title: Isolated diffusion restriction precedes the development of enhancing tumor in a subset of patients with glioblastoma.
abstract: OBJECTIVE
  Most response criteria for patients with glioblastoma rely on increases in the contrast enhancing abnormality to determine tumor progression. Our aim was to determine retrospectively in patients with glioblastoma whether diffusion restriction can predict the development of new enhancing mass lesions.
  
  
  METHODS
  We reviewed the brain MR imaging scans (including DWI and ADC maps) of 208 patients with glioblastoma. Patients with restricted diffusion in or adjacent to the tumor were identified, with further analysis only performed on those patients with low-ADC lesions without enhancement. These patients were followed to determine if new concordant enhancement developed at the site of the low-ADC lesion. A Wilcoxon signed rank test, competing risk analysis, and Kaplan-Meier curves were used to compare the mean drop in ADC values, assess enhancement-free survival, and determine overall survival, respectively.
  
  
  RESULTS
  In 67 of the 208 patients (32.2%), visibly detectable restricted diffusion was seen during treatment. The study cohort was formed by the 27 patients with low-ADC lesions and no corresponding enhancement. Twenty-three (85.2%) patients developed gadolinium-enhancing tumor at the site of restricted diffusion a median of 3.0 months later (95% CI, 2.6-4.1 months). The mean decrease in ADC was 22.9% from baseline (P < .001). The 3-month enhancement-free survival probability was 0.481 (95% CI, 0.288-0.675). The 12-month overall survival probability was 0.521 (95% CI, 0.345-0.788). Restricted diffusion predicted enhancement regardless of antiangiogenic therapy with bevacizumab.
  
  
  CONCLUSIONS
  In a subset of patients with glioblastoma, development of a new focus of restricted diffusion during treatment may precede the development of new enhancing tumor.
authors: Department of Radiology (A.G., R.J.Y., S.K., S.S., A.I.H.), Brain Tumor Center (R.J.Y., S.K., P.H.G., A.I.H., A.B.L.), Departments of Neurosurgery (P.H.G.), Epidemiology and Biostatistics (Z.Z., Q.M.), and Neurology (A.B.L.), Memorial Sloan-Kettering Cancer Center, New York, New York.
authors: A
authors: A
authors: Gupta
authors: Department of Radiology (A.G., R.J.Y., S.K., S.S., A.I.H.), Brain Tumor Center (R.J.Y., S.K., P.H.G., A.I.H., A.B.L.), Departments of Neurosurgery (P.H.G.), Epidemiology and Biostatistics (Z.Z., Q.M.), and Neurology (A.B.L.), Memorial Sloan-Kettering Cancer Center, New York, New York.
authors: R J
authors: RJ
authors: Young
authors: Department of Radiology (A.G., R.J.Y., S.K., S.S., A.I.H.), Brain Tumor Center (R.J.Y., S.K., P.H.G., A.I.H., A.B.L.), Departments of Neurosurgery (P.H.G.), Epidemiology and Biostatistics (Z.Z., Q.M.), and Neurology (A.B.L.), Memorial Sloan-Kettering Cancer Center, New York, New York.
authors: S
authors: S
authors: Karimi
authors: Department of Radiology (A.G., R.J.Y., S.K., S.S., A.I.H.), Brain Tumor Center (R.J.Y., S.K., P.H.G., A.I.H., A.B.L.), Departments of Neurosurgery (P.H.G.), Epidemiology and Biostatistics (Z.Z., Q.M.), and Neurology (A.B.L.), Memorial Sloan-Kettering Cancer Center, New York, New York.
authors: S
authors: S
authors: Sood
authors: Department of Radiology (A.G., R.J.Y., S.K., S.S., A.I.H.), Brain Tumor Center (R.J.Y., S.K., P.H.G., A.I.H., A.B.L.), Departments of Neurosurgery (P.H.G.), Epidemiology and Biostatistics (Z.Z., Q.M.), and Neurology (A.B.L.), Memorial Sloan-Kettering Cancer Center, New York, New York.
authors: Z
authors: Z
authors: Zhang
authors: Department of Radiology (A.G., R.J.Y., S.K., S.S., A.I.H.), Brain Tumor Center (R.J.Y., S.K., P.H.G., A.I.H., A.B.L.), Departments of Neurosurgery (P.H.G.), Epidemiology and Biostatistics (Z.Z., Q.M.), and Neurology (A.B.L.), Memorial Sloan-Kettering Cancer Center, New York, New York.
authors: Q
authors: Q
authors: Mo
authors: Department of Radiology (A.G., R.J.Y., S.K., S.S., A.I.H.), Brain Tumor Center (R.J.Y., S.K., P.H.G., A.I.H., A.B.L.), Departments of Neurosurgery (P.H.G.), Epidemiology and Biostatistics (Z.Z., Q.M.), and Neurology (A.B.L.), Memorial Sloan-Kettering Cancer Center, New York, New York.
authors: P H
authors: PH
authors: Gutin
authors: Department of Radiology (A.G., R.J.Y., S.K., S.S., A.I.H.), Brain Tumor Center (R.J.Y., S.K., P.H.G., A.I.H., A.B.L.), Departments of Neurosurgery (P.H.G.), Epidemiology and Biostatistics (Z.Z., Q.M.), and Neurology (A.B.L.), Memorial Sloan-Kettering Cancer Center, New York, New York.
authors: A I
authors: AI
authors: Holodny
authors: Department of Radiology (A.G., R.J.Y., S.K., S.S., A.I.H.), Brain Tumor Center (R.J.Y., S.K., P.H.G., A.I.H., A.B.L.), Departments of Neurosurgery (P.H.G.), Epidemiology and Biostatistics (Z.Z., Q.M.), and Neurology (A.B.L.), Memorial Sloan-Kettering Cancer Center, New York, New York.
authors: A B
authors: AB
authors: Lassman
references: J Neurooncol. 2010 Feb;96(3):423-31
references: 19859666
references: J Magn Reson Imaging. 2010 Oct;32(4):788-95
references: 20882608
references: AJNR Am J Neuroradiol. 2007 Oct;28(9):1693-9
references: 17885229
references: J Neurooncol. 2010 Aug;99(1):49-56
references: 20035366
references: Magn Reson Med. 1992 Mar;24(1):174-6
references: 1556924
references: J Clin Oncol. 2007 Oct 20;25(30):4714-21
references: 17947718
references: AJNR Am J Neuroradiol. 2001 Jan;22(1):60-4
references: 11158889
references: Neuro Oncol. 2010 May;12(5):466-72
references: 20406897
references: J Magn Reson Imaging. 1999 Jan;9(1):53-60
references: 10030650
references: Neurosurgery. 2006 Jun;58(6):1099-107; discussion 1099-107
references: 16723889
references: Int J Radiat Oncol Biol Phys. 2008 Aug 1;71(5):1553-62
references: 18538491
references: Radiology. 2002 Jul;224(1):177-83
references: 12091680
references: J Clin Oncol. 2010 Feb 20;28(6):e91-3
references: 19933906
references: Int J Radiat Oncol Biol Phys. 2009 Sep 1;75(1):156-63
references: 19167838
references: Acta Neuropathol. 2007 Aug;114(2):97-109
references: 17618441
references: Br J Radiol. 2006 Aug;79(944):652-8
references: 16641420
references: Radiology. 2006 Dec;241(3):839-46
references: 17032910
references: Cancer Cell. 2007 Jan;11(1):6-8
references: 17222788
references: Radiographics. 1996 Nov;16(6):1413-38; quiz 1462-3
references: 8946545
references: Neuro Oncol. 2008 Jun;10(3):361-7
references: 18401015
references: Radiology. 2007 May;243(2):493-9
references: 17356177
references: J Neurooncol. 2000 Dec;50(3):215-26
references: 11263501
references: J Magn Reson Imaging. 2006 Oct;24(4):709-24
references: 16958058
references: Magn Reson Med. 1999 Jan;41(1):2-7
references: 10025604
references: Radiology. 2008 Nov;249(2):624-30
references: 18936317
references: Radiology. 2009 Jul;252(1):182-9
references: 19561256
references: J Neurooncol. 2010 Feb;96(3):375-84
references: 19609489
references: NMR Biomed. 2007 Feb;20(1):49-57
references: 16986106
references: Radiographics. 2006 Oct;26 Suppl 1:S173-89
references: 17050514
references: J Clin Oncol. 2010 Apr 10;28(11):1963-72
references: 20231676
references: Radiology. 2002 Sep;224(3):797-803
references: 12202717
references: Eur J Radiol. 2005 Sep;55(3):393-400
references: 16129247
references: N Engl J Med. 2005 Mar 10;352(10):987-96
references: 15758009
references: J Neuroimaging. 2008 Jul;18(3):276-81
references: 18482368
references: J Comput Assist Tomogr. 2004 Nov-Dec;28(6):735-46
references: 15538145