IDH mutation status and role of WHO grade and mitotic index in overall survival in grade II-III diffuse gliomas.

Diffuse gliomas are up till now graded based upon morphology. Recent findings indicate that isocitrate dehydrogenase (IDH) mutation status defines biologically distinct groups of tumors. The role of tumor grade and mitotic index in patient outcome has not been evaluated following stratification by IDH mutation status. To address this, we interrogated 558 WHO grade II-III diffuse gliomas for IDH1/2 mutations and investigated the prognostic impact of WHO grade within IDH-mutant and IDH-wild type tumor subsets independently. The prognostic impact of grade was modest in IDH-mutant [hazard ratio (HR) = 1.21, 95 % confidence interval (CI) = 0.91-1.61] compared to IDH-wild type tumors (HR = 1.74, 95 % CI = 0.95-3.16). Using a dichotomized mitotic index cut-off of 4/1000 tumor cells, we found that while mitotic index was significantly associated with outcome in IDH-wild type tumors (log-rank p < 0.0001, HR = 4.41, 95 % CI = 2.55-7.63), it was not associated with outcome in IDH-mutant tumors (log-rank p = 0.5157, HR = 1.10, 95 % CI = 0.80-1.51), and could demonstrate a statistical interaction (p < 0.0001) between IDH mutation and mitotic index (i.e., suggesting that the effect of mitotic index on patient outcome is dependent on IDH mutation status). Patient age, an established prognostic factor in diffuse glioma, was significantly associated with outcome only in the IDH-wild type subset, and consistent with prior data, 1p/19q co-deletion conferred improved outcome in the IDH-mutant cohort. These findings suggest that stratification of grade II-III gliomas into subsets defined by the presence or absence of IDH mutation leads to subgroups with distinct prognostic characteristics. Further evaluation of grading criteria and prognostic markers is warranted within IDH-mutant versus IDH-wild type diffuse grade II-III gliomas as independent entities.

Symptoms and socio-economic impact of ependymoma on adult patients: results of the Adult Ependymoma Outcomes Project 2.

Ependymoma is a rare central nervous system tumor of adults. Reports of patient symptoms, interference patterns and costs encountered by patients and families are limited. Adult ependymoma patients completed the online Ependymoma Outcomes Questionnaire II. The survey assesses disease and functional status as well as socio-economic factors. Descriptive statistics were used to report disease characteristics as well as economic and social impact. Independent samples t test was used to test if differences exist between high- and low-income groups in terms of symptom severity. Correlations were calculated between symptoms and cost estimates. 86 international patients participated (male = 50 %). The economic analysis focused on 78 respondents from the US. 48 % were employed and 55 % earned ≥$60,000. Tumors were located in the brain (44 %), spine (44 %) or both (12 %). Spine patients compared to brain patients reported significantly worse pain (4.4 versus 2.2, p < .003), numbness (5.3 versus 2.2, p < .001), fatigue (5.1 versus 3.6, p < .03), changes in bowel patterns (3.8 versus 1.4, p < .003) and weakness (4.2 versus 2.1, p < .006). Brain patients compared with spine patients had increased lack of appetite (.4 versus 2, p < .014). Patients with lower income (≤$59,999) had more problems concentrating (p < .024) and worse cognitive module severity scores (p < .024). Estimated average monthly out-of-pocket spending was $168 for medical co-pays and $59 for prescription medication. Patients with ependymoma are highly affected by their symptoms. Spinal patients report higher severity of symptoms. Patients in the lower income group report significantly higher severity of cognitive symptoms independent of disease site.

Significant predictors of patients' uncertainty in primary brain tumors.

Patients with primary brain tumors (PBT) face uncertainty related to prognosis, symptoms and treatment response and toxicity. Uncertainty is correlated to negative mood states and symptom severity and interference. This study identified predictors of uncertainty during different treatment stages (newly-diagnosed, on treatment, followed-up without active treatment). One hundred eighty six patients with PBT were accrued at various points in the illness trajectory. Data collection tools included: a clinical checklist/a demographic data sheet/the Mishel Uncertainty in Illness Scale-Brain Tumor Form. The structured additive regression model was used to identify significant demographic and clinical predictors of illness-related uncertainty. Participants were primarily white (80 %) males (53 %). They ranged in age from 19-80 (mean = 44.2 ± 12.6). Thirty-two of the 186 patients were newly-diagnosed, 64 were on treatment at the time of clinical visit with MRI evaluation, 21 were without MRI, and 69 were not on active treatment. Three subscales (ambiguity/inconsistency; unpredictability-disease prognoses; unpredictability-symptoms and other triggers) were different amongst the treatment groups (P < .01). However, patients' uncertainty during active treatment was as high as in newly-diagnosed period. Other than treatment stages, change of employment status due to the illness was the most significant predictor of illness-related uncertainty. The illness trajectory of PBT remains ambiguous, complex, and unpredictable, leading to a high incidence of uncertainty. There was variation in the subscales of uncertainty depending on treatment status. Although patients who are newly diagnosed reported the highest scores on most of the subscales, patients on treatment felt more uncertain about unpredictability of symptoms than other groups. Due to the complexity and impact of the disease, associated symptoms, and interference with functional status, comprehensive assessment of patients is necessary throughout the illness trajectory.

Uncertainty, mood states, and symptom distress in patients with primary brain tumors: analysis of a conceptual model using structural equation modeling.

BACKGROUND: Patients with primary brain tumors (PBTs) face uncertainty related to prognosis, symptoms, treatment response, and toxicity. The authors of this report examined the direct/indirect relations among patients' uncertainty, mood states, and symptoms. METHODS: In total, 186 patients with PBTs were accrued at various points in the illness trajectory. Data-collection tools included an investigator-completed clinician checklist, a patient-completed demographic data sheet, the Mishel Uncertainty in Illness Scale-Brain Tumor Form (MUIS-BT), the MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT), and the Profile of Mood States-Short Form (POMS-SF). Structural equation modeling was used to explore correlations among variables. RESULTS: Participants were primarily white (80%) men (53%) with a variety of brain tumors. They ranged in age from 19 to 80 years (mean ± standard deviation, 44.2 ± 12.6 years). Lower functional status and earlier point in the illness trajectory were associated with greater uncertainty (P < .01 for both). Uncertainty (P < .05), except in the model of "confusion," and the 5 negative mood states measured by the POMS-SF were directly associated with symptom severity perceived by patients (P < .01 for all). The impact of uncertainty on perceived symptom severity also was mediated significantly by mood states. CONCLUSIONS: The results from the study clearly demonstrated distinct pathways for the relations between uncertainty-mood states-symptom severity for patients with PBTs. Uncertainty in patients with PBTs is higher for those who have a poor performance status and directly impacts negative mood states, which mediate patient-perceived symptom severity. This conceptual model suggests that interventions designed to reduce uncertainty or that target mood states may help lessen patients' perception of symptom severity, which, in turn, may result in better treatment outcomes and quality of life.

Congruence of primary brain tumor patient and caregiver symptom report.

BACKGROUND: Evaluating the severity of symptoms in patients with primary brain tumors (PBTs) is important in clinical care and research but may be difficult due to patient neurocognitive (NC) impairment. This study was conducted to evaluate the congruence of symptom reporting in patient and caregiver dyads, examining potential impact of NC impairment and Karnofsky performance status (KPS). METHODS: PBT patients undergoing NC testing and their caregivers were included in this study. These dyads (paired patient and caregiver group) completed the MD Anderson Symptom Inventory-Brain Tumor Module prior to testing, and impairment was categorized based on NC test scores. Concordance and equivalency was then assessed using Bland-Altman analysis and 2 one-sided techniques. RESULTS: A total of 115 dyads participated. Median patient and caregiver age was 49 and 51 years, respectively, and 63% of patients were male (73% female caregivers). Most patients had a good KPS (≥90, 66%) but were classified as NC impaired (58%). Caregiver's report of patient symptoms are congruent to the self-report of the patient. Equivalency between patient and caregiver report were found using prespecified confidence intervals. KPS group (good, ≥90; poor, ≤80) comparisons of equivalency indicated no significant differences in symptoms and interference reporting between dyads (good = 0.49, P > .05; and poor = 0.3, P > .05) overall, but there was a tendency for higher report by caregivers if the patients had a poor KPS. CONCLUSIONS: Caregivers of PBT patients have similar assessments of symptom severity (highly congruent) with patient self-report regardless of NC function or KPS. These findings suggest that caregivers may serve as proxy report of symptoms for primary brain tumor patients.

A prognostic gene expression signature in infratentorial ependymoma.

Patients with ependymoma exhibit a wide range of clinical outcomes that are currently unexplained by clinical or histological factors. Little is known regarding molecular biomarkers that could predict clinical behavior. Since recent data suggest that these tumors display biological characteristics according to their location (cerebral vs. infratentorial vs. spinal cord), rather than explore a broad spectrum of ependymoma, we focused on molecular alterations in ependymomas arising in the infratentorial compartment. Unsupervised clustering of available gene expression microarray data revealed two major subgroups of infratentorial ependymoma. Group 1 tumors over expressed genes that were associated with mesenchyme, Group 2 tumors showed no distinct gene ontologies. To assess the prognostic significance of these gene expression subgroups, real-time reverse transcriptase polymerase chain reaction assays were performed on genes defining the subgroups in a training set. This resulted in a 10-gene prognostic signature. Multivariate analysis showed that the 10-gene signature was an independent predictor of recurrence-free survival after adjusting for clinical factors. Evaluation of an external dataset describing subgroups of infratentorial ependymomas showed concordance of subgroup definition, including validation of the mesenchymal subclass. Importantly, the 10-gene signature was validated as a predictor of recurrence-free survival in this dataset. Taken together, the results indicate a link between clinical outcome and biologically identified subsets of infratentorial ependymoma and offer the potential for prognostic testing to estimate clinical aggressiveness in these tumors.

Validation of the Mishel's uncertainty in illness scale-brain tumor form (MUIS-BT).

The Mishel uncertainty in illness scale (MUIS) has been used extensively with other solid tumors throughout the continuum of illness. Interventions to manage uncertainty have been shown to improve mood and symptoms. Patients with primary brain tumors (PBT) face uncertainty related to diagnosis, prognosis, symptoms and response. Modifying the MUIS to depict uncertainty in PBT patients will help define this issue and allow for interventions to improve quality of life. Initially, 15 experts reviewed the content validity of the MUIS-brain tumor form (MUIS-BT). Patients diagnosed with PBT then participated in the study to test validity and reliability. Data was collected at one point in time. Six out of 33 items in the original MUIS were modified to better describe PBT patients' uncertainty. 32 of the 186 patients in the second-stage of the study were newly diagnosed with PBT, 85 were on treatment, and 69 were followed-up without active treatment. The validity of the MUIS-BT was demonstrated by its correlations with mood states (P < 0.01) and symptom severity (P < 0.01) and interference (P < 0.01). The MUIS-BT measures four constructs: ambiguity/inconsistency, unpredictability of disease prognosis, unpredictability of symptoms and other triggers, and complexity. Cronbach's alphas of the four subscales were 0.90, 0.77, 0.75 and 0.65, respectively. The 33-item MUIS-BT demonstrated adequate select measures of validity and reliability in PBT patients. Based on this initial validation and significant correlations with symptom distress and mood states, further understanding of uncertainty and evaluation of measures to help manage patients' uncertainty can be evaluated which in turn may improve coping and quality of life.

Clinical course of adult patients with ependymoma: results of the Adult Ependymoma Outcomes Project.

BACKGROUND: Ependymomas are a rare tumor in adults, and there are limited reports of the clinical course, treatment, and current health status of patients. METHODS: Patients with ependymoma completed an online survey regarding their diagnosis, treatment course, and current health status. Descriptive statistics were used to report the characteristics and degree of symptom severity. Correlations between demographic and clinical characteristics were explored with univariate analysis. RESULTS: One hundred eighteen adults participated, and there were more women (n = 68) than men (n = 50). The median age was 48 years (range, 22-77 years). Fifty-nine participants (48%) reported that they had not been able to work since their diagnosis, and 31% reported receiving disability benefits. Patients who had been treated for spine tumors had symptoms longer than those who had been treated for brain lesions (chi-square statistic, 7.294; P = .026), and the majority had 3 symptoms before diagnosis. Most patients reported undergoing complete resection (brain lesions, 62%; spine tumors, 58%), and patients with spine tumors were less likely to have received additional treatment (chi-square statistic, 9.687; P = .008). The majority had not had a recurrence and reported consulting a neurosurgeon for surveillance. Despite having stable disease and not receiving active treatment, most patients described moderate to severe symptoms, including fatigue (44%), numbness/tingling (39%), pain (36%), and disturbed sleep (34%) overall. Brain lesions were associated with altered vision (25%), difficulty concentrating (25%), weakness (19%), irritability (19%), difficulty speaking (19%), and understanding (17%); and spine lesions were associated with extremity weakness (55%), sexual dysfunction (48%), radiating pain (37%), and change in bowel pattern (35%). CONCLUSIONS: Treatment for adult patients with ependymoma is not standardized. Despite the low recurrence rate, patients reported significant symptoms and disability.

The impact of symptom interference using the MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) on prediction of recurrence in primary brain tumor patients.

BACKGROUND: Tumor grade, age, extent of resection, and performance status are established prognostic factors for survival in primary brain tumor (PBT) patients. Development of disease-related symptoms is predictive of tumor recurrence in other cancers but has not been reported in the PBT population. METHODS: A cross-sectional sample of 294 PBT patients participated. Progression was based on the radiologist report of the magnetic resonance imaging (MRI). The relation of clinical variables (age, extent of resection, tumor grade, and Karnofsky performance status [KPS]) and MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) mean symptom and interference subscales with progression was examined using logistic regression. RESULTS: The study enrolled more men (60%, n = 175); median age was 46 years. The majority had less than a gross total resection (n = 186, 64%), and a good KPS (KPS ≥ 90) (N = 208). The majority had a grade 3 or 4 tumor (n = 199) and 24% of patients had recurrence. Tumor grade and activity-related interference were significantly related to progression. Patients with tumor grade 4 were 2.4 times more likely to have recurrence (95% CI, 1.2-5.; P < .015). Patients with significant (ratings of ≥ 5) activity-related interference were 3.8 times more likely to have recurrence (95% CI, 2.14-6.80; P < .001). Mean activity-related score was 4.8 for those with progression on MRI and 2.2 for those with stable disease. CONCLUSIONS: Significant activity-related interference and tumor grade were associated with recurrence but not KPS, age, or extent of resection. These results provide preliminary support for the use of symptom interference in assessment of disease status. Because the authors used a cross-sectional sample, future studies evaluating change over time are needed.

Pregnenolone for cognition and mood in dual diagnosis patients.

Mood and substance-use disorders are both associated with cognitive deficits. Patients with mood and substance-use disorders have poorer cognition than patients with only a mood disorder. Pregnenolone may have beneficial effects on mood and cognition. In a proof-of-concept investigation, 70 participants with bipolar disorder or recurrent major depressive disorder and history of substance abuse/dependence (abstinent for > or =14days prior to enrollment) were randomly assigned to receive pregnenolone (titrated to 100mg/day) or placebo for 8weeks. Participants were assessed using the Mini International Neuropsychiatric Interview, Hamilton Rating Scale for Depression (HRSD), Young Mania Rating Scale (YMRS), Rey Auditory Verbal Learning Test (RAVLT), Trail Making Test (TMT-B), and Stroop Test. Mood was assessed bi-weekly, while cognition was evaluated at baseline, and weeks 4 and 8. Groups were compared using a random regression analysis that used all of the available data. The pregnenolone group showed trends toward greater improvement, relative to placebo, on the HRSD and YMRS. A post hoc analysis of completers found a statistically significant reduction in HRSD scores with pregnenolone as compared to placebo. Pregnenolone appeared to be safe and well tolerated. Findings suggest that pregnenolone use may be associated with some improvement in manic and depressive symptoms, but not cognition in depressed patients with a history of substance use. Larger trials examining the impact of pregnenolone on mood in more narrowly defined populations may be warranted.

The symptom burden of primary brain tumors: evidence for a core set of tumor- and treatment-related symptoms.

BACKGROUND: A set of symptoms common across cancers has been proposed to enhance quality of care and clinical research in solid tumor patients. Using data from several clinical studies, this study evaluated these symptoms in primary brain tumor patients. METHODS: Symptom report data using the MD Anderson Symptom Instrument -Brain Tumor (MDASI-BT) from 621 patients enrolled in 8 clinical studies was used. The prevalence and severity of symptoms were reported as they relate to tumor grade, treatment stage and KPS. RESULTS: The sample was primarily white (82.5%) males (59%) with high-grade gliomas (75%). More than 50% of patients reported at least 10 concurrent symptoms, and 40% of patients reporting having at least 3 moderate-to-severe symptoms. Fatigue, drowsiness, difficulty remembering, disturbed sleep, and distress were the most severe symptoms reported by all tumor grades. Functional interference of symptoms with ability to work, perform activities, walk, and enjoy life was reported by more than 25% of patients. CONCLUSIONS: These results support a core set of symptoms, common in other solid tumor patients, that may impact clinical care and assessment of treatment benefit. Although only 5 of the Center for Medical Technology Policy list of proposed core symptoms met criteria for inclusion in this sample, 5 of the other proposed core symptoms were also reported in similar frequency as reported in the other cancer populations. This primary brain tumor population differed from other solid tumor patients in that other symptoms, which could be disease related, were more prevalent and thus should also be collected for these patients.

Hope and mood changes throughout the primary brain tumor illness trajectory.

BACKGROUND: The ambiguity of defining hope impacts the level of readiness faced by health care professionals treating patients with glioma, a disease with unpredictable outcomes. This study describes the report of hope and the relationship between hope and mood in adult brain tumor patients at various points in the illness trajectory. METHODS: This was a cross-sectional study with data collection including use of the Herth Hope Index (HHI), the Profile of Mood States-Short Form (POMS-SF), and clinical information. Descriptive statistics were used to report sample characteristics. Spearman's rho and Mann-Whitney tests were used to compare and differentiate scores. RESULTS: Eighty-two patients ranging in age from 22 to 78 years (median, 44.5 y) participated in the study. Patients were primarily male (57.3%), married (76.8%), and had a high-grade glioma (35.4%). Nearly half had recurrence, and more than 20% were on active treatment. The overall HHI total score for the sample was 41.32 (range: 13-48). Patients with recurrence had a lower HHI interconnectedness (median = 14.00) score and higher total mood disturbance (median = 14.00) compared with patients without recurrence (median = 15.00 and median = 0.00, respectively; P < .05). All negative mood states on the POMS-SF were negatively correlated with HHI subscales. CONCLUSIONS: Overall, patients reporting more hope also reported less overall mood disturbance As expected, patients with tumor recurrence reported lower hope and higher mood disturbance than those who were newly diagnosed or without recurrence. Targeting interventions specifically tailored to an individual's needs for improvement in quality of life throughout the disease course may include measures to address hope in order to facilitate positive coping strategies.

The relationship between corticosteroids and symptoms in patients with primary brain tumors: utility of the Dexamethasone Symptom Questionnaire-Chronic.

BACKGROUND: Corticosteroids can have many side effects that impact the patient's quality of life and functional status. The Dexamethasone Symptom Questionnaire-Chronic (DSQ-C) was developed to report corticosteroid side effects. This study's objective was to evaluate the utility of the DSQ-C and report associated signs and symptoms in brain tumor patients. METHODS: Data collection included demographic and disease characteristics and the DSQ-C. Descriptive statistics were used to report associations among variables. Linear regression models were applied to assess the effects of the cumulative daily dose (mg/d × total d) on DSQ-C scores. Psychometrics included factor analysis to assess construct validity and Cronbach's alpha for internal consistency. RESULTS: Ninety-six adult patients with primary (77%) or metastatic (23%) brain tumors participated, with 74% on corticosteroids. Participants were primarily white (83%) males (65%) between 20 and 75 years of age (median, 53). Median corticosteroid dose duration was 4 mg/day for 1 month (range, 0-26 mo). The DSQ-C scores ranged from 17 to 54 (mean of 27), with 35% reporting increased appetite and trouble sleeping. Factor analysis indicated 6 underlying constructs explaining 53% of variance. DSQ-C internal consistency (reliability) was 0.77. The DSQ-C discriminated between patients who were on steroids and those who were not (P < .01), and cumulative dose predicted DSQ-C scores (P < .001). CONCLUSIONS: This study demonstrated the potential use of the DSQ-C as a screening tool for side effects associated with corticosteroid use in brain tumor patients. Future analyses should include longitudinal evaluation of severity and biologic underpinnings of variability of timing and severity of symptoms.

Clinical course and progression-free survival of adult intracranial and spinal ependymoma patients.

BACKGROUND: Ependymomas are rare CNS tumors. Previous studies describing the clinical course of ependymoma patients were restricted to small sample sizes, often with patients at a specific institution. METHODS: Clinically annotated ependymoma tissue samples from 19 institutions were centrally reviewed. Patients were all adults aged 18 years or older at the time of diagnosis. Potential prognostic clinical factors identified on univariate analysis were included in a multivariate Cox proportional hazards model with backwards selection to model progression-free survival. RESULTS: The 282 adult ependymoma patients were equally male and female with a mean age of 43 years (range, 18-80y) at diagnosis. The majority were grade II (78%) with the tumor grade for 20 cases being reclassified on central review (half to higher grade). Tumor locations were spine (46%), infratentorial (35%), and supratentorial (19%). Tumor recurrence occurred in 26% (n = 74) of patients with a median time to progression of 14 years. A multivariate Cox proportional hazards model identified supratentorial location (P < .01), grade III (anaplastic; P < .01), and subtotal resection, followed or not by radiation (P < .01), as significantly increasing risk of early progression. CONCLUSIONS: We report findings from an ongoing, multicenter collaboration from a collection of clinically annotated adult ependymoma tumor samples demonstrating distinct predictors of progression-free survival. This unique resource provides the opportunity to better define the clinical course of ependymoma for clinical and translational studies.

Impact of recall period on primary brain tumor patient's self-report of symptoms.

BACKGROUND: Understanding the severity of symptoms is an integral part of patient care. The MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) was developed using a 24-hour recall period. The choice of recall period is dependent on the treatment and disease of interest. The aim of this study was to evaluate the congruence and equivalency of 24-hour and 7-day symptom reporting using the MDASI-BT. METHOD: Adult brain tumor patients completed the MDASI-BT using 24-hour and 7-day recall periods and a tablet format. Equivalence and congruence were determined using equivalency testing and Bland-Altman analysis. Reliability and known group's validity were then assessed by use of Cronbach's alpha and evaluating differences based on performance status. RESULTS: One hundred patients (mean age, 48 y; range 19 y-77 y), who were primarily white (86%) males (62%) with a variety of brain tumors, most commonly glioblastoma (69%), participated. KPS scores ranged from 50%-100%, with 28% of participants scoring 80% or lower. Overall severity reporting using the 7-day recall was congruent and equivalent with the 24-hour rating, with difference scores of one point or less on the overall instrument and individual symptoms. The 7-day recall period instrument demonstrated psychometric properties similar to the established 24-hour recall instrument. CONCLUSION: This study supports the use of the 7-day recall period in addition to the 24-hour recall period for symptom reports of patients with primary brain tumors. Future studies should continue to explore the reliability and validity of this recall period and its utility in other central nervous system tumor populations.

Personal health records, symptoms, uncertainty, and mood in brain tumor patients.

BACKGROUND: The advantages of patient access to the electronic medical record (EMR) through integrated personal health records (PHR) may be substantial, and foremost is the enhanced information flow between patient and practitioner. Because this is an emerging technology, the actualized benefits to complex patient groups remain largely unknown. MD Anderson Cancer Center provides web-based PHR portal access to the EMR including clinic notes, MRI results, and pathology reports. This study sought to evaluate PHR use by glioma patients. METHODS: Cross-sectional survey and PHR-derived user data from 186 patients were analyzed using descriptive and inferential statistics. Logistic regression assessed disparities between users and nonusers. Dependence of PHR access on treatment stage was tested through linear regression. Path analysis evaluated PHR access, disease-related uncertainty, symptom experience, and mood. RESULTS: Patients averaged 44.2 years (range 19y-80y), 77% had a high-grade tumor, and 60% had accessed PHR at least one time (range 0-126). Strongest predictors of access included education level (college level or higher), low performance status, middle income, and in-state residency. Patients undergoing treatment were more active users. PHR access was associated with lower disease-related uncertainty and lower symptom severity. Mood was not directly related to PHR use but mediated an association between symptom severity and uncertainty. CONCLUSIONS: While many reports presume better disease and symptom understanding for patients with EMR access, this study is the first to correlate PHR use to lower patient uncertainty levels. Early examination of PHR provides an important basis for critical evaluation and optimization to better structure this benefit for brain tumor patients.

Histological predictors of outcome in ependymoma are dependent on anatomic site within the central nervous system.

Ependymomas originate in posterior fossa (PF), supratentorial (ST) or spinal cord (SC) compartments. At present, grading schemes are applied independent of anatomic site. We performed detailed histological examination on 238 World Health Organization grade II and III ependymomas. Among PF ependymomas, the presence of hypercellular areas, necrosis, microvascular proliferation and elevated mitotic rate (all P < 0.01) were significantly associated with worse progression-free survival (PFS), while extensive ependymal canal formation was not (P = 0.89). Similar to the PF tumors, microvascular proliferation (P = 0.01) and elevated mitotic rate (P = 0.03) were significantly associated with worse PFS in the ST tumors. However, in contrast to PF tumors, extensive ependymal canals (P = 0.03) were associated with worse clinical outcome in ST ependymomas, but hypercellularity (P = 0.57) and necrosis (P = 0.47) were not. On multivariate Cox regression, after adjusting for relevant clinical variables, individual histological factors and a composite histological score remained significant among ST and PF ependymoma. In contrast to both PF and ST ependymoma, histological features were not found to be associated with PFS in SC tumors. Taken together, the clinical relevance of specific histological features in ependymoma appears to be related to the anatomic site of origin and suggests that site-specific grading criteria be considered in future classification systems.

Adult ependymal tumors: prognosis and the M. D. Anderson Cancer Center experience.

Ependymomas in adults are rare and often misdiagnosed. This study reports on a series of adult patients with confirmed ependymoma treated at The University of Texas M. D. Anderson Cancer Center (MDACC). Patients aged >17 and with ependymoma were identified, and clinical data were collected by retrospective chart review. Descriptive statistics were used to describe the clinical data, Kaplan-Meier methods were used to generate survival curves, and Cox proportional hazards models were used to evaluate the association of clinical characteristics with survival. This series included 123 adult patients [51% male; median age 39 years (18-72)]. Forty had tumors in the brain, 80 in the spine, and 3 had both. The majority were Grade I/II lesions (108) vs Grade III (anaplastic; 15). Eighteen patients had tumors that were reclassified as ependymal tumors at MDACC. The most common presenting symptom was pain, with an average of 4 symptoms reported prior to diagnosis. Sixty-three percent of patients had a gross total resection, and 49% received radiation therapy. Average follow-up was 5.5 years, and 13% had died. Median time to recurrence was 21 months (Grade II) brain and 18 months (Grade III). Worse outcome measured by overall and progression-free survival were associated with brain location (P = .01, P = .04) and tumor anaplasia (P = .0025, P = .001). An MIB-1 > 10 was associated with worse outcome (P = .03). Tumor grade and brain location are associated with a worse prognosis. Reclassification of ependymoma by neuropathologists is common. Results of this study have lead to a multicenter study to further define important diagnostic and prognostic variables for adults with ependymoma.

Reliability and validity of the M. D. Anderson Symptom Inventory-Spine Tumor Module.

OBJECT: Tumors involving the spine have unique associated neurological symptoms. The occurrence of spine-related symptoms has been shown to predict treatment course and survival in several studies conducted in patients with solid tumors and consequent spinal cord dysfunction. Currently, no instrument that measures both neurological and cancer-related symptoms exists for patients with spine tumors. The objective of this study was to develop a reliable and valid self-reporting instrument for patients with spine tumors. METHODS: Patients with diagnosed tumors involving the spine (both primary and metastatic) participated in this study. Data collection tools included a patient-completed demographic data sheet, an investigator-completed clinician checklist, and the core M. D. Anderson Symptom Inventory to which were added 16 neurological symptoms (M. D. Anderson Symptom Inventory-Spine Tumor Module [MDASI-SP]). The authors evaluated the reliability and validity of the MDASI-SP in patients with spine tumors. RESULTS: One hundred twenty-six patients participated in the study. Participants were primarily white (73%) males (53%) with metastatic spine tumors (76%). They ranged in age from 18-81 years (median 56 years). Cognitive debriefing of the MDASI-SP was conducted showing the instrument was clear, concise, and easily understood by patients. The most severe core symptoms were pain, fatigue, numbness, disturbed sleep, and distress. The most severe spine module symptoms were spine pain, numbness, weakness in the legs, neck stiffness, and changes in bowel or sexual function. The mean symptom severity of items as well as a cluster analysis was used to reduce the number of total items to 18 (5 spine module items). Regression analysis showed that 57.4% of the variability in symptom interference with daily function was explained by the final instrument. Factor analysis was performed to determine the underlying constructs being evaluated by the symptom items. The 18-item MDASI-SP measures 4 underlying constructs including a disease, an autonomic, a constitutional/treatment, and an emotional factor. The internal consistency (reliability) of the MDASI-SP was 0.946, and the instrument was sensitive to disease severity based on the Karnofsky Performance Scale (KPS). The mean symptom severity was 1.52 for those with good KPS scores (80-100) versus 2.46 for those with poor scores (p < 0.01). The instrument was also sensitive to neurological status according to the Frankel grade (p < 0.001) and inpatient status (p < 0.01). CONCLUSIONS: The 18-item MDASI-SP demonstrated validity and reliability in patients with spine tumors as a composite measure of disease-related symptoms. This instrument can be used to describe symptom occurrence throughout the disease trajectory and to evaluate interventions designed for symptom management.

Risk analysis of severe myelotoxicity with temozolomide: the effects of clinical and genetic factors.

A benefit of temozolomide (TMZ) is that myelotoxicity is uncommon. Recently, several small series have reported significant myelotoxicity resulting in treatment delays or death. The ability to predict risk of myelotoxicity may influence patient care. We retrospectively reviewed 680 malignant glioma patients and developed a clinical risk formula for myelotoxicity for each gender by logistic regression. The variables that remained were assigned a score of 1 and added together for a final risk score. Women experienced more myelotoxicity than did men (p = 0.015). For males, risk factors included body surface area (BSA) > or = 2 m(2) (odds ratio [OR] = 2.712, p = 0.04), not on steroids (OR = 2.214, p = 0.06), and on bowel medication (OR = 3.955, p = 0.008). For females, final factors included no prior chemotherapy (OR = 3.727, p = 0.001), creatinine > or = 1 mg/dl (OR = 6.08, p = 0.002), platelets < 270,000/mm(3) (OR = 2.438, p = 0.03), BSA < 2 m(2) (OR = 4.178, p = 0.04), not on medication for gastroesophageal reflux disease (OR = 2.942, p = 0.01), and on analgesics (OR = 2.169, p = 0.05). Age was included because of observable trends. Risk of developing myelotoxicity ranged from 0% to 33% (male) and from 0% to 100% (females). Polymorphisms in NQO1 (NAD(P)H dehydrogenase, quinone 1), MGMT (O(6)-methylguanine-DNA methyltransferase), and GSTP1 (glutathione S-transferase pi 1) were related to risk of developing myelotoxicity in a subset of patients. Myelotoxicity with TMZ is a significant clinical issue for those at risk. Use of a clinical model to predict risk and evaluation of identified genetic polymorphisms related to myelotoxicity may allow for individualized dosing, optimizing patient management.