A prospective radiobiological study of acute esophagitis and swallowing dysfunction in head-and-neck radiotherapy

Introduction: Esophagitis is one of the main causes of swallowing dysfunction after radiation therapy (RT) for head and neck cancer (HNC).It significantly affects patients’ quality of life as well as having a potentially negative impact on their long term survival. However, little has been investigated on the dose-response and normal tissue complication probability (NTCP) of esophagitis in the cervical esophagus (CE), although it is often at risk in neck irradiation. The aim of this study was to investigate the incidence and dose-response relation for acute esophagitis in HNC patients undergoing 3D conformal RT.   Materials and Methods: This prospective study consisted of 50 HNC patients. The main studied endpoint was grade 2 or higher acute esophagitis according to the Common Terminology Criteria for Adverse Events v.4 scoring criteria within 9 weeks after the start of RT, assessed using the EORTC QLQ-H&N-35; questionnaire. The mean dose and dose-volume parameters were analyzed for CE and eight other swallowing-related structures including: superior, middle and inferior pharyngeal constrictor muscles (SPCM, MPCM and IPCM, respectively), esophagus inlet muscle (EIM), supraglottic larynx (SGL), base of tongue (BT), glottic larynx and cricopharyngeal muscle. Then, due to the lack of model parameters for acute esophagitis in the CE, the ability of four sets of LKB model parameters available for predicting the NTCP of this endpoint for middle and lower esophagus was evaluated based on the mean CE dose in these patients.   Results:  Forty three patients (86%) experienced grade ≥ 2 acute esophagitis in the follow-up period (no grades 4 or 5). The V30 of the SPCM, V30-V40 of the MPCM, V50 of the EIM, V40-V55 of the CE, V60 of the BT, and V20-V40 of the SGL, and the mean doses of these six structures, correlated with swallowing dysfunction. The mean dose to the CE was the most significant parameter. The LKB model parameters TD50= 47 Gy, m= 0.36, n= 0.069 showed the current best fit to the observed NTCP.   Conclusion: The mean dose and V40-V55 to the CE were significantly associated with swallowing dysfunction. The high number of patients who experienced swallowing complications in this study adds evidence to the necessity of advanced treatment planning and delivery techniques that offer dose optimization to reduce esophagitis in HNC RT. Better LKB model parameters for predicting swallowing dysfunction due to CE dose are also required.