The “fat heat-up” phenotype: adipose tissue hypermetabolism on 18 F-FDG PET/CT predicts frailty in older patients with solid tumours

Frailty in oncology is a major determinant of treatment toxicity and survival, and is often framed primarily as a muscle problem. Adipose tissue, however, is an active endocrine and metabolic organ, and its glycolytic activity on positron emission tomography/computed tomography with fluorodeoxyglucose (18 F-FDG PET/CT) may capture physiological vulnerability that is not reflected by body composition alone. We investigated the association between adipose glycolytic activity and frailty in older adults with solid tumours. We prospectively enrolled 104 adults (≥ 50 years) with solid malignancies (median age 63.5 years) who underwent clinical whole-body 18 F-FDG PET/CT and a comprehensive geriatric assessment on the same day. At the L3 level, adipose area and metabolic activity (SUVmean and rSUVmax; SUVp95-derived and reference-normalized hereafter referred as SUVmax for simplicity) were quantified using a deep learning segmentation pipeline (TotalSegmentator) with strict exclusion of visceral structures to isolate adipose signal. Frailty was assessed using the Clinical Frailty Scale (CFS) and the FRAIL Scale. Total adipose area did not differ between frail and non-frail phenotypes (425.64 vs. 424.38 cm², p = 0.45). In contrast, adipose glycolytic activity was significantly higher in frail patients (SUVmean 0.30 vs. 0.20, p < 0.001). In multivariable logistic regression adjusted for age and sex, each 0.1-unit increase in adipose SUVmean was associated with 1.78-fold higher odds of frailty (95% CI 1.10–2.88, p = 0.002). Associations were directionally consistent across both frailty instruments. Adipose hypermetabolism on 18 F-FDG PET/CT, despite low absolute SUV values, appears to track frailty independently of adipose quantity, supporting a “fat heat-up” phenotype as a marker of diminished physiological reserve. Routine oncologic PET/CT may therefore provide an opportunistic, imaging-derived frailty signal that can precede overt morphological deterioration in body composition. Frailty is a high-impact and frequently under-recognised driver of treatment intolerance and adverse outcomes in oncology, yet comprehensive geriatric assessment remains resource-intensive and inconsistently implemented. In this prospective cohort, adipose tissue was quantified using a fully automated Total Segmentator-based pipeline, providing an objective and reproducible measure of adipose FDG uptake at the L3 level. This single quantitative feature, already embedded in routine 18F-FDG PET/CT, aligned with frailty across two independent frailty scales and multiple geriatric assessment domains, independent of age and sex. If externally validated, adipose FDG uptake could function as an opportunistic imaging-derived frailty flag to trigger earlier geriatric input, support treatment individualisation, and enable physiologic risk stratification in trials and real-world practice.