Ketogenic diets in medical oncology: a systematic review with focus on clinical outcomes
Authors: Rainer J Klement
Reinhart A Sweeney
Nanina Brehm
Journal: Medical Oncology (2020)
Discipline: CLINICAL MEDICINE
Keywords: Cancer; Evidence; High-grade glioma; Ketone bodies; Metabolic therapy
Affiliations: Department of Radiotherapy and Radiation Oncology, Leopoldina Hospital Schweinfurt, Robert-Koch-Straße 10, 97422, Schweinfurt, Germany. ., Department of Radiotherapy and Radiation Oncology, Leopoldina Hospital Schweinfurt, Robert-Koch-Straße 10, 97422, Schweinfurt, Germany.

Abstract:  Preclinical data provide evidence for synergism between ketogenic diets (KDs) and other oncological therapies. The aim of this systematic review was to summarize data from clinical studies that have tested KDs along with other treatments used within medical oncology. The PubMed database was searched using the key words "ketogenic" AND ("cancer" OR "glioblastoma"). A secondary search was conducted by screening the reference lists of relevant articles on this topic. Relevant studies for this review were defined as studies in which KDs were used complementary to surgery, radio-, chemo-, or targeted therapy and at least one of the following four outcomes were reported: (i) Overall survival (OS); (ii) progression-free survival (PFS); (iii) local control rate; (iv) body composition changes. Twelve papers reporting on 13 clinical studies were identified. Nine studies were prospective and six had a control group, but only two were randomized. KD prescription varied widely between studies and was described only rudimentarily in most papers. Adverse events attributed to the diet were rare and only minor (grade 1-2) except for one possibly diet-related grade 4 event. Studies reporting body composition changes found beneficial effects of KDs in both overweight and frail patient populations. Beneficial effects of KDs on OS and/or PFS were found in four studies including one randomized controlled trial. Studies in high-grade glioma patients were not sufficiently powered to prove efficacy. Evidence for beneficial effects of KDs during cancer therapy is accumulating, but more high-quality studies are needed to assess the overall strength of evidence. 

Retracted: No

PubPeer comments:
 **Serious concerns.** Quite honestly, Figures 2 and 3 make **zero** sense. Follow-up in the study by Khodabakhshi et al (citation 42) was 3 months, not 30. Their own graph also reads 30 months which also seems to be incorrect and has been mentioned on PubPeer as well. Specifically, in this current study by Klement and colleagues, they say that follow-up was 3 months, then right after, say follow-up was 30 months. At first, I d consider it an error by Khodabakhshi et al in that they might have added extra zeros when creating the graph; however, given that the authors of this review (Klement and colleagues) include numbers such as 12, 18, and 24, it is easier to come to the conclusion that this was not a simple typo. This also couldn t be a graph that has been accidentally extended out too long, since patient survival is zero in both groups at 30 months. But in a recently published [study] by Khodabakhshi et al, comparisons are made at 3 months and all 30 patients are accounted for at 3 months. Thus this is not a graphical error. 3 months is also the indicated treatment time on the preregistered protocol. [https: www.irct.ir trial 30755] It is also unclear why and how follow-up is 60 months in the metastatic patients when once again, the ketogenic diet was administered for 3 months. **Given that the ketogenic diet was only administered for 3 months, it is entirely unclear, and unjustified, how comparisons and claims can be made longer than that, especially not up to 30 months.** **If the follow-up time is truly 3 months, there was no difference in survival between the two groups.** ,