title: True progression versus pseudoprogression in the treatment of glioblastomas: a comparison study of normalized cerebral blood volume and apparent diffusion coefficient by histogram analysis.
abstract: OBJECTIVE
  The purpose of this study was to differentiate true progression from pseudoprogression of glioblastomas treated with concurrent chemoradiotherapy (CCRT) with temozolomide (TMZ) by using histogram analysis of apparent diffusion coefficient (ADC) and normalized cerebral blood volume (nCBV) maps.
  
  
  METHODS
  Twenty patients with histopathologically proven glioblastoma who had received CCRT with TMZ underwent perfusion-weighted imaging and diffusion-weighted imaging (b = 0, 1000 sec/mm(2)). The corresponding nCBV and ADC maps for the newly visible, entirely enhancing lesions were calculated after the completion of CCRT with TMZ. Two observers independently measured the histogram parameters of the nCBV and ADC maps. The histogram parameters between the true progression group (n = 10) and the pseudoprogression group (n = 10) were compared by use of an unpaired Student's t test and subsequent multivariable stepwise logistic regression analysis to determine the best predictors for the differential diagnosis between the two groups. Receiver operating characteristic analysis was employed to determine the best cutoff values for the histogram parameters that proved to be significant predictors for differentiating true progression from pseudoprogression. Intraclass correlation coefficient was used to determine the level of inter-observer reliability for the histogram parameters.
  
  
  RESULTS
  The 5th percentile value (C5) of the cumulative ADC histograms was a significant predictor for the differential diagnosis between true progression and pseudoprogression (p = 0.044 for observer 1; p = 0.011 for observer 2). Optimal cutoff values of 892 × 10(-6) mm(2)/sec for observer 1 and 907 × 10(-6) mm(2)/sec for observer 2 could help differentiate between the two groups with a sensitivity of 90% and 80%, respectively, a specificity of 90% and 80%, respectively, and an area under the curve of 0.880 and 0.840, respectively. There was no other significant differentiating parameter on the nCBV histograms. Inter-observer reliability was excellent or good for all histogram parameters (intraclass correlation coefficient range: 0.70-0.99).
  
  
  CONCLUSIONS
  The C5 of the cumulative ADC histogram can be a promising parameter for the differentiation of true progression from pseudoprogression of newly visible, entirely enhancing lesions after CCRT with TMZ for glioblastomas.
authors.affiliation: Department of Radiology, Seoul National University College of Medicine, Seoul 110-744, Korea.
authors.forename: Yong Sub
authors.initials: YS
authors.lastname: Song
authors.forename: Seung Hong
authors.initials: SH
authors.lastname: Choi
authors.forename: Chul-Kee
authors.initials: CK
authors.lastname: Park
authors.forename: Kyung Sik
authors.initials: KS
authors.lastname: Yi
authors.forename: Woong Jae
authors.initials: WJ
authors.lastname: Lee
authors.forename: Tae Jin
authors.initials: TJ
authors.lastname: Yun
authors.forename: Tae Min
authors.initials: TM
authors.lastname: Kim
authors.forename: Se-Hoon
authors.initials: SH
authors.lastname: Lee
authors.forename: Ji-Hoon
authors.initials: JH
authors.lastname: Kim
authors.forename: Chul-Ho
authors.initials: CH
authors.lastname: Sohn
authors.forename: Sung-Hye
authors.initials: SH
authors.lastname: Park
authors.forename: Il Han
authors.initials: IH
authors.lastname: Kim
authors.forename: Geon-Ho
authors.initials: GH
authors.lastname: Jahng
authors.forename: Kee-Hyun
authors.initials: KH
authors.lastname: Chang
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy; D002560:Cerebrovascular Circulation / Q000502:physiology*; D003131:Combined Modality Therapy; D003937:Diagnosis, Differential; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D018450:Disease Progression; D005260:Female; D005909:Glioblastoma / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012372:ROC Curve; D012039:Regional Blood Flow; D015203:Reproducibility of Results; D012189:Retrospective Studies
keywords: Apparent diffusion coefficient; Cerebral blood volume; Glioblastoma multiforme; Histogram analysis; Pseudoprogression
references.citation: Lancet Oncol. 2008 May;9(5):453-61
references.pmid: 18452856
references.citation: J Neurosurg. 1993 Apr;78(4):638-44
references.pmid: 8450338
references.citation: Neuroradiology. 2004 Oct;46(10):805-11
references.pmid: 15448954
references.citation: Neoplasia. 2009 Feb;11(2):102-25
references.pmid: 19186405
references.citation: Neuroradiology. 2010 Apr;52(4):297-306
references.pmid: 19834699
references.citation: AJNR Am J Neuroradiol. 2011 May;32(5):882-9
references.pmid: 21330401
references.citation: J Clin Oncol. 2008 Sep 10;26(26):4359; author reply 4359-60
references.pmid: 18779626
references.citation: J Magn Reson Imaging. 1999 Jan;9(1):53-60
references.pmid: 10030650
references.citation: Radiology. 1986 Jan;158(1):149-55
references.pmid: 3940373
references.citation: Radiology. 2012 Sep;264(3):834-43
references.pmid: 22771885
references.citation: NMR Biomed. 2007 Feb;20(1):49-57
references.pmid: 16986106
references.citation: Neurology. 2004 Aug 10;63(3):535-7
references.pmid: 15304589
references.citation: Radiology. 2010 Sep;256(3):906-15
references.pmid: 20634429
references.citation: Magn Reson Med. 1990 May;14(2):249-65
references.pmid: 2345506
references.citation: Cancer. 2008 Jul 15;113(2):405-10
references.pmid: 18484594
references.citation: AJNR Am J Neuroradiol. 2005 Jun-Jul;26(6):1455-60
references.pmid: 15956515
references.citation: J Clin Oncol. 1990 Jul;8(7):1277-80
references.pmid: 2358840
references.citation: AJNR Am J Neuroradiol. 2000 May;21(5):881-90
references.pmid: 10815664
references.citation: Magn Reson Med. 1996 Nov;36(5):715-25
references.pmid: 8916022
references.citation: J Neurooncol. 1997 May;32(3):253-65
references.pmid: 9049887
references.citation: AJNR Am J Neuroradiol. 2000 May;21(5):901-9
references.pmid: 10815666
references.citation: AJNR Am J Neuroradiol. 2011 Feb;32(2):382-7
references.pmid: 21252041
references.citation: Magn Reson Imaging. 1999 Jan;17(1):21-7
references.pmid: 9888395
references.citation: Radiology. 2009 Nov;253(2):486-96
references.pmid: 19789240
references.citation: AJNR Am J Neuroradiol. 2004 Feb;25(2):201-9
references.pmid: 14970018
references.citation: Tumori. 2009 Mar-Apr;95(2):191-7
references.pmid: 19579865
references.citation: Neurosurgery. 2007 Jan;60(1):31-44; discussion 44-5
references.pmid: 17228251
references.citation: AJNR Am J Neuroradiol. 2009 Mar;30(3):552-8
references.pmid: 19056837
references.citation: AJNR Am J Neuroradiol. 2006 Apr;27(4):859-67
references.pmid: 16611779
references.citation: Radiology. 2009 Jul;252(1):182-9
references.pmid: 19561256
references.citation: Clin Neurol Neurosurg. 2009 Oct;111(8):679-82
references.pmid: 19640635
references.citation: Radiology. 2011 Dec;261(3):882-90
references.pmid: 21969667
references.citation: Surg Neurol. 2009 Oct;72(4):423-8
references.pmid: 19150114
references.citation: J Clin Oncol. 2010 Apr 10;28(11):1963-72
references.pmid: 20231676
references.citation: Radiology. 2002 Sep;224(3):797-803
references.pmid: 12202717
references.citation: Q J Med. 1994 Feb;87(2):119-29
references.pmid: 8153288
references.citation: N Engl J Med. 2005 Mar 10;352(10):987-96
references.pmid: 15758009
references.citation: Int J Radiat Oncol Biol Phys. 2007 May 1;68(1):151-8
references.pmid: 17289287