From: Subject: Survival following adjuvant PCV or temozolomide for anaplastic astrocytoma -- Brandes et al. 8 (3): 253 -- Neuro-Oncology Date: Tue, 13 Nov 2007 13:23:34 +0100 MIME-Version: 1.0 Content-Type: multipart/related; type="text/html"; boundary="----=_NextPart_000_0000_01C825F8.6435E570" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.3198 This is a multi-part message in MIME format. ------=_NextPart_000_0000_01C825F8.6435E570 Content-Type: text/html; charset="Windows-1252" Content-Transfer-Encoding: quoted-printable Content-Location: http://neuro-oncology.dukejournals.org/cgi/content/full/8/3/253 Survival following adjuvant PCV or temozolomide for = anaplastic astrocytoma -- Brandes et al. 8 (3): 253 -- = Neuro-Oncology
3DHome=20 3D"Duke 3D"
3D"=20
3D" QUICK = SEARCH:   [advanced] 3D"
3D"
Author:
 Keyword(s):
Year:  Vol:  Page: 
3D"
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of=20 Contents

First published on=20 May 24, 2006
This version was = published on July=20 1, 2006
Neuro Oncol 2006 8(3):253-260; DOI:10.1215/15228517-2006-005=20
This = Article
3D"
3D"Right Abstract=20 3D"Freely
3D"Right Full=20 Text (PDF)
3D"Right All Versions of this=20 Article:
8/3/253    most=20 recent
15228517-2006-005v1=20
3D"Right Alert=20 me when this article is cited
3D"Right Alert=20 me if a correction is posted
3D"Right Citation Map
3D"
Services
3D"
3D"Right Similar=20 articles in this journal
3D"Right Similar=20 articles in PubMed
3D"Right Alert=20 me to new issues of the journal
3D"Right Download=20 to citation manager
3D"Right 3D"reprints
3D"
Citing = Articles
3D"
3D"Right Citing Articles via Google = Scholar
3D"
Google = Scholar
3D"
3D"Right Articles by Brandes, A. A. =
3D"Right Articles by Ermani, M. =
3D"Right Search for Related Content =
3D"
PubMed
3D"
3D"Right PubMed=20 Citation=20
Duke = University=20 Press

Clinical Therapy Trials=97Drug

Survival following adjuvant PCV or temozolomide for anaplastic = astrocytoma=20

Alba A. Brandes2,1,=20 Linda Nicolardi, Alicia Tosoni, Marina=20 Gardiman, Paolo Iuzzolino, Claudio = Ghimenton,=20 Michele Reni, Antonino Rotilio, Guido=20 Sotti and Mario Ermani

Departments of Medical Oncology (A.A.B., L.N., = A.T.) and=20 Radiotherapy (G.S.), Istituto Oncologico Veneto-IRCCS Padova, 35128 = Padova;=20 Departments of Pathology (M.G.), Neurosurgery (A.R.), and Neurological = Sciences=20 (M.E.), Azienda Ospedale-Universit=E0 of Padova, 35128 Padova; = Department of=20 Pathology, Azienda Ospedaliera di Belluno, 32100 Belluno (P.I.); = Department of=20 Pathology, Azienda Ospedaliera di Verona, 37100 Verona (C.G.); and = Department of=20 Oncology, Ospedale San Raffaele, 20132 Milan (M.R.); Italy

1 Address correspondence to Alba A. = Brandes, M.D.,=20 Department of Medical Oncology, Azienda Ospedale-Universit=E0, Via = Gattamelata 64,=20 35128 Padova, Italy (aa.brandes{at}yahoo.it ).


3D"   =20 Abstract
Top
3D"Abstract
Introduction
Materials and Methods
Results
Discussion
References
 
W= e=20 compared survival in patients with anaplastic astrocytoma = (AA)=20 treated with adjuvant procarbazine, lomustine, and vincristine = (PCV)=20 with survival in patients treated with temozolomide. A = retrospective=20 analysis was made of patients with newly diagnosed AA treated = with=20 adjuvant postradiotherapy chemotherapy. Outcome analysis = included=20 progression-free survival and overall survival. The following = prognostic factors were taken into account: patient age, = extent of=20 resection, performance status, presence of contrast = enhancement in=20 presurgical imaging, and type of adjuvant treatment. Among = 109 AA=20 patients, 49 were treated with PCV and 60 with temozolomide. = The=20 treatment groups were well matched for pretreatment = characteristics,=20 except for the presence of contrast enhancement. Age, extent = of=20 surgery, performance status, and presence of contrast = enhancement=20 were statistically significant prognostic factors according = to the=20 Cox model analysis of survival. Type of adjuvant chemotherapy = was not=20 a significant factor, either for progression-free survival or = for=20 overall survival. Hematological toxicity, nonhematological = toxicity=20 grades 3-4, and premature discontinuation due to toxicity = were=20 observed in 9%, 3% to 5%, and 37%, respectively, of cases in = the PCV=20 group versus 4% to 5%, 0, and 0, respectively, in the = temozolomide=20 group. Although the present study was not randomized, it was = well=20 designed, and it reports on two homogeneous and consecutive = series=20 of patients, for whom histology was verified to obtain = survival=20 data only for patients with AA following the recent WHO 2000=20 classification. Even if no survival advantage has been = demonstrated=20 for temozolomide versus PCV, we conclude that temozolomide = should=20 be preferred because of its greater tolerability.

Key Words: adjuvant chemotherapy =95 anaplastic = astrocytoma =95=20 clinical trials =95 PCV =95 temozolomide


3D"   =20 Introduction
Top
Abstract
3D"Introduction
Materials and Methods
Results
Discussion
References
 
<= B>According=20 to the 2004 report from the Central Brain Tumor Registry of = the=20 United States (CBTRUS,=20 2004), the incidence of primary brain tumors is estimated = at 14=20 per 100,000 person-years; 40% of these tumors are gliomas. = Novel=20 treatment modalities, such as concomitant radiotherapy and=20 chemotherapy, are now considered standard for glioblastomas = (Stupp=20 et al., 2005). However, as anaplastic astrocytomas = (AA)3=20 account for 8.3% of all CNS gliomas, their low incidence = makes it=20 difficult to perform phase 3 studies and establish new = standards of=20 care. Moreover, most of the studies on AA performed in the = past=20 (Levin et al., 1990,=20 2003;=20 Prados=20 et al., 1999a, b)=20 also included anaplastic oligodendrogliomas and anaplastic=20 oligoastrocytomas, which have a higher chemosensitivity and=20 better prognosis (Donahue=20 et al., 1997), and all the studies were performed before = the 2000=20 WHO classification was applied (Kleihues=20 et al., 2002), thus precluding a reliable comparison of = findings=20 from studies made before with those made after the year 2000. = We=20 report findings from the analysis of large series of patients = treated=20 with different types of adjuvant chemotherapy, for whom a = rereview=20 was made on the basis of the 2000 WHO classification to = provide data=20 indicating the more promising type of therapeutic management=20 currently available and to yield parameters for future = studies.=20


3D"   =20 Materials and Methods
Top
Abstract
Introduction
3D"Materials and = Methods
Results
Discussion
References
 
<= STRONG>Patient=20 Eligibility
To be considered eligible for the present = study,=20 patients were required to participate in the two subsequent=20 prospective trials on adjuvant treatment for AA performed in = the=20 Neuro-Oncology Unit of Padova University Hospital. As it is = difficult=20 to make a histologic diagnosis of AA, and in view of the=20 disagreement between pathologists in >30% of samples (McDonald=20 et al., 2005; See=20 and Gilbert, 2004), a central pathology rereview (M.G., = P.I., and=20 C.G.) was performed to avoid the bias of subjective = interpretation=20 and interobserver variation. The diagnosis of AA was based on = a very=20 strict application of the criteria of the WHO classification = (Kleihues=20 et al., 2002). Accordingly, all cases with the following = were=20 confirmed as AA: increased cellularity, nuclear atypia, = marked=20 mitotic activity, absence of microvascular proliferation, or=20 necrosis. The diagnosis was made on the basis of both = morphological=20 aspects and immunohistochemical staining. Microscopic = features=20 confirming a diagnosis of AA included the following: cells = with=20 irregular, angulated, dark, and hyperchromatic nuclei, often = with=20 scant and sometimes gemistocytic cytoplasm, with marked, = diffuse=20 staining that was positive for glial fibrillary acidic = protein=20 (GFAP). Marked variations were found in cellularity and = mitotic=20 activity: Lesions with low cellularity, at least one or two = mitoses,=20 or an MIB1 labeling index greater than 4% to 5%, as well as = more=20 mitotically active tumors with greater cellularity, were = included. As=20 oligodendroglioma and mixed oligoastrocytoma may exhibit = sparse GFAP=20 staining, usually because of the presence of reactive = astrocytes or=20 because of the astrocytic component of the tumor, = respectively,=20 the presence of GFAP staining does not rule out the presence = of=20 an oligodendroglioma component. Special care was therefore = taken=20 to rule out other signs, such as microgemistocytes, = gliofibrillary=20 oligodendrocytes, and protoplasmic astrocytes, all of which=20 suggest that the tumor is of oligodendroglial origin. No = widely=20 accepted histological criteria are available for establishing = the extent to which oligodendroglial elements should be = present=20 in a predominantly astrocytic lesion for it to be considered = an=20 oligoastrocytoma; an arbitrary cutoff of more than 25% of=20 oligodendroglial elements was consequently chosen for the = rereview.=20

All patients underwent surgery and external beam radiation = therapy=20 to limited fields (60 Gy/30 fractions) and adjuvant = chemotherapy.=20 Enrollment criteria were as follows: age, 18 years or older;=20 Karnofsky performance status of 3D≥=2060 = on starting=20 chemotherapy; adequate laboratory test values, with normal = liver=20 function (serum bilirubin less than 1.5-fold the upper limit = of the=20 normal range and aspartate aminotransferase or alanine=20 aminotransferase less than three times the upper limit of the = normal=20 laboratory range, alkaline phosphatase less than twofold the = upper=20 limit of the normal laboratory value, and total bilirubin=20 <1.5 mg/dl) and with blood urea nitrogen and serum = creatinine=20 less than 1.5-fold the upper limit of the normal laboratory=20 range; and normal hemogram, including absolute neutrophil = count=20 of 3D≥=201500/mm3 and platelets of 3D≥=20100,000/mm3. Patients with childbearing = potential=20 had to use effective contraception, and a normal level of = beta human=20 chorionic gonadotropin was required for fertile females. = Patients who=20 were pregnant or breast-feeding were considered ineligible, = as were=20 patients who had previously received any type of cytotoxic = therapy,=20 presented active infection or other uncontrolled diseases, = exhibited=20 psychiatric disturbances, or had a history of cancer other = than=20 resected nonmelanoma skin cancer or carcinoma in situ of the = uterine=20 cervix. If progression was found, the patient was taken off = the study=20 and the case followed for survival. Where appropriate, = patients were=20 offered alternative treatments. If no evidence of progression = was=20 observed during adjuvant chemotherapy, cases were followed = with=20 physical and neurological evaluations every three months for = one=20 year, and then every four months up to progression. = Neuroimaging=20 was performed at each of these follow-up examinations and/or=20 when symptoms or clinical deterioration indicated that it was = required. Progression was defined as an increase of 25% or = more in=20 enhancing tumor size on consecutive MRIs (from one scan to = the=20 next), or any new tumoral areas (Macdonald=20 et al., 1990).

All patients signed a form giving their fully informed consent = to=20 take part in the study, which was approved by the Institutional=20 Review Board of Padova University Hospital, Italy, and = conducted=20 according to the principles of the Declaration of Helsinki = and=20 the rules of Good Clinical Practice.

Treatment
PCV Regimen. On = treatment day=20 1, oral lomustine (1-[2-chloroethyl]-3-cyclohexyl-1-nitrosourea; = also=20 termed CCNU) was given at a dose of 110 mg/m2. On day 8=20 through day 21, oral procarbazine was given at a dose of 60=20 mg/m2 per day. On days 8 and 29, i.v. vincristine was=20 given at a dose of 1.4 mg/m2 (maximum total dose, = 2.0 mg).=20 Patients were treated every six weeks for one year. =

Dose Modifications. CCNU was delayed for one week in cases = of=20 a leukocyte level of <2.5 x = 109 per liter, polymorphonuclear leukocyte level = of=20 <1.5 x 109 per liter, = or=20 platelet level of <100 x=20 109 per liter. In cases of persistent leukopenia = at=20 <2.5 x 109 leukocytes = per liter,=20 neutropenia at <1.5 x=20 109 neutrophil cells per liter, or thrombocytopenia at = <100=20 x 109 blood = platelets per=20 liter, treatment was delayed for a further week. Treatment = was=20 restored only when leukopenia, granulocytopenia, or = thrombocytopenia=20 levels returned to normal. If a cycle was delayed for two = weeks=20 because of hematological toxicity, CCNU and procarbazine = doses were=20 reduced by 25%. CCNU and procarbazine doses were reduced by = 25% in=20 cases of grade 3 or 4 leukopenia, granulocytopenia, or=20 thrombocytopenia. In cases of allergic skin reaction due to=20 procarbazine, this drug was discontinued. The vincristine = dose was=20 reduced by 50% in cases of grade 2 neurotoxicity or stopped = in cases=20 of grade 3 or greater neurotoxicity, but was neither adjusted = nor=20 delayed in cases of neutrocytopenia or thrombocytopenia. =

Temozolomide Regimen. Temozolomide was administered for a = maximum=20 of one year or until unacceptable toxicity or tumor = progression=20 occurred. Patients received temozolomide (150 mg/m2 per = day) for five days every four weeks in the first cycle (750=20 mg/m2 per cycle). In the absence of grade 3 or 4=20 hematologic toxicity, doses for the subsequent cycle were = increased=20 to 200 mg/m2per day for 5 days (1000 = mg/m2 per=20 cycle). Repeat cycles were administered according to the = schedule=20 only if, before the first day of the next cycle, the absolute = neutrophil count was 3D≥=201500/=B5l=20 and the platelet count was 3D≥=20100,000/=B5l.

Dose Modifications. Patients were closely monitored for = toxicity=20 in all cycles. Hematological evaluation was repeated at days = 21=20 and 28, whereas biochemistry was assessed only once per cycle,=20 preferably on day 21. The subsequent cycle could be = administered=20 only if, at day 28, neutrophils were 3D≥=201500/=B5l and=20 platelets 3D≥=20100,000/=B5l;=20 otherwise, chemotherapy was postponed for one or two weeks. = In cases=20 of grade 3 or greater hematological toxicity or reversible = grade 3=20 nonhematological toxicity (except for nausea/vomiting), = temozolomide=20 was reduced by 25%. In cases in which grade 4 hematological = or grade=20 3 nonhematological toxicity reappeared notwithstanding dose=20 reductions or in cases of nonhematological grade 4 toxicity,=20 chemotherapy was interrupted.

Prophylactic antiemetics were prescribed if considered = necessary.=20 Brain edema was treated by using the lowest possible dose of=20 corticosteroids. Administration of colony-stimulating = factors,=20 allowed only for rescue from grade 4 neutropenia, was = suspended=20 as early as possible.

Off-Study Criteria
Patients were = withdrawn from=20 the study for the following reasons: (a) progressive disease, = (b)=20 unacceptable toxicity even at reduced doses of chemotherapy, = (c)=20 refusal to continue therapy, and (d) noncompliance with = protocol=20 requirements.

Statistical Analysis
Progression-free = survival=20 (PFS), PFS at six months (PFS-6), and overall survival were=20 calculated according to the Kaplan and Meier (1958)=20 method with S-PLUS software (MathSoft, Inc., Seattle, Wash.), = and=20 differences in progression and survival according to = prognostic=20 factors were evaluated with the log-rank test. Parameters = possibly=20 correlated with disease progression and survival were age, = KPS at=20 diagnosis, extent of surgery (biopsy vs. partial resection = vs. gross=20 total resection), and presence or absence of contrast = enhancement=20 before surgery.

Multivariate analysis with the Cox (1972)=20 model, used to assess truly independent prognostic factors, = was=20 performed only on variables for which P < 0.05 was = obtained=20 at univariate analysis.

PFS was evaluated from the diagnosis to progression, and = survival=20 was calculated as median survival time (MST) from the = diagnosis=20 of AA to death for any reason.


3D"   =20 Results
Top
Abstract
Introduction
Materials and Methods
3D"Results
Discussion
References
 
I= n the two=20 protocols, a total of 109 patients with AA were treated with = adjuvant=20 chemotherapy, 49 patients being treated with PCV and 60 with=20 temozolomide. The pretreatment characteristics were well = balanced=20 between treatment groups (Table=20 1), and the only statistically significant difference = found=20 between the two groups was for presence of contrast = enhancement. The=20 median follow-up of patients was 37 months.


View = this=20 table:
[in=20 this window]
[in a new window]
  		Table 1. Characteristics = of=20 patients* =

 = ;

Progression-Free Survival
The median PFS = for the=20 entire population was 36 months (95% CI, 24 months-NR [upper = limit=20 not reached]); 58% (CI, 50%-69%) of the patients were = progression=20 free at two years and 49% (CI, 40%-60%) at three years (Fig.=20 1). In the PCV group, the median PFS was 34.4 months; 58% = (CI,=20 46%-74%) and 49% (CI, 37%-66%) of patients were progression = free at=20 two and three years, respectively. In the temozolomide group, = the=20 median PFS was 36.1 months; 59% (CI, 47%-73%) and 49% (CI, = 37%-65%)=20 of patients were progression free at two and three years,=20 respectively. According to univariate analysis, the following = characteristics were significantly predictive of PFS: age = (<40,=20 40-50, and >50 years of age; P =3D 0.01), KPS = (<80 vs.=20 3D≥80;=20 P =3D 0.00001), contrast enhancement (present vs. = absent,=20 P =3D 0.02), and extent of surgery (biopsy vs. partial = vs.=20 macroscopic radical, P =3D 0.001). Findings from = multivariate=20 analysis confirmed that PFS was significantly correlated with = age (P =3D 0.01), KPS (P =3D 0.0008), and extent of = surgery=20 (P =3D 0.006), but not with contrast enhancement. Type = of=20 adjuvant chemotherapy was not found to influence PFS (Fig.=20 2). Findings from the analysis of prognostic factors are=20 presented in Table=20 2.



View = larger=20 version (6K):
[in=20 this window]
[in a new window]
  		Fig. 1. Progression-free = survival (thin=20 line) and overall survival (thick line) of the study series. =

 = ;


View = larger=20 version (6K):
[in=20 this window]
[in a new window]
  		Fig. 2. Progression-free = survival=20 according to treatment. Thick line: patients treated with = adjuvant=20 PCV; thin line: patients treated with adjuvant temozolomide. =

 = ;

View = this=20 table:
[in=20 this window]
[in a new window]
  		Table 2. Median time to=20 progression, in months, based on prognostic factors =

 = ;

Survival
Median survival has not yet = been=20 obtained; 78% (CI, 70%-86%) of patients were alive at two = years and=20 66% (CI, 57%-76%) at three years (Fig.=20 1). In the PCV group, the MST has not yet been reached, = and 83%=20 (CI, 73%-94%) and 74% (CI, 63%-88%) of patients were alive at = two and=20 three years, respectively. In the temozolomide group, the MST = has not=20 yet been attained; 75% (CI, 65%-87%) and 59% (CI, 47%-75%) of = patients were alive at two and three years, = respectively.

Univariate analysis indicated that age (<40, 40-50, and = >50=20 years of age; P =3D 0.002), KPS (<80 vs. 3D≥=2080; P =3D=20 0.0001), presence of contrast enhancement (P =3D = 0.0001), and=20 extent of surgery (biopsy vs. partial resection vs. = macroscopic=20 radical; P =3D 0.0002) were significantly correlated = to overall=20 survival. Multivariate analysis confirmed that age (P = =3D 0.03),=20 KPS (P =3D 0.0003), presence of contrast enhancement = (P =3D=20 0.004), and extent of surgery (P =3D 0.0003) were = independent=20 predictors of survival. No correlation was found between type = of=20 chemotherapy regimen administered and survival (Fig.=20 3). Findings from the analysis of prognostic factors are=20 presented in Table=20 3.



View = larger=20 version (5K):
[in=20 this window]
[in a new window]
  		Fig. 3. Survival according to = treatment.=20 Thick line: patients treated with adjuvant PCV; thin line: = patients=20 treated with adjuvant temozolomide. =

 = ;

View = this=20 table:
[in=20 this window]
[in a new window]
  		Table 3. Median survival, = in=20 months, according to prognostic factors =

 = ;

Toxicity
All toxicities were recorded = and graded=20 according to Common Terminology Criteria for Adverse Events, = version=20 3.0 (http://ctep.cancer.gov/= forms/CTCAEv3.pdf).=20

There were neither drug-related deaths nor life-threatening=20 events. A total of 161 cycles of PCV were administered = (median,=20 3 cycles; range, 1-6 cycles). The most frequent grade 3/4 = toxicity=20 was hematological, observed in 9% of the cycles. = Nonhematological=20 grade 3/4 toxicity was mainly neurological (3% of cycles) or=20 hepatic (5% of cycles). Procarbazine was withheld because of = a=20 skin allergy in three patients. Vincristine was reduced to = 50%=20 because of neurological toxicity in 15 patients (31.9%). = Procarbazine=20 and lomustine dosages were reduced by 25% in 18% of the = cycles,=20 respectively. Adjuvant chemotherapy was interrupted for = prolonged=20 hematological and nonhematological toxicity in 37% of the=20 patients.

A total of 642 cycles of temozolomide were administered (median, = 10 cycles; range, 3-12 cycles). The toxicity was mainly=20 hematological, with grade 3/4 leukopenia reported in 4% = cycles and=20 thrombocytopenia grade 3/4 in 5% of cycles. Twenty-two cycles = (3.4%)=20 were reduced consequent to hematological toxicity. No = patients=20 interrupted adjuvant chemotherapy because of toxicity. =


3D"   =20 Discussion
Top
Abstract
Introduction
Materials and Methods
Results
3D"Discussion
References
 
R= andomized,=20 controlled trials and meta-analyses have demonstrated that=20 chemotherapy is of value in the management of patients with = malignant=20 glioma (Fine=20 et al., 1993; Stewart,=20 2002; Stupp=20 et al., 2005). However, evidence for the subgroup of = patients=20 with AA is weak. Adjuvant PCV after radiation and surgery has = been=20 widely used in the treatment of AA (Levin et al., 1990,=20 2003;=20 Prados=20 et al., 1999a, b),=20 although no randomized trial on a large number of patients = has=20 demonstrated the advantage of PCV over single-agent BCNU in = patients=20 with anaplastic gliomas. In 1999, a retrospective study (Prados=20 et al., 1999a), comparing (1) data from 257 AA patients = (11% with=20 an oligodendroglial component) from three Radiation Therapy = Oncology=20 Group (RTOG) studies who had been treated with BCNU adjuvant = to=20 radiotherapy with (2) data from 175 AA patients (23% with an=20 oligodendroglial component) from the RTOG 9404 study who had = been=20 treated with adjuvant PCV, found that survival outcomes in = the two=20 treatment arms were similar. In recent years, temozolomide = has been=20 used as standard therapy for patients with recurrent = anaplastic=20 glioma because temozolomide has a better toxicity profile and = is=20 considered comparable to the nitrosourea regimen (Dinnes=20 et al., 2002; Yung=20 et al., 1999). In 1998, the RTOG started a randomized trial=20 comparing temozolomide with BCNU in an adjuvant setting, but=20 the study is still ongoing (protocol 9813 [http://www.rtog.org/]).

In view of the paucity of data on patients with this rare = disease,=20 the main aim of the present study was to determine whether=20 temozolomide has advantages over PCV in this subset of = patients.=20 Although the study was not randomized, it was made on two=20 consecutive cohorts of patients that were homogeneous for = histology,=20 prognostic characteristics, and radiotherapy. Ideally, = decisions=20 regarding adjuvant chemotherapy should be based on findings = made in=20 well-designed, appropriately sized, prospective phase 3 = studies.=20 However, it may prove difficult to accrue patients for this = type of=20 study because of physician or patient bias, temozolomide = being=20 preferred because of its greater tolerability. Although the = present=20 study was not randomized, it was well designed, and it = reports=20 on two homogeneous and consecutive series of patients in whom = histology was verified to obtain survival data only for = patients=20 with AA according to the recent WHO 2000 classification; it = may=20 therefore be a useful basis for future studies on this = disease. The=20 process of diagnosing and grading gliomas is difficult and=20 somewhat subjective; to avoid any bias from subjective=20 interpretation, we performed a centralized review. Despite = our strict=20 application of histologic criteria proposed in the 2000 WHO=20 classification, we cannot rule out that patients who, = elsewhere,=20 might have been classified as having low-grade astrocytoma,=20 oligoastrocytoma, or glioblastoma may have been included in = the=20 present series. In general, diagnostic reliability is further = decreased in cases for which histologic material is limited, = because=20 AA frequently evolves from a less malignant precursor lesion = and may=20 transform into glioblastoma. Accordingly, areas with = different tumor=20 grade may coexist in the same mass, thus increasing the risk = of=20 sampling errors.

The favorable survival figures observed in our series may raise=20 the question of whether patients with low-grade tumors were=20 also included. It should therefore be emphasized that = survival=20 reported in the present study is only slightly better than = survival=20 reported in other recent studies in the literature (See=20 and Gilbert, 2004), and that most patients in our series = were in=20 recursive partitioning analysis class I or II, with an = estimated=20 median survival of almost five years and three years, = respectively=20 (Curran=20 et al., 1993). On the other hand, the use of the 2000 WHO = classification (Kleihues=20 et al., 2002), which allowed the identification of the = presence=20 of microvascular proliferation without necrosis as an = adequate=20 criterion for upgrading a grade III astrocytoma to grade IV=20 (glioblastoma multiforme), makes any comparison with = historical=20 controls (Curran=20 et al., 1993) particularly troublesome. Therefore, an = apparent=20 improvement in survival figures of patients with AA diagnosed = according to the 2000 WHO classification criteria may result = from a=20 differently defined population rather than from misdiagnosis, = and=20 this should be taken into account when assessing the activity = of=20 novel chemotherapy regimens.

In the present study, a large percentage (58%) of non-enhancing=20 tumors was observed. AA has been considered a typically = enhancing=20 tumor (Buckner,=20 2003), and the presence of contrast enhancement in our = study was=20 less frequent than in studies of patients with AA classified = before=20 2000. The degree of enhancement, which is correlated with the = biological and clinical behavior of the tumor, increases=20 proportionally with the degree of anaplasia. Again, this = difference=20 may reflect disagreement between neuropathologists and the = limited=20 reproducibility of neuropathological criteria for accurately=20 classifying gliomas. In fact, the cellularity and mitotic = activity of=20 AA varied considerably in our series. Furthermore, the = upgrading of=20 diagnosis to glioblastoma for patients with microvascular=20 proliferation, according to 2000 WHO classification criteria, = excludes a group of patients with a more aggressive tumor = that=20 typically presents contrast enhancement.

The presence of contrast enhancement was significantly greater = in=20 the temozolomide-treated group than in the PCV-treated group = (53% vs.=20 29%; P =3D 0.01). This difference may have masked an = advantage=20 of temozolomide treatment because the presence of = enhancement,=20 considered the expression of a greater aggressiveness, can = influence=20 survival. In patients without enhancement, median survival = has not=20 yet been reached, whereas in patients with enhancement, the = median=20 survival was 30.5 months. However, it is unlikely that the = presence=20 of enhancement could have masked an advantage of temozolomide = over=20 PCV because MST was 31 months in the 32 temozolomide-treated = patients=20 with enhancement and 30 months in the 14 PCV-treated patients = with=20 enhancement, no significant difference being found between = the groups=20 for this parameter.

Age and performance status were confirmed as highly significant=20 prognostic factors, in agreement with other reports (Buckner,=20 2003). Extent of resection is still a widely debated = issue. On=20 analyzing the outcomes of a mixed group of 85 patients with=20 anaplastic glioma (66 AA and 19 anaplastic oligoastrocytoma) = treated=20 between 1993 and 1999, Tortosa et al. (2003)=20 found no significant difference between the survival of = patients who=20 underwent gross complete resection and that of patients who = underwent=20 partial resection or biopsy. A recent interim report (Laws=20 et al., 2003) on a series of 147 patients with grade III = gliomas=20 showed that patients who underwent resection had a consistent = survival advantage with respect to patients that received = biopsy only=20 (MST, 87 weeks vs. 52 weeks). In another series consisting of = a=20 more homogeneous group of 78 AA patients treated between 1993 = and 2000, Cohen et al. (2002)=20 found that extent of tumor resection, based on T2 volume, was = an=20 independent predictor of increased survival. Our findings = confirm=20 that extent of surgery has a statistically significant impact = on both=20 PFS and overall survival. High-grade gliomas can present as = mixed=20 grade III and IV tumors, and the risk of identifying a mass = as AA=20 when it also contains areas of glioblastoma is inversely = correlated=20 with the amount of histologic material available. A diagnosis = based=20 on biopsy or on partial removal is thus less reliable than a=20 diagnosis based on an entire surgical specimen. In our = series,=20 biopsies or partial removals were more frequent in the=20 temozolomide-treated group than in the PCV-treated group, = suggesting=20 that the effect of temozolomide may have been masked by a = higher rate=20 of misdiagnosed glioblastoma multiforme. However, we consider = this=20 unlikely, because the difference between the two groups was = slight=20 (biopsy and partial removal, 63% vs. 55%) and was not=20 statistically significant (P =3D 0.38), and it may = simply have=20 been related to a less subjective evaluation of the extent of = removal=20 in the recently treated group of patients (e.g., more = frequent=20 use of postoperative neuroimaging to assess residual = disease).=20 In our study, no significant difference was observed either = in=20 terms of progression or in terms of survival between PCV and=20 temozolomide treatment. However, temozolomide should now = always be=20 considered first-line therapy for this disease in view of=20 temozolomide's greater tolerability. In fact, in our series, = grade=20 3/4 hematological toxicity was 9%, and discontinuation of = treatment=20 was due to failure to return to hematological normal levels, = which=20 occurred in 37% in the PCV group, whereas these rates were 4% = to 5%=20 (hematological toxicity) and 0 (premature discontinuation) in = the=20 temozolomide group. The two-year survival rate of 78% to 83% = observed=20 in the present trial is higher than the 25% to 31% previously = reported for patients with AA undergoing radiotherapy alone = (MRC,=20 2001). Although the aforementioned considerations = concerning=20 changes in the WHO classification and selection bias could in = part=20 explain this large difference, in the absence of large = randomized=20 trials addressing this issue, our data seem to further = support the=20 addition of chemotherapy to radiotherapy as first-line = treatment for=20 patients with anaplastic astrocytoma.

Although our understanding of anaplastic astrocytoma has greatly = improved, the prognosis for patients with the disease is = still=20 poor, and there is a need for large, cooperative, and = randomized=20 trials using concomitant treatment and/or new schedules. = Ideally,=20 uncertainties concerning histological classification will be=20 overcome by a classification based on genetic profile (such = as=20 1p/19q loss) predicting the prognosis and the chemoradiosensitivity = of the tumors, thus allowing better tailoring of treatment = choices.=20


3D"   =20 Acknowledgments
 
The = authors are=20 grateful to Gruppo Italiano Cooperativo di Neuro-Oncologia = for its=20 support and to Dr. Valeria Blatt for her help in manuscript=20 preparation.


3D"   =20 Footnotes
 
2 Alba A. Brandes has a = management/advisory=20 relationship with Schering Plough.

3 Abbreviations used are as = follows:=20 AA, anaplastic astrocytoma; CCNU,=20 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (lomustine); = MST, median=20 survival time; PCV, procarbazine, CCNU, and vincristine; = GFAP, glial=20 fibrillary acidic protein; MST, median survival time; PFS,=20 progression-free survival; PFS-6, progression-free survival = at six=20 months; RTOG, Radiation Therapy Oncology Group.

Received for publication November 2, 2005. Accepted for publication = March 13,=20 2006.


3D"   =20 References
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
3D"References
&nb= sp;

Buckner, J.C. (2003) Factors influencing survival in high-grade = gliomas.=20 Semin. Oncol. 30, 10-14.[Medline]

CBTRUS, Central Brain Tumor Registry of the United States (2004)=20 Primary Brain Tumors in the United States: Statistical Report, = 1997-2001. Available at http://www.cbtrus= .org/2004-2005/2004-2005.html.

Cohen, Z.R., Suki, D., Shi, W., Weinberg, J.S., DeMonte, F., = McCutcheon,=20 I.E., Hassenbusch, S.J., Gokaslan, Z.L., Rhines, L.D., Sawaya, R., and = Lang,=20 F.F. (2002) Surgical resection of anaplastic astrocytoma: Prognostic = factors and=20 outcome. Neuro-Oncology 4, 367 (abstract 216).

Cox, D. (1972) Regression models and life-tables. J. R. Stat. Soc. = B=20 34, 187-220.

Curran, W.J., Jr., Scott, C.B., Horton, J., Nelson, J.S., Weinstein, = A.S.,=20 Fischbach, A.J., Chang, C.H., Rotman, M., Asbell, S.O., Krisch, R.E., = and=20 Nelson, D.F. (1993) Recursive partitioning analysis of prognostic = factors in=20 three Radiation Therapy Oncology Group malignant glioma trials. J. = Natl.=20 Cancer Inst. 85, 704-710.[Abstract/Free Full Text]

Dinnes, J., Cave, C., Huang, S., and Milne, R. (2002) A rapid and = systematic=20 review of the effectiveness of temozolomide for the treatment of = recurrent=20 malignant glioma. Br. J. Cancer 86, 501-505.[CrossRef][ISI][Medline]

Donahue, B., Scott, C.B., Nelson, J.S., Rotman, M., Murray, K.J., = Nelson,=20 D.F., Banker, F.L., Earle, J.D., Fischbach, J.A., Asbell, S.O., Gaspar, = L.E.,=20 Markoe, A.M., and Curran, W. (1997) Influence of an oligodendroglial = component=20 on the survival of patients with anaplastic astrocytomas: A report of = Radiation=20 Therapy Oncology Group 83-02. Int. J. Radiat. Oncol. Biol. Phys.=20 38, 911-914.[CrossRef][ISI][Medline]

Fine, H.A., Dear, K.B., Loeffler, J.S., Black, P.M., and Canellos, = G.P.=20 (1993) Meta-analysis of radiation therapy with and without adjuvant = chemotherapy=20 for malignant gliomas in adults. Cancer 71, 2585-2597.3.0.CO;2-S&a= mp;link_type=3DDOI">[CrossRef][ISI][Medline]

Kaplan, E., and Meier, P. (1958) Nonparametric estimation for = incomplete=20 observations. J. Am. Stat. Assoc. 53, 457-481.[CrossRef][ISI]

Kleihues, P., Louis, D.N., Scheithauer, B.W., Rorke, L.B., = Reifenberger, G.,=20 Burger, P.C., and Cavenee, W.K. (2002) The WHO classification of tumors = of the=20 nervous system. J. Neuropathol. Exp. Neurol. 61, = 215-225.[ISI][Medline]

Laws, E.R., Parney, I.F., Huang, W., Anderson, F., Morris, A.M., = Asher, A.,=20 Lillehei, K.O., Bernstein, M., Brem, H., Sloan, A., Berger, M.S., and = Chang, S.=20 (2003) Survival following surgery and prognostic factors for recently = diagnosed=20 malignant glioma: Data from the Glioma Outcomes Project. J. = Neurosurg.=20 99, 467-473.[ISI][Medline]

Levin, V.A., Silver, P., Hannigan, J., Wara, W.M., Gutin, P.H., = Davis, R.L.,=20 and Wilson, C.B. (1990) Superiority of post-radiotherapy adjuvant = chemotherapy=20 with CCNU, procarbazine, and vincristine (PCV) over BCNU for anaplastic = gliomas:=20 NCOG 6G61 final report. Int. J. Radiat. Oncol. Biol. Phys. = 18,=20 321-324.[ISI][Medline]

Levin, V.A., Hess, K.R., Choucair, A., Flynn, P.J., Jaeckle, K.A., = Kyritsis,=20 A.P., Yung, W.K., Prados, M.D., Bruner, J.M., Ictech, S., Gleason, M.J., = and=20 Kim, H.W. (2003) Phase III randomized study of postradiotherapy = chemotherapy=20 with combination alpha-difluoromethylornithine-PCV versus PCV for = anaplastic=20 gliomas. Clin. Cancer Res. 9, 981-990.[Abstract/Free Full Text]

Macdonald, D.R., Cascino, T.L., Schold, S.C., Jr., and Cairncross, = J.G.=20 (1990) Response criteria for phase II studies of supratentorial = malignant=20 glioma. J. Clin. Oncol. 8, 1277-1280.[Abstract]

McDonald, J.M., See, S.J., Tremont, I.W., Colman, H., Gilbert, M.R., = Groves,=20 M., Burger, P.C., Louis, D.N., Giannini, C., Fuller, G., Passe, S., = Blair, H.,=20 Jenkins, R.B., Yang, H., Ledoux, A., Aaron, J., Tipnis, U., Zhang, W., = Hess, K.,=20 and Aldape, K. (2005) The prognostic impact of histology and 1p/19q = status in=20 anaplastic oligodendroglial tumors. Cancer 104, = 1468-1477.[CrossRef][ISI][Medline]

MRC, Medical Research Council (2001) Randomized trial of = procarbazine,=20 lomustine, and vincristine in the adjuvant treatment of high-grade = astrocytoma:=20 A Medical Research Council trial. J. Clin. Oncol. 19, = 509-518.[Abstract/Free Full Text]

Prados, M.D., Scott, C., Curran, W.J., Jr., Nelson, D.F., Leibel, S., = and=20 Kramer, S. (1999a) Procarbazine, lomustine, and vincristine (PCV) = chemotherapy=20 for anaplastic astrocytoma: A retrospective review of Radiation Therapy = Oncology=20 Group protocols comparing survival with carmustine or PCV adjuvant = chemotherapy.=20 J. Clin. Oncol. 17, 3389-3395.[Abstract/Free Full Text]

Prados, M.D., Scott, C., Sandler, H., Buckner, J.C., Phillips, T., = Schultz,=20 C., Urtasun, R., Davis, R., Gutin, P., Cascino, T.L., Greenberg, H.S., = and=20 Curran, W.J., Jr. (1999b) A phase 3 randomized study of radiotherapy = plus=20 procarbazine, CCNU, and vincristine (PCV) with or without BUdR for the = treatment=20 of anaplastic astrocytoma: A preliminary report of RTOG 9404. Int. J. = Radiat.=20 Oncol. Biol. Phys. 45, 1109-1115.[CrossRef][Medline]

See, S.J., and Gilbert, M.R. (2004) Anaplastic astrocytoma: = Diagnosis,=20 prognosis, and management. Semin. Oncol. 31, 618-634.[Medline]

Stewart, L.A. (2002) Chemotherapy in adult high-grade glioma: A = systematic=20 review and meta-analysis of individual patient data from 12 randomised = trials.=20 Lancet 359, 1011-1018.[CrossRef][ISI][Medline]

Stupp, R., Mason, W.P., van den Bent, M.J., Weller, M., Fisher, B., = Taphoorn,=20 M.J., Belanger, K., Brandes, A.A., Marosi, C., Bogdahn, U., Curschmann, = J.,=20 Janzer, R.C., Ludwin, S.K., Gorlia, T., Allgeier, A., Lacombe, D., = Cairncross,=20 J.G., Eisenhauer, E., and Mirimanoff, R.O. (2005) Radiotherapy plus = concomitant=20 and adjuvant temozolomide for glioblastoma. N. Engl. J. Med. = 352,=20 987-996.[Abstract/Free Full Text]

Tortosa, A., Vinolas, N., Villa, S., Verger, E., Gil, J.M., Brell, = M., Caral,=20 L., Pujol, T., Acebes, J.J., Ribalta, T., Ferrer, I., and Graus, F. = (2003)=20 Prognostic implication of clinical, radiologic, and pathologic features = in=20 patients with anaplastic gliomas. Cancer 97, = 1063-1071.[CrossRef][Medline]

Yung, W.K., Prados, M.D., Yaya-Tur, R., Rosenfeld, S.S., Brada, M., = Friedman,=20 H.S., Albright, R., Olson, J., Chang, S.M., O'Neill, A.M., Friedman, = A.H.,=20 Bruner, J., Yue, N., Dugan, M., Zaknoen, S., and Levin, V.A. (1999) = Multicenter=20 phase II trial of temozolomide in patients with anaplastic astrocytoma = or=20 anaplastic oligoastrocytoma at first relapse. Temodal Brain Tumor Group = (erratum=20 in J. Clin. Oncol. [1999] 17, 3693).[Free Full Text]J.=20 Clin. Oncol. 17, 2762-2771.




This = Article
3D"
3D"Right Abstract=20 3D"Freely
3D"Right Full=20 Text (PDF)
3D"Right All Versions of this=20 Article:
8/3/253    most=20 recent
15228517-2006-005v1=20
3D"Right Alert=20 me when this article is cited
3D"Right Alert=20 me if a correction is posted
3D"Right Citation Map
3D"
Services
3D"
3D"Right Similar=20 articles in this journal
3D"Right Similar=20 articles in PubMed
3D"Right Alert=20 me to new issues of the journal
3D"Right Download=20 to citation manager
3D"Right 3D"reprints
3D"
Citing = Articles
3D"
3D"Right Citing Articles via Google = Scholar
3D"
Google = Scholar
3D"
3D"Right Articles by Brandes, A. A. =
3D"Right Articles by Ermani, M. =
3D"Right Search for Related Content =
3D"
PubMed
3D"
3D"Right PubMed=20 Citation=20

  Home | Help | Feedback | Subscriptions | Archive | Search | Table of=20 Contents

------=_NextPart_000_0000_01C825F8.6435E570 Content-Type: image/gif Content-Transfer-Encoding: base64 Content-Location: http://neuro-oncology.dukejournals.org/icons/banner/title.gif R0lGODlhDASNAKIHAGxsUbm5i5iYcjg4KhAQDKamfAAAAMzMmSH5BAEAAAcALAAAAAAMBI0AAAP/ eLrc/jDKSau9OOvNu/9gKI5kaZ5oqq5s675wLM90bd94ru987//AoHBILBqPyKRyyWw6n9CodEqt Wq/YrHbL7Xq/4LB4TC6bz+i0es1uu9/wuHxOr9vv+Lx+z+/7/4CBgoOEhYaHiImKi4yNjo+QkZKT lJWWl5iZmpucnZ6foKGio6SlpqeoqaqrrK2ur7CxsrOQBQIFhra4oLYBUrq1t1G9tCcCx8jJysvM zc7LxR0FAAADBAbY2dkEA9S7dNPV19ra3N6R4dbk2gPdAkPp4+sG5gDfffHz2PX3PQHU6uZx69ZP j76DBnx1EIBwnoaGECNKNPBwYrYOFi9WzBhx/+C5H/8CZjSnkE1IeRZJruBYcgNDiytOcjTQreUN mRxVppg5BOfImjqmoZTI7V2JADMHhBgw06YFjgA8vJy4cabVg1WpcuCZ9WpEoDkCiPTKzSkZsUOt lt2ZMerCjCnQet03wCwMuXPp1UXBFeTYq2trAEibE4BdDkxHhiDcUOkGjo45TJXYNe/VyhAxcnxs 2SLYGWI7k9tbJrTobKRLQJYK14Tp04ZBJz5N87Dm1v5mn079QgBjtW5DAJhpVNrM4BlmFrwwOSJm 2pSTb946XTp0iARixxh+PRtyMNy7G/geQvlbmCXCQydQ3IX66+Q/9N3xHnp8FK9pE1i+4ffByP8c 1IfdbRbdV0FzmVknnlYYzKcggw0u2BB7L+QnHm9cWNgdhvJBdR6EIGhonwsiQschgSDepNuFtong m4QGYrBiRx/MCBGADxL1YXQRSsjjBQ72iF6OPq5zYgkF+Kcff1YkWeQ+TD6HEAE7OueikqIdOYKT T+4nQpA1cFmklykIeB2OLpnHAVIctUdkRG4yhxuQTyYoZIp0zplnnQJFCYKZMHIB6IIx3jlRnBYg 2JAIg57ZogeNdlfoU9XdECl8KFyaJQhYrjNpBJqW44FVaCaqZwV8Lvqmqpydimqq+pBpgqJPIjoF rUXaumpjkrmqAa4LlhoCsBLquieeMhC7oLH/AcIq7AWhbtOBjQ19GsFVjz6gLDlSptqtPij+eCys 5fi5gZiwyloFuqmqS11TaQ4pTadnmsAun+5+69AN99aZrwcFkDsewGpmwGZG5kpwlbUNbKuNvk9C zO278o4rMDZablBinRkzsfGTHVOwcLzIXvCxjwxXcLKPIStcqWwXY5ytyvRex+wENXu3QbT7dJgU yeK+GrNGhlrZasWUDs0OCTxLakXTmI5KKtBGNxszATNXAPWI4VY9w9a0pSwBtV1m7UDTz47todRW Jdywry4rTdGuWFFcctxyY3OzBQHn7bYRfcv99wNeDa6Aw0SfK3faGASutOEMgPmC40ND7gDi/xd2 cLBFZiuQMzadO+CV2AdgPnfRAkv8sN1BC503PSKQ7SwVsqfK+ASj/wp3BbXXuTcFvXPctZ0zBA8y CMYXO+3acmZ0u8iA6Y409HKrnjjd4Fr/JOmXv663FKb7+Dvh0WdgepUxPz9B+MofffcK7C/L2uId oJ1B09w3MNf4h+8OwevaO10A3Zc3KtXIezSRQvKOx7qM8K90/lPb6x7ogAUWSX2iexkMLMgyD3BQ PBRUwOYmYrbPJQQEc8Fg/6aHu7wNsIHEs9iN2kHDdpgQISFcwAjVQsMbriN0PtjhTAbyF6sA8QAp NF8EISDEnNAwLyp0QBN/YkPLAFFyLJhiSv96aMU15WUgPlwaYphHAS3qI4r/m4vZzoe9edTwjXCM oxzb8UICei1pLFyAAKqRxPoBBgCI2mMY88cDsGUnkIMZmR0zssYlPsCQgGxASLxyxANAEpGDXCSr tvNHTCpSA2D7zOE+mI0j2s8C+CvPXFLGRtRt0gZYpF4e8fY+HZISdMtLSotWdkYokLJjvHQjDAuE gVZm4Je2ARshkTmBYBpJkwihATMl4MzRjPE4EigAKfMXABNewIJYU6VXVGhMPNbSBbFsoSP1p0EJ JBKbGpuaBUhZybDIk3dGhKZEyLlOBpjxP1q7p8EEOgF61vEuBJUgSzTwT31MqpqoyaVF9tb/UGuK k5LNOyc7+6mCdNKydbLUqB4TaqqcZOCGOdQB+wx4AZTqUyJZK2dJFYPKIfbKpBhwaRvXMYOVnpQ4 0qMpBSgn0u45L6AO/FJeGCbTkIJUBh69VjudekcKQI2l94MntLS6BKiJzasvjQhTOaoAsLa0YBgw 61bJaM6nqkCtNWUrUtuy1qRy4HNYjQA4R2CZvEqgqeqcJQyimkayInGq1LwhEDno1wqYEI08YGx/ VhPAdTQWAoAtKE7rSkwNSFYDjz3oCz7706Mec7Mq4+pp7SqBz0G2sPubqVthW9SOIpaqMWxrVa0K VM9SdrWecQIHITvcsMJJtrvVrGlNptp5//5WRs/VbW5bUFzfLveb0QVedi9AVIgUKnyWo+1V1JdZ qRr2BIQln2HTy4Duete45OAe1JzQ3LkKVrwk1dZ65ard68qwWjtjrwIErFS6gpLA9XXnds+akgnw 7LLDXCgFyovf6c6AwAvAMIYPYELu9VaJtyXCh4up4c5ki8IVbggFT7lTcoSQfaJFZ5uoNlv1TnSg Qg0wwlpr4AIv9UBk3bAJhFzi81a3xdp4sZBzMOKM3tfGqwTykzPIWifXdsAzDuqUIxdivmQZxEH+ MoO3/ICKasNAZi4lCTY14TCfd8hdNi+ZMxznRy44sBOxnHtfmQS0crfIUJTylQ+7YzDPGf/Lhc7A nqOJ5OvJONGNQzBHIMfBAzYYAjx7rZzz8igUU/nQXn4zoAdtyVHXeNOnDgKR67zRLq5vv4aFcYz/ y2hX1nqwrP70lTHctJSWmpEQsCAhU5xgBni61aSGs6hzTefzyrrR2Bgen5GwalhbZlLHRnaqdb1t Li/bzaBGIbO9fWhei5mh/E0zLtcsGgiPtNzjDnW4CQ3qDT/b1nWD7+qYUO16t7vN/j6vqZOL22nj udt8jTei4W3YXlt6IqXKtLI7w6xsN3veqlE4vQdt74Fb2HXJZrLGPX6Vilub1CS/NbQFKF2Dr2Tk 48Zw+Hz9a85VsMcJZ3MELL7wkLP72wH/D7e6oz3rlqu8zzA/eaD/qnSCf9TpxM530Z/+cdsCfdfx nvkHhk6ez9Uz6vDaObh9nvN5p1zqK9e3o2mNdqRfHeE9dzVmm151qrvc7kdne/bwvXdcvx3q3Aa8 UW/88H2+LbgT70yMeL5xuMs72Wfve9qnXvC8H6HfHA8b04OO8nhjHu5LlrblQQ76rJ+bxhBpCc9o DvY7Q5DhGP+52T2v8EW3nfSCh7Ljd/D53JO7M2ljfON9/3vH977uuie+jyEf83jbfh6s5zDOc+Zu tp3mMIwPfdmZT/e7b777o6/87S+fdM6bWOzmV37c1X987ycf+egtP9YFXmWJGl4Bz7do/+IVj/75 x377uzd88Bd4Azh46VeABOh+QtB+4Ydq19Z/xqdwkbcvakd0fEeBfjd7Y7d71NCBHviBHvh1KzQk q/d4nQFh2adxGfd3CHhxpHZveoeBk8dv8heB+gGB7KdwILiDIFiBLHeBPDWDGch9sEd2MfA5RrFA 1Wd9p2ErKfhmK6iBB6iAdpZjMRiEPkhfNZiD0OGE4Dd+OsCAYOiALbh8AShpUPg1R6Vuw3ZwwDd3 RRiAUUiEmXdeLAaEE5OFTSCGkmd04wSHdfh/VieF/meElOeGZah9MZB/osIz4YV752eAyqeIF0WH NhhuR4aH+3aIQ8CHMuiHGCWJZSiAVP9IA56IhVeYh0N4hs2XhsXjQAukaZB4EDUTH08oiJXIil/Y h6A4Dx62haPIe8BYisU3IRNhi7v4iTxwiqrYi6j4Asy4ic7YjEXAM+8kEW2IiAcRKqVyi4YobixI jC7oeOwTQtG4duQXjg3YemcGcfo1hesIS8MYj9qmfuBIiKXnijIwdMDGFodSM07hjXIoe5bIhaD2 QZZzjha4BAr5g7OoDy8CU6IojusXjI+Gj5OogqI3htpIj8VokTZwSzfycoeSPOQhkPa4fyk5gc+Y Wqiliej4kBzZifM4k+93EAJgkhPpkR9Jkau4kq2Ii0I4lDLJi0QANu81iHCCOH6Fkh3/dI8FOYoE 9kGv1ZBaqI42mYAQyZQ7mZX1CJIsYJVE2QJiCZMLeQT8KJFKCRHvUDNu4pQSIovjCJTJ2JLKxV9F qYzTKI1uh5FSeWNueXiB+I3xh5VGiXdeSZC6GIcpeQMiCVAkKRHvwI2CmY98IpcV6ZOZyZNzWYAQ pQ1HVJYMWZOHiZjrMJnuaGx1SY3LSJp6aZqvuZZ0yZhgKRhRI5s4dACMSA8tAZfBkouzOZin9g9h pGmiqQTHuZcG8A67GU7vJpyNGZauaZcdmZgAGJyWSZhHeIPSeSgKoJPPmZ0M5DN+6ZNgEgDIwEdR FmHW2ZOc2QPJmZdJ9p3HqJrw2J4//2mRaCiUZumQynmW8smaRvCYz9SdkllWqTmC4nlBwKmftIdA zqmHEjqahhmbZIiTCHp/CmqQ2jmHi1mIA8mepVmdI3qT77kD8YOhBnpcB5BmJeGbmQOVH3qJrzNs 8ZmO5XmiduWi4cmhIYqbmkmK70mJY/mf/gmb1GkEYWRZF8miBwCerweiDCqj2OmjShOhE1qkRnCj JOpiCwClwkekhZmj7SmmqciXZxqTF3qi9CEa2aicxREqLAWjG9KgQcqSfEJzXFoEe7qm0LcActqj f6mP/kimJaqV+EmlDrqB0ckvovGIjVYcaWYUdFovinqnD5o3mNmnNFmhSYqk2SCphP8XphoZmVFJ kWZqpBt5qF8ZpDqwpNLSpGzJAMnjGJVqInbKpkKKn96DpSJqoaCKpjh6qjpKePR5f6RKqCZYpYlY qlnan7OWorrqYA8oqypmnx3hC7dKG5i5q6xqorxaQJDamZiqrBc2nQLapfMpqLSorasprGGIrvDq p9+qmMyKqu0krYlaRnK3orPKALUYpQv6lORJrOF6peNKrrqaqvlZrvd5mg0QsMnKnyq5qLTpqqsK rPSqsa2ad/par8CVX8uam7Tqjtu6G7m6r3gaLCKosCrrrDXAqeAKsSVreBPbofZqsVJam8+apgAq frz4sRyrY59ElsaKf5xzsjrHhDP/aqWpoh1meK/TigMyi6g0uwC7mRA3+6OFarAg661Dm7MOu7PT hpT7yq+haK0kC7DHqLRveKkLm6nOEn0d+7LmClXyqqYbu65si41b26hAGreMyrOcuLfparhoarZf C10iO7IqygBy6rY0MUeUW0NvWrV1KyEta7Vhm7mdC595+7NA66UNELnvqrc3gLkuu7hwa7cXm3eK +7lpVbRG652SVCCDi7HXqbM0+rRj6rVh+wzCO7zJMDiqu7qk60+4+7CyC42he6SIi7q/27TN6iqx +6khckO+6q/XenNEkbtTu7tj27uXOb1Sm5hTqqq/ir3sGKoPkDyf07PC6KmH277z/9q11Iuv1nsd K0CVeGu7pSsehVu7hiq7V2O+vOt76Rug9xus0su5fAu5AjzApvi8FCy2gvu6t3e99QsC5fi/BypF EwytIke/DTyzbhRH1HB6rcu6YMu+7rm0owvD9vvAnhvBOjTCJAwEx/vCHYzA45uR+wsd3Eu4kRps 3XHBgeu60Fl1rlWxQYyACzzDP1zDoquu7vu+SazEMdDDDEvFJ2zF0CvGVUgbRay7amcrHFzFMezC Hnq+ixtLe/XGCSzFBMvANgzBbNzGyRvA/MvFDZvBZBu+8ovHVxy9P7vGeby+eyy+EMlEsPq1XwzI m3mws6R1GMzE3TbFWBzGKEzDN/+cxVIUyQYMs44ryAOLxpTsw56MvHZJoM27w4H8p0hMxFraxRZM eUPXrXwMynrcypzswIfcyYtcyVfrvWa8ygQMvL5szLHMtHD8uWACy81cyEt8zJUpGsqcyS68sno7 x46syQp8x2BczK7cyM6Mw9h6GtZMtbksy85rwsW8YZN8zq0cztgcsbYMzzH7zvzsxxaRsL2Mzvac x8GMyGMszAn9yaL8AKRM0PQst/k7pKb8z+pr0eU8zCnrxhmrzhKczBiNy/Ks0Qx9v1zHzbHMXgdN xox8z+nc0GezzyGt0O1M07eMv9FczRF9tyVtzi3cxw6QtalMyBud0hINdeBc1NX/XNAkzdQ/47ML zdJHHAFC7bSa6c1N3dNZ7dTnOtJRPdAu/dJhfdOnTMsR8NDzXNHQXMfm2WVNI9Bi7dOsbNDkTMxb HcphXX8OgNZ3Hdd97ddfDdZyvZ84m9GBjddpTX88/ctyvdaPi2kgDdXx6tU1HT5vCtgdvccrrdWH Ldh/rdcA3Rk1LdUzbdOlDcSoLMThVs+YDcJOykSRfdGp68+STQF4hc9G3U+bzdh/3dpTHQFpacmd d7q9Pdd9zdqkTda83dm+jdNGDJM3Q83HrdaZPdbGzdxRxUGb28OtSdnWE93sTMlYzdzNLdvxXMA6 LYHUvdxdHcIKps3KvcwTLdyn/5ZKSk3Q5d2XzAzRRwvZ8B3f7L3KhM21AB7gp83ZZ0zUvw3c4X3g CS7Og/pkuxy1bK3g7b3fed3fZdbgDo7Yn03bhkzeBTvfkqzei+3hIu7Yj9xflrHNuL3U+R3iztWP I57T+D3Z6M3fAKxQeTHaCC7gQVnYdi3iA26PyI3cPb03HOziFB7Fbe1I9l3jFX627uzdCw4q/93h no3dIG7YF07i0hxv/PjgHN3Sy0kzol3g15zbzEvDE/7TMH7dV5njGb7jwP3QPm7gWr7lTA7k4Iuf MIjaVG7mv0PNfQ7nNz7eY0ZCiG7dSO7cTl6sdq5Xaa7mXO3nGlzmea7n5o1cBP+O0F/evQDX45Ze 1ituaE1cilFe3dmgZ49u6vPg6ke9tq/W4gGUkLPeELL+55p+64oT5GpJYuuN4qFO6zhj63sO6/ks aG3OxuGzqSw86hQr0hrO7Kl+6raN7P1JQYEe4koG7IAbQN/O62bNWUJ+6dT+2tRK6sku6NhuZeSL gCb0dU3m6eFewaAt7dde7us+Fz7I7eM97pn+zKz+PVo2yI8dVyfO5679rxVQ1WG+8CGLjUSboB3O QW1YbO8t8WTuixW/78sOARC/1BoPiM1+Zh8/1IPug/JV5EnJuBwv5w0v6o7F7rWNA5mIXf7V6Rtv 8RuQ8zOOeEwA9Pi083jMP5H//POu599CD/M+H/RP7+UyQPQsHvXHjnMuOewMn+4Ob19WcegfADWd w4+/2E/8WE+klVNLPwRpv+gaCt2z6+/WdWlO//Y6T/dqb/RD/opWaAGhNfE0Evdaj+6zHPKwLfft bgJw5fUUr8QYDyklH9N4aQSLz1uT78D8E9zmXPnUFPll3Fnm3viJD/mX//n1mVXRXsuDH+Md79E8 7vKqDAIj/zezv+k1Z/X2PiB5n+9G4FO7X+3l/ECPiXq6D/WTbu068vvHv/fJYlPK796h/xXwfu6s b6pdz/jkHucmcEMt85mwY/tVvYSd/9RFL2Ee07gNYFDfjfqXgW7k3+80jgFp/4lB6j/6moP+NWv+ f+b5/YIApst8D6OctLaLTd28ywwKnhSApjNGZ5a27jSsGSFyAiFjwwvlDY/zKWq8R0y4GAQ6gSPS sCtKpx0nUsm0CqM8JDFVeqJ4Wh+WAxBDp+XcedNUc11iKrUte1fi4rkr+ATQcaOmYDdSd9gl9JWC l7N4NTBJWWl5iWlZ4JJWOACwFBEA8CgjWJToUprh99IpRgDQ+CAAABiomDv1+hQ7e1B7i3QamfNb VahRxIvkOzG6akLMwyzkPBFcON3Sl+n9PZlS7XMtka223RINEhsKAZ1sqGvxNM/NSJ1cHM8/5BIg DBalgL3cvUjVQkAvKmHiEf8Y2M+gvYlw+j2cRPCJxHs+jqHRV6RhsovrVmxsIbIQyYxITnroxw+M RYj8XHpQ6JASTHkUe9TrycFLEZYr9u0s5LFCyaMnWnEUgupJUg9LmYJwCjRrVas6pggFUogNV092 to5lgPXlWR/q1vahQtStiawPENJVgY9M2INy86LsK8SmWiRFzKZzgROwjKl3dSVWfILxhq8vzC6Y 8hhyBsk2NK/gPMEzhoSiTYCmMK70GKB2Gx+gjHgvHdUYThuh3SAtop+uFt7Bjda1a8tjdQ82ViQz VLHA1xwiztV4UOCqmiuQzsT6D7qtG8P+o8YobtsHUtIWfJwtD/MyNk0poN3/vXC68K3Lj9pRSlwQ VOoDJ0+Bf8DdxxduLgiIG4GFaXcZd7zN910LqRVVoHUATgjZYbMRtuAwdmComIbzTQQiYCKmEKE4 4VFRolzYqQjciemV1luMigDEoDJZdXdXiiMgqN6GFkoBHUwvTsdhPs3YwYdqeowIVJOlPSmeaVIA CQlDRfJDAHr/bMkPlUKq9oKUoom5TI49PiicjyNYVqVqAB5QwH5nEaBgnHMVgeUKeR5o51h4Qula naoNaoebVPEIqGp/vhcoV4h6Rd0LhpY2qSJgHrVmkhD6paSnKDI4JzByKsKoB5EuIOMIyilWKqE8 vApYrD7lJ0WLFyhCq1yt/yZ3aqKVvtCrXLY+s+kKk1C4I5uuKZqdszOOx6Jov+4manVXKKIrU9fK mku3R33bAbQcsMfsh56RW6Nm7NJjYJrrUnTpnQGgu1pPqbIGql7ZTkubrYQARoMu+3amkSL1ypUp uI0t7FbDVJjLgVm6QLzWu5au6tCjFZJ5JccjeWwHxjshukqny41I8Qbi8vRUc8cWkGxTJH+cZUhi aEyBmcV56fBEPkcHdMyfVfvvFEMzVfBdSzOFJn60adlX1Lk8PTIExerIb9IO4ioFvvzhTO0ho7gF ij0HV/zEkSO8jEvQssLtodr9limtumdZTSLadseL9Fk8r1fzdRIRpXKQn/+CTaTXk5GqC9aeFE12 uqEGNo/kclAuN0Wa98G50ZGV5bjShSvQ9Iiftx06tlObfbrhIw4c5kYYJp7z4shRsfWulQd7cc0D 3Exp6dHWnfkAImPwUOude678TM6PyjiwKwsdfZiDX519TtMDrFnk3Y/Ed1a2jHQMjix8fX2bd4Ol OPVDCk3K8g+l3azxHYjs9j/1C4S/5z0PGvb7xPfkt5hDrIouBOxDAOXWwF4YMH+vi9z/JPhAcJGi FzKaEO5kIMAQEksAJCyhCU+IwhSqcIUpPOCPAHBB5n0CAMQToQ0tBcPxNeB+NLzhDQuQQ5bwsIY+ LCIHgBjDC0xCFi6kTxDX2TFDItqBhVSsohVLCBQk6pABQ7xhAGqxxQXcT4pGLKMZz6g6ATQRjWwU hQDI2EZwfRGOcayjG9fYuTnacY/leSMf+1hCPP5xkIQspCEPichEKnKRjGykIx8JyUhKcpKUrKQl L4nJTGpyk5zspCc/CcpQinKUpCylKU+JylSqcpWsbKUrXwnLWMpylrSspS1victc6nKXvOylL38J zGAKc5jELKYxj4nMZCpzmcxspjOfCc1oSnOa1KymNa+JzWxqc5vc7KY3vwnOcIpznOQspznPic4z JgAAOw== ------=_NextPart_000_0000_01C825F8.6435E570 Content-Type: image/gif Content-Transfer-Encoding: base64 Content-Location: http://neuro-oncology.dukejournals.org/icons/duke_logo_header.gif R0lGODlhcAAyAKIFAI6OkMPExTs5Of///wMAAAAAAAAAAAAAACH5BAEAAAUALAAAAABwADIAAAP/ SLrc/jDKSau9OOvNu/9gKI5kaZ5oqq5s675wLM90bd94ru/d4P++AKATAA4WAODwkgQyjAJM0Whc LqjAQFQz/SGVmKZXIR4EMl3swKpQ/7Rc4/fHppSPinSdksbW3XRxTmRgTHIEAodSgGsNRgF9A1sX fXM+exJ3hIFoVQCfoI5gd5gSlZuXYYdpk5RZFFVtr4uDBGWlEJqJnJ1vsIWnrrW3qk7EgkG/nHet fIrHFpqKvckTsbbXFsHQFaSFyGbKqdjfFdvldo/owtUS16S0Y+Tj0YwcfaCfD+/Z5s/rmRg10+bm jAN+ACOc49WNES5TBfcVgsfOh6VGhgA9VBjx/+DEfs6GJczFCA81KgZFLQM5YSG9huqADAxJJ5/E lSMfuMRYr4oecCkjIGRI0yIqnjCN5YSQJiiEoS+LmuSWbtQ0gr6sfZQZz+g8pFV/RNkl9qTTm+OC YZVHdYImWUSLnvUYiGy7nmy5ZpT3s+tclZcEUNzrY8vVsF7fVvz7pOTMgD4Pu/2nd60apyU3PrCr RnMDxQRYQgSE2d6GO1QeRwDd1zKW0p09RIqL2ORX21JRkhH8WoiA38CDCx8OfDYA4siD9wnOLPnw kpIEFJhOvbr169izUweivbv37+DDix9Pvrz58+jTq1/PvjoASAS2vxfiPgD1TwXe3/9kf3q+6uFC JCHfAPvh5x8A+fV3XYACTsege6BAqGABAR6hD3VnCBYfdbZQ99sZCiIimIcLKDgJhgT054B/tqSY nRUIskgGiQrch0hoNA5xoYMKRFFdhywO8eOIJOrIITYoTljjdj1qpyOQ+bUYYwFRNBglkdMRYouQ PC7w45QGTVkAImJuIR2GYyX544YkTmjdEgIoCGd1J06HkYJwVOkjj0t8uaaYthRRJJuSHMcmiGu+ ySZ2Q7j5JIHTRQHJfRrGWOhYM/IIh59trglllS5GmimFoWa5aJTdNaroGVOaiSIikEZpSwIAOw== ------=_NextPart_000_0000_01C825F8.6435E570 Content-Type: image/gif Content-Transfer-Encoding: base64 Content-Location: http://neuro-oncology.dukejournals.org/icons/spacer.gif R0lGODlhAQABAIAAAP///wAAACH5BAEAAAAALAAAAAABAAEAQAICRAEAOw== ------=_NextPart_000_0000_01C825F8.6435E570 Content-Type: image/gif Content-Transfer-Encoding: base64 Content-Location: http://neuro-oncology.dukejournals.org/icons/shared/misc/arrowTtrim.gif R0lGODlhBAAJAIABAGZmZv///yH5BAEAAAEALAAAAAAEAAkAAAIKjAMHidsLm2HHFAA7 ------=_NextPart_000_0000_01C825F8.6435E570 Content-Type: image/gif Content-Transfer-Encoding: base64 Content-Location: http://neuro-oncology.dukejournals.org/icons/shared/toc/free.gif R0lGODlhIAAHAIABANYTNP///yH5BAEAAAEALAAAAAAgAAcAQAIjjI+pqwDpTAzzVPjQ3Nl2Boah Q0pkd2YpVq1mW2IypZ5vVQAAOw== ------=_NextPart_000_0000_01C825F8.6435E570 Content-Type: image/gif Content-Transfer-Encoding: base64 Content-Location: http://neuro-oncology.dukejournals.org/icons/misc/permissions.gif R0lGODlhZQAPAMQAACkpqSAgg/Hx+YeHz8nJ6ff3/ENDs9bW7nJyxqys3Zqa1+Hh87y85Orq9/// /1tbvf7+//z8/gAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAACH5BAAA AAAALAAAAABlAA8AQAX/oOMEZGmeaKqubOu+qBgAdPMABUEDBl3shsYOICAOjgjAYTAkNgmMI3Og UzKLzsGB9jgIkgaGIOEsU8vY8HhHAhZ6B4ijoAA0mLtFHcCoPvE7WDhNhIWGh4iIbUMGCzkEDV+J k5SVlpdNizsDBUsDDAUMmKOkpZOaAj0Qe0M/NGdNCToMoktNBUcMCwAPDQYIQgOpSgwGdMAAWgAI OgRJbwxkWHdBSRAIyDhhZDSaREkPfQoGBgI3QF4FDWACAgVJCQznNII7BwUFZLC2WEXK5QJsKCkg 4AoNBPi2oKFxryAbGTAiSpxIUaKIEYQUECCQoIepjyBJBcC4Q8GbJgsUsQJxVGCBxybYmkBol48U LET1MGmKNvDGgDq9gAgpSYOAgCoRXAVaCkCBAJfLvDyQNcZoEgTcjDpr+jSJwkYC9hw4sI6GU6jd ZtCj4QAQ02RV2hU5urGIrSERNmZdsDECXIYGs2xhBqjm2kFNdfTzwY2NWgCymkLgezTZrjzchBGz bKVJTgVCjP3tvFhZAjIaH+wqV+bkgTqLVfMQ5A1BBLcPDIfczdvQyMdApPQeTvxhCAA7 ------=_NextPart_000_0000_01C825F8.6435E570 Content-Type: image/gif Content-Transfer-Encoding: base64 Content-Location: http://neuro-oncology.dukejournals.org/icons/toc/rarrow.gif R0lGODlhCgAVAPcAAP//////zP//mf//Zv//M///AP/M///MzP/Mmf/MZv/MM//MAP+Z//+ZzP+Z mf+ZZv+ZM/+ZAP9m//9mzP9mmf9mZv9mM/9mAP8z//8zzP8zmf8zZv8zM/8zAP8A//8AzP8Amf8A Zv8AM/8AAMz//8z/zMz/mcz/Zsz/M8z/AMzM/8zMzMzMmczMZszMM8zMAMyZ/8yZzMyZmcyZZsyZ M8yZAMxm/8xmzMxmmcxmZsxmM8xmAMwz/8wzzMwzmcwzZswzM8wzAMwA/8wAzMwAmcwAZswAM8wA AJn//5n/zJn/mZn/Zpn/M5n/AJnM/5nMzJnMmZnMZpnMM5nMAJmZ/5mZzJmZmZmZZpmZM5mZAJlm /5lmzJlmmZlmZplmM5lmAJkz/5kzzJkzmZkzZpkzM5kzAJkA/5kAzJkAmZkAZpkAM5kAAGb//2b/ zGb/mWb/Zmb/M2b/AGbM/2bMzGbMmWbMZmbMM2bMAGaZ/2aZzGaZmWaZZmaZM2aZAGZm/2ZmzGZm mWZmZmZmM2ZmAGYz/2YzzGYzmWYzZmYzM2YzAGYA/2YAzGYAmWYAZmYAM2YAADP//zP/zDP/mTP/ ZjP/MzP/ADPM/zPMzDPMmTPMZjPMMzPMADOZ/zOZzDOZmTOZZjOZMzOZADNm/zNmzDNmmTNmZjNm MzNmADMz/zMzzDMzmTMzZjMzMzMzADMA/zMAzDMAmTMAZjMAMzMAAAD//wD/zAD/mQD/ZgD/MwD/ AADM/wDMzADMmQDMZgDMMwDMAACZ/wCZzACZmQCZZgCZMwCZAABm/wBmzABmmQBmZgBmMwBmAAAz /wAzzAAzmQAzZgAzMwAzAAAA/wAAzAAAmQAAZgAAMwAAAPz9/fLz8GlpN2xsO3d3Snl5TH5+U39/ VIKCWPX18f///wAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAACH5BAEAAOIALAAAAAAKABUA AAhVAAEIHEiwYEFw4QwK7PYtoUFu2ho+FBTR4UBugihKvJhRo0WMHSsKBBlSIsmQ3rKd7LgN3EqK KVdqS4nt5Mxs2GqixJkTpEiOPy8GHcjQIkGECgEEBAA7 ------=_NextPart_000_0000_01C825F8.6435E570 Content-Type: image/gif Content-Transfer-Encoding: base64 Content-Location: http://neuro-oncology.dukejournals.org/icons/toc/uarrow.gif R0lGODlhCwAJAPcAAP//////zP//mf//Zv//M///AP/M///MzP/Mmf/MZv/MM//MAP+Z//+ZzP+Z mf+ZZv+ZM/+ZAP9m//9mzP9mmf9mZv9mM/9mAP8z//8zzP8zmf8zZv8zM/8zAP8A//8AzP8Amf8A Zv8AM/8AAMz//8z/zMz/mcz/Zsz/M8z/AMzM/8zMzMzMmczMZszMM8zMAMyZ/8yZzMyZmcyZZsyZ M8yZAMxm/8xmzMxmmcxmZsxmM8xmAMwz/8wzzMwzmcwzZswzM8wzAMwA/8wAzMwAmcwAZswAM8wA AJn//5n/zJn/mZn/Zpn/M5n/AJnM/5nMzJnMmZnMZpnMM5nMAJmZ/5mZzJmZmZmZZpmZM5mZAJlm /5lmzJlmmZlmZplmM5lmAJkz/5kzzJkzmZkzZpkzM5kzAJkA/5kAzJkAmZkAZpkAM5kAAGb//2b/ zGb/mWb/Zmb/M2b/AGbM/2bMzGbMmWbMZmbMM2bMAGaZ/2aZzGaZmWaZZmaZM2aZAGZm/2ZmzGZm mWZmZmZmM2ZmAGYz/2YzzGYzmWYzZmYzM2YzAGYA/2YAzGYAmWYAZmYAM2YAADP//zP/zDP/mTP/ ZjP/MzP/ADPM/zPMzDPMmTPMZjPMMzPMADOZ/zOZzDOZmTOZZjOZMzOZADNm/zNmzDNmmTNmZjNm MzNmADMz/zMzzDMzmTMzZjMzMzMzADMA/zMAzDMAmTMAZjMAMzMAAAD//wD/zAD/mQD/ZgD/MwD/ AADM/wDMzADMmQDMZgDMMwDMAACZ/wCZzACZmQCZZgCZMwCZAABm/wBmzABmmQBmZgBmMwBmAAAz /wAzzAAzmQAzZgAzMwAzAAAA/wAAzAAAmQAAZgAAMwAAAGtrOra2ntjYy+zs5f///wAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAACH5BAEAANwALAAAAAALAAkA AAgmAAEIHEiwoEGD2w4K1IYt20GGggQ5JAgxosSBFS1ezKjxokKBAQEAOw== ------=_NextPart_000_0000_01C825F8.6435E570 Content-Type: image/gif Content-Transfer-Encoding: base64 Content-Location: http://neuro-oncology.dukejournals.org/icons/toc/dot.gif R0lGODlhEQAVAPcAAP//////zP//mf//Zv//M///AP/M///MzP/Mmf/MZv/MM//MAP+Z//+ZzP+Z mf+ZZv+ZM/+ZAP9m//9mzP9mmf9mZv9mM/9mAP8z//8zzP8zmf8zZv8zM/8zAP8A//8AzP8Amf8A Zv8AM/8AAMz//8z/zMz/mcz/Zsz/M8z/AMzM/8zMzMzMmczMZszMM8zMAMyZ/8yZzMyZmcyZZsyZ M8yZAMxm/8xmzMxmmcxmZsxmM8xmAMwz/8wzzMwzmcwzZswzM8wzAMwA/8wAzMwAmcwAZswAM8wA AJn//5n/zJn/mZn/Zpn/M5n/AJnM/5nMzJnMmZnMZpnMM5nMAJmZ/5mZzJmZmZmZZpmZM5mZAJlm /5lmzJlmmZlmZplmM5lmAJkz/5kzzJkzmZkzZpkzM5kzAJkA/5kAzJkAmZkAZpkAM5kAAGb//2b/ zGb/mWb/Zmb/M2b/AGbM/2bMzGbMmWbMZmbMM2bMAGaZ/2aZzGaZmWaZZmaZM2aZAGZm/2ZmzGZm mWZmZmZmM2ZmAGYz/2YzzGYzmWYzZmYzM2YzAGYA/2YAzGYAmWYAZmYAM2YAADP//zP/zDP/mTP/ ZjP/MzP/ADPM/zPMzDPMmTPMZjPMMzPMADOZ/zOZzDOZmTOZZjOZMzOZADNm/zNmzDNmmTNmZjNm MzNmADMz/zMzzDMzmTMzZjMzMzMzADMA/zMAzDMAmTMAZjMAMzMAAAD//wD/zAD/mQD/ZgD/MwD/ AADM/wDMzADMmQDMZgDMMwDMAACZ/wCZzACZmQCZZgCZMwCZAABm/wBmzABmmQBmZgBmMwBmAAAz /wAzzAAzmQAzZgAzMwAzAAAA/wAAzAAAmQAAZgAAMwAAAISBgpORkvz7/GdnNmhoN2pqOnR0SIKC X5iYd7KynMjIt9/f1fDw7Pn598bGxWRjPW5tSHZ1U5STgre2saakoHBtbYeFhdbV1dXU1NTT07y7 u/7+/v39/fr6+vb29vT09O/v7+zs7Onp6eTk5OPj49zc3NfX1////yH5BAEAAP8ALAAAAAARABUA AAibAAEIHEiw4MB588oZXAjAXr5v5BgW3CdPkLdxEgf6yyZIUDdxGQG8w9axY7iMI0t2BKdwYUqV giAu9OfuHEyLGCeya2cT5seC9uBZ4XlTUE6B8/DJQ3eTWzhtBIN6u9mNnT56BPexu4lunT6oBGnC TGcOH9aCLwVt+xbv3jyXJNWq62fvLVyP7PjVy7ix69eQFMuezejQbUgAAQEAOw== ------=_NextPart_000_0000_01C825F8.6435E570 Content-Type: image/gif Content-Transfer-Encoding: base64 Content-Location: http://neuro-oncology.dukejournals.org/icons/toc/darrow.gif R0lGODlhCwAJAPcAAP//////zP//mf//Zv//M///AP/M///MzP/Mmf/MZv/MM//MAP+Z//+ZzP+Z mf+ZZv+ZM/+ZAP9m//9mzP9mmf9mZv9mM/9mAP8z//8zzP8zmf8zZv8zM/8zAP8A//8AzP8Amf8A Zv8AM/8AAMz//8z/zMz/mcz/Zsz/M8z/AMzM/8zMzMzMmczMZszMM8zMAMyZ/8yZzMyZmcyZZsyZ M8yZAMxm/8xmzMxmmcxmZsxmM8xmAMwz/8wzzMwzmcwzZswzM8wzAMwA/8wAzMwAmcwAZswAM8wA AJn//5n/zJn/mZn/Zpn/M5n/AJnM/5nMzJnMmZnMZpnMM5nMAJmZ/5mZzJmZmZmZZpmZM5mZAJlm /5lmzJlmmZlmZplmM5lmAJkz/5kzzJkzmZkzZpkzM5kzAJkA/5kAzJkAmZkAZpkAM5kAAGb//2b/ zGb/mWb/Zmb/M2b/AGbM/2bMzGbMmWbMZmbMM2bMAGaZ/2aZzGaZmWaZZmaZM2aZAGZm/2ZmzGZm mWZmZmZmM2ZmAGYz/2YzzGYzmWYzZmYzM2YzAGYA/2YAzGYAmWYAZmYAM2YAADP//zP/zDP/mTP/ ZjP/MzP/ADPM/zPMzDPMmTPMZjPMMzPMADOZ/zOZzDOZmTOZZjOZMzOZADNm/zNmzDNmmTNmZjNm MzNmADMz/zMzzDMzmTMzZjMzMzMzADMA/zMAzDMAmTMAZjMAMzMAAAD//wD/zAD/mQD/ZgD/MwD/ AADM/wDMzADMmQDMZgDMMwDMAACZ/wCZzACZmQCZZgCZMwCZAABm/wBmzABmmQBmZgBmMwBmAAAz /wAzzAAzmQAzZgAzMwAzAAAA/wAAzAAAmQAAZgAAMwAAAGtrOra2ntjYy+zs5f///wAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAACH5BAEAANwALAAAAAALAAkA AAgnAAEIHEiwoMGDBbVhE8SwIcNsABQ6fDhQYkOIBC1iTIhto8FtBQMCADs= ------=_NextPart_000_0000_01C825F8.6435E570 Content-Type: image/gif Content-Transfer-Encoding: base64 Content-Location: http://neuro-oncology.dukejournals.org/math/ge.gif R0lGODlhCAAKAKIAAAAAACQkJElJSW1tbZKSkra2ttvb2////yH5BAEAAAcALAAAAAAIAAoAQAMd GHXc/swMYpoho54i1hsdxBTBEIHakTpC4LrCkQAAOw== ------=_NextPart_000_0000_01C825F8.6435E570 Content-Type: image/gif Content-Transfer-Encoding: base64 Content-Location: http://neuro-oncology.dukejournals.org/content/vol8/issue3/images/small/Brandes_1.gif R0lGODdhyACWAIQeABAQECkpKSAgIEpKShgYGEFBQTk5Of///5SUlKysrDExMWJiYt7e3tXV1b29 vYuLi1paWoODg83NzbS0tFJSUu7u7nt7e6SkpObm5nNzc8XFxZycnPb29mpqagAAAAAAACwAAAAA yACWAEAF/+AhjmRpnmiqrmzrvnAszzR6SWrGidwWAZOacEgsGo+jRidyuHQczcsKg2ApCZYKcsvt emUJzevm4gQMwa96zSaSY5mhBiBt2+9DjAGiO2mbYkIOVUUcGQEPeIqLNBeBWxZGDQuUlQsCCBx/ jJxEGBoOjwwLDxUbHTgXUHcYHRudLgoMsGoSFws7KY60IwgICcDBabwiCQoXG8jKyczLzs3Qz9LR 1NPDIxYRCStvxHYOq96KEwiPSkwNEDuq4u3EFYRIFxR9KWHu+PlCGxSRKt36Agp0g2OgwYMxACJc eHDUg1mZojCcSHHErooYDypJJCMDqAwYYHC4EMHBAhkTHv+Q3OTigscF22A8QOCgQzwXDCxIQPAK xoYFGjo8cjEhA4IM4TLWuIAgJ59+GgZ0OFBhwQUIEFydemBhQQYID6Q+OLUzptIWE4IguCClQQRf cDNkiFChrt2zeBUpLFHBnwkJAhQECNAgr+Eie08YCsmiQgQBLA9LHvFADIMNWhKjMFQnBgMAQycv 5NAgsgnNLRL4pTGAguiADBA02JDrQAMODCrkQh1DQocJSWtMEMD4dacJEeL8C81FQ/LCaxoQyDDL uBvTp5njuSmOdAQIkxs07XlAAwIm5lMpH8ghrS/rbRhU5lYQfmMGGPDrx0AFuuEJHXRmQ332UQQP FxOQQsL/BLNgsApvBUY4w0USVghDAgw0MEhIEFro4XIfhpiQdiKGaF4ia0kRlAUstujiiy5GsAAE MNZYYwcQRGDjjixmMACPL+oopAX9DGlkNkge+SOLRzaZpAVLDokkkERmQGWNEVAAVIlcduklG7kU 9+WXO/yRWAUZRpCfBAQIOKZxvCVwjQgIdIDJm5NBmMwKDhBQHZ4HcWDBBA1IUEoT/qWQHE4EBAfo QR0W42gKXz26EIUsaGBWCxwgIABMf1raiQRzHbCBBWL4EEMEBL7AQQKYaFCbqLREypcEDqwnAzwE bEorEggEMNU/rcpQjiARPLaBmL/WkGUHuZjHxAERkUSE/wbZHMFHszR0MIAB3GW3hQSr1ZCBAAUU y20KtnSAC4hcYOAEf11UwF8BGUwAzATMPsoABa6JUEGA5dHVhLpdNODWpPIIYMDDEEcs8cQGKACe cTWFW4KtSNg7Sr/EDDDnYVeVK+6o4BTlDgMFGNByAQUIYDJDCDygJQkY7MBBQZjiM4EFDwi1LgsY yEiCzgfshjB7PCRdAXUMRC311FE3EOqHG8hF34ccdN11AxxFKEECGpPAcYjkPqD22my37fbbcMNt AXlHPMDHHxyUJAEDF2S29NBfHLiFBvMRC/giDgSj+OKML+7oAwlkAK0uJB7OUE2dSZAsVcdaa3lG OE6uwv89n9vXc+lKac4EPFBcEDbqr50N+0Syz57PwK88LULttkNaee8ZnQ78WcIPjxADHOScqPGG CTpyC3tH8MCsjVllCvUsXJAA2CCr0MAFsS2faVMWMJyCwqP8fYIEGzAQSgwYPIDBBs9LWFfXzOOF 6/wXaDiBoXX4jab4poF89U1ObDEF2Aj3u/w5kAiDOkACIKC+B+oDFN+DQGHYMYK8UeAMgnmYxSyY j+IlbVrUIoArSCgOEx4gAld7AABUgj0W4sGF5kEBAihwPxsuwoUHAMlmMFABCgzLh11wQEgqEAgI xYYFFChAAmqIxBoYigkM+I2pULgZXalgAgoIWBW9AET/OnFRBRYQgJvGaIQyimAD4kuBAXzFRjc0 MAkL6N5fFFBHeVRwBAkwnwkaYAECTK+PQ+CYoWTgAAgYQIyIZNfmNgABMbAFBhjw4gsKqclIkmB7 e5vAOv5IAufU4AExm5knTyYTlZDyBA8QwBlXubE7Ugo7L3gAAfT4wLBYgIq7s6WislCDBgiAD2XL XwM00EDekcAB9YvBAwYjyN5NICu5GJgUSCWGBLwSBVWRADAxiQAAfPNwDUgAeRySH0IgwwgZiOMM EjAdB2ZgAQZo5jlV8JF9nqAA0UQdBiRA0K1tgStE2BkEBgAXuFxgnLRywEzodgJnrmAs8iTCBtBV MV4+/yos6jCcFybgBH+2ZACtocAIf8UWj1oUBgVkC0SHkAADMMFrOM2pTnEKH5fUR1oH4AqHVOkF B1C0C/xJqlKXytSkSkABHsUIIVeYBNyQJpiK4EAH1EZHbxSgmhlxQD+4IcwuqCYfdjLAGvGSnKNu zKSFQBUzM8qJCRSAmaBg5kwH4oDvjPOlSIjAXmExj7OoppqAPUIFQoFXZsZTN8TAwIywQtnKWvay mM2sZjer2XIRyW5/cAi1JpfYNpALFLhcF+HAN4Kq9I9wGwwoPgyRrNoma27rSpZs3XiQBGiPLb5l i3CBi6oSFdCtZiurYRpglJk8IAKylYz0RGcD5b5mYP8NzW5EDKOBrAkWXqJyhG7Gq4nykve85k0v etdr3i48gBK1YZAIeGbdMVbgdZIg2wgIxwQLGGCDRKXlfZuzAfXxto8DhsQe/lrfKj6tsRCOsIQ1 ID6VNLPBtBTCd/Al0gzbQQnA6bCH2WCBBHTgD8xdXQdmcckRt2EDSuyg3rrLIbi6+AV2pStWb6yG sODrrzbm8RFKK2SaYrjINCiJbdR0MCR/eC6k+aVEnMyJA1N5C1a+8pCPrOWlBLnLYOAymPlZsxNm ZpZjNgLylri7L6e5JW5+c/biLGcR17kLRL4z7g6QoA1iOD80uCoNdOy9Yhp60DVAXgvYScmClPfR uoHLdNcifb+dWtrSkb70TjOtaa+N99OTBvX9Ri3qSZtX1Kh+9KnTK+lWc7rTofYaDRxwNRfcZpko mQWh/3IbUcqgMA4YbGuDHWMYOOACGJhAasEpBiLGgANQkMCuTXCiGThAAvKSgQYANIBln0A8FsjA NzmAlcitFY1G2QB+WXAZCU67F1YqQDJRwIC5UPXO+H5zA771P01AtjbtK6/ABk5QIVKFWt6mMtnS AQHVBE0qdTFKnRK0gARREEfX/NcE2YLcfJcy4SaIrse9FAIAOw== ------=_NextPart_000_0000_01C825F8.6435E570 Content-Type: image/gif Content-Transfer-Encoding: base64 Content-Location: http://neuro-oncology.dukejournals.org/content/vol8/issue3/images/small/Brandes_2.gif R0lGODdhyACWAIQAAAAAAAgICBAQECkpKSAgIBgYGEFBQf///1JSUmpqat7e3rS0tDk5OZSUlNXV 1TExMWJiYqSkpL29vXt7e4uLi83Nze7u7kpKSqysrIODg+bm5nNzc8XFxZycnPb29lpaWiwAAAAA yACWAEAF/+AhjmRpnmiqrmzrvnAszzQaVakTQFzt/8CgcJhLZA6RhAQZUXEuIoqGSK1ar1dMT7WA iiQYrHhMLpdur86HdDS733CXRRTZzhSM0UYR7/uHFBcQHip1VBUIDXN/jI0sFg04IgoQFBYdCT0R S24VHwaOoX4WEWGFko4ZCxUcHKwVA6iiszQOGB0rhrQ1GA2+v8DADG2TDbtiHBScBw5GzAiEm8dw GhTTVxIJTYV2195kkH5o3+Ri4X3j5epU53Hp6/BA7ViUUh4dcxHb8fw182+6+gmM8c9MM2syNnCQ sGHKCw8RMkiAIENChoiLXkRQCMHUCwoNshmDoWBChQa4YP904MEjxoINDTYsG+gjQoOSEBIgmMAB AUUPECJ8QJCgw0oKGSBs+BAoAYWVJ/fRbLFgwYEG+phlAEYhwYJWHPBNHfsnoAkNDzTIJMvWzbsT DFJqaUs3CIUeCsS+TYGhQI8JGesKrtmtRYIBhERwsDq48YEMDAaNUGBBgYbEe2NQKMBHBAYHjtt6 SJzCLBEPDww8YGCgtQHQoctNYEr6RGYzfUE2YBw7VMwNiTk0OCIcR4cN6jpcWHBcwkLnEpw77A0k w4cEgU2Ypn525AkIKdteTJCg9pnC3NcV/KETO4kFfDRIiCYrvXrvcG7b97a+CgYFDkjQwBT67TdN f2RsZyD/f/gBVN+CDJIhnDVYNcFBAhNkqOGGHG6Y1AcZZBjiiBOQaGKGCXxQ4oontljiBhe4KOOK E+w0I40dXrCBiDzSGKKPGV6g4Y9E9ljkBgZ0qOSSPs0E4ZNQRvlGYtNJaeUIFniwyDuoYRgkelf2 NhcKFRhgATFhUlfgA7hglWZdHkywgAMVWIIEbChYMMAcGPD2ZmMFHtCVYlL9WZeCJTjAgQG4YOCk ofFUsMERHfB0QAdoruDUAQpgEBGkbCGKAgd7ilBBc6DSJCoKqCklk6QNeJSqKLUJ10YD0WQagwQE WKUBT2DO+oYGMU5g3nlA+PRLBw7oKqwbC2iQnXbB+kDB/wQQFPASns+SEcgEWGpzAAcZ5POgFRXI yUCD3RLRwQMJ5HKuGB7odIEAD7QrRE8TsHvGvGZM4NwCiOlbQ4ZSXXaAB5Ks+oYC+niKwS0MCCBA AAhgkEF4Bk8mEQmEzIEZwNewAhZY77byiissr1xBdDB3gBB3AlZLh82NdUAAAhfwbMAAFwTds9AI fFAlWQuIy42UCvgrAsMVRC311FRXbfXVWGettdTc0vEBcCNIVAHE5koZZwZIZaA22my3vfbbcMct 99xyT1BoEEnPbAPOHROBYA0RQGDs0n2X8bcQFah9ACSaOFt4FYdjEejjQUR+hcOUy+M0EYkfoUEH S0Sgd//mkG8+xuSk+2O6GKinPoPlP1hQ1OLIIUGy66qLwzfuMsDu3+68w+A7FZgHL/zqQijggbSd GS+anDOMjfaxKgAVwSXUF4JBnUez4EAETTfvQp0lPbpCBQ5QcrsJJ2nwVQzVQCyrgRZkmb3z67z8 +Q0SrELBNl7hwGccJafr9Ukfl2hWMoCHvwbCAHoY+MD6HLiLhUDsA6CRxgjQQhpmUfAaptEYBboC APN90BGiKpMDOHbCUOinTGdqIS30gxoLOABsMoSDBKZggS0UqAGgsMAGppVDLNTpCArwyqUcJwIH 5OEqXStifmzmgQHwgRLikyJAcLYjEVRFi+jAGQYQMAn/CEwQjEQIlAMKYAAEKKACEOgeGiV3Rgwd IHFzrELnLvUBTdwtBeC5yiaymEcffAZ9C6DPCzIQr7AVko4vkEABKCICgTngfo+kQetGMIBuLCaT aTwjlh5Amv6BcgibHIEIIZCHyozulCuQXRMk1YPt1UADBHCPBP4ISyQwZTKVqMxIIsBCGSBgG/3b Qy9JkBecpRIFBrCDpF4JysDVrjSiTMECIMBNCASNApic4wKuJS8qOGAABthABBZgQjROIJ3ltIIF 8vDMDyovnlbQAPocgBIFIKCYRaSAASQzruEIagIEAlcZLLMBAVxTixnYCWkoozzYFG8IFoBAABgQ mSh+/1ACDiAiCS5qhQ8MoIiYcBPh/LCTCRwmnDkkKbrYuQACMEBoQTPAB2BqsGvNj1qi6MAq0Cc1 NtFJaiJtVwWUxqlKXKU8B7ClNzyQvgwtjpft2gpUFxcUBUiAAhlsJy0ckFMAmPWsZ33AxNbK1ra6 9T/pEY4RMClTb+CSPHjNq14bQoLhjYUC3KRrNtkSIhJoAHl0scXq6jkWD1TlsSt5rGSrota6nOp2 jK3LYVOQAZty9LOgDa1oR0va0pr2tJ+lJAkmwICdjgA+TaTDYAfTNPtcBBXJOMI7M6hQKCmAmgsb AU/VAVgdrbSX1aiCAjbwPmwuUwQWAK4PJoABgtpgtv8yjG4VGsABOY4Uuy3ULhEwcIH1ZfaE4h1C AxCwkxE0w3PKzMpz04sFD0hEUYqw3XMXJ93TMVCK9N3ifgPsFvCit79iGNMyCWwFZWiFQAb+IIMP MSmGZSAaWC3khBP03yJu2L8DRrDkOpzDD7MuwhQ0MRYU3EsVA2FCCysXEpioYREHQXmX2RKKHehi K5xXwjb2MYmzG+Qq/DjFRSbejhvYYx/IDhfbzOCQD6ABQrrAA1Z2gUe1XIMtt8DLsWzkHXhaj0tI 8Gn2S/No1KylNY+mzVmqn5biTOc5vxnOdZaznums5j3b2c96XnOe49zmOxfazYRONJwXvWhFO/rQ hWaqs6TdPNwTSCDLK7ikoioCGjCTiTLzkcElOZBUFMjHAzuMAQci4L5Sn6CHVHa1CVB9R0+PqgFJ HoEEKqCBDI8qaReQdaKGs4FseuADH8CAOmOwI5TkOi9RtXUJYvJOgKqgJIy09n63ze0gkNUAqyh0 cEXQAeVlCboLm0PU+Lq4qwh7v71wQNEWMIGuXAA7avGFEri5TQmmaAEf8Gd19eHrbrOA1DLwk8EL FwIAOw== ------=_NextPart_000_0000_01C825F8.6435E570 Content-Type: image/gif Content-Transfer-Encoding: base64 Content-Location: http://neuro-oncology.dukejournals.org/content/vol8/issue3/images/small/Brandes_3.gif R0lGODdhyACWAIQdABgYGCkpKSAgIDk5OVJSUjExMUpKSv///0FBQXNzc2JiYtXV1YuLi7S0tO7u 7lpaWqysrIODg+bm5t7e3qSkpGpqapycnM3NzZSUlMXFxb29vfb29nt7ewAAAAAAAAAAACwAAAAA yACWAEAF/+AhjmRpnmiqrmzrvnAsz3RKvRrVTIf01MCgcEgsHhoazcbC2RwsQ8boITFar9is7IbF LEo/rXhMpnHJGY1kTaJAy/C4sdqjn+WjSePgfHEyeIGCJXeDKAuAMxILjI2Oj5ALGgSGYw4DHBVf IhkYFxMUXG+VKg4REBQQqquqqaioe0QZCRy0tAiFpDILFQkVPCq5usPEWBQVGizCxczNNA4NDVIj EEkHDBwiEQ7O3d5ay9/i4zHh5OfowBPcB+bo7/Du8PPFFxYXi3b0+/Ty/P/DIKSRcQHQBQgy7hGI BSNUgmQvNihg0CDCJhcTFGiAgCiGtQaJXmDAkMHABRhLOP9guwiQhkUKGAgYeIAhgoAKPRJQkKkg g0wIAxREMEAhaE0EEiKEbLliww0HOZxAsBCKqpsKVt3AZMm0qxh/JRbco8Nn6DSvaGeAhTFVgYIK BBKknXvgAgYeqUSsjXHhFCEEDwIj4Er3394iOU4UVcCucLcJG8i2K4ah1ckWFR4wiMCZM0THQvqs OCyHNBEFDSSjxUBBteK0FjRkmE27tu3buG1rsICBt+/ewH8LDz5yuPHixHknX8668QgNExtXS2bP CQfXoLO7yBCBgfPX2sMbE0+eRiceqPSWXy/ENPvwDjY4mK/+vf1y9/O7cK9/bjQNDqDCjQQXFGhg BgUiWFD/ggwuaOCDEEbYoIQUPqhghRVeiGGGG2KoYYcQfgjigZf1Z+KJKF6xgWgp5reiBPRNZgIm m3UXQWab1chQi16RxoATizACgQI8tsTfXRJAdoQBnxXpjQQUTDCBNTIGAQEwTlDh5Dv8pTBBNSJM UEAto2zJTJcqaFCiCA5UgJCZgjRAQQYOWGCBE9toMVU0DbB4QAQPWIAdnGWgScObfCSRhAJlEvqV IA4wsMAFfh5QAQO0yWYbpY6+IFAyIGnz3SABYtSbBQOs2el+zmyA6C44rWqDNwtEMAgCo3plAQAD AHMEBZRGEIuhYoAyiF9zARWArygQWwwElRbhRlfREiJr/1cRIFCArxJAewREzl5byUa5WisuQL6U 28a5AEnQgAGEmcsuPRIoAFNj7rKxSbjzesNvv878C/AgcirRiRONDoyWwAoPw3DDcUBwwR5LiHAd xGk9jPEgGm8sRgNgSioCBtV6PE/HJseBcspWgMINEvWx/I+6LQyqgnw04GwzCzSjEF8PMsAIdAw4 z7Di0DSoihKAMUxKwyIHLFDyzfGuMEEVSrPgBFRTn3A1DVLWld8Es9HctQiqnS3zEFInecECE3yR mgi/MHK1BAY5sAA0F+jt7gEJ7Lz24C4sgAEfVKlN+DB7LBAKwiY4YIAJUy5OTMJ18fmfBhzEpkED FlBief8gexH41AAVpM7o6IXKIFAJEhhAJ+uPyvD5WSJoYCvtQoDiRKhVEgQByFA4gAECivOOwvDJ QJCAdYK3wAE7CsiUvPLKDGGXnRYMqYGUSmJfg8AMMB01keKbgUXFnMiJfPoNZaEBVwjAC/8JlT7c AGEM3Lni9TIDSTJGIoIfZcEBFPDTiuLzkPtBZQ1vi9n6kgQlrkwAAwY43P3kNQYJZEWD7RhAAkaY gKrRbmUnsECuerNBFEbuVSSYwANMaDkXUu4gTRJBA0jIQx4WYCkDy4AFvgCBbAQvEMZDhQV2pIIE MCpxA8sBnVQ4sp7BwVUySEDWFGZDrc2nWy6QQBKQkIT/G3GxG3Zi1gsWgLrUufGNcIxjBSZioi7C YAFMvCIBAEgXO74gUoMggBrRkgEEXEwEG7hM2I54Jk8EInQDAGJXoNSnEQhwAxVI4AEO2Q0wCoID HGAQgvjYDCbciQROYJEfiQYjB8BoDa78oixJpifMwaMmglyBLfnRMQggoBep8wUwhynMYgbzmMRE pjGTycxlClNpFgiAloKRFjGmITfYzGZuClIbbt7GmwiaDTjF2U1ylpOb4Ewngk6whuitUnwT4MAD BsnBDY4hA3gUDcgysIEHJGKX9rQCL3o1ArEswF3DCigZjPcWeq5LoR1MAAC2OIJ3Yo8BBPAWNSH6 MQUY/0BwFlVeAzigSRE4rgpilCBHrdCAtxCgRP8BHPowYMWVjiGkNmVkTkuzU0PgdIPsOJpOe8rS gWxAg5wk6vr6tghg/HSlT+VoVCE6VYVWVXm7OYkGpgFQpQpBiHQqn0q9Soar2tOsLSQrT9V6BQck InxoZZ0AD4BPi9WUrUZ7KF5vutey9pWvfwVHYIcQDTrJyQmYmhCIOiGiEZFkRBF6LGQNpAFPTJay lr1sQTJ72U5oNkFewEiU3JXDwVrBLhRNgUDqVNoVVBaBqT2BZ0UGgwwI5C4wMJ5sLOBQ1V7HkREJ xTWih8pQZIABxD2BFHfBz+nFAHRt6qoJ7NGAyqAEG2rVpaEJJFAZVMTWBDSN5/WWACx/PrcyczKt enuqgQI8QGLRaI2r2MGBBawiagiRkwwjQABBedABzu1rAoTIAFpggAMYKIAUJpAACGDjFA9AQANm mIAIWOABF9BiAKTR2vUeoLcq0K6H8xMCADs= ------=_NextPart_000_0000_01C825F8.6435E570 Content-Type: image/gif Content-Transfer-Encoding: base64 Content-Location: http://neuro-oncology.dukejournals.org/icons/back.gif R0lGODlhDAAMAPcAAP//////zP//mf//Zv//M///AP/M///MzP/Mmf/MZv/MM//MAP+Z//+ZzP+Z mf+ZZv+ZM/+ZAP9m//9mzP9mmf9mZv9mM/9mAP8z//8zzP8zmf8zZv8zM/8zAP8A//8AzP8Amf8A Zv8AM/8AAMz//8z/zMz/mcz/Zsz/M8z/AMzM/8zMzMzMmczMZszMM8zMAMyZ/8yZzMyZmcyZZsyZ M8yZAMxm/8xmzMxmmcxmZsxmM8xmAMwz/8wzzMwzmcwzZswzM8wzAMwA/8wAzMwAmcwAZswAM8wA AJn//5n/zJn/mZn/Zpn/M5n/AJnM/5nMzJnMmZnMZpnMM5nMAJmZ/5mZzJmZmZmZZpmZM5mZAJlm /5lmzJlmmZlmZplmM5lmAJkz/5kzzJkzmZkzZpkzM5kzAJkA/5kAzJkAmZkAZpkAM5kAAGb//2b/ zGb/mWb/Zmb/M2b/AGbM/2bMzGbMmWbMZmbMM2bMAGaZ/2aZzGaZmWaZZmaZM2aZAGZm/2ZmzGZm mWZmZmZmM2ZmAGYz/2YzzGYzmWYzZmYzM2YzAGYA/2YAzGYAmWYAZmYAM2YAADP//zP/zDP/mTP/ ZjP/MzP/ADPM/zPMzDPMmTPMZjPMMzPMADOZ/zOZzDOZmTOZZjOZMzOZADNm/zNmzDNmmTNmZjNm MzNmADMz/zMzzDMzmTMzZjMzMzMzADMA/zMAzDMAmTMAZjMAMzMAAAD//wD/zAD/mQD/ZgD/MwD/ AADM/wDMzADMmQDMZgDMMwDMAACZ/wCZzACZmQCZZgCZMwCZAABm/wBmzABmmQBmZgBmMwBmAAAz /wAzzAAzmQAzZgAzMwAzAAAA/wAAzAAAmQAAZgAAMwAAAP///wAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAACH5BAEAANgALAAAAAAMAAwA AAggAAUJHEiwoMGDCAsCAJBw4cKDDh0ifNiQYcWEGDNmDAgAOw== ------=_NextPart_000_0000_01C825F8.6435E570 Content-Type: application/octet-stream Content-Transfer-Encoding: quoted-printable Content-Location: http://neuro-oncology.dukejournals.org/javascript/ajax/xmlhttprequest.js /*=0A= =0A= Cross-Browser XMLHttpRequest v1.2=0A= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=0A= =0A= Emulate Gecko 'XMLHttpRequest()' functionality in IE and Opera. 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_0000_01C825F8.6435E570 Content-Type: application/octet-stream Content-Transfer-Encoding: quoted-printable Content-Location: http://neuro-oncology.dukejournals.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 =3D=3D "layout-grid-type") {=0A= e.style.layoutGridType =3D value;=0A= }=0A= else if (name =3D=3D "left") {=0A= e.style.left =3D value;=0A= }=0A= else if (name =3D=3D "letter-spacing") {=0A= e.style.letterSpacing =3D value;=0A= }=0A= else if (name =3D=3D "line-break") {=0A= e.style.lineBreak =3D value;=0A= }=0A= else if (name =3D=3D "line-height") {=0A= e.style.lineHeight =3D value;=0A= }=0A= else if (name =3D=3D "list-style") {=0A= e.style.listStyle =3D value;=0A= }=0A= else if (name =3D=3D "list-style-image") {=0A= e.style.listStyleImage =3D value;=0A= }=0A= else if (name =3D=3D "list-style-position") {=0A= e.style.listStylePosition =3D value;=0A= }=0A= else if (name =3D=3D "list-style-type") {=0A= e.style.listStyleType =3D value;=0A= }=0A= else if (name =3D=3D "margin") {=0A= e.style.margin =3D value;=0A= }=0A= else if (name =3D=3D "margin-bottom") {=0A= e.style.marginBottom =3D value;=0A= }=0A= else if (name =3D=3D "margin-left") {=0A= e.style.marginLeft =3D value;=0A= }=0A= else if (name =3D=3D "margin-right") {=0A= e.style.marginRight =3D value;=0A= }=0A= else if (name =3D=3D "margin-top") {=0A= e.style.marginTop =3D value;=0A= }=0A= else if (name =3D=3D "min-height") {=0A= e.style.minHeight =3D value;=0A= }=0A= else if (name =3D=3D "overflow") {=0A= e.style.overflow =3D value;=0A= }=0A= else if (name =3D=3D "overflow-x") {=0A= e.style.overflowX =3D value;=0A= }=0A= else if (name =3D=3D "overflow-y") {=0A= e.style.overflowY =3D value;=0A= }=0A= else if (name =3D=3D "padding") {=0A= e.style.padding =3D value;=0A= }=0A= else if (name =3D=3D "padding-bottom") {=0A= e.style.paddingBottom =3D value;=0A= }=0A= else if (name =3D=3D "padding-left") {=0A= e.style.paddingLeft =3D value;=0A= }=0A= else if (name =3D=3D "padding-right") {=0A= e.style.paddingRight =3D value;=0A= }=0A= else if (name =3D=3D "padding-top") {=0A= e.style.paddingTop =3D value;=0A= }=0A= else if (name =3D=3D "page-break-after") {=0A= e.style.pageBreakAfter =3D value;=0A= }=0A= else if (name =3D=3D "page-break-before") {=0A= e.style.pageBreakBefore =3D value;=0A= }=0A= else if (name =3D=3D "pixelBottom") {=0A= e.style.pixelBottom =3D value;=0A= }=0A= else if (name =3D=3D "pixelHeight") {=0A= e.style.pixelHeight =3D value;=0A= }=0A= else if (name =3D=3D "pixelLeft") {=0A= e.style.pixelLeft =3D value;=0A= }=0A= else if (name =3D=3D "pixelRight") {=0A= e.style.pixelRight =3D value;=0A= }=0A= else if (name =3D=3D "pixelTop") {=0A= e.style.pixelTop =3D value;=0A= }=0A= else if (name =3D=3D "pixelWidth") {=0A= e.style.pixelWidth =3D value;=0A= }=0A= else if (name =3D=3D "posBottom") {=0A= e.style.posBottom =3D value;=0A= }=0A= else if (name =3D=3D "posHeight") {=0A= e.style.posHeight =3D value;=0A= }=0A= else if (name =3D=3D "position") {=0A= e.style.position =3D value;=0A= }=0A= else if (name =3D=3D "posLeft") {=0A= e.style.posLeft =3D value;=0A= }=0A= else if (name =3D=3D "posRight") {=0A= e.style.posRight =3D value;=0A= }=0A= else if (name =3D=3D "posTop") {=0A= e.style.posTop =3D value;=0A= }=0A= else if (name =3D=3D "posWidth") {=0A= e.style.posWidth =3D value;=0A= }=0A= else if (name =3D=3D "right") {=0A= e.style.right =3D value;=0A= }=0A= else if (name =3D=3D "ruby-align") {=0A= e.style.rubyAlign =3D value;=0A= }=0A= else if (name =3D=3D "ruby-overhang") {=0A= e.style.rubyOverhang =3D value;=0A= }=0A= else if (name =3D=3D "ruby-position") {=0A= e.style.rubyPosition =3D value;=0A= }=0A= else if (name =3D=3D "scrollbar-3dlight-color") {=0A= e.style.scrollbar3dLightColor =3D value;=0A= }=0A= else if (name =3D=3D "scrollbar-arrow-color") {=0A= e.style.scrollbarArrowColor =3D value;=0A= }=0A= else if (name =3D=3D "scrollbar-base-color") {=0A= e.style.scrollbarBaseColor =3D value;=0A= }=0A= else if (name =3D=3D "scrollbar-darkshadow-color") {=0A= e.style.scrollbarDarkShadowColor =3D value;=0A= }=0A= else if (name =3D=3D "scrollbar-face-color") {=0A= e.style.scrollbarFaceColor =3D value;=0A= }=0A= else if (name =3D=3D "scrollbar-highlight-color") {=0A= e.style.scrollbarHighlightColor =3D value;=0A= }=0A= else if (name =3D=3D "scrollbar-shadow-color") {=0A= e.style.scrollbarShadowColor =3D value;=0A= }=0A= else if (name =3D=3D "scrollbar-track-color") {=0A= e.style.scrollbarTrackColor =3D value;=0A= }=0A= else if (name =3D=3D "float") {=0A= e.style.styleFloat =3D value;=0A= }=0A= else if (name =3D=3D "table-layout") {=0A= e.style.tableLayout =3D value;=0A= }=0A= else if (name =3D=3D "text-align") {=0A= e.style.textAlign =3D value;=0A= }=0A= else if (name =3D=3D "text-align-last") {=0A= e.style.textAlignLast =3D value;=0A= }=0A= else if (name =3D=3D "text-autospace") {=0A= e.style.textAutospace =3D value;=0A= }=0A= else if (name =3D=3D "text-decoration") {=0A= e.style.textDecoration =3D value;=0A= }=0A= else if (name =3D=3D "textDecorationBlink") {=0A= e.style.textDecorationBlink =3D value;=0A= }=0A= else if (name =3D=3D "textDecorationLineThrough") {=0A= e.style.textDecorationLineThrough =3D value;=0A= }=0A= else if (name =3D=3D "textDecorationNone") {=0A= e.style.textDecorationNone =3D value;=0A= }=0A= else if (name =3D=3D "textDecorationOverline") {=0A= e.style.textDecorationOverline =3D value;=0A= }=0A= else if (name =3D=3D "textDecorationUnderline") {=0A= e.style.textDecorationUnderline =3D value;=0A= }=0A= else if (name =3D=3D "text-indent") {=0A= e.style.textIndent =3D value;=0A= }=0A= else if (name =3D=3D "text-justify") {=0A= e.style.textJustify =3D value;=0A= }=0A= else if (name =3D=3D "text-kashida-space") {=0A= e.style.textKashidaSpace =3D value;=0A= }=0A= else if (name =3D=3D "text-overflow") {=0A= e.style.textOverflow =3D value;=0A= }=0A= else if (name =3D=3D "text-transform") {=0A= e.style.textTransform =3D value;=0A= }=0A= else if (name =3D=3D "text-underline-position") {=0A= e.style.textUnderlinePosition =3D value;=0A= }=0A= else if (name =3D=3D "top") {=0A= e.style.top =3D value;=0A= }=0A= else if (name =3D=3D "unicode-bidi") {=0A= e.style.unicodeBidi =3D value;=0A= }=0A= else if (name =3D=3D "vertical-align") {=0A= e.style.verticalAlign =3D value;=0A= }=0A= else if (name =3D=3D "visibility") {=0A= e.style.visibility =3D value;=0A= }=0A= else if (name =3D=3D "white-space") {=0A= e.style.whiteSpace =3D value;=0A= }=0A= else if (name =3D=3D "width") {=0A= e.style.width =3D value;=0A= }=0A= else if (name =3D=3D "word-break") {=0A= e.style.wordBreak =3D value;=0A= }=0A= else if (name =3D=3D "word-spacing") {=0A= e.style.wordSpacing =3D value;=0A= }=0A= else if (name =3D=3D "word-wrap") {=0A= e.style.wordWrap =3D value;=0A= }=0A= else if (name =3D=3D "writing-mode") {=0A= e.style.writingMode =3D value;=0A= }=0A= else if (name =3D=3D "z-index") {=0A= e.style.zIndex =3D value;=0A= }=0A= else if (name =3D=3D "zoom") {=0A= e.style.zoom =3D value;=0A= }=0A= }=0A= catch (e) {=0A= /* ignore error on attempt to set e.style.[property] */=0A= }=0A= }=0A= }=0A= }=0A= ------=_NextPart_000_0000_01C825F8.6435E570 Content-Type: application/octet-stream Content-Transfer-Encoding: quoted-printable Content-Location: http://neuro-oncology.dukejournals.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. For now we have to disable=0A= * the callback until we can track down a proper fix=0A= * (or everybody sanely upgrades to version 6 or 7!).=0A= */=0A= if (navigator) {=0A= var appname =3D navigator.appName;=0A= if (appname =3D=3D "Microsoft Internet Explorer") {=0A= var userAgent =3D navigator["userAgent"];=0A= var s =3D "MSIE ";=0A= var n =3D -1; =0A= if ((n =3D userAgent.indexOf(s)) !=3D -1) {=0A= var v =3D parseFloat(userAgent.substring(n+s.length));=0A= if (v < 6) {=0A= return;=0A= }=0A= }=0A= }=0A= }=0A= =0A= /*=0A= * Acquire table row element to update, initiate callback=0A= * to update table with Entrez Links.=0A= */=0A= var tr =3D document.getElementById('entrez_callback_'+pmid);=0A= if (!tr) {=0A= return;=0A= }=0A= var req =3D new XMLHttpRequest();=0A= if (!req) {=0A= return;=0A= }=0A= req.onreadystatechange =3D function() {=0A= if (req.readyState =3D=3D 4 && (req.status =3D=3D 200 || req.status = =3D=3D 304)) {=0A= var src =3D req.responseXML.documentElement;=0A= var dst =3D document.createDocumentFragment();=0A= for (var i =3D 0; i < src.childNodes.length; i++) {=0A= copy_xml_to_html(src.childNodes[i], dst);=0A= }=0A= var tbl =3D tr.parentNode;=0A= tbl.replaceChild(dst, tr);=0A= }=0A= }=0A= req.open('GET', callback_url, true);=0A= req.send(null);=0A= }=0A= ------=_NextPart_000_0000_01C825F8.6435E570--