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.

Background/Objectives: Over 60% of diagnoses of head and neck squamous cell carcinoma (HNSCC) occur in patients aged over 65. The benefits of radiotherapy (RT) combined with chemotherapy remain controversial in geriatric patients. Frailty stratification is underutilized in clinical practice despite evidence suggesting its predictive power. We aimed to assess the impact of pre-treatment frailty stratification on overall survival (OS) and acute radiation-related toxicity in a cohort of older patients with HNSCC. Methods: A prospective cohort of 117 patients aged ≥65 years with newly diagnosed HNSCC was enrolled between 2017 and 2022. Patients received RT with or without chemotherapy. Frailty was assessed using the 40-item Frailty Index (FI) as part of a comprehensive geriatric assessment. The primary outcomes were OS and acute RT toxicity, defined as a grade ≥ 3 based on CTCAE 5.0. Cox proportional hazard models and logistic regression models, adjusted for age, tumor stage, and chemotherapy, were used. Results: After a median follow-up of 819 days, FI (HR 1.478, 95% CI 1.182–1.848, p < 0.001) was an independent predictor of OS. Grade ≥ 3 toxicities were observed in 38% of patients, but frailty was not significantly associated with toxicity. A sub-analysis of oropharyngeal carcinoma patients demonstrated improved OS in HPV-positive patients (HR 0.231, 95% CI 0.078–0.686, p = 0.008). Conclusions: the standardized introduction of frailty assessment in the evaluation of older HNSCC patients holds great promise for predicting long-term survival. This approach could be crucial in tailoring treatment protocols that account for the biological heterogeneity of older adults.

Background/Objectives: The Rapid Geriatric Assessment (RGA) is a tool designed to screen for frailty, sarcopenia, anorexia related to aging, and cognitive impairment. This study aimed to translate and validate the RGA for use among Italian community-dwelling older adults. Methods: This cross-cultural study involved 100 community-dwelling older adults randomly recruited through convenience sampling from general practitioner offices in Genoa (Italy), between January and June 2019. The RGA includes the Simple FRAIL Questionnaire Screening Tool, SARC-F Screening for Sarcopenia, Simplified Nutritional Assessment Questionnaire (SNAQ), and Rapid Cognitive Screening (RCS). These were validated against gold-standard tools: the Abbreviated Comprehensive Geriatric Assessment (aCGA) and Multidimensional Prognostic Index (MPI). Additional assessments included the Timed Up and Go (TUG) and Handgrip test. The validation process included forward–backward translation, synthesis, and consensus by independent reviewers. Psychometric properties, internal consistency (Cronbach alpha), and validity correlations were analyzed. Results: The RGA demonstrated satisfactory psychometric properties, with internal consistency (Cronbach alpha = 0.59) and significant validity correlations (RGA and aCGA, rho = 0.34, p = 0.001; RGA and MPI, rho = 0.49, p < 0.001). Discriminant validity was confirmed by significant correlations between specific subitems and reference measures: FRAIL with TUG (p < 0.05), SARC-F with Handgrip strength (p = 0.013), SNAQ with BMI, and RCS with MMSE (p < 0.001). Conclusions: The Italian version of the RGA is a reliable screening tool for geriatric syndromes in community-dwelling older adults. While it does not replace a CGA, the RGA may identify individuals who may benefit from further evaluation using a complete CGA.