From: Subject: Immediate post-radiotherapy changes in malignant glioma can mimic tumor progression -- de Wit et al. 63 (3): 535 -- Neurology Date: Thu, 11 Sep 2008 10:31:53 +0200 MIME-Version: 1.0 Content-Type: multipart/related; type="text/html"; boundary="----=_NextPart_000_007D_01C913F9.9BB4C670" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.5579 This is a multi-part message in MIME format. ------=_NextPart_000_007D_01C913F9.9BB4C670 Content-Type: text/html; charset="Windows-1252" Content-Transfer-Encoding: quoted-printable Content-Location: http://www.neurology.org/cgi/content/full/63/3/535?ijkey=62d7f99e12b63739e22335ffc375a44a8d92069f Immediate post-radiotherapy changes in malignant = glioma can mimic tumor progression -- de Wit et al. 63 (3): 535 -- = Neurology
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NEUROLOGY 2004;63:535-537
=A9 2004 American Academy of=20 Neurology
Brief Communications

Immediate post-radiotherapy changes in malignant glioma can mimic = tumor=20 progression

M. C.Y. de Wit, MD, = H. G. de=20 Bruin, MD, W. Eijkenboom, MD, P. A.E. Sillevis = Smitt,=20 MD PhD and M. J. van den Bent, MD PhD

From the Departments of Neuro-oncology/Neurology = (Drs. de Wit,=20 Sillevis Smitt, and van den Bent), Radiology (Dr. de Bruin), and = Radiotherapy=20 (Dr. Eijkenboom), Daniel den Hoed Cancer Center/Erasmus Medical Center,=20 Rotterdam, The Netherlands.

Address correspondence and reprint requests to Dr. = M.J. van den=20 Bent, Department of Neuro-oncology/Neurology, Daniel den Hoed Cancer=20 Center/Erasmus Medical Center, PO Box 5201, 3008 AE Rotterdam, The = Netherlands;=20 e-mail: m.vandenbent{at}erasmusmc.nl


3D"   =20 Abstract
Top.
3D"Abstract
Index case.
Patients and methods.
Results.
Discussion.
References
 
T= o=20 determine the frequency of progressive MRI lesions shortly = after=20 radiotherapy for glioma with spontaneous improvement or=20 stabilization, the authors studied a cohort of patients = treated=20 within two prospective phase III trials with radiotherapy = only.=20 In 9 out of 32 patients, the first post-radiotherapy MRI = showed=20 progressive enhancement. In 3 of these 9 the MRI improved or=20 stabilized for 6 months without additional treatment. The = authors=20 conclude that patients with progressive lesions within 3 = months=20 after radiotherapy should not be eligible for phase II trials = on recurrent glioma.

Most phase II and phase III trials on recurrent anaplastic glioma=20 require radiologic evidence of progression as a mandatory = inclusion=20 criterion. As a rule, this requires either an increase in = area=20 of gadolinium uptake on MRI or the appearance of new lesions. = This is unspecific, as radiation therapy induced lesions may=20 mimic recurrent tumor.1,2=20 Due to inherent risks and invasiveness of a stereotactic = biopsy, it=20 is generally considered unethical to include mandatory repeat = tumor=20 biopsies in protocols on recurrent high grade glioma. Most = protocols=20 deal with this in part by avoiding patients with an increased = risk of=20 radionecrosis by precluding patients treated with high dose=20 radiotherapy, stereotactic radiosurgery, or interstitial=20 radiotherapy.3=20

In the last years we observed several patients with radiologic=20 deterioration on MRI shortly after the end of radiotherapy,=20 which proved to be a transient phenomenon even when no = further=20 treatment was initiated. Some articles mention the = possibility=20 of early post-radiotherapy changes, but virtually no data on=20 this phenomenon are available.4,5=20 Moreover, many phase II studies on recurrent glioma still = accept=20 patients with progressive lesions within the first 3 months = after=20 radiotherapy. Cases similar to the index patient described = below led=20 us to investigate the clinical relevance of this phenomenon = by=20 reviewing a cohort of patients included in prospective phase = III=20 trials on newly diagnosed glioma treated with radiotherapy = only and=20 for whom strict follow-up at three monthly intervals was=20 available.


3D"    Index=20 case.
Top.
Abstract
3D"Index case.
Patients and methods.
Results.
Discussion.
References
 
A= =20 previously healthy 47-year-old man presented with seizures = and=20 underwent a gross total resection of a right frontal anaplastic=20 astrocytoma, followed by radiation therapy (64 Gy). A brain = MRI=20 made immediately following radiotherapy (figure,=20 A and B) was unchanged compared to the pre-radiotherapy = scan,=20 showing the resection cavity but no gadolinium uptake. Two = months=20 after the completion of radiotherapy he developed headache,=20 drowsiness, and nausea. Repeat MRI (figure,=20 C and D) showed a new area of gadolinium uptake and = edema.=20 Dexamethasone resulted in a complete disappearance of all = signs and=20 symptoms; no other treatment was given. Dexamethasone was = then=20 discontinued. Follow-up MRI at 12 months after the end of=20 radiotherapy (figure,=20 E and F) showed a complete resolution of the gadolinium = uptake=20 and edema.



View = larger=20 version (91K):
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  		Figure. (A through F) Index = case:=20 T1-weighted images after gadolinium administration. (A, B)=20 Immediately following the end of radiotherapy showing the=20 post-resection cavity; (C, D) 2 months after radiation = therapy at=20 the time of clinical signs and symptoms showing a new area = of=20 gadolinium uptake and edema causing a slight midline shift; = (E, F) 1=20 year after the end of radiotherapy: resolution of edema and=20 enhancement. =

 = ;

3D"   =20 Patients and methods.
Top.
Abstract
Index case.
3D"Patients and methods.
Results.
Discussion.
References
 
F= or this=20 study, we reviewed all patients included in our center in = EORTC=20 studies 25951 and 26981. Both studies addressed the value of = adjuvant=20 chemotherapy in high-grade glioma (EORTC 26951: = PCV-chemotherapy;=20 EORTC 26981: temozolomide); both had a control arm with = radiation=20 therapy only. At our center, all eligible patients were = routinely=20 asked to participate, to which the majority consented. Only = patients=20 randomized to the control arms were used for the present = study.=20

All pre- and post-radiotherapy brain MRI up to and including = the=20 MRIs made after 12 months were reviewed by two independent = observers:=20 a radiologist (H.G.d.B.) and a neuro-oncologist (M.J.v.d.B.). = The=20 timing of MRIs was prescribed by the EORTC protocol and is = shown for=20 patients with progression on the first post-radiotherapy MRI = in the=20 table.=20 The evaluation was primarily based on T1-weighted pre- and=20 postcontrast MR images. Macdonald=92s criteria were used to = assess the=20 response to radiotherapy.6=20 In case of disagreement on progressive lesions the scans were = jointly=20 re-evaluated. Patients showing radiologic deterioration at = the first=20 MRI following radiotherapy were examined more closely, and=20 information was collected on radiation dose, timing of the = MRI in=20 relation to the start and end of radiotherapy, clinical = performance,=20 dexamethasone dose, histology, and survival.


View = this=20 table:
[in=20 this window]
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  		Table Description of=20 demographics, interval between pre-RT MRI and start RT, = interval=20 between end of RT and first post-RT MRI, dexamethasone = dosage on the=20 day of pre- and post-RT MRI, and outcome in the nine = patients with=20 an increasing lesion at the time of the first follow-up MRI = scan=20 after radiotherapy=20
 

3D"   =20 Results.
Top.
Abstract
Index case.
Patients and methods.
3D"Results.
Discussion.
References
 
S= eventy-three=20 patients were included in these studies by our center; 32 had = been=20 randomized in the control arm. Mean age was 49 years, and 22 = were=20 men. One patient was lost to follow-up during radiation = therapy. In=20 nine patients the first follow-up scan after radiotherapy = showed=20 progression as compared to the pre-radiotherapy imaging (see = the table).=20 Six of these nine patients developed further progression at = further=20 follow-up or died within a year, but two showed subsequent=20 improvement and one stabilized for 6 months without = additional=20 treatment (Patients 1=963). Both reviewers identified these = three=20 patients as progressive at the first post-radiotherapy MRI. = In=20 one case the radiologic progression was accompanied by clinical=20 deterioration, which then stabilized (Patient 3). The = individual=20 charts were checked for other explanations of remission, but=20 none were found. In particular, no new treatments had been = initiated=20 and changes in dexamethasone dose could not explain the = observed=20 changes.


3D"   =20 Discussion.
Top.
Abstract
Index case.
Patients and methods.
Results.
3D"Discussion.
References
 
F= rom this=20 cohort of 32 trial patients treated with radiotherapy only, = in three=20 of the nine patients with a progressive lesion at the first = tumor=20 evaluation after radiotherapy further follow-up showed that = the=20 progressive enhancement was not due to tumor progression. In = two=20 patients, the lesions decreased to a PR during follow-up, = whereas the=20 third patient remained stable for 6 months. Both decrease and = absence=20 of progression for 6 months have been considered endpoints in = recent=20 phase II studies on recurrent high grade glioma.7=20 With a traditional two-step statistical design used for phase = II=20 studies in GBM aiming at a response rate of at least 25% = these three=20 out of nine patients would have sufficed to initiate the = second step=20 and might have lead to a false positive result of the = study.8=20 The three patients with transient increased gadolinium = enhancement=20 also had a much longer survival than the remaining six = patients with=20 a progressive lesion on the first post-radiotherapy MRI. = Others have=20 observed apparent tumor progression on radiologic examination = followed by spontaneous remission, but the frequency of this=20 occurrence has remained unclear. An article on 51 patients = from the=20 pre-MRI era using neurologic examination, brain CTs, and=20 radionucleotide scans noted in 25 patients clear = deterioration in any=20 of the three tests within the first 18 weeks.4=20 Seven of those 25 showed subsequent improvement without any = change in=20 therapy, but all patients were treated with adjuvant = chemotherapy,=20 which may have contributed to the observed improvement. It is = clear=20 though from our series and from other studies that immediate=20 progression after radiotherapy in general heralds a poor = outcome.9=20 Five of the other six patients with progressive lesion at the = end of radiotherapy died within 8 months from the start of=20 radiotherapy.

The intermediate and late sequelae of radiotherapy to the brain=20 have been well documented.10=20 The characteristic difference between the early somnolence = syndrome=20 and the patients described in this report is the focal = increase in=20 gadolinium enhancement, with or without focal signs and = symptoms. The=20 explanation of this early post-radiotherapy deterioration may = be=20 manifold, including tumor progression during the first part = of=20 radiotherapy and subsequent response, and radiation-induced = vascular=20 changes.

The classic article on the WHO-based response criteria for = glioma=20 mentions the possibility of early post-radiotherapy changes=20 without further details.6=20 The authors advised not to start investigational treatments = within=20 the 2 months following conventional radiotherapy. The = protocols=20 according to which the patients of this cohort were treated = required=20 a first post radiotherapy MRI within 4 weeks after the end of = radiotherapy. However, the index case (which was not included = in any=20 of the EORTC protocols) shows that such transient increase in = size=20 may occur well after these first 4 weeks.

Because the value of metabolic imaging like PET in this = situation=20 is unclear, the most prudent approach to this methodologic = problem=20 is to exclude patients with progression within the first 3 = months=20 of radiotherapy from trials on recurrent glioma, unless = histologic=20 proof of the recurrence is obtained. This is already current=20 practice in some cooperative groups (NABTT, NCCTG, EORTC). = Our=20 data show that this should be the rule for all phase II = studies=20 on recurrent glioma after radiotherapy. For the individual = patient=20 an increase in gadolinium enhancement is most likely to = represent=20 tumor progression, and they should be managed accordingly, = but=20 preferably outside clinical trials.

Received December 4, 2003. Accepted in final form April 13, 2004.

See Commentary, page 407


3D"   =20 References
Top.
Abstract
Index case.
Patients and methods.
Results.
Discussion.
3D"References
&nb= sp;

  1. Kumar AJ, Leeds NE, Fuller GN, et al. Malignant gliomas: = MR=20 imaging spectrum of radiation therapy- and chemotherapy-induced = necrosis of=20 the brain after treatment. Radiology. 2000; 217: 377=96384.[Abstract/Free Full Text]=20
  2. Norris AM, Carrington BM, Slevin NJ. Late radiation = change in the=20 CNS: MR imaging following gadolinium enhancement. Clin Radiol. 1997; = 52:=20 356=96362.[Medline]=20
  3. Bakardjiev AI, Barnes PD, Goumnerova LC, et al. Magnetic = resonance=20 imaging changes after stereotactic radiation therapy for childhood low = grade=20 astrocytoma. Cancer. 1996; 78: 864=96873.[Medline]=20
  4. Hoffman WF, Levin VA, Wilson CB. Evaluation of malignant = glioma=20 patients during the postirradiation period. J Neurosurg. 1979; 50: = 624=96628.[Medline]=20
  5. Cascino TL, Kimmel DW, Dinapoli RP, O=92Neill BP, = Scheithauer B.=20 Report of four cases with a resolving syndrome which otherwise = simulates=20 recurrent brain tumor. Neurology. 1988; 38 (suppl 1): 306. = Abstract.=20
  6. Macdonald DR, Cascino TL, Schold SC, Cairncross JG. = Response=20 criteria for phase II studies of supratentorial malignant glioma. J = Clin=20 Oncol. 1990; 8: 1277=961280.[Abstract]=20
  7. Yung WKA, Albright RE, Olson J, et al. A phase II study = of=20 temozolomide vs. procarbazine in patients with glioblastoma multiforme = at=20 first relapse. Br J Cancer. 2000; 83: 588=96593.[Medline]=20
  8. Simon R. Optimal two-stage designs for phase II clinical = trials.=20 Control Clin Trials. 1989; 10: 1=9610.[Medline]=20
  9. Gaspar LE, Fisher BJ, Macdonald DR, et al. Malignant = glioma=97timing=20 of response to radiation therapy. Int J Radiation Oncol Biol Phys. = 1993; 25:=20 877=96879.[Medline]=20
  10. Jennings MT. Neurological complications of = radiotherapy. In:=20 Wiley RG, ed. Neurological complications of cancer. New York: Marcel = Dekker,=20 1995; 219=96240.

Related=20 articles in Neurology:=20

August 10 Highlight and Commentary=20

Neurology 2004 63: 407. [Full = Text]=20  =20



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Opera = requires=0A= the Sun Java Runtime Environment .=0A= =0A= by Andrew Gregory=0A= http://www.scss.com.au/family/andrew/webdesign/xmlhttprequest/=0A= =0A= This work is licensed under the Creative Commons Attribution License. To = view a=0A= copy of this license, visit = http://creativecommons.org/licenses/by-sa/2.5/ or=0A= send a letter to Creative Commons, 559 Nathan Abbott Way, Stanford, = California=0A= 94305, USA.=0A= =0A= Attribution: Leave my name and web address in this script intact.=0A= =0A= Not Supported in Opera=0A= ----------------------=0A= * user/password authentication=0A= * responseXML data member=0A= =0A= Not Fully Supported in Opera=0A= ----------------------------=0A= * async requests=0A= * abort()=0A= * getAllResponseHeaders(), getAllResponseHeader(header)=0A= =0A= */=0A= // IE support=0A= if (window.ActiveXObject && !window.XMLHttpRequest) {=0A= window.XMLHttpRequest =3D function() {=0A= var msxmls =3D new Array(=0A= 'Msxml2.XMLHTTP.5.0',=0A= 'Msxml2.XMLHTTP.4.0',=0A= 'Msxml2.XMLHTTP.3.0',=0A= 'Msxml2.XMLHTTP',=0A= 'Microsoft.XMLHTTP');=0A= for (var i =3D 0; i < msxmls.length; i++) {=0A= try {=0A= return new ActiveXObject(msxmls[i]);=0A= } catch (e) {=0A= }=0A= }=0A= return null;=0A= };=0A= }=0A= // Gecko support=0A= /* ;-) */=0A= // Opera support=0A= if (window.opera && !window.XMLHttpRequest) {=0A= window.XMLHttpRequest =3D function() {=0A= this.readyState =3D 0; // = 0=3Duninitialized,1=3Dloading,2=3Dloaded,3=3Dinteractive,4=3Dcomplete=0A= this.status =3D 0; // HTTP status codes=0A= this.statusText =3D '';=0A= this._headers =3D [];=0A= this._aborted =3D false;=0A= this._async =3D true;=0A= this._defaultCharset =3D 'ISO-8859-1';=0A= this._getCharset =3D function() {=0A= var charset =3D _defaultCharset;=0A= var contentType =3D = this.getResponseHeader('Content-type').toUpperCase();=0A= val =3D contentType.indexOf('CHARSET=3D');=0A= if (val !=3D -1) {=0A= charset =3D contentType.substring(val);=0A= }=0A= val =3D charset.indexOf(';');=0A= if (val !=3D -1) {=0A= charset =3D charset.substring(0, val);=0A= }=0A= val =3D charset.indexOf(',');=0A= if (val !=3D -1) {=0A= charset =3D charset.substring(0, val);=0A= }=0A= return charset;=0A= };=0A= this.abort =3D function() {=0A= this._aborted =3D true;=0A= };=0A= this.getAllResponseHeaders =3D function() {=0A= return this.getAllResponseHeader('*');=0A= };=0A= this.getAllResponseHeader =3D function(header) {=0A= var ret =3D '';=0A= for (var i =3D 0; i < this._headers.length; i++) {=0A= if (header =3D=3D '*' || this._headers[i].h =3D=3D header) {=0A= ret +=3D this._headers[i].h + ': ' + this._headers[i].v + '\n';=0A= }=0A= }=0A= return ret;=0A= };=0A= this.getResponseHeader =3D function(header) {=0A= var ret =3D getAllResponseHeader(header);=0A= var i =3D ret.indexOf('\n');=0A= if (i !=3D -1) {=0A= ret =3D ret.substring(0, i);=0A= }=0A= return ret;=0A= };=0A= this.setRequestHeader =3D function(header, value) {=0A= this._headers[this._headers.length] =3D {h:header, v:value};=0A= };=0A= this.open =3D function(method, url, async, user, password) {=0A= this.method =3D method;=0A= this.url =3D url;=0A= this._async =3D true;=0A= this._aborted =3D false;=0A= this._headers =3D [];=0A= if (arguments.length >=3D 3) {=0A= this._async =3D async;=0A= }=0A= if (arguments.length > 3) {=0A= opera.postError('XMLHttpRequest.open() - user/password not = supported');=0A= }=0A= this.readyState =3D 1;=0A= if (this.onreadystatechange) {=0A= this.onreadystatechange();=0A= }=0A= };=0A= this.send =3D function(data) {=0A= if (!navigator.javaEnabled()) {=0A= alert("XMLHttpRequest.send() - Java must be installed and = enabled.");=0A= return;=0A= }=0A= if (this._async) {=0A= setTimeout(this._sendasync, 0, this, data);=0A= // this is not really asynchronous and won't execute until the = current=0A= // execution context ends=0A= } else {=0A= this._sendsync(data);=0A= }=0A= }=0A= this._sendasync =3D function(req, data) {=0A= if (!req._aborted) {=0A= req._sendsync(data);=0A= }=0A= };=0A= this._sendsync =3D function(data) {=0A= this.readyState =3D 2;=0A= if (this.onreadystatechange) {=0A= this.onreadystatechange();=0A= }=0A= // open connection=0A= var url =3D new java.net.URL(new = java.net.URL(window.location.href), this.url);=0A= var conn =3D url.openConnection();=0A= for (var i =3D 0; i < this._headers.length; i++) {=0A= conn.setRequestProperty(this._headers[i].h, this._headers[i].v);=0A= }=0A= this._headers =3D [];=0A= if (this.method =3D=3D 'POST') {=0A= // POST data=0A= conn.setDoOutput(true);=0A= var wr =3D new = java.io.OutputStreamWriter(conn.getOutputStream(), this._getCharset());=0A= wr.write(data);=0A= wr.flush();=0A= wr.close();=0A= }=0A= // read response headers=0A= // NOTE: the getHeaderField() methods always return nulls for me :(=0A= var gotContentEncoding =3D false;=0A= var gotContentLength =3D false;=0A= var gotContentType =3D false;=0A= var gotDate =3D false;=0A= var gotExpiration =3D false;=0A= var gotLastModified =3D false;=0A= for (var i =3D 0; ; i++) {=0A= var hdrName =3D conn.getHeaderFieldKey(i);=0A= var hdrValue =3D conn.getHeaderField(i);=0A= if (hdrName =3D=3D null && hdrValue =3D=3D null) {=0A= break;=0A= }=0A= if (hdrName !=3D null) {=0A= this._headers[this._headers.length] =3D {h:hdrName, = v:hdrValue};=0A= switch (hdrName.toLowerCase()) {=0A= case 'content-encoding': gotContentEncoding =3D true; break;=0A= case 'content-length' : gotContentLength =3D true; break;=0A= case 'content-type' : gotContentType =3D true; break;=0A= case 'date' : gotDate =3D true; break;=0A= case 'expires' : gotExpiration =3D true; break;=0A= case 'last-modified' : gotLastModified =3D true; break;=0A= }=0A= }=0A= }=0A= // try to fill in any missing header information=0A= var val;=0A= val =3D conn.getContentEncoding();=0A= if (val !=3D null && !gotContentEncoding) = this._headers[this._headers.length] =3D {h:'Content-encoding', v:val};=0A= val =3D conn.getContentLength();=0A= if (val !=3D -1 && !gotContentLength) = this._headers[this._headers.length] =3D {h:'Content-length', v:val};=0A= val =3D conn.getContentType();=0A= if (val !=3D null && !gotContentType) = this._headers[this._headers.length] =3D {h:'Content-type', v:val};=0A= val =3D conn.getDate();=0A= if (val !=3D 0 && !gotDate) this._headers[this._headers.length] = =3D {h:'Date', v:(new Date(val)).toUTCString()};=0A= val =3D conn.getExpiration();=0A= if (val !=3D 0 && !gotExpiration) = this._headers[this._headers.length] =3D {h:'Expires', v:(new = Date(val)).toUTCString()};=0A= val =3D conn.getLastModified();=0A= if (val !=3D 0 && !gotLastModified) = this._headers[this._headers.length] =3D {h:'Last-modified', v:(new = Date(val)).toUTCString()};=0A= // read response data=0A= var reqdata =3D '';=0A= var stream =3D conn.getInputStream();=0A= if (stream) {=0A= var reader =3D new java.io.BufferedReader(new = java.io.InputStreamReader(stream, this._getCharset()));=0A= var line;=0A= while ((line =3D reader.readLine()) !=3D null) {=0A= if (this.readyState =3D=3D 2) {=0A= this.readyState =3D 3;=0A= if (this.onreadystatechange) {=0A= this.onreadystatechange();=0A= }=0A= }=0A= reqdata +=3D line + '\n';=0A= }=0A= reader.close();=0A= this.status =3D 200;=0A= this.statusText =3D 'OK';=0A= this.responseText =3D reqdata;=0A= this.readyState =3D 4;=0A= if (this.onreadystatechange) {=0A= this.onreadystatechange();=0A= }=0A= if (this.onload) {=0A= this.onload();=0A= }=0A= } else {=0A= // error=0A= this.status =3D 404;=0A= this.statusText =3D 'Not Found';=0A= this.responseText =3D '';=0A= this.readyState =3D 4;=0A= if (this.onreadystatechange) {=0A= this.onreadystatechange();=0A= }=0A= if (this.onerror) {=0A= this.onerror();=0A= }=0A= }=0A= };=0A= };=0A= }=0A= // ActiveXObject emulation=0A= if (!window.ActiveXObject && window.XMLHttpRequest) {=0A= window.ActiveXObject =3D function(type) {=0A= switch (type.toLowerCase()) {=0A= case 'microsoft.xmlhttp':=0A= case 'msxml2.xmlhttp':=0A= case 'msxml2.xmlhttp.3.0':=0A= case 'msxml2.xmlhttp.4.0':=0A= case 'msxml2.xmlhttp.5.0':=0A= return new XMLHttpRequest();=0A= }=0A= return null;=0A= };=0A= }=0A= ------=_NextPart_000_007D_01C913F9.9BB4C670 Content-Type: application/octet-stream Content-Transfer-Encoding: quoted-printable Content-Location: http://www.neurology.org/javascript/ajax/utility.js /************************************************************************= *****=0A= * javascript/ajax/utility.js=0A= *=0A= * Utility functions for working with XMLHttpRequest data.=0A= *=0A= * Copyright 2006 Board of Trustees of the Leland Stanford Junior = University.=0A= = *************************************************************************= ***/=0A= =0A= /*=0A= * Copy XML nodes into an HTMLElement. This effectively=0A= * clones XML markup which uses XHTML naming conventions=0A= * into an HTML DOM.=0A= */=0A= function copy_xml_to_html(src, dst) {=0A= if (src.nodeType =3D=3D 1) { /* Node.ELEMENT_NODE */=0A= var e =3D document.createElement(src.nodeName);=0A= for (var i =3D 0; i < src.childNodes.length; i++) {=0A= copy_xml_to_html(src.childNodes[i], e);=0A= }=0A= for (var i =3D 0; i < src.attributes.length; i++) {=0A= var n =3D src.attributes[i].name;=0A= var v =3D unescape_xml_string(src.attributes[i].value); =0A= e.setAttribute(n, v);=0A= if (n =3D=3D "class") {=0A= e.className =3D v;=0A= }=0A= else if (n =3D=3D "style") {=0A= set_css_style(v, e, "");=0A= }=0A= }=0A= dst.appendChild(e);=0A= }=0A= else if (src.nodeType =3D=3D 3) { /* Node.TEXT_NODE */=0A= dst.appendChild(document.createTextNode(src.nodeValue));=0A= }=0A= }=0A= =0A= /* =0A= * It is unclear that this is the right thing to be calling=0A= * from copy_xml_to_html, but it appears that Safari decides=0A= * to convert & to the NCR #, and then encodes that=0A= * NCR to &%26%2338;. So, I'm going to treat the DOM Attr=0A= * value as a plain string, and run our XML string input=0A= * through the decoding routine below.=0A= */=0A= function unescape_xml_string(s) {=0A= return s.replace(/'/g, "'")=0A= .replace(/'/g, "'")=0A= .replace(/"/g, "\"")=0A= .replace(/"/g, "\"")=0A= .replace(/>/g, ">")=0A= .replace(/>/g, ">")=0A= .replace(/</g, "<")=0A= .replace(/</g, "<")=0A= .replace(/&/g, "&")=0A= .replace(/&/g, "&");=0A= }=0A= =0A= /*=0A= * Parse set of CSS rules and apply them to an element.=0A= * This is quite horrifying, but I'm unable to determine=0A= * how else to handle this with IE 6. FireFox and other=0A= * sane browsers let you simply set the style attribute=0A= * or use e.style.setProperty(rule, value, priority),=0A= * IE 6 appears to have neither of these capabilities..=0A= */=0A= function set_css_style(css, e, priority) {=0A= var rules =3D css.split(";");=0A= for (var i =3D 0; i < rules.length; i++) {=0A= var nvpair =3D rules[i].split(":");=0A= if (nvpair.length =3D=3D 2) {=0A= try {=0A= var name =3D nvpair[0]; /* style attribute */=0A= var value =3D nvpair[1]; /* attribute value */=0A= =0A= /*=0A= * For each possible style attribute, set the=0A= * appropriate style property in the element.=0A= */=0A= if (name =3D=3D "background") {=0A= e.style.background =3D value;=0A= }=0A= else if (name =3D=3D "background-attachment") {=0A= e.style.backgroundAttachment =3D value;=0A= }=0A= else if (name =3D=3D "background-color") {=0A= e.style.backgroundColor =3D value;=0A= }=0A= else if (name =3D=3D "background-image") {=0A= e.style.backgroundImage =3D value;=0A= }=0A= else if (name =3D=3D "background-position") {=0A= e.style.backgroundPosition =3D value;=0A= }=0A= else if (name =3D=3D "background-position-x") {=0A= e.style.backgroundPositionX =3D value;=0A= }=0A= else if (name =3D=3D "background-position-y") {=0A= e.style.backgroundPositionY =3D value;=0A= }=0A= else if (name =3D=3D "background-repeat") {=0A= e.style.backgroundRepeat =3D value;=0A= }=0A= else if (name =3D=3D "behavior") {=0A= e.style.behavior =3D value;=0A= }=0A= else if (name =3D=3D "border") {=0A= e.style.border =3D value;=0A= }=0A= else if (name =3D=3D "border-bottom") {=0A= e.style.borderBottom =3D value;=0A= }=0A= else if (name =3D=3D "border-bottom-color") {=0A= e.style.borderBottomColor =3D value;=0A= }=0A= else if (name =3D=3D "border-bottom-style") {=0A= e.style.borderBottomStyle =3D value;=0A= }=0A= else if (name =3D=3D "border-bottom-width") {=0A= e.style.borderBottomWidth =3D value;=0A= }=0A= else if (name =3D=3D "border-collapse") {=0A= e.style.borderCollapse =3D value;=0A= }=0A= else if (name =3D=3D "border-color") {=0A= e.style.borderColor =3D value;=0A= }=0A= else if (name =3D=3D "border-left") {=0A= e.style.borderLeft =3D value;=0A= }=0A= else if (name =3D=3D "border-left-color") {=0A= e.style.borderLeftColor =3D value;=0A= }=0A= else if (name =3D=3D "border-left-style") {=0A= e.style.borderLeftStyle =3D value;=0A= }=0A= else if (name =3D=3D "border-left-width") {=0A= e.style.borderLeftWidth =3D value;=0A= }=0A= else if (name =3D=3D "border-right") {=0A= e.style.borderRight =3D value;=0A= }=0A= else if (name =3D=3D "border-right-color") {=0A= e.style.borderRightColor =3D value;=0A= }=0A= else if (name =3D=3D "border-right-style") {=0A= e.style.borderRightStyle =3D value;=0A= }=0A= else if (name =3D=3D "border-right-width") {=0A= e.style.borderRightWidth =3D value;=0A= }=0A= else if (name =3D=3D "border-style") {=0A= e.style.borderStyle =3D value;=0A= }=0A= else if (name =3D=3D "border-top") {=0A= e.style.borderTop =3D value;=0A= }=0A= else if (name =3D=3D "border-top-color") {=0A= e.style.borderTopColor =3D value;=0A= }=0A= else if (name =3D=3D "border-top-style") {=0A= e.style.borderTopStyle =3D value;=0A= }=0A= else if (name =3D=3D "border-top-width") {=0A= e.style.borderTopWidth =3D value;=0A= }=0A= else if (name =3D=3D "border-width") {=0A= e.style.borderWidth =3D value;=0A= }=0A= else if (name =3D=3D "bottom") {=0A= e.style.bottom =3D value;=0A= }=0A= else if (name =3D=3D "clear") {=0A= e.style.clear =3D value;=0A= }=0A= else if (name =3D=3D "clip") {=0A= e.style.clip =3D value;=0A= }=0A= else if (name =3D=3D "color") {=0A= e.style.color =3D value;=0A= }=0A= else if (name =3D=3D "cssText") {=0A= e.style.Sets =3D value;=0A= }=0A= else if (name =3D=3D "cursor") {=0A= e.style.cursor =3D value;=0A= }=0A= else if (name =3D=3D "direction") {=0A= e.style.direction =3D value;=0A= }=0A= else if (name =3D=3D "display") {=0A= e.style.display =3D value;=0A= }=0A= else if (name =3D=3D "font") {=0A= e.style.font =3D value;=0A= }=0A= else if (name =3D=3D "font-family") {=0A= e.style.fontFamily =3D value;=0A= }=0A= else if (name =3D=3D "font-size") {=0A= e.style.fontSize =3D value;=0A= }=0A= else if (name =3D=3D "font-style") {=0A= e.style.fontStyle =3D value;=0A= }=0A= else if (name =3D=3D "font-variant") {=0A= e.style.fontVariant =3D value;=0A= }=0A= else if (name =3D=3D "font-weight") {=0A= e.style.fontWeight =3D value;=0A= }=0A= else if (name =3D=3D "height") {=0A= e.style.height =3D value;=0A= }=0A= else if (name =3D=3D "ime-mode") {=0A= e.style.imeMode =3D value;=0A= }=0A= else if (name =3D=3D "layout-flow") {=0A= e.style.layoutFlow =3D value;=0A= }=0A= else if (name =3D=3D "layout-grid") {=0A= e.style.layoutGrid =3D value;=0A= }=0A= else if (name =3D=3D "layout-grid-char") {=0A= e.style.layoutGridChar =3D value;=0A= }=0A= else if (name =3D=3D "layout-grid-line") {=0A= e.style.layoutGridLine =3D value;=0A= }=0A= else if (name =3D=3D "layout-grid-mode") {=0A= e.style.layoutGridMode =3D value;=0A= }=0A= else if (name 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quoted-printable Content-Location: http://www.neurology.org/javascript/entrez/callback.js /************************************************************************= *****=0A= * javascript/entrez/callback.js=0A= *=0A= * Entrez Linking callback to populate content box.=0A= *=0A= * Copyright 2006 Board of Trustees of the Leland Stanford Junior = University.=0A= = *************************************************************************= ***/=0A= =0A= /*=0A= * Execute callback to fill content box with Entrez Linking information.=0A= */=0A= function entrez_callback(pmid, callback_url) {=0A= /*=0A= * MSIE 5.5 and below have issues with the JavaScript=0A= * used for Entrez Linking. 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