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Subject: Evidence-based adjuvant therapy for gliomas: Current concepts and newer developments Khan MK, Hunter GK, Vogelbaum M, Suh JH, Chao ST - Indian J Cancer
Date: Sat, 9 May 2009 13:13:08 +0200
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}
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	FONT-SIZE: 9pt; COLOR: #000000; LINE-HEIGHT: 50%; FONT-FAMILY: Verdana, =
Arial, Helvetica, sans-serif
}
.PrePublication {
	BORDER-RIGHT: #eaead7 1px solid; BORDER-TOP: #eaead7 1px solid; =
FONT-SIZE: 11px; BORDER-LEFT: #eaead7 1px solid; COLOR: #464646; =
BORDER-BOTTOM: #eaead7 1px solid; FONT-FAMILY: Arial, Verdana, =
Helvetica, sans-serif; BACKGROUND-COLOR: #e1e3ed
}
.sitethis {
	BORDER-RIGHT: #eaead1 1px solid; BORDER-TOP: #eaead1 1px solid; =
FONT-SIZE: 11px; BORDER-LEFT: #eaead1 1px solid; LINE-HEIGHT: 135%; =
BORDER-BOTTOM: #eaead1 1px solid; FONT-FAMILY: Arial, Verdana, =
Helvetica, sans-serif; BACKGROUND-COLOR: #eaead7
}
.topBand1 {
	FONT-SIZE: 12px; COLOR: #ffffff; FONT-FAMILY: Arial, Verdana, =
Helvetica, sans-serif; BACKGROUND-COLOR: #eaead7
}
.topBand11 {
	FONT-SIZE: 12px; FONT-FAMILY: Arial, Verdana, Helvetica, sans-serif; =
BACKGROUND-COLOR: #9bb4cb
}
.topBand1MO {
	FONT-SIZE: 12px; COLOR: #ffffff; FONT-FAMILY: Arial, Verdana, =
Helvetica, sans-serif; BACKGROUND-COLOR: #c5c1bd
}
.topBand2MO {
	BORDER-RIGHT: #ffffff 1px solid; BORDER-TOP: #ffffff 1px solid; =
FONT-WEIGHT: bold; FONT-SIZE: 1px; BORDER-LEFT: #ffffff 1px solid; =
COLOR: #ffffff; BORDER-BOTTOM: #ffffff 1px solid; FONT-FAMILY: Arial, =
Verdana, Helvetica, sans-serif; BACKGROUND-COLOR: #9bb4cb
}
.buttonCell {
	BACKGROUND-COLOR: #eaead7
}
.leftnavover {
	BORDER-RIGHT: #ffffff 1px solid; BORDER-TOP: #ffffff 1px solid; =
FONT-WEIGHT: bold; FONT-SIZE: 8pt; BORDER-LEFT: #ffffff 1px solid; =
COLOR: #ffffff; BORDER-BOTTOM: #ffffff 1px solid; FONT-FAMILY: Arial, =
Verdana, Helvetica, sans-serif; BACKGROUND-COLOR: #fcf7e9
}
.sublinkFont {
	FONT-WEIGHT: bold; FONT-SIZE: 8pt; COLOR: #ffffff; FONT-FAMILY: Arial, =
Verdana, Helvetica, sans-serif
}
.topTable {
	FONT-SIZE: 12px; COLOR: #000000; FONT-FAMILY: Arial, Verdana, =
Helvetica, sans-serif; TEXT-DECORATION: none
}
.topBand2 {
	FONT-SIZE: 12px; COLOR: #000000; FONT-FAMILY: Arial, Verdana, =
Helvetica, sans-serif; BACKGROUND-COLOR: #757373; TEXT-DECORATION: none
}
.rightTopCorner {
	BORDER-RIGHT: #e1c876 1px solid; BORDER-TOP: #e1c876 1px solid; =
FONT-SIZE: 12px; BORDER-LEFT: #e1c876 1px solid; COLOR: #000000; =
BORDER-BOTTOM: #e1c876 1px solid; FONT-FAMILY: Arial, Verdana, =
Helvetica, sans-serif; BACKGROUND-COLOR: #ffffff
}
.Highlight {
	FONT-WEIGHT: bold; FONT-SIZE: 12pt; COLOR: #194d78; FONT-FAMILY: Arial, =
Verdana, Helvetica, sans-serif
}
.HighlightArticleTitle {
	FONT-WEIGHT: bold; FONT-SIZE: 12px; COLOR: #ff6600; FONT-FAMILY: =
verdana ,Arial , Helvetica, sans-serif
}
.toctab {
	PADDING-RIGHT: 5px; BORDER-TOP: #eaead7 5px solid; PADDING-LEFT: 5px; =
FONT-SIZE: 9pt; BORDER-BOTTOM-COLOR: #ffffff; BORDER-LEFT: #f3f0ed 1px =
solid; LINE-HEIGHT: 135%; FONT-FAMILY: Verdana, Arial, Helvetica, =
sans-serif; BACKGROUND-COLOR: white; BORDER-RIGHT-COLOR: #ffffff
}
.tochead {
	BORDER-TOP: #cccccc 1px solid; FONT-WEIGHT: bold; FONT-SIZE: 14px; =
COLOR: #ac3232; BORDER-BOTTOM: #cccccc 1px solid; FONT-FAMILY: Arial, =
Verdana, Helvetica, sans-serif
}
.tocAT {
	FONT-WEIGHT: bold; FONT-SIZE: 14px; COLOR: #ac3232; FONT-FAMILY: Arial, =
Verdana, Helvetica, sans-serif
}
.line {
	BACKGROUND-COLOR: #eaead7
}
.HighlightVol {
	FONT-SIZE: 12px; COLOR: #194d78; FONT-FAMILY: Arial,Verdana,Helvetica, =
sans-serif
}
.HighlightAbstract {
	FONT-SIZE: 12px; COLOR: #222222; FONT-FAMILY: Arial, Verdana, =
Helvetica, sans-serif
}
.textBox {
	BORDER-RIGHT: #c0c0c0 1px solid; BORDER-TOP: #c0c0c0 1px solid; =
FONT-SIZE: 8pt; BORDER-LEFT: #c0c0c0 1px solid; BORDER-BOTTOM: #c0c0c0 =
1px solid; FONT-FAMILY: Verdana, Arial, Helvetica, sans-serif
}
.searchtable {
	BORDER-RIGHT: #e4e4de 1px solid; PADDING-RIGHT: 5px; BORDER-TOP: =
#e4e4de 6px solid; PADDING-LEFT: 5px; FONT-SIZE: 10pt; BORDER-LEFT: =
#e4e4de 1px solid; LINE-HEIGHT: 125%; BORDER-BOTTOM: #e4e4de 1px solid; =
FONT-FAMILY: Verdana, Arial, Helvetica, sans-serif
}
.articlepage {
	PADDING-RIGHT: 5px; BORDER-TOP: #eaead7 5px solid; PADDING-LEFT: 5px; =
FONT-SIZE: 9pt; BORDER-BOTTOM-COLOR: #ffffff; BORDER-LEFT: #f3f0ed 1px =
solid; LINE-HEIGHT: 135%; FONT-FAMILY: Verdana, Arial, Helvetica, =
sans-serif; BACKGROUND-COLOR: white; BORDER-RIGHT-COLOR: #ffffff
}
.parameter {
	FONT-SIZE: 12px; COLOR: #113452; FONT-FAMILY: Arial, Verdana, =
Helvetica, sans-serif
}
.parameterhead {
	FONT-WEIGHT: bold; FONT-SIZE: 12px; COLOR: #113452; FONT-FAMILY: Arial, =
Verdana, Helvetica, sans-serif
}
.parametertext {
	FONT-WEIGHT: bold; FONT-SIZE: 12px; COLOR: #113452; FONT-FAMILY: Arial, =
Verdana, Helvetica, sans-serif
}
.pageHead {
	FONT-WEIGHT: bold; FONT-SIZE: 16px; COLOR: #113452; FONT-FAMILY: Arial, =
Verdana, Helvetica, sans-serif
}
.other {
	FONT-WEIGHT: normal; FONT-SIZE: 12px; COLOR: #1f1f3f; FONT-FAMILY: =
Arial, Verdana, Helvetica, sans-serif
}
.sTitle {
	FONT-SIZE: 18px; COLOR: #ff6600; LINE-HEIGHT: 110%; FONT-FAMILY: Arial, =
Verdana, Helvetica, sans-serif
}
.ref {
	FONT-SIZE: 11px; COLOR: #cc6601; FONT-FAMILY: Arial, Verdana, =
Helvetica, sans-serif
}
.empty {
	PADDING-RIGHT: 2px; PADDING-LEFT: 2px; FONT-SIZE: 9pt; PADDING-TOP: =
2px; FONT-FAMILY: Verdana, Arial, Helvetica, sans-serif; =
BACKGROUND-COLOR: white
}
.footer {
	COLOR: #ffffff; LINE-HEIGHT: 110%; BACKGROUND-COLOR: #d0dbe5
}
.menu {
	BORDER-RIGHT: #a1a1a1 10px solid; BORDER-TOP: #a1a1a1 10px solid; =
BORDER-LEFT: #a1a1a1 10px solid; BORDER-BOTTOM: #a1a1a1 10px solid
}
.sj {
	FONT-SIZE: 11px; BORDER-BOTTOM-COLOR: #f8c301; BORDER-LEFT: #757373 3px =
solid; COLOR: #333333; BORDER-TOP-COLOR: #f8c301; FONT-FAMILY: Arial, =
Verdana, Helvetica, sans-serif; BACKGROUND-COLOR: #eaead7; =
BORDER-RIGHT-COLOR: #f8c301
}
.menutable {
	BORDER-TOP: #dfd9da 1px solid; BACKGROUND-COLOR: #ffffff
}
.Footertab {
	FONT-SIZE: 10px; COLOR: #000000; FONT-FAMILY: Verdana, Arial, =
Helvetica, sans-serif; BACKGROUND-COLOR: #d9e1e8
}
.foot {
	FONT-SIZE: 10px; COLOR: #000000; FONT-FAMILY: Verdana,  Arial, =
Helvetica, sans-serif
}
.medknow {
	FONT-SIZE: 10px; COLOR: #444444; FONT-FAMILY: Verdana, Arial, =
Helvetica, sans-serif
}
.adlink {
	FONT-SIZE: 9px; COLOR: #000000; FONT-FAMILY: Arial, Verdana, Helvetica, =
sans-serif
}
.hban {
	FONT-SIZE: 12px; COLOR: #000000; FONT-FAMILY: Arial, Verdana, =
Helvetica, sans-serif
}
.rtcm {
	BORDER-RIGHT: #ffffff 1px solid; FONT-WEIGHT: bold; FONT-SIZE: 11px; =
COLOR: #ffffff; BORDER-BOTTOM: #a2a2a1 2px solid; FONT-FAMILY: Arial, =
Verdana, Helvetica, sans-serif; BACKGROUND-COLOR: #eaead7
}
.w3c {
	FONT-WEIGHT: bold; FONT-SIZE: 11px; COLOR: #000000; FONT-FAMILY: Arial, =
Verdana, Helvetica, sans-serif
}
.vld {
	FONT-WEIGHT: normal; FONT-SIZE: 10px; COLOR: #000000; FONT-FAMILY: =
Arial, Verdana, Helvetica, sans-serif
}
.ftl {
	CURSOR: hand
}
.bl {
	FONT-WEIGHT: normal; FONT-SIZE: 10px; COLOR: #000000; FONT-FAMILY: =
Arial, Verdana, Helvetica, sans-serif; BACKGROUND-COLOR: #ffffff
}
.spl {
	BORDER-RIGHT: #ffffff 3px dotted; BORDER-TOP: #ffffff 3px dotted; =
FONT-SIZE: 12px; MARGIN-LEFT: 2px; BORDER-LEFT: #ffffff 3px dotted; =
COLOR: #000000; MARGIN-RIGHT: 2px; BORDER-BOTTOM: #ffffff 3px dotted; =
FONT-STYLE: italic; FONT-FAMILY: Arial, verdana Helvetica, sans-serif; =
BACKGROUND-COLOR: #cdd8ba
}
.splnote {
	BORDER-RIGHT: #a6adc4 1px solid; BORDER-TOP: #a6adc4 1px solid; =
FONT-SIZE: 11px; BORDER-LEFT: #a6adc4 1px solid; LINE-HEIGHT: 135%; =
BORDER-BOTTOM: #a6adc4 1px solid; FONT-FAMILY: Arial, Verdana, =
Helvetica, sans-serif; BACKGROUND-COLOR: #e1f3ef
}
.jh {
	BACKGROUND-COLOR: #ffffff
}
.btm {
	BORDER-TOP: #eaead7 1px solid; BACKGROUND: =
url(http://www.indianjcancer.com/images/btm.gif) #eaead7 no-repeat right =
top; COLOR: #555555
}
.ft {
	BACKGROUND: url(http://www.indianjcancer.com/images/ft.gif)
}

------=_NextPart_000_0011_01C9D0A7.E5537EA0
Content-Type: application/octet-stream
Content-Transfer-Encoding: quoted-printable
Content-Location: http://www.indianjcancer.com/templates/layer.js

var link=3Dnew Array()
var delay_hide=3D500
var menuobj;
var menu;
var default_menu_item;



function lib_bwcheck(){ //Browsercheck (needed)
	this.ver=3Dnavigator.appVersion
	this.agent=3Dnavigator.userAgent
	this.dom=3Ddocument.getElementById?1:0
	this.opera5=3Dthis.agent.indexOf("Opera 5")>-1
	this.ie5=3D(this.ver.indexOf("MSIE 5")>-1 && this.dom && =
!this.opera5)?1:0;=20
	this.ie6=3D(this.ver.indexOf("MSIE 6")>-1 && this.dom && =
!this.opera5)?1:0;
	this.ie4=3D(document.all && !this.dom && !this.opera5)?1:0;
	this.ie=3Dthis.ie4||this.ie5||this.ie6
	this.mac=3Dthis.agent.indexOf("Mac")>-1
	this.ns6=3D(this.dom && parseInt(this.ver) >=3D 5) ?1:0;=20
	this.ns4=3D(document.layers && !this.dom)?1:0;
	this.bw=3D(this.ie6 || this.ie5 || this.ie4 || this.ns4 || this.ns6 || =
this.opera5)
	return this
}
var bw=3Dnew lib_bwcheck();

function  x(obj,visible)
{	this.evnt=3Dbw.dom? 	=
document.getElementById(obj):bw.ie4?document.all[obj]:bw.ns4?document.lay=
ers[obj]:0;

	if(!this.evnt) return false
	this.css=3Dbw.dom||bw.ie4?this.evnt.style:bw.ns4?this.evnt:0;=09
   	this.wref=3Dbw.dom||bw.ie4?this.evnt:bw.ns4?this.css.document:0;=09
	this.css.visibility =3D visible;
	this.css.width=3D'100%';

}

function showHideLayer(obj,visible){							=09
   	this.evnt=3Dbw.dom? =
document.getElementById(obj):bw.ie4?document.all[obj]:bw.ns4?document.lay=
ers[obj]:0;

	if(!this.evnt) return false
	this.css=3Dbw.dom||bw.ie4?this.evnt.style:bw.ns4?this.evnt:0;=09
   	this.wref=3Dbw.dom||bw.ie4?this.evnt:bw.ns4?this.css.document:0;=09
	this.css.visibility =3D visible;
	this.css.top=3D'94px';
	bw.ns4||bw.ns6?this.css.left=3D'-8px':
	this.css.left=3D'0px';
	this.css.width=3D'100%';
	this.css.position=3D"absolute";
}


function writeSubmenu(obj,item){							=09
   /*	this.evnt=3Dbw.dom? =
document.getElementById(obj):bw.ie4?document.all[obj]:bw.ns4?document.lay=
ers[obj]:0;
	if(!this.evnt) return false
	this.css=3Dbw.dom||bw.ie4?this.evnt.style:bw.ns4?this.evnt:0;=09
   	this.wref=3Dbw.dom||bw.ie4?this.evnt:bw.ns4?this.css.document:0;=09
	thecontent=3D(item=3D=3D-1)? "" : link[item]
	this.wref.innerHTML=3Dthecontent;*/

}


function clearContent(obj){=09
					=09
   	this.evnt=3Dbw.dom? =
document.getElementById(obj):bw.ie4?document.all[obj]:bw.ns4?document.lay=
ers[obj]:0;
	if(!this.evnt) return false
	this.css=3Dbw.dom||bw.ie4?this.evnt.style:bw.ns4?this.evnt:0;=09
   	this.wref=3Dbw.dom||bw.ie4?this.evnt:bw.ns4?this.css.document:0;=09
	thecontent=3D(item=3D=3D-1)? "" : link[item]
	this.wref.innerHTML=3D"";

}


function clear_delayhide()
{
	alert("asdASD");
	if (window.delayhide)
	{onlpgld(default_menu_item)
	clearTimeout(delayhide)
}
}

function contains_ns6(a, b)=20
{
	while (b.parentNode)
	if ((b =3D b.parentNode) =3D=3D a)
		return true;
	return false;
}



////


function navleftMouseOver(src)
{=20

	src.className=3D"leftnavcellover"
}=20



function navleftMouseOut(src)
{=20
	src.className=3D"leftnavcell"
}

function navtabMouseOver(src)
{=20

		src.className=3D"topBand1MO"
}=20



function navtabMouseOut(src)
{=20
	src.className=3D"topBand2"
}

////



function navMouseOver(src,item)
{=20

	src.className=3D"topBand1MO"
	//writeSubmenu("submenu",item);
	//showHideLayer("submenu","visible");=09
=09

}=20



function navMouseOut(src,lyr)
{=20
	src.className=3D"topBand1";
//	onlpgld(default_menu_item);
=09
}

function onload(item)
{
//	writeSubmenu("submenu",item);
//	showHideLayer("submenu","visible");
	=09
}

function onlpgld(item)
{
	default_menu_item=3Ditem;=09
	writeSubmenu("submenu",item);
	showHideLayer("submenu","visible");

	=09
}

function navMouseOversUB(src)
{=20
	src.className=3D"topBand2MO"

}=20
function navMouseOutsUB(src)
{=20
	src.className=3D"topBand2"
}
function navMouseBotOut(src)
{
	src.className=3D"leftnavcell"
}
function navMouseBotOver(src)
{
	src.className=3D"leftnavcellover"
}

function loadMenu(index)
{
	writeMenu("menu",item);
	showHideLayer("menu","visible");=09
	if (index >=3D 0)
	{
		onload(index)	=09
	}
}


function showMenu(e,f)
{
	var ie4=3Ddocument.all&&navigator.userAgent.indexOf("Opera")=3D=3D-1
	var ns6=3Ddocument.getElementById&&!document.all
	var ns4=3Ddocument.layers
	eventX=3Die4? event.clientX : ns6? e.clientX : e.x
	eventY=3Die4? event.clientY : ns6? e.clientY : e.y
	var rightedge=3Die4? document.body.clientWidth-eventX : =
window.innerWidth-eventX
	var bottomedge=3Die4? document.body.clientHeight-eventY : =
window.innerHeight-eventY

	var obj=3D"floatmenu";
	this.evnt=3Dbw.dom? 	=
document.getElementById(obj):bw.ie4?document.all[obj]:bw.ns4?document.lay=
ers[obj]:0;
	if(!this.evnt) return false
	this.css=3Dbw.dom||bw.ie4?this.evnt.style:bw.ns4?this.evnt:0;=09
   	this.wref=3Dbw.dom||bw.ie4?this.evnt:bw.ns4?this.css.document:0;=09
	this.css.visibility =3D "visible";
	this.css.left=3Die4? document.body.scrollLeft+eventX : ns6? =
window.pageXOffset+eventX : eventX
	 if (bottomedge<this.css.contentheight)
		this.css.top=3Die4? =
document.body.scrollTop+eventY-this.css.contentheight : ns6? =
window.pageYOffset+eventY-this.css.contentheight : =
eventY-this.css.contentheight;
	 else
		 this.css.top=3Die4? document.body.scrollTop+event.clientY : ns6? =
window.pageYOffset+eventY : eventY=20

	this.css.visibility=3D"visible";
	this.css.top=3DeventX;

	alert(eventX);

}


function writeMenu(obj,item)
{
  	this.evnt=3Dbw.dom? =
document.getElementById(obj):bw.ie4?document.all[obj]:bw.ns4?document.lay=
ers[obj]:0;
	if(!this.evnt) return false
	this.css=3Dbw.dom||bw.ie4?this.evnt.style:bw.ns4?this.evnt:0;=09
   	this.wref=3Dbw.dom||bw.ie4?this.evnt:bw.ns4?this.css.document:0;=09
	thecontent=3D(item=3D=3D-1)? "" : menu;
	this.wref.innerHTML=3Dthecontent;

}

function setCSS(typ)
{=20
	var i, a, main;
  for(i=3D0; (a =3D document.getElementsByTagName("link")[i]); i++)=20
	{

	    if(a.getAttribute("rel").indexOf("style") !=3D -1 && 	=
a.getAttribute("title")) {
      	    a.disabled =3D true;
            if(a.getAttribute("title") =3D=3D typ) a.disabled =3D false;
    }
  }
=09
}



function getActiveStyleSheet() {
  var i, a;
  for(i=3D0; (a =3D document.getElementsByTagName("link")[i]); i++) {
    if(a.getAttribute("rel").indexOf("style") !=3D -1 && =
a.getAttribute("title") && !a.disabled) return a.getAttribute("title");
  }
  return null;
}
function openWin(pg)
{

if (pg.indexOf('special') >=3D 0 || pg.indexOf('changeaddress') >=3D 0 )
{
var attributes =3D 'toolbar=3D0,location=3D0,directories=3D0,status=3D0, =
menubar=3D0,scrollbars=3DYes,resizable=3D1,width=3D800,height=3D600,left=3D=
0,top=3D0';
}
else
{
var attributes =3D 'toolbar=3D0,location=3D0,directories=3D0,status=3D0, =
menubar=3D0,scrollbars=3D1,resizable=3D1,width=3D600,height=3D400,left=3D=
0,top=3D0';
}

sealWin=3Dwindow.open(pg ,'',attributes);=20
self.name =3D pg;=20
}
function valfld(field)
{

	var valid =3D "0123456789"; // these are allowed values
	var ok =3D "yes";
	var temp;
	if (field.value.length =3D=3D 0 )
	{
		//alert("Invalid entry! please enter number");
		field.value =3D ""
		field.focus();
		field.select();
		return false;=09
	}
	for (var i=3D0; i<field.value.length; i++)
	{
		temp =3D "" + field.value.substring(i, i+1);
		if (valid.indexOf(temp) =3D=3D "-1")=20
		ok =3D "no";
	}
	if (ok =3D=3D "no")=20
	{
		alert("Invalid entry! Only numbers are allowed!");
		field.value =3D ""
		field.focus();
		field.select();

		return false;
	}
	else
		return true;
	}


function chkvldemail(email_address)
   {
         //Assumes that valid email addresses consist of =
user_name@domain.tld
         at =3D email_address.indexOf('@');
         dot =3D email_address.indexOf('.');
        =20
         if(at =3D=3D -1 ||=20
            dot =3D=3D -1 ||        =20
            dot =3D=3D 0 )
		{=09
			alert("Please enter valid email address 1.");
            return(false);
		}
           =20
         user_name =3D email_address.substr(0, at);
         domain_name =3D email_address.substr(at + 1, =
email_address.length);                 =20

         if(Validate_String(user_name) =3D=3D=3D false || =
Validate_String(domain_name) =3D=3D=3D false)
		{=09
			alert("Please enter valid email address.");
	            return(false);=20
                }
         else
		 return(true);
}

function Validate_String(string, return_invalid_chars)
         {
         valid_chars =3D =
'1234567890-_.^~abcdefghijklmnopqrstuvwxyzABCDEFGHIJKLMNOPQRSTUVWXYZ';
         invalid_chars =3D '';
        =20
         if(string =3D=3D null || string =3D=3D '')
            return(true);
        =20
         //For every character on the string.  =20
         for(index =3D 0; index < string.length; index++)
            {
            charx =3D string.substr(index, 1);                       =20
           =20
            //Is it a valid character?
            if(valid_chars.indexOf(charx) =3D=3D -1)
              {
              //If not, is it already on the list of invalid characters?
              if(invalid_chars.indexOf(charx) =3D=3D -1)
                {
                //If it's not, add it.
                if(invalid_chars =3D=3D '')
                   invalid_chars +=3D charx;
                else
                   invalid_chars +=3D ', ' + charx;
                }
              }
            }                    =20
           =20
         //If the string does not contain invalid characters, the =
function will return true.
         //If it does, it will either return false or a list of the =
invalid characters used
         //in the string, depending on the value of the second =
parameter.
         if(return_invalid_chars =3D=3D true && invalid_chars !=3D '')
           {
           last_comma =3D invalid_chars.lastIndexOf(',');
          =20
           if(last_comma !=3D -1)
              invalid_chars =3D invalid_chars.substr(0, $last_comma) +=20
              ' and ' + invalid_chars.substr(last_comma + 1, =
invalid_chars.length);
                     =20
           return(invalid_chars);
           }
         else
           return(invalid_chars =3D=3D '');=20
         }

function trimstr(par)
{

while (par.charAt(0)=3D=3D" "){
par=3Dpar.replace(" ","")
}
i=3Dpar.length-1
while(par.charAt(i)=3D=3D" "){
par=3Dpar.slice(0,i)
i=3Di-1
}
return par
}

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Content-Location: http://www.indianjcancer.com/article.asp?issn=0019-509X;year=2009;volume=46;issue=2;spage=96;epage=107;aulast=Khan

<!DOCTYPE HTML PUBLIC "-//W3C//DTD HTML 4.01 Transitional//EN" =
"http://www.w3c.org/TR/1999/REC-html401-19991224/loose.dtd">
<HTML><HEAD><TITLE>Evidence-based adjuvant therapy for gliomas: Current =
concepts and newer developments Khan MK, Hunter GK, Vogelbaum M, Suh JH, =
Chao ST - Indian J Cancer</TITLE>
<META http-equiv=3DContent-Type content=3D"text/html; =
charset=3Dwindows-1252">
<META=20
content=3D"Indian J Cancer, full-text, online, electronic, e-journal, =
free access, open access, online submission"=20
name=3Dkeywords>
<META=20
content=3D"The Indian Journal of Cancer is an official publication of =
the Indian Cancer Society and Indian Society of Oncology."=20
name=3Ddescription><!--DC META DATA START-->
<META=20
content=3D"Evidence-based adjuvant therapy for gliomas: Current concepts =
and newer developments"=20
name=3DDC.Title><LINK =
href=3D"http://purl.org/metadata/dublin_core_elements#title"=20
rel=3DSCHEMA.dc>
<META content=3DKhan name=3DDC.Creator><LINK=20
href=3D"http://purl.org/metadata/dublin_core_elements#creator" =
rel=3DSCHEMA.dc>
<META=20
content=3D"Adjuvant therapy, anaplastic astrocytoma, anaplastic =
oligoastrocytoma, anaplastic oligodendroglioma, bevacizumab, CDX-110, =
glioblastoma multiforme, glioma, low-grade glioma, O<sup> 6</sup> =
-methylguanine-DNA methyltransferase status, radiation, temozolomide, =
1p/19q deletion"=20
name=3DDC.Subject>
<META=20
content=3D"The incidence of gliomas is increasing worldwide, including =
India. Of the 18,820 new cases of primary central nervous system (CNS) =
tumors diagnosed annually in the United States, gliomas account for over =
60% with 30-40% of them being glioblastoma multiforme (GBM), 10% being =
anaplastic astrocytoma (AA), and 10% being low grade gliomas (LGGs). =
This is in contrast to one study from West Bengal, India, in which only =
7.9% of the brain tumors were GBMs, while 46.8% were astrocytomas. Of =
all adult primary CNS tumors, GBM is the most common and the most =
malignant with about 7,000 to 8,000 new cases annually in the United =
States. Given poor outcomes, a number of treatment approaches have been =
investigated. Common to these approaches is the use of adjuvant =
radiation therapy, even as surgery alone, with or without chemotherapy, =
may be the mainstay for some lower grade and low-risk gliomas. Today, =
treatment typically involves external beam radiation, with concurrent =
and adjuvant chemotherapy for more aggressive histologies. Although =
gliomas are relatively uncommon, active research is ongoing. Results of =
landmark trials along with some of the recently published trials are =
presented. These trials and management strategies as well as evolving =
concepts are found by reviewing over 200 articles in the National =
Library Medical (NLM) database, PubMed, more than 60 of which are =
refrenced. Specifically, the database is searched using the following =
keywords, with various combinations: glioma, low-grade, anaplastic, =
astrocytoma, oligodendroglioma, oligoastrocytoma, glioblastoma =
multiforme, chemotherapy, radiation, new concepts, phase III, MGMT, =
CDX-110 (Celldex), temozolomide, 1p/19q deletion, and bevacizumab."=20
name=3DDC.Description><LINK=20
href=3D"http://purl.org/metadata/dublin_core_elements#description" =
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<META content=3D"Khan MK, Hunter GK, Vogelbaum M, Suh JH, Chao ST"=20
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<B>In this=20
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          onmouseout=3DnavleftMouseOut(this); colSpan=3D2=20
            height=3D20>&nbsp;<B>=BB</B>&nbsp;&nbsp;<A=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#abstract"=
>Abstract</A></TD></TR>
        <TR>
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        <TR>
          <TD class=3Dleftnavcell onmouseover=3DnavleftMouseOver(this);=20
          onmouseout=3DnavleftMouseOut(this); colSpan=3D2=20
            height=3D20>&nbsp;<B>=BB</B>&nbsp;&nbsp;<A =
title=3DIntroduction=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#Introduct=
ion">Introduction</A></TD></TR>
        <TR>
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        <TR>
          <TD class=3Dleftnavcell onmouseover=3DnavleftMouseOver(this);=20
          onmouseout=3DnavleftMouseOut(this); colSpan=3D2=20
            height=3D20>&nbsp;<B>=BB</B>&nbsp;&nbsp;<A title=3D"Low =
Grade Gliomas"=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#Low =
Grade Gliomas">Low=20
            Grade Gliomas</A></TD></TR>
        <TR>
          <TD colSpan=3D2 height=3D1></TD></TR>
        <TR>
          <TD class=3Dleftnavcell onmouseover=3DnavleftMouseOver(this);=20
          onmouseout=3DnavleftMouseOut(this); colSpan=3D2=20
            height=3D20>&nbsp;<B>=BB</B>&nbsp;&nbsp;<A =
title=3D"High-Grade Gliomas"=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#High-Grad=
e Gliomas">High-Grade=20
            Gliomas</A></TD></TR>
        <TR>
          <TD colSpan=3D2 height=3D1></TD></TR>
        <TR>
          <TD class=3Dleftnavcell onmouseover=3DnavleftMouseOver(this);=20
          onmouseout=3DnavleftMouseOut(this); colSpan=3D2=20
            height=3D20>&nbsp;<B>=BB</B>&nbsp;&nbsp;<A=20
            title=3D"Anaplastic Oligodendroglioma/Anaplastic =
Oligoastrocytoma"=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#Anaplasti=
c Oligodendroglioma/Anaplastic Oligoastrocytoma">Anaplastic=20
            Oligo...</A></TD></TR>
        <TR>
          <TD colSpan=3D2 height=3D1></TD></TR>
        <TR>
          <TD class=3Dleftnavcell onmouseover=3DnavleftMouseOver(this);=20
          onmouseout=3DnavleftMouseOut(this); colSpan=3D2=20
            height=3D20>&nbsp;<B>=BB</B>&nbsp;&nbsp;<A=20
            title=3D"Anaplastic Astrocytoma"=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#Anaplasti=
c Astrocytoma">Anaplastic=20
            Astro...</A></TD></TR>
        <TR>
          <TD colSpan=3D2 height=3D1></TD></TR>
        <TR>
          <TD class=3Dleftnavcell onmouseover=3DnavleftMouseOver(this);=20
          onmouseout=3DnavleftMouseOut(this); colSpan=3D2=20
            height=3D20>&nbsp;<B>=BB</B>&nbsp;&nbsp;<A=20
            title=3D"Glioblastoma Multiforme"=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#Glioblast=
oma Multiforme">Glioblastoma=20
            Mul...</A></TD></TR>
        <TR>
          <TD colSpan=3D2 height=3D1></TD></TR>
        <TR>
          <TD class=3Dleftnavcell onmouseover=3DnavleftMouseOver(this);=20
          onmouseout=3DnavleftMouseOut(this); colSpan=3D2=20
            height=3D20>&nbsp;<B>=BB</B>&nbsp;&nbsp;<A=20
            title=3D"Radiation Dose for Glioblastoma Multiformes"=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#Radiation=
 Dose for Glioblastoma Multiformes">Radiation=20
            Dose f...</A></TD></TR>
        <TR>
          <TD colSpan=3D2 height=3D1></TD></TR>
        <TR>
          <TD class=3Dleftnavcell onmouseover=3DnavleftMouseOver(this);=20
          onmouseout=3DnavleftMouseOut(this); colSpan=3D2=20
            height=3D20>&nbsp;<B>=BB</B>&nbsp;&nbsp;<A=20
            title=3D"Radiation Volume for Glioblastoma Multiformes"=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#Radiation=
 Volume for Glioblastoma Multiformes">Radiation=20
            Volume...</A></TD></TR>
        <TR>
          <TD colSpan=3D2 height=3D1></TD></TR>
        <TR>
          <TD class=3Dleftnavcell onmouseover=3DnavleftMouseOver(this);=20
          onmouseout=3DnavleftMouseOut(this); colSpan=3D2=20
            height=3D20>&nbsp;<B>=BB</B>&nbsp;&nbsp;<A=20
            title=3D"Glioblastoma Multiformes in Elderly/Poor =
Performance Patients"=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#Glioblast=
oma Multiformes in Elderly/Poor Performance Patients">Glioblastoma=20
            Mul...</A></TD></TR>
        <TR>
          <TD colSpan=3D2 height=3D1></TD></TR>
        <TR>
          <TD class=3Dleftnavcell onmouseover=3DnavleftMouseOver(this);=20
          onmouseout=3DnavleftMouseOut(this); colSpan=3D2=20
            height=3D20>&nbsp;<B>=BB</B>&nbsp;&nbsp;<A =
title=3D"Radiation Sensitizers"=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#Radiation=
 Sensitizers">Radiation=20
            Sensit...</A></TD></TR>
        <TR>
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        <TR>
          <TD class=3Dleftnavcell onmouseover=3DnavleftMouseOver(this);=20
          onmouseout=3DnavleftMouseOut(this); colSpan=3D2=20
            height=3D20>&nbsp;<B>=BB</B>&nbsp;&nbsp;<A title=3DFollow-up =

            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#Follow-up=
">Follow-up</A></TD></TR>
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          onmouseout=3DnavleftMouseOut(this); colSpan=3D2=20
            height=3D20>&nbsp;<B>=BB</B>&nbsp;&nbsp;<A title=3D"Future =
Directions"=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#Future =
Directions">Future=20
            Directions</A></TD></TR>
        <TR>
          <TD colSpan=3D2 height=3D1></TD></TR>
        <TR>
          <TD class=3Dleftnavcell onmouseover=3DnavleftMouseOver(this);=20
          onmouseout=3DnavleftMouseOut(this); colSpan=3D2=20
            height=3D20>&nbsp;<B>=BB</B>&nbsp;&nbsp;<A =
title=3DConclusions=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#Conclusio=
ns">Conclusions</A></TD></TR>
        <TR>
          <TD colSpan=3D2 height=3D1></TD></TR>
        <TR>
          <TD class=3Dleftnavcell onmouseover=3DnavleftMouseOver(this);=20
          onmouseout=3DnavleftMouseOut(this); colSpan=3D2=20
            height=3D20>&nbsp;<B>=BB</B>&nbsp;&nbsp;<A=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#Reference=
">References</A></TD></TR>
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        <TR>
          <TD class=3Dleftnavcell onmouseover=3DnavleftMouseOver(this);=20
          onmouseout=3DnavleftMouseOut(this); colSpan=3D2=20
            height=3D20>&nbsp;<B>=BB</B>&nbsp;&nbsp;<A title=3Databs=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#atabs">Ar=
ticle=20
            Tables</A></TD></TR></TBODY></TABLE><BR>
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          <TD height=3D20>&nbsp;&nbsp;&nbsp;&nbsp;Comments&nbsp;</TD>
          <TD align=3Dright><A=20
            =
href=3D"http://www.indianjcancer.com/addremark.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan;aid=3DInd=
ianJournalofCancer_2009_46_2_96_49147">[Add]</A>&nbsp;&nbsp;&nbsp;&nbsp;<=
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                  class=3DtocAT><B>SYMPOSIUM</B></FONT></TD></TR>
              <TR>
                <TD width=3D"33%" height=3D5></TD>
                <TD width=3D"33%" height=3D5></TD>
                <TD width=3D"34%" height=3D5></TD></TR>
              <TR>
                <TD class=3Dother width=3D"100%" colSpan=3D3><B>Year =
</B>:=20
                  2009&nbsp; |&nbsp; <B>Volume</B> : 46&nbsp; |&nbsp;=20
                  <B>Issue</B> : 2&nbsp; |&nbsp; <B>Page</B> : =
96-107</TD></TR>
              <TR>
                <TD class=3Dother width=3D"100%"=20
            colSpan=3D3>&nbsp;</TD></TR></TBODY></TABLE>
            <P><FONT class=3DsTitle>Evidence-based adjuvant therapy for =
gliomas:=20
            Current concepts and newer developments</FONT><BR><BR><FONT=20
            class=3DarticleAuthor>MK Khan<SUP>1</SUP>, GK =
Hunter<SUP>1</SUP>, M=20
            Vogelbaum<SUP>2</SUP>, JH Suh<SUP>1</SUP>, ST=20
            Chao<SUP>1</SUP></FONT><BR><FONT=20
            class=3DAuthorAff><SUP>1</SUP>&nbsp;Department of Radiation =
Oncology,=20
            Brain Tumor and Neuro-Oncology Center, Taussig Cancer =
Institute,=20
            Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, =
Ohio=20
            44195, USA<BR><SUP>2</SUP>&nbsp;Department of Neurosurgery, =
Brain=20
            Tumor and Neuro-Oncology Center, Taussig Cancer Institute, =
Cleveland=20
            Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio =
44195,=20
            USA<BR></FONT><BR></P>
            <P><FONT class=3DCorrsAdd><B>Correspondence =
Address</B>:<BR>S T=20
            Chao<BR>Department of Radiation Oncology, Brain Tumor and=20
            Neuro-Oncology Center, Taussig Cancer Institute, Cleveland =
Clinic=20
            Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195 =
<BR>USA<BR><A=20
            =
href=3D"http://www.indianjcancer.com/login.asp?rd=3Darticle.asp?issn=3D00=
19-509X;year=3D2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3D=
Khan"><IMG=20
            alt=3D"Login to access the Email id"=20
            src=3D"http://www.medknow.com/images/email.gif" =
border=3D0></A>
            <P><B>Source of Support:</B> None, <B>Conflict of =
Interest:</B>=20
            None</P><B>DOI</B>:&nbsp;10.4103/0019-509X.49147<BR></FONT>
            <P></P>
            <TABLE cellSpacing=3D0 cellPadding=3D0 width=3D"100%" =
border=3D0>
              <TBODY>
              <TR>
                <TD class=3DinsideLine width=3D"100%"=20
height=3D1></TD></TR></TBODY></TABLE>
            <TABLE class=3DleftNav cellSpacing=3D0 cellPadding=3D0 =
width=3D"100%"=20
            border=3D0>
              <TBODY>
              <TR>
                <TD class=3DpageSub width=3D"85%" =
height=3D15>&nbsp;=BB<A=20
                  name=3Dabstract></A>&nbsp;Abstract</TD>
                <TD class=3Dinthis align=3Dright>&nbsp;</TD>
                <TD width=3D"15%" height=3D15></TD></TR></TBODY></TABLE>
            <P class=3Dabst>The incidence of gliomas is increasing =
worldwide,=20
            including India. Of the 18,820 new cases of primary central =
nervous=20
            system (CNS) tumors diagnosed annually in the United States, =
gliomas=20
            account for over 60% with 30-40% of them being glioblastoma=20
            multiforme (GBM), 10% being anaplastic astrocytoma (AA), and =
10%=20
            being low grade gliomas (LGGs). This is in contrast to one =
study=20
            from West Bengal, India, in which only 7.9% of the brain =
tumors were=20
            GBMs, while 46.8% were astrocytomas. Of all adult primary =
CNS=20
            tumors, GBM is the most common and the most malignant with =
about=20
            7,000 to 8,000 new cases annually in the United States. =
Given poor=20
            outcomes, a number of treatment approaches have been =
investigated.=20
            Common to these approaches is the use of adjuvant radiation =
therapy,=20
            even as surgery alone, with or without chemotherapy, may be =
the=20
            mainstay for some lower grade and low-risk gliomas. Today, =
treatment=20
            typically involves external beam radiation, with concurrent =
and=20
            adjuvant chemotherapy for more aggressive histologies. =
Although=20
            gliomas are relatively uncommon, active research is ongoing. =
Results=20
            of landmark trials along with some of the recently published =
trials=20
            are presented. These trials and management strategies as =
well as=20
            evolving concepts are found by reviewing over 200 articles =
in the=20
            National Library Medical (NLM) database, PubMed, more than =
60 of=20
            which are refrenced. Specifically, the database is searched =
using=20
            the following keywords, with various combinations: glioma,=20
            low-grade, anaplastic, astrocytoma, oligodendroglioma,=20
            oligoastrocytoma, glioblastoma multiforme, chemotherapy, =
radiation,=20
            new concepts, phase III, MGMT, CDX-110 (Celldex), =
temozolomide,=20
            1p/19q deletion, and bevacizumab.</P><BR>
            <P class=3Dkyds><B>Keywords:</B>&nbsp;Adjuvant therapy, =
anaplastic=20
            astrocytoma, anaplastic oligoastrocytoma, anaplastic=20
            oligodendroglioma, bevacizumab, CDX-110, glioblastoma =
multiforme,=20
            glioma, low-grade glioma, O<SUP> 6</SUP> -methylguanine-DNA=20
            methyltransferase status, radiation, temozolomide, 1p/19q=20
            deletion</P><BR>
            <TABLE class=3Dsitethis width=3D"100%" border=3D0>
              <TBODY>
              <TR>
                <TD class=3Dother><B>How to cite this =
article:</B><BR>Khan MK,=20
                  Hunter GK, Vogelbaum M, Suh JH, Chao ST. =
Evidence-based=20
                  adjuvant therapy for gliomas: Current concepts and =
newer=20
                  developments. Indian J Cancer=20
            2009;46:96-107</TD></TR></TBODY></TABLE><BR>
            <TABLE class=3Dsitethis width=3D"100%" border=3D0>
              <TBODY>
              <TR>
                <TD class=3Dother><B>How to cite this URL:</B><BR>Khan =
MK,=20
                  Hunter GK, Vogelbaum M, Suh JH, Chao ST. =
Evidence-based=20
                  adjuvant therapy for gliomas: Current concepts and =
newer=20
                  developments. Indian J Cancer [serial online] 2009=20
                  [cited&nbsp;2009 May 9];46:96-107. Available =
from:&nbsp;<A=20
                  =
href=3D"http://www.indianjcancer.com/text.asp?2009/46/2/96/49147">http://=
www.indianjcancer.com/text.asp?2009/46/2/96/49147</A></TD></TR></TBODY></=
TABLE><BR><BR><BR>
            <TABLE class=3DleftNav cellSpacing=3D0 cellPadding=3D0 =
width=3D"100%"=20
            border=3D0>
              <TBODY>
              <TR>
                <TD class=3DpageSub><A=20
                  =
name=3DIntroduction></A>&nbsp;=BB&nbsp;Introduction</TD>
                <TD class=3Dinthis align=3Dright>&nbsp;</TD>
                <TD align=3Dright width=3D"15%"><A=20
                  =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#top"><IMG=
=20
                  alt=3DTop=20
                  =
src=3D"http://www.indianjcancer.com/images/arrow_top.gif"=20
                  border=3D0></A></TD></TR></TBODY></TABLE><BR><BR>This =
incidence of=20
            gliomas is in contrast to one study from West Bengal, India, =
in=20
            which only 7.9% of brain tumors were GBMs, while 46.8% were=20
            astrocytomas.<SUP> <A class=3Dref=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#ref1"=20
            name=3Dft1>[1]</A> </SUP>In order to review the pertinent =
clinical=20
            trials, the electronic database of the US National Library =
of=20
            Medicine and the National Institute of Health (PubMed) was =
reviewed,=20
            looking for literature pertaining to the adjuvant management =
of=20
            gliomas. Over 200 articles were reviewed, 64 of which are=20
            referenced. The focus was on evidence-based adjuvant =
management=20
            strategies based on historic phase III trials, as well as,=20
            describing trends based on recently reported trials and =
those trials=20
            that are currently underway. Furthermore, emerging concepts=20
            pertaining to the use of temozolomide - an alkylating=20
            chemotherapeutic agent, as well as, the importance of 1p/19q =

            molecular cytogenetics, and an understanding of the O<SUP> =
6</SUP>=20
            -methylguanine-DNA methyltransferase (MGMT) methyl status =
are also=20
            highlighted in this study. <BR><BR>While reviewing and =
highlighting=20
            some of the pertinent clinical trials it is important to =
realize=20
            that the histological classification scheme, namely the =
World Health=20
            Organization (WHO) classification system, used to classify =
gliomas,=20
            has repeatedly and substantially changed over the pertinent =
time=20
            period. In recognition of the emerging role of molecular =
diagnostic=20
            approaches to tumor classification, recent WHO updates have=20
            emphasized with greater detail, various pertinent genetic =
profiles.=20
            The first edition of the classification of nervous system =
tumors was=20
            published in 1979, and took almost a decade to complete. The =
second=20
            edition followed in 1993, and was a step forward, as it =
incorporated=20
            the advances in classification resulting from the =
introduction of=20
            immunohistochemistry. The third edition was published in =
2000, and=20
            the most recent edition was published in 2007, with each =
edition=20
            based on increasingly more specific immunohistochemical and =
genetic=20
            markers. In light of these changes in the classification =
criteria,=20
            it is important to realize that the results of clinical =
trials=20
            cannot be fully appreciated without considering the =
classification=20
            system that is pertinent at that particular time. It is =
beyond the=20
            scope of this review to correlate previous clinical trials =
to the=20
            current WHO classification scheme, however, this does not =
detract=20
            from the applicable information gained from prior trials.=20
            <BR><BR><BR>
            <TABLE class=3DleftNav cellSpacing=3D0 cellPadding=3D0 =
width=3D"100%"=20
            border=3D0>
              <TBODY>
              <TR>
                <TD class=3DpageSub><A=20
                  name=3D"Low Grade Gliomas"></A>&nbsp;=BB&nbsp;Low =
Grade Gliomas</TD>
                <TD class=3Dinthis align=3Dright>&nbsp;</TD>
                <TD align=3Dright width=3D"15%"><A=20
                  =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#top"><IMG=
=20
                  alt=3DTop=20
                  =
src=3D"http://www.indianjcancer.com/images/arrow_top.gif"=20
                  border=3D0></A></TD></TR></TBODY></TABLE><BR><BR>Low =
grade gliomas=20
            (LGGs) typically occur in younger adults, normally before =
age 40,=20
            and encompass a spectrum of histological subtypes that =
resemble=20
            differentiated macroglial cells, without evidence of =
anaplasia.=20
            Diffuse astrocytomas represent 60 - 70% of the LGGs and are =
the most=20
            common of LGGs. The subtypes of low-grade astrocytomas =
include=20
            fibrillary, protoplasmic, pilocytic, and gemistocytic =
astrocytoma.=20
            The fibrillary subtype is the most common in adults while =
the=20
            gemistocytic subtype is less common, but has a higher =
potential for=20
            anaplastic transformation. Other histological subtypes of =
the LGGs=20
            include the juvenile pilocytic astrocytoma (JPA), which =
usually=20
            occurs before age 25, oligodendroglioma/oligoastrocytoma =
(LGO/LGOA),=20
            ganglioglioma, pleomorphic xanthoastrocytoma (PXA), =
subependymal=20
            giant cell astrocytoma (SEGA), subependymomas, and =
desmoplastic=20
            gangliomas. Different gliomas occur in different age groups =
and some=20
            entities such are PXA are more common in adolescents, while =
others=20
            are more common in the elderly, such as GBM. For a majority =
of the=20
            favorable histological LGG subtypes such as JPA, low-grade =
PXA,=20
            gangliogliomas, SEGA, and subependymomas, gross total =
resection=20
            (GTR) alone is sufficient for the asymptomatic patient. =
Often,=20
            adjuvant treatment is delayed until there is evidence of =
symptomatic=20
            or radiographic progression. For gemistocytic astrocytomas =
and for=20
            patients with high-risk features predictive of poor outcome, =
active=20
            research is underway to determine the benefits of adjuvant =
radiation=20
            delivered immediately versus delayed, with or without=20
            chemotherapy.<BR><BR>Of the LGGs, the gemistocytic subtype =
has over=20
            a 70-80% likelihood of anaplastic transformation and is =
therefore=20
            generally treated aggressively, and often treated as =
anaplastic=20
            astrocytoma with immediate adjuvant high-dose=20
            radiation.<BR><BR>Several retrospective reviews have =
questioned the=20
            role of observation and high-dose radiation for =
oligoastrocytoma and=20
            ordinary astrocytoma. A 1989 retrospective review of 167 =
patients=20
            with grade 1 - 2 supratentorial pilocytic astrocytoma, =
ordinary=20
            astrocytoma, or mixed oligoastrocytoma, diagnosed from 1960 =
- 1982,=20
            found that high-dose radiation (&gt;53 Gy) after resection =
was=20
            associated with better survival compared to low-dose =
radiation or=20
            surgery in patients with nonpilocytic LGGs.<SUP> <A =
class=3Dref=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#ref2"=20
            name=3Dft2>[2]</A> </SUP>The Radiation Therapy Oncology =
Group (RTOG)=20
            phase II portion of the 98-02 trial published in 2005, =
prospectively=20
            evaluated the role of observation after GTR in 111 low risk =
patients=20
            younger than age of 40. This trial 98 concluded that =
observation is=20
            a reasonable strategy for some subsets of patients and that=20
            postoperative adjuvant treatment should be considered for =
higher=20
            risk patients.<SUP> <A class=3Dref=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#ref3"=20
            name=3Dft3>[3]</A> </SUP><BR><BR>The European Organization =
for=20
            Research and Treatment of Cancer (EORTC) conducted two large =
phase=20
            III trials, EORTC 22844 and 22845, which were published in =
1996 and=20
            2006 respectively. The EORTC 22844 trial evaluated 379 =
patients=20
            randomized to either 45 Gy in 25 fractions versus 59.4 Gy in =
30=20
            fractions, and concluded that there was no difference =
between the=20
            59.4 Gy arm and the 45 Gy arm in terms of overall survival =
(OS) (59=20
            vs. 58%) or progression free survival (PFS) (50 vs. 47%) at =
five=20
            years, respectively.<SUP> <A class=3Dref=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#ref4"=20
            name=3Dft4>[4]</A></SUP> <BR><BR>Similarly, the RTOG 91-10 =
trial which=20
            was published in 2002, six years later than the EORTC 22844, =

            randomized 203 patients to 50.4 Gy in 28 fractions (101 =
patients)=20
            versus 64.8 Gy in 36 fractions (102 patients) and found no=20
            difference in OS or time to progression between the two =
arms.<SUP>=20
            <A class=3Dref=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#ref5"=20
            name=3Dft5>[5]</A></SUP> The incidence of Grade 3 to 5 =
neurotoxicity,=20
            however, was 5% for the 64.8 Gy arm versus 2.5% for the 50.4 =
Gy arm.=20
            Results from these two trials are summarized in <A =
class=3Dref=20
            =
onmouseover=3D"omovimg('viewimaget.asp?img=3DIndianJournalofCancer_2009_4=
6_2_96_49147_b1.jpg')"=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#">[Table =

            1]</A>. Thus, the benefit of higher dose for low grade =
gliomas is=20
            not justified, unlike that for the higher grade gliomas, =
such as,=20
            anaplastic astrocytomas and glioblastomas.<BR><BR>The EORTC =
22845=20
            study included 311 patients randomized to either observation =
with=20
            delayed radiation only at time of progression or upfront =
radiation=20
            using 54 Gy to localized treatment fields.<SUP> <A =
class=3Dref=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#ref4"=20
            name=3Dft4>[4]</A>,<A class=3Dref=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#ref5"=20
            name=3Dft5>[5]</A>,<A class=3Dref=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#ref6"=20
            name=3Dft6>[6]</A>,<A class=3Dref=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#ref7"=20
            name=3Dft7>[7]</A></SUP> The five-year PFS rates were 55% =
for=20
            immediate adjuvant radiation versus 35% for delayed adjuvant =

            radiation, for all LGG histologies. Pilocytic astrocytoma =
patients=20
            were not included in the study. Although the PFS was =
improved with=20
            immediate adjuvant radiation, the median OS times of 7.4 =
years for=20
            upfront radiation versus 7.2 years for delayed radiation =
were not=20
            statistically significant. Additionally, there were no =
statistical=20
            differences in the two arms with respect to headaches, =
cognitive=20
            deficits, and performance status at two years. However, =
seizures at=20
            one year were significantly more in the observation group =
(41%)=20
            compared to the irradiated group (25%). Furthermore, the =
time to=20
            progression was also reduced in the immediate radiation arm =
versus=20
            delayed radiation (5.3 vs. 3.4 years). These findings =
suggest that=20
            observation is a reasonable strategy in low-risk adults with =

            asymptomatic supratentorial low-grade gliomas. Adults with =
high-risk=20
            features as described in the EORTC trials or those with =
symptomatic=20
            LGGs, should be managed on a case by case basis and =
appropriate=20
            treatment and timing of radiation should be=20
            individualized.<BR><BR>The EORTC from the randomized studies =

            mentioned earlier identified poor prognostic factors: age 40 =
years=20
            or more, astrocytoma histology subtype, tumor diameter of 6 =
cm or=20
            more, tumor crossing midline, and presence of neurological =
deficits,=20
            before surgery.<SUP> <A class=3Dref=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#ref4"=20
            name=3Dft4>[4]</A>,<A class=3Dref=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#ref5"=20
            name=3Dft5>[5]</A>,<A class=3Dref=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#ref6"=20
            name=3Dft6>[6]</A>,<A class=3Dref=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#ref7"=20
            name=3Dft7>[7]</A></SUP> The presence of fewer than three of =
these=20
            factors was identified as low-risk group with a median OS of =
7.7=20
            years, whereas, three or more risks were identified as a =
high-risk=20
            group with a median OS of 3.2 years.<BR><BR>The use of PCV=20
            (procarbazine, Lomustine [CCNU], and vincristine) and CCNU=20
            chemotherapy is investigational for LGGs. A small Southwest =
Oncology=20
            Group (SWOG) study published in 1993 consisting of 60 adult =
patients=20
            who underwent subtotal resection were randomized to =
radiation alone=20
            (55 Gy in 32 fractions) or radiation with concurrent CCNU=20
            chemotherapy (100 mg/m<SUP> 2</SUP> ). The radiographic =
response=20
            rate was 79% for radiation alone versus 54% for radiation =
plus CCNU.=20
            This raised questions about the merits of concurrent =
chemotherapy=20
            for LGGs. The median OS was 4.45 years for all patients and =
no=20
            significant statistical difference was noted between the two =
arms,=20
            at the expense of hematological toxicity with the CCNU =
group.<SUP>=20
            <A class=3Dref=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#ref8"=20
            name=3Dft8>[8]</A></SUP> However, another phase II trial =
published in=20
            2003, examined the use of PCV chemotherapy delivered for six =
cycles,=20
            eight weeks apart, followed by radiation of 50.4 Gy with a =
boost of=20
            either 3.6 Gy or 9 Gy, in patients with low-grade =
oligodendroglioma=20
            or oligoastrocytoma, showed evidence of tumor regression =
following=20
            PCV chemotherapy in 52% of the enrolled patients (13 of 25) =
at the=20
            expense of myelosupression.<SUP> <A class=3Dref=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#ref9"=20
            name=3Dft9>[9]</A></SUP> The recently closed phase II part =
of the RTOG=20
            98-02 trial was designed to evaluate the role of =
postoperative=20
            observation alone in favorable LGGs, and the phase III =
portion of=20
            this study randomized unfavorable LGG patients into the =
radiation=20
            alone (54 Gy in 30 fractions) arm with that of radiation =
followed by=20
            six cycles of PCV. Those considered unfavorable were =
patients of age=20
            &#8805; 40 or those undergoing subtotal resection or only =
biopsy. Results=20
            from this trial published in 2008, showed that PFS improved =
for=20
            patients with LGGs, with the addition of PCV to =
radiation.<SUP> <A=20
            class=3Dref=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#ref10"=20
            name=3Dft10>[10]</A>,<A class=3Dref=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#ref11"=20
            name=3Dft11>[11]</A></SUP> This trial also suggested an OS =
benefit=20
            with the addition of PCV, but this was seen only in =
survivors beyond=20
            two years.<BR><BR>The role of temozolomide chemotherapy is =
also=20
            under investigation in several phase II and phase III =
trials. The=20
            National Cancer Institute and EORTC are conducting a phase =
III trial=20
            (EORTC 22033) and the RTOG is conducting a phase II trial =
(RTOG=20
            0424), both of which will help elucidate the emerging role =
of=20
            temozolomide in LGGs. The National Cancer Institute =
(NCI)/EORTC=20
            trial (EORTC 22033) is evaluating radiation alone versus=20
            temozolomide alone in a phase III trial, while the phase II =
RTOG=20
            trial (0424) used concurrent radiation with temozolomide, =
followed=20
            by adjuvant temozolomide for 12 cycles, for patients with =
three or=20
            more high-risk features. The high-risk features per the RTOG =
0424=20
            study include astrocytoma dominant histology, age &#8805; =
40, tumor that=20
            crosses midline, size &#8805; 6 cm, and neurological =
function greater than=20
            1. Results of these ongoing trials are awaited and will help =

            determine the role of temozolomide with or without radiation =
in=20
            LGGs. Additional trials comparing PCV to temozolomide will =
be needed=20
            in future for LGGs.<BR><BR><BR>
            <TABLE class=3DleftNav cellSpacing=3D0 cellPadding=3D0 =
width=3D"100%"=20
            border=3D0>
              <TBODY>
              <TR>
                <TD class=3DpageSub><A=20
                  name=3D"High-Grade =
Gliomas"></A>&nbsp;=BB&nbsp;High-Grade=20
                Gliomas</TD>
                <TD class=3Dinthis align=3Dright>&nbsp;</TD>
                <TD align=3Dright width=3D"15%"><A=20
                  =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#top"><IMG=
=20
                  alt=3DTop=20
                  =
src=3D"http://www.indianjcancer.com/images/arrow_top.gif"=20
                  =
border=3D0></A></TD></TR></TBODY></TABLE><BR><BR>Anaplastic=20
            astrocytomas (AA) and glioblastoma multiforme (GBM) behave =
much more=20
            aggressively with poor outcome and are regarded as =
high-grade=20
            gliomas. Anaplastic oligodendrogliomas (AO) and anaplastic=20
            oligoastrocytomas (AOA) were thought to behave aggressively =
and are=20
            classified as WHO Grade 3 tumors. Recent studies have shown =
that=20
            depending on molecular analysis, patients with AO and AOA =
may have a=20
            better outcome, as described a little later in this article. =
The=20
            management of malignant gliomas involves maximum safe =
resection=20
            followed by adjuvant radiation and chemotherapy. At least =
three=20
            prospective randomized trials have assessed the role of =
adjuvant=20
            radiation with or without adjuvant chemotherapy. The Brain =
Tumor=20
            Study Group (BTSG) performed three protocols from 1966 to =
1975. The=20
            BTSG 6901 evaluated the role of radiation with or without =
carmustine=20
            (BCNU) chemotherapy over best supportive care. This showed =
that the=20
            median OS improved from 14 weeks to approximately 35 weeks =
with the=20
            addition of radiation (1978).<SUP> <A class=3Dref=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#ref10"=20
            name=3Dft10>[10]</A> </SUP>Chemotherapy alone showed a =
slight=20
            improvement over best supportive care with a median OS of =
18.5=20
            months, but was inferior to the radiation arms. The addition =
of BCNU=20
            to radiation did not improve the outcome. Another study =
published in=20
            1980, BTSG 7201, randomized patients to receive one of the =
four=20
            regimens: semustine (MeCCNU), radiation alone, BCNU plus =
radiation,=20
            or MeCCNU plus radiation.<SUP> <A class=3Dref=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#ref12"=20
            name=3Dft12>[12]</A></SUP> Again, this study showed that =
radiation,=20
            either alone or in combination with chemotherapy, improved =
the=20
            chances of survival over chemotherapy alone. Based on these =
studies,=20
            which are summarized in <A class=3Dref=20
            =
onmouseover=3D"omovimg('viewimaget.asp?img=3DIndianJournalofCancer_2009_4=
6_2_96_49147_b2.jpg')"=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#">[Table =

            2]</A>, radiation plays an essential role in the management =
of=20
            high-grade gliomas.<BR><BR><BR>
            <TABLE class=3DleftNav cellSpacing=3D0 cellPadding=3D0 =
width=3D"100%"=20
            border=3D0>
              <TBODY>
              <TR>
                <TD class=3DpageSub><A=20
                  name=3D"Anaplastic Oligodendroglioma/Anaplastic =
Oligoastrocytoma"></A>&nbsp;=BB&nbsp;Anaplastic=20
                  Oligodendroglioma/Anaplastic Oligoastrocytoma</TD>
                <TD class=3Dinthis align=3Dright>&nbsp;</TD>
                <TD align=3Dright width=3D"15%"><A=20
                  =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#top"><IMG=
=20
                  alt=3DTop=20
                  =
src=3D"http://www.indianjcancer.com/images/arrow_top.gif"=20
                  border=3D0></A></TD></TR></TBODY></TABLE><BR><BR>The =
use of adjuvant=20
            chemotherapy with PCV either before or after radiation has =
been=20
            evaluated in two prospective randomized control trials. The =
RTOG=20
            94-02 was a prospective randomized control trial that was =
published=20
            in 2006, of 289 patients, which compared the role of =
adjuvant PCV=20
            (lomustine 130 mg/m<SUP> 2</SUP> d1, procarbazine 75 =
mg/m<SUP>=20
            2</SUP> d8-21, and vincristine 1.4 mg/m<SUP> 2</SUP> d 8-29) =
for=20
            four cycles followed by radiation of 59.4 Gy in 33 fx.<SUP> =
<A=20
            class=3Dref=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#ref13"=20
            name=3Dft13>[13]</A></SUP> Radiation was started within six =
weeks of=20
            completion of chemotherapy. This trial demonstrated that PCV =
given=20
            prior to radiation prolonged PFS (2.6 years vs. 1.7 years), =
over=20
            radiation alone. The OS was not statistically significant at =
4.9=20
            years for the PCV arm versus 4.7 years for the radiation =
alone arm.=20
            The most notable difference in survival was for the patients =
with=20
            1p/19q loss where the median OS was not reached, compared to =
2.8=20
            years for those with 1p/19q intact.<SUP> <A class=3Dref=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#ref13"=20
            name=3Dft13>[13]</A></SUP> This was regardless of the =
treatment arm.=20
            The role of PCV chemotherapy after radiation was also =
evaluated in=20
            EORTC 26951 (2006). This prospective phase III trial of 368 =
patients=20
            evaluated the role of adjuvant radiation of 59.4 Gy in 33 =
fractions=20
            to six cycles of PCV (lomustine 110 mg/m<SUP> 2</SUP> d1,=20
            procarbazine 60 mg/m<SUP> 2</SUP> d8-21, and vincristine 1.4 =

            mg/m<SUP> 2</SUP> d8 - 29). Patients began radiation within =
six=20
            weeks of surgery, and chemotherapy was started within one =
month=20
            after completion of radiation. Similar findings were found =
within=20
            this trial as those for RTOG 94-02. Radiation followed by =
PCV=20
            prolonged PFS at 32 months versus 13.2 months for the =
radiation=20
            alone arm. However, the five-year OS was no different at =
41.9% for=20
            the combined arm versus 35% for radiotherapy (RT) alone arm, =
but the=20
            grade III-IV toxicities were 65% in the PCV arm. Similarly, =
the=20
            median OS of 40.3 months for the combined arm versus 30.6 =
months for=20
            the radiation alone arm was not statistically significant. =
Patients=20
            with 1p/19q loss did significantly better than those without =
1p/19q=20
            loss. The five-year overall survival for the 1p/19q loss =
patients=20
            was 74.7% versus 27.5% for those without 1p/19q loss.<SUP> =
<A=20
            class=3Dref=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#ref14"=20
            name=3Dft14>[14]</A></SUP> The 1p/19q status is strongly =
prognostic=20
            and is now required in many of the newer trials. Results =
from these=20
            two prospective randomized control trials are summarized in =
<A=20
            class=3Dref=20
            =
onmouseover=3D"omovimg('viewimaget.asp?img=3DIndianJournalofCancer_2009_4=
6_2_96_49147_b3.jpg')"=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#">[Table =

            3]</A>.<BR><BR>Use of temozolomide has been recently studied =
in a=20
            phase II trial, RTOG 0131.<SUP> <A class=3Dref=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#ref15"=20
            name=3Dft15>[15]</A></SUP> This trial evaluated the efficacy =
of pre-RT=20
            TMZ and the toxicity of concurrent RT and (temozolomide) TMZ =
in=20
            patients with newly diagnosed AO/AOA. It was noted that 6.3% =
of the=20
            patients had a complete response, 28.1% experienced a =
partial=20
            response, 50% of the patients were stable, while only 28.1% =
had=20
            progression.<SUP> <A class=3Dref=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#ref15"=20
            name=3Dft15>[15]</A></SUP> <BR><BR><BR>
            <TABLE class=3DleftNav cellSpacing=3D0 cellPadding=3D0 =
width=3D"100%"=20
            border=3D0>
              <TBODY>
              <TR>
                <TD class=3DpageSub><A=20
                  name=3D"Anaplastic =
Astrocytoma"></A>&nbsp;=BB&nbsp;Anaplastic=20
                  Astrocytoma</TD>
                <TD class=3Dinthis align=3Dright>&nbsp;</TD>
                <TD align=3Dright width=3D"15%"><A=20
                  =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#top"><IMG=
=20
                  alt=3DTop=20
                  =
src=3D"http://www.indianjcancer.com/images/arrow_top.gif"=20
                  =
border=3D0></A></TD></TR></TBODY></TABLE><BR><BR>Anaplastic=20
            Astrocytomas (AA) are pathologically classified as WHO grade =
III=20
            tumors as they tend to behave more aggressively compared to =
some of=20
            the lower grade gliomas. Patients with AA have a median OS =
in the=20
            order of 11 months to 59 months, depending on certain =
prognostic=20
            factors such as age &gt;50, histology, mental status, =
Karnofsky=20
            performance status, length of symptoms prior to surgery, =
extent of=20
            resection, neurological functional status, and the RT dose =
used.=20
            Unfavorable prognostic factors predict shorter survival =
times based=20
            on nonparametric recursive analysis.<SUP> <A class=3Dref=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#ref16"=20
            name=3Dft16>[16]</A> </SUP>Given the aggressive and =
infiltrative=20
            nature of this tumor, immediate adjuvant radiation is the =
standard=20
            within the United States. The role of concurrent or adjuvant =

            chemotherapy and the selection of appropriate chemotherapy =
are under=20
            active investigation. To date, adjuvant chemotherapy has not =
been=20
            validated in a prospective randomized trial for WHO III =
gliomas.=20
            Additional clinical trials are needed. <BR><BR>The =
management of AA=20
            begins with maximal surgical resection as shown in several=20
            retrospective reviews. Adequate randomized control trials =
are=20
            lacking.<SUP> <A class=3Dref=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#ref17"=20
            name=3Dft17>[17]</A></SUP> One 1989 study showed that a =
radical=20
            surgical resection resulting in less than 5% of tumor =
impacts=20
            favorably on prognosis and confers both a survival advantage =
and=20
            palliation of symptoms.<SUP> <A class=3Dref=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#ref18"=20
            name=3Dft18>[18]</A></SUP> Another retrospective review =
published in=20
            1992 showed that patients undergoing partial or total =
resection had=20
            a median survival time of 49 months versus 18 months for =
those=20
            undergoing biopsy only.<SUP> <A class=3Dref=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#ref19"=20
            name=3Dft19>[19]</A> </SUP>Thus, maximal surgical resection, =
if=20
            feasible, without major additive neurological deficit, =
continues to=20
            be the standard. This is then followed immediately by =
radiation at a=20
            minimum.<BR><BR>Radiation has been shown to be the single =
most=20
            effective adjuvant treatment in two prospective randomized =
clinical=20
            trials conducted by the BTSG in 1978 and 1980.<SUP> <A =
class=3Dref=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#ref20"=20
            name=3Dft20>[20]</A>,<A class=3Dref=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#ref21"=20
            name=3Dft21>[21]</A></SUP> Both these trials showed =
improvements in=20
            median OS from four to eight months and increased the number =
of=20
            patients alive at 18 months from 10% to 15-20%.<SUP> <A =
class=3Dref=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#ref20"=20
            name=3Dft20>[20]</A>,<A class=3Dref=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#ref21"=20
            name=3Dft21>[21]</A></SUP> Furthermore, the role of 60.2 Gy =
to the=20
            whole brain as used in the earlier trials was challenged in =
a=20
            randomized trial published in 1989 and compared with 43 Gy =
to the=20
            whole brain followed by a cone-down of 17.2 Gy to the tumor =
volume,=20
            and it showed no difference between the two radiation=20
            techniques.<SUP> <A class=3Dref=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#ref22"=20
            name=3Dft22>[22]</A></SUP> The standard within the United =
States is=20
            the use of immediate adjuvant radiation therapy after =
maximal safe=20
            surgical debulking.<BR><BR>The role of chemotherapy for AA =
is=20
            controversial, and appropriate chemotherapy is the basis of =
the=20
            ongoing phase II and phase III trials within the United =
States. The=20
            first prospective trial to suggest the benefit of =
chemotherapy was=20
            reported by the BTCG in 1978.<SUP> <A class=3Dref=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#ref23"=20
            name=3Dft23>[23]</A></SUP> This trial evaluated the role of =
radiation=20
            with or without BCNU in 222 patients, in a four-arm =
randomized=20
            control trial, with radiation doses ranging from 50 Gy to 60 =
Gy. The=20
            arms consisted of the best supportive group, the BCNU alone =
group,=20
            the radiation alone group, and the combined BCNU and =
radiation=20
            group. The combined group was shown to have a median OS of =
34.5=20
            weeks versus 35 weeks for the radiation alone group, at the =
expense=20
            of increased toxicity.<SUP> <A class=3Dref=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#ref24"=20
            name=3Dft24>[24]</A></SUP> Thus, the use of chemotherapy has =
been and=20
            continues to be questioned for the management of AA. Since =
BCNU=20
            combined with radiation did not show efficacy, the role of =
other=20
            chemotherapy regimens have been tried. One 1983 phase III =
trial=20
            evaluated the role of procarbazine and high-dose =
prednisolone=20
            combined with radiation, and compared with BCNU + RT, it =
showed no=20
            significant difference between them and the radiation alone=20
            arm.<SUP> <A class=3Dref=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#ref24"=20
            name=3Dft24>[24]</A></SUP> <BR><BR>Additional trials =
evaluated PCV=20
            compared to BCNU. One phase III clinical trial in 1989 =
evaluated=20
            BCNU to PCV followed by standard radiation and showed PCV to =
be=20
            superior to BCNU.<SUP> <A class=3Dref=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#ref25"=20
            name=3Dft25>[25]</A>,<A class=3Dref=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#ref26"=20
            name=3Dft26>[26]</A></SUP> This trial showed that the median =
survival=20
            was 157 weeks for the PCV group versus 82.1 weeks for the =
BCNU=20
            group, and thus became the standard for additional =
trials.<SUP> <A=20
            class=3Dref=20
            =
href=3D"http://www.indianjcancer.com/article.asp?issn=3D0019-509X;year=3D=
2009;volume=3D46;issue=3D2;spage=3D96;epage=3D107;aulast=3DKhan#ref25"=20