title: Differentiation of true progression from pseudoprogression in glioblastoma treated with radiation therapy and concomitant temozolomide: comparison study of standard and high-b-value diffusion-weighted imaging.
abstract: OBJECTIVE
  To explore the role of histogram analysis of apparent diffusion coefficient (ADC) maps obtained at standard- and high-b-value (1000 and 3000 sec/mm(2), respectively) diffusion-weighted (DW) imaging in the differentiation of true progression from pseudoprogression in glioblastoma treated with radiation therapy and concomitant temozolomide.
  
  
  METHODS
  This retrospective study was approved by the institutional review board of Seoul National University Hospital, and informed consent requirement was waived. Thirty patients with histopathologically proved glioblastoma who had undergone concurrent chemotherapy and radiation therapy (CCRT) with temozolomide underwent diffusion-weighted MR imaging with b values of 1000 and 3000 sec/mm(2), and corresponding ADC maps were calculated from entire newly developed or enlarged enhancing lesions after completion of CCRT. Histogram parameters of each ADC map between true progression (n = 15) and pseudoprogression (n = 15) groups were compared by using the unpaired Student t test. Receiver operating characteristic analysis was used to determine the best cutoff values for predictors in the differentiation of true progression from pseudoprogression. Results were validated in an independent test set of nine patients by using the best cutoff value to predict differentiation of true progression from pseudoprogression. The accuracy of the selected best cutoff value in the independent test set was then calculated.
  
  
  RESULTS
  In terms of cumulative histograms, the fifth percentile of both ADC at b value of 1000 sec/mm(2) (ADC1000) and the ADC at b value of 3000 sec/mm(2) (ADC3000) were significantly lower in the true progression group than in the pseudoprogression group (P = .049 and P < .001, respectively). In contrast, neither the mean ADC1000 nor the mean ADC3000 was significantly different between the two groups. The diagnostic values of the parameters derived from ADC1000 and ADC3000 were compared, and a significant difference (0.224, P = .016) was found between the area under the receiver operating characteristic curve of the fifth percentile for ADC1000 and that for ADC3000. The accuracies were 66.7% (six of nine patients) and 88.9% (eight of nine patients) based on the fifth percentile of both ADC1000 and ADC3000 in the independent test set, respectively.
  
  
  CONCLUSIONS
  The fifth percentile of the cumulative ADC histogram obtained at a high b value was the most promising parameter in the differentiation of true progression from pseudoprogression of the newly developed or enlarged enhancing lesions after CCRT with temozolomide for glioblastoma treatment. Online supplemental material is available for this article.
authors.affiliation: From the Department of Radiology (H.H.C., S.H.C., I.R., S.C.K., J.A.Y., H.S., S.C.J., A.L.L., T.J.Y., J.H.K., C.H.S.), Department of Internal Medicine, Cancer Research Institute (T.M.K., S.H.L.), Department of Neurosurgery (C.K.P.), Department of Pathology (S.H.P.), and Department of Radiation Oncology, Cancer Research Institute (I.H.K.), Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-744, Korea; and Center for Nanoparticle Research, Institute for Basic Science, and School of Chemical and Biological Engineering, Seoul National University, Seoul, Korea (S.H.C.).
authors.forename: Hee Ho
authors.initials: HH
authors.lastname: Chu
authors.forename: Seung Hong
authors.initials: SH
authors.lastname: Choi
authors.forename: Inseon
authors.initials: I
authors.lastname: Ryoo
authors.forename: Soo Chin
authors.initials: SC
authors.lastname: Kim
authors.forename: Jeong A
authors.initials: JA
authors.lastname: Yeom
authors.forename: Hwaseon
authors.initials: H
authors.lastname: Shin
authors.forename: Seung Chai
authors.initials: SC
authors.lastname: Jung
authors.forename: A Leum
authors.initials: AL
authors.lastname: Lee
authors.forename: Tae Jin
authors.initials: TJ
authors.lastname: Yoon
authors.forename: Tae Min
authors.initials: TM
authors.lastname: Kim
authors.forename: Se-Hoon
authors.initials: SH
authors.lastname: Lee
authors.forename: Chul-Kee
authors.initials: CK
authors.lastname: Park
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
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000473:pathology* / Q000628:therapy*; D059248:Chemoradiotherapy; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D038524:Diffusion Magnetic Resonance Imaging; D018450:Disease Progression; D005260:Female; D005909:Glioblastoma / Q000473:pathology* / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D000077204:Temozolomide; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide