- © 2006 by American Society of Clinical Oncology
Prevention and Treatment of Dysphagia and Aspiration After Chemoradiation for Head and Neck Cancer
- From the Department of Head and Neck Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, TX, and the Department of Radiation Oncology, the University of Michigan, Ann Arbor, MI
- Address reprint requests to David I. Rosenthal, MD, The University of Texas M. D. Anderson Cancer Center, Department of Radiation Oncology, 1515 Holcombe Blvd, Unit 97, Houston, TX 77030; e-mail: dirosenthal{at}mdanderson.org
Abstract
Safe, successful swallowing depends on complex events affected by head and neck cancers and their treatment. This article reviews the swallowing process, how it is affected by chemoradiotherapy, and the evaluation, prevention, and treatment of swallowing disorders. Specific recommendations are made to promote maintenance and recovery of swallowing function.
INTRODUCTION
Eating together is a defining social activity among family, friends, and colleagues. For many, the ability to enjoy eating helps to define quality of life (QOL).1 Although the effects of head and neck cancer (HNC) and radiation therapy (RT) on swallowing may vary, all patients will be affected to some degree, and up to one half may have significant dysphagia.2 Labored swallowing, prolonged eating times, and the limited range of foods that can be swallowed lead to disruption of relationships and social isolation.3
Recent gains in local control and survival for HNC have come largely from altered fractionation (AFX) RT and concurrent chemoradiotherapy (CRT).4-6 The commonplace use of these high-intensity treatments has resulted in higher rates of swallowing dysfunction prompting some to conclude that mucositis and dysphagia are a “barrier to winning the battle with HNC.”7
SWALLOWING EVENTS, RADIATION EFFECTS, AND THEIR EVALUATION
There are four stages of swallowing that involve a series of coordinated events involving more than 30 pairs of muscles and six cranial nerves (Fig 1). 8 Speech-language pathologists (SLPs) define the oropharyngeal swallow to include all events from the lips to the upper esophageal sphincter (UES), also known as the cricopharyngeal inlet (CPI). This definition reflects that only these stages can be addressed by functional therapies. The esophagus is a relatively less complex muscular tube, for which the main therapeutic maneuver is dilation. Patients can learn to bypass the voluntary oral preparatory and oral stages of swallowing, but the completion of swallowing is an involuntary reflex that must be triggered.9-11
The trigger sets subsequent events into motion. The soft palate elevates to seal the nasopharynx to prevent regurgitation (velopharyngeal insufficiency [VPI]). The tongue pushes backward to meet the forward-bulging posterior pharyngeal wall to create the main driving pressure (Fig 2). The airway is protected by the adduction of the vocal folds and cephalad laryngeal excursion, leading to epiglottic closure. The cricopharyngeus muscle (CPM) relaxes, but the larynx must also move anteriorly to open the CPI (UES), and allow the bolus to enter the esophagus to prevent retention as a “residual” (Fig 3).
One study showed 40% of HNC patients had some, and 4% had moderate to severe dysphagia at presentation. Larynx and hypopharynx tumors caused worse function than those in the oral cavity and oropharynx.12 More generally, however, anything that restricts driving pressure or limits UES opening leads to swallowing residuals that may spill into the airway (Fig 4). Aspiration is, thus, a consequence of dysphagia. The trigger and cough reflexes are essential to prevent aspiration. Although silent aspiration is probably widely under-recognized and under-reported, its magnitude as a clinically significant problem is not known. The only way to accurately capture this would be to test for it, or else estimate it by capturing the incidence of pneumonias. Incomplete reporting is a recognized shortcoming in cooperative trial data.13-18
There are two main instrumental studies of swallowing. The videofluoroscopic (VF) evaluation of swallowing is the modified barium swallow (MBS). The MBS is performed by an SLP and a radiologist, and is recognized as the gold-standard evaluation because it shows the entire oropharyngeal swallow. Information is provided regarding all events, allowing for the diagnosis of specific swallowing disorders and causes of aspiration. The swallowing of radio-opaque thin and thick liquids and pastes, and solids are assessed.19-20 Interventions appropriate to the disorder to allow safe oral alimentation can then be used, and their immediate effectiveness is verified by another observed swallow.9
The fiberoptic endoscopic evaluation of swallowing (FEES) is a videoendoscopic tool21 used in the clinic by a single clinician. The FEES is sensitive to detect residuals, laryngeal penetration, and aspiration, and avoids radiation exposure.22 It does not show the oral phase, pharyngeal stripping, transit through the UES, or the extent of aspiration.21
MBS and/or FEES are indicated for all HNC patients with or at risk for dysphagia or aspiration. Patients who can clear the penetration/aspiration may be allowed to continue oral alimentation with therapeutic precautions, but must be followed serially for decompensation. Feeding tubes (FTs) and tracheotomies will not prevent aspiration, but they may reduce it and improve tracheopulmonary toilet.23
There are two commonly used questionnaires for subjective swallowing assessment. The Performance Status Scale for Head and Neck Cancer Patients (PSS-H&N) is a rapid, clinician rated instrument consisting of three subscales: normalcy of diet, public eating, and understandability of speech.3 The M.D. Anderson Dysphagia Inventory (MDADI) is a more detailed patient-completed measure of function and QOL.24
DETERMINATES OF DYSPHAGIA
The goals of organ-preservation strategies are cancer control with preservation of function. Swallowing ability after treatment represents a combination of pretreatment tumor-related dysfunction, treatment-related dysfunction, and the patient's ability to compensate spontaneously or with therapy. Patients who cannot swallow adequately before treatment are at higher risk for chronic dysphagia after treatment, and at risk for permanent feeding-tube dependence. This underscores the observation that conservation of structure and function do not necessarily go hand in hand.25,26
A recent CRT study included longitudinal swallowing function questionnaires and MBS. Many patients report normal swallowing at diagnosis, despite abnormal MBS. Swallowing declined for some after CRT, suggesting that patients may compensate for tumor-related dysfunction before CRT, but may lose this ability afterwards.27
Patients' perceptions of their swallowing disabilities may be inconsistent with their actual swallowing ability. Radiation-induced xerostomia may diminish patient perception of swallowing abilities regardless of normal VF swallowing physiology.28 Likewise, subjective reports of dysphagia do not always correlate with VF findings, particularly during the pharyngeal phase.29 These findings strongly underscore the importance of instrumental testing before, during, and after RT/CRT to document function.17
FTS AND DYSPHAGIA
Weight loss and associated micronutrient deficiencies before and during RT have been shown to be prognostic factors for HNC outcomes.30-34
Dys-/odynophagia secondary to acute radiation-induced mucositis can be addressed by nasogastric (NG-FT) or gastrostomy (G-) FTs. Prophylactic FTs have been shown to reduce weight loss, unplanned hospitalizations, and treatment interruptions, but there have also been reports that nutritional support may decrease local control and survival.35,36 Tube feedings are also subject to dysfunction, so require experienced dietician support for optimal function.37-39
There is controversy about the relative benefits of (1) prophylactic versus therapeutic G-FT placement, and (2) nasogastric (NG-) versus G-FTs.40 NG-FTs are less cosmetic, more uncomfortable, and have the risk for nasal soft-tissue injury, sinusitis, and aspiration.41-43 G-FT risks include abdominal infection, and, with endoscopic placement, a small but finite risk for tumor seeding.44-46
A retrospective review of NG-FT and G-FT use found that patients with NG-FTs may have less long-term dysphagia, FT duration, and need for pharyngo-esophageal dilation.47 The authors postulated that the NG-FTs might perform a stenting function serving to limit synechia formation and maintain luminal patency, and motivate patients to swallow sooner. These findings have not been confirmed in a prospective trial, and another retrospective review showed that FTs made no difference.48 Nonetheless, nothing-by-mouth (NPO) intervals as short as 2 weeks have been shown to predict poor swallowing outcomes.49
RADIOSENSITIZERS, MUCOSITIS, AND DYSPHAGIA
Rates of many toxicities are underappreciated because there is interobserver variation, trials do not report on all relevant end points, different toxicity scales are used, and there may be less-rigorous toxicity data collection during therapeutic CRT as compared with during symptom-control trials.18 Dysphagia was reported in only 12% and feeding-tube rates in only 3% trials included in a systematic literature review on mucositis and its consequences.34 For example, the therapeutic trial Radiation Therapy Oncology Group (RTOG) 90-03 reported a 25% rate of grade 3 mucositis with standard RT as compared with 65% with standard RT in a mucositis intervention trial.4,50
Acute mucositis is the dose-limiting toxicity of CRT, and is associated with long-term dysphagia (Tables 1 and 2).34 Thick, ropey, copious oropharyngeal secretions are associated with high-grade mucositis. The secretions interfere with swallowing, cause gagging and regurgitation, and predispose to aspiration.51 The high-grade mucositis associated with these intensive therapies occurs earlier, is more severe, and lasts longer than that associated with more standard regimens. There is increased risk for prolonged mucosal ulceration that may eventually result in scarring and organ dysfunction. This cascade of injury has been termed a consequential late effect”of RT.52
Severe acute ulcerative mucositis is a surrogate risk index for and may partially contribute to long-term dysphagia that persists after re-epithelialization, but it does not explain all issues. Insensate aspiration, for example, may occur even when the larynx and CPI are not directly involved by cancer, and when the larynx and CPI are mostly shielded from the radiation beam by a divergence block in the anterior supraclavicular field.29,53,54 This suggests that there are neurological causes for loss of laryngeal sensation and the cough reflex leading to aspiration that are not directly related to high-dose tongue base or laryngeal irradiation. Dysphagia and aspiration additionally may have onset or worsen years after CRT because of submucosal effects, including fibrosis, and vascular and nerve (sensory and motor) injury.55-58 The explanation of these various types of normal tissue injury has more recently been categorized as cytocidal, indirect, and functional.59
Current clinical radiosensitizers are typically chemotherapy drugs that sensitize the tumor to radiation effects, but there is no selectivity, so nontumor tissues are similarly affected.60 In contrast, Bonner et al61 reported on a phase III trial comparing RT alone with RT with cetuximab as a radiosensitizer for HNC. In this trial, the magnitude of gain in local control and survival with cetuximab was similar to that seen with cisplatin in other trials, but there was no increase in mucositis or dysphagia. Future investigation is required to determine whether targeted agents are equally effective but less toxic radiosensitizers than cytotoxics for patients intermediate-stage disease and may be safely used with increased efficacy in addition to cytotoxics for those with advanced disease.
PREVENTION AND TREATMENT STRATEGIES
There are no large, multi-institution, prospective, controlled swallowing intervention series. Rather, most data is retrospective, and composed of smaller, single-institution series. Additionally, multi-institutional dysphagia studies ideally require central review of MBS studies to reduce inter-rater variation in the evaluation of and therapeutic recommendations for specific swallowing disorders.62 These caveats must be kept in mind when weighing the evidence in the dysphagia literature.
Early therapeutic regimens of swallowing exercises that are designed to strengthen musculature, increase the precision of movements, and maintain range of motion provide the best prevention of long-term swallowing dysfunction in patients who have undergone RT/CRT for HNC.63,64 Some studies have shown that there is less benefit to delayed swallowing therapy.65 Other data suggest that function at 6 months predicts long-term function.9 It therefore seems reasonable to aim for maximal swallowing recovery by 6 months post-CRT.
Since even brief NPO intervals portend poorer swallowing outcomes, we recommend that patients swallow as large a volume of the maximally tolerated food viscosity as frequently as possible during and after treatment, even if they have a FT, for swallowing exercise. We also provide a swallowing therapy regimen that includes exercises that have been demonstrated to improve swallowing ability (Table 3).
The unnecessary irradiation of the uninvolved larynx has been eschewed in RT treatment planning.66,67 There are different techniques used during intensity-modulated RT (IMRT) to treat the entire neck with IMRT, or split the field, and treat the lower neck with an anterior supra-clavicular field. The latter limits larynx dose. Additionally, the use of a full-length, tapered midline block in the anterior supra-clavicular field may be used for appropriately selected patients from the beginning of treatment to more fully block the larynx, the cricopharyngeal inlet, and cervical esophagus.68
On the basis of a limited number of early studies, IMRT does not appear to reduce peak mucositis severity or acute FT rates as compared with older techniques.69,70 Eisbruch et al,16 however, have recently developed IMRT planning algorithms to limit radiation dose to the tongue base, pharyngeal constrictors and autonomic neural plexus, and the larynx that were found to be associated with long-term dysphagia and aspiration (Fig 5). Clinical data have not yet been reported.
Xerostomia is the most prevalent late effect of RT for HNC, and occurs after only modest RT doses.71-73 Salivary mucins protect the mechanical surface integrity of the mucosa, and by means of salivary antimicrobial effects and growth factors.74,75 An inverse relationship has been demonstrated between the levels of salivary epidermal growth factor and the grade of mucositis.76,77 IMRT and amifostine are associated with less decline in measured salivary flow and less patient-reported xerostomia in some studies.78,79
THERAPEUTIC SWALLOWING INTERVENTIONS
The evaluation of patients with dysphagia by instrumental studies is useful to identify specific abnormalities for which interventions can be used, and their effectiveness subsequently verified. Therapeutic interventions may include (1) pharyngeal or cervical esophageal dilation that can be performed from above, or below in cases in which the lumen from above cannot be located80,81; (2) dietary modifications (eg, thin liquids to follow solids, or thickening agents for thinner liquids); (3) postural strategies (eg, head positioning); (4) swallowing maneuvers such as the super-supraglottic swallow and the Mendelsohn Maneuver; (5) therapeutic exercises that target strength and range of motion for lips, tongue, and larynx; and (6) prosthetics (eg, palatal obturators to prevent VPI).9 Interventions specific to the disorders identified on MBS have been shown to result in some swallowing improvement in approximately 75% of RT patients.82 It is not yet proven, however, that similar gains are possible after CRT. We make recommendations for patient management (Table 4), and to patients for exercises (Table 3).
Patients who aspirate or who are at risk for aspiration can be taught to protect their airway. The supraglottic swallow protects the airway at the level of the vocal folds while the super-supraglottic swallow prevents aspirate from entering the airway at the level of the laryngeal vestibule. To perform the supraglottic swallow, patients learn to hold their breath, swallow, cough or clear their throat, or may also bear down during this same therapeutic sequence to perform the super-supraglottic swallow.83 To increase hyolaryngeal excursion and CPI opening, patients are taught the Mendelsohn maneuver to maintain laryngeal elevation throughout the entire swallow.84,85
CONCLUSION
Dysphagia and aspiration are under-reported and underappreciated consequences of HNC and its treatment. Successful pretreatment swallowing is a positive predictor for most patients to achieve safe, successful post-treatment swallowing. There is an association between the intensity of CRT treatment regimens, and the rates of acute and long-term dysphagia and FT dependence. Neuropathic, vascular, and fibrotic changes may also contribute to the pathophysiology.
We believe that treatment regimens that are prospectively designed and implemented are the best methods for avoiding long-term complications. Patients should be encouraged to swallow throughout their course of CRT, and even brief NPO intervals should be avoided. We believe that the appropriate and timely use of instrumental evaluation, adherence to swallowing exercise during RT/CRT—even if an FT is in place—and rapid rehabilitation all optimize outcomes. Minimizing RT dose and dose inhomogeneity to the tongue base, pharyngeal (wall and autonomic plexus) and laryngeal structures may also decrease risk for long-term dysphagia; however, confirmation is needed.
Future improvements in swallowing outcome will require confirmation of the specific radiation dose–sensitive structures and optimal methods for their protection with physical techniques, or biologic approaches with tumor-selective radiosensitizers, and/or normal tissue-specific radioprotectors. There are no current prospective, randomized data to support the use of electrical stimulation of swallowing muscles. Future studies are needed to compare the effectiveness of intensive swallowing therapy in patients treated with CRT as opposed to RT alone. In the meantime, we recommend that patients be encouraged to swallow as much as possible during treatment regimen, perform swallowing exercises, and strive for swallowing recovery as quickly as possible.
Authors' Disclosures of Potential Conflicts of Interest
The author or immediate family members indicated a financial interest. No conflict exists for drugs or devices used in a study if they are not being evaluated as part of the investigation. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors.
| Authors | Employment | Leadership | Consultant | Stock | Honoraria | Research Funds | Testimony | Other |
|---|---|---|---|---|---|---|---|---|
| David I. Rosenthal | Amgen (A); Imclone (A) | MedImmune (A) |
Dollar Amount Codes (A) < $10,000 (B) $10,000-99,999 (C) ≥ $100,000 (N/R) Not Required
Author Contributions
Conception and design: David I. Rosenthal, Jan S. Lewin, Avraham Eisbruch
Provision of study materials or patients: Avraham Eisbruch
Collection and assembly of data: David I. Rosenthal, Jan S. Lewin
Data analysis and interpretation: Jan S. Lewin, Avraham Eisbruch
Manuscript writing: David I. Rosenthal, Jan S. Lewin, Avraham Eisbruch
Final approval of manuscript: David I. Rosenthal, Jan S. Lewin, Avraham Eisbruch
Swallowing stages and interventions.
Base of tongue in opposition to posterior pharyngeal wall. (A) Normal; (B) reduced after chemoradiotherapy. Arrows indicate tongue base.
(A) Normal hyolaryngeal motion (elevation plus anterior excursion); (B) reduced hyolaryngeal motion. Arrow indicates hyoid.
(A) Pharyngeal residue on modified barium swallow (MBS); (B) pharyngeal residue on fiberoptic endoscopic evaluation of swallowing; (C) aspiration on MBS. Arrow indicates tracheal aspiration.
Radiation-induced changes on segmental imaging. (A) Preradiation; (B) postradiation. Supraglottic (white arrow) and paraspinal musculature edema (dark arrow) after chemoradiotherapy.
Altered Fractionation Trials: Therapeutic and Functional Outcomes
Chemoradiation Trials: Therapeutic and Functional Outcomes
Radiation Therapy Swallowing Exercises
Ten Recommendations to Maximize Postradiation Swallowing Recovery
Footnotes
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Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.
- Received February 1, 2006.
- Accepted April 3, 2006.
