Metabolic and Clinical–Nutritional Correlation Patterns in Relation to 3-Year Disease-Free Survival in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Preliminary Analysis

This retrospective study characterizes the complex associations between serum 1H-NMR metabolomics, clinical nutritional status, and laboratory blood parameters in men with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) in relation to 3-year disease-free survival (DFS). A total of 536 serum samples from 67 patients, collected weekly during radiotherapy or chemoradiotherapy, were analyzed to characterize the metabolic-nutritional landscape. The patients with 3-year DFS exhibited stronger biological links between elevated levels of serum lipids, phosphocholine, branched-chain amino acids (BCAAs), and clinical markers such as BMI, albumin, and prealbumin compared to those with disease recurrence. Furthermore, our findings highlight a novel pattern of disrupted correlations (metabolic decoupling) between body fat distribution, overall obesity, and lipid metabolism, as well as the links between BCAAs and nutritional status, in patients with disease recurrence. This observed breakdown of internal coordination suggests that the survival advantage associated with body fat arises not just from adiposity, but from the body’s ability to metabolically coordinate fat and amino acid turnover with overall energy demands—a trait known as metabolic flexibility. In conclusion, we hypothesize that disease recurrence in men with LA-HNSCC is driven by failure of this system, manifested as a breakdown in the coordination between metabolic and nutritional profiles. The preserved metabolic-nutritional axis between fat turnover and nutrient availability is associated with 3-year disease-free survival in this patient group, although more research is required to fully elucidate the underlying mechanisms.