Lotte Noorlag1, Filip Y De Vos2, Annemieke Kok3, Marike L D Broekman4, Tatjana Seute1, Pierre A Robe5, Tom J Snijders6. 1. Brain Center Rudolf Magnus, Department of Neurology, University Medical Center Utrecht, G03.232, PO Box 85500, 3508 GA, Utrecht, the Netherlands. 2. Department of Medical Oncology, Internal Medicine and Dermatology, University Medical Center Utrecht, Utrecht, the Netherlands. 3. Department of Dietetics, University Medical Center Utrecht, Utrecht, the Netherlands. 4. Brain Center Rudolf Magnus, Department of Neurosurgery, University Medical Center Utrecht, Utrecht, the Netherlands; Department of Neurosurgery, Leiden University Medical Center, Leiden, the Netherlands; Department of Neurosurgery, Haaglanden Medical Center, The Hague, the Netherlands. 5. Brain Center Rudolf Magnus, Department of Neurosurgery, University Medical Center Utrecht, Utrecht, the Netherlands. 6. Brain Center Rudolf Magnus, Department of Neurology, University Medical Center Utrecht, G03.232, PO Box 85500, 3508 GA, Utrecht, the Netherlands. Electronic address: T.J.Snijders@umcutrecht.nl.
Abstract
BACKGROUND & AIMS: Patients with malignant gliomas have a poor prognosis. Diets that lower blood glucose, such as ketogenic or caloric restricted diets (KCRDs), are hypothesized to reduce tumor growth and improve survival. In this systematic review, we summarize preclinical and clinical data on KCRDs in gliomas. METHODS: We searched PubMed and Embase for preclinical and clinical studies on KCRDs in gliomas, and extracted data on surrogate and clinically relevant endpoints, in accordance with PRISMA statement. Quality assessment of clinical studies was performed with use of Cochrane Collaboration's tool. We performed Fisher's exact test to examine associations between surrogate and clinically relevant endpoints. RESULTS: We included 24 preclinical studies, seven clinical studies and one mixed study. Both preclinical and clinical studies were highly heterogeneous. Preclinically, KCRDs reduced tumor growth, but only a small majority of the in vivo studies found improved survival. These effects were stronger in groups with decreased blood glucose than in those with increased ketones, and also when other therapies were used concomitantly. Finally, KCRDs influence multiple molecular-biological pathways, including the PTEN/Akt/TSC2 and NF-kB pathway. In clinical studies, KCRDs seem to be safe and feasible in glioma patients. Clinical data were insufficient to draw conclusions regarding efficacy. CONCLUSIONS: KCRDs have positive effects on malignant gliomas in published preclinical studies. Preliminary clinical data suggest that KCRDs are safe and feasible. However, because of the paucity of clinical data, the efficacy of KCRDs for improving survival and quality of life of glioma patients remains to be proven in prospective studies.
BACKGROUND & AIMS:Patients with malignant gliomas have a poor prognosis. Diets that lower blood glucose, such as ketogenic or caloric restricted diets (KCRDs), are hypothesized to reduce tumor growth and improve survival. In this systematic review, we summarize preclinical and clinical data on KCRDs in gliomas. METHODS: We searched PubMed and Embase for preclinical and clinical studies on KCRDs in gliomas, and extracted data on surrogate and clinically relevant endpoints, in accordance with PRISMA statement. Quality assessment of clinical studies was performed with use of Cochrane Collaboration's tool. We performed Fisher's exact test to examine associations between surrogate and clinically relevant endpoints. RESULTS: We included 24 preclinical studies, seven clinical studies and one mixed study. Both preclinical and clinical studies were highly heterogeneous. Preclinically, KCRDs reduced tumor growth, but only a small majority of the in vivo studies found improved survival. These effects were stronger in groups with decreased blood glucose than in those with increased ketones, and also when other therapies were used concomitantly. Finally, KCRDs influence multiple molecular-biological pathways, including the PTEN/Akt/TSC2 and NF-kB pathway. In clinical studies, KCRDs seem to be safe and feasible in gliomapatients. Clinical data were insufficient to draw conclusions regarding efficacy. CONCLUSIONS: KCRDs have positive effects on malignant gliomas in published preclinical studies. Preliminary clinical data suggest that KCRDs are safe and feasible. However, because of the paucity of clinical data, the efficacy of KCRDs for improving survival and quality of life of gliomapatients remains to be proven in prospective studies.
Authors: Thomas N Seyfried; Laura Shelton; Gabriel Arismendi-Morillo; Miriam Kalamian; Ahmed Elsakka; Joseph Maroon; Purna Mukherjee Journal: Neurochem Res Date: 2019-04-25 Impact factor: 3.996
Authors: Elles J T M van der Louw; Joanne F Olieman; Patricia M L A van den Bemt; Jacoline E C Bromberg; Esther Oomen-de Hoop; Rinze F Neuteboom; Coriene E Catsman-Berrevoets; Arnaud J P E Vincent Journal: Ther Adv Med Oncol Date: 2019-06-21 Impact factor: 8.168