Katharina J Wenger1,2,3,4, Marlies Wagner1,2,3,4, Patrick N Harter2,3,4,5, Kea Franz2,3,4,6, Jörg Bojunga4,7, Emmanouil Fokas2,3,4,8, Detlef Imhoff2,3,4,8, Claus Rödel2,3,4,8, Johannes Rieger9,10, Elke Hattingen1,2,3,4, Joachim P Steinbach2,3,4,9, Ulrich Pilatus1,2,3,4, Martin Voss2,3,4,9. 1. Institute of Neuroradiology, University Hospital Frankfurt, Goethe University, 60528 Frankfurt am Main, Germany. 2. University Cancer Center Frankfurt (UCT), University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany. 3. German Cancer Consortium (DKTK) Partner Site Frankfurt/Mainz, 60590 Frankfurt am Main, Germany. 4. Frankfurt Cancer Institute (FCI), 60590 Frankfurt am Main, Germany. 5. Neurological Institute (Edinger-Institute), University Hospital Frankfurt, Goethe University, 60528 Frankfurt am Main, Germany. 6. Department of Neurosurgery, University Hospital Frankfurt, Goethe University, 60528 Frankfurt am Main, Germany. 7. Department of Medicine, University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany. 8. Department of Radiotherapy and Oncology, University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany. 9. Dr. Senckenberg Institute of Neurooncology, University Hospital Frankfurt, Goethe University, 60528 Frankfurt am Main, Germany. 10. Interdisciplinary Division of Neuro-Oncology, University Hospital Tübingen, 72076 Tübingen, Germany.
Abstract
Background: The ERGO2 (Ernaehrungsumstellung bei Patienten mitRezidiv eines Glioblastoms) MR-spectroscopic imaging (MRSI) subtrial investigated metabolism in patients randomized to calorically restricted ketogenic diet/intermittent fasting (crKD-IF) versus standard diet (SD) in addition to re-irradiation (RT) for recurrent malignant glioma. Intracerebral concentrations of ketone bodies (KB), intracellular pH (pHi), and adenosine triphosphate (ATP) were non-invasively determined. Methods:50 patients were randomized (1:1): Group A keeping a crKD-IF for nine days, and Group B a SD. RT was performed on day 4-8. Twenty-three patients received an extended MRSI-protocol (1H decoupled 31P MRSI with 3D chemical shift imaging (CSI) and 2D 1H point-resolved spectroscopy (PRESS)) at a 3T scanner at baseline and on day 6. Voxels were selected from the area of recurrent tumor and contralateral hemisphere. Spectra were analyzed with LCModel, adding simulated signals of 3-hydroxybutyrate (βOHB), acetone (Acn) and acetoacetate (AcAc) to the standard basis set. Results: Acn was the only reliably MRSI-detectable KB within tumor tissue and/or normal appearing white matter (NAWM). It was detected in 4/11 patients in Group A and in 0/8 patients in Group B. MRSI results showed no significant depletion of ATP in tumor tissue of patients at day 6 during crKD-IF, even though there were a significant difference in ketone serum levels between Group A and B at day 6 and a decline in fasting glucose in Group A from baseline to day 6. The tumor specific alkaline pHi was maintained. Conclusions: Our metabolic findings suggest that tumor cells maintain energy homeostasis even with reduced serum glucose levels and may generate additional ATP through other sources.
RCT Entities:
Background: The ERGO2 (Ernaehrungsumstellung bei Patienten mit Rezidiv eines Glioblastoms) MR-spectroscopic imaging (MRSI) subtrial investigated metabolism in patients randomized to calorically restricted ketogenic diet/intermittent fasting (crKD-IF) versus standard diet (SD) in addition to re-irradiation (RT) for recurrent malignant glioma. Intracerebral concentrations of ketone bodies (KB), intracellular pH (pHi), and adenosine triphosphate (ATP) were non-invasively determined. Methods: 50 patients were randomized (1:1): Group A keeping a crKD-IF for nine days, and Group B a SD. RT was performed on day 4-8. Twenty-three patients received an extended MRSI-protocol (1H decoupled 31P MRSI with 3D chemical shift imaging (CSI) and 2D 1H point-resolved spectroscopy (PRESS)) at a 3T scanner at baseline and on day 6. Voxels were selected from the area of recurrent tumor and contralateral hemisphere. Spectra were analyzed with LCModel, adding simulated signals of 3-hydroxybutyrate (βOHB), acetone (Acn) and acetoacetate (AcAc) to the standard basis set. Results:Acn was the only reliably MRSI-detectable KB within tumor tissue and/or normal appearing white matter (NAWM). It was detected in 4/11 patients in Group A and in 0/8 patients in Group B. MRSI results showed no significant depletion of ATP in tumor tissue of patients at day 6 during crKD-IF, even though there were a significant difference in ketone serum levels between Group A and B at day 6 and a decline in fasting glucose in Group A from baseline to day 6. The tumor specific alkaline pHi was maintained. Conclusions: Our metabolic findings suggest that tumor cells maintain energy homeostasis even with reduced serum glucose levels and may generate additional ATP through other sources.
Entities:
Keywords:
ATP; MR-spectroscopy; fasting; glioblastoma; ketogenic diet; ketone body
Authors: Joachim P Steinbach; Claus Rödel; Johannes Rieger; Martin Voss; Katharina J Wenger; Nina von Mettenheim; Jörg Bojunga; Manuela Vetter; Bianca Diehl; Kea Franz; Ruediger Gerlach; Michael W Ronellenfitsch; Patrick N Harter; Elke Hattingen Journal: Eur J Nutr Date: 2021-09-06 Impact factor: 5.614
Authors: Karisa C Schreck; Fang-Chi Hsu; Adam Berrington; Bobbie Henry-Barron; Diane Vizthum; Lindsay Blair; Eric H Kossoff; Linda Easter; Christopher T Whitlow; Peter B Barker; Mackenzie C Cervenka; Jaishri O Blakeley; Roy E Strowd Journal: Neurology Date: 2021-07-07 Impact factor: 11.800