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Clinical research framework proposal for ketogenic metabolic therapy in glioblastoma

Authors: Tomás Duraj,Miriam Kalamian,Giulio Zuccoli,Joseph C. Maroon,Dominic P. D’Agostino,Adrienne C. Scheck,Angela Poff,Sebastian F. Winter,Jethro Hu,Rainer J. Klement,Alicia Hickson,Derek C. Lee,Isabella Cooper,Barbara Kofler,Kenneth A. Schwartz,Matthew C. L. Phillips,Colin E. Champ,Beth Zupec-Kania,Jocelyn Tan-Shalaby,Fabiano M. Serfaty,Egiroh Omene,Gabriel Arismendi-Morillo,Michael Kiebish,Richard Cheng,Ahmed M. El-Sakka,Axel Pflueger,Edward H. Mathews,Donese Worden,Hanping Shi,Raffaele Ivan Cincione,Jean Pierre Spinosa,Abdul Kadir Slocum,Mehmet Salih Iyikesici,Atsuo Yanagisawa,Geoffrey J. Pilkington,Anthony Chaffee,Wafaa Abdel-Hadi,Amr K. Elsamman,Pavel Klein,Keisuke Hagihara,Zsófia Clemens,George W. Yu,Athanasios E. Evangeliou,Janak K. Nathan,Kris Smith,David Fortin,Jorg Dietrich,Purna Mukherjee,Thomas N. Seyfried
Publisher: Springer Science and Business Media LLC
Publish date: 2024-12-5
ISSN: 1741-7015 DOI: 10.1186/s12916-024-03775-4
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The proposal for ketogenic metabolic therapy as a baseline for glioblastoma treatment is compelling. However, a few points warrant further discussion:

The article emphasizes the utility of the Glucose-Ketone Index (GKI) for monitoring therapeutic efficacy, yet the variability of GKI responses across patient populations with differing metabolic baselines (e.g., insulin resistance or cancer cachexia) remains underexplored. Could the authors elaborate on how GKI targets are adapted for such heterogeneous groups, particularly in relation to individual caloric and macronutrient needs?
While the study highlights KMT’s synergy with chemoradiotherapy, the potential risks of delaying standard-of-care treatments for interim KMT evaluation might raise ethical concerns. How do the authors propose addressing patient safety and long-term outcomes during such delays, especially for aggressive tumor subtypes?
The reliance on self-reported dietary compliance or intermittent biological markers in earlier studies is noted as a limitation. Could the authors suggest specific technologies (e.g., wearable glucose-ketone monitors) or protocols that future studies should adopt to ensure real-time, high-fidelity data collection?

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