Objective assessment of swallowing dysfunction and aspiration after radiation concurrent with chemotherapy for head-and-neck cancer

Abstract

$\text{Purpose:}$To objectively assess swallowing function after an intensive chemoradiation regimen for locally advanced head-and-neck cancer and to assess the clinical implications of swallowing dysfunction.

$\text{Patients and Methods:}$Twenty-nine patients with nonresectable Stage IV head-and-neck cancer participated in a Phase I study of radiation, 70 Gy/7 weeks, concurrent with weekly gemcitabine. Because of a high rate of mucosal toxicity, reduced drug doses were delivered to subsequent patient groups: 300, 150, 50, and 10 mg/m²/week. Twenty-six of these patients underwent prospective evaluation of swallowing function with videofluoroscopy and esophagogram. Studies were performed pretherapy, early post-therapy (1–3 months), and late post-therapy (6–12 months).

$\text{Results:}$Complete tests were performed pretherapy in 22 patients, early post-therapy in 20, and late post-therapy in 13. Twenty-five patients had at least one post-therapy study. Post-therapy dysfunction was characterized by reduced inversion of the epiglottis, delayed swallow initiation and uncoordinated timing of the propulsion of the bolus, opening of the cricopharyngeal muscle, and closure of the larynx, all of which promoted aspiration during and after the swallow. In addition, reduced base-of-tongue retraction with reduced contact to the posterior pharyngeal wall and incomplete cricopharyngeal relaxation resulted in pooling in the pyriform sinuses and vallecula of residue, which was frequently aspirated after the swallow. Post-therapy aspirations were typically “silent,” eliciting no cough reflex, or the cough was delayed and noneffective in expelling the residue. Aspiration was observed in 3 patients (14%) in the pretherapy studies, in 13 (65%) in the early post-therapy studies, and in 8 (62%) in the late post-therapy studies (aspiration rates post-therapy vs. pretherapy: p = 0.0002). Six patients had pneumonia requiring hospitalization 1–14 months after therapy (median: 2.5 months), being the likely cause of death in 2 patients. Five cases of pneumonia occurred among 17 patients who had demonstrated aspiration in the post-therapy studies, compared with no cases of pneumonia among 8 patients who had not demonstrated aspiration (p = 0.1). Of the 4 patients who had not undergone any post-therapy study, 1 developed pneumonia. Mucositis scores, prolonged tube feeding, presence of tracheostomy tube, and gemcitabine doses were not found to be related to aspiration or pneumonia risk.

$\text{Conclusions:}$After intensive chemoradiotherapy, significant objective swallowing dysfunction is prevalent. It promotes aspiration, which may not elicit a cough reflex and may be associated with pneumonia. Aspiration pneumonia may be an underdocumented complication of chemoradiotherapy for head-and-neck cancer. Future studies should examine whether routine post-therapy videofluoroscopy and training aspirating patients in safe swallowing strategies can reduce this risk.

Introduction

Improved locoregional control of advanced head-and-neck cancer has been reported using altered fractionated radiation (RT) or concurrent radiation and chemotherapy 1, 2, 3, 4. In most cases, altered fractionation or the addition of concurrent chemotherapy resulted in increased severity and duration of acute mucositis. The rates of late pharyngeal fibrosis and long-term dysphagia were reported to be similar to the rates expected after standard radiation in some of these studies 1, 2, 3, but they were more severe than expected in others 5, 6, 7, 8, 9, 10, 11. Some of the late toxicity is thought to represent a consequential effect of severe acute depletion of mucosal and submucosal stem cells (12). Thus, acute mucositis and consequential late fibrosis and dysphagia are major factors limiting the intensity of therapeutic regimens for head-and-neck cancer 13, 14.

We have recently reported the results of a Phase I study of radiation concurrent with low-dose gemcitabine for locally advanced head-and-neck cancer (15). Gemcitabine is a potent radiosensitizer at subcytotoxic doses, and its administration concurrent with radiation resulted in a high rate of complete tumor response. However, reduction of drug doses was required in subsequent patient cohorts because of dose-limiting mucosal toxicity.

Observations in the initial patients in this study of significant mucosal toxicity prompted a prospective assessment of the anatomic and physiologic characteristics of therapy-related dysphagia. Detailed swallowing studies, including videofluoroscopic assessment of swallowing and esophagogram, were performed before, and periodically after, therapy in all subsequent patients accrued to the trial. The results of the swallowing studies and their clinical implications are presented in this paper.