Multidimensional physiological impairments are associated with frailty and survival in older patients with cancer

Frailty, which is influenced by the intricate interactions between malnutrition, metabolism, and systemic inflammation, is highly prevalent in the elderly and constitutes a significant barrier to the effective treatment of older patients with cancer. Assessing specific biomarker patterns may enhance our understanding of the mechanisms underlying the intricate networks that contribute to frailty in this population. This study aimed to examine the association between frailty and malnutrition, metabolism, and systemic inflammation in older patients with cancer, and to further assess their prognostic value.

This multicenter cohort study included 2219 older patients with cancer categorized as non-frail (n = 533), pre-frail (n = 1084), or frail (n = 602) according to the Fried frailty criteria at a single time point. Principal component analysis (PCA) was performed on 18 variables encompassing nutritional, metabolic, and inflammatory biomarkers to derive the principal components (PCs). Cox proportional hazards and logistic regression models were used to assess the associations between PCs, frailty, and overall survival (OS).

Three PCs were identified among 18 variables. PC1 represented a malnutrition-associated pattern. PC2 represented a metabolism-associated pattern. PC4 represented an inflammation-associated pattern. PC3 was excluded because of its redundancy with PC1. Frail patients exhibited significantly higher factor scores compared to pre-frail and robust patients in PC1 (median [IQR]: 1.03 [1.82] vs. -0.12 [1.65] vs. -0.93 [1.52]; P < 0.001), PC2 (0.20 [1.90] vs. -0.03 [1.29] vs. -0.17 [1.03]; P < 0.001), and PC4 (0.07 [1.27] vs. -0.04 [0.97] vs. -0.06 [0.75]; P = 0.049). Furthermore, patients with higher factor scores in PC1, PC2, or PC4 were significantly associated with frailty [adjusted OR: 2.13, 95% CI: 1.90-2.39, P < 0.001 for PC1; adjusted OR: 1.13, 95% CI: 1.03-1.23, P = 0.008 for PC2; adjusted OR: 1.12, 95% CI: 1.03-1.22, P = 0.011 for PC4]. Frail patients exhibited significantly worse survival outcomes compared to pre-frail individuals (adjusted HR = 1.67, 95% CI: 1.45-1.92; P < 0.001).

Frailty is significantly associated with decreased survival in older patients with cancer and coexists with multidimensional physiological impairments, including nutritional deficits, metabolic disturbances, and systemic inflammation.