A Practice Pilot Survey on the Current Use of Corticosteroid Therapy in Brain Tumor Patients
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.359216
Source of Support: None, Conflict of Interest: None
Keywords: Brain tumor, corticosteroid, dexamethasone, health care professional, survey
Corticosteroid therapy has been proven to be an integral component of the management of brain tumor patients both in the primary and metastatic settings. Dexamethasone due to its higher potency and longer half-life as compared to other corticosteroids in its class has been a popular corticosteroid of choice among health care professionals in this patient population.,,, However, despite the common usage of dexamethasone, few clinical practice guideline recommendations have been formulated to determine its optimal dose and schedule in patients with primary and metastatic brain tumors, following radiation therapy including gamma knife radiosurgery as a result of which there are wide variations among health care professionals with respect to scheduling, dosage, and tapering regimens.,,, In order to bring about uniformity in the prescription of corticosteroids by practitioners in brain tumor patients, it has become imperative to develop comprehensive clinical practice guidelines regarding the use of the same in brain tumor patients. This pilot survey aims to provide an insight into the variations of corticosteroid prescription among health care professionals across the Indian subcontinent and eventually serve as a prerequisite for the future development of corticosteroid therapy guidelines in brain tumor patients.
The pilot study was granted exemption from full board review by the institutional ethics committee. The participants of this online questionnaire-based survey were health care professionals who have been involved in treating brain tumor patients and which included radiation oncologists, neurosurgeons, neurologists, medical oncologists, and psychiatrists from all over India. We were cognizant that the routine postoperative care of such patients is taken care of by clinical oncology teams which in India primarily consist of clinical/radiation oncologists, medical oncologists, and neurosurgeons. An anonymized online pilot survey using SurveyMonkey was designed and was administered from 1st June 2017 till 30th June 2017. Participation in this survey was voluntary. Unique links were electronically mailed to 3205 health care professionals from a database populated initially from Indian Society of Neuro-Oncology (ISNO) and further expanded to other professional associations of concerned specialties. No other personal identification details were solicited during the course of the survey. The contact between the research team and the participant was strictly in a collective manner and in no way on person-to-person basis. The participants had the option to exit the survey at any point during the online survey. Responses under such circumstances have neither been recorded nor archived.
The structured questionnaire consisted of 20 questions which included both open-ended and objectively answerable questions.
Descriptive statistical analysis was applied to the closed-ended questions, expressed as frequency (percentages) for categorical variables. The Chi-square test and/or exact test was used for comparisons between factors, including patterns of practice. Statistical analyses were performed using SPSS version 21.0 (SPSS, Inc, USA)™.
In the first phase of the survey, out of the mails sent across to 3205 oncologists, 319 valid responses were received within the 30 days' duration of the survey invitation and the survey was locked for analysis after that duration. The key responses from the survey have been summarized in a tabular form (additional file). The majority of the responses- as expected - were from radiation/clinical oncologists (232/317; 73%) followed by neurosurgeons (73/317; 23%). The cohort of respondents regarding their experience in managing brain tumor patients was fairly a balanced one with 51% of the respondents being involved in the management of brain tumor patients for less than 10 years as compared to 47% of them having experience of more than 10 years. While 78% of the respondents treat less than 100 brain tumor patients (primary and metastatic) on an average per year, 22% of them treat more than 100 brain tumor patients annually.
Dexamethasone (95%) was the most preferred corticosteroid being prescribed in brain tumor patients, and the commonly available strengths of oral dexamethasone in the pharmacies of the respective practicing centers of the respondents were 4 mg (85%), 0.5 mg (62%), and 2 mg (43%) [Figure 1]. The majority of the respondents (90%) used a flat dosage pattern for determining the starting dose of corticosteroids in their patients while only 7% of them determined the starting dose on the basis of body weight. For patients with mildly raised intracranial pressure, most practitioners preferred to prescribe corticosteroids twice daily (44%) or thrice daily (37%) as per the need. Intravenous (IV) administration of corticosteroids was the route of choice for patients with severely raised intracranial pressure (60%) followed by patients with mildly raised intracranial pressure (16%).
In our survey, raised intracranial pressure was the commonest indication (90%) for prescribing corticosteroids among the respondents, followed by focal neurological deficits (30%) and seizures (19%). In patients undergoing surgical treatment, 50% of the neurosurgeons preferred corticosteroids to be given routinely for all patients undergoing surgery and 32% of the radiation/clinical oncologists responded saying they would prescribe corticosteroids if postoperative imaging showed significant edema or mass effect in the immediate postoperative settings. In addition, another 32% of radiation/clinical oncologists stated that they would prescribe corticosteroids only if the patient developed neurologic symptoms irrespective of imaging findings in a similar situation.
For patients undergoing adjuvant radiation therapy, 46% of the radiation/clinical oncologists said that they prescribed corticosteroids only when patients presented with neurologic symptoms irrespective of imaging findings, while 33% of neurosurgeons preferred corticosteroids to be given routinely to such patients and 26% of them said they would prescribe only if a patient developed neurological symptoms. During the course of chemotherapy, 34% of the responding radiation/clinical oncologists and 45% of the neurosurgeons said they would prescribe corticosteroids if postoperative imaging of the patient showed significant mass effect or edema.
Around 47% of the respondents preferred the last dose of corticosteroid for the day to be given between 1800 and 2000 hours, while 30% of them preferred it to be given late evening after 2000 hours. The tapering schedule of corticosteroids for patients with mildly raised intracranial pressure was commonly after 3–5 days (79%) while for patients with moderately raised intracranial pressure the practitioners preferred to taper the dosage of corticosteroids after 7–10 days (59.8%). In cases of patients with severely raised intracranial pressure, practitioners preferred to taper the dosage after 7–10 days (46%) or even after 10 days (44%) [Figure 2].
Hyperglycemia, Cushingoid features, and gastrointestinal (GI) toxicity such as peptic ulceration and GI bleeding were the most commonly observed in patients undergoing corticosteroid therapy [Figure 3], while the commonly undertaken prophylactic measures by practitioners for such patients were anti-peptic ulceration medications, screening for opportunistic infections, and prescribing calcium supplements. Fifty-two percent of the respondents believed that benefits outweigh risks in using corticosteroids in brain tumor patients. 52% of the respondents were unaware of emerging data that suggests that the long-term use of corticosteroids may have a negative impact on the survival of brain tumor patients.
Most of the practitioners (94%) agreed regarding the formulation of evidence-based guidelines for prescribing corticosteroids in brain tumor patients.
Corticosteroids have been used along with radiation therapy and chemotherapy in the management of brain tumors for controlling cerebral edema and other neurologic symptoms since Ingraham et al. in 1952 used adrenocorticotropic hormone as an adjunct to surgery in a patient of pituitary adenoma. Subsequently, cortisone also was used as an adjunct in three pediatric patients undergoing surgery for craniopharyngioma. Since 1961, dexamethasone has been gradually accepted as the choice of drug for treating cerebral edema in brain tumor patients. Given its favorable half-life and minimal mineralocorticoid activity, oral dexamethasone has been the choice of corticosteroid among practitioners in major parts of the world including India, as is evident from our survey. Our detailed survey included 319 respondents primarily associated with the ISNO the premier such society of health care professionals involved in taking care of neuro-oncology practice. The survey in this sense does provide a fairly comprehensive view of the current practices of using corticosteroid therapy in brain tumor patients both in the primary and metastatic settings. Even though some of the earlier studies have defined corticosteroid dosage regimens, those have not been widely incorporated into daily clinical practices as such.,,,, Data from our survey regarding health care professionals' current practices for prescribing corticosteroids during various phases of treatment (such as surgery, radiotherapy, and chemotherapy) of brain tumor patients showed wide variations in terms of dosage and frequency even within professionals of same specialty.,, Such variations have also been recorded in other parts of the world, for example, Sturdza et al. in their survey of Canadian oncologists (n = 34) reported that among respondents, 4 mg four times daily was the most common starting dose of dexamethasone for patients with brain metastases.
Raised intracranial pressures and focal neurological deficits corroborated by clinico-radiological observations were the major factors taken into consideration for prescribing corticosteroids. A wide range of dose strengths (0.5–8 mg) of oral dexamethasone was observed to be available in pharmacies where the respondents practiced which may be a reason for the varied pattern of prescription in certain remote areas which do not have access to most of the standard dose strengths. A major issue of concern which came to light in our survey was that most of the health care professionals used a flat dosage pattern instead of the more standardized methods such as per kilogram body weight and/or body surface area of the patient while prescribing corticosteroids during their practice. There have been varying recommendations regarding the optimal tapering of schedule and doses. While some favor tapering until a physiologic equivalent of 20 mg of cortisol daily is achieved (equivalent to 0.25 mg dexamethasone daily), others determine the tapering schedule as per the patients' symptoms.,, Even though almost half of the respondents in our survey disagreed that the risk of using corticosteroids outweighs the benefits, a still sizeable proportion of them were unsure about the risk–benefit ratio of using corticosteroids. Responses from our survey corroborate with international data regarding the side effects of corticosteroids. Toxicities such as hyperglycemia, Cushingoid features, GI symptoms, psychiatric disorders, opportunistic infections, myopathy, and steroid withdrawal symptoms are among the commonly observed due to increased dose and prolonged duration of dexamethasone usage.,,,,, Prophylactic measures such as anti-peptic ulceration medications, calcium supplementations, regular screening for opportunistic infections such as candidiasis and other fungal or viral infections, physiotherapeutic rehabilitation, and counseling should be undertaken for the patients under corticosteroid therapy especially for longer durations. The majority of the respondents of our survey were seemingly unaware of the pieces of evidence that have been emerging lately indicating a negative impact on the survival of brain tumor patients due to long-term use of corticosteroids. These findings all the more preclude the need to limit the usage of corticosteroids only in symptomatic patients., Smaller response rate, responses primarily by one group of specialty with skewed representation across specialties, and lack of data related to prolonged usage of corticosteroids were some of the limitations of our survey. Results from this pilot study will be used to subsequently design a larger survey that will examine the use of corticosteroids in brain tumors in varied clinical settings across different specialties. Our survey primarily assessed toxicities reported by health care professionals whereas the significance of patient-reported toxicities after dexamethasone usage seems to have gathered momentum in recent times.
Corticosteroids such as dexamethasone have proven to be beneficial in managing brain tumor patients who present with neurologic symptoms caused mainly by cerebral edema. In spite of various studies available regarding appropriate dosage and tapering regimens, uniform adherence to any of these recommendations is still empirical to a major extent. Complications related to prolonged usage of dexamethasone need to be addressed in a more objective manner. Future guidelines should invariably incorporate patient-reported toxicities along with those assessed by health care professionals in order to maintain a more favorable risk to benefit ratio of using corticosteroids in brain tumor patients.
The present pilot survey is first of its kind in the Indian subcontinent and would act as a suitable benchmark to conduct a larger survey and subsequently develop consensus guidelines for uniform practice of corticosteroid therapy.
We thank all our colleagues across India for their active participation in the survey.
Financial support and sponsorship
We thank the Brain Tumour Foundation of India for providing us the financial assistance for conducting the online survey through SurveyMonkey.
Conflicts of interest
There are no conflicts of interest.
[Figure 1], [Figure 2], [Figure 3]