Keto-Brain:Investigating the Use of Ketogenic Diets in Brain Metastases

Neurological tissues are among the most common (\>10% of cancer patients) and debilitating sites for metastatic disease to develop. The brain is a 'sanctuary site' for many cancer cells and remains a challenging site to treat. Surgery and radiation therapies are the most common treatments. The investigators hypothesize that the metabolic adaptations associated with a well-formulated ketogenic diet that induces nutritional ketosis will significantly improve the response to surgery and radiation in patients with brain metastases. To date, numerous preclinical studies have demonstrated the ability of nutritional ketosis and caloric restriction to augment the therapeutic efficacy of radiotherapy. Use of a ketogenic diet is known to decrease the protein expression of HIF-1 and VEGFR2, and may increase radio sensitivity by normalizing tumor vasculature and increasing facilitated oxygen delivery to tumor cells. Several additional proposed mechanisms exist for enhancing radiosensitivity of the malignancy including: HDAC dependent mechanisms, ATP deprivation, mitochondrial ROS production and downregulation of IGF-1 receptor. Short-term fasting, a way to increase ketones acutely, has been demonstrated to speed up mitotic rates and thus facilitate a DNA damage sensitization. Lastly, a recent study showed that glucose restriction lowered Ki-67 expression, clonogenic frequency and rate of proliferation in gliomaspheres in vitro. The investigating team team has an established expertise in conducting ketogenic diet interventions. Many individuals have adopted a low-carbohydrate diet for health reasons, yet there is scarce professional support available to provide guidance and support, especially for ketogenic diets. The investigators have scientific expertise and practical knowledge of both ketogenic and current standard of care cancer diets combined with a passion to empower people with the tools to implement these eating approaches into the participant's lifestyle. This project is highly patient-centered. The investigators will support patients who are randomized into either one of the intervention groups and provide them with a personalized eating plan designed to have maximal therapeutic impact and positively impact their lives. To that end, this project is unique in that it is highly patient-centered while also designed to have a substantial scientific and practical impact on medical management of brain metastasis treatments.