Anderson Symptom Inventory-Brain Tumor Module Research Articles

Assessing mobility in primary brain tumor patients: A descriptive feasibility study using two established mobility tests.

Patients with primary brain tumors (PBT) face significant mobility issues related to their disease and/or treatment. Here, the authors describe the preliminary utility and feasibility of two established mobility measures, the Timed-Up-and-Go (TUG) and Five-Times Sit-to-Stand (TSS) tests, in quickly and objectively assessing the mobility status of PBT patients at a single institution's neuro-oncology clinic. Adult patients undergoing routine PBT care completed the TUG/TSS tests and MD Anderson Symptom Inventory-Brain Tumor module (MDASI-BT), which assessed symptom burden and interference with daily life, during clinic visits over a 6-month period. Research staff assessed feasibility metrics, including test completion times/rates, and collected demographic, clinical, and treatment data. Mann-Whitney tests, Kruskal-Wallis tests, and Spearman's rho correlations were used to interrogate relationships between TUG/TSS test completion times and patient characteristics. The study cohort included 66 PBT patients, 59% male, with a median age of 47 years (range: 20-77). TUG/TSS tests were completed by 62 (94%) patients. Older patients (P < .001) and those who were newly diagnosed (P = .024), on corticosteroids (P = .025), or had poor (≤80) KPS (P < .01) took longer to complete the TUG/TSS tests. Worse activity-related (work, activity, and walking) interference was associated with longer TUG/TSS test completion times (P < .001). The TUG/TSS tests are feasible for use among PBT patients and may aid in clinical care. Older age, being newly diagnosed, using corticosteroids, poor (≤80) KPS, and high activity-related interference were associated with significant mobility impairment, highlighting the tests' potential clinical utility. Future investigations are warranted to longitudinally explore feasibility and utility in other practice and disease settings.

Abstract CT115: Phase II study of dianhydrogalactitol (VAL-083) in patients with MGMT-unmethylated, bevacizumab-naïve recurrent glioblastoma

Abstract Glioblastoma (GBM) is the most common and aggressive primary brain cancer. Current standard-of-care includes surgery followed by concurrent therapy with radiation and temozolomide (TMZ) and maintenance TMZ. Almost all GBM patients experience recurrent/progressive disease, and median survival after recurrence is 3-9 months. Effective therapies for recurrent GBM (rGBM) are lacking, representing a significant unmet medical need. The unmethylated promoter for O6-methylguanine-DNA-methyltransferase (MGMT) is a validated biomarker for TMZ-resistance and is correlated with poor prognoses. Second-line treatment with the anti-angiogenic agent bevacizumab (BEV) has not improved survival, and 5-year survival is less than 3%. VAL-083 is a bi-functional DNA-targeting agent that rapidly induces interstrand cross-links at N7-guanine, leading to DNA double-strand breaks and cell-death. VAL-083’s cytotoxicity is independent of MGMT status, and VAL-083 overcomes TMZ-resistance in GBM in vitro and in vivo models. We previously completed a 3+3 dose-escalation trial of VAL-083 in TMZ- and BEV-refractory rGBM. 40mg/m2/day given on days 1-3 of a 21-day cycle was generally well-tolerated, and this dose was selected for further clinical evaluation in Phase II trials. The trial described here is an ongoing single-arm, biomarker-driven Phase II trial in MGMT-unmethylated BEV-naïve adult rGBM. In this trial, patients are receiving VAL-083 at 30 or 40mg/m2/day on days 1-3 of a 21-day cycle. Tumor response is assessed by MRI approximately every 42 days, per RANO criteria. The primary objective of this study is to determine if VAL-083 improves median overall survival (mOS) for MGMT-unmethylated rGBM patients compared to a historical mOS of 7.1 months for such patients treated with lomustine (EORTC26101). Secondary efficacy endpoints include progression-free survival (PFS), overall response rate (ORR), duration of response (DOR), and quality-of-life (QOL) evaluation using the MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) self-reporting tool. Thirty-five (35) subjects have received 40 mg/m2/day VAL-083 as the starting dose. Consistent with prior studies, myelosuppression (thrombocytopenia and neutropenia) is the most common adverse event in this study, and we observed that a higher potential for myelosuppression appears to be inversely correlated with the number of cycles of prior TMZ maintenance therapy, (&amp;gt;5 cycles vs. ≤5 cycles, p&amp;lt;0.05). Therefore, to minimize the potential for hematological toxicity in patients who have had significant prior TMZ maintenance therapy, subsequent patients in this study have initiated treatment with a starting VAL-083 dose of 30 mg/m2/d x 3 every 21 days. Earlier initiation of maintenance treatment with VAL-083 in the therapeutic management plan, in lieu of maintenance TMZ in MGMT-unmethylated GBM patients is currently under consideration. Enrollment, safety data and protocol updates will be provided at the meeting. Clinicaltrials.gov identifier: NCT02717962. Citation Format: Barbara O'Brien, John De Groot, Carlos Kamiya-Matsuoka, Shiao-Pei Weathers, Jeffrey Bacha, Dennis Brown, Anne Steino, John Langlands, Richard Schwartz, Sarath Kanekal, Lorena Lopez, Marta Penas-Prado. Phase II study of dianhydrogalactitol (VAL-083) in patients with MGMT-unmethylated, bevacizumab-naïve recurrent glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT115.

Pilot randomized, controlled trial of a dyadic yoga program for glioma patients undergoing radiotherapy and their family caregivers.

While the use of behavioral medicine in managing glioma patients' symptoms is not well studied, the high symptom burden in patients and their family caregivers is well established. We conducted a pilot randomized, controlled trial to examine the feasibility and preliminary efficacy of a dyadic yoga (DY) intervention as a supportive care strategy. Glioma patients undergoing radiotherapy and their caregivers were randomized to a 12-session DY or waitlist control (WLC) group. Prior to radiotherapy and randomization, both groups completed measures of cancer-related symptoms (MD Anderson Symptom Inventory-Brain Tumor module), depressive symptoms (Center for Epidemiological Studies-Depression measure), fatigue (Brief Fatigue Inventory), and overall quality of life (QOL; Medical Outcomes Study 36-item short-form survey). Dyads were reassessed at the last day of radiotherapy. Twenty patients (mean age: 46 years, 50% female, 80% WHO grade IV and caregivers (mean age: 50 years, 70% female, 50% spouses) participated in the trial. A priori feasibility criteria were met regarding consent (70%), adherence (88%), and retention (95%) rates. Controlling for relevant covariates, change score analyses revealed clinically significant improvements for patients in the DY compared with the WLC group for overall cancer symptom severity (d = 0.96) and symptom interference (d = 0.74), depressive symptoms (d = 0.71), and mental QOL (d = 0.69). Caregivers in the DY group reported clinically significant improvements in depressive symptoms (d = 1.12), fatigue (d = 0.89), and mental QOL (d = 0.49) relative to those in the WLC group. A DY intervention appears to be a feasible and beneficial symptom and QOL management strategy for glioma patients undergoing radiotherapy and their caregivers. An efficacy trial with a more stringent control group is warranted. NCT02481349.

Abstract CT167: Phase II study of dianhydrogalactitol (VAL-083) in patients with bevacizumab-naive recurrent glioblastoma, MGMT-unmethylated

Abstract Glioblastoma (GBM) is the most common and aggressive primary brain cancer. Current standard of care includes surgery followed by concurrent therapy with radiation and temozolomide (TMZ) and maintenance TMZ. The vast majority of GBM patients experience recurrent/progressive disease within a year from initial diagnosis, and median survival after recurrence is 3-9 months. Effective therapies for recurrent GBM (rGBM) are lacking and these patients have a dismal prognosis, representing a significant unmet medical need. Unmethylated promoter status for O6-methylguanine-DNA-methyltransferase (MGMT), a validated biomarker for TMZ-resistance, is strongly correlated with TMZ-resistance. Second-line treatment with the anti-angiogenic agent bevacizumab has not improved survival and 5-year survival is less than 3%. VAL-083 is a bi-functional DNA-targeting agent rapidly inducing interstrand cross-links at N7-guanine, leading to DNA double-strand breaks and cell-death. VAL-083's cytotoxicity is independent of MGMT status in vitro and VAL-083 overcomes TMZ-resistance in GBM cell lines, GBM cancer stem cells and in vivo GBM models. We completed a 3:3 dose-escalation trial of VAL-083 in TMZ- and bevacizumab-refractory rGBM. 40mg/m2/day given on days 1, 2, and 3 of a 21-day cycle was well-tolerated with 6% grade 3 or 4 thrombocytopenia. This dose was selected for further clinical development in a pivotal Phase 3 study in TMZ- and bevacizumab-refractory rGBM. The trial described here is an ongoing single-arm, biomarker-driven Phase 2 clinical trial in MGMT-unmethylated bevacizumab-naïve adult rGBM. 48 patients will receive VAL-083 40mg/m2/day on days 1, 2, and 3 of a 21-day cycle. Tumor response will be assessed by MRI approximately every 42 days, according to RANO criteria. The primary objective of this study is to determine if VAL-083 improves overall survival (OS) for MGMT-unmethylated rGBM patients compared to a historical median survival control of 7.2 months for MGMT-unmethylated rGBM patients treated with lomustine (Wick et al, EORTC26101). Secondary efficacy endpoints include progression-free survival (PFS), overall response rate (ORR), duration of response (DOR), and to evaluate the occurrence of symptoms and to evaluate quality of life (QOL) measures during the progression-free period using the MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) self-reporting tool. Enrollment and safety data update will be provided at the meeting. Clinicaltrials.gov identifier: NCT02717962. Citation Format: Barbara J. O'Brien, John De Groot, Carlos Kamiya-Matsuoka, Shiao-Pei Weathers, Jeffrey A. Bacha, Dennis M. Brown, Anne Steino, John Langlands, Richard Schwartz, Sarath Kanekal, Lorena Lopez, Marta Penas-Prado. Phase II study of dianhydrogalactitol (VAL-083) in patients with bevacizumab-naive recurrent glioblastoma, MGMT-unmethylated [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT167.

Differences in Type Composition of Symptom Clusters as Predictors of Quality of Life in Patients with Meningioma and Glioma

Objectives of this study were to identify and compare symptom clusters in patients with meningioma and glioma and to assess and compare predictors of quality of life (QoL) in both patient groups. Data were collected using the MD Anderson Symptom Inventory-Brain Tumor Module, Functional Assessment of Cancer Therapy-General, and Karnofsky Performance Sale. Of 158 participating patients, 77 had meningioma, and 81 had glioma. In patients with meningioma, 4 symptom clusters were identified with 55.4% total variance: 1) physical, 2) cognitive, 3) elimination-appearance, and 4) motor-sensory symptoms. In patients with glioma, 4 clusters with 67.3% total variance were identified: 1) treatment-related, 2) cognitive, 3) appearance-elimination, and 4) gastrointestinal symptoms. Predictors of QoL in patients with meningioma were Karnofsky Performance Scale score(β= 0.41, P < 0.001), cognitive symptom cluster (β=-0.36, P < 0.001), and physical symptom cluster (β=-0.32, P= 0.001), whereas treatment-related symptom cluster (β=-0.55, P < 0.001) was identified as a predictor of QoL in patients with glioma. In this study, the type and composition of symptom clusters differed between patients with meningioma and glioma. Our data also provide evidence that even when participants reported mild symptoms, these clusters could be used to predict QoL in patients with meningioma and glioma.

Net Clinical Benefit Analysis of Radiation Therapy Oncology Group 0525: A Phase III Trial Comparing Conventional Adjuvant Temozolomide With Dose-Intensive Temozolomide in Patients With Newly Diagnosed Glioblastoma

Radiation Therapy Oncology Group trial 0525 tested whether dose-intensifying temozolomide versus standard chemoradiotherapy improves overall survival (OS) or progression-free survival (PFS) in newly diagnosed glioblastoma. Tests of neurocognitive function (NCF) and symptoms (using the MD Anderson Symptom Inventory-Brain Tumor module; MDASI-BT) and of quality of life (European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ] -C30/BN20) examined the net clinical benefit (NCB) of therapy. NCF tests (Hopkins Verbal Learning Test-Revised, Trail Making Test, and Controlled Oral Word Association), MDASI-BT, and EORTC QLQ-C30/BN20 were completed in a subset of patients. Multivariate Cox proportional hazard regression modeling determined the prognostic value of baseline and early change from baseline to cycle 1 for OS and PFS. Two-sample proportional test statistic was used to evaluate differences between treatments (dose-dense v standard-dose) on NCB measures from baseline to cycle 4 in stable patients. Overall, 182 patients participated in the study. Baseline NCF tests and the physical functioning quality of life scale were associated with OS and PFS. Baseline to cycle 1 in all NCB components were associated with OS and PFS. There was greater deterioration in the dose-dense arm from baseline to cycle 4 in the Global Health and Motor Function subscales (EORTC QLQ-C30/BN20) as well as in overall symptom burden, overall symptom interference, and activity-related symptom interference subscales (MDASI-BT). There were no between-arm differences in NCF. Longitudinal collection of NCB measures is feasible in cooperative group studies and provides an added dimension to standard outcome measures. Greater adverse symptom burden and functional interference, as well as decreased global health and motor function were observed in patients randomly assigned to the dose-dense arm. Baseline and early change in NCB measures were associated with decreased rates of survival.

Comparative impact of treatment on patient reported outcomes (PROs) in patients with glioblastoma (GBM) enrolled in RTOG 0825.

2003 Background: RTOG 0825 tested if adding bevicizumab (BEV) to standard chemoradiation improves survival (OS) or progression free survival (PFS) in newly diagnosed GBM. While OS was equivalent, PFS was longer with Bev (Arm 2) than with placebo (Arm 1). Patients completed quality of life and symptom PROs to evaluate clinical benefit. Methods: The M.D. Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) and the EORTC core Quality of life Questionnaire and brain tumor module (EORTC QLQ-C30/BN20), were completed by pts at baseline (B) and longitudinally (wk 6, 10, 22, 34, and 46) while on study. The difference between treatment arms were compared from B with evaluation in subsequent weeks in those pts without disease progression; and early change (EC) (baseline to wk 10) between those with and without progression as predictors for OS and PFS. Results: 542pts consented to participate on this trial, and 507 randomized pts participated, with completion of forms by 94% at baseline, 75% at wk 10, 61% at wk 22, and 58% at wk 34. There was a trend for all MDASI-BT symptom groupings to be worse in Arm 2, with significant findings in treatment symptoms at wk 22 and wk 34; both affective and generalized disease symptoms were also significantly worse. For EORTCQLQ30/BN20, differential effects varied at each time point, with no persistent differences. For the MDASI-BT, B neurologic symptom grouping and EC in cognitive symptoms were prognostic for both OS and PFS. For the EORTC QLQ30/BN20, global QOL and motor dysfunction at B as well as EC in communication and leg weakness were prognostic for OS; whereas physical function at B and EC in headaches, seizures, and weak legs were prognostic for PFS. Conclusions: The longitudinal collection of PROs in this phase III trial revealed important treatment-related differences as there was overall more deterioration in symptoms and QOL in Arm 2 as compared to Arm 1, with persistent significant differences in treatment associated symptoms. B and EC tumor associated symptoms on both PRO tools were prognostic for OS and PFS. Longitudinal modeling is ongoing to further assess for differential impact of treatment on symptoms and QOL. Support: U10 CA21661, U10 CA37422 and Genentech, Inc. Clinical trial information: NCT00884741.

Uncertainty, mood states, and symptom distress in patients with primary brain tumors

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. 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. 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. 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

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). 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. 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. 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.

Clinical utility of neurocognitive function (NCF), quality of life (QOL), and symptom assessment as prognostic factors for survival and measures of treatment effects on RTOG 0525.

2016 Background: RTOG 0525, a randomized phase III study compared dose-dense (dd) versus standard dose (sd) temozolomide in patients with newly diagnosed glioblastoma. NCF tests, and Symptom and QOL questionnaires examined the Net Clinical Benefit (NCB) of therapy. The prognostic value of NCB measures for survival outcomes and the differential impact of therapy are reported here. Methods: NCF (Hopkins Verbal Learning Test-Revised, Trail Making Test, Controlled Oral Word Association), and Symptom (M. D. Anderson Symptom Inventory-Brain Tumor Module [MDASI-BT]) and QOL questionnaires (EORTC QLQ-C30/BN20) were completed in a subset of patients at baseline (B) and longitudinally while on study. Univariate (UV) and multivariate (MV) Cox proportional hazard regression modeling determined the prognostic value of a priori selected assessments at baseline (B) and early change from B to cycle 1 (C1Δ) for overall (OS) and progression free survival (PFS). Two-sample proportional test statistic was used to evaluate differences between treatments (dd vs sd) in symptomatic worsening from B to cycle 4 (C4Δ) in patients without progression. Results: Of 182 randomized patients (246 consented) > 85% completed assessment at B. NCF tests and the physical functioning QOL scale were associated with OS and PFS at B. C1Δ in all NCB components were associated with OS and PFS. The MDASI-BT and global QOL detected symptomatic differences between arms (dd > sd) at C4Δ. Conclusions: Longitudinal collection of NCB measures is feasible and complementary (Table) in cooperative group studies providing an added dimension to standard outcome measures. NCF and QOL at baseline were prognostic for OS and PFS and may impact stratification; NCB early changes were associated with OS and PFS and may help to assess response or progression; and MDASI-BT and QOL changes demonstrated sensitivity to adverse treatment effects (dd>sd) arm and may help in risk/benefit analyses. Support: NCI U10CA 21661, U10CA37422, ABC2, and Merck Pharmaceuticals. P<0.05 OS PFS Toxicity dd vs sd + = 1, ++ > 1 module UV MV UV MV B NCF ++ ++ ++ + MDASI QOL + + + + B→C1Δ NCF ++ ++ ++ + MDASI ++ + + + QOL + + B→C4Δ NCF MDASI ++ QOL +

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

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. 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. 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. 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.

Risk factors for fatigue severity in primary brain tumor patients

In addition to neurologic symptoms, fatigue is commonly reported in patients with primary brain tumors during radiation therapy and in long-term survivors of low-grade brain tumors. Other factors have not been explored. The aim of this study was to identify demographic and clinical factors that predict fatigue severity and to evaluate the association of fatigue with other symptoms throughout the disease trajectory. Two hundred one patients with primary brain tumors completed the M. D. Anderson Symptom Inventory-Brain Tumor Module and a demographic checklist. Clinical data, including treatment, tumor grade, and performance status, were also collected. Correlations among fatigue and other recorded symptoms were evaluated. Logistic regression modeling was performed to evaluate factors associated with fatigue severity. Fatigue severity was associated with symptoms including pain, drowsiness, distress, difficulty sleeping, and weakness as well as overall symptom severity and interference. Poor performance status (Karnofsky scale) (odds ratio [OR], 5.73; P = .001), female sex (OR, 2.48; P = .005), and disease status (OR, 2.20; P = .013) were the strongest predictors of fatigue. Severity of fatigue for women was primarily predicted by disease status (OR, 3.33; P = .01) For men, antidepressant use (OR, 4.43; P = .013) in addition to opioids (OR, 3.46; P = .017) and performance status (OR, 12.47; P = .0001) predicted fatigue severity. Fatigue should not be considered a solitary symptom with 1 root cause, but a complex symptom related to the severity of other symptoms and potentially having various etiologies. Future studies should consider these factors in planning interventions and assessing response.

Clinical Utility of the MDASI-BT in Patients with Brain Metastases

Symptom occurrence has been shown to predict treatment course and survival in cancer patients. The M. D. Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) was recently validated as a tool for primary brain tumor patient self-report of symptoms. This study evaluated the reliability and validity of the MDASI-BT in patients with brain metastases. Data collection included demographic and clinical factors, and the MDASI-BT (0–10 scale). Construct validity was assessed using confirmatory factor analysis, and known-group validity was evaluated by detecting group differences due to disease severity and treatment approach. For reliability, Cronbach's alpha values were computed for each subscale. A sample of 124 patients participated, of which 53.2% were women. Participants were primarily white (79.8%) and married (78.2%), and a variety of solid tumor malignancies were represented. Factor analysis revealed six underlying constructs, including affective symptoms, cognitive dysfunction, focal neurologic deficits, constitutional and gastrointestinal symptoms, and interference with life. The solution with these factors explained 68.4% of the variance. Mean symptom scores were 1.2 and 2.6, and mean interference scores were 1.8 and 4.3 for patients with good and poor Karnofsky scores, respectively ( P < 0.001). These subscales were also sensitive to opioid analgesic use, with group differences of 1.5 and 2.2 ( P < 0.001). Cronbach's alpha was 0.9 for each of the two subscales. Fatigue, sleep disturbance, drowsiness, distress, and dry mouth were the most severe symptoms. The MDASI-BT demonstrated validity and reliability in brain metastases patients and can be used to identify and monitor symptom occurrence in relation to treatment course and survival.

The utility of the MDASI-BT in assessing symptoms in patients with brain metastases

2052 Background: Symptom occurrence has been shown to predict treatment course and survival in patients with solid tumors. The M. D. Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) was recently validated in patients with primary brain. This study evaluated the reliability and validity of the MDASI-BT as well as symptom severity and prevalence in patients with brain metastases. Methods: Patients diagnosed with systemic cancer with brain metastases participated in this cross-sectional study. Data collection included demographic and clinical factors, and the MDASI-BT (0–10 scale). The average for the 22 symptoms and 6 interference items scores the MDASI-BT was computed. Construct validity was assessed using confirmatory factor analysis, and known-group validity was evaluated by detecting group differences due to disease severity and performance status. For reliability, Cronbach’s alpha values were computed for each subscale. Results: A sample of 124 patients participated, of which 53.2% females. Participants were primarily white (79.8%) and married (78.2%), with a variety of solid tumor malignancies represented. Factor analysis revealed six underlying constructs including affective, cognitive, focal neurologic deficit, constitutional, gastrointestinal, and interference with life. This solution explained 68.4% of the variance, and satisfied Harman’s criteria for model fit. Known-group validity was established for the MDASI-BT using the Karnofsky performance status (KPS). Mean symptom scores were 1.2 and 2.6, and mean interference were 1.8 and 4.3, for patients with good (90–100) and poor KPS (80 and below) respectively (p&lt;0.001). These subscales were also sensitive to opioid analgesic use with group differences of 1.5 and 2.2 (p&lt;0.001). Cronbach’s alpha was 0.9 for each of the two subscales. Fatigue, sleep disturbance, drowsiness, distress, and dry mouth were the most severe symptoms. Conclusions: The MDASI-BT demonstrated validity and reliability in patients with brain metastases and can be used to identify symptom occurrence related to the tumor and therapies. No significant financial relationships to disclose.

Validation of the M. D. Anderson symptom inventory (MDASI-BT)

1546 Background: The occurrence of symptoms has been shown to predict treatment course and survival in a number of solid tumor patients. Primary brain tumor patients are unique in the neurologic symptoms that occur. Currently, no instrument exists that measures both neurologic and cancer-related symptoms. Methods: Patients diagnosed with Primary Brain Tumors (PBT) 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 18 neurologic symptoms were added (M.D. Anderson Symptom Inventory-Brain Tumor Module, MDASI-BT). The study evaluated the reliability and validity of the MDASI-BT in primary brain tumor patients. Results: 201 patients participated in this study. Mean symptom severity of items as well as cluster analysis was used to reduce the number of total items to 22. Regression analysis showed more than half (56%) of the variability in symptom severity was explained by the 9 remaining brain tumor items. Factor analysis was then performed to determine the underlying constructs being evaluated by the remaining items. The 22 item MDASI-BT measures six underlying constructs including affective, cognitive, focal neurologic deficit, constitutional, generalized symptom, and a gastrointestinal related factor. The internal consistency (reliability) of the sets of items comprising the six factors and also the interference scale were .87, .82, .72, .81, .69, .67 and .91 respectively). Test-retest reliability was good in a subset of 19 patients completing the instrument at two points in time. The MDASI-BT was sensitive to disease severity based on Karnofsky performance status (KPS) based on mean symptom severity (1.7 versus 3.8, p &lt; .001) and mean symptom interference (2.2 versus 6.1, p &lt; .001). Conclusions: The 22 item MDASI-BT demonstrated validity and reliability in patients with PBT. This instrument can be used to describe symptom occurrence throughout the disease trajectory and to evaluate interventions designed for symptom management. [Table: see text]

Validation of the M.D. Anderson Symptom Inventory Brain Tumor Module (MDASI-BT)

Symptom occurrence has been shown to predict treatment course and survival in patients with solid tumors. Primary brain tumor (PBT) patients are unique in the occurrence of neurologic symptoms. Currently, no instrument exists that measures both neurologic and cancer-related symptoms. Patients diagnosed with PBT participated in this study. Data was collected at one point in time and included demographic and clinical factors, and the M.D. Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT). The study evaluated the reliability and validity of the MDASI-BT in primary brain tumor patients. Two hundred and one patients participated in this study. Mean symptom severity of items as well as cluster analysis was used to reduce the number of total items to 22 (13 core, 9 brain tumor items). Regression analysis showed more than half (56%) of the variability in symptom severity was explained by brain module items. The MDASI-BT measures six underlying constructs including affective, cognitive, focal neurologic deficit, constitutional, generalized symptom, and a gastrointestinal related factor. The internal consistency (reliability) of the instrument was 0.91. The MDASI-BT was sensitive to disease severity based on performance status (P<0.001), tumor recurrence (P<0.01), and mean symptom interference (P<0.001). The 22 item MDASI-BT demonstrated validity and reliability in patients with PBT. This instrument can be used to identify symptom occurrence throughout the disease trajectory and to evaluate interventions designed for symptom management.