Diagnostic dilemma of pseudoprogression in the treatment of newly diagnosed glioblastomas: the role of assessing relative cerebral blood flow volume and oxygen-6-methylguanine-DNA methyltransferase promoter methylation status.
OBJECTIVE
Methylation of the MGMT gene promoter is associated with a favorable prognosis in adult patients with GBM treated with TMZ. We determined the incidence of pseudoprogression according to the MGMT methylation status and the potential value of DSC perfusion MR images for predicting pseudoprogression.


METHODS
New or enlarged enhancing lesions after CCRT in adult patients with newly diagnosed GBMs were prospectively assessed by measuring their rCBV by using DSC perfusion MR images. Tumor tissue was assayed to determine MGMT promoter methylation status. All patients were regularly followed up at an interval of 2 months by MR images, including DSC perfusion MR images.


RESULTS
Ninety eligible patients were enrolled in this study. After CCRT, new or enlarged enhanced lesions were found in 59 of 90 patients, which were subsequently classified as pseudoprogression (26 patients, 28.9%) and real progression (33 patients, 36.7%). Overall, there was a significant difference in the mean rCBV between pseudoprogression and real tumor progression (P = .003). The ROC curve revealed that an rCBV ratio >1.47 had an 81.5% sensitivity and a 77.8% specificity. The unmethylated MGMT promoter group had a significant difference of mean rCBV between pseudoprogression and real progression (P = .009), though the methylated MGMT promoter group had no significant difference (P = .258).


CONCLUSIONS
The current study suggests that rCBV measured by DSC perfusion MR images has a differential impact on the predictability of pseudoprogression in patients with GBM.
Department of Neurosurgery, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea.
D-S
DS
Kong
S T
ST
Kim
E-H
EH
Kim
D H
DH
Lim
W S
WS
Kim
Y-L
YL
Suh
J-I
JI
Lee
K
K
Park
J H
JH
Kim
D-H
DH
Nam
D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000502:physiology*; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000502:physiology; D012372:ROC Curve; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes
Lancet Oncol. 2008 May;9(5):453-61
18452856
Int J Radiat Oncol Biol Phys. 2006 Jun 1;65(2):499-508
16517093
Cancer Res. 2000 Nov 1;60(21):5954-8
11085511
Neuroradiology. 2002 Mar;44(3):216-22
11942375
AJNR Am J Neuroradiol. 2000 May;21(5):901-9
10815666
J Neurosurg. 2003 May;98(5):1056-64
12744366
Ann Nucl Med. 2004 Jun;18(4):291-6
15359921
J Clin Oncol. 2009 Jun 20;27(18):2905-8
19451418
Surg Neurol. 2009 Oct;72(4):423-8
19150114
J Clin Oncol. 2008 May 1;26(13):2192-7
18445844
AJNR Am J Neuroradiol. 2007 Jun-Jul;28(6):1078-84
17569962
Jpn J Clin Oncol. 2008 Feb;38(2):140-2
18245515
Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9821-6
8790415
Cancer. 2008 Jul 15;113(2):405-10
18484594
Methods Mol Biol. 2009;520:297-314
19381963
N Engl J Med. 2005 Mar 10;352(10):997-1003
15758010
J Clin Oncol. 1990 Jul;8(7):1277-80
2358840
Radiology. 2002 Apr;223(1):11-29
11930044
Neuro Oncol. 2008 Jun;10(3):361-7
18401015
J Neurooncol. 2007 Mar;82(1):81-3
16944309
J Clin Oncol. 2008 Sep 10;26(26):4359; author reply 4359-60
18779626
J Clin Oncol. 2002 Jan 15;20(2):396-404
11786566
Oncologist. 2004;9(5):528-37
15477637
Int J Cancer. 2001 Jun 20;96(3):191-7
11410888
AJNR Am J Neuroradiol. 2009 Mar;30(3):552-8
19056837
J Neurol. 2009 Jun;256(6):878-87
19274425
J Clin Oncol. 2008 Sep 1;26(25):4189-99
18757334