Ketogenic Metabolic Therapy for Glioma

Abstract

Purpose: This study describes a retrospective case series of patients with glioma who received ketogenic metabolic therapy through dietary adherence and intermittent fasting.

Methods: A retrospective chart review of a single surgeon's clinic records was performed to identify patients who maintained nutritional ketosis for at least four months between January 2015 and October 2020.

Results: Sixteen patients who met the inclusion criteria constituted a heterogeneous population of patients with diagnoses including eight World Health Organization (WHO) grade IV gliomas (seven glioblastoma, one gliosarcoma), seven WHO grade III gliomas (three oligodendroglioma, four astrocytoma), and one WHO grade II oligodendroglioma. IDH1 mutation status was present for 12 patients, and MGMT methylation status was present for eight patients. The mean (standard deviation [SD]) duration of ketogenic metabolic therapy was 20.6 (13.8) months. The Response Assessment in Neuro-oncology Criteria was applied during the ketogenic metabolic therapy interval, indicating a complete response in eight patients and partial response in eight patients. The mean (SD) progression-free survival while patients maintained ketogenic metabolic therapy was 20.0 (14.4) months.

Conclusion: Ketogenic metabolic therapy appears to convey a survival advantage within this patient series, which highlights the possibility that this therapy, when strictly applied, can augment the standard of care. Further exploration of this modality in a prospective series is warranted to formally explore this therapy.

Keywords: glioblastoma; high-grade glioma; ketones; ketosis; metabolism.

Figure 1. MRIs for patient 3

Axial magnetic resonance imaging (MRI) for patient 3 showing multiple enhancing nodules at the time of recurrence (2018) within the right frontal lobe (A). Annual follow-up T1-enhanced axial MRIs from 2019 (B), 2020 (C), and 2021 (D), obtained during 36 months of continuous ketogenic metabolic therapy, show that the patient experienced complete resolution of tumor enhancement. The patient demonstrated increased fluid-attenuated inversion recovery (FLAIR) signal intensity at the time of recurrence (2018) (E), with progressive improvement in FLAIR signal intensity and distribution in 2019 (F), 2020 (G), and 2021 (H). Used with permission from Barrow Neurological Institute, Phoenix, Arizona.

Figure 2. MRIs for patient 10

Patient 10 had continued disease progression after a second surgical resection as evidenced by increasingly nodular enhancement (A, sagittal magnetic resonance imaging [MRI]) and progressive cerebral edema (B, axial MRI). The patient subsequently initiated ketogenic metabolic therapy, and imaging obtained at the next follow-up evaluation (four months later) showed significant improvement in lesional enhancement (C, sagittal MRI) and markedly reduced cerebral edema (D, axial MRI). Used with permission from Barrow Neurological Institute, Phoenix, Arizona.

Figure 3. MRIs for patient 1

Axial magnetic resonance images (MRIs) for patient 1, who underwent repeat surgical resection, show that afterward the patient had continued progression of the tumor within the right insula, thalamus, basal ganglia, basal forebrain (A), and cerebellomedullary region (C). After initiation of ketogenic metabolic therapy, tumor-treating fields therapy, and temozolomide therapy, imaging shows near-complete resolution of the diffuse multifocal fluid-attenuated inversion recovery anomaly in the right insula, thalamus, basal ganglia, basal forebrain (B), and cerebellomedullary region (D). After a period of time during which the patient did not achieve ketosis, subsequent imaging showed progression of the tumor within the right medial temporal lobe and right medulla (E). Metabolic genomic profiling identified the cause of the patient’s inability to achieve ketosis, and he reinitiated ketogenic metabolic therapy. Because of its severity, the cerebellomedullary lesion was treated with Zap-X stereotactic radiosurgery. Follow-up imaging showed that the size of the lesion was greatly reduced (F). Used with permission from Barrow Neurological Institute, Phoenix, Arizona.