Evaluation of dietary habits and lifestyle in patients with bone sarcoma: Pilot study results of the Italian Metabol Sarc study (NCT04735289).

e23503 Background: Dietary behavior, lifestyle, and metabolic alterations such as obesity and insulin resistance are well established contributors to various cancers, with diet alone implicated in up to 40% of all cancers (Steck SE et al., 2020). In pediatric populations, maternal obesity and elevated birth weight, factors known to be influenced by dietary habits, are associated with increased risk of acute lymphoblastic leukemia and other malignancies (Stacy SL,2019). While the connections between diet, lifestyle, metabolic alterations (like obesity and insulin resistance), and cancer prognosis are well-recognized for many tumors, these relationships have not been thoroughly studied in bone sarcoma patients. We report here the results of a pilot cohort in Metabol Sarc protocol (NCT 04735289), a case-control study, conceived to investigate dietary, lifestyle, metabolomic, microbiota, and immune factors in patients with primary bone sarcoma. Methods: Participants aged ≥12 years with newly diagnosed primary bone sarcoma (osteosarcoma, Ewing sarcoma, spindle cell sarcoma, or dedifferentiated chondrosarcoma) were enrolled from multiple centers primarily the Rizzoli Institute, beginning March 2021. Controls were matched to cases by sex and age (±1 year for ages <21 years; ±2 years for ages ≥21 years). All participants completed the validated EPIC dietary questionnaire and lifestyle questionnaire (physical activity, education, electromagnetic exposure). Biological samples included fasting blood for routine laboratory tests and lymphocyte subpopulation phenotyping (CD3, CD4, CD8, NK cells). Results: The complete case pilot analysis included 73 patients (44 osteosarcoma, 29 Ewing sarcoma) and 139 matched controls (median age 23 years). After conditional logistic regression adjusted for weight, sex, and energy intake, linoleic acid intake was positively associated with bone sarcoma risk across all subtypes. Ewing sarcoma specifically showed stronger associations with animal-derived nutrients (animal fat, animal protein, total polyunsaturated fat). Conversely, body composition markers (Body Mass Index, lean mass, fat mass) showed no significant association with bone sarcoma risk. Immunological analysis revealed no distinctive serum markers for overall bone sarcoma; however, elevated CD4/CD8 ratio was positively associated with Ewing sarcoma. Controls had significantly higher educational attainment than cases. Conclusions: These preliminary findings support continued enrollment to achieve the planned sample size of 270 cases and matched controls. Currently, 133 patients and their matched controls have been enrolled. Results suggest potentially biologically plausible directional relationships that might be of interest, including associations related to dietary lipid composition.