Background
Glioblastoma (GBM) is the most common and devastating malignant brain tumor in adults.
Patients with glioblastoma face a poor prognosis. Despite maximal treatment, most
patients suffer tumor progression after 6-7 months and die within 1-2 years. Standard
treatment for newly diagnosed glioblastoma contains maximal safe surgery and adjuvant
radiochemotherapy with temozolomide. Additional administration of steroids has
established as standard of care during treatment of GBM. It is widely used during the
entire course of the disease including pre- and postoperative management, chemotherapy
and radiotherapy. Dexamethasone (DEX) is the most frequently used steroid. The main
purpose is to reduce the tumor associated vasogenic cerebral edema, to prevent or treat
increased intracranial pressure. In addition, DEX helps to cope with adverse effects of
GBM-treatment like nausea, vomiting and fatigue. However, steroids are also linked to a
multitude of adverse side effects that may affect the survival of GBM patients such as
major immunosuppression, and metabolic changes like hyperglycemia. The use of steroids
during radiotherapy is associated with reduced overall- and progression-free survival and
has been identified as an independent poor prognostic factor. DEX was also related to a
poor prognosis in recurrent GBM. Despite these findings, in routine clinical practice,
the suspicion of glioblastoma often triggers the administration of DEX, regardless of
neurologic symptoms or the extension of cerebral edema. Many patients are treated with
larger doses of DEX per day before being referred to a neurosurgical center and are kept
on steroids during the entire treatment. On the other hand, the clinical experience shows
that GBM-patients with no, or only mild neurologic symptoms, normal intracranial pressure
and relatively small cerebral edema can be managed without administration of DEX. The
rationale for this study is to objectify the criteria and safety of a restrictive DEX
regimen (based on standardized clinical and radiological criteria). A restrictive DEX
regimen may help to reduce over-use, limit the number of patients exposed to the adverse
effects of DEX, and potentially improve survival in GBM-patients. The purpose of this
study is to assess whether selected GBM patients can be treated safely with a restrictive
DEX regimen from referral to the neurosurgical center until discharge.
Objective
The primary objective is to determine the failure rate of a restrictive DEX regimen
defined as edema or mass effect leading to any of the following: GCS deterioration ≥ 2
points, NIHSS increase ≥ 3 points, increase of midline Shift ≥ 2mm, or any surgical
rescue procedure for increasing mass effect.
Methods
All patients referred to the neurosurgical center with suspicion of glioblastoma are
screened for inclusion- and exclusion criteria. If eligible and consenting of the patient
to the study protocol, no steroids will be administered until discharge (except optional
intraoperative single shot dexamethasone of max. 4mg if necessary). If steroids have been
administered for a maximum of one day before referral, they will be stopped immediately.
Patients are followed clinically. If one of the above-described failure criteria occurs,
the primary endpoint is reached and DEX will be administered.
