Gut Microbiota, Metabolome, and Body Composition Signatures of Response to Therapy in Patients with Advanced Melanoma.

Despite the recent breakthroughs in targeted and immunotherapy for melanoma, the overall survival rate remains low. In recent years, considerable attention has been paid to the gut microbiota and other modifiable patient factors (e.g., diet and body composition), though their role in influencing therapeutic responses has yet to be defined. Here, we characterized a cohort of 31 patients with unresectable IIIC-IV-stage cutaneous melanoma prior to initiation of targeted or first-line immunotherapy via the following methods: (i) fecal microbiome and metabolome via 16S rRNA amplicon sequencing and gas chromatography/mass spectrometry, respectively, and (ii) anthropometry, body composition, nutritional status, physical activity, biochemical parameters, and immunoprofiling. According to our data, patients subsequently classified as responders were obese (i.e., with high body mass index and high levels of total, visceral, subcutaneous, and intramuscular adipose tissue), non-sarcopenic, and enriched in certain fecal taxa (e.g., Phascolarctobacterium) and metabolites (e.g., anethole), which were potentially endowed with immunostimulatory and oncoprotective activities. On the other hand, non-response was associated with increased proportions of Streptococcus, Actinomyces, Veillonella, Dorea, Fusobacterium, higher neutrophil levels (and a higher neutrophil-to-lymphocyte ratio), and higher fecal levels of butyric acid and its esters, which also correlated with decreased survival. This exploratory study provides an integrated list of potential early prognostic biomarkers that could improve the clinical management of patients with advanced melanoma, in particular by guiding the design of adjuvant therapeutic strategies to improve treatment response and support long-term health improvement.

Preterm birth and metabolic implications on later life: A narrative review focused on body composition.

Preterm newborn infants are characterized by low body weight and lower fat mass at birth compared with full-term newborn neonates. Conversely, at term corrected age, body fat mass is more represented in preterm newborn infants, causing a predisposition to developing metabolic syndrome and cardiovascular diseases in later life with a different risk profile in men as compared with women. Postnatal growth is a complex change in anthropometric parameters and body composition. Both quantity and quality of growth are regulated by several factors such as fetal programming, early nutrition, and gut microbiota. Weight gain alone is not an optimal indicator of nutritional status as it does not accurately describe weight quality. The analysis of body composition represents a potentially useful tool to predict later metabolic and cardiovascular risk as it detects the quality of growth by differentiating between fat and lean mass. Longitudinal follow-up of preterm newborn infants could take advantage of body composition analysis in order to identify high-risk patients who apply early preventive strategies. This narrative review aimed to examine the state-of-the-art body composition among born preterm children, with a focus on those in the pre-school age group.

Exploiting FAsting-mimicking Diet and MEtformin to Improve the Efficacy of Platinum-pemetrexed Chemotherapy in Advanced LKB1-inactivated Lung Adenocarcinoma: The FAME Trial.

Advanced lung adenocarcinoma with inactive liver kinase B1 (LKB1) tumor suppressor protein is associated with poor response to immune checkpoint inhibitors and molecularly targeted agents, and with dismal patient prognosis. LKB1 is a central orchestrator of cancer cell metabolism, and halts tumor growth/proliferation during metabolic stress. Recent preclinical evidence suggests that LKB1-inactive lung adenocarcinoma is highly sensitive to metformin, a safe and low-cost antidiabetic compound that inhibits mitochondrial oxidative phosphorylation. The effects of metformin can be enhanced by nutrient deprivation (ie, glucose, amino acids), which reduces intracellular levels of ATP and anabolic precursors and can be achieved by the fasting mimicking diet (FMD). Noticeably, metformin also prevents resistance to cisplatin in preclinical in vitro and in vivo models of LKB1-inactive lung adenocarcinoma. Based on such preclinical evidence, the phase II FAME trial was designed to test the hypothesis that the addition of metformin, with or without cyclic FMD, to standard platinum-based chemotherapy improves the progression-free survival of patients with advanced, LKB-1 inactive lung adenocarcinoma. Enrolled patients will be randomized in a 1:1 ratio to receive cisplatin/carboplatin and pemetrexed with the addition of metformin alone (Arm A) or metformin plus FMD (Arm B). The FAME study will use a "pick-the-winner" design with the aim of establishing which of the 2 experimental treatments is superior in terms of antitumor efficacy and safety. The primary assumption of the study is that the combination of the 2 experimental treatments shall improve median progression-free survival from 7.6 months (historical data with chemotherapy alone) to 12 months. Secondary study endpoints are: objective response rate, overall survival, treatment tolerability, and compliance to the experimental treatment.

Changes in food habits in cancer patients in Italy: a survey. AIOM - SINPE - FAVO.

OBJECTIVES: The aim of this study was to investigate the prevalence of cancer patients changing their diet in relation to cancer site, sex, age and geographic distribution. Furthermore, we aimed to explore the rationale behind dietary changes and to identify sources of information in order to plan specific educational training. METHODS: Patients ≥18 y of age who accessed the Italian Cancer Patients, Families and Friends Association information points were invited to participate. An ad hoc self-report questionnaire was used. The questionnaire asked patients about changes made to the major food groups. A minimum sample of 100 patients for the most common cancers was planned. We analyzed 1257 questionnaires. We assessed the prevalence of, reasons for, and type of dietary changes. Logistic regression was used to analyze the main determinants of dietary changes. RESULTS: Of the 1257 patients, 705 (56.1%) reported changes since receiving the diagnosis of cancer. On the logistic regression analysis, age and tumor site were significantly associated with dietary changes (P <0.001), mainly in patients <50 y of age and in those with upper gastrointestinal cancers. Slightly more than half (50.8%) of patients adopted a healthier diet, with 31.3% doing so to deal with eating-related side effects and 17.9% due to cancer sites. Regardless of the reasons for changing, the most common food items to result in a decrease in consumption were alcohol, red and processed meats, and sugary drinks. Only 15% of patients reported receiving specific nutrition indication. CONCLUSION: Italian patients are attentive to the importance of diet during cancer treatment. Personal choices reflect some indications for cancer prevention as there is still a shortage of guidelines for a correct diet during treatment. Nutrition indications are rarely given within the oncologic center.