From: Subject: Quality of life in adults with brain tumors: Current knowledge and future directions Date: Mon, 1 Nov 2010 22:27:59 +0100 MIME-Version: 1.0 Content-Type: multipart/related; type="text/html"; boundary="----=_NextPart_000_0000_01CB7A14.0A304020" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.5994 This is a multi-part message in MIME format. ------=_NextPart_000_0000_01CB7A14.0A304020 Content-Type: text/html; charset="utf-8" Content-Transfer-Encoding: quoted-printable Content-Location: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2718978/?tool=pubmed =EF=BB=BF Quality of life in adults = with brain tumors: Current knowledge and future directions
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Neuro Oncol. 2009 June; 11(3):=20 330=E2=80=93339.
PMCID:=20 = PMC2718978
Copyright=20 =C2=A9 2009 by the Society for Neuro-Oncology
Quality of life in adults with brain tumors: = Current=20 knowledge and future directions
Raymond Liu, Margaretta = Page, Karla=20 Solheim, Sherry Fox, and Susan M. Chang
Department of Neurological Surgery, = University of=20 California, San Francisco, San Francisco, CA (R.L., M.P., K.S., = S.M.C.);=20 and Cullather Brain Tumor Quality of Life Center, Bon Secours = Richmond=20 Health System/ St. Mary=E2=80=99s Hospital, Richmond, VA (S.F.); = USA
Address = correspondence to Susan=20 M. Chang, Department of Neurological Surgery, University of = California,=20 San Francisco, 400 Parnassus Ave., A-808, San Francisco, CA = 94143-0350,=20 USA, ( Email: changs/at/neurosurg.ucsf.edu ).
Received July 23, 2008; Accepted October = 14,=20 2008.
Abstract
Quality of life is = an=20 important area of clinical neurooncology that is increasingly = relevant as=20 survivorship increases and as patients experience potential = morbidities=20 associated with new therapies. This review of quality-of-life = studies in=20 the brain tumor population aims to summarize what is currently = known about=20 quality of life in patients with both low-grade and high-grade = tumors and=20 suggest how we may use this knowledge to direct future research. = To date,=20 reports on quality of life have been primarily qualitative and = focused on=20 specific symptoms such as fatigue, sleep disorders, and cognitive=20 dysfunction, as well as some symptom clusters. However, the = increasing=20 interest in exploring quality of life as a primary end point for = cancer=20 therapy has established a need for prospective, controlled studies = to=20 assess baseline and serial quality-of-life parameters in brain = tumor=20 patients in order to plan and evaluate appropriate and timely=20 interventions for their symptoms.
Keywords: brain tumor, clinical trial end points, quality = of life,=20 survivorship, symptom management
 
Quality of life (QOL) = is a concept=20 that encompasses the multidimensional well-being of a person and = reflects=20 an individual=E2=80=99s overall satisfaction with life. QOL is a = broad term that=20 involves several dimensions, including physical or functional = status,=20 emotional well-being, and social well-being.1
Patients with primary brain = tumors face=20 serious challenges to their QOL. They have difficulties with = general=20 symptoms such as headache, anorexia, nausea, seizures, and = insomnia. These=20 patients also face symptoms secondary to focal neurologic = deterioration,=20 including motor deficits, personality changes, cognitive deficits, = aphasia, or visual field defects.2,3
Despite these many challenges, = there are few=20 well-tested interventions to improve QOL and no established = systematic way=20 to study it in these patients. Few adequately controlled or = powered=20 studies have addressed QOL, and clinical guidelines are limited on = how to=20 manage symptoms in primary brain tumor patients. This review = summarizes=20 what is currently known about the QOL of adult primary brain tumor = patients, the challenges to QOL research, and future directions = for QOL=20 research in brain tumor patients.
QOL in Brain Tumor Patients: Current Knowledge
The overall symptom = burden and=20 disability for glioma patients are significant, especially in = those with=20 high-grade or recurrent disease.3,4 Malignant glioma patients = score=20 significantly lower in all domains of functioning compared to = age-matched=20 and sex-matched healthy controls and have lower social functioning = and=20 more problems with vision, motor functions, communication, = headaches, and=20 seizures than do matched, non-small-cell lung cancer = patients.5 Patients with high-grade = tumors do not=20 appear to differ in QOL between those with grade III and grade IV=20 tumors,3,6=E2=80=938 although perceived QOL in = patients with=20 grade III tumors may be better.9 The difference in QOL may be = less=20 dependent on the grade of tumor and more dependent on whether the = tumor is=20 stable or progressive. For example, one study found that patients = with=20 malignant gliomas with low QOL at baseline tended to deteriorate = over=20 time.10
Patients with low-grade = glioma also=20 have a significant symptom burden.11 In one study, 45% of = patients with=20 low-grade glioma reported low overall QOL, with fewer than half = able to=20 carry out normal activities without restriction. Fatigue, sleep=20 disturbance, and pain were the most frequent symptom complaints, = but=20 patients also had difficulties with other realms of QOL, including = difficulties with cognitive and emotional dimensions.12 Compared to control groups = of patients=20 with non-CNS cancers and healthy patients, low-grade glioma = patients=20 specifically report more fatigue, cognitive dysfunction, and = altered mood=20 states.11,13=E2=80=9315 The prognostic significance = of symptom=20 burden in low-grade glioma patients is unclear because studies = have shown=20 contradictory findings.16,17
Specific Symptoms
Research addressing = specific=20 symptoms that affect QOL has focused on fatigue, sleep, pain, = seizures,=20 mood disturbance, and cognitive function. This research has been = mostly=20 descriptive, and most studies examine a heterogeneous group of = patients=20 receiving different therapies at different stages of their = illness.
Fatigue appears to be the most = significant=20 symptom facing patients with high-grade gliomas3,6 and may be more significant a = problem=20 compared to patients with low-grade tumors.18 In patients with recurrent = malignant=20 gliomas, the incidence of fatigue may approach = 89%=E2=80=9394%.3 In a study evaluating patients = with=20 high-grade gliomas enrolled in three phase II protocols, = significant=20 fatigue was found in one-third of patients and independently = predicted=20 poorer overall survival.6 In that study, Eastern = Cooperative=20 Oncology Group performance status was correlated with overall QOL, = excessive daytime somnolence, and increased fatigue. For low-grade = glioma=20 patients, one small study showed that of all QOL variables tested, = fatigue=20 had the strongest relationship with overall QOL.12
Sleep disturbance is also a = common problem in=20 primary brain tumor patients.12,19 For example, one study = evaluating the=20 incidence of major depressive disorder in a neurooncology clinic = showed=20 some type of sleep disturbance in 31.6%=E2=80=9352% of the = patients=20 evaluated.19 Other patient series suggest = that=20 high-grade glioma patients may have an even higher prevalence of = sleep=20 disturbance.3,20
Pain is another symptom that = glioma patients=20 often face.21 Headache is the most common = type of=20 pain, which more than 50% of patients with high-grade gliomas=20 experience.3 Unfortunately, studies to date = have not=20 examined the type, location, or intensity of headache pain, the = distress=20 it caused, or its overall relationship to QOL in brain tumor=20 patients.
Seizures in glioma patients are = associated=20 with deterioration in multiple cognitive domains.13 Low-grade glioma patients = may have a=20 higher incidence of epileptic seizures than do high-grade glioma = patients,=20 and in one study, antiepileptic therapy was able to control = seizures only=20 in approximately 50% of patients.13 The presence of seizures has = not been=20 shown to be a prognostic factor in some studies17 and was a positive = prognostic factor=20 in other studies when no other symptoms were present.16,22,23
Studies on mood disturbance in = brain tumor=20 patients have reported varying results, noting depression in = anywhere=20 between 7.9% and 90% of cases8,19,24=E2=80=9326 and significant anxiety in = 29%=E2=80=9360% of=20 cases.8,25,27 The use of formal criteria = from the=20 Diagnostic and Statistical Manual of Mental Disorders, = 4th=20 edition, was employed in only a few studies to study = depression.19,26 Of note, in some cohorts of = primary=20 brain tumor patients, depression was the most important = independent=20 predictor of QOL28,29 and has been shown to have = an adverse=20 impact on survival.26,30,31 Depression may also be = under-treated.=20 For example, in one study, only 60% of patients reported by their=20 physicians to be depressed received antidepressants.26
Depression and anxiety may both = have biologic=20 foundations in brain tumor patients. In particular, measurable = serotonin=20 binding sites and strong peripheral benzo-diazepine receptor = expression=20 were present in the tumors of rats implanted with gliomas.32 Expression of certain = serotonin=20 receptors has also been found in human fetal astrocytes and glioma = cell=20 lines.33 The biologic connections = between tumor=20 and symptoms could suggest that symptoms in some cases may not = only be=20 prognostic, but may be a surrogate marker for disease.
Cognitive functioning has also = been studied=20 in brain tumor patients and has been recently reviewed.34 Malignant glioma patients, = in=20 particular, deal with a significant burden in terms of cognitive=20 dysfunction, with as many as 49% experiencing cognitive = impairment.5 In smaller trials, there is = evidence=20 that cognitive dysfunction is present even prior to = treatment.35 There is an unmet need for = early=20 neurocognitive evaluation and intervention. In addition, the = prevalence of=20 neurocognitive dysfunction has implications for decision making = and=20 informed consent.
Evaluation of cognitive function = also has=20 prognostic value.9,36,37 For example, one study of = recurrent=20 malignant gliomas showed that cognitive deterioration may precede=20 radiographic evidence of progression by almost 6 weeks.36 A simple screening = examination such as=20 the Mini Mental Status Examination (MMSE) can have prognostic = significance=20 in glioma patients.38=E2=80=9340 However, while the MMSE is = feasible=20 and convenient to use in brain tumor patients, it has not = consistently=20 been shown to detect cognitive decline in brain tumor = patients.6 Moreover, the test has been = validated=20 for dementia screening but does not have a high degree of = sensitivity for=20 other cognitive domains.41 New neuropsychologic tests = need to be=20 validated in this population, because many of the standard tests = lack=20 sensitivity, especially at the lower end of the impaired = range.42 In fact, attempts are being = made in=20 large cooperative trials to standardize the measurement of = cognitive=20 status. Numerous brain studies being conducted by cooperatives = such as the=20 Radiation Therapy Oncology Group are using well-known tests of=20 neurocognitive function, such as the Hopkins Verbal Learning Test, = the=20 Trail Making Test, and the Controlled Word Association Test.
In summary, brain tumor = patients=20 deal with a significant symptom burden. The main areas of concern = are in=20 fatigue, sleep, pain, seizures, mood, and cognitive function. = Malignant=20 glioma patients are particularly affected by fatigue, whereas = low-grade=20 glioma patients have a large symptom burden from seizures. Further = research is necessary not only to better define this symptom = burden, but=20 also to examine individual symptoms within specific=20 populations.
Long-Term Symptoms: Survivorship
The current literature = on=20 survivorship in brain tumor patients consists of small, mostly=20 retrospective, noncontrolled studies. Moreover, they follow = patients over=20 varying amounts of time.43 Patients in survivorship = studies are=20 also highly selected, as they tend to be young, have high = pretreatment=20 performance status, and often have had a gross total resection of = their=20 tumor. Prospective studies evaluating survivorship would be ideal, = but=20 these studies pose special difficulties because compliance with=20 self-reported questionnaires declines over time, with the sickest = patients=20 unable to complete follow-up. For example, one study following=20 neuropsychologic impairments in adults with brain tumors showed=20 heterogeneous results, with only 5 of 49 patients completing the = third=20 follow-up assessment.44
Despite the many limitations on = survivorship=20 studies, there is some indication that long-term survivors may = have=20 acceptable long-term QOL. When compared to a heterogeneous group = of=20 inpatients with chronic neurologic diseases, patients with = malignant brain=20 tumors had comparable levels of QOL, and 73% of them were able to = continue=20 or resume previous work activity.45 Other studies have found = that between=20 44% and 60% of patients were able to go back to work, although = mostly on a=20 part-time basis.46 In a study of interstitial=20 implantation of brachytherapy, survivors of recurrences were = generally=20 able to maintain their functional status, as measured by = KPS.47
The most serious challenge = survivors of brain=20 tumors face may be cognitive dysfunction, and this is especially = true for=20 patients with malignant glioma.42,43,48=E2=80=9350 Cognitive decline was found = in 50% of=20 glioblastoma patients surviving up to 6 years.48 Cognitive deficits have been = noted on=20 formal testing of supposedly symptom-free survivors of malignant = brain=20 tumors, suggesting that cognitive deficits may be present even in = those=20 patients without overt evidence of impairment.51 However, malignant glioma = survivors=20 may still report experiencing good overall QOL despite suffering = from=20 cognitive impairments.46
Survivors of malignant = gliomas also=20 deal with significant mood disturbance. A small study examining 10 = patients with glioblastoma surviving for more than 5 years found = that=20 depression or anxiety affected a significant proportion of the = patients (4=20 of the 10 patients).50 Larger prospective studies = are needed=20 to better describe the long-term QOL of brain tumor patients. The = urgent=20 need for research in this field is driven by the growing = population of=20 brain tumor survivors.
A Common Etiology to Symptoms: Symptom Clusters
Although symptoms have = been studied=20 separately, they are often interrelated and may in some cases have = a=20 common etiology. The interrelationship between symptoms has been = studied=20 in the symptom cluster literature.52,53 In general cancer patients, = anxiety,=20 depression, pain, fatigue, and sleep disturbance have been = consistently=20 studied as potential components of symptom clusters, and studies = have=20 found relationships among these symptoms in various = configurations.53 Research specifically = concerning=20 symptom clusters in primary brain tumor patients has been = extremely=20 limited. In a high-grade glioma study, depression, fatigue, sleep=20 disturbance, and cognitive impairment formed a symptom cluster = that=20 explained 29% of the variance in QOL, and depression, fatigue, = sleep=20 disturbance, cognitive impairment, and pain formed a symptom = cluster that=20 explained 62% of the variance in functional status.54
Cognitive function has been = correlated to=20 increased fatigue and depression in newly diagnosed malignant = glioma=20 patients.6 Performance status was also = strongly=20 correlated with cognitive function, as measured by the MMSE, in = one study=20 evaluating two large, prospective, randomized trials of newly = diagnosed=20 malignant glioma patients.55 Fatigue, in turn, may be = related to=20 other aspects of QOL and was found to have negative effects on all = components of QOL in glioblastoma patients, with the exception of=20 nutritional well-being.56
The etiologies of = specific clusters=20 of symptoms are generally unknown. Expression of proinflammatory = cytokines=20 such as tumor necrosis factor-=CE=B1, interleukin-1, and = interleukin-6 has been=20 proposed as one mechanism for common symptoms.52,53 Support for this hypothesis = is=20 provided by studies that show an elevation in fatigue, anxiety, = sleep=20 disturbance, and pain sensitivity when these cytokines are = introduced into=20 animal models.52,53 Increased levels of these = cytokines=20 are also seen in depressed patients and cancer patients with=20 fatigue.52,53 Although there is some = evidence that=20 cytokines contribute to symptom clusters, it is very possible that = other=20 explanations exist, or that clustered symptoms do not share a = common=20 etiology.53 Other biologic mechanisms = for symptom=20 clusters are being studied as well. For example, the symptom = cluster of=20 fatigue, appetite loss, and sleep disruption may result from = interference=20 by epidermal growth factor receptor (EGFR) ligands with the = hypothalamic=20 modulation of circadian rhythms, as EGFR ligands and members of = the EGFR=20 family are overexpressed in tumor cells.52 More research needs to be = done on=20 biologic mechanisms of symptoms to better understand the = connection=20 between symptoms and tumor factors and to develop better targeted=20 interventions.
Symptom Management
Despite the significant = burden of=20 symptoms that brain tumor patients face, few QOL interventions = have been=20 tested in brain tumor patients. Of all symptoms, interventions for = fatigue=20 and cognitive dysfunction have been the most widely studied. A = phase II=20 study of donepezil in 24 irradiated brain tumor patients showed=20 statistically significant improvements in cognitive functioning, = mood, and=20 health-related QOL.57 Methylphenidate has also = been used to=20 improve cognitive dysfunction and fatigue. In a pilot study,=20 methylphenidate improved cognitive function and fatigue in = patients with=20 brain tumors.58 A randomized trial of = methylphenidate=20 in a heterogeneous population of brain tumor patients receiving = radiation=20 therapy was closed early due to lack of accrual, high dropout = rates, an=20 interim analysis showing no effect, and withdrawal of drug company = support.59 Modafinil is another = wake-promoting=20 agent used for fatigue, although no large-scale studies have been=20 performed in brain tumor patients. A pilot study of modafinil in = brain=20 tumor patients showed some improvement in cognitive, mood, and = fatigue=20 outcome measures, although the study randomized patients to two = different=20 doses of modafinil rather than to placebo.60
Nonpharmacologic = interventions such=20 as exercise are thought to potentially improve QOL outcomes, as = well, and=20 will likely be tested in brain tumor patients in the near = future.61 Complementary alternative = medicine=20 (CAM) is also commonly used, although studies to date have failed = to show=20 a clear correlation between use of CAM and improved QOL.62,63 In addition, cognitive = training=20 modules have been developed and tested in non-cancer = patients64 and will likely be tested in = brain=20 tumor patients in the future.
A Model for Future QOL Research
Because of the = difficulty of=20 studying symptoms that may have many potential contributing = etiologies,=20 better research models are needed to understand what contributes = to=20 decreased QOL and symptom burden in order to develop targeted=20 interventions to improve patients=E2=80=99 QOL. Figure 1 describes = one way=20 of examining the individual contributions to a patient=E2=80=99s = overall QOL.=20 Patient factors that can contribute to QOL include demographic=20 characteristics and comorbidities that may affect a = patient=E2=80=99s perception=20 and symptom experience. Tumor factors include tumor laterality, = size, and=20 location, which may, in brain tumor patients, affect the specific=20 neurologic symptoms they experience. Finally, treatment factors = include=20 surgery, radiation, chemotherapies, and concomitant medications = that can=20 cause or relieve symptoms that affect QOL.
3D"Fig.
Fig. 1
Model to evaluate effects of = different=20 factors on brain tumor patients=E2=80=99 overall quality of life=20 (QOL).
Patient Factors
Studies focusing = on brain=20 tumor patient comorbidities and demographics and their effects on = QOL are=20 largely lacking. Gender differences in brain tumor = patients=E2=80=99 reported QOL=20 have been the most studied patient factor, although results have = been=20 mixed. A correlation between lower QOL scores and being female has = been=20 shown in several studies,29,65 although not in = others.6,12 Higher levels of mood = disturbance have=20 been found in women with brain tumors than in men,66,67 but not in all = studies.25 The etiology of this = proposed=20 difference remains unexplained, but reporting bias could certainly = contribute.
Tumor Factors
Tumor location and = laterality has=20 been shown to be correlated to several specific symptoms in some = studies=20 but not in others. Because patients with tumors in the left = hemisphere may=20 have greater problems with communication even before treatment is=20 initiated,35 the reliability of = conclusions about=20 laterality based on self-reported symptoms and QOL is sometimes in = question.
Mood changes may be affected by = lesion=20 location. For example, depression may arise from left brain = injury,67 and anxious states may arise = from=20 right brain injury.68 Depression may also be more = frequent=20 in malignant glioma patients with left-hemisphere tumors.7 Another study showed that = patients with=20 a right-hemisphere primary brain tumor had statistically = significantly=20 higher mean anxiety scores, which improved 3 months and 1 year = after=20 surgical resection.67 Low-grade glioma patients = with lesions=20 in the ventral frontal cortex or lesions in the temporoparietal = cortex=20 were reported to have statistically significantly worse mood = states after=20 surgery than those patients with lesions in other regions of the=20 brain.69
Cognitive function may = also be=20 related to tumor laterality. For example, left-hemisphere tumors = have in=20 general been associated with lower scores on verbal tests,7 while right-hemisphere lesions = have been=20 related to lower scores on facial recognition tests.70 In another study, cognitive=20 functioning in patients referred for neuropsychiatric evaluation = was poor=20 but was better in younger patients and in those with frontal brain = tumors.71 In low-grade glioma = patients, greater=20 cognitive disability has been noted in those with tumors in the = dominant=20 hemisphere.11,15 Patients with tumors in the = left=20 hemisphere report more difficulty concentrating than do patients = with=20 right-hemisphere lesions,2,11 although patients with=20 right-hemisphere lesions report more tension.11 The effect of tumor = laterality may=20 differ between brain tumor patients and other populations. For = example,=20 one small study compared 17 brain tumor patients to 17 stroke = patients=20 with similar laterality and found that these two populations = differed=20 tremendously in their neuropsychologic profiles. In this study, = brain=20 tumor patients tended to have more global cognitive deficits = compared to=20 the site-specific deficits apparent in stroke patients.72 Tumor progression may have = more of an=20 impact on declining cognitive function in patients than do = treatment=20 factors such as radiation,38 but the difficulty in = separating these=20 effects often makes it difficult to attribute symptomatic = progression to a=20 single cause.
Treatment Factors
Treatment factors that = can affect=20 brain tumor patients=E2=80=99 overall QOL include surgery, = radiation,=20 chemotherapy, and concomitant medications. Relationships between = QOL and=20 these treatments have been studied, although they suffer from lack = of=20 adequate power and control populations.
In surgical series of high-grade = glioma=20 patients, the extent of resection may correlate with QOL outcomes, = with=20 biopsy patients having worse QOL than those who have undergone = gross total=20 resection.5,10,15,26 Unfortunately, selection = bias of=20 patients who undergo either a gross total resection or a biopsy = based on=20 factors such as tumor size, multifocality, location, and = functionality may=20 confound these findings.
Radiation therapy may adversely = affect QOL in=20 brain tumor patients by leading to increased fatigue in the short = term and=20 by contributing to cognitive dysfunction in the long term. Both=20 radiation-induced fatigue and cognitive dysfunction have been = reviewed in=20 the literature.73,74 One extensive review of = clinical=20 studies published on the neurobehavioral sequelae of therapeutic = cranial=20 irradiation in adults found significant cognitive deterioration in = at=20 least 92 of 748 patients reviewed.73 In long-term survivors who = received=20 radiation therapy, cognitive functioning was more significantly = impaired=20 in those that had received whole-brain irradiation compared to = focused=20 radiotherapy.74 Although these studies = attribute=20 cognitive decline to treatment effect, it is often difficult to=20 differentiate tumor factors from treatment factors. For example, = some=20 studies show that patients with tumors have poor QOL regardless of = whether=20 radiation has been administered.11,15 Furthermore, modern = radiotherapy=20 techniques may not cause the same types of long-term cognitive = effects as=20 whole-brain radiotherapy.14,15,75=E2=80=9377
The few studies that have = evaluated=20 chemotherapy-related QOL suffer from an inability to differentiate = between=20 the effects of chemotherapy and the effects of other treatments or = the=20 tumor itself. The QOL in newly diagnosed glioblastoma patients = receiving=20 either radio-therapy alone or radiotherapy with concomitant and = adjuvant=20 temozolomide (TMZ) has been reported.20 Both groups were = substantially=20 impaired compared to historical controls, but no significant = decrease in=20 overall QOL was noted throughout treatment. Patients receiving TMZ = had=20 more vomiting, anorexia, constipation, and decreased social = functioning.=20 Fatigue during radiation therapy was more frequent in those = assigned to=20 TMZ. Not surprisingly, patients who responded to TMZ reported = improvement=20 in multiple domains of QOL.78
Concurrent medication use may = confound the=20 study of therapy-related symptoms. Medications commonly given to = brain=20 tumor patients include seizure medications and steroids. Both = these=20 medications can adversely affect physical, emotional, and = cognitive=20 functioning.79 Anti-epileptics, in = particular, have=20 been linked to cognitive dysfunction.5,13,15 Analysis of this link is = confounded by=20 whether symptoms are caused by antiepileptics or by seizure = activity.=20 Corticosteroids have been linked to depression in high-grade = glioma=20 patients19,26 and to lower survival in = recurrent=20 malignant glioma patients.80
While treatment-related = effects on=20 QOL have been examined, existing studies are often retrospective = and not=20 controlled. In addition, it has not been clear which concurrent or = sequential treatments are affecting QOL and whether patient = factors or=20 tumor factors are contributing to loss of QOL. Further research = that=20 accounts for confounding factors is necessary in order to define = specific=20 treatment-related symptoms and their contribution to decreased=20 QOL.
QOL Measurement
Another challenge in = QOL research=20 is finding validated instruments to use. Early QOL reports in = brain tumor=20 patients evaluated only the functional domain of QOL using KPS=20 scores.81,82 A review of studies up to = 1998 in=20 brain tumor patients81 suggests that functional = status as=20 measured by KPS remains high until near the time of death. KPS = generally=20 correlates with overall QOL83,5 and appears to have prognostic = value.80 However, using the KPS to = measure QOL=20 is problematic because it is only a single measurement of = functional=20 ability, and its reliability and validity depend on the observer. = Methods=20 of obtaining more information about a patient=E2=80=99s QOL = include considering=20 the patient=E2=80=99s level of independence, training observers in = KPS=20 measurement,84 and developing adjunctive=20 questionnaires such as the independent-living score to corroborate = KPS=20 scores.85
More recent studies have assessed = the=20 multidimensional aspect of QOL. However, conclusions are still = difficult=20 to make given that the questionnaires are often not validated in = the brain=20 tumor population and heterogeneous groups of brain tumor patients = at all=20 stages in their disease course are assessed. Attempts to validate=20 questionnaires in the brain tumor population have been made, but = large,=20 well-run studies that employ these questionnaires remain = lacking.86,87
In order to address these = questions, new=20 instruments that can measure the multidimensional nature of QOL in = brain=20 tumor patients have been developed. The two multidimensional QOL=20 instruments that have been employed most extensively in brain = tumor=20 patients are the Functional Assessment of Cancer = Therapy=E2=80=93Brain (FACT-Br)=20 and the Brain Cancer Module=E2=80=9320 (BCM-20).
The Functional Assessment of = Cancer Therapy=E2=80=93=20 General (FACT-G) is an instrument that has been used to measure = QOL and=20 has been modified in brain tumor patients in the FACT-Br.87 In contrast, the BCM-20 is = designed as=20 a supplement to other general cancer-specific = questionnaires.86 It contains questions = targeted at four=20 different areas: future uncertainty, visual disorder, = communication=20 deficit, and motor dysfunction. In addition, it has seven = single-item=20 questions that address physical symptoms regarding headache, = seizure,=20 drowsiness, hair loss, itching, weakness, and loss of bladder = function.=20 Whereas the BCM-20 groups items into four subscales with symptom = domains=20 and additional individual items, FACT-Br groups all 19 of its = brain=20 tumor=E2=80=93specific questions into a single subscale. The two = questionnaires=20 have not been compared to each other.
Other questionnaires are = also being=20 developed. Recently, a single-item linear analog scale assessment = of QOL=20 in neurooncology patients has been validated. This simple = instrument may=20 allow a quick assessment of the different dimensions of QOL in = brain tumor=20 patients, especially when further detail into specific areas of = QOL is not=20 the primary objective.88 In addition, the M. D. = Anderson=20 Symptom Inventory Brain Tumor Module is a validated 22-item = questionnaire=20 that identifies spe-cific symptoms that brain tumor patients = face.89 More research is needed to = better=20 utilize existing instruments and to validate new ones in brain = tumor=20 patients designed to answer specific questions.
Other QOL Research Challenges
Additional challenges = face=20 investigators interested in pursuing QOL research in brain tumor = patients.=20 Foremost among these challenges is finding the right instruments = to=20 measure QOL. There must be a balance between collecting detailed=20 information with well-validated questionnaires and minimizing=20 questionnaire burden. QOL studies in brain tumor patients that are = prospective, randomized, and hypothesis driven will allow = investigators to=20 pick appropriate instruments that will answer their specific = questions=20 without running into difficulties with compliance and the hazards = of=20 multiple unintended comparisons.
Questionnaire burden and = resulting=20 noncompliance have been a major problem with existing instruments. = While=20 semistructured interviews may elicit more information from = patients and=20 caregivers, the interview format can be quite demanding on the = brain tumor=20 population.90 Many patients with recurrent = malignant=20 glioma who filled out a baseline FACT-Br questionnaire were unable = to=20 complete it at their first follow-up assessment.36,91 Another study examining = longitudinal=20 questionnaire compliance among newly diagnosed malignant glioma = patients=20 showed that compliance dropped to less than 50% at 6 months, with=20 administrative failure being by far the largest reason for failure = of=20 compliance.92
One way of improving compliance = is by=20 simplifying the questionnaires; another is by providing more time = for=20 administration. For example, a 10-point Likert scale with brain=20 tumor-specific questions was investigated in a preliminary study = and found=20 to be feasible in an unselected brain tumor population.65 Another strategy to improve = compliance=20 has been to use proxy raters. The reliability of proxy raters has = been=20 examined, and results have been mixed.7 Further study into proxy = raters is=20 needed, and documentation of whether or not questionnaires were = obtained=20 from proxy raters should be incorporated into QOL studies.
Another challenge with QOL = research in brain=20 tumor patients is related to the potential lack of correlation = between=20 self-reported measures and objective measurements. For example, = poor=20 correlation exists between self-report and objective measures of = cognitive=20 functioning in patients with low-grade tumors15 and in an unselected = population of=20 brain tumor patients prior to treatment.35 The problem of = self-reporting=20 cognitive dysfunction is exacerbated in patients with frontal = tumors, who=20 may underreport cognitive dysfunction due to impaired judgment, or = in=20 patients with anxiety, depression, or fatigue who may overreport = cognitive=20 dysfunction.34 Unfortunately, physicians = may not be=20 better at determining the severity of symptoms, and in low-grade = glioma=20 patients may in fact be underestimating the severity of most=20 symptoms.76
Missing data is another major = challenge that=20 faces a QOL researcher. It is critical to document the reason for = missing=20 data and to prospectively design a trial to account for missing = data. One=20 of the dangers of not adequately considering missing data is that = the=20 sickest patients with the highest symptom burden do not fill out=20 questionnaires and are underrepresented in studies. This is a = particular=20 challenge with longitudinal QOL studies in which patients who have = the=20 highest symptom burden are often the ones that may find it most = difficult=20 to complete questionnaires. Again, the careful selection of = instruments=20 that have minimal item burden and instruments that still capture = the=20 needed data are crucial to the success of such a study.
Once data are collected in brain = tumor=20 patients, they should be analyzed with consideration for response = shifts.=20 Response shifts are natural changes in a patient=E2=80=99s = perception of their QOL=20 over time in response to changing internal standards when they are = faced=20 with a life-threatening illness. If these natural changes and = adaptations=20 over time are not considered, data from longitudinal QOL studies = may=20 incorrectly attribute changes in QOL to other external factors. = Research=20 on accounting for this phenomenon is still ongoing, and models to = account=20 for response shift have been proposed.93
Finally, because the = symptoms and=20 realms of QOL can be interrelated (e.g., insomnia can cause = fatigue, which=20 leads to decreased social interaction), and because an individual = patient=20 is subject to different environmental and demographic factors that = can=20 independently affect individual symptoms and realms of QOL, the = study of=20 QOL can become quite complex. The large number of interdependent = variables=20 may explain why many QOL studies have produced mixed results. The = best way=20 to account for these interactions in a trial is to have a focused = question=20 that is prospectively measured and ideally compared between = adequately=20 powered randomized groups in order to reduce the number of=20 confounders.
Future Directions
Several exciting = avenues of=20 research remain in the vastly unexplored area of QOL in brain = tumor=20 patients. Research needs to be performed on validation of = easy-to-use=20 questionnaires and cognitive tests with incorporation of these = instruments=20 into ongoing clinical trials. Moreover, a better description of=20 longitudinal QOL and exploration into specific causes of symptoms = and=20 survivorship is necessary. In addition, the significance of other=20 nontraditional patient factors that contribute to QOL, such as = caregiver,=20 spiritual, and financial aspects of a patient=E2=80=99s life, need = to be better=20 explored. Finally, once QOL in brain tumor patients has been = adequately=20 described, interventions=E2=80=94both pharmacologic and = nonpharmacologic=E2=80=94are=20 necessary in order to improve QOL. Ultimately, the exploration of = imaging,=20 serum, genetic, or other biomarkers that can more objectively = quantify=20 symptoms not only will allow the field of QOL to be more = consistently=20 described, but also will likely have significant diagnostic, = prognostic,=20 and treatment value. While funding may be limited to pursue these = primary=20 QOL research goals, efforts should be made to incorporate QOL = research as=20 secondary end points into ongoing therapy trials. Few trials have = done=20 this to date,94 although the potential = impact of QOL=20 on survival and prognosis makes incorporation of QOL end points = especially=20 important.95=E2=80=9397
Conclusions
QOL in brain tumor = patients is=20 complex and multidimensional in nature, with symptoms having=20 interrelationships with each other as well as patient, tumor, and=20 treatment factors. Assessing QOL is challenging given the scarcity = of=20 well-validated instruments, difficulty with compliance especially = in=20 longitudinal measurements over time, and the lack of well-designed = trials.=20 Assessing QOL in brain tumor patients is additionally complicated = by the=20 relative rarity of the disease compared to other malignancies, = functional=20 limitations to self-reporting, and concurrent medications such as = steroids=20 and antiepileptics.
Despite these limitations, some = conclusions=20 can be made regarding QOL studied to date on brain tumor patients. = Specifically, the burden of symptoms that affect QOL is = significant, but=20 understudied. There are limited therapeutic options to improve = QOL. The=20 incorporation of QOL as both primary and secondary end points is = crucial=20 because QOL can have prognostic value, and improvement of QOL may = in turn=20 increase overall survival. As such, QOL should be included as a = secondary=20 outcome measure and also be tested as a primary outcome measure in = intervention studies designed to improve the lives of brain tumor=20 patients.
Clearly, more work is = needed in the=20 field of QOL in brain tumor patients. Adequately powered, = high-quality=20 studies from descriptive to diagnostic to interventional in nature = are=20 needed in order to increase both the quality and quantity of these = patients=E2=80=99 lives.
Acknowledgment
We are grateful to Ilona Garner, = Department=20 of Neurological Surgery, University of California, San Francisco, = for=20 editorial support.
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Articles from Neuro-Oncology are = provided here=20 courtesy of
Society for Neuro-Oncology and Oxford = University=20 Press
Fig.=20 1
Model to = evaluate=20 effects of different factors on brain tumor = patients=E2=80=99 overall=20 quality of life (QOL).

PubMed articles by these = authors

  • Liu,=20 R.
  • Page,=20 M.
  • Solheim,=20 K.
  • Chang,=20 S.

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.x-panel-btns-ct .x-btn-over .x-btn-right { BACKGROUND-POSITION: 0px -84px } .x-panel-btns-ct .x-btn-over .x-btn-center { BACKGROUND-POSITION: 0px -105px } .x-panel-btns-ct .x-btn-click .x-btn-center { BACKGROUND-POSITION: 0px -126px } .x-panel-btns-ct .x-btn-click .x-btn-right { BACKGROUND-POSITION: 0px -84px } .x-panel-btns-ct .x-btn-click .x-btn-left { BACKGROUND-POSITION: 0px -63px } ------=_NextPart_000_0000_01CB7A14.0A304020 Content-Type: text/css; charset="iso-8859-1" Content-Transfer-Encoding: quoted-printable Content-Location: http://www.ncbi.nlm.nih.gov/core/ext.ncbi/1/css/themes/xtheme-oldentrez.css .x-panel { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-STYLE: solid; BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-STYLE: = solid; BORDER-LEFT-STYLE: solid; BORDER-RIGHT-COLOR: #d0d0d0; = BORDER-BOTTOM-STYLE: solid } .x-panel-header { BORDER-RIGHT: #d0d0d0 1px solid; BORDER-TOP: #d0d0d0 1px solid; = BACKGROUND-IMAGE: url(../../img/oldentrez/panel/white-top-bottom.gif); = BORDER-LEFT: #d0d0d0 1px solid; COLOR: #333; BORDER-BOTTOM: #d0d0d0 1px = solid } .x-panel-body { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-panel-bbar .x-toolbar { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-panel-tbar .x-toolbar { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-panel-tbar-noheader .x-toolbar { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-panel-mc .x-panel-tbar .x-toolbar { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-panel-body-noheader { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-panel-mc .x-panel-body { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-panel-tl .x-panel-header { COLOR: #333 } .x-panel-tc { BACKGROUND-IMAGE: url(../../img/oldentrez/panel/top-bottom.gif) } .x-panel-tl { BORDER-LEFT-COLOR: #d0d0d0; BACKGROUND-IMAGE: = url(../../img/oldentrez/panel/corners-sprite.gif); BORDER-BOTTOM-COLOR: = #d0d0d0; BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-panel-tr { BACKGROUND-IMAGE: url(../../img/oldentrez/panel/corners-sprite.gif) } .x-panel-bc { BACKGROUND-IMAGE: url(../../img/oldentrez/panel/top-bottom.gif) } .x-panel-bl { BACKGROUND-IMAGE: url(../../img/oldentrez/panel/corners-sprite.gif) } .x-panel-br { BACKGROUND-IMAGE: url(../../img/oldentrez/panel/corners-sprite.gif) } .x-panel-mc { BACKGROUND: #f1f1f1 } .x-panel-mc .x-panel-body { BORDER-RIGHT: 0px; BORDER-TOP: 0px; BACKGROUND: none transparent scroll = repeat 0% 0%; BORDER-LEFT: 0px; BORDER-BOTTOM: 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BORDER-LEFT-COLOR: #e0e0e0; BORDER-BOTTOM-COLOR: #e0e0e0; = BORDER-TOP-COLOR: #e0e0e0; BACKGROUND-COLOR: #eee; BORDER-RIGHT-COLOR: = #e0e0e0 } .x-layout-collapsed-over { BACKGROUND-COLOR: #fbfbfb } .x-tip .x-tip-top { BACKGROUND-IMAGE: url(../../img/oldentrez/qtip/tip-sprite.gif) } .x-tip .x-tip-top-left { BACKGROUND-IMAGE: url(../../img/oldentrez/qtip/tip-sprite.gif) } .x-tip .x-tip-top-right { BACKGROUND-IMAGE: url(../../img/oldentrez/qtip/tip-sprite.gif) } .x-tip .x-tip-ft { BACKGROUND-IMAGE: url(../../img/oldentrez/qtip/tip-sprite.gif) } .x-tip .x-tip-ft-left { BACKGROUND-IMAGE: url(../../img/oldentrez/qtip/tip-sprite.gif) } .x-tip .x-tip-ft-right { BACKGROUND-IMAGE: url(../../img/oldentrez/qtip/tip-sprite.gif) } .x-tip .x-tip-bd-left { BACKGROUND-IMAGE: url(../../img/oldentrez/qtip/tip-sprite.gif) } .x-tip .x-tip-bd-right { BACKGROUND-IMAGE: url(../../img/oldentrez/qtip/tip-sprite.gif) } .x-toolbar { BORDER-LEFT-COLOR: #d0d0d0; BACKGROUND: = url(../../img/oldentrez/toolbar/bg.gif) #f0f4f5 repeat-x left top; = BORDER-BOTTOM-COLOR: #d0d0d0; BORDER-TOP-COLOR: #d0d0d0; = BORDER-RIGHT-COLOR: #d0d0d0 } .x-toolbar BUTTON { COLOR: #444 } .x-toolbar .x-btn-menu-arrow-wrap .x-btn-center BUTTON { BACKGROUND-IMAGE: url(../../img/oldentrez/toolbar/btn-arrow.gif) } .x-toolbar .x-btn-text-icon .x-btn-menu-arrow-wrap .x-btn-center BUTTON = { BACKGROUND-IMAGE: url(../../img/oldentrez/toolbar/btn-arrow.gif) } .x-toolbar .x-btn-over .x-btn-left { BACKGROUND-IMAGE: url(../../img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-over .x-btn-right { BACKGROUND-IMAGE: url(../../img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-over .x-btn-center { BACKGROUND-IMAGE: url(../../img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-over BUTTON { COLOR: #111 } .x-toolbar .x-btn-click .x-btn-left { BACKGROUND-IMAGE: url(../../img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-pressed .x-btn-left { BACKGROUND-IMAGE: url(../../img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-menu-active .x-btn-left { BACKGROUND-IMAGE: url(../../img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-click .x-btn-right { BACKGROUND-IMAGE: url(../../img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-pressed .x-btn-right { BACKGROUND-IMAGE: url(../../img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-menu-active .x-btn-right { BACKGROUND-IMAGE: url(../../img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-click .x-btn-center { BACKGROUND-IMAGE: url(../../img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-pressed .x-btn-center { BACKGROUND-IMAGE: url(../../img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-menu-active .x-btn-center { BACKGROUND-IMAGE: url(../../img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .ytb-sep { BACKGROUND-IMAGE: url(../images/default/grid/grid-split.gif) } .x-tab-panel-header { BORDER-LEFT-COLOR: #d0d0d0; BACKGROUND: #eaeaea; BORDER-BOTTOM-COLOR: = #d0d0d0; BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-tab-panel-footer { BORDER-LEFT-COLOR: #d0d0d0; BACKGROUND: #eaeaea; BORDER-BOTTOM-COLOR: = #d0d0d0; BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-tab-panel-header { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-tab-panel-footer { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } UL.x-tab-strip-top { BORDER-LEFT-COLOR: #d0d0d0; BACKGROUND: = url(../../img/oldentrez/tabs/tab-strip-bg.gif) #dbdbdb repeat-x left = top; BORDER-BOTTOM-COLOR: #d0d0d0; BORDER-TOP-COLOR: #d0d0d0; = PADDING-TOP: 2px; BORDER-RIGHT-COLOR: #d0d0d0 } UL.x-tab-strip-bottom { BORDER-LEFT-COLOR: #d0d0d0; BACKGROUND-IMAGE: = url(../../img/oldentrez/tabs/tab-strip-btm-bg.gif); BORDER-BOTTOM-COLOR: = #d0d0d0; BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-tab-strip SPAN.x-tab-strip-text { COLOR: #333 } .x-tab-strip-over SPAN.x-tab-strip-text { COLOR: #111 } .x-tab-strip-active SPAN.x-tab-strip-text { COLOR: #333 } .x-tab-strip-disabled .x-tabs-text { COLOR: #aaaaaa } .x-tab-strip-top .x-tab-right { BACKGROUND-IMAGE: url(../../img/oldentrez/tabs/tabs-sprite.gif) } .x-tab-strip-top .x-tab-left { BACKGROUND-IMAGE: url(../../img/oldentrez/tabs/tabs-sprite.gif) } .x-tab-strip-top .x-tab-strip-inner { BACKGROUND-IMAGE: url(../../img/oldentrez/tabs/tabs-sprite.gif) } .x-tab-strip-bottom .x-tab-right { BACKGROUND-IMAGE: = url(../../img/oldentrez/tabs/tab-btm-inactive-right-bg.gif) } .x-tab-strip-bottom .x-tab-left { BACKGROUND-IMAGE: = url(../../img/oldentrez/tabs/tab-btm-inactive-left-bg.gif) } .x-tab-strip-bottom .x-tab-strip-active .x-tab-right { BACKGROUND-IMAGE: url(../../img/oldentrez/tabs/tab-btm-right-bg.gif) } .x-tab-strip-bottom .x-tab-strip-active .x-tab-left { BACKGROUND-IMAGE: url(../../img/oldentrez/tabs/tab-btm-left-bg.gif) } 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url(../../img/oldentrez/window/right-corners.png) } .x-window-mc { BORDER-RIGHT: #d0d0d0 1px solid; BORDER-TOP: #d0d0d0 1px solid; = BACKGROUND: #e8e8e8; BORDER-LEFT: #d0d0d0 1px solid; BORDER-BOTTOM: = #d0d0d0 1px solid } .x-window-ml { BACKGROUND-IMAGE: url(../../img/oldentrez/window/left-right.png) } .x-window-mr { BACKGROUND-IMAGE: url(../../img/oldentrez/window/left-right.png) } .x-panel-ghost .x-window-tl { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-panel-collapsed .x-window-tl { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-window-plain .x-window-mc { BORDER-RIGHT: #eee 1px solid; BORDER-TOP: #d0d0d0 1px solid; = BACKGROUND: #e8e8e8; BORDER-LEFT: #d0d0d0 1px solid; BORDER-BOTTOM: #eee = 1px solid } .x-window-plain .x-window-body { BORDER-RIGHT: #d0d0d0 1px solid; BORDER-TOP: #eee 1px solid; = BACKGROUND: none transparent scroll 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.x-panel-btns-center TABLE { MARGIN: 0px auto } .x-panel-btns-ct TABLE TD.x-panel-btn-td { PADDING-RIGHT: 3px; PADDING-LEFT: 3px; PADDING-BOTTOM: 3px; = PADDING-TOP: 3px } .x-panel-btns-ct .x-btn-focus .x-btn-left { BACKGROUND-POSITION: 0px -147px } .x-panel-btns-ct .x-btn-focus .x-btn-right { BACKGROUND-POSITION: 0px -168px } .x-panel-btns-ct .x-btn-focus .x-btn-center { BACKGROUND-POSITION: 0px -189px } .x-panel-btns-ct .x-btn-over .x-btn-left { BACKGROUND-POSITION: 0px -63px } .x-panel-btns-ct .x-btn-over .x-btn-right { BACKGROUND-POSITION: 0px -84px } .x-panel-btns-ct .x-btn-over .x-btn-center { BACKGROUND-POSITION: 0px -105px } .x-panel-btns-ct .x-btn-click .x-btn-center { BACKGROUND-POSITION: 0px -126px } .x-panel-btns-ct .x-btn-click .x-btn-right { BACKGROUND-POSITION: 0px -84px } .x-panel-btns-ct .x-btn-click .x-btn-left { BACKGROUND-POSITION: 0px -63px } .x-btn-menu-wrap { WIDTH: 0px! important } .x-menu { BACKGROUND: #f0f0f0 0px 0px } .x-menu-list-item IMG { DISPLAY: none } .x-menu-list-item A.x-menu-item { PADDING-LEFT: 8px } .port H1.x-panel-header-text { PADDING-RIGHT: 0px; PADDING-LEFT: 0px; FONT-SIZE: 100%; PADDING-BOTTOM: = 0px; MARGIN: 0px; PADDING-TOP: 0px } .port H2.x-panel-header-text { PADDING-RIGHT: 0px; PADDING-LEFT: 0px; FONT-SIZE: 100%; PADDING-BOTTOM: = 0px; MARGIN: 0px; PADDING-TOP: 0px } .port H3.x-panel-header-text { PADDING-RIGHT: 0px; PADDING-LEFT: 0px; FONT-SIZE: 100%; PADDING-BOTTOM: = 0px; MARGIN: 0px; PADDING-TOP: 0px } .port H4.x-panel-header-text { PADDING-RIGHT: 0px; PADDING-LEFT: 0px; FONT-SIZE: 100%; PADDING-BOTTOM: = 0px; MARGIN: 0px; PADDING-TOP: 0px } .port H5.x-panel-header-text { PADDING-RIGHT: 0px; PADDING-LEFT: 0px; FONT-SIZE: 100%; PADDING-BOTTOM: = 0px; MARGIN: 0px; PADDING-TOP: 0px } .port H6.x-panel-header-text { PADDING-RIGHT: 0px; PADDING-LEFT: 0px; FONT-SIZE: 100%; PADDING-BOTTOM: = 0px; MARGIN: 0px; PADDING-TOP: 0px } DIV.x-panel-body { PADDING-RIGHT: 5px; PADDING-LEFT: 5px; PADDING-BOTTOM: 5px; = PADDING-TOP: 5px } .port .x-panel-header { PADDING-RIGHT: 3px; PADDING-LEFT: 5px; PADDING-BOTTOM: 4px; = PADDING-TOP: 5px } .x-panel { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-STYLE: solid; BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-STYLE: = solid; BORDER-LEFT-STYLE: solid; BORDER-RIGHT-COLOR: #d0d0d0; = BORDER-BOTTOM-STYLE: solid } .x-panel-header { BORDER-RIGHT: #d0d0d0 1px solid; BORDER-TOP: #d0d0d0 1px solid; = BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/panel/white-top-bottom.gif); = BORDER-LEFT: #d0d0d0 1px solid; COLOR: #333; BORDER-BOTTOM: #d0d0d0 1px = solid } .x-panel-body { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-panel-bbar .x-toolbar { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-panel-tbar .x-toolbar { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-panel-tbar-noheader .x-toolbar { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-panel-mc .x-panel-tbar .x-toolbar { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-panel-body-noheader { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-panel-mc .x-panel-body { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-panel-tl .x-panel-header { COLOR: #333 } .x-panel-tc { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/panel/top-bottom.gif) } .x-panel-tl { BORDER-LEFT-COLOR: #d0d0d0; BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/panel/corners-sprite.gif); = BORDER-BOTTOM-COLOR: #d0d0d0; BORDER-TOP-COLOR: #d0d0d0; = BORDER-RIGHT-COLOR: #d0d0d0 } .x-panel-tr { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/panel/corners-sprite.gif) } .x-panel-bc { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/panel/top-bottom.gif) } .x-panel-bl { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/panel/corners-sprite.gif) } .x-panel-br { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/panel/corners-sprite.gif) } .x-panel-mc { BACKGROUND: #f1f1f1 } .x-panel-mc .x-panel-body { BORDER-RIGHT: 0px; BORDER-TOP: 0px; BACKGROUND: none transparent scroll = repeat 0% 0%; BORDER-LEFT: 0px; BORDER-BOTTOM: 0px } .x-panel-ml { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/panel/left-right.gif) } .x-panel-mr { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/panel/left-right.gif) } .x-tool { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/panel/tool-sprites.gif) } .x-panel-ghost { BACKGROUND: #e0e0e0 } .x-panel-ghost UL { BORDER-LEFT-COLOR: #b0b0b0; BORDER-BOTTOM-COLOR: #b0b0b0; = BORDER-TOP-COLOR: #b0b0b0; BORDER-RIGHT-COLOR: #b0b0b0 } .x-grid-panel .x-panel-mc .x-panel-body { BORDER-RIGHT: #d0d0d0 1px solid; BORDER-TOP: #d0d0d0 1px solid; = BORDER-LEFT: #d0d0d0 1px solid; BORDER-BOTTOM: #d0d0d0 1px solid } .x-btn-left { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/button/btn-sprite.gif) } .x-btn-right { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/button/btn-sprite.gif) } .x-btn-center { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/button/btn-sprite.gif) } .x-border-layout-ct { BACKGROUND: #f0f0f0 } .x-accordion-hd { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/panel/light-hd.gif) } .x-layout-collapsed { BORDER-LEFT-COLOR: #e0e0e0; BORDER-BOTTOM-COLOR: #e0e0e0; = BORDER-TOP-COLOR: #e0e0e0; BACKGROUND-COLOR: #eee; BORDER-RIGHT-COLOR: = #e0e0e0 } .x-layout-collapsed-over { BACKGROUND-COLOR: #fbfbfb } .x-tip .x-tip-top { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/qtip/tip-sprite.gif) } .x-tip .x-tip-top-left { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/qtip/tip-sprite.gif) } .x-tip .x-tip-top-right { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/qtip/tip-sprite.gif) } .x-tip .x-tip-ft { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/qtip/tip-sprite.gif) } .x-tip .x-tip-ft-left { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/qtip/tip-sprite.gif) } .x-tip .x-tip-ft-right { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/qtip/tip-sprite.gif) } .x-tip .x-tip-bd-left { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/qtip/tip-sprite.gif) } .x-tip .x-tip-bd-right { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/qtip/tip-sprite.gif) } .x-toolbar { BORDER-LEFT-COLOR: #d0d0d0; BACKGROUND: = url(/core/ext.ncbi/1/img/oldentrez/toolbar/bg.gif) #f0f4f5 repeat-x left = top; BORDER-BOTTOM-COLOR: #d0d0d0; BORDER-TOP-COLOR: #d0d0d0; = BORDER-RIGHT-COLOR: #d0d0d0 } .x-toolbar BUTTON { COLOR: #444 } .x-toolbar .x-btn-menu-arrow-wrap .x-btn-center BUTTON { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/toolbar/btn-arrow.gif) } .x-toolbar .x-btn-text-icon .x-btn-menu-arrow-wrap .x-btn-center BUTTON = { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/toolbar/btn-arrow.gif) } .x-toolbar .x-btn-over .x-btn-left { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-over .x-btn-right { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-over .x-btn-center { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-over BUTTON { COLOR: #111 } .x-toolbar .x-btn-click .x-btn-left { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-pressed .x-btn-left { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-menu-active .x-btn-left { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-click .x-btn-right { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-pressed .x-btn-right { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-menu-active .x-btn-right { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-click .x-btn-center { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-pressed .x-btn-center { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-menu-active .x-btn-center { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .ytb-sep { BACKGROUND-IMAGE: = url(/core/extjs/ext-2.1/resources/images/default/grid/grid-split.gif) } .x-tab-panel-header { BORDER-LEFT-COLOR: #d0d0d0; BACKGROUND: #eaeaea; BORDER-BOTTOM-COLOR: = #d0d0d0; BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-tab-panel-footer { BORDER-LEFT-COLOR: #d0d0d0; BACKGROUND: #eaeaea; BORDER-BOTTOM-COLOR: = #d0d0d0; BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-tab-panel-header { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-tab-panel-footer { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } UL.x-tab-strip-top { BORDER-LEFT-COLOR: #d0d0d0; BACKGROUND: = url(/core/ext.ncbi/1/img/oldentrez/tabs/tab-strip-bg.gif) #dbdbdb = repeat-x left top; BORDER-BOTTOM-COLOR: #d0d0d0; BORDER-TOP-COLOR: = #d0d0d0; PADDING-TOP: 2px; BORDER-RIGHT-COLOR: #d0d0d0 } UL.x-tab-strip-bottom { BORDER-LEFT-COLOR: #d0d0d0; BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/tabs/tab-strip-btm-bg.gif); = BORDER-BOTTOM-COLOR: #d0d0d0; BORDER-TOP-COLOR: #d0d0d0; = BORDER-RIGHT-COLOR: #d0d0d0 } .x-tab-strip SPAN.x-tab-strip-text { COLOR: #333 } .x-tab-strip-over SPAN.x-tab-strip-text { COLOR: #111 } .x-tab-strip-active SPAN.x-tab-strip-text { COLOR: #333 } .x-tab-strip-disabled .x-tabs-text { COLOR: #aaaaaa } .x-tab-strip-top .x-tab-right { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/tabs/tabs-sprite.gif) } .x-tab-strip-top .x-tab-left { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/tabs/tabs-sprite.gif) } .x-tab-strip-top .x-tab-strip-inner { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/tabs/tabs-sprite.gif) } .x-tab-strip-bottom .x-tab-right { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/tabs/tab-btm-inactive-right-bg.gif) } .x-tab-strip-bottom .x-tab-left { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/tabs/tab-btm-inactive-left-bg.gif) } .x-tab-strip-bottom .x-tab-strip-active .x-tab-right { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/tabs/tab-btm-right-bg.gif) } .x-tab-strip-bottom .x-tab-strip-active .x-tab-left { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/tabs/tab-btm-left-bg.gif) } .x-tab-strip .x-tab-strip-closable A.x-tab-strip-close { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/tabs/tab-close.gif) } .x-tab-strip .x-tab-strip-closable A.x-tab-strip-close:hover { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/tabs/tab-close.gif) } .x-tab-panel-body { BORDER-LEFT-COLOR: #d0d0d0; BACKGROUND: #fff; BORDER-BOTTOM-COLOR: = #d0d0d0; BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-tab-panel-bbar .x-toolbar { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-tab-panel-tbar .x-toolbar { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-tab-panel-header-plain .x-tab-strip-spacer { BORDER-LEFT-COLOR: #d0d0d0; BACKGROUND: #eaeaea; BORDER-BOTTOM-COLOR: = #d0d0d0; BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-tab-scroller-left { BORDER-LEFT-COLOR: #aeaeae; BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/tabs/scroll-left.gif); = BORDER-BOTTOM-COLOR: #aeaeae; BORDER-TOP-COLOR: #aeaeae; = BORDER-RIGHT-COLOR: #aeaeae } .x-tab-scroller-right { BORDER-LEFT-COLOR: #aeaeae; BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/tabs/scroll-right.gif); = BORDER-BOTTOM-COLOR: #aeaeae; BORDER-TOP-COLOR: #aeaeae; = BORDER-RIGHT-COLOR: #aeaeae } .x-window-proxy { BORDER-LEFT-COLOR: #b0b0b0; BACKGROUND: #e0e0e0; BORDER-BOTTOM-COLOR: = #b0b0b0; BORDER-TOP-COLOR: #b0b0b0; BORDER-RIGHT-COLOR: #b0b0b0 } .x-window-tl .x-window-header { COLOR: #555 } .x-window-tc { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/window/top-bottom.png) } .x-window-tl { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/window/left-corners.png) } .x-window-tr { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/window/right-corners.png) } .x-window-bc { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/window/top-bottom.png) } .x-window-bl { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/window/left-corners.png) } .x-window-br { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/window/right-corners.png) } .x-window-mc { BORDER-RIGHT: #d0d0d0 1px solid; BORDER-TOP: #d0d0d0 1px solid; = BACKGROUND: #e8e8e8; BORDER-LEFT: #d0d0d0 1px solid; BORDER-BOTTOM: = #d0d0d0 1px solid } .x-window-ml { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/window/left-right.png) } .x-window-mr { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/window/left-right.png) } .x-panel-ghost .x-window-tl { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-panel-collapsed .x-window-tl { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-window-plain .x-window-mc { BORDER-RIGHT: #eee 1px solid; BORDER-TOP: #d0d0d0 1px solid; = BACKGROUND: #e8e8e8; BORDER-LEFT: #d0d0d0 1px solid; BORDER-BOTTOM: #eee = 1px solid } .x-window-plain .x-window-body { BORDER-RIGHT: #d0d0d0 1px solid; BORDER-TOP: #eee 1px solid; = BACKGROUND: none transparent scroll repeat 0% 0%; BORDER-LEFT: #eee 1px = solid; BORDER-BOTTOM: #d0d0d0 1px solid } BODY.x-body-masked .x-window-mc { BACKGROUND-COLOR: #e4e4e4 } BODY.x-body-masked .x-window-plain .x-window-mc { BACKGROUND-COLOR: #e4e4e4 } .x-html-editor-wrap { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-panel-noborder .x-panel-body-noborder { BORDER-TOP-WIDTH: 0px; BORDER-LEFT-WIDTH: 0px; BORDER-BOTTOM-WIDTH: = 0px; BORDER-RIGHT-WIDTH: 0px } .x-panel-noborder .x-panel-header-noborder { BORDER-TOP-WIDTH: 0px; BORDER-LEFT-WIDTH: 0px; BORDER-BOTTOM: #d0d0d0 = 1px solid; BORDER-RIGHT-WIDTH: 0px } .x-panel-noborder .x-panel-tbar-noborder .x-toolbar { BORDER-TOP-WIDTH: 0px; BORDER-LEFT-WIDTH: 0px; BORDER-BOTTOM: #d0d0d0 = 1px solid; BORDER-RIGHT-WIDTH: 0px } .x-panel-noborder .x-panel-bbar-noborder .x-toolbar { BORDER-TOP: #d0d0d0 1px solid; BORDER-LEFT-WIDTH: 0px; = BORDER-BOTTOM-WIDTH: 0px; BORDER-RIGHT-WIDTH: 0px } .x-window-noborder .x-window-mc { BORDER-TOP-WIDTH: 0px; BORDER-LEFT-WIDTH: 0px; BORDER-BOTTOM-WIDTH: = 0px; BORDER-RIGHT-WIDTH: 0px } .x-window-plain .x-window-body-noborder { BORDER-TOP-WIDTH: 0px; BORDER-LEFT-WIDTH: 0px; BORDER-BOTTOM-WIDTH: = 0px; BORDER-RIGHT-WIDTH: 0px } .x-tab-panel-noborder .x-tab-panel-body-noborder { BORDER-TOP-WIDTH: 0px; BORDER-LEFT-WIDTH: 0px; BORDER-BOTTOM-WIDTH: = 0px; BORDER-RIGHT-WIDTH: 0px } .x-tab-panel-noborder .x-tab-panel-header-noborder { BORDER-TOP-WIDTH: 0px; BORDER-LEFT-WIDTH: 0px; BORDER-RIGHT-WIDTH: 0px } .x-tab-panel-noborder .x-tab-panel-footer-noborder { BORDER-LEFT-WIDTH: 0px; BORDER-BOTTOM-WIDTH: 0px; BORDER-RIGHT-WIDTH: = 0px } .x-tab-panel-bbar-noborder .x-toolbar { BORDER-TOP: #d0d0d0 1px solid; BORDER-LEFT-WIDTH: 0px; = 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