Wordenskjold Stougaard Sarah, Zukauskaite Ruta, Röttger Richard, Laugaard Lorenzen Ebbe, Lukas Konrad Maximilian, Long Krogh Simon, Panduro Nielsen Camilla, Frieda Aviaya Sommer Jeanette, Johansen Jørgen, Grau Eriksen Jesper, Kjaer Lonkvist Camilla, Friborg Jeppe, Brink Carsten, Rønn Hansen Christian
Laboratory of Radiation Physics, Odense University Hospital, Odense, Denmark; Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
Department of Oncology, Odense University Hospital, Odense, Denmark.
Acta Oncol. 2025 Sep 18;64:1253-1261. doi: 10.2340/1651-226X.2025.44021.
This multicentre, retrospective study aimed to develop a predictive model for radiation-induced dysphagia in head and neck cancer patients, focusing on the role of gross tumour volume (GTV) to high dose CTV (CTV1) margin size and dose-related factors. Unlike previous studies focused on peak or single time-point dysphagia, this study modelled symptom trajectories using repeated follow-up data for a more complete picture. Patient/material and methods: Between 2010 and 2015, 1,948 patients with pharyngeal or laryngeal squamous cell carcinoma received definitive intensity-modulated radiotherapy (IMRT) at three Danish centres. Data included physician-rated dysphagia (grade 0-4), tumour and treatment characteristics, and AI-based segmentations of organs at risk (OARs). Predictors included GTV-CTV1 margin size, mean doses to the oral cavity and pharyngeal constrictor muscles (PCM), GTV volume, chemotherapy, tumour site, fractionation, nimorazole, sex, smoking status, baseline dysphagia, and age. A logistic ordinal mixed-effects model was fitted with patient ID as random effect. Data were split into training (70%) and test (30%) sets. Model performance was assessed using calibration plots and area under the curve (AUC).
After excluding incomplete cases, 1,685 patients (7,829 visits) were analysed. GTV-CTV1 margin size was not significantly associated with dysphagia, although larger margins correlated with higher OAR doses. Higher doses to the lower PCM (odds ratio [OR] = 1.30 per 5 Gy) and oral cavity (OR = 1.32 per 5 Gy) increased risk. The model demonstrated good calibration and robust discrimination (AUC = 0.77-0.84).
Radiation dose to the oral cavity and lower PCM were the strongest modifiable predictors of dysphagia risk. Margin size was not independently associated, possibly due to confounding by clinical judgement.
这项多中心回顾性研究旨在建立头颈部癌患者放射性吞咽困难的预测模型，重点关注大体肿瘤体积（GTV）至高剂量临床靶区（CTV1）的边缘大小及剂量相关因素。与以往专注于吞咽困难峰值或单一时间点的研究不同，本研究使用重复随访数据对症状轨迹进行建模，以获得更完整的情况。患者/材料与方法：2010年至2015年期间，1948例咽或喉鳞状细胞癌患者在丹麦三个中心接受了根治性调强放疗（IMRT）。数据包括医生评定的吞咽困难（0 - 4级）、肿瘤及治疗特征，以及基于人工智能的危及器官（OAR）分割。预测因素包括GTV - CTV1边缘大小、口腔和咽缩肌（PCM）的平均剂量、GTV体积、化疗、肿瘤部位、分割方式、尼莫唑、性别、吸烟状况、基线吞咽困难和年龄。采用以患者ID为随机效应的逻辑顺序混合效应模型。数据被分为训练集（70%）和测试集（30%）。使用校准图和曲线下面积（AUC）评估模型性能。
排除不完整病例后，分析了1685例患者（7829次就诊）。GTV - CTV1边缘大小与吞咽困难无显著相关性，尽管较大的边缘与较高的OAR剂量相关。较低PCM（每5 Gy优势比[OR] = 1.30）和口腔（每5 Gy OR = 1.32）的较高剂量会增加风险。该模型显示出良好的校准和稳健的区分能力（AUC = 0.77 - 0.84）。
口腔和较低PCM的放射剂量是吞咽困难风险最强的可改变预测因素。边缘大小无独立相关性，可能是由于临床判断的混杂因素所致。
