Feasibility and Safety of a Combined Metabolic Strategy in Glioblastoma Multiforme: A Prospective Case Series

Phillips, Matthew; Leyden, J.; McManus, Eileen J.; Lowyim, D. G.; Ziad, Fouzia; Moon, Ben G; Yasin, Nur; Tan, Alvin Boon Tee; Thotathil, Ziad; Jameson, Michael B.

doi:10.1155/2022/4496734

Cited by 4 publications

(1 citation statement)

References 44 publications

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“…Despite these theoretical advantages, supportive interventional evidence in patients with GBM remains limited (25). Only one study has incorporated a combined fasting and ketogenic diet protocol in a rigorous manner (26). This study showed that an intensive, combined KMT program was feasible and safe in patients with GBM.…”

Section: Introductionmentioning

confidence: 92%

Ketogenic metabolic therapy in conjunction with standard treatment for glioblastoma: A case report

Phillips,

Thotathil,

Hari Dass

et al. 2024

Oncol Lett

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Glioblastoma (GBM) is the most common primary malignant brain tumour in adults. The standard of care consists of surgical resection and concurrent chemoradiation, followed by adjuvant temozolomide chemotherapy. This protocol is associated with a median survival of 12-15 months, and <5% of patients survive >3 years. Ketogenic metabolic therapy (KMT) targets cancer cell metabolism by restricting glucose availability and evoking differential stress resistance and sensitization, which may augment the standard treatments and lead to therapeutic benefit. The present study reports the case of a 64-year-old woman with isocitrate dehydrogenase (IDH)-wildtype GBM who pursued the standard treatment protocol in conjunction with an intensive, multimodal KMT program for 3 years. The KMT program consisted of a series of prolonged (7-day, fluid-only) fasts, which were specifically timed to maximize the tolerability and efficacy of the standard treatments, combined with a time-restricted ketogenic diet on all other days. During the first and second treatment years the patient sustained a glucose ketone index (GKI) of 1.65 and 2.02, respectively, which coincided with complete clinical improvement, a healthy body-mass index and a high quality of life, with no visible progressive tumour detected on imaging at the end of the second year. In the setting of the death of an immediate family member leading to increased life stress, slightly relaxed KMT adherence, and a higher GKI of 3.20, slow cancer progression occurred during the third year. The adverse effects attributed to KMT were mild. Despite the limitations of this case report, it highlights the feasibility of implementing the standard treatment protocol for GBM in conjunction with an intensive, long-term, multimodal and specifically timed KMT program, the potential therapeutic efficacy of which may depend upon achieving as low a GKI as possible.

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Section: Introductionmentioning

confidence: 92%

Ketogenic metabolic therapy in conjunction with standard treatment for glioblastoma: A case report

Phillips,

Thotathil,

Hari Dass

et al. 2024

Oncol Lett

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Intermittent fasting and its impact on toxicities, symptoms and quality of life in patients on active cancer treatment

Li Sucholeiki,

Propst,

Hong

et al. 2024

Cancer Treatment Reviews

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Clinical research framework proposal for ketogenic metabolic therapy in glioblastoma

Duraj,

Kalamian,

Zuccoli

et al. 2024

BMC Med

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Glioblastoma (GBM) is the most aggressive primary brain tumor in adults, with a universally lethal prognosis despite maximal standard therapies. Here, we present a consensus treatment protocol based on the metabolic requirements of GBM cells for the two major fermentable fuels: glucose and glutamine. Glucose is a source of carbon and ATP synthesis for tumor growth through glycolysis, while glutamine provides nitrogen, carbon, and ATP synthesis through glutaminolysis. As no tumor can grow without anabolic substrates or energy, the simultaneous targeting of glycolysis and glutaminolysis is expected to reduce the proliferation of most if not all GBM cells. Ketogenic metabolic therapy (KMT) leverages diet-drug combinations that inhibit glycolysis, glutaminolysis, and growth signaling while shifting energy metabolism to therapeutic ketosis. The glucose-ketone index (GKI) is a standardized biomarker for assessing biological compliance, ideally via real-time monitoring. KMT aims to increase substrate competition and normalize the tumor microenvironment through GKI-adjusted ketogenic diets, calorie restriction, and fasting, while also targeting glycolytic and glutaminolytic flux using specific metabolic inhibitors. Non-fermentable fuels, such as ketone bodies, fatty acids, or lactate, are comparatively less efficient in supporting the long-term bioenergetic and biosynthetic demands of cancer cell proliferation. The proposed strategy may be implemented as a synergistic metabolic priming baseline in GBM as well as other tumors driven by glycolysis and glutaminolysis, regardless of their residual mitochondrial function. Suggested best practices are provided to guide future KMT research in metabolic oncology, offering a shared, evidence-driven framework for observational and interventional studies.

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Feasibility and Safety of a Combined Metabolic Strategy in Glioblastoma Multiforme: A Prospective Case Series

Cited by 4 publications

References 44 publications

Ketogenic metabolic therapy in conjunction with standard treatment for glioblastoma: A case report

Ketogenic metabolic therapy in conjunction with standard treatment for glioblastoma: A case report

Intermittent fasting and its impact on toxicities, symptoms and quality of life in patients on active cancer treatment

Clinical research framework proposal for ketogenic metabolic therapy in glioblastoma

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