TMET-38. Prospective registry trial of 48 patients with high grade gliomas treated with ketogenic metabolic therapy (KMT) with long-term follow up MRI and survival data

Abstract Despite advances in surgical, radiation, and chemotherapeutic interventions, high grade gliomas remain a therapeutic challenge. The mutations status of the IDH metabolism regulation genes is the most important prognostic factor for survival, suggesting that metabolic targeting could be significant for treatment strategies for these tumors. Ketogenic metabolic therapy (KMT), inducing nutritional ketosis through high-fat, low-carbohydrate diets, leverages the metabolic dichotomy between glucose-dependent tumor cells and ketone-utilizing healthy tissues. We created a prospective registry trial, enrolling 48 consecutive patients with high grade gliomas interested in using KMT, in addition to standard therapies and we incorporated a) dietary counseling from a cancer genomics trained dietician, b) monitoring of the level of therapeutic ketosis and tracked compliance, c) tumor surveillance with serial MRIs and clinical follow up were performed regularly on all patients in addition to dietary monitoring. Responses to treatment were categorized as Complete Response (CR) with resolution of prior disease and no evidence of disease for at least 2 successive MRI scans, Partial response (PR) with small volume persistent enhancement and/or edema, which diminished in volume on MRIs after diet compliance for at least 3 months but did not completely resolve, or No response (NR) if disease continued to progress despite dietary intervention.Tumor types included 28 GBMs (IDH wild type 17, mutant 10, 1 unknown), 11 Anaplastic Oligodendrogliomas, 7 Anaplastic Astrocytomas, and 2 Gliosarcomas. N=38 (79%) achieved ketosis. Of those 38 who achieved ketosis, complete or partial response was identified in 34 (89.5%) vs 8 in patients without ketosis evidence. N=19 out of 28 GBMs achieved complete or partial response. GBM median survival was 28.1 months [19.5 95.3] with 95% confidence intervals. Complete or Partial response was an independent factor of Overall Survival (p=0.004, log-rank test). KMT appears to significantly increase survival of HGG patients when maintained chronically.