Maintenance of Energy Homeostasis during Calorically Restricted Ketogenic Diet and Fasting-MR-Spectroscopic Insights from the ERGO2 Trial
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. Patient Characteristics and Prior Treatment MRSI Substudy
2.2. Adherence to Radiation Study Protocol
2.3. Patients’ Adherence to Recommended Dietary Intervention
2.4. Detectability of Ketone Bodies in Urine and Blood Samples
2.5. Intracerebral Detectability and Quantitation of Ketone Bodies Using MRSI
2.6.Intracellular pH and Energy Metabolism
3. Discussion
3.1. Discussion
3.2. Limitations
4. Materials and Methods
4.1. Patients and Study Design
4.2. Magnetic Resonance Imaging
4.3. Data Analysis
4.4. 31P MRSI Model
4.5. Simulation of Basis Set for 1H MRSI
4.6. Phantom Replacement
4.7. Laboratory Testing
4.8. Statistics
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Characteristics | All Patients (n = 19) | Group B (n = 8) |
---|---|---|
Group A (n = 11) | ||
General | ||
Age, median | 53 (range 38–64) | 42.5 (range 25–61) |
Age, mean | 53 (SD = 7) | 41 (SD = 14) |
Karnofsky index, mean rounded to nearest tenth (SD) | 90 (SD = 13) | 90 (SD = 6) |
Histology | ||
Glioblastoma, IDH wildtype, WHO IV (n) | 5 | 3 |
Glioblastoma IDH-mutant, WHO IV (n) | 1 | 1 |
Glioblastoma IDH-mutant, IDH unknown, WHO IV (n) | 4 | 1 |
Anaplastic astrocytoma, IDH wildtype, WHO III (n) | 1 | 0 |
Oligodendroglioma, IDH-mutant and 1p/19q co-deleted, WHO II (n) | 0 | 1 |
Pleomorphic Xanthoastrocytoma, IDH wildtype (n) | 0 | 1 |
Undifferentiated neuroepithelial tumor, NOS, WHO IV (n) | 0 | 1 |
MGMT promotor methylation status | ||
Not methylated | 46% (n = 5) | 63% (n = 5) |
Methylated | 46% (n = 5) | 25% (n = 2) |
Not known | 9% (n = 1) | 13% (n = 1) |
Prior treatment | ||
Radiation therapy up to 60 Gy | 100% (n = 11) | 100% (n = 8) |
Concomitant TMZ | 100% (n = 11) | 88% (n = 7) |
Median of adjuvant cycles of TMZ | 6 | 3 |
Prior treatment with Bevacizumab | 18% (n = 2) | 13% (n = 1) |
Resection prior to study treatment | 9% (n = 1) | 50% (n = 4) |
Time interval first and second irradiation (months) | ||
Median | 9 | 11 |
Mean | 14 (SD = 9) | 17 (SD = 16) |
Patient ID | Group | Drop out during 9 Days of crKD-IF | Histology at First Diagnosis | Glucose Baseline (mg/dL) | Glucose Day 6 (mg/dL) | Blood Ketone Levels Day 6 (mmol/L) | Urine Ketosis Day 6 (mmol/L) | Acn Signal Quantitation (mmol/L) |
---|---|---|---|---|---|---|---|---|
26 | A | yes | Glioblastoma | 78.0 | 59.0 | 0.1 | 0 | tumor tissue 0.12; NAWM 0.14 |
27 | A | yes | Glioblastoma | 84.0 | 98.0 | N/A | N/A | NAWM 0.28 |
34 | A | no | Anaplastic astrocytoma | 112.0 | 78.0 | 0.4 | 1.5 | NAWM 0.21 |
38 | A | no | Glioblastoma | 81.0 | 54.0 | 4.5 | N/A | NAWM 0.25 |
Sequence | Slice Thickness | TR; Excitation Flip Angle | TE | Matrix Size; in Plane Resolution | Vector Size; Bandwidth | Scan Time |
---|---|---|---|---|---|---|
3D FID 31P CSI | 25 mm * | 2000 ms; 60° | 2.3 *** ms | 8 × 8 × 8 at 240 × 240 × 200 mm3 FOV interpolated to 16 × 16 × 16; 30 × 30 mm2 * | 1024; 2000 Hz | 10:44 m |
2D 1H PRESS sequence | 12.5 mm ** | 1500 ms; 90° | 30 ms | 16 × 16 at 240 × 240, interpolated to 32 × 32; 15 × 15 mm2 * | 1024; 2000 Hz | 4:45 m |
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Wenger, K.J.; Wagner, M.; Harter, P.N.; Franz, K.; Bojunga, J.; Fokas, E.; Imhoff, D.; Rödel, C.; Rieger, J.; Hattingen, E.; et al. Maintenance of Energy Homeostasis during Calorically Restricted Ketogenic Diet and Fasting-MR-Spectroscopic Insights from the ERGO2 Trial. Cancers 2020, 12, 3549. https://doi.org/10.3390/cancers12123549
Wenger KJ, Wagner M, Harter PN, Franz K, Bojunga J, Fokas E, Imhoff D, Rödel C, Rieger J, Hattingen E, et al. Maintenance of Energy Homeostasis during Calorically Restricted Ketogenic Diet and Fasting-MR-Spectroscopic Insights from the ERGO2 Trial. Cancers. 2020; 12(12):3549. https://doi.org/10.3390/cancers12123549
Chicago/Turabian StyleWenger, Katharina J., Marlies Wagner, Patrick N. Harter, Kea Franz, Jörg Bojunga, Emmanouil Fokas, Detlef Imhoff, Claus Rödel, Johannes Rieger, Elke Hattingen, and et al. 2020. "Maintenance of Energy Homeostasis during Calorically Restricted Ketogenic Diet and Fasting-MR-Spectroscopic Insights from the ERGO2 Trial" Cancers 12, no. 12: 3549. https://doi.org/10.3390/cancers12123549