Swallowing disorders after treatment for head and neck cancer

In 2015, head and neck cancer (HNC) represented 3.5% of all cancer cases in Slovenia. It was the 7^th most common type of cancer in the population and with the share of 5.2% the 5^th most common cancer in males. Among 459 new HNC cases in Slovenia in 2015, there were 144 oral cavity primaries, 122 oropharyngeal, 70 hypopharyngeal, and 90 laryngeal primary tumors. Locally advanced disease stages (UICC TNM stages III or IVA-B) were diagnosed in 32%, 92%, 90% and 53% of patients with oral cavity, oropharyngeal, hypopharyngeal, and laryngeal primaries, respectively.1

Due to its invasive growth with destruction of neighboring anatomical structures, HNC has an adverse effect on important functions, including swallowing, breathing, coughing and speech. Thus, it can profoundly influence quality of life of the patient. Treatment of the tumor may significantly deteriorate these functions. Treatment modalities, including surgery, irradiation and systemic therapy, either alone or combined, can result in tissue defects, excessive scarring, and changed anatomical setting and function of the involved organs.2, 3, 4, 5, 6 The treatment options in late sequelae of different therapies are limited and of variable benefit.7

Dysphagia is an important cause of malnutrition, dehydration, weight loss, chronic aspiration and aspiration pneumonia. All these complications can lead to not only serious health issues and even death, but may also result in depression and social isolation.8, 9, 10, 11, 12, 13, 14, 15 In addition, late dysphagia, even of a mild grade, is one of the most important factors adversely influencing quality of life of HNC patients, with feeding-tube dependency having the most negative impact.9

In the present cross-sectional study, we investigated the most common dysphagia-related factors and problems in a group of survivors who were treated for HNC in the last decade at two tertiary centers. The primary aim was to identify factors that participate to the development of dysphagia in studied cohort of HNC patients.

The management of locally advanced HNC still represents a challenge to the clinicians despite recent improvements in diagnostics and treatment. Excessive scarring secondary to aggressive surgery, intensive irradiation and systemic therapy may result in different degree of swallowing disorders.17, 18 Malnutrition, the need for enteral tube feeding, social isolation and the feeling of hopelessness may significantly impair quality of patient’s life.19, 20 The results of our study confirmed these observations. Almost 40% of patients from the present study had problems with feeding out of their homes and almost half of the patients avoided going to public areas and thus had social life impaired. Majority of patients from the DG reported problems with feeding (77.8%), feeding in public (80%), and even feeding in the presence of the family (62.2%). In the OTH patients, these problems were recorded significantly less often. Discomfort when eating in presence of other people was probably one of the important reasons that 75.6% of the patients who reported difficulties with swallowing also reported avoiding public places, which makes dysphagia an important reason for their social isolation.

The prevalence of dysphagia in our study was 41.3%, which is less than in some other series.3, 4, 6, 7 We assume that differences in studied populations of patients in regard to distribution of primary tumor sites and treatment modalities used as well as methods for dysphagia assessment are the reasons for this discrepancy.

As expected, among our patients a higher prevalence of dysphagia was significantly related to primaries originated in the swallowing-related areas of the head and neck and to more advanced disease stages, which is in line with other reports.7 In addition, radiation therapy also appeared to be a significant causative factor for dysphagia in univariate analysis. Among 45 patients with dysphagia, almost all (93.3%) were treated with radiation therapy, either as the sole therapy or in combination with surgery and/or chemotherapy. One of the reasons for more aggressive treatment scenario could be more advanced tumor stage that necessitates addition of radiotherapy to surgery or intensification of radiotherapy with concurrent chemotherapy. However, using multiple regression analysis with disease stage taking into account, radiotherapy did not remain in the final model. This result supports the observation of other authors who found no differences in the severity of dysphagia or aspiration according to type of treatment.7, 15

Pathophysiological mechanisms implicated in development of swallowing disorders after HNC treatment differ according to modality used. In case of surgery, tissue defect resulted from tumor removal adversely effects organ’s function because its integrity is truncated. When organs crucial for swallowing are the site of primary tumor (e.g. tongue, velopharyngeal orifice, larynx, pharyngeal wall, and upper esophageal sphincter), dysphagia appears. With destruction of primary tumor, radiation therapy induces scarring at the site of its origin and fibrotic changes elsewhere in tissues inside irradiation field, which reduces their elasticity and flexibility. Thus, the dose-volume relationship in case of pharyngeal constrictor muscles appears to be the most important predictor of later swallowing disorders.21

Sensory impairment of the upper aerodigestive tract mucosa as a result of tissue loss or post-radiotherapy changes seems also to be an important causative mechanism of swallowing disorders and especially aspiration. Thus, both, surgical treatment and radiation therapy, can adversely influence laryngeal innervation and alter its functions, including its role in swallowing. In the present study, 62.2% of the patients with dysphagia reported hoarseness, and 84.4% of them reported persistent cough. In multiple regression modelling only persistent cough remained significant factor related to dysphagia. The cough can be a consequence of hyposensibility of the larynx after surgery or irradiation, leading to persistent micro aspiration in the trachea. When the secretions or food come in contact with intact tracheal mucosa with preserved sensibility, they induce protective coughing which successfully clears the airway.12, 15 This cough can be the reason that in our series only 8.2% of the patients experienced pneumonia. The flexible endoscopic evaluation of swallowing could prove this hypothesis; however, no such examination was foreseen in the study protocol.

There are other symptoms which can cause dysphagia that appeared more often in the DG than in the OTH, i.e. oral pain (31.1% vs. 6.3%), throat pain (40% vs. 18.8%), oral mucosa irritability (62.2% vs. 35.9%), thick saliva (84.4% vs. 54.7%), impaired sense of taste (75.6% vs. 28.1%), change of smelling abilities (33.3% vs. 10.9%). The highest prevalence was reported for problems related to production of saliva and to impaired tasting abilities, which can be interconnected.5 However, in our analysis, none of these parameters demonstrated to be significantly related to dysphagia in multiple regression testing.

Dysphagia was repeatedly reported to be a chronic problem in HNC patients cured of their cancer. Nguyen et al. showed by means of repeated modified barium swallow that up to two years post-surgery dysphagia disappeared in 8% and decreased in its severity in 32% of the patients; in all others patients it worsened or remained unchanged.15 This observation confirms our finding that dysphagia was more often reported in patients with a less than 2 years of follow-up after treatment.

Other late sequel in patients treated for HNC is changed quality of mucus in the upper aerodigestive tract. Among our DG patients, thick and sticky mucus was reported in 84.4% of cases. We hypothesize that alterations in mucus quality are responsible for improper dissolution of taste molecules, which resulted in impaired sense of taste. The other cause of (partial) taste loss are postirradiation changes of the taste buds in oral cavity and oropharynx or loss of receptors because of surgical excision.22 However, a well-known interconnection between the sense of taste and the sense of smell could participate to decreased smelling ability which was reported in one third of our patients with dysphagia.23

An interesting finding of the present study is a connection between dysphagia and the symptoms of gastroesophageal reflux. Reflux of gastric acid and pepsin is well-recognized etiologic factor in dysphagia even in subjects without cancer, simply by causing inflammation of the laryngeal and hypopharyngeal mucosa.24, 25 Such inflammation can additionally aggravate pre-existing radiomucositis in irradiated patients, leading to scarring and impaired sensitivity of involved mucosa. Reflux to the level above the upper esophageal sphincter was found to impair the sensibility of the throat and hypopharynx in otherwise healthy subjects.26

The only significant variable in multiple regression analysis was persistent cough. The gastroesophageal reflux to the level of laryngopharynx can also be the reason for persistent cough, induced by altered mucosal sensitivity and mobility impairment of the cilia of respiratory epithelium of the larynx.27 Consequently, mucus accumulated at the laryngeal inlet causes throat clearing and persistent cough. The causative role of microaspiration and impaired mucosal sensitivity in persistent cough has already been mentioned.

The third association between the gastroesophageal reflux and persistent cough is managed through the neural reflexes. The vagus nerve-mediated reflex arc originates at distal esophagus and can initiate a reflex coughing when the receptors in the esophageal wall are stimulated by the reflux.28, 29 Therefore, in order to decrease the incidence of coughing in the patients after HNC treatment, pre-treatment identification and proper management of patients with gastroesophageal reflux symptoms is mandatory.

We acknowledge the limitations of our study. This is a questionnaire-based review of a small number of patients who might be too subjective in their answers. There is also a heterogeneity of population regarding the cancer location, stage of the disease, and treatment modalities used. The exact data from the medical documentation regarding anatomical details of cancer extension, treatment intensity and its complications and assessment of dysphagia with objective methods would add significantly to the quality of study.

In conclusion, in order to enable safe swallowing and to reduce the risk of aspiration in HNC patients, a systematic assessment and rehabilitation of swallowing should be organized before and after treatment. According to presented results, special emphasis should be put on gastroesophageal reflux screening and treatment before, during and after the therapy. Only with implementation of these interventions in the routine management algorithms used in HNC patients, a quality of life improvement can be expected.