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

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.