Progress in head and neck cancer (HNC) therapies has improved tumor response, loco-regional control, and survival. However, treatment intensification also increases early and late toxicities. Dysphagia is an underestimated symptom in HNC patients. Impairment of swallowing process could cause malnutrition, dehydration, aspiration, and pneumonia. A comprehensive literature review finalized in May 2012 included searches of electronic databases (Medline, Embase, and CAB abstracts) and scientific societies meetings materials (American Society of Clinical Oncology, Associazione Italiana Radioterapia Oncologica, Associazione Italiana di Oncologia Cervico-Cefalica, American Head and Neck Society, and European Society for Medical Oncology). Hand-searches of HNC journals and reference lists were carried out. Approximately one-third of dysphagia patients developed pneumonia requiring treatment. Aspiration pneumonia associated mortality ranged from 20% to 65%. Unidentified dysphagia caused significant morbidity, increased mortality, and decreased the quality of life. In this review we underline definition, causes, predictive factors of dysphagia and report on pretreatment and on-treatment evaluation, suggesting some key points to avoid underestimation. A multi-parameter assessment of swallowing problems may allow an earlier diagnosis. An appropriate evaluation might lead to a better treatment of both symptoms and cancer.
Progress in head and neck cancer (HNC) treatments has improved tumour response and loco-regional control rates. However, despite improved diagnostic and therapeutic approaches, mortality remains high [
Intensification of treatment with chemoradiotherapy (CRT) or altered fractionation radiotherapy (RT) is associated with improved outcome, but causes severe early and late mucosal and pharyngeal toxicities. Oropharyngeal dysphagia is an underestimated symptom in HNC patients [
Frequent causes of dysphagia in this population include neurological and neuromuscular impairment, and structural and iatrogenic causes. Dysphagia should not be neglected, as it can profoundly diminish the quality of life (QoL) [
Acute dysphagia is often considered of less concern due to its transient nature. Nevertheless, it is a well recognized cause of malnutrition that leads to significant morbidity, higher mortality, and decreased QoL [
It is important that clinicians are aware of correlations between acute and late toxicities, and are capable of recognizing patients at risk for severe acute dysphagia, to reduce late dysphagia, prevent malnutrition, and provide aspiration, with the goal of providing the proper supportive care for these patients.
Adequate diagnosis and care during the treatment may increase compliance with the therapeutic protocol with a complete dose delivery of chemotherapy (CT) and RT. With this aim, we presently reviewed the relevant literature in terms: 1) definition, physiology and causes, 2) pretreatment evaluation of swallowing disorders and predictive factors, and 3) evaluation and support measures during treatment, and offer conclusions and recommendations.
A comprehensive literature review was finalized in May 2012. Electronic databases (Medline, Embase, and CAB abstracts) and scientific societies meeting materials (American Society of Clinical Oncology, Associazione Italiana Radioterapia Oncologica, Associazione Italiana di Oncologia Cervico-Cefalica, American Head and Neck Society, and European Society for Medical Oncology) were searched with the date parameters of January 1990 through May 2012. The decision concerning this range was made on the basis of the publication dates of the most important research clinical trials, investigating dysphagia in acute and late toxicities of HNC treatment.
Electronic search results were supplemented with hand searching of selected reviews, expert consensus meeting notes, and reference lists from selected articles. The literature search was limited to articles in English concerned with human patients. Medical subject headings (MeSH) terms and keywords used in the search were dysphagia, malnutrition, weight loss, head and neck cancer, chemoradiotherapy, acute toxicity, and late toxicity.
Dysphagia is defined as the difficulty or impossibility to swallow liquids, food, or medication. Dysphagia can occur during the oropharyngeal or oesophageal phase of swallowing. Normal swallowing is a complex and well-coordinated process, which requires neural control regulated by interactions between cortical centres in both hemispheres, the swallowing centre in the brainstem, cranial nerves (V, VII, IX sensory, IX motor, X, and XII), and pharyngeal receptors for touch, pressure, chemical stimuli, and water. Normal swallowing comprises four phases: oral preparation, oral, pharyngeal, and oesophageal [
During the oral preparatory phase of swallowing, the food is ground and mixed with saliva to form a bolus. In the oral phase, the bolus is transported to the pharynx. The swallowing reflex is triggered during the pharyngeal phase, resulting in closure of the larynx to prevent aspiration, contraction of the pharyngeal constrictors from superior to inferior, laryngeal elevation and epiglottis inversion, and relaxation of the crico-pharyngeus to allow the food bolus to pass into the oesophagus. During the final phase, the peristalsis of the oesophageal muscles results in movement of the bolus into the stomach. Deregulation in any of these functions can result in dysphagia. Additionally, swallowing and neck movement require that the pharyngeal structures and carotid sheath move easily relative to the spine and prevertebral space. The pharynx is essentially a muscular tube suspended from the skull base. The fat in the retropharyngeal and para-pharyngeal spaces allow for this necessary movement and pharyngeal expansion as well [
Causes of dysphagia include different alterations of the swallowing process that can interfere with physiological functions in each step of these described. Damage at anatomical structures or neurological damage may hinder normal physiology. Most common alterations include structural incontinence of the oral cavity; incorrect movement of the supraglottic larynx, epiglottis, and vestibule; reduced pharyngeal peristalsis; alterations of prevertebral space; and other muscular and neurological dysfunctions. All these types of damage contribute differently and to varying degrees to dysphagia after HNC treatment (
Swallowing disorders may cause aspiration that is usually prevented by an intact cough reflex. Aspiration causes can be divided to those occurring before, during, and after swallowing (
In HNC patients, structural impairment generally prevails even if both these problems can be contemporaneous, as a consequence of structural damage involving nerve or muscles or related to the consumption of certain medications. Anticholinergic drugs, steroids, asthma medications, vasoconstrictors, or expectorants can cause xerostomia. Antidepressants, anti-anxiety agents, antipsychotic, sedatives, and hypnotic agents can depress the central nervous system. Some antipsychotics may also cause extra-pyramidal effects with facial and mouth dyskinesias. Penicillamine or antibiotics like aminoglycosides and erythromycin may block the neuromuscular junction. Corticosteroids or lipid lowering agents can cause drug-induced myopathy [
Evaluation of swallowing disorders in naïve HNC patients is complex and requires a multi-team collaborative effort involving head and neck surgeons, speech pathologists, radiation oncologists, medical oncologists, radiologists, and nutritionists. All patients at risk should be screened by a multimetric model in which more than one parameter indicates dysphagia. Murphy's trigger symptoms, excessive chewing, drooling, and complaint of food sticking in the throat are suggestive of dysphagia (
Instrumental assessment of swallowing in HNC patients provides useful information about both the structure and function of this mechanism. Two procedures are usually performed: video-fluoroscopic modified barium swallow (VMBS) and fiberoptic endoscopic evaluation (FEES).
VMBS is a video-fluoroscopic examination that allows evaluation of oral and pharyngeal function by successive records of images, while FEES is a fiber-optic endoscopic examination (which avoids radiation exposure) that allows an excellent visualization of anatomy, including postsurgical or postradiation modifications or lesions. Both VMBS and FEES identify disorders that impair swallowing, cause aspiration, and increasing the risk for pneumonia. Additionally, they provide an evaluation of a patient's ability to maintain nutrition and hydration. Standardized protocols have been established for VMBS that test swallowing capacity using contrast containing food boluses of varying sizes and consistencies, thus allowing a Speech Language Pathologist to make dietary recommendations for patients with impaired swallowing. If abnormalities are identified, various compensatory measures including postural techniques, increased sensory input, and voluntary swallowing manoeuvres can be assessed for efficacy [
The penetration-aspiration scale has been developed to allow objective reports of penetration and aspiration events. The 8-point scale provides reliable quantification of selected penetration and aspiration events observed during video-fluoroscopic swallowing evaluations. Other systems can be used to specify the amount and timing of penetration and aspiration events. These scoring systems do not substitute for other perceptual measures of swallowing tested with VMBS and FEES. However, the use of these scales permits a numeric quantification of dysphagia, facilitating accurate communication among clinicians.
In clinical practice, FEES is more convenient and less expensive than VMBS, and can be performed repeatedly [
Instrumental examinations only assess the structures and dynamics of the swallowing process, and do not assess the influence of the swallowing problems on a patient's overall QoL (i.e., personal perception of well-being). HNC and its treatment can affect both disease-specific health-related QoL (HRQoL), such as salivary and swallowing functions, and the general domains of HRQoL, such as physical, mental, and social health [
Despite the plethora of available indices for cancer in general, few measurement tools are specific to HNC. Most of those HNC-specific tools measure QoL and few measure the common comorbidities of speech and swallowing. As a result, there is a gap of outcome measures specific to speech and swallowing that requires addressing [
Van der Molen [
Recently Christianen et al. [
T and N stage, primary site, type of treatment, extension of treated region (volume of tissue and anatomic structures), patient characteristics (baseline swallowing function, performance status [PS], smoking and alcohol abuse, age, lean mass, gender) predict the risk of acute and late dysphagia.
All treatment modalities, whether involving surgery or organ sparing protocols, and CRT result in swallowing problems along with aspiration. Therefore, we can classify factors predictive of dysphagia as patient-related, tumor-related, and treatment-related [
Whether a different primary tumor site is better related with frequency and severity of acute and late dysphagia is contentious. Aspiration is most frequent in hypopharynx or larynx cancer patients before treatment; the worst base-line function could account for higher rate of swallow impairment in this subset of patients [
Logemann [
In a similar study, Frowen et al. [
Patients with oropharyngeal tumors reportedly have significantly worse activity limitation for semisolids than patients with laryngeal tumours (
The type of treatment (organ anatomic preservation vs. surgery, demolitive vs. partial surgery, concurrent CRT vs. RT) and the extension of treated region (volume of tissue and anatomic structures) results in different severity of this sequelae [
Surgery in HNC patients may cause dysphagia by damage/resection of muscular, bony, cartilaginous, or nervous structures (swallowing anatomical structures and neurological structure) as well as by neck fascia removal. The severity of the swallowing deficit is dependent on the size and location of the lesion, and the degree and extent of surgical resection [
The importance of the anatomical region of excision has been highlighted by several reports. The size of the lesion excised is less prognostic than the excised area. Therefore, dysphagia can be accurately predicted for some surgeries, such as the base of the tongue and arytenoid cartilage resections [
Despite the fact that modern RT protocols are designed to spare normal tissue and preserve structure and function, dysphagia remains a potentially life-threatening occurrence in HNC patients treated with RT or CRT. Irradiation of swallowing structures and altered dose fractionation contributes to worsened dysphagia. Eisbruch et al. [
Bilateral neck RT has been identified as a prognostic factor for dysphagia and weight loss in early stage laryngeal cancer (T1/T2), although it is difficult to discern whether a larger tumor (high stage) or treatment protocols per se most affect dysphagia. Langius et al. [
Levendag et al. [
A correlation between food consistency and anatomical cause of dysphagia was reported by Christianen et al. [
Although CRT improves locoregional control and overall survival, and allows for organ preservation, it increases toxicities compared with RT alone [
Concomitant CT emerged as the strongest independent factor correlated with acute morbidity in several studies [
Data from randomized trials have added further evidence. In the RTOG 91-11 randomized trial, the incidence of severe (grade 3, 4) stomatitis and dysphagia increased with CT, respectively, from 24% and 19% (RT alone) to 43% and 35% (concomitant CRT), although skin effects were not altered (7% vs. 9%) [
Additionally, it is not known if the combination of epidermal growth factor receptor (EGFR) inhibitors and RT results in lower rates of swallowing disability. In 2006, Bonner et al. [
Dysphagia can directly result in decreased eating, malnutrition, and weight loss [
Weight loss is associated with a significantly lower survival rate and is an independent predictor for mortality in patients with stage III and IV tumors. Body weight loss also causes RT dose problems. The risk of delivering an inadequate radiation dose to the target volume and critical structures may arise if coordinated re-planning is not performed during the course of the therapy, especially when using highly conformal methods [
A secondary analysis of RTOG 90-03 reported that nutritional support before RT is associated with poorer treatment outcome [
Prevention and treatment of mucositis and swallowing-induced pain are areas of great interest, but a golden standard is still not available. In a majority of patients, pain (tumor- and treatment-related) can be severe and require major analgesics. Both pain and opioids can contribute to decreased dietary intake and the latter increases gastro-intestinal motility alterations [
A recent Cochrane review [
We suggest elective use of PEG to reduce swallowing difficulties, as secondary consequences of prolonged enteral status. Timely identification of the subgroup of patients with dysphagia or with a risk of developing severe dysphagia that will require a PEG before or during treatment is critical to maximize benefits [
Emerging data indicate that early intervention with swallowing exercises may improve dysphagia, whereas delayed swallowing therapy achieves only minor benefit [
Dysphagia is an increasingly recognized problem in the treatment of HNC. It affects QoL and survival. To ensure adequate therapies for RT and/or CRT candidates, a pretreatment evaluation of swallowing function and nutritional status is needed. A new standard of multidisciplinary approach in HNC should include routine diagnostic swallowing assessments and therapeutic interventions before, during, and after therapy. Data collected in the present systematic literature review indicate that surgery and RT or CRT can impair swallowing. Swallowing and neck movement require that pharyngeal structures, visceral fascia, and sheath move easily relative to the spine and prevertebral space. Surgical or RT fibrosis and anatomic concerns hinder this necessary movement and pharyngeal expansion as well. Dysphagia has been not adequately considered during HNC treatment plans. However, in the past several years there has been a growing interest around the major common sequelae of surgery and CRT. Understanding of the pathophysiology through the identification of DARS (muscles, glottic and supraglottic larynx, nerves) may allow radiation oncologists to reduce the dose delivered to the swallowing organs. At the same time, ear/nose/throat specialists should avoid aggressive surgery when it is not needed to improve survival outcomes. Dysphagia evaluation should help physicians to determine appropriate cancer therapy, increase patient compliance, and provide adequate posttreatment care. Immediate treatment of dysphagia will increase adherence to treatment protocol, while nutritional support will avoid critical weight loss. Additionally, awareness of dysphagia will also help pain management. For instance, starting intensive rehabilitation with pretreatment swallowing exercises improves posttreatment swallowing function. In Table 5, we summarize some helpful recommendations for early diagnosis and as a guide for the multidisciplinary team.
A multi-parameter assessment of dysphagia that considers the objective-instrumental examinations (e.g., residue research), patient-rated assessment (e.g., pain), and clinician-rated assessment (e.g., weight loss) of swallowing problems can allow for a better diagnosis, based on a better understanding of symptoms. This allows, on one hand, a proper prediction of late dysphagia and, on the other hand, accurate supporting care during the treatment. The diffusion of an adequate HRQoL questionnaire could further contribute to enhanced information from the patients' point of view.
Laurence Preston revised the English text of the manuscript.
No potential conflict of interests relevant to this article was reported.
Causes of damage: correlations with head and neck cancer treatment or neurologic damage
Adapted from Russi et al. [
Aspiration in relation of timing of swallowing: pathophysiology
Adapted from Russi et al. [
Triggers for dysphagia evaluation
Adapted from Murphy and Gilbert [
Treatment related dysphagia
RT, radiation therapy; CT, chemotherapy.
Dysphagia evaluation during head and neck cancer treatment
All, oral cavity, oropharynx, larynx, nasopharynx, hypopharynx; NR, not reported; PAS, penetration aspiration scale.
*Severe.