Safety and Feasibility of Fasting-Mimicking Diet and Effects on Nutritional Status and Circulating Metabolic and Inflammatory Factors in Cancer Patients Undergoing Active Treatment.

In preclinical studies, fasting was found to potentiate the effects of several anticancer treatments, and early clinical studies indicated that patients may benefit from regimes of modified fasting. However, concerns remain over possible negative impact on the patients' nutritional status. We assessed the feasibility and safety of a 5-day "Fasting-Mimicking Diet" (FMD) as well as its effects on body composition and circulating growth factors, adipokines and cyto/chemokines in cancer patients. In this single-arm, phase I/II clinical trial, patients with solid or hematologic malignancy, low nutritional risk and undergoing active medical treatment received periodic FMD cycles. The body weight, handgrip strength and body composition were monitored throughout the study. Growth factors, adipokines and cyto/chemokines were assessed by ELISA. Ninety patients were enrolled, and FMD was administered every three weeks/once a month with an average of 6.3 FMD cycles/patient. FMD was largely safe with only mild side effects. The patients' weight and handgrip remained stable, the phase angle and fat-free mass increased, while the fat mass decreased. FMD reduced the serum c-peptide, IGF1, IGFBP3 and leptin levels, while increasing IGFBP1, and these modifications persisted for weeks beyond the FMD period. Thus, periodic FMD cycles are feasible and can be safely combined with standard antineoplastic treatments in cancer patients at low nutritional risk. The FMD resulted in reduced fat mass, insulin production and circulating IGF1 and leptin. This trial was registered on Clinicaltrials.gov in July 2018 with the identifier NCT03595540.

Fasting-mimicking diet and hormone therapy induce breast cancer regression.

Approximately 75% of all breast cancers express the oestrogen and/or progesterone receptors. Endocrine therapy is usually effective in these hormone-receptor-positive tumours, but primary and acquired resistance limits its long-term benefit1,2. Here we show that in mouse models of hormone-receptor-positive breast cancer, periodic fasting or a fasting-mimicking diet3-5 enhances the activity of the endocrine therapeutics tamoxifen and fulvestrant by lowering circulating IGF1, insulin and leptin and by inhibiting AKT-mTOR signalling via upregulation of EGR1 and PTEN. When fulvestrant is combined with palbociclib (a cyclin-dependent kinase 4/6 inhibitor), adding periodic cycles of a fasting-mimicking diet promotes long-lasting tumour regression and reverts acquired resistance to drug treatment. Moreover, both fasting and a fasting-mimicking diet prevent tamoxifen-induced endometrial hyperplasia. In patients with hormone-receptor-positive breast cancer receiving oestrogen therapy, cycles of a fasting-mimicking diet cause metabolic changes analogous to those observed in mice, including reduced levels of insulin, leptin and IGF1, with the last two remaining low for extended periods. In mice, these long-lasting effects are associated with long-term anti-cancer activity. These results support further clinical studies of a fasting-mimicking diet as an adjuvant to oestrogen therapy in hormone-receptor-positive breast cancer.

Clinical indications for image-guided interventional procedures in the musculoskeletal system: a Delphi-based consensus paper from the European Society of Musculoskeletal Radiology (ESSR)-Part II, elbow and wrist.

BACKGROUND: Although image-guided interventional procedures of the elbow and wrist are routinely performed, there is poor evidence in the literature concerning such treatments. Our aim was to perform a Delphi-based consensus on published evidence on image-guided interventional procedures around the elbow and wrist and provide clinical indications on this topic. METHODS: A board of 45 experts in image-guided interventional musculoskeletal procedures from the European Society of Musculoskeletal Radiology were involved in this Delphi-based consensus study. All panelists reviewed and scored published papers on image-guided interventional procedures around the elbow and wrist updated to September 2018 according to the Oxford Centre for Evidence-based Medicine levels of evidence. Consensus on statements drafted by the panelists about clinical indications was considered as "strong" when more than 95% of panelists agreed and as "broad" if more than 80% agreed. RESULTS: Eighteen statements were drafted, 12 about tendon procedures and 6 about intra-articular procedures. Only statement #15 reached the highest level of evidence (ultrasound-guided steroid wrist injections result in greater pain reduction and greater likelihood of attaining clinically important improvement). Seventeen statements received strong consensus (94%), while one received broad consensus (6%). CONCLUSIONS: There is still poor evidence in published papers on image-guided interventional procedures around the elbow and wrist. A strong consensus has been achieved in 17/18 (94%) statements provided by the panel on clinical indications. Large prospective randomized trials are needed to better define the role of these procedures in clinical practice. KEY POINTS: • The panel provided 18 evidence-based statements on clinical indications of image-guided interventional procedures around the elbow and wrist. • Only statement #15 reached the highest level of evidence: ultrasound-guided steroid wrist injections result in greater pain reduction and greater likelihood of attaining clinically important improvement. • Seventeen statements received strong consensus (94%), while broad consensus was obtained by 1 statement (6%).