Abstract
BackgroundManagement of glioblastoma multiforme (GBM) has been difficult using standard therapy (radiation with temozolomide chemotherapy). The ketogenic diet is used commonly to treat refractory epilepsy in children and, when administered in restricted amounts, can also target energy metabolism in brain tumors. We report the case of a 65-year-old woman who presented with progressive memory loss, chronic headaches, nausea, and a right hemisphere multi-centric tumor seen with magnetic resonance imaging (MRI). Following incomplete surgical resection, the patient was diagnosed with glioblastoma multiforme expressing hypermethylation of the MGMT gene promoter.MethodsPrior to initiation of the standard therapy, the patient conducted water-only therapeutic fasting and a restricted 4:1 (fat: carbohydrate + protein) ketogenic diet that delivered about 600 kcal/day. The patient also received the restricted ketogenic diet concomitantly during the standard treatment period. The diet was supplemented with vitamins and minerals. Steroid medication (dexamethasone) was removed during the course of the treatment. The patient was followed using MRI and positron emission tomography with fluoro-deoxy-glucose (FDG-PET).ResultsAfter two months treatment, the patient's body weight was reduced by about 20% and no discernable brain tumor tissue was detected using either FDG-PET or MRI imaging. Biomarker changes showed reduced levels of blood glucose and elevated levels of urinary ketones. MRI evidence of tumor recurrence was found 10 weeks after suspension of strict diet therapy.ConclusionThis is the first report of confirmed GBM treated with standard therapy together with a restricted ketogenic diet. As rapid regression of GBM is rare in older patients following incomplete surgical resection and standard therapy alone, the response observed in this case could result in part from the action of the calorie restricted ketogenic diet. Further studies are needed to evaluate the efficacy of restricted ketogenic diets, administered alone or together with standard treatment, as a therapy for GBM and possibly other malignant brain tumors.
Highlights
Glioblastoma multiforme (GBM) is the most malignant primary brain tumor in adults and children
In this case report we describe the management of a highly invasive multi-centric glioblastoma multiforme (GBM) in an older patient following partial tumor resection and treatment with a combination of standard therapy, fasting, and a R-ketogenic diet (KD)
The patient in this study expressed hypermethylation of the methylguanine methyltransferase (MGMT) gene promoter, which enhances the therapeutic action of temozolomide and is prognostic for increased survival [26], no prior cases of rapid GBM regression have been reported in patients with the MGMT hypermethylation phenotype to our knowledge
Summary
Glioblastoma multiforme (GBM) is the most malignant primary brain tumor in adults and children. In contrast to normal brain cells, which evolved to metabolize ketone bodies for energy when glucose levels are reduced, most brain tumor cells are dependent on glycolysis for survival and are unable to metabolize ketone bodies for energy due to impaired mitochondrial function [9]. The ketogenic diet, administered in restricted amounts, is ideally suited as a non-toxic metabolic therapy for managing malignant brain cancer because the diet naturally lowers circulating glucose levels while elevating levels of ketone bodies [9,10,11]. The ketogenic diet administered in restricted amounts (R-KD) has potential as a non-toxic metabolic therapy against malignant brain cancer. The ketogenic diet is used commonly to treat refractory epilepsy in children and, when administered in restricted amounts, can target energy metabolism in brain tumors. The patient was diagnosed with glioblastoma multiforme expressing hypermethylation of the MGMT gene promoter
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