High-grade malignant = glioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and = follow-up =E2=80=94 Ann Oncol

High-grade malignant glioma: ESMO Clinical = Practice=20 Guidelines for diagnosis, treatment and follow-up

R.=20 Stupp1,=20
J.-C.=20 Tonn2,=20
M.=20 Brada3,=20
G.=20 Pentheroudakis4 and=20
On = behalf of the=20 ESMO Guidelines Working Group*

¹Centre Hospitalier Universitaire Vaudois (CHUV) = and=20 University of Lausanne, Lausanne, and Department of = Oncology-Hematology=20 Riveria-Chablais, Vevey, Switzerland
²Department of Neurosurgery, = Universit=C3=A4tsklinikum=20 Grosshadern, Ludwig-Maximilians-University Munich, Munich, Germany =
³Institute of Cancer Research and the Royal = Marsden NHS=20 Foundation Trust, Sutton, UK
⁴Department of Medical Oncology, Ioannina = University=20 Hospital, Ioannina, Greece

*Correspondence=20 to: ESMO Guidelines Working Group, ESMO Head Office, Via L. = Taddei 4,=20 CH-6962 Viganello-Lugano, Switzerland; E-mail:=20 clinicalrecommendations@esmo.org

incidence

The incidence of malignant glioma is =E2=88=BC5/100 000. = Malignant glioma may=20 develop at all ages, the peak incidence being in the fifth and sixth = decades of=20 life.

diagnosis

Malignant glioma comprises glioblastoma [World Health = Organization=20 (WHO) grade IV], anaplastic astrocytoma (WHO grade III), mixed = anaplastic=20 oligoastrocytoma (WHO grade III) and anaplastic oligodendroglioma (WHO = grade=20 III). Diagnosis after biopsy or tumour resection is made according to = the=20 revised WHO classification. Prognosis depends on tumour grade and = histology.=20 Glioblastoma carries the worst prognosis, while pure oligodendroglioma = tends to=20 have the best outcome and higher response rates to both chemotherapy and = radiation. Prognosis of mixed anaplastic oligoastrocytoma and anaplastic = astrocytoma is intermediate between glioblastoma and pure anaplastic=20 oligodendroglioma. Concordance between local diagnosis and central=20 neuropathology review can be as low as 50%, thus careful review of the = histology=20 is recommended.

Primary brain tumours only very rarely disseminate outside = the central=20 nervous system, thus no systemic staging is required except for = differential=20 diagnosis of brain metastasis.

molecular markers

Genetic loss on chromosomes 1p/19q (LOH 1p/19q), recently = recognized=20 as a chromosomal translocation has been advocated as a marker for = responsiveness=20 to chemotherapy. However, it describes a distinct tumour entity with a = prolonged=20 natural history irrespective of treatment. LOH 1p/19q should be = performed to=20 support a diagnosis of oligodendroglioma.

Epigenetic silencing of the methyl-guanine methyl = transferase=20 (MGMT) gene promoter by methylation suggests a partial = inability of the=20 tumour to repair the chemotherapy-induced DNA damage. In retrospective = analyses=20 it has been correlated with outcome to alkylating agent chemotherapy = [II, B].=20 MGMT determination by immunohistochemistry has been suggested; however, = this=20 method lacks standardization, reproducibility and correlation with = clinical=20 outcome [III, C]. Short of established alternative treatments and in the = absence=20 of clinical consequences routine determination of the MGMT = promoter=20 methylation status does not (yet) add to the patient management outside = clinical=20 =E2=80=A6

[F= ull Text=20 of this Article]

ESMO=20 clinical recommendations:

R. Stupp,
F. Roila,
and=20 On behalf of the ESMO Guidelines = Working=20 Group

Malignant glioma: = ESMO Clinical=20 Recommendations for diagnosis, treatment and follow-up = Ann Oncol (2009) = 20(suppl 4): iv126-iv128=20 doi:10.1093/annonc/mdp151

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$(this).attr("id");=0A= /* allow em-link or em{\d+} */=0A= if ((spanClass !=3D undefined) && = (spanClass.match(/em((\d+)|(-link))/)) ||=0A= (spanId !=3D undefined) && (spanId.match(/em\d+/)))=0A= {=0A= var addr;=0A= var addrEl =3D $(this).children(".em-addr");=0A= if (addrEl.length) {=0A= addr =3D addrEl.text().replace(/{at}/,'@');=0A= }=0A= else {=0A= addr =3D $(this).text().replace(/{at}/,'@');=0A= }=0A= var link =3D 'mailto:' + addr;=0A= var linkContents =3D $(this).attr("title");=0A= var newHtml =3D '';=0A= if ((linkContents =3D=3D undefined) || !(linkContents.length)) {=0A= if ($(this).children("span.mail2-orig-content").length) {=0A= var tempSpan =3D $(this).children("span.mail2-orig-content");=0A= var classStr =3D '';=0A= =0A= var tempClassArr =3D tempSpan.attr("class").split(' ');=0A= if (tempClassArr.length > 1) {=0A= for (var i =3D 0; i < tempClassArr.length; i++) {=0A= if (tempClassArr[i] !=3D 'mail2-orig-content') {=0A= classStr +=3D (' ' + tempClassArr[i].replace(/^x-/,''));=0A= }=0A= }=0A= }=0A= linkContents =3D tempSpan.html().replace(/{at}/,'@');=0A= newHtml =3D '' + linkContents + '';=0A= }=0A= else {=0A= linkContents =3D addr;=0A= }=0A= }=0A= if (newHtml =3D=3D '') {=0A= newHtml =3D '' + linkContents + '';=0A= }=0A= $(this).replaceWith(newHtml);=0A= }=0A= }=0A= );=0A= =0A= /* make links with rel=3D"external-nw" target a new window */=0A= $("a[rel*=3Dexternal-nw]").each(=0A= function(i) {=0A= var id =3D $(this).attr("id");=0A= var targetName =3D "_blank";=0A= var config =3D null;=0A= if ((id !=3D undefined) && id && !(id =3D=3D '') &&=0A= !(gSiteOptions.openWindowDetails =3D=3D undefined)) {=0A= var newLinkOptions =3D gSiteOptions.openWindowDetails[id];=0A= if ((newLinkOptions !=3D undefined) && newLinkOptions) {=0A= var overrideTarget =3D newLinkOptions.target;=0A= var overrideConfig =3D newLinkOptions.config;=0A= if ((overrideTarget !=3D undefined) && overrideTarget && = (overrideTarget.length > 0)) {=0A= targetName =3D overrideTarget;=0A= }=0A= if ((overrideConfig !=3D undefined) && overrideConfig && = (overrideConfig.length > 0)) {=0A= config =3D overrideConfig;=0A= }=0A= }=0A= }=0A= var origTitle =3D $(this).attr("title");=0A= var newTitle =3D '';=0A= if ((origTitle =3D=3D undefined) || (!origTitle)) {=0A= origTitle =3D '';=0A= }=0A= else {=0A= newTitle =3D origTitle + ' ';=0A= }=0A= newTitle +=3D '[opens in a new window]';=0A= $(this).attr("target", targetName).attr("title", newTitle);=0A= if (config !=3D null) {=0A= $(this).click(function() {=0A= window.open(this.href, targetName, config);=0A= return false;=0A= });=0A= }=0A= }=0A= );=0A= =0A= /* attach onFocus handlers to quick-search fields, to clear the=0A= field when it receives focus IF it contains the default=0A= value (such as "Search the site") */=0A= updateFormInput("#header-qs-search-label", "#header-qs-input", '', '');=0A= =0A= /* handle collapsing content-box areas, with user prefs */=0A= setupCollapsibles();=0A= =0A= /* handle "most" boxes */=0A= handleMostBoxes();=0A= });=0A= =0A= =0A= function setupCollapsibles() {=0A= // sites can override this if they want to target different elements=0A= prepCollapsibles("div.content-box div.collapsible");=0A= }=0A= =0A= /* handle collapsing content-box areas, with optional user prefs */=0A= function prepCollapsibles(parentJQueryEl, setPrefs) {=0A= if (typeof(setPrefs) =3D=3D "undefined") {=0A= setPrefs =3D true;=0A= }=0A= var expandStr, contractStr;=0A= if (gSiteOptions =3D=3D undefined) {=0A= expandStr =3D '+';=0A= contractStr =3D '-';=0A= }=0A= else {=0A= if (gSiteOptions.cbExpandString !=3D undefined) {=0A= expandStr =3D gSiteOptions.cbExpandString;=0A= }=0A= else if (gSiteOptions.expandString !=3D undefined) {=0A= expandStr =3D gSiteOptions.expandString;=0A= }=0A= else { expandStr =3D '+'; }=0A= if (gSiteOptions.cbContractString !=3D undefined) {=0A= contractStr =3D gSiteOptions.cbContractString;=0A= }=0A= else if (gSiteOptions.contractString !=3D undefined) {=0A= contractStr =3D gSiteOptions.contractString;=0A= }=0A= else { contractStr =3D '-'; }=0A= }=0A= $(parentJQueryEl).each(=0A= function(i) {=0A= var $this =3D $(this);=0A= var id =3D $this.attr("id");=0A= if (id !=3D null) {=0A= var $labelElement, $label;=0A= for (var i =3D 0; i < gSiteOptions.collapsibleLabels.length; i++) {=0A= $labelElement =3D gSiteOptions.collapsibleLabels[i];=0A= $label =3D $this.find($labelElement);=0A= if ($label.length) {=0A= // get first one=0A= if ($label.length > 1) {=0A= $label =3D $label.eq(0);=0A= }=0A= break;=0A= }=0A= }=0A= =0A= // if there's already a toggle leave this as is=0A= var alreadyHasToggle =3D ($label.length && = $label.find("a.collapse-toggle").length);=0A= if ($label.length) {=0A= if (!(alreadyHasToggle)) {=0A= var labelText =3D $label.html();=0A= $label.empty().append('' + contractStr + = ' ' + labelText + '');=0A= }=0A= }=0A= =0A= var isOpen =3D true;=0A= if (setPrefs) {=0A= var statePref =3D getPrefValue(id + "-state");=0A= if (statePref && ((statePref =3D=3D 'open') || (statePref =3D=3D = 'closed'))) {=0A= if (statePref =3D=3D 'closed') {=0A= isOpen =3D false;=0A= }=0A= }=0A= else {=0A= // no pref, or unknown value=0A= if ($this.hasClass('default-closed')) {=0A= isOpen =3D false;=0A= }=0A= }=0A= }=0A= var childListType;=0A= if ($this.children("ol").length) {=0A= childListType =3D "ol";=0A= }=0A= else {=0A= childListType =3D "ul";=0A= }=0A= if (!isOpen && !(alreadyHasToggle)) {=0A= toggleCollapse($this, childListType, ($labelElement + " a = span.view-more"), expandStr, contractStr);=0A= }=0A= $this.find("a.collapse-toggle").click(=0A= function(e) {=0A= // need to find first parent that is in either state...=0A= // $(this).parents(".collapsible, .collapsed").each(=0A= $(this).parents().each(=0A= function(i) {=0A= if ($(this).hasClass('collapsible') || = $(this).hasClass('collapsed')) {=0A= var isCollapsed =3D $this.hasClass('collapsed');=0A= if (setPrefs) {=0A= var prefName =3D id + "-state";=0A= if (isCollapsed) {=0A= setPref(prefName, "open");=0A= }=0A= else {=0A= setPref(prefName, "closed");=0A= }=0A= }=0A= toggleCollapse($(this), childListType, ($labelElement + " a = span.view-more"), expandStr, contractStr);=0A= fixColHeights(-1);=0A= return false;=0A= }=0A= }=0A= );=0A= e.preventDefault();=0A= }=0A= );=0A= }=0A= }=0A= );=0A= }=0A= =0A= function handleMostBoxes() {=0A= var hadMostBoxes =3D false;=0A= $("div.most-links-box").each(=0A= function(i) {=0A= var $this =3D $(this);=0A= modClass($this, '', 'js-marker');=0A= hadMostBoxes =3D true;=0A= // 1) get the

child:=0A= var hasSelected =3D false;=0A= var mostHdrList =3D null;=0A= if ($mostlist.length) {=0A= var hasItems =3D false;=0A= var hdrList =3D '
';=0A= var $mostli =3D $mostlist.children("li");=0A= if ($mostli.length) {=0A= hasItems =3D true;=0A= $mostli.each(=0A= function(i) {=0A= var $hdr =3D $(this).children("h4").html();=0A= if ($(this).hasClass("most-cur-sel")) {=0A= hasSelected =3D true;=0A= hdrList +=3D '
' + $hdr + '
';=0A= }=0A= else {=0A= hdrList +=3D '
' + $hdr + '
';=0A= }=0A= }=0A= );=0A= }=0A= hdrList +=3D '
';=0A= if (hasItems) {=0A= var header =3D $this.find("div.most-header h3");=0A= if (header.length) {=0A= header.after(hdrList);=0A= }=0A= }=0A= mostHdrList =3D $this.find("div.most-header ul");=0A= }=0A= // 3) if none of the items are selected, make the first one be=0A= if (((mostHdrList !=3D null) && mostHdrList.length) && = (!hasSelected)) {=0A= modClass(mostHdrList.find("li:first"), "most-cur-sel", "");=0A= modClass($this.children("ul").children("li:first"), "most-cur-sel", = "");=0A= }=0A= // 4) bind a handler to each heading li a to toggle = class=3D"most-cur-sel" for =0A= // that item and its corresponding item in the list below=0A= if (((mostHdrList !=3D null) && mostHdrList.length)) {=0A= mostHdrList.find("li a").click(=0A= function(e) {=0A= var curA =3D $(this);=0A= toggleMostSelection(e, $this, curA.text());=0A= }=0A= );=0A= }=0A= }=0A= );=0A= if (hadMostBoxes) {=0A= fixColHeights(-1);=0A= }=0A= }=0A= =0A= function toggleMostSelection(e, mostItemDiv, groupName) {=0A= if (mostItemDiv.length) {=0A= var hdrItems =3D mostItemDiv.find("div.most-header ul li");=0A= if (hdrItems.length) {=0A= hdrItems.each(=0A= function() {=0A= var hdrName =3D $(this).text();=0A= var isChoice =3D (hdrName =3D=3D groupName);=0A= if (isChoice) {=0A= modClass($(this), 'most-cur-sel', '');=0A= }=0A= else {=0A= modClass($(this), '', 'most-cur-sel');=0A= }=0A= }=0A= );=0A= }=0A= var listItems =3D mostItemDiv.children("ul").find("li");=0A= if (listItems.length) {=0A= listItems.each(=0A= function() {=0A= var itemName =3D $(this).children("h4").text();=0A= var isChoice =3D (itemName =3D=3D groupName);=0A= if (isChoice) {=0A= modClass($(this), 'most-cur-sel', '');=0A= }=0A= else {=0A= modClass($(this), '', 'most-cur-sel');=0A= }=0A= }=0A= );=0A= }=0A= }=0A= fixColHeights(-1);=0A= e.preventDefault();=0A= }=0A= =0A= function toggleCollapse(collapsibleEl, hideTagExpr, modTextTagExpr, = expandStr, contractStr) {=0A= if (typeof(expandStr) =3D=3D "undefined") {=0A= expandStr =3D getSiteOption('expandString','+');=0A= }=0A= if (typeof(contractStr) =3D=3D "undefined") {=0A= contractStr =3D getSiteOption('contractString','-');=0A= }=0A= =0A= var $this =3D collapsibleEl;=0A= if ($this.hasClass('collapsed')) {=0A= modClass($this, 'collapsible', 'collapsed');=0A= }=0A= else if ($this.hasClass('collapsible')) {=0A= modClass($this, 'collapsed', 'collapsible');=0A= }=0A= var $toToggle =3D $this.find(hideTagExpr);=0A= if ($toToggle.length) {=0A= $toToggle.toggle();=0A= }=0A= var $rewrite =3D $this.find(modTextTagExpr);=0A= if ($rewrite.length) {=0A= $rewrite.each(=0A= function(i, e) {=0A= var txt =3D $(e).text();=0A= if (txt =3D=3D expandStr) {=0A= $(e).empty().append(contractStr);=0A= }=0A= else if (txt =3D=3D contractStr) {=0A= $(e).empty().append(expandStr);=0A= }=0A= }=0A= );=0A= }=0A= }=0A= =0A= function setupDockBlock(col, dockId, dockClass, contentRules) {=0A= if ((col =3D=3D 2) || (col =3D=3D 3)) {=0A= var navOrigHeight =3D ((col =3D=3D 2) ? gColOrigHeights.col2 : = gColOrigHeights.col3);=0A= var gColNum =3D col;=0A= var gNav =3D ((col =3D=3D 2) ? gCol2 : gCol3);=0A= var gNavHeight =3D ((gNav.length) ? navOrigHeight : 0);=0A= var gNavTopOffset =3D (gNavHeight > 0 ? gNav.offset().top : 0);=0A= var gScrollPos =3D 0;=0A= var gNavDocked =3D false;=0A= /* this won't work in IE 6, so skip it /=0A= / article navigation docking block /=0A= $(window).scroll(function () {=0A= if (gNavHeight > 0 && !isIE6) {=0A= var offsets =3D getPageOffset();=0A= var origHeight =3D ((gColNum =3D=3D 2) ? gColOrigHeights.col2 : = gColOrigHeights.col3);=0A= var navBottom =3D (gNavTopOffset + origHeight) - offsets.y;=0A= if (gScrollPos !=3D offsets.y) {=0A= gScrollPos =3D offsets.y;=0A= if ((navBottom <=3D 0) && !gNavDocked) {=0A= / dock the nav /=0A= gNavDocked =3D true;=0A= addDockBlock(col, dockId, dockClass, contentRules);=0A= }=0A= else if (gNavDocked && (navBottom > 0)) {=0A= / undock the nav /=0A= gNavDocked =3D false;=0A= removeDockBlock(col, dockId);=0A= }=0A= }=0A= }=0A= });=0A= }=0A= }=0A= function addDockBlock(col, dockId, dockClass, contentRules) {=0A= // get direct children li elements only=0A= var colId =3D ("col-" + col);=0A= var newDiv =3D ' 1) {=0A= for (var i =3D 0; i < (contentRules.length - 1); i =3D i + 2) {=0A= var addTo =3D processDockingRule(contentRules[i]);=0A= var add =3D processDockingRule(contentRules[i + 1]);=0A= var addTarget, addVal;=0A= if (addTo.ruleType =3D=3D 'empty') {=0A= addTarget =3D newDivJQuery;=0A= }=0A= else if (addTo.ruleType =3D=3D 'jQuery') {=0A= addTarget =3D $(addTo.rule);=0A= }=0A= if (add.ruleType =3D 'jQuery') {=0A= var addJQEl =3D $(add.rule);=0A= if (addJQEl.length) {=0A= addVal =3D addJQEl.clone();=0A= }=0A= else {=0A= addVal =3D '';=0A= }=0A= }=0A= else if (add.ruleType =3D 'html') {=0A= addVal =3D add.rule;=0A= }=0A= if (addTarget.length && !(addVal =3D=3D '')) {=0A= addTarget.append(addVal);=0A= }=0A= else {=0A= }=0A= }=0A= }=0A= var newDockJQrule =3D "#" + colId + " #" + dockId;=0A= var newDock =3D $(newDockJQrule);=0A= if (newDock.length) {=0A= prepCollapsibles(newDockJQrule + " div.collapsible, " + newDockJQrule = + " div.collapsed", false);=0A= newDock.fadeIn(250);=0A= }=0A= }=0A= =0A= function processDockingRule(rule) {=0A= var retObj =3D new Object();=0A= retObj.empty =3D (((rule !=3D undefined) && (!(rule =3D=3D ''))) ? = false : true);=0A= if (rule =3D=3D '') {=0A= retObj.ruleType =3D 'empty';=0A= }=0A= else if (/^\$$.+$$/.test(rule)) {=0A= retObj.ruleType =3D 'jQuery';=0A= retObj.rule =3D rule.replace(/^\$$(.+)$$/,"$1");=0A= }=0A= else {=0A= retObj.ruleType =3D 'html';=0A= retObj.rule =3D rule;=0A= }=0A= return retObj;=0A= }=0A= =0A= function removeDockBlock(col, dockId) {=0A= var dockedNav =3D $("div#" + dockId);=0A= if(dockedNav.length) {=0A= dockedNav.fadeOut(250, function() { dockedNav.remove(); });=0A= }=0A= }=0A= =0A= =0A= function updateFormInput(labelMatchString, inputMatchString, = defaultColorString, textColorString) {=0A= if ((defaultColorString =3D=3D null) || (defaultColorString =3D=3D '')) = {=0A= defaultColorString =3D "#A0A0A0";=0A= }=0A= if ((textColorString =3D=3D null) || (textColorString =3D=3D '')) {=0A= textColorString =3D "black";=0A= }=0A= var label =3D $(labelMatchString);=0A= var input =3D $(inputMatchString);=0A= if (input.length) {=0A= if ((label.length) && (input.val() =3D=3D '')) {=0A= input.val(label.text()).css("color",defaultColorString);=0A= }=0A= input.focus(=0A= function(e) {=0A= if ((label.length) && ($(this).val() =3D=3D label.text())) {=0A= $(this).val('').css("color",textColorString);=0A= }=0A= }=0A= );=0A= input.blur(=0A= function(e) {=0A= if ((label.length) && ($(this).val() =3D=3D '')) {=0A= $(this).val(label.text()).css("color",defaultColorString);=0A= }=0A= }=0A= );=0A= }=0A= var parentForm =3D label.parents("form").eq(0);=0A= if (parentForm.length) {=0A= parentForm.submit(=0A= function() {=0A= if ((label.length) && (input.length) && (input.val() =3D=3D = label.text())) {=0A= input.val('');=0A= }=0A= return true;=0A= }=0A= );=0A= }=0A= }=0A= =0A= function checkUnloadedImgs(lookupRule) {=0A= if (lookupRule =3D=3D null) {=0A= lookupRule =3D "img";=0A= }=0A= var imageNum =3D -1;=0A= var images =3D $(lookupRule);=0A= if (images.length) {=0A= imageNum =3D 0;=0A= images.each(=0A= function() {=0A= //if ($(this).height() =3D=3D 0) {=0A= if (this.offsetHeight =3D=3D 0) {=0A= imageNum++;=0A= }=0A= }=0A= );=0A= }=0A= return imageNum;=0A= }=0A= =0A= function fixHeightForImages(iter, numImagesToLoad, lookupRule) {=0A= if (lookupRule =3D=3D null) {=0A= lookupRule =3D "img";=0A= }=0A= if (numImagesToLoad > 0) {=0A= var lastNumImagesToLoad =3D numImagesToLoad;=0A= var newNumImagesToLoad =3D checkUnloadedImgs(lookupRule);=0A= if (newNumImagesToLoad < lastNumImagesToLoad) {=0A= fixColHeights(1);=0A= if ((newNumImagesToLoad > 0) && (iter < 10)) {=0A= setTimeout("fixHeightForImages(" + (iter+1) + "," + = newNumImagesToLoad + ",'" + lookupRule + "')", 1000);=0A= }=0A= }=0A= }=0A= }=0A= function getColInfo(colJQEl) {=0A= var colInfo =3D { valid: false, height: 0, bottom: 0, lastElBottom: 0, = extra: 0, fix: false };=0A= if (colJQEl.length) {=0A= var c =3D colJQEl.children();=0A= if (c.length) {=0A= colInfo.height =3D getObjHeight(colJQEl);=0A= colInfo.bottom =3D colJQEl.offset().top + colInfo.height;=0A= var last =3D c.eq(c.length - 1);=0A= colInfo.lastElBottom =3D last.offset().top + getObjHeight(last);=0A= colInfo.extra =3D colInfo.bottom - colInfo.lastElBottom;=0A= colInfo.valid =3D true;=0A= }=0A= }=0A= return colInfo;=0A= }=0A= function checkColHeights() {=0A= var colToFix =3D 0;=0A= if ((gIsMultiCol || gColTempResize) && ((gColOrigHeights.main + = gColOrigHeights.col2 + gColOrigHeights.col3) > 0)) {=0A= var colMainInfo =3D getColInfo(gColMain);=0A= var col2Info =3D getColInfo(gCol2);=0A= var col3Info =3D getColInfo(gCol3);=0A= if (colMainInfo.valid && (gColLows.main =3D=3D 0)) { gColLows.main =3D = colMainInfo.lastElBottom; }=0A= if (col2Info.valid && (gColLows.col2 =3D=3D 0)) { gColLows.col2 =3D = col2Info.lastElBottom; }=0A= if (col3Info.valid && (gColLows.col3 =3D=3D 0)) { gColLows.col3 =3D = col3Info.lastElBottom; }=0A= // check if low point in any column has changed=0A= if ((colMainInfo.valid) && (colMainInfo.lastElBottom !=3D = gColLows.main)) {=0A= colMainInfo.fix =3D true;=0A= }=0A= if ((col2Info.valid) && (col2Info.lastElBottom !=3D gColLows.col2)) {=0A= col2Info.fix =3D true;=0A= }=0A= if ((col3Info.valid) && (col3Info.lastElBottom !=3D gColLows.col3)) {=0A= col3Info.fix =3D true;=0A= }=0A= // check for columns not having same bottom points=0A= if ((colMainInfo.valid) &&=0A= (((col2Info.valid) && (colMainInfo.height < col2Info.height)) ||=0A= ((col3Info.valid) && (colMainInfo.height < col3Info.height)))) {=0A= colMainInfo.fix =3D true;=0A= }=0A= if ((col2Info.valid) &&=0A= (((colMainInfo.valid) && (col2Info.height < colMainInfo.height)) ||=0A= ((col3Info.valid) && (col2Info.height < col3Info.height)))) {=0A= col2Info.fix =3D true;=0A= }=0A= if ((col3Info.valid) &&=0A= (((colMainInfo.valid) && (col3Info.height < colMainInfo.height)) ||=0A= ((col2Info.valid) && (col3Info.height < col2Info.height)))) {=0A= col3Info.fix =3D true;=0A= }=0A= =0A= if (colToFix > -1) {=0A= if (colMainInfo.valid && colMainInfo.fix) {=0A= if ((col2Info.valid && col2Info.fix) || (col3Info.valid && = col3Info.fix)) {=0A= colToFix =3D -1;=0A= }=0A= else { colToFix =3D 1; }=0A= }=0A= else if (col2Info.valid && col2Info.fix) {=0A= if (col3Info.valid && col3Info.fix) {=0A= colToFix =3D -1;=0A= }=0A= else { colToFix =3D 2; }=0A= }=0A= else if (col3Info.valid && col3Info.fix) {=0A= colToFix =3D 3;=0A= }=0A= }=0A= =0A= if (colToFix !=3D 0) {=0A= fixColHeights(colToFix);=0A= }=0A= if (colMainInfo.valid) { gColLows.main =3D colMainInfo.lastElBottom; }=0A= if (col2Info.valid) { gColLows.col2 =3D col2Info.lastElBottom; }=0A= if (col3Info.valid) { gColLows.col3 =3D col3Info.lastElBottom; }=0A= }=0A= setTimeout("checkColHeights()", 5000);=0A= }=0A= function fixColHeights(colChanged) {=0A= if ((gIsMultiCol || gColTempResize) && getSiteOption('setColSizes', = true)) {=0A= var setAll =3D false;=0A= if (colChanged =3D=3D 1) {=0A= if (gColMain.length) {=0A= setObjHeight(gColMain,'auto');=0A= gColOrigHeights.main =3D getObjHeight(gColMain);=0A= }=0A= }=0A= else if (colChanged =3D=3D 2) {=0A= if (gCol2.length) {=0A= setObjHeight(gCol2,'auto');=0A= gColOrigHeights.col2 =3D getObjHeight(gCol2);=0A= }=0A= }=0A= else if (colChanged =3D=3D 3) {=0A= if (gCol3.length) {=0A= setObjHeight(gCol3,'auto');=0A= gColOrigHeights.col3 =3D getObjHeight(gCol3);=0A= }=0A= }=0A= else {=0A= if (colChanged =3D=3D -1) {=0A= // force resize all 3=0A= if (gColMain.length) { setObjHeight(gColMain,'auto'); }=0A= if (gCol2.length) { setObjHeight(gCol2,'auto'); }=0A= if (gCol3.length) { setObjHeight(gCol3,'auto'); }=0A= }=0A= gColOrigHeights.main =3D ((gColMain.length) ? = (getObjHeight(gColMain)) : 0);=0A= gColOrigHeights.col2 =3D ((gCol2.length) ? (getObjHeight(gCol2)) : 0);=0A= gColOrigHeights.col3 =3D ((gCol3.length) ? (getObjHeight(gCol3)) : 0);=0A= setAll =3D true;=0A= }=0A= if ((gColOrigHeights.main + gColOrigHeights.col2 + = gColOrigHeights.col3) > 0) {=0A= var colInfo;=0A= var maxH =3D Math.max(Math.max(gColOrigHeights.main, = gColOrigHeights.col2), gColOrigHeights.col3);=0A= if ((gColMain.length) && ((gColOrigHeights.main < maxH) || = (getObjHeight(gColMain) > maxH) || setAll)) {=0A= setObjHeight(gColMain, maxH);=0A= colInfo =3D getColInfo(gColMain);=0A= if (colInfo.valid) { gColLows.main =3D colInfo.lastElBottom; }=0A= }=0A= if ((gCol2.length) && ((gColOrigHeights.col2 < maxH) || = (getObjHeight(gCol2) > maxH) || setAll)) {=0A= setObjHeight(gCol2, maxH);=0A= colInfo =3D getColInfo(gCol2);=0A= if (colInfo.valid) { gColLows.col2 =3D colInfo.lastElBottom; }=0A= }=0A= if ((gCol3.length) && ((gColOrigHeights.col3 < maxH) || = (getObjHeight(gCol3) > maxH) || setAll)) {=0A= setObjHeight(gCol3, maxH);=0A= colInfo =3D getColInfo(gCol3);=0A= if (colInfo.valid) { gColLows.col3 =3D colInfo.lastElBottom; }=0A= }=0A= }=0A= }=0A= }=0A= =0A= function getObjHeight(obj) {=0A= if (obj instanceof jQuery) {=0A= return obj.get(0).offsetHeight;=0A= }=0A= else if (obj instanceof Array) {=0A= return obj[0].offsetHeight;=0A= }=0A= else {=0A= return obj.offsetHeight;=0A= }=0A= }=0A= function getObjWidth(obj) {=0A= if (obj instanceof jQuery) {=0A= return obj.get(0).offsetWidth;=0A= }=0A= else if (obj instanceof Array) {=0A= return obj[0].offsetWidth;=0A= }=0A= else {=0A= return obj.offsetWidth;=0A= }=0A= }=0A= function setObjHeight(obj, h) {=0A= if (typeof(h) =3D=3D 'number') {=0A= h =3D "" + h + "px";=0A= }=0A= if (obj instanceof jQuery) {=0A= obj.get(0).style.height =3D h;=0A= }=0A= else if (obj instanceof Array) {=0A= obj[0].style.height =3D h;=0A= }=0A= else {=0A= obj.style.height =3D h;=0A= }=0A= }=0A= function setObjWidth(obj, w) {=0A= if (typeof(w) =3D=3D 'number') {=0A= w =3D "" + w + "px";=0A= }=0A= if (obj instanceof jQuery) {=0A= obj.get(0).style.width =3D w;=0A= }=0A= else if (obj instanceof Array) {=0A= obj[0].style.width =3D w;=0A= }=0A= else {=0A= obj.style.width =3D w;=0A= }=0A= }=0A= =0A= / num pixels top of page has been scrolled offscreen /=0A= function getPageOffset() {=0A= var offset =3D new Object();=0A= if( typeof( window.pageXOffset ) =3D=3D 'number' ) {=0A= offset.x =3D window.pageXOffset;=0A= offset.y =3D window.pageYOffset;=0A= } else if( document.body && ( document.body.scrollTop ) ) {=0A= offset.x =3D document.body.scrollLeft;=0A= offset.y =3D document.body.scrollTop;=0A= } else if( document.documentElement && ( = document.documentElement.scrollTop ) ) {=0A= offset.x =3D document.documentElement.scrollLeft;=0A= offset.y =3D document.documentElement.scrollTop;=0A= }=0A= if (typeof(offset.x)=3D=3D"undefined") { offset.x =3D 0; }=0A= if (typeof(offset.y)=3D=3D"undefined") { offset.y =3D 0; }=0A= return offset;=0A= }=0A= function getViewportDim() {=0A= var dim =3D new Object();=0A= // non-IE=0A= if (typeof window.innerWidth !=3D 'undefined') {=0A= dim.x =3D window.innerWidth;=0A= dim.y =3D window.innerHeight;=0A= }=0A= // IE6 in standards compliant mode=0A= else if (typeof document.documentElement !=3D 'undefined'=0A= && typeof document.documentElement.clientWidth !=3D=0A= 'undefined' && document.documentElement.clientWidth !=3D 0) {=0A= dim.x =3D document.documentElement.clientWidth;=0A= dim.y =3D document.documentElement.clientHeight;=0A= }=0A= // older versions of IE=0A= else {=0A= dim.x =3D document.getElementsByTagName('body')[0].clientWidth;=0A= dim.y =3D document.getElementsByTagName('body')[0].clientHeight;=0A= }=0A= return dim;=0A= }=0A= =0A= function newWindowTargets() {=0A= var newWins =3D $("a.in-nw");=0A= if (newWins.length) {=0A= newWins.each(=0A= function() {=0A= var $this =3D $(this);=0A= $this.attr("target", "_blank");=0A= modClass($this, 'in-nw-vis', 'in-nw');=0A= }=0A= );=0A= }=0A= }=0A= =0A= function getSiteOption(optionName, defaultVal) {=0A= if (typeof(defaultVal) =3D=3D "undefined") {=0A= defaultVal =3D gSiteOptionUnknown;=0A= }=0A= if (gSiteOptions =3D=3D undefined) {=0A= return defaultVal;=0A= }=0A= else if (gSiteOptions[optionName] =3D=3D undefined) {=0A= return defaultVal;=0A= }=0A= else {=0A= return gSiteOptions[optionName];=0A= }=0A= }=0A= =0A= function addPartHeaders(req) {=0A= req.setRequestHeader('Accept', 'application/xhtml+xml');=0A= req.setRequestHeader('Range', 'part=3Dvariant-contents');=0A= }=0A= function addCommonHeaders(req) {=0A= if (typeof(callbackToken) !=3D 'undefined') {=0A= req.setRequestHeader('X-Token', callbackToken);=0A= }=0A= }=0A= function allowsCookies() {=0A= if (hasTestCookie()) {=0A= return true;=0A= }=0A= else {=0A= setTestCookie();=0A= return hasTestCookie();=0A= }=0A= }=0A= function setTestCookie() {=0A= setCookie('cks','allowed',7,'/',null,null);=0A= }=0A= function hasTestCookie() {=0A= var ckVal =3D getCookie('cks');=0A= if ((ckVal !=3D null) && (ckVal =3D=3D 'allowed')) {=0A= return true;=0A= }=0A= else {=0A= return false;=0A= }=0A= }=0A= =0A= var UIPrefsCk=3D{=0A= name: "UIPrefs",=0A= expDays: 3652,=0A= path: '/'=0A= };=0A= =0A= function prefDefined(name) {=0A= var val =3D getPrefValue(name);=0A= if (val =3D=3D null) {=0A= return false;=0A= }=0A= else {=0A= return true;=0A= }=0A= }=0A= function getPrefValue(name) {=0A= var prefArray =3D getPrefArray();=0A= if (prefArray) {=0A= name =3D convertPrefString(name);=0A= var match =3D name + ":";=0A= for (var i =3D 0; i < prefArray.length; i++) {=0A= if (prefArray[i].indexOf(match) =3D=3D 0) {=0A= return prefArray[i].substring(match.length);=0A= }=0A= else if (prefArray[i] =3D=3D name) {=0A= // name only, no value, return boolean true=0A= return true;=0A= }=0A= }=0A= }=0A= return null;=0A= }=0A= function convertPrefString(str) {=0A= if (str) {=0A= return str.replace(/[,:=3D]/g,"");=0A= }=0A= return str;=0A= }=0A= function removePref(name) {=0A= var prefArray =3D getPrefArray();=0A= name =3D convertPrefString(name);=0A= if (prefDefined(name)) {=0A= var newArray =3D new Array(prefArray.length - 1);=0A= var match =3D name + ":";=0A= var newArrIndex =3D 0;=0A= for (var i =3D 0; i < prefArray.length; i++) {=0A= if (!((prefArray[i].indexOf(match) =3D=3D 0) || (prefArray[i] =3D=3D = name))) {=0A= newArray[newArrIndex++] =3D prefArray[i];=0A= }=0A= }=0A= setPrefCookie(newArray);=0A= if (prefArray.length =3D=3D 1) {=0A= return null;=0A= }=0A= else {=0A= return newArray;=0A= }=0A= }=0A= else {=0A= return prefArray;=0A= }=0A= }=0A= =0A= function setPref(name, value) {=0A= if (typeof(value) =3D=3D "undefined") {=0A= value =3D null;=0A= }=0A= if (name) {=0A= name =3D convertPrefString(name);=0A= var prefArray =3D removePref(name);=0A= if (prefArray =3D=3D null) {=0A= prefArray =3D new Array;=0A= }=0A= var newArray =3D new Array(prefArray.length + 1);=0A= var newPref =3D name + (((value !=3D null) && (value !=3D '')) ? (':' = + value) : '');=0A= newArray[0] =3D newPref;=0A= for (var i =3D 0; i < prefArray.length; i++) {=0A= newArray[i+1] =3D prefArray[i];=0A= }=0A= setPrefCookie(newArray);=0A= return newArray;=0A= }=0A= else {=0A= return getPrefArray();=0A= }=0A= }=0A= function setPrefCookie(prefs) {=0A= if (prefs && (prefs.length > 0)) {=0A= var prefString;=0A= if (typeof(prefs) =3D=3D 'string') {=0A= prefString =3D prefs;=0A= }=0A= else {=0A= if (prefs.length =3D=3D 1) {=0A= prefString =3D prefs[0];=0A= }=0A= else {=0A= prefString =3D prefs.join(',');=0A= }=0A= }=0A= setCookie(UIPrefsCk.name, prefString, UIPrefsCk.expDays, = UIPrefsCk.path, false, false);=0A= }=0A= else {=0A= deleteCookie(UIPrefsCk.name, UIPrefsCk.path, false);=0A= }=0A= }=0A= // individual pref items in the cookie are separated by ',' and=0A= // nv pref pairs are joined by ':', i.e. n1:v1,n2:v2,n3:v3,etc.=0A= // values are optional. 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';expires=3D'+expires_date.toGMTString() : '' ) +=0A= ( ( path ) ? ';path=3D' + path : '' ) +=0A= ( ( domain ) ? ';domain=3D' + domain : '' ) +=0A= ( ( secure ) ? ';secure' : '' );=0A= }=0A= =0A= function deleteCookie( name, path, domain ) {=0A= if ( getCookie( name ) ) document.cookie =3D name + '=3D' +=0A= ( ( path ) ? ';path=3D' + path : '') +=0A= ( ( domain ) ? 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Annals of Oncology=20

High-grade malignant glioma: ESMO Clinical = Practice=20 Guidelines for diagnosis, treatment and follow-up

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