Abstract
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.
Keywords: brain tumor, corticosteroids, patient-reported outcomes, symptoms
Corticosteroids are routinely used for the control of peritumoral edema in patients with brain tumors.1 They are generally used as adjuncts to tumor-directed therapies, including surgery, radiation, and chemo. The mechanisms of action of corticosteroids leading to the control of vasogenic edema and, conversely, their lack of efficacy with intracellular or toxic edema are not fully understood.1,2 Dexamethasone is the most commonly prescribed corticosteroid for this patient population, primarily because of its low mineralocorticoid activity.3 However, there has been limited study of the efficacy of other types of synthetic corticosteroids in this population. Corticosteroid dosing is often determined based on clinical evaluation and imaging findings. A common dose prescribed at the time of diagnosis of a brain tumor is in the range of 8 to 16 mg/day in divided doses, which is thought to be derived from the dose–response curves generated in the first case series of preoperative dexamethasone use in patients with primary brain tumors3,4 Corticosteroids are also commonly used at the time of tumor recurrence or to manage treatment-related reactions such as radionecrosis, but there has been little investigation about the optimal dose and duration of corticosteroids in these settings.1,5,6
Despite the well-established morbidity associated with corticosteroid use, the reporting of actual dose and duration and associated side effects is often not routine and they are not usually assessed in patients with brain tumors.1 As a result, we have limited data regarding the severity and frequency of signs and symptoms associated with the use of corticosteroids in patients with both primary and metastatic brain tumors. One retrospective study of neuro-oncology patients found that 51% (30/59) had at least one steroid toxicity and 19% (11/59) required hospital admission due to steroid-related complications.7 Another study, of 88 patients with brain metastases, reported more toxicity in those who received more than 16 mg of dexamethasone per day at the time of commencement of radiotherapy, with 91% reporting at least one dexamethasone-related side effect at some point in the treatment course.8 The use of prolonged corticosteroids has been shown to impact functional status in select patients.9 Vecht and colleagues reported that mean improvement in KPS during radiation in patients with metastatic brain tumors was less in those who experienced a corticosteroid-related side effect such as ankle edema, proximal myopathy, or Cushingoid facies.
The Dexamethasone Symptom Questionnaire (DSQ) is a self-report intended as a descriptive measure to determine the incidence and severity of side effects over the last week and to examine changes in side effects associated with dexamethasone when used longitudinally. Items were generated by literature review and expert opinion and were then reviewed for content validity by the use of focus groups of cancer patients receiving dexamethasone.10 Responses are formatted using a 4-point Likert scale (1 = not at all, 2 = a little bit, 3 = quite a bit, 4 = very much). The burden of completing the DSQ is low, taking 2–3 minutes to complete. The DSQ has demonstrated face and content validity and has been used to evaluate corticosteroid-related symptoms in breast cancer patients receiving dexamethasone as an anti-emetic10,11 and to evaluate the impact in brain metastases patients undergoing radiation therapy.12 The “Chronic” revision of the questionnaire (DSQ-C) contains the original 13 items with additional sign/symptom items (for roundness of face, anger/irritability, difficulty standing from a seated position or walking, problems with fragile skin, stretch marks or easy bruising, and headaches) added by the original developers after focus-group input to better measure long-term complications associated with dexamethasone use.
Given the prolonged course of corticosteroid use to control cerebral edema in brain tumor patients and the few studies on the associated signs and symptoms, we undertook this study to redress the paucity of data and evaluate the utility of the DSQ-C in brain tumor patients.
Methods
Study Population
Approval for this study was obtained from the M.D. Anderson Cancer Center institutional review board. This study population included a cross-sectional sample of adult patients with either primary or metastatic brain tumors who were evaluated in the outpatient Brain and Spine Clinic at M.D. Anderson Cancer Center as part of routine care. Subjects were screened and approached for participation, and informed consent was obtained if they were ≥18 years of age and able to speak, read, and write English.
Data collection tools included a patient-completed demographic data sheet, an investigator-completed clinician checklist, and the patient-reported DSQ-C. Patient sex, ethnicity, race, age, level of education, marital status, and employment status were collected using the demographic information sheet. The clinician checklist was used to collect information on tumor type and characteristics, KPS, and current corticosteroid use, including type, dose, and duration of therapy.
Statistical Analysis
Variables of interest were identified, and hypotheses related to the relationships were formulated prior to study initiation and outlined in the objectives and analysis plan of the protocol. Data were first summarized using standard descriptive statistics and contingency tables. Relationships among continuous variables were assessed using Pearson correlation coefficients. Associations between categorical variables were examined by chi-square test or Fisher's exact test. Total steroid dose was the product of the daily dose (mg/d) and total days of use. We adjusted/controlled for age, KPS, and patient type by including them as covariates in our regression models. We used a linear regression model for chronic DSQ (a continuous outcome) and a logistic model for binary outcomes. Linear regression models were applied to assess the effect of variables of interest (ie, steroid dose and the duration of use) on the DSQ-C total score. Logistic regression models were employed to determine whether the variables of interest had significant effects on each of the 17 symptoms. Psychometrics included factor analysis to assess construct validity. The DSQ-C's internal consistency was evaluated by calculation of Cronbach's alpha. All computations were carried out in SAS 9.3 and R 3.0.1.
Results
Patient Characteristics
Table 1 provides an overview of the clinical features and demographics of the sample. Ninety-six patients participated in the study. Participants were primarily white (83%) males (65%) with primary (77%) or metastatic (23%) brain tumors. Ages ranged from 20 to 75 years (mean, 53). Seventy-one patients (74%) were treated with corticosteroids, with a median dose of 4 mg/d for a median duration of 1 month (range, 0–26 mo), while 25 patients (26%) received no corticosteroids, as a comparison group. The mean total cumulative dose was 377 mg (SD ± 638; median, 130; range, 4–3196). Figure 1 provides a graphic representation of the daily steroid dose, steroid use in days, and the total cumulative steroid dose. All clinical and demographic characteristics were similar between patients taking corticosteroids and patients not taking corticosteroids, except KPS. Patients who were not on corticosteroids had a median KPS of 90 (range, 80–100), whereas those taking corticosteroids had a median KPS of 80 (range, 50–100, P = .03).
Table 1.
Sample characteristics and comparison
| Characteristics | Entire Sample (N = 96) | On Corticosteroids, n = 71 (74%) | Not on Corticosteroids, n = 25 (26%) | P-value |
|---|---|---|---|---|
| Corticosteroids, | ||||
| mean total dose* (SD) | 0.378 (0.638) | N/A | ||
| range, 0.004–3.196 | ||||
| Sex | ||||
| Male | 62 (65%) | 47 (66%) | 15 (60%) | .06 |
| Female | 34 (35%) | 24 (34%) | 10 (40%) | |
| Age | ||||
| Mean | 52 | 52 | 48 | .56 |
| Median (range) | 53 (20–75) | 53 (20–64) | 51 (25–68) | |
| Patient group | ||||
| Primary brain | 74 (77%) | 56 (79%) | 18 (72%) | .73 |
| Brain metastasis | 22 (23%) | 15 (21%) | 7 (28%) | |
| Primary cancer | ||||
| Primary, grade II | 5 (7%) | 2 | 3 | |
| Primary, grade III | 12 (16%) | 8 | 4 | |
| Primary, grade IV | 57 (77%) | 46 | 11 | |
| Metastases (Mets) | ||||
| Mets from lung | 8 (36%) | 5 | 3 | |
| Mets from breast | 6 (27%) | 4 | 2 | |
| Mets from melanoma | 4 (18%) | 3 | 1 | |
| Mets from renal | 3 (14%) | 2 | 1 | |
| Mets from other Location | 1 (5%) | 1 | 0 | |
| KPS | ||||
| Median/range | 50–100 | 80/50–100 | 90/60–100 | .03** |
| Poor (50–80) | 40 (42%) | 33 (47%) | 7 (28%) | |
| Good (90–100) | 56 (58%) | 38 (54%) | 18 (72%) | |
| Recurrence at assessment | ||||
| Yes | 29 (30%) | 21 (30%) | 8 (32%) | .58 |
| No | 67 (70%) | 50 (70%) | 17 (68%) | |
*Total dose (g) = dose (g/day) × Days of use.
**Significantly different between groups.
Fig. 1.
Diagram of steroid dose, steroid use in days, and total dose (steroid use × days of steroid use) showing the range and count of participants.
Corticosteroid-Associated Signs and Symptoms
The mean DSQ-C total score was 27 (range,17–54). The DSQ-C total score was able to distinguish between patients on steroids (mean DSQ-C total score = 14.86, SD = − 4.02) and patients who were not on steroids (mean DSQ-C total score = 12.44, SD = − 2.69) (P < .01). DSQ-C total scores were higher for younger patients (≤52 y) than for older patients (>53 y) (28.8 vs 25.5, P = .02).
Table 2 provides data on symptom reporting by patients on corticosteroids. Over 35% of the patients on corticosteroids experienced “quite a bit” to “very much” increased appetite and trouble sleeping. Using the DSQ-C rating, the 3 most frequently reported symptoms for those on corticosteroids were trouble with sleep, increased appetite, and anger. Patients ranked the 3 most bothersome symptoms as appetite change/weight gain, anxiety/irritability, and changes in sleep pattern. The following symptoms were significantly associated with the use of steroids: increased appetite (P < .01), weight gain (P = .03), roundness of face (P < .01), and difficulty standing (P = .02).
Table 2.
DSQ-C symptom report by those on corticosteroids
| In the last week, how often did you experience … | |||||
|---|---|---|---|---|---|
| DSQ-C Item | Not at All | A little | Quite a Bit | Very Much | Mean Score (SD) |
| Indigestion | 57 (59%) | 25 (26%) | 12 (13%) | 2 (2%) | 1.6 (0.8) |
| Trouble with sleep | 37 (39%) | 22 (23%) | 27 (28%) | 10 (10%) | 2.1 (1.0) |
| Nausea | 71 (74%) | 17 (18%) | 5 (5%) | 3 (3%) | 1.4 (0.7) |
| Vomiting | 88 (92%) | 6 (6%) | 1 (1%) | 1 (1%) | 1.1 (0.4) |
| Lack of appetite | 76 (79%) | 11 (12%) | 5 (5%) | 4 (4%) | 1.3 (0.8) |
| Increased appetite | 37 (39%) | 24 (25%) | 19 (20%) | 16 (17%) | 2.2 (1.1) |
| Hiccups | 84 (88%) | 5 (5%) | 4 (4%) | 3 (3%) | 1.2 (0.7) |
| Weight loss | 58 (60%) | 32 (33%) | 4 (4%) | 2 (2%) | 1.5 (0.7) |
| Weight gain | 51 (53%) | 23 (24%) | 9 (9%) | 13 (14%) | 1.8 (1.1) |
| Agitation/nervousness | 28 (29%) | 51 (53%) | 11 (12%) | 6 (6%) | 2.0 (0.8) |
| Rash/acne | 74 (77%) | 12 (13%) | 7 (7%) | 3 (3%) | 1.4 (0.8) |
| Thrush | 87 (90%) | 6 (6%) | 2 (2%) | 1 (1%) | 1.1 (0.5) |
| Roundness of face | 56 (58%) | 12 (13%) | 18 (19%) | 10 (10%) | 1.8 (1.1) |
| Depression | 51 (53%) | 34 (35%) | 8 (8%) | 3 (3%) | 1.6 (0.8) |
| Anger | 44 (45%) | 38 (40%) | 11 (12%) | 3 (3%) | 1.7 (0.8) |
| Difficulty standing | 51 (53%) | 25 (26%) | 14 (15%) | 6 (6%) | 1.7 (0.9) |
| Fragile skin | 59 (62%) | 25 (26%) | 10 (10%) | 2 (2%) | 1.5 (0.8) |
The 3 most frequently reported symptoms were trouble with sleep, increased appetite, and anger.
The relationship between each DSQ-C item duration of steroid dosing and the total cumulative dose (steroid dose/per day × duration of steroid use in days) was examined. For each DSQ-C item, “not at all” and “a little” were combined, and “quite a bit” and “very much” were combined, except for the items “vomited” and “thrush (oral candidiasis).” For these 2 items, “a little,” “quite a bit,” and “very much” were combined to maintain group sizes appropriate for statistical evaluation. The effects of steroid dose and duration of use were evaluated simultaneously by regression analysis after controlling for age, KPS, and patient type as covariates. Because we evaluated their effects simultaneously, the effects of steroid dose were controlled for duration of use, and the effects of use were controlled for steroid dose. As shown in Table 3, duration of steroid use, in days, was associated with change in appetite (both loss of and increased; P = .05 and .02, respectively). A higher rate of self-reported thrush was associated with longer duration of steroid use (P = .04). Finally, greater self-reported difficulty standing from a seated position was associated with longer duration of steroid use (P = .02). Table 4 shows the effects of total cumulative dose after controlling for age, KPS, and patient type. Total cumulative steroid dose (steroid dose per day × duration of steroid use in days) after adjusting for age, KPS, and patient type predicted for DSQ-C scores (P < .001) and increased the odds of experiencing a number of individual symptoms, including increased appetite (P = .05), hiccups (P = .03), roundness of face (P = .04), depression (P = .05), and difficulty standing from a seated position (P = .03).
Table 3.
The effects of steroid dose and duration of use (mo) on various outcome variables after controlling for age, KPS, and patient type
| Outcome | Steroid Dose |
Duration of Use |
||||
|---|---|---|---|---|---|---|
| Estimate | 95% CI | P-value | Estimate | 95% CI | P-value | |
| Chronic DSQ | 0.1987 | (0.019, 0.378) | .0332 | 0.310 | (0.134, 0.486) | .0009 |
| Odds ratio | Odds ratio | |||||
| Lacked appetite | 0.960 | (0.780, 1.181) | .6980 | 1.135 | (1.001, 1.287) | .0481 |
| Increased appetite | 1.089 | (0.972, 1.220) | .1420 | 1.205 | (1.030, 1.410) | .0197 |
| Thrush | 0.949 | (0.757, 1.188) | .6462 | 1.141 | (1.009, 1.290) | .0355 |
| Difficulty standing | 1.076 | (0.948, 1.222) | .2563 | 1.164 | (1.025, 1.321) | .0193 |
Table 4.
The effects of total cumulative dose, g, on various outcome variables, after controlling for age, KPS, and patient type
| Outcome | Estimate | 95% CI | P-value |
|---|---|---|---|
| Chronic DSQ | 2.660 | (1.398, 3.922) | <.001 |
| Odds ratio | |||
| Increased appetite | 2.579 | (1.014, 6.558) | .0467 |
| Hiccups | 3.196 | (1.154, 8.850) | .0253 |
| Roundness of face | 2.715 | (1.060, 6.954) | .0374 |
| Difficulty standing | 2.657 | (1.120, 6.303) | .0266 |
| Depression | 3.059 | (1.125, 8.312) | .0284 |
Psychometric Evaluation of the Dexamethasone Symptom Questionnaire–Chronic
The DSQ-C demonstrated select measures of feasibility, reliability, and validity. The DSQ-C was feasible, with all consenting patients able to complete it without assistance in 2–4 min. Factor analysis was then performed as a measure of construct validity, with the ultimate goal being to arrive at a parsimonious and clinically relevant set of factors describing the structure of the interrelationships among the items. Factor analysis revealed that 6 underlying constructs were being measured by the 17-item DSQ-C. These included an emotional factor (agitation, anger, depression), Cushingoid weight (weight gain, increased appetite, roundness of face), Cushingoid dermatologic/motor (thrush, fragile skin, rash/acne, difficulty standing), sleep disorder (sleep, hiccups), and gastrointestinal (vomiting, nausea, lack of appetite, weight loss). Two items did not load as cleanly. Rash/acne had the strongest positive loading with Cushingoid dermatologic/motor, and indigestion loaded positively with sleep disorder. These 6 constructs explained 53% of variance, an indicator of construct validity (Table 5). However, it was very uncommon for patients to report vomiting, hiccups, or thrush, which could impact any factor solution. Confirmatory factor analysis in a second sample would strengthen this finding. The DSQ-C demonstrated very good internal consistency reliability (Cronbach's alpha, 0.77).
Table 5.
Psychometric evaluation of underlying construct validity
| Pattern Matrixa | ||||||
|---|---|---|---|---|---|---|
| Factor |
||||||
| 1 | 2 | 3 | 4 | 5 | 6 | |
| Agitation | 0.895 | 0.053 | 0.018 | 0.131 | −0.058 | 0.056 |
| Anger | 0.479 | −0.215 | 0.149 | −0.023 | 0.245 | −0.090 |
| Depression | 0.440 | 0.057 | −0.070 | 0.083 | 0.348 | −0.250 |
| Weight gain | −0.174 | −0.989 | 0.020 | 0.111 | −0.027 | −0.099 |
| Increased appetite | 0.096 | −0.728 | −0.002 | 0.140 | −0.012 | 0.207 |
| Roundness of face | −0.003 | −0.581 | 0.042 | −0.156 | 0.036 | −0.236 |
| Thrush | −0.045 | 0.032 | 0.640 | 0.109 | −0.091 | −0.122 |
| Fragile skin | 0.171 | −0.137 | 0.363 | −0.203 | 0.014 | −0.035 |
| Difficulty standing | 0.189 | −0.066 | 0.354 | −0.250 | 0.278 | 0.216 |
| Sleep | 0.199 | −0.114 | −0.074 | 0.482 | −0.006 | −0.050 |
| Hiccups | 0.005 | −0.009 | 0.049 | 0.418 | 0.061 | 0.029 |
| Vomiting | 0.100 | −0.045 | −0.154 | −0.094 | 0.764 | 0.025 |
| Nausea | 0.157 | 0.027 | −0.091 | 0.063 | 0.677 | −0.239 |
| Lacked appetite | −0.209 | 0.036 | 0.246 | 0.272 | 0.670 | 0.102 |
| Weight loss | −0.103 | 0.335 | 0.159 | 0.204 | 0.412 | 0.081 |
| Rash/acne | −0.014 | −0.082 | 0.433 | −0.061 | 0.031 | −0.794 |
| Indigestion | 0.146 | −0.184 | 0.023 | 0.271 | 0.073 | −0.309 |
Extraction method: principal axis factoring. Rotation method: Oblimin with Kaiser normalization.
Discussion
This study demonstrates the utility of the DSQ-C in self-report of corticosteroid-associated symptoms in brain tumor patients and provides support for the association of total cumulative steroid dose and more severe symptoms in this population. Corticosteroids are well established as effective agents for the management of cerebral edema in brain tumor patients.3,4 The earliest reports of clinical improvement with cortisone replacement therapy date back to 1952,13 and the first large case series demonstrating improved morbidity and mortality with the use of preoperative dexamethasone is from 1961.3 However, despite their widespread use over decades in patients with brain tumors and their recognized toxicities, sometimes causing symptoms that are indistinguishable from disease progression, there have been limited studies evaluating corticosteroid-related toxicities, signs, and symptoms or efforts to determine the optimal dosing schedule14 for the brain tumor population. This report provides preliminary evidence for the utility of the DSQ-C in evaluating symptoms associated with corticosteroid use and the impact of the total cumulative dose on the severity of symptoms.
In the general medical population, there is consensus that the development of corticosteroid toxicity is related to the cumulative dose and the duration of use.15–17 It is recognized that brain tumor patients may continue on corticosteroids for many months. In a small study of brain tumor patients, Weissman and colleagues7 reported that patients who received a total cumulative dose of dexamethasone of >400 mg had an incidence of toxicity of 75% compared with 13% of those receiving <400 mg. In one prospective cohort study of patients treated with radiation for malignant glioma, 71% of patients were still taking corticosteroids 3 months after completing radiotherapy, suggesting that the impact of chronic corticosteroid use is an important clinical issue in this patient population.18 Another small retrospective study showed that patients required corticosteroids for an average of 23 weeks post-radiotherapy, whereas those with metastatic brain tumors required corticosteroids for an average of 7 weeks.19
In the present study, patients were on corticosteroids for an average of 1 month prior to completion of the questionnaire, which also supports patients’ reported signs and symptoms being related to both the duration and the total cumulative corticosteroid dose received. In this report, the total cumulative dose of dexamethasone was 377.7 mg (median, 130; range, 4–2196), indicating that patients experience symptoms at even lower total cumulative doses than previously prescribed. However, the great variability in the total cumulative dose of this cross-sectional sample limits our ability to further refine dosing parameters that may be associated with more severe individual symptoms. The cumulative total dose impacted the overall DSQ-C score as well as specific self-reported symptoms, including increased appetite, roundness of face, depression, and difficulty standing from a seated position. It is important to note that except for tradition, there is not much rationale behind long-term treatment with corticosteroids in the brain tumor population. There were a subset of patients in this study who were on corticosteroids for an extended period of time. Although this was the experience at a single institution, further evaluation of use in other centers and, more importantly, evaluation of shorter treatment courses and lower doses and patient outcomes are needed. In this study, patients with higher DSQ-C scores also had a significantly lower KPS score. Our regression analysis can establish only the association, not the causal relationship, between variables; so further evaluation of this is warranted to further understand the relationship between functional status and higher severity of reported symptoms.
Prospective studies appear to report higher frequencies of side effects than retrospective studies, presumably due to limited documentation of toxicity in retrospective studies.1 Future evaluation of the relationship between total cumulative dose and self-report of signs and symptoms would require longitudinal prospective evaluation to assess impact in patients before and after receiving corticosteroids.
Whereas patients are more likely to report toxicity with higher total cumulative doses of corticosteroids, there are individual variations in the timing and severity of toxicity, with some patients experiencing more severe toxicity much earlier than others. Weissman et al7 reported that one-third of patients developed toxicity within the first 3 weeks. This first evaluation of the utility of the DSQ-C in the brain tumor population demonstrated that the cumulative steroid dose (dose and duration of therapy) predicted the total DSQ-C score and the occurrence of specific symptoms and signs. There were several symptoms included in the DSQ-C that were not significantly associated with the total cumulative dose. This may suggest that the DSQ-C could be further refined to measure symptoms that commonly develop after long-term corticosteroid use in this patient population. In addition, it has been suggested that individual variability in both therapeutic response and toxicity timing and severity related to the total cumulative dose may be influenced by individual genomic differences.20,21 Future studies should consider evaluation of both clinical factors and genomic differences associated with signs and symptoms in the brain tumor population.
In the general medical literature, a study by the Boston Collaborative Drug Surveillance Program22 with 676 patients showed that severe psychiatric illness was uncommon (1.3%) at doses <40 mg per day of prednisolone, which is an intermediate-acting corticosteroid (equivalent to dexamethasone 6.4 mg, which is a longer-acting corticosteroid). Our findings indicate that 35% of patients report significant difficulty with sleeping, anger, and irritability, and these symptoms, along with weight gain and change in appetite, are most frequently reported as the most bothersome for patients. Understanding this impact from the perspective of the patient in terms of quality of life and daily functioning is important in evaluating the clinical impact of corticosteroid use. Future studies could be focused on further characterizing these symptoms and evaluating targeted interventions to address toxicities. In this era of anti-angiogenic agents that may alter corticosteroid requirements, there is growing value in measuring the impact of corticosteroids on patients.
There are several limitations to this analysis, including its cross-sectional design and the variability of the sample in terms of total cumulative dose, tumor type, and treatment history, in addition to the limitations mentioned earlier in this discussion. Despite these limitations, this study provides preliminary evidence that the DSQ-C can be used as a tool for future prospective evaluations of the impact of corticosteroid use. Select psychometric analysis demonstrated its reliability and ability to distinguish patients who are currently on a corticosteroid regimen from those who are not. Future evaluation of the factor solution should occur in another patient population to confirm this structure. Additional evaluation is needed of test–retest reliability and sensitivity to change in patients evaluated longitudinally, and the utility of this measure would be strengthened by the identification of clinically meaningful change in addition to further exploration of the biologic underpinnings of the variability of timing and severity in both primary and metastatic brain tumor patients.
Conclusions
This pilot study demonstrates the potential of the DSQ-C to be used as a screening tool for signs and symptoms associated with corticosteroid use in brain tumor patients. The results from this report indicate that the DSQ-C is able to determine which patients are on corticosteroids, thus providing a tool to help identify the impact of corticosteroid use in the context of clinical trials and clinical care.
Funding
This work was partially supported by the Collaborative Ependymoma Research Foundation (CERN) (grant to A.A.A., E.V-B.).
Conflict of interest statement. There is no conflict of interest related to this work for any author.
References
- 1.Ryan R, Booth S, Price S. Corticosteroid-use in primary and secondary brain tumour patients: a review. J Neurooncol. 2012;106(3):449–459. [DOI] [PubMed] [Google Scholar]
- 2.Sandercock PA, Soane T. Corticosteroids for acute ischaemic stroke. Cochrane Database Syst Rev. 2011;(9):article CD000064 doi:10.1002/14651858. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Galicich JH, French LA, Melby JC. Use of dexamethasone in treatment of cerebral edema associated with brain tumors. J Lancet. 1961;81(Feb):46–53. [PubMed] [Google Scholar]
- 4.Galicich JH, French LA. Use of dexamethasone in the treatment of cerebral edema resulting from brain tumors and brain surgery. Am Pract Dig Treat. 1961;12(March):169–174. [PubMed] [Google Scholar]
- 5.Shaw PJ, Bates D. Conservative treatment of delayed cerebral radiation necrosis. J Neurol Neurosurg Psychiatry 1984;47(12):1338–1341. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Parvez K, Parvez A, Zadeh G. The diagnosis and treatment of pseudoprogression, radiation necrosis and brain tumor recurrence. Int J Mol Sci 2014;15(7):11832–11846. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Weissman DE, Dufer D, Vogel V, et al. Corticosteroid toxicity in neuro-oncology patients. J Neurooncol. 1987;5(2):125–128. [DOI] [PubMed] [Google Scholar]
- 8.Sturdza A, Miller BA, Bana N, et al. The use and toxicity of steroids in the management of patients with brain metastases. Support Care Cancer. 2008;16(9):1041–1048. [DOI] [PubMed] [Google Scholar]
- 9.Vecht CJ, Hovestadt A, Verbiest HB, et al. Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain tumors: a randomized study of doses of 4, 8, and 16 mg per day. Neurology. 1994;44(4):675–680. [DOI] [PubMed] [Google Scholar]
- 10.Vardy J, Chiew KS, Galica J, et al. Side effects associated with the use of dexamethasone for prophylaxis of delayed emesis after moderately emetogenic chemotherapy. Br J Cancer. 2006;94(7):1011–1015. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Vardy J, Pond G, Dodd A, et al. A randomized double-blind placebo-controlled cross-over trial of the impact on quality of life of continuing dexamethasone beyond 24h following adjuvant chemotherapy for breat cancer. Breast Cancer Res Treat. 2012;136(1):143–151. [DOI] [PubMed] [Google Scholar]
- 12.Nguyen J, Caissie A, Zhang L, et al. Dexamethasone toxicity and quality of life in patients with brain metastases following palliative whole-brain radiotherapy. J Radiat Oncol. 2013;2(4):435–443. [Google Scholar]
- 13.Ingraham FD, Matson DD, Mc LR. Cortisone and ACTH as an adjunct to the surgery of craniopharyngiomas. N Engl J Med. 1952;246(15):568–571. [DOI] [PubMed] [Google Scholar]
- 14.Hardy JR, Rees E, Ling J, et al. A prospective survey of the use of dexamethasone on a palliative care unit. Palliat Med. 2001;15(1):3–8. [DOI] [PubMed] [Google Scholar]
- 15.Stanbury RM, Graham EM. Systemic corticosteroid therapy—side effects and their management. Br J Ophthalmol. 1998;82(6):704–708. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Benvenuti S, Brandi ML. Corticosteroid-induced osteoporosis: pathogenesis and prevention. Clin Exp Rheumatol. 2000;18(4 Suppl 20):S64–S66. [PubMed] [Google Scholar]
- 17.Manson SC, Brown RE, Cerulli A, et al. The cumulative burden of oral corticosteroid side effects and the economic implications of steroid use. Respir Med. 2009;103(7):975–994. [DOI] [PubMed] [Google Scholar]
- 18.Marantidou A, Levy C, Duquesne A, et al. Steroid requirements during radiotherapy for malignant gliomas. J Neurooncol. 2010;100(1):89–94. [DOI] [PubMed] [Google Scholar]
- 19.Hempen C, Weiss E, Hess CF. Dexamethasone treatment in patients with brain metastases and primary brain tumors: do the benefits outweigh the side-effects? Support Care Cancer. 2002;10(4):322–328. [DOI] [PubMed] [Google Scholar]
- 20.Huizenga NA, Koper JW, De Lange P, et al. A polymorphism in the glucocorticoid receptor gene may be associated with an increased sensitivity to glucocorticoids in vivo. J Clin Endocrinol Metab. 1998;83(1):144–151. [DOI] [PubMed] [Google Scholar]
- 21.van Rossum EF, Lamberts SW. Polymorphisms in the glucocorticoid receptor gene and their associations with metabolic parameters and body composition. Recent Prog Horm Res. 2004;59:333–357. [DOI] [PubMed] [Google Scholar]
- 22.Boston Collaborative Drug Surveillance Program. Acute adverse reactions to prednisone in relation to dosage. Clin Pharmacol Ther. 1972;13(5):694–698. [DOI] [PubMed] [Google Scholar]