Analysis of nutritional risk, skeletal muscle depletion, and lipid metabolism phenotype in acute radiation enteritis

Abstract

Background: Radiation enteritis, which often occurs during radiation-induced acute intestinal symptoms (RIAIS), is the most common and important complication during radiotherapy for cervical cancer. RIAIS caused by abdominal and pelvic radiotherapy will affect nutrient intake, digestion, absorption, and metabolism, leading to malnutrition or poorer nutritional status. In patients with malignant tumors, malnutrition can adversely affect the curative effect and response of radiotherapy by reducing radiosensitivity, affecting the precision of radiotherapy placement and increasing the incidence of radiotherapy-related adverse reactions.

Aim: To analyze nutritional risk, skeletal muscle depletion, and lipid metabolism phenotype in acute radiation enteritis.

Methods: Fifty patients with cervical cancer received external beam radiotherapy, and 15 patients received brachytherapy after external beam radiotherapy. Body weight, body composition parameters, nutritional risk screening (NRS) 2002 score, and blood biochemical indices of patients with cervical cancer during periradiation were tested by a one-way repeated measures analysis of variance. Metabolomics analysis was used to identify characteristic lipid metabolism pathways. Clinical factors that affect linoleic acid changes were screened using the generalized evaluation equation.

Results: Among the 50 patients, 37 had RIAIS, including 34 patients with grade 1-2 RIAIS and 3 patients with grade 3 RIAIS. The NRS 2002 score of patients who underwent cervical cancer radiotherapy continued to increase during the periradiation period, and 42 patients who underwent cancer radiotherapy had nutritional deficits (NRS 2002 score ≥ 3 points) at the end of radiotherapy. Correlation analyses revealed that body weight and body mass index changes were closely associated with body fat content (R² = 0.64/0.51). The results of the univariate analysis showed that radiotherapy time, percentage reduction of serum albumin, and percentage reduction of serum prealbumin were the key factors affecting skeletal muscle exhaustion (P < 0.05). Metabolomic analysis of fecal supernatants of cervical cancer patients during the periradiation period revealed the involvement of linoleic acid, cholic acid, arachidonic acid, and N-acetyl-L-benzene alanine in the metabolic pathway of linoleic acid.

Conclusion: Cervical cancer radiotherapy patients faced nutritional risks, decreased serum albumin synthesis, and increased risk of skeletal muscle exhaustion. Linoleic acid was a biomarker of high nutritional risk.

Keywords: Cervical cancer; Linoleic acid; Metabolomics; Nutritional risk; Radiation-induced acute intestinal symptoms.

Figure 1

Metabolomics analysis of fecal supernatants of patients with cervical cancer during the periradiation period. A-D: Interaction pathways of differential metabolites in stool supernatant samples of patients undergoing radiotherapy for cervical cancer; A: Kyoto Encyclopedia of Genes and Genomes network level (yellow is the differential metabolite); B: Differential metabolite level; C: Co-differential metabolite level with time characteristics; D: Representative differential metabolic pathway levels; E: 26 co-differential metabolites selected in stool samples; F: Pathway impact factor diagram of stool supernatant samples; G: N-formyl-L-methionine; H: Cholic acid; I: Linoleic acid (LC); J: Arachidonic acid (AA) (metabolic changes in enoic acids, from left to right). 1: LC metabolic pathway; 2: AA metabolic pathway; 3: Phenylalanine metabolic pathway).

Figure 2

Incidence of radiation-induced acute intestinal symptoms in patients with cervical cancer and changes in the nutritional risk screening 2002 score, blood biochemical indicators, and body composition during the periradiation period. A: Diarrhea, abdominal pain, colitis, anal swelling, hematochezia, and bone marrow suppression in patients with cervical cancer; B-I: Changes in clinical observation indices during periradiation therapy, nutritional risk screening (NRS) 2002 score (B), body weight (C), body mass index (BMI) (D), serum albumin (E), serum prealbumin (F), body fat content (G), skeletal muscle content (H), and phase angle change (I) during periradiation therapy in patients with cervical cancer; J: Correlation analysis of body weight, BMI, skeletal muscle content, body fat content, phase angle, serum albumin, serum prealbumin, NRS 2002 score, and linoleic acid (LC) content in stool supernatant (red indicates positive correlation, blue indicates a negative correlation, and the value in the box is the correlation system R²). RIAIS: Radiation-induced acute intestinal symptoms.