Wiley = InterScience :: Article :: HTML Full Text

From: Subject: Wiley InterScience :: Article :: HTML Full Text Date: Fri, 8 Feb 2008 13:59:58 +0100 MIME-Version: 1.0 Content-Type: multipart/related; type="multipart/alternative"; boundary="----=_NextPart_000_0059_01C86A5A.E3C79D50" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.3198 This is a multi-part message in MIME format. ------=_NextPart_000_0059_01C86A5A.E3C79D50 Content-Type: multipart/alternative; boundary="----=_NextPart_001_005A_01C86A5A.E3C79D50" ------=_NextPart_001_005A_01C86A5A.E3C79D50 Content-Type: text/html; charset="Windows-1252" Content-Transfer-Encoding: quoted-printable Content-Location: http://www3.interscience.wiley.com/cgi-bin/fulltext/94517441/HTMLSTART Wiley = InterScience :: Article :: HTML Full Text ------=_NextPart_001_005A_01C86A5A.E3C79D50 Content-Type: text/html; charset="Windows-1252" Content-Transfer-Encoding: quoted-printable Content-Location: http://www3.interscience.wiley.com/blank.html UNTITLED_PAGE= 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document.writeln('

3D"Click

');=0A= }=0A= =0A= function get_text_link(url, linktext)=0A= {=0A= document.writeln('' + = linktext + '');=0A= }=0A= =0A= function get_htmlftext_link(a, b) {=0A= document.writeln("" + = b + ", ");=0A= }=0A= =0A= ------=_NextPart_000_0059_01C86A5A.E3C79D50 Content-Type: application/octet-stream Content-Transfer-Encoding: quoted-printable Content-Location: http://download.interscience.wiley.com/freeflow/js/personalisation.js /*=0A= * Project : Interscience Redesign=0A= * File : personalisation.js=0A= * Creation Date : 25th March 2003=0A= * Author : Jonathan Sugar=0A= *=0A= * Various functions to deliver personalisation functionality.=0A= */=0A= =0A= // Pre-declare userName so it's available when we need to test if the = page=0A= // assembler ran OK=0A= var userName =3D null;=0A= var shcrtCookie =3D null;=0A= =0A= // Browser detect globals:=0A= var uaStr =3D navigator.userAgent.toLowerCase();=0A= var uaVer =3D parseInt(navigator.appVersion);=0A= // for detecting netscape 4=0A= var netscape =3D (uaStr.indexOf("mozilla") > -1);=0A= var netscape4 =3D (netscape && uaVer < 5);=0A= =0A= // Factory Methods=0A= =0A= // Simple wraper object to encapsulate the data for a co-branding item.=0A= function coBrandingItem(image, imageAltText, href)=0A= {=0A= //alert("Making new coBrandingItem:\nImage: " + image + = "\nimageAltText" + imageAltText + "\nhref: " + href);=0A= this.image =3D image;=0A= this.imageAltText =3D imageAltText;=0A= this.href =3D href;=0A= }=0A= =0A= /*=0A= * Insert the 'Customer co-branding' section.=0A= * -----------------------------=0A= *=0A= * Author: Jonathan Sugar, March 2003.=0A= *=0A= * 1. Insert customer co branding. Loop through 'customerCoBranding' array=0A= * inserting XHTML where needed.=0A= *=0A= * NOTE: the array contains ONLY the resource location (the location of a = gif=0A= * on the file system), the required XHTML is then added where needed. = This way=0A= * we maintain the seperation between presentation and content.=0A= */=0A= function insertCustomerCoBranding(maxBranding)=0A= {=0A= if( customerCoBranding[0].image !=3D "none")=0A= {=0A= document.writeln('

');=0A= document.writeln('

');=0A= document.writeln('

' + imageAltText + '
' + imageAltText + = '
More Providers

');=0A= document.writeln('

');=0A= document.writeln('

3D""

');=0A= }=0A= }=0A= =0A= /*=0A= * Insert the 'My Area' section.=0A= * -----------------------------=0A= *=0A= * Author: Jonathan Sugar, March 2003.=0A= * Updated: Ben Marvell, April 2006=0A= *=0A= * My profile link absolute as this file isnt only run from w3 anymore.=0A= */=0A= function insertMyArea(userdata)=0A= {=0A= // just in case the page assembler isn't running.=0A= =0A= =0A= if (userName !=3D null)=0A= {=0A= document.writeln("

" + = userName.substring(0,33) + "..., access your
" + userName + = ", access your

My Profile"); =0A= document.writeln(getLoginOutLink());=0A= document.writeln("

");=0A= }=0A= if (menuloadedflag){=0A= wisMenu();=0A= }=0A= }=0A= =0A= /*=0A= * Insert the Customer Admin 'Login/Logout' link=0A= * -----------------------------=0A= *=0A= * Author: Bobby Jack, December 2004.=0A= *=0A= */=0A= function insertAdminLink(page)=0A= {=0A= val =3D getCookie("AID");=0A= =0A= if (val && val !=3D "-1")=0A= {=0A= document.writeln('

Logout');=0A= }=0A= else=0A= {=0A= document.writeln('

');=0A= }=0A= }=0A= =0A= /*=0A= * Insert the username section.=0A= * -----------------------------=0A= *=0A= * Author: Jonathan Sugar, March 2003.=0A= *=0A= * 1. Insert the username.=0A= */=0A= function insertUserName()=0A= {=0A= document.write(userName);=0A= }=0A= =0A= /*=0A= * Return the appropriate link to the login/logout cgi=0A= * ---------------------------------------------------=0A= *=0A= * Author: Jonathan Sugar, March 2003.=0A= * Updated: Ben Marvell, April 2006=0A= * Had to change the links absolute as this file isnt only run from w3 = anymore.=0A= */=0A= function getLoginOutLink()=0A= {=0A= if(userName !=3D "")=0A= {=0A= return "

";=0A= }else=0A= {=0A= return "

";=0A= }=0A= }=0A= =0A= /*=0A= * Return the appropriate link to the shopping cart content page=0A= * ---------------------------------------------------=0A= *=0A= * Author: Zhiming & Warrell June 2007=0A= */=0A= function getShCrtLink(logged)=0A= {=0A= if(logged =3D=3D true )=0A= return "

";=0A= else=0A= return "

";=0A= }=0A= =0A= function toggleShCrtLink()=0A= {=0A= shcrtCookie =3D readCookie("SHCRT");=0A= if(shcrtCookie !=3D null)=0A= {=0A= if(document.all)=0A= {=0A= return true;=0A= }=0A= else=0A= {=0A= document.getElementById("shcrt_id").style.display =3D "block";=0A= }=0A= }=0A= else=0A= {=0A= if(document.all)=0A= {=0A= return true;=0A= }=0A= else=0A= {=0A= document.getElementById("shcrt_id").style.display =3D "none";=0A= }=0A= }=0A= }=0A= =0A= =0A= =0A= function readCookie(name)=0A= {=0A= var nameEQ =3D name + "=3D";=0A= var ca =3D document.cookie.split(';');=0A= for(var i=3D0; i tags with images = display both an image and=0A= the default bullet. =0A= =0A= = *************************************************************************= **************************/=0A= =0A= var http =3D false;=0A= if(navigator.appName =3D=3D "Microsoft Internet Explorer") {=0A= http =3D new ActiveXObject("Microsoft.XMLHTTP");=0A= } else {=0A= http =3D new XMLHttpRequest();=0A= } =0A= =0A= // Global Variables=0A= var debug =3D false;=0A= var first =3D true;=0A= =0A= // Browser detect globals:=0A= var uaStr =3D navigator.userAgent.toLowerCase();=0A= var uaVer =3D parseInt(navigator.appVersion);=0A= // for detecting netscape 4=0A= var netscape =3D (uaStr.indexOf("mozilla") > -1);=0A= var netscape4 =3D (netscape && uaVer < 5);=0A= =0A= /*=0A= * Used to switch search mode between APS and TitleFinder on quicksearch = boxes=0A= * = -------------------------------------------------------------------------= --=0A= *=0A= * 1. Decides which search is required based on the value of the radio = buttons=0A= * in 'document.formSelector.whichForm'.=0A= *=0A= * 2. Calls individual functions to process the forms and submit them.=0A= *=0A= */=0A= function selectAndSubmit()=0A= {=0A= var formSelection;=0A= =0A= // find out which form we need to process.=0A= var selector =3D document.formSelector.whichForm;=0A= for (var i =3D 0; i < selector.length; i++){=0A= if (selector[i].checked){=0A= formSelection =3D selector[i].value;=0A= }=0A= }=0A= =0A= // Call the relevent function to process the required form.=0A= if(formSelection =3D=3D "allContentSearch"){=0A= processallContentSearch(document.allContentSearchForm, = document.formSelector)=0A= }=0A= else if(formSelection =3D=3D "searchTitles"){=0A= processTitleSearch(document.searchTitles, document.formSelector)=0A= }=0A= else{=0A= return false;=0A= }=0A= =0A= //@@@DM It was anoying me this error =0A= return false;=0A= }=0A= =0A= /*=0A= * Process the allContentSearch form=0A= * ---------------------------------=0A= * 1. Perform form validation, checking for empty fields.=0A= * Give the user a relevent message if required.=0A= *=0A= * 2. Process/Assign the appropriate form elements and submit the form.=0A= */=0A= function processallContentSearch(hiddenForm, queryForm)=0A= {=0A= var formToSubmit =3D hiddenForm;=0A= var formToProcess =3D queryForm;=0A= =0A= // Do some basic form validation=0A= if(formToProcess.terms.value !=3D "")=0A= {=0A= formToSubmit.WISsearch1.value =3D formToProcess.terms.value;=0A= formToSubmit.submit(); =0A= }=0A= else=0A= {=0A= alert("You must enter a search term in the text box before you click = go.");=0A= }=0A= }=0A= =0A= /*=0A= * Process the Title Search form=0A= * -----------------------------=0A= * 1. Perform form validation, checking for empty fields.=0A= * Give the user a relevent message if required.=0A= *=0A= * 2. Process/Assign the appropriate form elements and submit the form.=0A= */=0A= =0A= function processTitleSearch(hiddenForm, queryForm)=0A= {=0A= var formToSubmit =3D hiddenForm;=0A= var formToProcess =3D queryForm;=0A= =0A= // Do some basic form validation=0A= if(formToProcess.terms.value !=3D "")=0A= {=0A= formToSubmit.query.value =3D formToProcess.terms.value;=0A= formToSubmit.submit();=0A= }=0A= else=0A= {=0A= alert("You must enter a search term in the text box before you click = go.");=0A= }=0A= }=0A= =0A= function doCitationSearch()=0A= {=0A= var form =3D document.citsearchform;=0A= if(checkCitationSearch())=0A= {=0A= form.action =3D "/search/allsearch";=0A= form.submit();=0A= }=0A= }=0A= =0A= // Preprocesses the arguments sent to CitationSearch and checks validity = of user inputs.=0A= function checkCitationSearch()=0A= {=0A= var supplementFound =3D 0; //increment if found;=0A= var hyphenFound =3D 0; //increment if found;=0A= var fm =3D document.citsearchform;=0A= var errmsg =3D "Please use the valid digits '0' to '9'";=0A= // remove all spaces=0A= fm.volume.value =3D fm.volume.value.replace(/ /g, "");=0A= fm.issue.value =3D fm.issue.value.replace(/ /g, "");=0A= fm.pages.value =3D fm.pages.value.replace(/ /g, "");=0A= =0A= if (fm.issn.value.length > 0 && fm.volume.value.length > 0 && = fm.pages.value.length > 0)=0A= {=0A= // check page range=0A= var pageRange =3D fm.pages.value;=0A= var volume =3D fm.volume.value;=0A= var issue =3D fm.issue.value;=0A= var continueFlag =3D 0;=0A= //check the volume=0A= // if (isNaN(volume))=0A= // {=0A= // // volume failed checking=0A= // alert("Volume is invalid. "+errmsg+".");=0A= // return false;=0A= // }=0A= //check the issue=0A= if ((issue.length !=3D 0) && isNaN(issue))=0A= {=0A= // issue failed checking=0A= alert("Issue is invalid. "+errmsg+" or leave blank.");=0A= return false;=0A= }=0A= //check the page range=0A= if (isNaN(pageRange))=0A= {=0A= var isValid =3D false;=0A= // check for hyphen=0A= var hyphenIndex =3D pageRange.indexOf("-");=0A= if ((hyphenIndex !=3D -1) && (hyphenIndex =3D=3D = pageRange.lastIndexOf("-")))=0A= {=0A= // we have only one hyphen, so extract each number=0A= var firstNum =3D pageRange.substring(0, hyphenIndex);=0A= var secondNum =3D pageRange.substring(hyphenIndex + 1);=0A= // check for S=0A= var firstS =3D firstNum.indexOf("S");=0A= var secondS =3D secondNum.indexOf("S");=0A= if (firstS =3D=3D secondS)=0A= {=0A= if ((firstS =3D=3D -1) && isNum(firstNum) && isNum(secondNum) && = (firstNum.length > 0) && (secondNum.length > 0))=0A= isValid =3D true; // both inputs are digits=0A= else if (firstS =3D=3D 0)=0A= {=0A= var firstNumNoS =3D firstNum.substring(1);=0A= var secondNumNoS =3D secondNum.substring(1);=0A= if (isNum(firstNumNoS) && isNum(secondNumNoS) && = (firstNumNoS.length > 0) && (secondNumNoS.length > 0))=0A= isValid =3D true; // both inputs are Sdigits=0A= }=0A= =0A= }=0A= }=0A= if (isValid)=0A= {=0A= return true;=0A= }=0A= else=0A= {=0A= alert("The page range is invalid. "+errmsg+" and a hyphen '-' if = required.");=0A= return false;=0A= }=0A= }=0A= return true;=0A= }=0A= else=0A= {=0A= alert("Volume and pages are required fields. Please make sure data has = been entered for both fields.");=0A= return false;=0A= }=0A= }=0A= =0A= // returns true if a is an Integer.=0A= function isNum(a)=0A= { return !(isNaN(a)); }=0A= =0A= function fixInlineLists() {=0A= if (!document.getElementById) return;=0A= var allLIs =3D document.getElementsByTagName('li');=0A= var bulletNode =3D document.createElement('img');=0A= bulletNode.src = =3D"http://download.interscience.wiley.com/images/icon.bullet.gif";=0A= =0A= for (var i=3D0; iAbstract | References';=0A= }=0A= //alert("URL: " + loc + "\nStart Index: " + startIndex + "\nEnd Index: = " + endIndex + "\nPage: " + page + "\nLink Text: " + links);=0A= return links;=0A= }=0A= =0A= =0A= function selectAll(fm)=0A= {=0A= //var fm =3D document.viewSelectedForm;=0A= =0A= for (var i =3D 0; i < fm.elements.length; i++)=0A= {=0A= if (fm.elements[i].type =3D=3D 'checkbox' /*&& fm.elements[i].name = =3D=3D 'ID'*/)=0A= {=0A= fm.elements[i].checked =3D true;=0A= }=0A= }=0A= }=0A= =0A= =0A= function do_popup(file)=0A= {=0A= var w =3D window.open(file, 'popWin', = 'width=3D350,height=3D500,scrollbars=3Dyes');=0A= =0A= }=0A= =0A= =0A= function mailTool(itemID, useurl, skin)=0A= {=0A= //var url =3D "/cgi-bin/mailform?item=3D"+itemID;=0A= var url =3D "/cgi-bin/mailform?item=3D" + itemID + "&skin=3D" + skin;=0A= var parameters =3D = 'status=3Dno,scrollbars=3Dno,resizable=3Dyes,width=3D400,height=3D475';=0A= =0A= if (useurl !=3D "")=0A= {=0A= url +=3D "&useurl=3D"+useurl;=0A= }=0A= =0A= if (arguments.length >=3D 4 && arguments[3] =3D=3D 'cluster')=0A= {=0A= url +=3D '&type=3Dcluster';=0A= }=0A= =0A= eval("wileyMailTool =3D = window.open('"+url+"','MailTool','"+parameters+"')");=0A= =0A= // If object exists ensure has focus=0A= if (eval("wileyMailTool") && window.focus)=0A= eval("wileyMailTool").focus();=0A= }=0A= =0A= =0A= /*=0A= * 1. Find the links we need to alter.=0A= * 2. For each link apply the new styles we need.=0A= */=0A= function fixAbsRefRendering()=0A= { =0A= var table =3D document.getElementById('prerendered');=0A= var anchors =3D table.getElementsByTagName('a');=0A= for (var i =3D 1; i < anchors.length; i++)=0A= {=0A= if(anchors[i].href !=3D"") =0A= { =0A= applyAbsRefStyleCorrection(anchors[i]);=0A= =0A= }=0A= }=0A= }=0A= =0A= function applyAbsRefStyleCorrection(currentLink)=0A= {=0A= currentLink.style["color"] =3D "#369";=0A= currentLink.style["fontWeight"] =3D "normal";=0A= currentLink.style["marginLeft"] =3D "3px";=0A= currentLink.style["marginRight"] =3D "5px";=0A= }=0A= =0A= function populatePage(formName)=0A= {=0A= if (formName.Page.value =3D=3D '')=0A= {=0A= formName.Page.value =3D document.location;=0A= }=0A= }=0A= =0A= function equalizeColumnWidth(numFeatures)=0A= {=0A= var numberOfFeatures =3D numFeatures; =0A= // Percentage width of table to use for each column.=0A= var percentPerFeature =3D Math.floor(100 / numberOfFeatures); =0A= // Number of columns in total. Content cols + seperators. =0A= =0A= document.writeln("");=0A= for(var i =3D 0; i < numberOfFeatures; i++)=0A= { =0A= document.writeln(' 3D"blank"

');=0A= }=0A= document.writeln("");=0A= }=0A= =0A= function old_equalizeColumnWidth(numFeatures)=0A= {=0A= var numberOfFeatures =3D numFeatures; =0A= // Percentage width of table to use for each column.=0A= var percentPerFeature =3D Math.floor(100 / numberOfFeatures); =0A= // Number of columns in total. Content cols + seperators. =0A= =0A= if(debug)=0A= {=0A= alert("Number of feature boxes: " + numberOfFeatures + "\nPercent per = feature: " + percentPerFeature);=0A= }=0A= =0A= document.writeln("");=0A= for(var i =3D 0; i < numberOfFeatures; i++)=0A= { =0A= if (netscape4 =3D=3D false)=0A= {=0A= document.writeln(' 3D"blank"

'); =0A= }=0A= }=0A= document.writeln("");=0A= }=0A= =0A= function writeFBoxCell()=0A= {=0A= if(first)=0A= {=0A= document.write('');=0A= }else=0A= {=0A= document.write('');=0A= }=0A= numFeatures ++;=0A= }=0A= =0A= =0A= //=0A= // escape apostrophe characters within a string=0A= //=0A= function encode(str)=0A= {=0A= out =3D '';=0A= =0A= for (a =3D 0; a < str.length; a++)=0A= {=0A= c =3D str.charAt(a);=0A= =0A= if (c =3D=3D "'")=0A= {=0A= out +=3D '\\';=0A= }=0A= =0A= out +=3D c;=0A= }=0A= =0A= return out;=0A= }=0A= =0A= =0A= //=0A= //=0A= //=0A= function escapeEntities(str)=0A= {=0A= while (str.indexOf("'") > -1)=0A= {=0A= pos =3D str.indexOf("'");=0A= str =3D str.substr(0, pos) + '\\\'' + str.substr(pos + 6);=0A= }=0A= =0A= return str;=0A= }=0A= =0A= =0A= // new popup function less intrusive just uses the DOM to pickup links = with an exwin class.=0A= // currently implemented for Figure popups on D&T homepage.=0A= =0A= function exLinks()=0A= {=0A= if (document.getElementById)=0A= {=0A= var aObject =3D document.getElementsByTagName("a");=0A= for (var x=3D0; x" + = liels[j].innerHTML + "

You do not have = anything saved in this menu.

";=0A= else=0A= tmpinnerhtml +=3D "

" = + liels[j].innerHTML + "

"; =0A= } =0A= } else {=0A= //setup var to see if more is required=0A= var more =3D (subnodeslength < lilength) ? true : = false; =0A= var flag =3D true;=0A= for (var j=3D0; j" + liels[j].innerHTML + = "";=0A= } else if (j > lilength-3){=0A= if (j =3D=3D lilength-2){=0A= var url =3D liels[j].innerHTML.split('"')[1];=0A= tmpinnerhtml +=3D "

" + liels[j].innerHTML + "

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Cancer
ISSN: 1097-0142 = (Online)
ISSN:=20 0008-543X (Print)

Volume 94, Issue 12, 2002.
Pages: = 3219-3224

Top of page
Abstract
MATERIALS AND METHODS
RESULTS
DISCUSSION
References

Tables: 1
List of=20 Images
Abstract=20 Only

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Online ISSN: 1097-0142 Print ISSN: = 0008-543X
Cancer
Volume 94, Issue 12, 2002. Pages: 3219-3224

Copyright © 2002 American Cancer = Society

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Volume 94, Issue 12, Pages 3219-3224

Published Online: 12 Jun 2002

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Original Article
<= /TABLE>

^*Correspondence to Lauren E. = Abrey,=20 Department of Neurology, Memorial Sloan-Kettering Cancer Center, = 1275 York=20 Avenue, New York, NY 10021

Fax: (917) 432-2310

High-grade gliomas in = patients with=20 prior systemic malignancies

Fernando C. Maluf, M.D.^=
1, Lisa=20 M. DeAngelis, M.D.², = Jeffrey J.=20 Raizer, M.D.², Lauren E. = Abrey,=20 M.D.^{2=20
*}

¹Department of Medicine, = Memorial Sloan-Kettering Cancer Center, New York, New=20 York
²Department of = Neurology,=20 Memorial Sloan-Kettering Cancer Center, New York, New = York

email: Lauren E. Abrey (abreyl@mskcc.org)

Keywords

glioma =95 glioblastoma multiforme (GBM) =95 anaplastic = astrocytoma=20 (AA) =95 oligodendroglioma (AO) =95 chemotherapy =95 = radiation therapy =95=20 brain metastases

Abstract

3DAbstract=20

BACKGROUND

The current study was conducted to characterize the impact = of a=20 prior malignancy on the diagnosis, treatment, and outcome of = high-grade glioma.

METHODS

A retrospective study of 21 patients with a histologic = diagnosis=20 of glioblastoma multiforme (GBM), anaplastic astrocytoma = (AA), or=20 anaplastic oligodendroglioma (AO) after a prior diagnosis of = solid=20 tumor or hematologic malignancy was conducted. Glioma = histology (GBM=20 vs. AA/AO), patient age ( 60 years vs. > 60 years), and extent of = resection=20 (biopsy vs. subtotal vs. complete) were evaluated for their=20 prognostic influence.

RESULTS

Of the 21 patients studied, 17 had GBM, 3 had AA, and 1 = patient=20 had high-grade AO. There were 25 systemic carcinomas = diagnosed in 21=20 patients (18 solid tumors including breast carcinoma, = prostate=20 carcinoma, and melanoma and 7 hematologic malignancies). The = glioma=20 occurred within a previous radiation field in only three = patients,=20 two of whom had solid tumors and one of whom had a childhood = hematologic malignancy. Surgical resection was the initial = treatment=20 for the brain tumor in 17 patients, and the majority of = patients=20 received radiation therapy and adjuvant chemotherapy. Four = patients=20 who initially were misdiagnosed as having brain metastases = received=20 whole brain radiation therapy as their initial treatment, = thereby=20 compromising optimal care. The overall median survival for = all the=20 patients in the current study was 14 months (range, 1-44 = months)=20 from the time of brain tumor diagnosis. The extent of = resection was=20 found to be the only prognostic variable that was associated = with=20 survival (P =3D 0.03).

CONCLUSIONS

Secondary glioma may occur in patients as a consequence of = therapy for a prior malignancy, but most often represents a = sporadic=20 event. The outcome and recommended treatment are identical = to those=20 for patients with primary gliomas. Accurate diagnosis is = essential;=20 neuroimaging often is suggestive of a primary brain tumor = and should=20 initiate surgical intervention so that histopathology can be = obtained early and appropriate treatment instituted. Cancer=20 2002;94:3219-24. =A9 2002 American Cancer Society.

DOI 10.1002/cncr.10595

Received: 17 July 2001; Revised: 10 December 2001; Accepted: 9 = January=20 2002

Digital Object Identifier=20 = (DOI)

10.1002/cncr.10595 = ; About=20 DOI

Article=20 Text

High-grade gliomas are aggressive primary brain tumors with few = known=20 etiologic risk factors. Familial brain tumor syndromes and genetic = disorders account for approximately 1-10% of all gliomas.[1][2]=20 To our knowledge, ionizing radiation is the only known = environmental risk=20 factor for the development of high-grade gliomas,[3]=20 but is reported to be a contributing etiologic factor in < 1% = of=20 patients. Therefore, it appears that the majority of patients lack = obvious=20 risk factors. To our knowledge, in previous epidemiologic studies, = prior=20 systemic malignancies (other than hematologic malignancies[4][5])=20 have not been examined as potential risk factors for the = development of a=20 glioma.

Furthermore, to our knowledge, the affect of a prior cancer = diagnosis=20 on the diagnosis, treatment, and prognosis of patients with = high-grade=20 glioma has not previously been described to date. Patients with a = history=20 of another malignancy may be at risk of various impediments to = treatment,=20 including delayed diagnosis, inability to tolerate further = aggressive=20 therapy, and perceived poor prognosis. In the current study, we = report 21=20 patients with high-grade glioma after a prior systemic malignancy = with the=20 purpose of characterizing the impact of a prior tumor and its = treatment on=20 the diagnosis, treatment, and outcome of a secondary high-grade=20 glioma.

MATERIALS AND=20 METHODS

3D"MATERIALS

A query of the Memorial Sloan-Kettering Cancer Center (MSKCC) = Neurology=20 database identified 21 patients, treated between August 1993 and = December=20 2000, who had a histologic diagnosis of glioblastoma multiforme = (GBM),=20 anaplastic astrocytoma (AA), or anaplastic oligodendroglioma (AO) = after a=20 prior diagnosis of a solid tumor or hematologic malignancy. In the = same=20 time interval, a total of 703 patients with high-grade glioma were = identified in the same database, indicating that these 21 patients = represent approximately 3% of the malignant glioma patients seen = at MSKCC.=20 Basal cell carcinoma, squamous cell carcinoma of the skin, and in = situ=20 carcinoma of the cervix were not considered prior neoplasms. = Hospital=20 charts were reviewed for clinical information.

The stage of the primary tumor was categorized according to the = American Joint Committee on Cancer (AJCC) cancer staging system[6]=20 as locoregional (TNM0) or metastatic (TNM1). The treatment of the = primary=20 malignancy, including surgery, radiation therapy, chemotherapy, = hormonal=20 therapy, immunotherapy, or experimental agents, was recorded for = each=20 patient. Patients were considered to be free of the first = malignancy if,=20 at the time of the glioma diagnosis, clinical, laboratory, and=20 radiographic evaluation had not revealed any evidence of systemic=20 malignancy for at least 2 years. The interval between the first = malignancy=20 and the diagnosis of glioma was recorded in years. The date of the = glioma=20 diagnosis was the date of the first pathology diagnosis; otherwise = the=20 date of the first neuroimaging test was used.

Glioma resection was categorized according to the surgical = report and=20 postoperative imaging as biopsy, subtotal resection, or complete=20 resection. Standard radiation therapy was used to treat all = patients; no=20 radiosurgery or hyperfractionated radiation therapy was = administered. All=20 chemotherapy agents administered were recorded. Glioma histology = (GBM vs.=20 anaplastic glioma), patient age ( 60=20 years vs. > 60 years), and extent of resection (biopsy vs. = subtotal=20 resection vs. complete resection) were evaluated for prognostic=20 influence.

Survival was calculated from the date of glioma diagnosis to = the date=20 of last follow-up or death. Survival was analyzed using the = Kaplan-Meier=20 product-limit method.[7]=20 The Wilcoxon test was used to determine any significant difference = in the=20 median survival time according to the clinical prognostic = variables on=20 univariate analysis. All log-rank tests were assessed at a 5% = significance=20 level. The Cox logistic regression method was used for = multivariate=20 analysis.

RESULTS

3DRESULTS=20

The 14 men and 7 women in the current study ranged in age from = 23-75=20 years (median age, 60 years). Of these 21 patients, 17 had GBM, 3 = patients=20 had AA, and 1 patient had AO. Seven patients had first-degree = relatives=20 affected by cancer, seven had no contributory family history, and = the=20 family history was not properly recorded in seven patients. Of = those=20 family members with a history of cancer, only one had a brain = tumor, and=20 in two women with breast carcinoma there was a family history of = breast=20 carcinoma.

There were 25 systemic malignancies in 21 patients: 18 solid = tumors and=20 7 hematologic malignancies (Table 1).=20 Of the 15 patients with solid tumors, 13 had no evidence of active = tumor=20 at the time of glioma diagnosis and 2 patients had metastatic = disease. The=20 median age at the time of diagnosis of a primary solid malignancy = was 57=20 years (range, 26-73 years), and the median time interval between = the=20 diagnosis of a systemic solid tumor and glioma was 6.5 years = (range,=20 0.5-31 years). Glioma occurred within a previous radiation field = in 2=20 patients; a 38-year-old man with liposarcoma of the left temple = received=20 6600 centigrays (cGy) of focal brain radiation and developed a = left=20 frontal GBM 6 years later and a 58-year-old woman with breast = carcinoma=20 that was metastatic to the brain received whole brain radiotherapy = 19=20 years prior to the development of a right parietal AO.=20

Table 1. Patient Characteristics, = Treatment Received, And Outcome

Age (glioma dx)	Gender	Primary lesion	Glioma histology	Interval (yrs)	Prior CT	Prior cranial RT	Glioma treatment	Survival = (mos)

58	F	Breast	AO	24	Yes	Yes	B	1 (D)
69	F	Breast	GBM	8	Yes	No	SB/RT/CT	14 (D)
68	F	Breast	GBM	9	No	No	C/RT/CT	13 (D)
64	F	Breast	GBM	7	Yes	No	SB/RT	8 (D)
63	F	Breast/melanoma	GBM	3/1	No	No	C/RT/CT	6 (AWD)
35	F	Melanoma	GBM	9	No	No	B/RT/CT	10 (D)
62	M	Melanoma	GBM	6	No	No	SB/RT/CT	6 (D)
64	M	Prostate	AA	7	No	No	SB/NA/NA	5 (AWD)
73	M	Prostate	GBM	1	No	No	C/RT/CT	5 (AWD)
75	M	Prostate	GBM	2	No	No	B/RT	7 (D)
44	M	Liposarcoma/prostate	GBM	6/2	No	Yes	SB/RT/CT	12 (AWD)
38	M	Liposarcoma^a	GBM	1	No	No	SB/CT	8 (D)
60	M	Thyroid	GBM	0.5	No	No	C/RT/CT	13 (AWD)
67	M	Thyroid/renal	GBM	NA	No	No	B/NA/NA	29 (D)
65	M	CLL	GBM	3	No	No	SB/RT/CT	14 (D)
56	M	CLL	GBM	1	Yes	No	C/RT/CT	14 (D)
49	F	CLL/vulvar	AA	31/4	No	No	SB/CT	3 (AWD)
53	M	CML	GBM	2	Yes	No	C/RT/CT	3 (D)
23	M	ALL	AA	8	Yes	Yes	SB/RT/CT	11 (D)
35	M	HD	GBM	18	Yes	No	C/RT/CT	43 (D)
48	M	NHL	GBM	1	No	No	C/RT/CT	11 = (D)

DX: diagnosis; CT: = chemotherapy;=20 RT: radiation therapy; F: female; AO: anaplastic = oligodendroglioma;=20 B: biopsy; D; died; GBM: glioblastoma multiforme; SB: = subtotal=20 resection; C: complete resection; AWD: alive with disease; = M: male;=20 AA: anaplastic astrocytoma; NA: not available; CLL: CLL: = chronic=20 lymphocytic leukemia; CML: chronic myelogenous leukemia; = ALL: acute=20 lymphocytic leukemia; HD: Hodgkin disease; NHL: non-Hodgkin=20 lymphoma.
^a Patient was = infected with=20 human immunodeficiency=20 virus.

Seven patients had hematologic malignancies at a median age of = 57 years=20 (range, 15-63 years) followed by glioma at a median interval of 3 = years=20 (range, 1-31 years). Of these patients, 2 with childhood = hematologic=20 malignancies who were heavily exposed to chemotherapy including=20 antimetabolites and cranial radiation therapy developed high-grade = gliomas=20 at a young age; 1 patient with acute lymphocytic leukemia (ALL) = who=20 received 2400 cGy of prophylactic cranial irradiation developed AA = 8 years=20 later at the age of 23 years and another patient with Hodgkin = disease=20 developed a GBM 18 years later at the age of 35 years.

Surgical resection was the initial treatment of the brain tumor = in 17=20 patients; all patients had histologic confirmation of their = glioma.=20 Complete resection was achieved in nine patients, subtotal = resection was=20 performed in six patients, and two patients underwent a biopsy.=20 Information regarding postsurgical treatment was available for 16 = of these=20 patients. Eleven patients received radiation therapy and adjuvant=20 chemotherapy, 2 patients received adjuvant chemotherapy alone, 1 = patient=20 received radiation therapy alone, and 2 patients received no = treatment.=20 The most common cytotoxic agents used included carmustine, = temozolomide,=20 procarbazine, and the combination of procarbazine, lomustine, and=20 vincristine (PCV).

Four patients had biopsy confirmation of their glioma after = initial=20 treatment for presumed brain metastases. All received whole brain=20 radiation therapy as the initial treatment for intracranial = lesions=20 revealed by neuroimaging that were presumed to be metastatic on = the basis=20 of the patient's history of prior systemic malignancy. However, = none of=20 these patients had evidence of active systemic disease, and all = were >=20 5 years from their original cancer diagnosis. A 62-year-old man = who was 6=20 years disease-free from a Clark Stage III melanoma developed an = isolated=20 brain lesion that was treated with concurrent whole brain = radiation=20 therapy (3600 cGy) and paclitaxel. A subsequent limited resection = revealed=20 a GBM and the patient died 6 months later from brain tumor = progression. A=20 35-year-old woman with a diagnosis of resected melanoma 9 years = prior to=20 the appearance of an isolated left parietal mass was treated with = 6000cGy=20 whole brain radiation therapy. Subsequent MRIs were highly = suspicious of a=20 high-grade glioma as opposed to metastatic disease, and a biopsy = revealed=20 a GBM. This patient received carmustine and died 10 months after = surgery.=20 A 69-year-old woman with a prior diagnosis of Stage II breast = carcinoma=20 who was treated with surgery and adjuvant chemotherapy was = diagnosed with=20 an isolated brain lesion 8 years later and treated with whole = brain=20 radiation therapy The pattern of radiographic progression raised a = diagnostic concern and a subtotal tumor resection was performed, = revealing=20 GBM. The patient received additional postoperative radiation = therapy as=20 well as carmustine and procarbazine; however, despite undergoing a = second=20 resection, she died of progressive GBM 14 months after diagnosis. = A=20 64-year-old woman with Stage II breast carcinoma who was treated = with=20 surgery and adjuvant doxorubicin-based chemotherapy followed by = tamoxifen=20 developed 2 separate brain lesions 7 years later and was treated = with=20 whole brain radiation therapy with rapid disease progression. A = subtotal=20 resection revealed GBM, but due to poor neurologic status, no = further=20 treatment was given. The patient died 8 months later.

The median survival for all patients was 14 months (range, 1-44 = months)=20 from the time of diagnosis of the brain tumor (Fig. 1).=20 The median survival for patients who underwent biopsy, subtotal = resection,=20 and optimal resection was 8 months (range, 1-29 months), 12 months = (range,=20 3-14 months), and 14 months (range, 3-43 months), respectively = (P =3D=20 0.09) (Fig. 2).=20 Patient age at the time of the diagnosis of high-grade glioma and = tumor=20 histology did not appear to be correlated with survival (P = =3D 0.7=20 and P =3D 0.7, respectively). Regression analysis = demonstrated that=20 the extent of resection was the only prognostic variable = associated with=20 survival time (P =3D 0.03).=20

Figure 1. Survival = distribution=20 of 21 patients with a secondary glioma.
[Normal View 9K | = Magnified View=20 12K]

Figure 2. Survival = distribution=20 of 21 patients based the extent of resection. The dashed = line=20 represents those patients who underwent a biopsy, the solid = line=20 represents those patients who underwent a subtotal = resection, and=20 the dotted line represents those patients who underwent a = complete=20 resection.
[Normal View=20 14K | Magnified = View=20 19K]

DISCUSSION

3DDISCUSSION=20

In the current retrospective study of patients with secondary = malignant=20 gliomas, it would appear that the majority of gliomas develop as a = sporadic event without any clear etiologic precipitant. The = clinical=20 outcome of this small series is similar to that observed in = sporadic=20 primary high-grade gliomas, suggesting that patients with = secondary=20 malignant gliomas merit the same treatment and have the same = prognosis as=20 those with no prior history of malignancy. Regression analysis = found the=20 extent of resection to be the only clinical variable associated = with=20 outcome (P =3D 0.03). However, the small sample size and = the=20 heterogeneity of the patient population in the current study = likely=20 limited our ability to identify other prognostic factors known to = affect=20 outcome, such as patient age and tumor histology.

Carcinomas of the breast and prostate were the most common = primary=20 neoplasms observed in patients with secondary gliomas and, not=20 coincidentally, are the most prevalent tumors affecting women and = men,=20 respectively. Both tumors usually affect patients age > 50 = years and=20 are associated with favorable long-term survival, thus permitting=20 patients to develop a brain tumor at a later age. There was no = obvious=20 etiologic relation between the systemic tumor and the development = of=20 glioma in these patients. In a Swedish study of 154,414 patients, = no=20 correlation was found between breast carcinoma and the development = of=20 secondary gliomas.[8]=20 None of the patients in the current study had lung carcinoma = preceding=20 glioma, despite the high incidence of lung carcinoma in the = general=20 population. This may be explained by the poor survival of most = patients=20 with small and nonsmall cell lung carcinoma,[9][10]=20 so there is no opportunity=20 for a brain tumor to become manifest. This hypothesis has been = studied as=20 a possible explanation for the apparent increasing incidence of = brain=20 tumors among the elderly. As other diseases that used to lead to = early=20 death become curable or controllable, patients live long enough to = develop=20 less common illnesses such as brain tumors that then appear to = increase in=20 incidence.[11]

In 4 of the 21 patients studied (19%), there was a possible = correlation=20 between glioma development and prior therapy. Three patients (14%) = developed malignant glioma within a prior radiotherapy port, a = known cause=20 for gliomas. One patient with Hodgkin disease who was heavily = exposed to=20 antimetabolites, a suspected risk factor,[12]=20 developed GBM. The dose of cranial radiation therapy was different = for all=20 patients, although all patients received doses known to predispose = to=20 glioma formation. In addition ALL itself is a risk factor for = glioma=20 formation,[13]=20 independent of the administration of cranial radiation therapy.[4][5]=20 The cumulative 20-year risk of developing secondary high-grade = gliomas in=20 patients with ALL was reported to be 0.7%, and the median interval = from=20 the time of ALL diagnosis to the appearance of a high-glioma was = 9.1=20 years.[3]=20 Bhatia et al. also have demonstrated a higher incidence of = secondary=20 gliomas in patients with childhood Hodgkin disease treated with=20 chemotherapy and radiation therapy.[14]

The most important clinical observation is the risk of = misdiagnosis of=20 brain metastases in patients with a prior history of systemic = malignancy.=20 In the current study, four patients who were misdiagnosed with = brain=20 metastases received inappropriate whole brain radiation therapy, = and=20 complete surgical resection was compromised by the delay. Several=20 radiographic and clinical factors may be helpful in = differentiating=20 between a brain metastasis and a new primary brain tumor. The lack = of=20 active systemic disease (particularly lung metastases[12]),=20 a long disease-free interval between the first malignancy and the=20 appearance of the brain lesion, a primary neoplasm that does not = usually=20 metastasize to the brain (e.g., prostate carcinoma), and prior = exposure to=20 cranial radiation therapy should raise the suspicion of a primary = brain=20 tumor. Of equal importance, the magnetic resonance imaging (MRI)=20 characteristics of the lesion may provide direct clues that the = lesion is=20 a primary brain tumor and not metastatic. Infiltrative lesions = with=20 involvement of the corpus callosum, lesions involving deep white = matter=20 structures as opposed to the gray-white cortical junction, and = extensive=20 infiltration involving gray matter and not just white matter all = suggest a=20 glioma (Fig. 3).=20 If clinical and MRI findings are suggestive of glioma, a surgical=20 procedure should be considered to obtain a pathologic diagnosis = and=20 delineate optimal therapy. In those patients in whom radiographic = features=20 are consistent with either a primary or metastatic lesion and the = clinical=20 situation does not clarify the issue, resection therefore is = indicated.=20 Macroscopic total resection prolongs survival for patients with = gliomas[15]=20 and patients with single brain metastasis as well.[16]=20 Therefore, therapeutic benefit is achieved as well as diagnosis in = either=20 situation.=20

Figure 3. = Gadolinium-enhanced=20 (A) axial and (B) sagittal magnetic resonance imaging scan = of a=20 breast carcinoma patient treated with suboptimal radiation = doses for=20 misdiagnosed brain metastasis. This scan demonstrates = infiltration=20 of the corpus callosum that would be extremely unusual for a = metastatic lesion.
[Normal=20 View 49K | Magnified View=20 111K]

Our conclusions are limited by the small sample size in the = current=20 study and the fact that this it was a retrospective review from a = single=20 institution. The clinical outcome of the patients with secondary=20 malignancies in the current study was identical to that for = patients with=20 primary gliomas despite the prior malignancy and treatment of the = patients=20 herein. However, accurate diagnosis is essential and usually = suggestive on=20 neuroimaging; biopsy or resection is critical in these patients = and should=20 be performed early so appropriate treatment can be instituted. To=20 determine whether patients with solid tumor, particularly those = with=20 breast and prostate carcinomas, are at increased risk of = developing a=20 secondary glioma would require a larger epidemiologic study.

References

3DReferences=20

1 Chadduck WM, Netsky MG. Familial gliomas: = report of=20 four families, with chromosome studies. Neurosurgery. = 1982;=20 10(4): 445-449.

2 Lossignol D, Grossman SA, Sheidler VR, = Griffin CA,=20 Piantadosi S. Familial clustering of malignant astrocytomas. = J=20 Neurooncol. 1990; 9(2): 139-145.

3 Walter AW, Hancock ML, Pui CH, et al. = Secondary=20 brain tumors in children treated for acute lymphoblastic = leukemia at=20 St Jude Children's Research Hospital. J Clin Oncol. = 1998;=20 16(12): 3761-3767.

4 Meadows AT, D'Angio GJ, Mike V, et al. = Patterns of=20 second malignant neoplasms in children. Cancer. 1977; = 40( 4 Suppl): 1903-1911.

6 American Joint Committee on Cancer cancer = staging=20 handbook. Philadelphia: Lippincott-Raven, 1998.

7 Kaplan E, Meier F. Nonparametric estimation = from=20 incomplete observations. J Am Stat Assoc. 1958; = 58:=20 457-481.

8 Malmer B, Tavelin B, Henriksson R, Gronberg = H.=20 Primary brain tumours as second primary: a novel association = between=20 meningioma and colorectal cancer. Int J Cancer. 2000; = 85(1): 78-81.

9 Souhami RL, Law K. Longevity in small cell = lung=20 cancer. A report to the Lung Cancer Subcommittee of the = United=20 Kingdom Coordinating Committee for Cancer Research. Br J=20 Cancer. 1990; 61(4): 584-589.

10 Lin AY, Ihde DC. Recent developments in = the=20 treatment of lung cancer. JAMA. 1992; 267(12): = 1661-1664.

13 Relling MV, Rubnitz JE, Rivera GK, et al. = High=20 incidence of secondary brain tumours after radiotherapy and=20 antimetabolites. Lancet. 1999; 354(9172): = 34-39.

14 Bhatia S, Robison LL, Oberlin O, et al. = Breast=20 cancer and other second neoplasms after childhood Hodgkin's = disease.=20 N Engl J Med. 1996; 334(12): 745-751.

15 Keles GE, Anderson B, Berger MS. The = effect of=20 extent of resection on time to tumor progression and = survival in=20 patients with glioblastoma multiforme of the cerebral = hemisphere.=20 Surg Neurol. 1999; 52(4): 371-379.

16 Patchell RA, Tibbs PA, Walsh JW, et al. A=20 randomized trial of surgery in the treatment of single = metastases to=20 the brain. N Engl J Med. 1990; 322(8): = 494-500.

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