Irradiation dose to the swallowing apparatus impacts nutritional status in head and neck cancer patients—results from the prospective randomized HEADNUT trial

Abstract

Purpose: To investigate the influence of radiation dose to the swallowing muscles on the nutritional status in patients with head and neck cancer undergoing primary or adjuvant (chemo)radiotherapy (C)RT. Methods: Between 2018 and 2020, 61 patients were prospectively randomized into the so-called HEADNUT trial (head and neck cancer patients undergoing nutritional intervention). Follow-up was continued until 2022. Contouring of the swallowing apparatus included the superior (scm), middle (mcm), and inferior constrictor muscle (icm), the cricopharyngeal muscle (cphm), and the esophageal inlet. Nutritional status was assessed by bioelectrical impedance analysis (BIA) at the beginning and the end of radiotherapy. The posttherapeutic nutritional status was evaluated by the BIA-derived fat-free mass index (FFMI; kg/m2). Malnutrition was assumed at FFMI values of < 15 (women) and < 17 (men) kg/m2. To find differences between dosimetric parameters in well- and malnourished patients, Mann–Whitney U test was used. To model the association between malnutrition and its potentially influencing variables, several logistic regression models were built. Results: The following parameters differed between well- and malnourished patients at the end of therapy: icm Dmean, V40Gy (%), V50Gy (%), and V60Gy (%), and sphm V40Gy (%). After entering these parameters into a multivariable logistic regression model (dosimetric model), icm Dmean (b = −0.12; Exp(b) = 0.88; 95% CI: 0.78–1.0; p = 0.06) and icm V40Gy (%; b = 0.06; Exp(b) = 1.07; 95% CI: 1–1.13; p = 0.04) proved to be independent dosimetric predictors of malnutrition. We only determined the cut-off value for predicting malnutrition for icm V40Gy (%) since it was the only parameter which met p < 0.05. The optimal cut-off value for the predictor V40Gy (%) based on the Youden Index was 85.6%. Another logistic regression model (dosimetric-clinical model) consisted of icm V40 (%) and the clinical parameters tumor localization, malnutrition before RT, gender, and combined chemotherapy. It was confirmed that both icm V40% (b = −1.9; Exp(b) = −2.7; 95% CI: 0.01–0.8; p = 0.03) and malnutrition at baseline (b = −1.9; Exp(b) = 4.4; 95% CI: 8.4–816.6; p = 0.0002) were independent predictors of subsequent malnutrition the end of RT. Conclusion: Establishment of a normal nutritional status before the start of RT and adherence to dose constraints for the swallowing apparatus may prevent malnutrition in head and neck cancer patients at the end of therapy. Specifically, we suggest an icm V40Gy (%) of more than 86% to be predictive for nutritional complications.