 months (95% CI = 7.2-14.3). At the second post-bevacizumab scan, the volume of the low-ADC lesion (median: 12.94 cm(3)) was inversely associated with OS, with larger volumes predicting shorter OS (HR = 1.014 [95% CI = 1.003-1.025], P = .009). The percent change in low-ADC volume (median: 6.8%) trended toward increased risk of death with growing volumes (P = .08). Normalized 5th percentile low-ADC value and its percent change were not associated with OS (P > .51). Also correlated with shorter OS were the pre-bevacizumab nonenhancing volume (P = .025), the first post-bevacizumab enhancing volume (P = .040), and the second post-bevacizumab enhancing volume (P = .004).
  
  
  
  The volume of low-ADC lesions at the second post-bevacizumab scan predicted shorter OS. This suggests that low-ADC lesions may be considered important imaging markers and included in treatment decision algorithms.
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York (M.Z., B.G., S.K., J.A.-P., A.I.H., R.J.Y.); Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York (A.T., T.K., I.G.); Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York (K.M.W., Z.Z.); Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York (M.R.); Brain Tumor Center, Memorial Sloan Kettering Cancer Center, New York, New York (T.K., S.K., I.G., A.I.H., M.R., R.J.Y.).
authors.forename: Myron
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York (M.Z., B.G., S.K., J.A.-P., A.I.H., R.J.Y.); Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York (A.T., T.K., I.G.); Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York (K.M.W., Z.Z.); Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York (M.R.); Brain Tumor Center, Memorial Sloan Kettering Cancer Center, New York, New York (T.K., S.K., I.G., A.I.H., M.R., R.J.Y.).
authors.forename: Bryanna
authors.initials: B
authors.lastname: Gulotta
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York (M.Z., B.G., S.K., J.A.-P., A.I.H., R.J.Y.); Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York (A.T., T.K., I.G.); Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York (K.M.W., Z.Z.); Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York (M.R.); Brain Tumor Center, Memorial Sloan Kettering Cancer Center, New York, New York (T.K., S.K., I.G., A.I.H., M.R., R.J.Y.).
authors.forename: Alissa
authors.initials: A
authors.lastname: Thomas
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York (M.Z., B.G., S.K., J.A.-P., A.I.H., R.J.Y.); Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York (A.T., T.K., I.G.); Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York (K.M.W., Z.Z.); Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York (M.R.); Brain Tumor Center, Memorial Sloan Kettering Cancer Center, New York, New York (T.K., S.K., I.G., A.I.H., M.R., R.J.Y.).
authors.forename: Thomas
authors.initials: T
authors.lastname: Kaley
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York (M.Z., B.G., S.K., J.A.-P., A.I.H., R.J.Y.); Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York (A.T., T.K., I.G.); Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York (K.M.W., Z.Z.); Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York (M.R.); Brain Tumor Center, Memorial Sloan Kettering Cancer Center, New York, New York (T.K., S.K., I.G., A.I.H., M.R., R.J.Y.).
authors.forename: Sasan
authors.initials: S
authors.lastname: Karimi
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York (M.Z., B.G., S.K., J.A.-P., A.I.H., R.J.Y.); Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York (A.T., T.K., I.G.); Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York (K.M.W., Z.Z.); Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York (M.R.); Brain Tumor Center, Memorial Sloan Kettering Cancer Center, New York, New York (T.K., S.K., I.G., A.I.H., M.R., R.J.Y.).
authors.forename: Igor
authors.initials: I
authors.lastname: Gavrilovic
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York (M.Z., B.G., S.K., J.A.-P., A.I.H., R.J.Y.); Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York (A.T., T.K., I.G.); Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York (K.M.W., Z.Z.); Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York (M.R.); Brain Tumor Center, Memorial Sloan Kettering Cancer Center, New York, New York (T.K., S.K., I.G., A.I.H., M.R., R.J.Y.).
authors.forename: Kaitlin M
authors.initials: KM
authors.lastname: Woo
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York (M.Z., B.G., S.K., J.A.-P., A.I.H., R.J.Y.); Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York (A.T., T.K., I.G.); Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York (K.M.W., Z.Z.); Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York (M.R.); Brain Tumor Center, Memorial Sloan Kettering Cancer Center, New York, New York (T.K., S.K., I.G., A.I.H., M.R., R.J.Y.).
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York (M.Z., B.G., S.K., J.A.-P., A.I.H., R.J.Y.); Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York (A.T., T.K., I.G.); Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York (K.M.W., Z.Z.); Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York (M.R.); Brain Tumor Center, Memorial Sloan Kettering Cancer Center, New York, New York (T.K., S.K., I.G., A.I.H., M.R., R.J.Y.).
authors.forename: Julio
authors.initials: J
authors.lastname: Arevalo-Perez
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York (M.Z., B.G., S.K., J.A.-P., A.I.H., R.J.Y.); Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York (A.T., T.K., I.G.); Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York (K.M.W., Z.Z.); Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York (M.R.); Brain Tumor Center, Memorial Sloan Kettering Cancer Center, New York, New York (T.K., S.K., I.G., A.I.H., M.R., R.J.Y.).
authors.forename: Andrei I
authors.initials: AI
authors.lastname: Holodny
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York (M.Z., B.G., S.K., J.A.-P., A.I.H., R.J.Y.); Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York (A.T., T.K., I.G.); Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York (K.M.W., Z.Z.); Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York (M.R.); Brain Tumor Center, Memorial Sloan Kettering Cancer Center, New York, New York (T.K., S.K., I.G., A.I.H., M.R., R.J.Y.).
authors.forename: Marc
authors.initials: M
authors.lastname: Rosenblum
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York (M.Z., B.G., S.K., J.A.-P., A.I.H., R.J.Y.); Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York (A.T., T.K., I.G.); Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York (K.M.W., Z.Z.); Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York (M.R.); Brain Tumor Center, Memorial Sloan Kettering Cancer Center, New York, New York (T.K., S.K., I.G., A.I.H., M.R., R.J.Y.).
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Young
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012189:Retrospective Studies
chemical_list: D000970:Antineoplastic Agents; D000068258:Bevacizumab
keywords: (ADC); apparent diffusion coefficient; bevacizumab; diffusion; glioblastoma