Efficacy of ketogenic metabolic therapy as an adjuvant to the current standard of care in the treatment of glioblastoma: A systematic review of clinical trials

Glioblastoma is a diffuse, heterogenous tumour with a poor prognosis as current therapeutic options have limited efficacy. As a result, research aims to explore new treatment options which exploit the hallmarks of cancer. This review aimed to understand the breadth of research considering ketogenic metabolic therapy (KMT) as an adjuvant to standard therapy. KMT aims to improve overall survival by exploiting the metabolic reprogramming exclusive to neoplastic cells. Preclinical trials show benefits in KMT when used alongside radiotherapy, through increasing anti-tumour effects compared to controls. Literature searches conducted over three databases, in line with PRISMA guidelines, collated studies relevant to KMT and glioblastoma. Six prospective studies and one retrospective study met the inclusion criteria for this review. Data regarding participants, interventions and survival were extracted. Studies included used small numbers of participants, as many aimed to assess the feasibility of larger-scale trials, which increases errors and bias of results. Furthermore, direct comparison between trials was limited due to study heterogeneity, as each trial used differing parameters and diet compositions. As a result, no definitive conclusions could be made. Future studies should use larger cohorts with standardised parameters so results are representative, and comparisons can be made to evaluate efficacy.