Ketogenic diet treatment in diffuse intrinsic pontine glioma in children: Retrospective analysis of feasibility, safety, and survival data

Abstract

Background: Diffuse intrinsic pontine glioma (DIPG) is one of the most devastating diseases among children with cancer, thus novel strategies are urgently needed.Aims: We retrospectively evaluated DIPG patients exposed to the carbohydrate restricted ketogenic diet (KD) with regard of feasibility, safety, and overall survival (OS).Methods and results: Searches of MEDLINE and Embase identified five hits meeting the search criteria (diagnosis of DIPG and exposure to KD). One additional case was identified by contact with experts. Individual patient data were extracted from publications or obtained from investigators. The inclusion criteria for analysis of the data were defined as DIPG patients who were exposed to the KD for ≥3 months. Feasibility, as described in the literature, was the number of patients able to follow the KD for 3 months out of all DIPG patients identified. OS was estimated by the Kaplan-Meier method.Five DIPG patients (males, n = 3; median age 4.4 years; range, 2.5-15 years) meeting the inclusion criteria were identified. Analysis of the available data suggested that the KD is generally relatively well tolerated. Only mild gastro-intestinal complaints, one borderline hypoglycemia (2.4 mmol/L) and one hyperketosis (max 7.2 mmol/L) were observed. Five out of six DIPG patients identified adhered for ≥3 months (median KD duration, 6.5 months; range, 0.25-2 years) to the diet. The median OS was 18.7 months. Conclusion:Our study provides evidence that it may be feasible for pediatric DIPG patients to adhere for at least 3 months to KD. In particular cases, diet modifications were done. The clinical outcome and OS appear not to be impacted in a negative way. KD might be proposed as adjuvant therapy when large prospective studies have shown feasibility and safety. Future studies might ideally assess the impact of KD on clinical outcome, quality of life, and efficacy.

Effects of the Ketogenic Diet in the Treatment of Gliomas: A Systematic Review

“…Weight loss was reported in studies by Rieger et al [ 8 ], Champ et al [ 16 ], Klein et al [ 29 ], and Panhans et al [ 28 ]. Vomiting was reported in the two studies by van der Louw et al [ 10 , 15 ], in the study by Panhans et al [ 28 ], and in that of Perez et al [ 27 ]. Nausea was reported in the studies by van der Louw et al, 2019b [ 15 ], Klein et al [ 29 ], and Panhans et al [ 28 ].…”

“…However, these were not the only interventions applied. Drugs such as temozolomide, gemcitabine, prednisolone, bevacizumab, and lomustine were applied individually in four different studies (33.3%): temozolomide in the studies by van der Louw et al, 2019b [ 15 ] and Perez et al [ 27 ]; bevacizumab and lomustine in the study by Rieger et al [ 8 ]; lomustine in the study by Martin-McGill et al, 2018 [ 17 ]; and gemcitabine and prednisolone in the study by van der Louw 2019a [ 10 ]. In one study, patients received chemotherapy and concomitant radiotherapy as therapeutic interventions since the initial treatment with radiotherapy had no effect [ 28 ].…”

“…Perez et al grouped patients undergoing various types of KD, including KD with MCT, CKD, and MAD. However, this study did not specify the proportions or amounts of macronutrients applied [ 27 ].…”

“…The estimated overall survival was 18.7 months. There were also two patients who achieved survival times of 22 and 30 months [ 27 ].…”

The efficacy of an unrestricted cycling ketogenic diet in preclinical models of IDH wild-type and IDH mutant glioma

“…efficacy against some cancers, clinical studies have been limited in glioma patients, and have so far mostly focused on feasibility, not outcomes [15,[21][22][23][24][25][26]. At the preclinical level, some studies showed that mice engrafted with IDH1 wt GBM did not benefit from KD [13,27], although others have suggested otherwise [28], and to the best of our knowledge, there has not yet been a direct experimental comparison of IDH1 wt and IDH1 mut gliomas exposed to KD.…”