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<meta name="DC.Title" content="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" />
<meta name="DC.Identifier" content="10.3174/ajnr.A2286" />
<meta name="DC.Date" content="2011-02-01" />
<meta name="DC.Publisher" content="American Journal of Neuroradiology" />
<meta name="DC.Rights" content="Copyright © American Society of Neuroradiology" />
<meta name="DC.AccessRights" content="restricted" />
<meta name="DC.Description" content="BACKGROUND AND PURPOSE: 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.

MATERIALS AND 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 &gt;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.

CBV
:   cerebral blood volume
CCRT
:   concomitant chemoradiotherapy
CI
:   confidence interval
Cum
:   cumulative
DSC
:   dynamic susceptibility-weighted contrastenhanced
FA
:   flip angle
FLAIR
:   fluid-attenuated inversion recovery
GBM
:   glioblastoma
MGMT 
:   O6-methylguanine-DNA methyltransferase
MSP
:   methylation-specific polymerase chain reaction
O6
:   oxygen-6
OS
:   overall survival
pseudo
:   pseudoprogression
pts
:   patients
rCBV
:   relative cerebral blood volume
ROC
:   receiver operating characteristic analysis
TMZ
:   temozolomide
WHO
:   World Health Organization" />
<meta name="DC.Contributor" content="D.-S. Kong" />
<meta name="DC.Contributor" content="S.T. Kim" />
<meta name="DC.Contributor" content="E.-H. Kim" />
<meta name="DC.Contributor" content="D.H. Lim" />
<meta name="DC.Contributor" content="W.S. Kim" />
<meta name="DC.Contributor" content="Y.-L. Suh" />
<meta name="DC.Contributor" content="J.-I. Lee" />
<meta name="DC.Contributor" content="K. Park" />
<meta name="DC.Contributor" content="J.H. Kim" />
<meta name="DC.Contributor" content="D.-H. Nam" />
<meta name="article:published_time" content="2011-02-01" />
<meta name="article:section" content="Brain" />
<meta name="citation_title" content="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" />
<meta name="citation_abstract" lang="en" content="&lt;h3&gt;BACKGROUND AND PURPOSE:&lt;/h3&gt;
&lt;p&gt;Methylation of the &lt;i&gt;MGMT&lt;/i&gt; 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 &lt;i&gt;MGMT&lt;/i&gt; methylation status and the potential value of DSC perfusion MR images for predicting pseudoprogression.&lt;/p&gt;&lt;h3&gt;MATERIALS AND METHODS:&lt;/h3&gt;
&lt;p&gt;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 &lt;i&gt;MGMT&lt;/i&gt; promoter methylation status. All patients were regularly followed up at an interval of 2 months by MR images, including DSC perfusion MR images.&lt;/p&gt;&lt;h3&gt;RESULTS:&lt;/h3&gt;
&lt;p&gt;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 (&lt;i&gt;P&lt;/i&gt; = .003). The ROC curve revealed that an rCBV ratio &amp;gt;1.47 had an 81.5% sensitivity and a 77.8% specificity. The unmethylated &lt;i&gt;MGMT&lt;/i&gt; promoter group had a significant difference of mean rCBV between pseudoprogression and real progression (&lt;i&gt;P&lt;/i&gt; = .009), though the methylated &lt;i&gt;MGMT&lt;/i&gt; promoter group had no significant difference (&lt;i&gt;P&lt;/i&gt; = .258).&lt;/p&gt;&lt;h3&gt;CONCLUSIONS:&lt;/h3&gt;
&lt;p&gt;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.&lt;/p&gt;" />
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<meta name="twitter:title" content="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" />
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<meta name="twitter:description" content="BACKGROUND AND PURPOSE: 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.

MATERIALS AND 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 &gt;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.

CBV
:   cerebral blood volume
CCRT
:   concomitant chemoradiotherapy
CI
:   confidence interval
Cum
:   cumulative
DSC
:   dynamic susceptibility-weighted contrastenhanced
FA
:   flip angle
FLAIR
:   fluid-attenuated inversion recovery
GBM
:   glioblastoma
MGMT 
:   O6-methylguanine-DNA methyltransferase
MSP
:   methylation-specific polymerase chain reaction
O6
:   oxygen-6
OS
:   overall survival
pseudo
:   pseudoprogression
pts
:   patients
rCBV
:   relative cerebral blood volume
ROC
:   receiver operating characteristic analysis
TMZ
:   temozolomide
WHO
:   World Health Organization" />
<meta name="og-title" property="og:title" content="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" />
<meta name="og-url" property="og:url" content="http://ajnr-stage2.stage.highwire.org/content/32/2/382" />
<meta name="og-site-name" property="og:site_name" content="American Journal of Neuroradiology" />
<meta name="og-description" property="og:description" content="BACKGROUND AND PURPOSE: 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.

MATERIALS AND 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 &gt;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.

CBV
:   cerebral blood volume
CCRT
:   concomitant chemoradiotherapy
CI
:   confidence interval
Cum
:   cumulative
DSC
:   dynamic susceptibility-weighted contrastenhanced
FA
:   flip angle
FLAIR
:   fluid-attenuated inversion recovery
GBM
:   glioblastoma
MGMT 
:   O6-methylguanine-DNA methyltransferase
MSP
:   methylation-specific polymerase chain reaction
O6
:   oxygen-6
OS
:   overall survival
pseudo
:   pseudoprogression
pts
:   patients
rCBV
:   relative cerebral blood volume
ROC
:   receiver operating characteristic analysis
TMZ
:   temozolomide
WHO
:   World Health Organization" />
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    <title>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 | American Journal of Neuroradiology</title>  
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    <div class="highwire-article-citation highwire-citation-type-highwire-article node9354--5" data-node-nid="9354" id="top-node-9354--62028662509" data-pisa="ajnr;32/2/382" data-pisa-master="ajnr;ajnr.A2286" data-apath="/ajnr/32/2/382.atom" data-hw-author-tooltip-instance="highwire_author_tooltip"><div class="highwire-cite highwire-cite-highwire-article highwire-citation-jcore-article-title-complete clearfix has-author-tooltip highwire-citation-highwire-article-top-a">
  
  
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      <h1 class="highwire-cite-title" id="page-title">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</h1>  
    	<div class="highwire-cite-authors"><span  class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0">D.-S. Kong</span>, <span class="highwire-citation-author" data-delta="1">S.T. Kim</span>, <span class="highwire-citation-author" data-delta="2">E.-H. Kim</span>, <span class="highwire-citation-author" data-delta="3">D.H. Lim</span>, <span class="highwire-citation-author" data-delta="4">W.S. Kim</span>, <span class="highwire-citation-author" data-delta="5">Y.-L. Suh</span>, <span class="highwire-citation-author" data-delta="6">J.-I. Lee</span>, <span class="highwire-citation-author" data-delta="7">K. Park</span>, <span class="highwire-citation-author" data-delta="8">J.H. Kim</span> and <span class="highwire-citation-author" data-delta="9">D.-H. Nam</span></span></div>
  
    	<div class="highwire-cite-metadata"><span  class="highwire-cite-metadata-journal highwire-cite-metadata">American Journal of Neuroradiology </span><span  class="highwire-cite-metadata-date highwire-cite-metadata">February 2011,  </span><span  class="highwire-cite-metadata-volume highwire-cite-metadata">32 </span><span  class="highwire-cite-metadata-issue highwire-cite-metadata">(2) </span><span  class="highwire-cite-metadata-pages highwire-cite-metadata">382-387; </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata">DOI: https://doi.org/10.3174/ajnr.A2286 </span></div>
  
  
  
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<div id="hw-article-author-popups-top-node-9354--62028662509" style="display: none;"><div class="author-tooltip-0"><div class="author-tooltip-name">D.-S. Kong </div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=D.-S.%2BKong%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Kong%20D&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link last"><a href="/search/author1%3AD.-S.%2BKong%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li></ul></div><div class="author-tooltip-1"><div class="author-tooltip-name">S.T. 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<p id="p-2"><strong>BACKGROUND AND PURPOSE:</strong> Methylation of the <em>MGMT</em> 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 <em>MGMT</em> methylation status and the potential value of DSC perfusion MR images for predicting pseudoprogression.</p>
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<p id="p-3"><strong>MATERIALS AND METHODS:</strong> 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 <em>MGMT</em> promoter methylation status. All patients were regularly followed up at an interval of 2 months by MR images, including DSC perfusion MR images.</p>
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<p id="p-4"><strong>RESULTS:</strong> 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 (<em>P</em> = .003). The ROC curve revealed that an rCBV ratio &gt;1.47 had an 81.5% sensitivity and a 77.8% specificity. The unmethylated <em>MGMT</em> promoter group had a significant difference of mean rCBV between pseudoprogression and real progression (<em>P</em> = .009), though the methylated <em>MGMT</em> promoter group had no significant difference (<em>P</em> = .258).</p>
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<p id="p-5"><strong>CONCLUSIONS:</strong> 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.</p>
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</div><div class="section glossary" id="glossary-1"><h2>Abbreviations</h2><dl id="def-list-1"><dt id="def-item-1">CBV<span class="def-item-dt-sep"></span></dt><dd>cerebral blood volume<span class="def-item-dd-sep"></span></dd><dt id="def-item-2">CCRT<span class="def-item-dt-sep"></span></dt><dd>concomitant chemoradiotherapy<span class="def-item-dd-sep"></span></dd><dt id="def-item-3">CI<span class="def-item-dt-sep"></span></dt><dd>confidence interval<span class="def-item-dd-sep"></span></dd><dt id="def-item-4">Cum<span class="def-item-dt-sep"></span></dt><dd>cumulative<span class="def-item-dd-sep"></span></dd><dt id="def-item-5">DSC<span class="def-item-dt-sep"></span></dt><dd>dynamic susceptibility-weighted contrastenhanced<span class="def-item-dd-sep"></span></dd><dt id="def-item-6">FA<span class="def-item-dt-sep"></span></dt><dd>flip angle<span class="def-item-dd-sep"></span></dd><dt id="def-item-7">FLAIR<span class="def-item-dt-sep"></span></dt><dd>fluid-attenuated inversion recovery<span class="def-item-dd-sep"></span></dd><dt id="def-item-8">GBM<span class="def-item-dt-sep"></span></dt><dd>glioblastoma<span class="def-item-dd-sep"></span></dd><dt id="def-item-9"><em>MGMT</em><span class="def-item-dt-sep"></span></dt><dd>O<sup>6</sup>-methylguanine-DNA methyltransferase<span class="def-item-dd-sep"></span></dd><dt id="def-item-10">MSP<span class="def-item-dt-sep"></span></dt><dd>methylation-specific polymerase chain reaction<span class="def-item-dd-sep"></span></dd><dt id="def-item-11">O<sup>6</sup><span class="def-item-dt-sep"></span></dt><dd>oxygen-6<span class="def-item-dd-sep"></span></dd><dt id="def-item-12">OS<span class="def-item-dt-sep"></span></dt><dd>overall survival<span class="def-item-dd-sep"></span></dd><dt id="def-item-13">pseudo<span class="def-item-dt-sep"></span></dt><dd>pseudoprogression<span class="def-item-dd-sep"></span></dd><dt id="def-item-14">pts<span class="def-item-dt-sep"></span></dt><dd>patients<span class="def-item-dd-sep"></span></dd><dt id="def-item-15">rCBV<span class="def-item-dt-sep"></span></dt><dd>relative cerebral blood volume<span class="def-item-dd-sep"></span></dd><dt id="def-item-16">ROC<span class="def-item-dt-sep"></span></dt><dd>receiver operating characteristic analysis<span class="def-item-dd-sep"></span></dd><dt id="def-item-17">TMZ<span class="def-item-dt-sep"></span></dt><dd>temozolomide<span class="def-item-dd-sep"></span></dd><dt id="def-item-18">WHO<span class="def-item-dt-sep"></span></dt><dd>World Health Organization</dd></dl></div><ul class="copyright-statement"><li class="fn" id="copyright-statement-1">Copyright © American Society of Neuroradiology</li></ul><span class="highwire-journal-article-marker-end"></span></div><span class="related-urls"></span></div><a href="http://ajnr-stage2.stage.highwire.org/content/32/2/382.full" class="hw-link hw-link-article-full-text" data-icon-position="" data-hide-link-title="0">View Full Text</a></div>  </div>

  
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        	<div class="highwire-cite-metadata"><span  class="highwire-cite-metadata-volume highwire-cite-metadata">Vol. 32</span>, <span  class="highwire-cite-metadata-issue highwire-cite-metadata">Issue 2 </span><div  class="highwire-cite-metadata-pubdate highwire-cite-metadata">1 Feb 2011 </div></div>
      
      
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    	<div class="highwire-cite-authors"><span  class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0"><span class="nlm-given-names">D.-S.</span> <span class="nlm-surname">Kong</span></span>, <span class="highwire-citation-author" data-delta="1"><span class="nlm-given-names">S.T.</span> <span class="nlm-surname">Kim</span></span>, <span class="highwire-citation-author" data-delta="2"><span class="nlm-given-names">E.-H.</span> <span class="nlm-surname">Kim</span></span>, <span class="highwire-citation-author" data-delta="3"><span class="nlm-given-names">D.H.</span> <span class="nlm-surname">Lim</span></span>, <span class="highwire-citation-author" data-delta="4"><span class="nlm-given-names">W.S.</span> <span class="nlm-surname">Kim</span></span>, <span class="highwire-citation-author" data-delta="5"><span class="nlm-given-names">Y.-L.</span> <span class="nlm-surname">Suh</span></span>, <span class="highwire-citation-author" data-delta="6"><span class="nlm-given-names">J.-I.</span> <span class="nlm-surname">Lee</span></span>, <span class="highwire-citation-author" data-delta="7"><span class="nlm-given-names">K.</span> <span class="nlm-surname">Park</span></span>, <span class="highwire-citation-author" data-delta="8"><span class="nlm-given-names">J.H.</span> <span class="nlm-surname">Kim</span></span>, <span class="highwire-citation-author" data-delta="9"><span class="nlm-given-names">D.-H.</span> <span class="nlm-surname">Nam</span></span></span></div>
  
    	<div class="highwire-cite-metadata"><span  class="highwire-cite-metadata-journal highwire-cite-metadata">American Journal of Neuroradiology </span><span  class="highwire-cite-metadata-date highwire-cite-metadata">Feb 2011, </span><span  class="highwire-cite-metadata-volume highwire-cite-metadata">32 </span><span  class="highwire-cite-metadata-issue highwire-cite-metadata">(2) </span><span  class="highwire-cite-metadata-pages highwire-cite-metadata">382-387; </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata"><span class="label">DOI:</span> 10.3174/ajnr.A2286 </span></div>
  
  
  
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    	<div class="highwire-cite-authors"><span  class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0"><span class="nlm-given-names">D.-S.</span> <span class="nlm-surname">Kong</span></span>, <span class="highwire-citation-author" data-delta="1"><span class="nlm-given-names">S.T.</span> <span class="nlm-surname">Kim</span></span>, <span class="highwire-citation-author" data-delta="2"><span class="nlm-given-names">E.-H.</span> <span class="nlm-surname">Kim</span></span>, <span class="highwire-citation-author" data-delta="3"><span class="nlm-given-names">D.H.</span> <span class="nlm-surname">Lim</span></span>, <span class="highwire-citation-author" data-delta="4"><span class="nlm-given-names">W.S.</span> <span class="nlm-surname">Kim</span></span>, <span class="highwire-citation-author" data-delta="5"><span class="nlm-given-names">Y.-L.</span> <span class="nlm-surname">Suh</span></span>, <span class="highwire-citation-author" data-delta="6"><span class="nlm-given-names">J.-I.</span> <span class="nlm-surname">Lee</span></span>, <span class="highwire-citation-author" data-delta="7"><span class="nlm-given-names">K.</span> <span class="nlm-surname">Park</span></span>, <span class="highwire-citation-author" data-delta="8"><span class="nlm-given-names">J.H.</span> <span class="nlm-surname">Kim</span></span>, <span class="highwire-citation-author" data-delta="9"><span class="nlm-given-names">D.-H.</span> <span class="nlm-surname">Nam</span></span></span></div>
  
    	<div class="highwire-cite-metadata"><span  class="highwire-cite-metadata-journal highwire-cite-metadata">American Journal of Neuroradiology </span><span  class="highwire-cite-metadata-date highwire-cite-metadata">Feb 2011, </span><span  class="highwire-cite-metadata-volume highwire-cite-metadata">32 </span><span  class="highwire-cite-metadata-issue highwire-cite-metadata">(2) </span><span  class="highwire-cite-metadata-pages highwire-cite-metadata">382-387; </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata"><span class="label">DOI:</span> 10.3174/ajnr.A2286 </span></div>
  
  
  
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