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<meta name="DC.Title" content="Pretreatment ADC Histogram Analysis Is a Predictive Imaging Biomarker for Bevacizumab Treatment but Not Chemotherapy in Recurrent Glioblastoma" />
<meta name="DC.Identifier" content="10.3174/ajnr.A3748" />
<meta name="DC.Date" content="2014-04-01" />
<meta name="DC.Publisher" content="American Journal of Neuroradiology" />
<meta name="DC.Rights" content="© 2014 by American Journal of Neuroradiology. Indicates open access to non-subscribers at www.ajnr.org" />
<meta name="DC.AccessRights" content="open-access" />
<meta name="DC.Description" content="BACKGROUND AND PURPOSE: Pre-treatment ADC characteristics have been shown to predict response to bevacizumab in recurrent glioblastoma multiforme. However, no studies have examined whether ADC characteristics are specific to this particular treatment. The purpose of the current study was to determine whether ADC histogram analysis is a bevacizumab-specific or treatment-independent biomarker of treatment response in recurrent glioblastoma multiforme.

MATERIALS AND METHODS: Eighty-nine bevacizumab-treated and 43 chemotherapy-treated recurrent glioblastoma multiformes never exposed to bevacizumab were included in this study. In all patients, ADC values in contrast-enhancing ROIs from MR imaging examinations performed at the time of recurrence, immediately before commencement of treatment for recurrence, were extracted and the resulting histogram was fitted to a mixed model with a double Gaussian distribution. Mean ADC in the lower Gaussian curve was used as the primary biomarker of interest. The Cox proportional hazards model and log-rank tests were used for survival analysis.

RESULTS: Cox multivariate regression analysis accounting for the interaction between bevacizumab- and non-bevacizumab-treated patients suggested that the ability of the lower Gaussian curve to predict survival is dependent on treatment (progression-free survival, P = .045; overall survival, P = .003). Patients with bevacizumab-treated recurrent glioblastoma multiforme with a pretreatment lower Gaussian curve &gt; 1.2 μm2/ms had a significantly longer progression-free survival and overall survival compared with bevacizumab-treated patients with a lower Gaussian curve &lt; 1.2 μm2/ms. No differences in progression-free survival or overall survival were observed in the chemotherapy-treated cohort. Bevacizumab-treated patients with a mean lower Gaussian curve &gt; 1.2 μm2/ms had a significantly longer progression-free survival and overall survival compared with chemotherapy-treated patients.

CONCLUSIONS: The mean lower Gaussian curve from ADC histogram analysis is a predictive imaging biomarker for bevacizumab-treated, not chemotherapy-treated, recurrent glioblastoma multiforme. Patients with recurrent glioblastoma multiforme with a mean lower Gaussian curve &gt; 1.2 μm2/ms have a survival advantage when treated with bevacizumab.

ADCL
:   apparent diffusion coefficient in the lower Gaussian curve
GBM
:   glioblastoma multiforme
HR
:   hazard ratio
OS
:   overall survival
PFS
:   progression-free survival
UCLA
:   University of California, Los Angeles
VEGF
:   vascular endothelial growth factor" />
<meta name="DC.Contributor" content="B.M. Ellingson" />
<meta name="DC.Contributor" content="S. Sahebjam" />
<meta name="DC.Contributor" content="H.J. Kim" />
<meta name="DC.Contributor" content="W.B. Pope" />
<meta name="DC.Contributor" content="R.J. Harris" />
<meta name="DC.Contributor" content="D.C. Woodworth" />
<meta name="DC.Contributor" content="A. Lai" />
<meta name="DC.Contributor" content="P.L. Nghiemphu" />
<meta name="DC.Contributor" content="W.P. Mason" />
<meta name="DC.Contributor" content="T.F. Cloughesy" />
<meta name="article:published_time" content="2014-04-01" />
<meta name="article:section" content="Brain" />
<meta name="citation_title" content="Pretreatment ADC Histogram Analysis Is a Predictive Imaging Biomarker for Bevacizumab Treatment but Not Chemotherapy in Recurrent Glioblastoma" />
<meta name="citation_abstract" lang="en" content="&lt;h3&gt;BACKGROUND AND PURPOSE:&lt;/h3&gt;
&lt;p&gt;Pre-treatment ADC characteristics have been shown to predict response to bevacizumab in recurrent glioblastoma multiforme. However, no studies have examined whether ADC characteristics are specific to this particular treatment. The purpose of the current study was to determine whether ADC histogram analysis is a bevacizumab-specific or treatment-independent biomarker of treatment response in recurrent glioblastoma multiforme.&lt;/p&gt;&lt;h3&gt;MATERIALS AND METHODS:&lt;/h3&gt;
&lt;p&gt;Eighty-nine bevacizumab-treated and 43 chemotherapy-treated recurrent glioblastoma multiformes never exposed to bevacizumab were included in this study. In all patients, ADC values in contrast-enhancing ROIs from MR imaging examinations performed at the time of recurrence, immediately before commencement of treatment for recurrence, were extracted and the resulting histogram was fitted to a mixed model with a double Gaussian distribution. Mean ADC in the lower Gaussian curve was used as the primary biomarker of interest. The Cox proportional hazards model and log-rank tests were used for survival analysis.&lt;/p&gt;&lt;h3&gt;RESULTS:&lt;/h3&gt;
&lt;p&gt;Cox multivariate regression analysis accounting for the interaction between bevacizumab- and non-bevacizumab-treated patients suggested that the ability of the lower Gaussian curve to predict survival is dependent on treatment (progression-free survival, &lt;i&gt;P&lt;/i&gt; = .045; overall survival, &lt;i&gt;P&lt;/i&gt; = .003). Patients with bevacizumab-treated recurrent glioblastoma multiforme with a pretreatment lower Gaussian curve &amp;gt; 1.2 μm&lt;sup&gt;2&lt;/sup&gt;/ms had a significantly longer progression-free survival and overall survival compared with bevacizumab-treated patients with a lower Gaussian curve &amp;lt; 1.2 μm&lt;sup&gt;2&lt;/sup&gt;/ms. No differences in progression-free survival or overall survival were observed in the chemotherapy-treated cohort. Bevacizumab-treated patients with a mean lower Gaussian curve &amp;gt; 1.2 μm&lt;sup&gt;2&lt;/sup&gt;/ms had a significantly longer progression-free survival and overall survival compared with chemotherapy-treated patients.&lt;/p&gt;&lt;h3&gt;CONCLUSIONS:&lt;/h3&gt;
&lt;p&gt;The mean lower Gaussian curve from ADC histogram analysis is a predictive imaging biomarker for bevacizumab-treated, not chemotherapy-treated, recurrent glioblastoma multiforme. Patients with recurrent glioblastoma multiforme with a mean lower Gaussian curve &amp;gt; 1.2 μm&lt;sup&gt;2&lt;/sup&gt;/ms have a survival advantage when treated with bevacizumab.&lt;/p&gt;" />
<meta name="citation_journal_title" content="American Journal of Neuroradiology" />
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<meta name="twitter:title" content="Pretreatment ADC Histogram Analysis Is a Predictive Imaging Biomarker for Bevacizumab Treatment but Not Chemotherapy in Recurrent Glioblastoma" />
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<meta name="twitter:description" content="BACKGROUND AND PURPOSE: Pre-treatment ADC characteristics have been shown to predict response to bevacizumab in recurrent glioblastoma multiforme. However, no studies have examined whether ADC characteristics are specific to this particular treatment. The purpose of the current study was to determine whether ADC histogram analysis is a bevacizumab-specific or treatment-independent biomarker of treatment response in recurrent glioblastoma multiforme.

MATERIALS AND METHODS: Eighty-nine bevacizumab-treated and 43 chemotherapy-treated recurrent glioblastoma multiformes never exposed to bevacizumab were included in this study. In all patients, ADC values in contrast-enhancing ROIs from MR imaging examinations performed at the time of recurrence, immediately before commencement of treatment for recurrence, were extracted and the resulting histogram was fitted to a mixed model with a double Gaussian distribution. Mean ADC in the lower Gaussian curve was used as the primary biomarker of interest. The Cox proportional hazards model and log-rank tests were used for survival analysis.

RESULTS: Cox multivariate regression analysis accounting for the interaction between bevacizumab- and non-bevacizumab-treated patients suggested that the ability of the lower Gaussian curve to predict survival is dependent on treatment (progression-free survival, P = .045; overall survival, P = .003). Patients with bevacizumab-treated recurrent glioblastoma multiforme with a pretreatment lower Gaussian curve &gt; 1.2 μm2/ms had a significantly longer progression-free survival and overall survival compared with bevacizumab-treated patients with a lower Gaussian curve &lt; 1.2 μm2/ms. No differences in progression-free survival or overall survival were observed in the chemotherapy-treated cohort. Bevacizumab-treated patients with a mean lower Gaussian curve &gt; 1.2 μm2/ms had a significantly longer progression-free survival and overall survival compared with chemotherapy-treated patients.

CONCLUSIONS: The mean lower Gaussian curve from ADC histogram analysis is a predictive imaging biomarker for bevacizumab-treated, not chemotherapy-treated, recurrent glioblastoma multiforme. Patients with recurrent glioblastoma multiforme with a mean lower Gaussian curve &gt; 1.2 μm2/ms have a survival advantage when treated with bevacizumab.

ADCL
:   apparent diffusion coefficient in the lower Gaussian curve
GBM
:   glioblastoma multiforme
HR
:   hazard ratio
OS
:   overall survival
PFS
:   progression-free survival
UCLA
:   University of California, Los Angeles
VEGF
:   vascular endothelial growth factor" />
<meta name="og-title" property="og:title" content="Pretreatment ADC Histogram Analysis Is a Predictive Imaging Biomarker for Bevacizumab Treatment but Not Chemotherapy in Recurrent Glioblastoma" />
<meta name="og-url" property="og:url" content="http://ajnr-stage2.stage.highwire.org/content/35/4/673" />
<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: Pre-treatment ADC characteristics have been shown to predict response to bevacizumab in recurrent glioblastoma multiforme. However, no studies have examined whether ADC characteristics are specific to this particular treatment. The purpose of the current study was to determine whether ADC histogram analysis is a bevacizumab-specific or treatment-independent biomarker of treatment response in recurrent glioblastoma multiforme.

MATERIALS AND METHODS: Eighty-nine bevacizumab-treated and 43 chemotherapy-treated recurrent glioblastoma multiformes never exposed to bevacizumab were included in this study. In all patients, ADC values in contrast-enhancing ROIs from MR imaging examinations performed at the time of recurrence, immediately before commencement of treatment for recurrence, were extracted and the resulting histogram was fitted to a mixed model with a double Gaussian distribution. Mean ADC in the lower Gaussian curve was used as the primary biomarker of interest. The Cox proportional hazards model and log-rank tests were used for survival analysis.

RESULTS: Cox multivariate regression analysis accounting for the interaction between bevacizumab- and non-bevacizumab-treated patients suggested that the ability of the lower Gaussian curve to predict survival is dependent on treatment (progression-free survival, P = .045; overall survival, P = .003). Patients with bevacizumab-treated recurrent glioblastoma multiforme with a pretreatment lower Gaussian curve &gt; 1.2 μm2/ms had a significantly longer progression-free survival and overall survival compared with bevacizumab-treated patients with a lower Gaussian curve &lt; 1.2 μm2/ms. No differences in progression-free survival or overall survival were observed in the chemotherapy-treated cohort. Bevacizumab-treated patients with a mean lower Gaussian curve &gt; 1.2 μm2/ms had a significantly longer progression-free survival and overall survival compared with chemotherapy-treated patients.

CONCLUSIONS: The mean lower Gaussian curve from ADC histogram analysis is a predictive imaging biomarker for bevacizumab-treated, not chemotherapy-treated, recurrent glioblastoma multiforme. Patients with recurrent glioblastoma multiforme with a mean lower Gaussian curve &gt; 1.2 μm2/ms have a survival advantage when treated with bevacizumab.

ADCL
:   apparent diffusion coefficient in the lower Gaussian curve
GBM
:   glioblastoma multiforme
HR
:   hazard ratio
OS
:   overall survival
PFS
:   progression-free survival
UCLA
:   University of California, Los Angeles
VEGF
:   vascular endothelial growth factor" />
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      <div class="highwire-cite-overline"><span  class="highwire-cite-metadata-article-type highwire-cite-metadata">Research Article</span><span class="separator-pipe"></span><span  class="highwire-cite-metadata-art-cat highwire-cite-metadata"><span class="wrapper">Brain</span></span></div>
  
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      <h1 class="highwire-cite-title" id="page-title">Pretreatment ADC Histogram Analysis Is a Predictive Imaging Biomarker for Bevacizumab Treatment but Not Chemotherapy in Recurrent Glioblastoma</h1>  
    	<div class="highwire-cite-authors"><span  class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0">B.M. Ellingson</span>, <span class="highwire-citation-author" data-delta="1">S. Sahebjam</span>, <span class="highwire-citation-author" data-delta="2">H.J. Kim</span>, <span class="highwire-citation-author" data-delta="3">W.B. Pope</span>, <span class="highwire-citation-author" data-delta="4">R.J. Harris</span>, <span class="highwire-citation-author" data-delta="5">D.C. Woodworth</span>, <span class="highwire-citation-author" data-delta="6">A. Lai</span>, <span class="highwire-citation-author" data-delta="7">P.L. Nghiemphu</span>, <span class="highwire-citation-author" data-delta="8">W.P. Mason</span> and <span class="highwire-citation-author" data-delta="9">T.F. Cloughesy</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">April 2014,  </span><span  class="highwire-cite-metadata-volume highwire-cite-metadata">35 </span><span  class="highwire-cite-metadata-issue highwire-cite-metadata">(4) </span><span  class="highwire-cite-metadata-pages highwire-cite-metadata">673-679; </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata">DOI: https://doi.org/10.3174/ajnr.A3748 </span></div>
  
  
  
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<div id="hw-article-author-popups-top-node-13419--6628302814" style="display: none;"><div class="author-tooltip-0"><div class="author-tooltip-name">B.M. Ellingson </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>From the Departments of Radiological Sciences (B.M.E., H.J.K., W.B.P., R.J.H., D.C.W.)</div><div class='author-affiliation'><span class='nlm-sup'>b</span>Biomedical Physics (B.M.E., R.J.H., D.C.W.)</div><div class='author-affiliation'><span class='nlm-sup'>c</span>Bioengineering (B.M.E.)</div></span></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=B.M.%2BEllingson%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=Ellingson%20B&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%3AB.M.%2BEllingson%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. Sahebjam </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>e</span>Department of Medicine (S.S., W.P.M.), Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada.</div></span></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=S.%2BSahebjam%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=Sahebjam%20S&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%3AS.%2BSahebjam%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-2"><div class="author-tooltip-name">H.J. Kim </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>From the Departments of Radiological Sciences (B.M.E., H.J.K., W.B.P., R.J.H., D.C.W.)</div></span></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=H.J.%2BKim%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=Kim%20H&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%3AH.J.%2BKim%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-3"><div class="author-tooltip-name">W.B. Pope </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>From the Departments of Radiological Sciences (B.M.E., H.J.K., W.B.P., R.J.H., D.C.W.)</div></span></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=W.B.%2BPope%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=Pope%20W&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%3AW.B.%2BPope%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-4"><div class="author-tooltip-name">R.J. Harris </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>From the Departments of Radiological Sciences (B.M.E., H.J.K., W.B.P., R.J.H., D.C.W.)</div><div class='author-affiliation'><span class='nlm-sup'>b</span>Biomedical Physics (B.M.E., R.J.H., D.C.W.)</div></span></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=R.J.%2BHarris%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=Harris%20R&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%3AR.J.%2BHarris%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-5"><div class="author-tooltip-name">D.C. Woodworth </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>From the Departments of Radiological Sciences (B.M.E., H.J.K., W.B.P., R.J.H., D.C.W.)</div><div class='author-affiliation'><span class='nlm-sup'>b</span>Biomedical Physics (B.M.E., R.J.H., D.C.W.)</div></span></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.C.%2BWoodworth%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=Woodworth%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.C.%2BWoodworth%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-6"><div class="author-tooltip-name">A. Lai </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>d</span>Neurology (A.L., P.L.N., T.F.C.), David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California</div></span></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=A.%2BLai%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=Lai%20A&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%3AA.%2BLai%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-7"><div class="author-tooltip-name">P.L. Nghiemphu </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>d</span>Neurology (A.L., P.L.N., T.F.C.), David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California</div></span></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=P.L.%2BNghiemphu%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=Nghiemphu%20P&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%3AP.L.%2BNghiemphu%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-8"><div class="author-tooltip-name">W.P. Mason </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>e</span>Department of Medicine (S.S., W.P.M.), Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada.</div></span></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=W.P.%2BMason%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=Mason%20W&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%3AW.P.%2BMason%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-9"><div class="author-tooltip-name">T.F. 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<p id="p-3"><strong>BACKGROUND AND PURPOSE:</strong> Pre-treatment ADC characteristics have been shown to predict response to bevacizumab in recurrent glioblastoma multiforme. However, no studies have examined whether ADC characteristics are specific to this particular treatment. The purpose of the current study was to determine whether ADC histogram analysis is a bevacizumab-specific or treatment-independent biomarker of treatment response in recurrent glioblastoma multiforme.</p>
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<p id="p-4"><strong>MATERIALS AND METHODS:</strong> Eighty-nine bevacizumab-treated and 43 chemotherapy-treated recurrent glioblastoma multiformes never exposed to bevacizumab were included in this study. In all patients, ADC values in contrast-enhancing ROIs from MR imaging examinations performed at the time of recurrence, immediately before commencement of treatment for recurrence, were extracted and the resulting histogram was fitted to a mixed model with a double Gaussian distribution. Mean ADC in the lower Gaussian curve was used as the primary biomarker of interest. The Cox proportional hazards model and log-rank tests were used for survival analysis.</p>
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<p id="p-5"><strong>RESULTS:</strong> Cox multivariate regression analysis accounting for the interaction between bevacizumab- and non-bevacizumab-treated patients suggested that the ability of the lower Gaussian curve to predict survival is dependent on treatment (progression-free survival, <em>P</em> = .045; overall survival, <em>P</em> = .003). Patients with bevacizumab-treated recurrent glioblastoma multiforme with a pretreatment lower Gaussian curve &gt; 1.2 μm<sup>2</sup>/ms had a significantly longer progression-free survival and overall survival compared with bevacizumab-treated patients with a lower Gaussian curve &lt; 1.2 μm<sup>2</sup>/ms. No differences in progression-free survival or overall survival were observed in the chemotherapy-treated cohort. Bevacizumab-treated patients with a mean lower Gaussian curve &gt; 1.2 μm<sup>2</sup>/ms had a significantly longer progression-free survival and overall survival compared with chemotherapy-treated patients.</p>
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<p id="p-6"><strong>CONCLUSIONS:</strong> The mean lower Gaussian curve from ADC histogram analysis is a predictive imaging biomarker for bevacizumab-treated, not chemotherapy-treated, recurrent glioblastoma multiforme. Patients with recurrent glioblastoma multiforme with a mean lower Gaussian curve &gt; 1.2 μm<sup>2</sup>/ms have a survival advantage when treated with bevacizumab.</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">ADC<sub>L</sub><span class="def-item-dt-sep"></span></dt><dd>apparent diffusion coefficient in the lower Gaussian curve<span class="def-item-dd-sep"></span></dd><dt id="def-item-2">GBM<span class="def-item-dt-sep"></span></dt><dd>glioblastoma multiforme<span class="def-item-dd-sep"></span></dd><dt id="def-item-3">HR<span class="def-item-dt-sep"></span></dt><dd>hazard ratio<span class="def-item-dd-sep"></span></dd><dt id="def-item-4">OS<span class="def-item-dt-sep"></span></dt><dd>overall survival<span class="def-item-dd-sep"></span></dd><dt id="def-item-5">PFS<span class="def-item-dt-sep"></span></dt><dd>progression-free survival<span class="def-item-dd-sep"></span></dd><dt id="def-item-6">UCLA<span class="def-item-dt-sep"></span></dt><dd>University of California, Los Angeles<span class="def-item-dd-sep"></span></dd><dt id="def-item-7">VEGF<span class="def-item-dt-sep"></span></dt><dd>vascular endothelial growth factor</dd></dl>
</div><ul class="copyright-statement"><li class="fn" id="copyright-statement-1">© 2014 by American Journal of Neuroradiology</li></ul><div class="license" id="license-1"><p id="p-2">Indicates open access to non-subscribers at <a href="http://www.ajnr.org">www.ajnr.org</a></p></div><span class="highwire-journal-article-marker-end"></span></div><span class="related-urls"></span></div><a href="http://ajnr-stage2.stage.highwire.org/content/35/4/673.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. 35</span>, <span  class="highwire-cite-metadata-issue highwire-cite-metadata">Issue 4 </span><div  class="highwire-cite-metadata-pubdate highwire-cite-metadata">1 Apr 2014 </div></div>
      
      
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      <div class="highwire-cite-title">Pretreatment ADC Histogram Analysis Is a Predictive Imaging Biomarker for Bevacizumab Treatment but Not Chemotherapy in Recurrent Glioblastoma</div>  
    	<div class="highwire-cite-authors"><span  class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0"><span class="nlm-given-names">B.M.</span> <span class="nlm-surname">Ellingson</span></span>, <span class="highwire-citation-author" data-delta="1"><span class="nlm-given-names">S.</span> <span class="nlm-surname">Sahebjam</span></span>, <span class="highwire-citation-author" data-delta="2"><span class="nlm-given-names">H.J.</span> <span class="nlm-surname">Kim</span></span>, <span class="highwire-citation-author" data-delta="3"><span class="nlm-given-names">W.B.</span> <span class="nlm-surname">Pope</span></span>, <span class="highwire-citation-author" data-delta="4"><span class="nlm-given-names">R.J.</span> <span class="nlm-surname">Harris</span></span>, <span class="highwire-citation-author" data-delta="5"><span class="nlm-given-names">D.C.</span> <span class="nlm-surname">Woodworth</span></span>, <span class="highwire-citation-author" data-delta="6"><span class="nlm-given-names">A.</span> <span class="nlm-surname">Lai</span></span>, <span class="highwire-citation-author" data-delta="7"><span class="nlm-given-names">P.L.</span> <span class="nlm-surname">Nghiemphu</span></span>, <span class="highwire-citation-author" data-delta="8"><span class="nlm-given-names">W.P.</span> <span class="nlm-surname">Mason</span></span>, <span class="highwire-citation-author" data-delta="9"><span class="nlm-given-names">T.F.</span> <span class="nlm-surname">Cloughesy</span></span></span></div>
  
    	<div class="highwire-cite-metadata"><span  class="highwire-cite-metadata-oa-ind highwire-cite-metadata"><i class="highwire-oa-indicator"></i> </span><span  class="highwire-cite-metadata-journal highwire-cite-metadata">American Journal of Neuroradiology </span><span  class="highwire-cite-metadata-date highwire-cite-metadata">Apr 2014, </span><span  class="highwire-cite-metadata-volume highwire-cite-metadata">35 </span><span  class="highwire-cite-metadata-issue highwire-cite-metadata">(4) </span><span  class="highwire-cite-metadata-pages highwire-cite-metadata">673-679; </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata"><span class="label">DOI:</span> 10.3174/ajnr.A3748 </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">B.M.</span> <span class="nlm-surname">Ellingson</span></span>, <span class="highwire-citation-author" data-delta="1"><span class="nlm-given-names">S.</span> <span class="nlm-surname">Sahebjam</span></span>, <span class="highwire-citation-author" data-delta="2"><span class="nlm-given-names">H.J.</span> <span class="nlm-surname">Kim</span></span>, <span class="highwire-citation-author" data-delta="3"><span class="nlm-given-names">W.B.</span> <span class="nlm-surname">Pope</span></span>, <span class="highwire-citation-author" data-delta="4"><span class="nlm-given-names">R.J.</span> <span class="nlm-surname">Harris</span></span>, <span class="highwire-citation-author" data-delta="5"><span class="nlm-given-names">D.C.</span> <span class="nlm-surname">Woodworth</span></span>, <span class="highwire-citation-author" data-delta="6"><span class="nlm-given-names">A.</span> <span class="nlm-surname">Lai</span></span>, <span class="highwire-citation-author" data-delta="7"><span class="nlm-given-names">P.L.</span> <span class="nlm-surname">Nghiemphu</span></span>, <span class="highwire-citation-author" data-delta="8"><span class="nlm-given-names">W.P.</span> <span class="nlm-surname">Mason</span></span>, <span class="highwire-citation-author" data-delta="9"><span class="nlm-given-names">T.F.</span> <span class="nlm-surname">Cloughesy</span></span></span></div>
  
    	<div class="highwire-cite-metadata"><span  class="highwire-cite-metadata-oa-ind highwire-cite-metadata"><i class="highwire-oa-indicator"></i> </span><span  class="highwire-cite-metadata-journal highwire-cite-metadata">American Journal of Neuroradiology </span><span  class="highwire-cite-metadata-date highwire-cite-metadata">Apr 2014, </span><span  class="highwire-cite-metadata-volume highwire-cite-metadata">35 </span><span  class="highwire-cite-metadata-issue highwire-cite-metadata">(4) </span><span  class="highwire-cite-metadata-pages highwire-cite-metadata">673-679; </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata"><span class="label">DOI:</span> 10.3174/ajnr.A3748 </span></div>
  
  
  
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