Morphofunctional and Molecular Assessment of Nutritional Status in Head and Neck Cancer Patients Undergoing Systemic Treatment: Role of Inflammasome in Clinical Nutrition

Abstract

Malnutrition in patients with head and neck cancer is frequent, multifactorial and widely associated with clinical evolution and prognosis. Accurate nutritional assessments allow for early identification of patients at risk of malnutrition in order to start nutritional support and prevent sarcopenia. We aimed to perform a novel morphofunctional nutritional evaluation and explore changes in inflammasome-machinery components in 45 patients with head and neck cancer who are undergoing systemic treatment. To this aim, an epidemiological/clinical/anthropometric/biochemical evaluation was performed. Serum RCP, IL6 and molecular expression of inflammasome-components and inflammatory-associated factors (NOD-like-receptors, inflammasome-activation-components, cytokines and inflammation/apoptosis-related components, cell-cycle and DNA-damage regulators) were evaluated in peripheral-blood mononuclear-cells (PBMCs). Clinical-molecular correlations/associations were analyzed. Coherent and complementary information was obtained in the morphofunctional nutritional assessment of the patients when bioimpedance, anthropometric and ultrasound data were analyzed. These factors were also correlated with different biochemical and molecular parameters, revealing the complementary aspect of the whole evaluation. Serum reactive C protein (RCP) and IL6 were the most reliable parameters for determining patients with decreased standardized phase angle, which is associated with increased mortality in patients with solid malignancies. Several inflammasome-components were dysregulated in patients with malnutrition, decreased phase angle and dependency grade or increased circulating inflammation markers. A molecular fingerprint based on gene-expression of certain inflammasome factors (p27/CCL2/ASC) in PBMCs accurately differentiated patients with and without malnutrition. In conclusion, malnutrition induces a profound alteration in the gene-expression pattern of inflammasome-machinery components in PBMCs. A comprehensive nutritional assessment including novel morphofunctional techniques and molecular markers allows a broad characterization of the nutritional status in cancer patients. Profile of certain inflammasome-components should be further studied as potential targets for nutrition-focused treatment strategies in cancer patients.

Phase Angle, a Cornerstone of Outcome in Head and Neck Cancer

“…Our results shown in Table 2 coincide with those of the report by León-Idougurram and Do-Amaral-Paes, where we found alterations in the anthropometric and nutritional parameters and inflammatory markers in all three groups at the expense of subjects with low PA [ 30 , 32 ]. However, in 2020, some authors, such as Yasui-Yamada, considered the clinical nutritional significance of PA to be ambiguous [ 24 ].…”

“…Low PA values in chronic diseases and cancer are associated with an adverse prognosis, prolonged hospital stay, and worse survival than normal values [ 25 , 27 , 28 , 29 , 30 , 31 ]. We found that the same situation is present in the number of deceased subjects with low PA (70%), oral cavity involvement and low PA (69.8%), or the presence of low PA in terminally ill patients (CS lV 63.5%) and the proportion of sarcopenia/sarcopenic obesity among patients related to low PA (63%), coinciding with the findings of Do-Amaral-Paes [ 30 ] and Leon-Idougurram [ 32 ] in 2018 and 2022, respectively. Our current results reveal the relationship between PA, clinical, biochemistry, PRO (patient-reported outcomes), and survival/death risk in Mexican H&NC subjects with a high prevalence of overweight-obesity [ 33 , 34 ].…”

“…Accurate nutritional diagnosis could allow early detection of nutritional risks prior to worsening of HRQoL secondary to complications and death related to impaired nutritional status [ 29 , 31 , 32 , 33 ].…”

“…It is essential to highlight the role of tumor cachexia and inflammatory mediators such as C-reactive protein, with a significant increase in patients with PA < 4.42° and sarcopenia, and its relationship with a decreased hand grip strength and gait speed and its negative impact on functional markers in this group of patients. Other altered biochemical indicators reflecting malnutrition and its deleterious cellular effect are low hemoglobin, absolute lymphocyte, and albumin levels in blood patients with low PA, as recently described by the Leon-Idougurram group [ 32 ].…”

“…As previously described, malnutrition affects 50% of patients with H&NC [ 36 ] and more than 20% are classified as severe [ 32 , 37 ], leading to high rates of treatment complications and poor response, increasing the risk of delayed wound healing, infections, and deleterious effect on HRQoL [ 32 , 33 , 38 ]. In the specific EORTC QLQ-H&N35 module, the scales mainly affected are pain, swallowing, sense problem, trouble with social eating, teeth, opening mouth, dry mouth, sticky saliva, felt ill, pain killers, and nutritional supplements, all with higher scores for the low-PA group than the normal-PA group.…”