Following the completion of treatment with primary radiation or chemoradiation for head and neck squamous cell carcinoma, acute toxicities such as mucositis and odynophagia resolve, but persistent swallowing impairment is common(12
). Advanced age, T-stage and primary tumor site have been associated with late chronic dysphagia in patients undergoing primary radiation, and post-radiation neck dissection has also been identified as a potential risk factor for poor swallowing outcome(4
). In this study, we hypothesize that neck dissection independently exacerbates post-radiotherapy dysphagia, increasing the risk of feeding tube dependence. Measuring the effect of neck dissection on chronic dysphagia is inherently problematic as patients who undergo neck dissection potentially represent a different population than patients who do not. Matching using propensity score adjustment has been used to minimize selection bias when a randomized clinical trial is not ethical or feasible (14
). In this analysis, covariates thought to have an effect on the outcome were balanced between patients whose treatment included neck dissection and those spared a neck dissection, controlling for numerous potential confounders including advanced patient age, pre-treatment weight loss and numerous other potential factors. In adjusted analyses, the probability of feeding tube dependence increased significantly with a post-treatment neck dissection, and increased over time relative to the probability of feeding tube dependence without a neck dissection. In the present study, we present evidence supporting the notion that neck dissection contributes to chronic severe late toxicity after concurrent chemoradiation for head and neck cancer(4
). To our knowledge, this is the first study to use propensity score matching to investigate the effect of neck dissection on feeding tube dependence.
In order to exclude the possibility that long-term feeding tube dependence is a result of larger radiation treatment volumes used to treat patients with bulky nodal disease rather than neck dissection, the length of the high dose radiation field was measured in all patients. An increase in craniocaudal length of the radiation treatment field, used as a surrogate for radiation treatment volume, has been associated with an increased incidence of grade 4 swallowing toxicity in patients treated with radiation(11
). Larger treatment fields might also be expected to contribute to chronic swallowing toxicity. In the current study, both the radiation fields used and radiation dose were essentially identical between groups, regardless of neck dissection status. Radiation field size was related to primary tumor site and T-stage and affected little by nodal tumor bulk. Information regarding smoking history and history of depression, which could have an impact on our results, was not available and thus not included. Smoking may promote the development of fibrosis and exacerbate post-radiotherapy dysphagia. Depression has been linked to worse functional outcomes following chemoradiation due to diminished patient capacity to follow through on swallowing rehabilitation(15
Although the use of radiation has been linked to the development of severe upper cervical esophageal/ hypopharyngeal strictures(16
), most patients who develop chronic dysphagia after radiation have no evidence of narrowing on imaging studies. Upper cervical esophageal and hypopharyngeal stenosis, estimated to occur in 12-21% of patients receiving aggressive chemoradiation regimens(18
), are believed to be a sequelae of radiation, and may however secondarily exacerbate oropharyngeal dysphagia. Oropharyngeal dysphagia, characterized by inhibited tongue base retraction, laryngeal elevation and pharyngeal constriction necessary to propel the bolus through the upper aerodigestive tract(17
) may persist despite dilatation of a stricture, contributing to long-term feeding tube dependence. In our analysis, neck dissection was found to contribute to feeding tube dependence, regardless of whether patients with radiographically-confirmed strictures were included or not. We observed a slightly higher rate of stricture in patients with neck dissection. By exacerbating swallowing dysfunction, neck dissection may delay swallowing rehabilitation in a patient with a radiation-induced stricture, enabling a radiation-induced injury in the hypopharynx and upper cervical esophagus to become fixed. Nevertheless, we observed that approximately one half of patients with strictures were ultimately able to have their feeding tubes removed.
The mechanism by which a post-treatment neck dissection contributes to chronic dysphagia is uncertain. Radiation is believed to damage soft tissue by means of oxidative stress secondary to hypoxia, perpetuating tissue damage and increasing fibrosis long after radiation is completed(24
). Patients treated with intense organ preservation protocols may be vulnerable to increasingly severe chronic dysphagia, as a result of cumulative side effects of treatment with multiple modalities. Radiation disrupts the coordinated activity of multiple adjacent structures and complex sensory feedback necessary for normal swallowing. Neck dissection may exacerbate post-treatment fibrosis of the neck and edema of the upper aerodigestive tract while also causing structural and sensory changes. In the present series, all patients undergoing neck dissection underwent a comprehensive dissection of levels I-V. A less extensive dissection of the neck, via a selective neck dissection of “at risk” levels, may potentially have less of an impact on swallowing by causing less tethering of the larynx and pharynx. Advances in radiation delivery may also diminish tissue fibrosis that predisposes to poor swallowing outcome, diminishing the effect of post-radiotherapy neck dissection. Results using IMRT in which uninvolved constrictor musculature is spared high dose radiation has been found to yield improved swallowing outcomes relative to traditional radiotherapy techniques(25
). Neck dissection likely contributes to long-term toxicity burden in patients undergoing multimodality treatment for head and neck cancer, but remains potentially therapeutic in appropriate patients. The indications for neck dissection following chemoradiation for head and neck cancer continue to evolve.