Elsevier

World Neurosurgery

Volume 109, January 2018, Pages e845-e852
World Neurosurgery

Original Article
Results of a Policy of Fast Tapering of Steroids After Resection Surgery in Glioblastoma

https://doi.org/10.1016/j.wneu.2017.10.110Get rights and content

Background

Corticosteroids are routinely used to treat brain tumors. Although steroids have an immediate clinical benefit, their use can lead to a number of relevant complications, and a negative association with overall survival has been shown in glioblastoma (GBM) patients. There is no evidence in the literature regarding the ideal dose. We assessed the use of steroids in patients with GBM after resection surgery.

Methods

This is a cohort study of 131 newly diagnosed GBM patients that underwent tumor resection surgery. Dose of steroids was as low as possible, without a formal guideline. Fifteen patients were lost at baseline (retention rate, 88.5%). Our population for analysis included 114 patients that were still at risk of death at a landmark time point 2 months after surgery.

Results

Within 1 month of surgery, 93.9% of patients came off steroids, and 84.7% came off steroids before 2 weeks. One month after radiotherapy, 86 (75.4%) patients remained steroid-free and 28 (24.6%) were steroid-dependent. During 2235 person-months of follow-up, we documented 101 incident deaths. After adjusting for age, sex, Karnofsky Performance Scale score, MGMT promoter methylation, and extent of tumor resection, and time to surgery, the hazard ratio for the steroid-free group of patients was 0.46 (95% confidence interval, 0.28–0.77) compared with steroid-dependent patients.

Conclusions

This study provides evidence for an inverse association between the lack of steroid dependency and mortality risk in patients whose steroid dosage was rapidly tapered after surgery. After resection, most patients can stop steroids within 2 weeks and finish radiotherapy without steroids.

Introduction

Potent corticosteroids are routinely used for the treatment of edema associated with brain tumors. Dexamethasone has been considered the standard since the early 1960s. Although the acute effect is a marked clinical improvement, their chronic use can lead to a number of relevant complications. Deleterious side effects can include a rise in serum glucose, weight gain, lymphopenia, immunosuppression, psychiatric disorders, gastrointestinal problems, osteoporosis, myopathy, and an increased risk of deep vein thrombosis and pulmonary embolism.1, 2 Negative effects on neurocognitive function and quality of life are also well documented in patients with tumors who are administered corticosteroids.2

Because recurrence is to be expected in malignant brain tumors, most patients will require prolonged steroids use and will have secondary effects from steroid treatment at the end of the disease. Experimental data also suggest that dexamethasone can diminish the effect of chemotherapy.3, 4 and radiotherapy.5 Three recent papers found worse overall survival (OS) in patients receiving greater amounts of dexamethasone.5, 6, 7 Additionally, the potential role of immune therapies in many malignant tumors is being increasingly recognized, and steroids have the potential to interfere with immunologic responses.8

Although there is ample data to justify an as low as possible steroids policy, there are also concerns about the risk of rebounding edema and triggering adrenal insufficiency. Evidence available on the ideal dose and timing of its use is scarce, and different tapering strategies have not been compared prospectively. Even for brain metastasis, in which more studies have been conducted, the available recommendations are only level 3 and with few details.9

European Association of Neurooncology (EANO) guidelines point out that for malignant glioma management, there is an option to rapidly taper steroids after resection surgery that should not be missed.10 However, very few data are available on how rapidly this can be done, and in how many patients.

In this paper, we studied a cohort of newly diagnosed glioblastoma (GBM) patients who were rapidly tapered off steroids after GBM surgery and estimated the frequency of patients who maintained this status before starting adjuvant chemotherapy. We also assessed potential factors influencing their status. Finally, we evaluated the relationship between steroid dependency and OS.

Section snippets

Materials and Methods

This was a single hospital-based cohort study that included patients with newly diagnosed GBM who underwent tumor resection surgery during the period from August 2007 to November 2015 at University Clinic of Navarra, Spain. Data were collected from the prospective database on brain tumor cases at the department of neurosurgery and in hospital and ambulatory medical care. Patients with biopsy only were excluded, and any type of resection, partial or total, was included in the review. Patient

Results

Between August 2007 and November 2015, 131 newly diagnosed GBM patients underwent tumor resection surgery at University Clinic of Navarra, Spain. Total withdrawal of steroids after surgery was possible in 126 cases (93.2%); steroid withdrawal was performed within ≤1 week in 65 patients (49.6%), in ≤2 weeks in 111 patients (84.7%), and within 1 month in 123 patients (93.9%). Patients in whom steroids were never withdrawn (4.3%) all had neurologic deficits that did not completely disappear after

Discussion

In this cohort study of GBM patients who underwent resection surgery using a policy of rapid tapering of steroids, the absence of steroid dependency was associated with a lower incidence of mortality, even after adjusting for established risk factors of death. The inverse association was not explained by potentially confounding factors, including age, sex, KPS score, MGMT promoter methylation, extent of tumor resection, and TTS.

The variability of the prescribing practices of corticosteroids in

Conclusions

This cohort study shows our results of using a steroid dose that was previously recommended in patients with a recent diagnosis of GBM. A randomized trial using different doses would be needed to provide high-level evidence of the best dose, and the effect on OS. This study also provides evidence for an inverse association between the lack of steroid dependency and mortality risk in patients who were rapidly tapered off steroids after GBM surgery.

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Cited by (6)

Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Ricardo Díez Valle and Victoria Becerra Castro are co–first authors.

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