title: Identification of early and distinct glioblastoma response patterns treated by boron neutron capture therapy not predicted by standard radiographic assessment using functional diffusion map.
abstract: BACKGROUND
  Radiologic response of brain tumors is traditionally assessed according to the Macdonald criteria 10 weeks from the start of therapy. Because glioblastoma (GB) responds in days rather than weeks after boron neutron capture therapy (BNCT) that is a form of tumor-selective particle radiation, it is inconvenient to use the Macdonald criteria to assess the therapeutic efficacy of BNCT by gadolinium-magnetic resonance imaging (Gd-MRI). Our study assessed the utility of functional diffusion map (fDM) for evaluating response patterns in GB treated by BNCT.
  
  
  METHODS
  The fDM is an image assessment using time-dependent changes of apparent diffusion coefficient (ADC) in tumors on a voxel-by-voxel approach. Other than time-dependent changes of ADC, fDM can automatically assess minimum/maximum ADC, Response Evaluation Criteria In Solid Tumors (RECIST), and the volume of enhanced lesions on Gd-MRI over time. We assessed 17 GB patients treated by BNCT using fDM. Additionally, in order to verify our results, we performed a histopathological examination using F98 rat glioma models.
  
  
  RESULTS
  Only the volume of tumor with decreased ADC by fDM at 2 days after BNCT was a good predictor for GB patients treated by BNCT (P value = 0.022 by log-rank test and 0.033 by wilcoxon test). In a histopathological examination, brain sections of F98 rat glioma models treated by BNCT showed cell swelling of both the nuclei and the cytoplasm compared with untreated rat glioma models.
  
  
  CONCLUSIONS
  The fDM could identify response patterns in BNCT-treated GB earlier than a standard radiographic assessment. Early detection of treatment failure can allow a change or supplementation before tumor progression and might lead to an improvement of GB patients' prognosis.
authors.affiliation: Department of Neurosurgery, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki City, Osaka 569-8686, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Hiramatsu
authors.forename: Shinji
authors.initials: S
authors.lastname: Kawabata
authors.forename: Motomasa
authors.initials: M
authors.lastname: Furuse
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Miyatake
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Kuroiwa
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D000818:Animals; D016754:Boron Neutron Capture Therapy; D001932:Brain Neoplasms / Q000532:radiotherapy*; D004058:Diffusion; D005260:Female; D005682:Gadolinium / Q000494:pharmacology; D005909:Glioblastoma / Q000401:mortality / Q000532:radiotherapy*; D005910:Glioma / Q000532:radiotherapy*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D051381:Rats; D011916:Rats, Inbred F344; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D005682:Gadolinium
references.citation: Cancer. 1981 Jan 1;47(1):207-14
references.pmid: 7459811
references.citation: Appl Radiat Isot. 2009 Jul;67(7-8 Suppl):S15-8
references.pmid: 19398348
references.citation: J Clin Oncol. 1990 Jul;8(7):1277-80
references.pmid: 2358840
references.citation: Cancer Res. 2004 Apr 1;64(7):2317-23
references.pmid: 15059878
references.citation: Neuroimaging Clin N Am. 2003 Nov;13(4):717-39
references.pmid: 15024957
references.citation: Radiology. 2000 Nov;217(2):377-84
references.pmid: 11058631
references.citation: Clin Cancer Res. 1997 Sep;3(9):1457-66
references.pmid: 9815831
references.citation: J Natl Cancer Inst. 2000 Feb 2;92(3):205-16
references.pmid: 10655437
references.citation: Neuro Oncol. 2013 Mar;15(3):382-90
references.pmid: 23275575
references.citation: Magn Reson Med. 2000 Jun;43(6):828-36
references.pmid: 10861877
references.citation: N Engl J Med. 2005 Mar 10;352(10):987-96
references.pmid: 15758009
references.citation: J Clin Oncol. 1994 Sep;12(9):1886-9
references.pmid: 8083712
references.citation: J Clin Oncol. 2008 Jul 10;26(20):3387-94
references.pmid: 18541899
references.citation: Med Image Anal. 1997 Apr;1(3):195-206
references.pmid: 9873906
references.citation: Proc Natl Acad Sci U S A. 2005 Nov 15;102(46):16759-64
references.pmid: 16267128
references.citation: J Neurooncol. 2008 Sep;89(2):239-46
references.pmid: 18566749
references.citation: AJNR Am J Neuroradiol. 2008 Mar;29(3):419-24
references.pmid: 18272557
references.citation: Int J Radiat Biol. 2006 Jan;82(1):21-9
references.pmid: 16546900
references.citation: Cancer Res. 2001 Jul 1;61(13):4971-3
references.pmid: 11431326
references.citation: Cancer. 2008 Jul 15;113(2):405-10
references.pmid: 18484594
references.citation: J Neurosurg. 1980 Dec;53(6):808-15
references.pmid: 7003068
references.citation: Magn Reson Imaging. 2007 Apr;25(3):303-10
references.pmid: 17371718
references.citation: J Neurosurg. 2005 Dec;103(6):1000-9
references.pmid: 16381186
references.citation: Neuro Oncol. 1999 Oct;1(4):282-8
references.pmid: 11550320
references.citation: J Natl Cancer Inst. 2000 Dec 20;92(24):2029-36
references.pmid: 11121466
references.citation: Int J Radiat Oncol Biol Phys. 2003 Jan 1;55(1):5-15
references.pmid: 12504030
references.citation: Neuro Oncol. 2012 Mar;14(3):333-43
references.pmid: 22270220
references.citation: Neoplasia. 2006 Apr;8(4):259-67
references.pmid: 16756718
references.citation: J Neurooncol. 1998 Jan;36(1):91-102
references.pmid: 9525831
references.citation: Cancer Gene Ther. 1998 Mar-Apr;5(2):101-9
references.pmid: 9570301
references.citation: Brain Tumor Pathol. 2007;24(1):7-13
references.pmid: 18095138
references.citation: J Clin Oncol. 2003 Mar 15;21(6):1094-100
references.pmid: 12637476
references.citation: J Clin Oncol. 1988 Feb;6(2):338-43
references.pmid: 3339397
references.citation: J Radiat Res. 2009 Jan;50(1):51-60
references.pmid: 18957828
references.citation: Radiology. 1988 Aug;168(2):497-505
references.pmid: 3393671
references.citation: Nat Clin Pract Oncol. 2008 Nov;5(11):634-44
references.pmid: 18711427
references.citation: Curr Opin Neurol. 2009 Dec;22(6):633-8
references.pmid: 19770760