Starmer, Heather M.
Dysphagia is a common sequela of head and neck cancer (HNCA) and its treatment. Although surgery is expected to result in predictable alterations in swallowing function, the increased use of nonoperative treatment for organ preservation in recent years has led to a growing awareness of dysphagia associated with radiation fibrosis and changes in innervation of the muscles of swallowing. The use of radiation and chemotherapy has been beneficial in sparing the consequences of surgical exposure and removal of tissues involved in swallowing. However, organ preservation does not necessarily equate to preservation of function. A substantial body of evidence suggests that patients receiving nonsurgical treatment for HNCA are at risk for both acute toxicities and long-term alteration of swallow function [1–4]. Such alterations may contribute to long-term decrements in health status and quality of life [5–8]. It has become increasingly apparent that prevention of dysphagia through active participation with swallowing therapists is of paramount importance in this population. In this article, we will review and discuss current research regarding dysphagia in the HNCA population.
PRETREATMENT ASSESSMENT VALUE
Recent studies have shown pretreatment swallowing deficits to be common in HNCA patients, particularly those with advanced-stage disease [9,10]. Further, it has been demonstrated that there is poor correlation between measurable deficits and patients’ perceptions of these deficits [11–13]. Owing to the elevated risk of silent dysphagia in HNCA, instrumental assessment is essential prior to oncologic therapy, particularly for those individuals at greatest risk for dysfunction . Pretreatment dysphagia may lead to adverse outcomes during treatment such as aspiration pneumonia, dehydration, and malnutrition. Such events may compromise oncologic outcomes because of treatment breaks. Determining aspiration risk prior to treatment may assist in ensuring optimal intervention by the swallowing therapist through application of compensatory maneuvers, dietary modifications, and rehabilitative interventions. Understanding which patients are at highest risk for dysphagia prior to treatment may assist in efficient, cost-effective allocation of resources. Further, understanding pretreatment organ function may influence determination of the oncologic treatment approach most appropriate in order to maximize overall function and quality of life posttreatment. For instance, in patients determined at baseline to have poor laryngeal function, application of organ sparing treatments is unlikely to restore adequate function for well tolerated and efficient swallowing. These patients must be educated regarding anticipated outcomes and the potential for permanent deficits. We have found in our practice that when faced with realistic discussions of long-term function, many patients will choose surgical intervention, including total laryngectomy, in order to have a better chance at oral eating.
Instrumental swallowing evaluation can be accomplished through videofluoroscopic swallowing studies (VFSS) or fiberoptic endoscopic evaluations of swallowing (FEES). These tools are complementary and both have an important role in the assessment of dysphagia in patients with HNCA. VFSS is generally considered the gold standard for assessment of oropharyngeal disorders because of its ability to provide visualization of the coordinated stages of swallowing as well as specific physiology. In addition, use of VFSS allows for evaluation of the oral and esophageal aspects of swallowing. In contrast, FEES provides the benefits of avoiding radiation exposure, a flexible service delivery model, and direct visualization of relevant anatomy. Investigation of the comparability of these tools has revealed high levels of agreement, sensitivity, specificity, and positive and negative predictive values . The FEES evaluation has also been shown to demonstrate greater sensitivity to laryngeal penetration and aspiration, when compared with VFSS . We have found, in our institution, that use of a FEES evaluation as part of the multidisciplinary HNCA evaluation yields important information, without the need to schedule additional appointments or expose patients to unnecessary radiation. A thorough FEES evaluation conducted by an experienced speech-language pathologist can provide anatomic and physiologic information, assessment of swallowing abilities across viscosities and textures, and implementation of compensatory postures and strategies when dysfunction is identified. We have found that integrating this practice into the standard assessment of newly diagnosed HNCA patients has streamlined patient care and contributed to clinical decision making. When necessary, a VFSS can be added to answer additional questions regarding issues such as physiology or esophageal dysfunction. VFSS may also be required in cases in which significant alteration of anatomy owing to tumor precludes adequate visualization of structures of interest for swallowing. Based upon a systematic review of the literature, Mylnarek et al. proposed that instrumental swallowing evaluation, assessment of speech intelligibility, supplemental speech evaluation when indicated, and patient reported swallowing outcomes should be measured prior to, during, and following treatment for oral and oropharyngeal cancers.
In the past several years, there has been significant accumulation of data regarding the importance of prophylactic swallowing therapy during nonoperative HNCA treatments. A retrospective case–control study by Carroll et al. demonstrated the value of initiating prophylactic therapy prior to chemoradiotherapy (CRT). Nine individuals receiving prophylactic intervention prior to CRT were matched with patients receiving swallowing therapy after the completion of CRT. All patients completed a series of exercises targeting the tongue base, pharyngeal constrictors, and laryngeal elevators and then completed a VFSS 3 months after completion of CRT. Individuals performing exercises prior to and during CRT demonstrated more normal tongue base apposition to the posterior pharyngeal wall during swallowing (P = 0.025) as well as more normal epiglottic inversion (P = 0.02). This was an important study in that it provided evidence for what swallowing therapists knew from their practice – initiation of exercises before onset of dysphagia was more likely to benefit the patient than waiting until dysfunction appeared. A randomized controlled trial by Kotz et al.[19▪] further demonstrated that those patients receiving prophylactic swallowing therapy had more favorable diet levels 3–6 months following completion of treatment. These two papers together demonstrated that both physiology and function are optimized with application of preventive dysphagia exercises. Van der Molen et al. demonstrated the feasibility of initiating prophylactic swallowing therapy during CRT and patient adherence to treatment recommendations. In their series, 69% of subjects were able to immediately implement therapeutic exercises following training, and an additional 31% were able to follow through within the first week of treatment. Following completion of CRT, 57% of subjects were judged to be ‘very familiar’ with their exercises, supporting patient reported adherence with home exercises. These data support the feasibility of implementation of a prophylactic swallowing therapy programme.
Objective functional data regarding the clinical impact of preventive swallowing therapy in HNCA patients undergoing CRT was recently published by Carnaby-Mann et al.[21▪▪]. Six months post-CRT, muscle size/composition on MRI was the primary outcome. In the active treatment arm, in which patients performed swallowing exercises twice daily over the duration of treatment, there was less structural change in the genioglossus, hyoglossus, and myohyloid muscles than in the other two treatment groups. Individuals in the active treatment group were more likely to continue oral diet during treatment than those in the usual care group. A composite measure was designed to designate a favorable swallowing related outcome and included weight loss less than 10%, maintenance of oral diet, and a change of less than 10 points on the Mann Assessment of Swallowing Ability. In the active treatment arm, 86% of patients achieved this desirable outcome, whereas only 47% of those who were not actively engaged in treatment achieved this (P = 0.009). Their data revealed a 36% absolute risk reduction for loss of swallowing ability when participating in preventive exercise. This is the first placebo controlled investigation of the impact of swallowing therapy in this population. The positive results serve as strong evidence that patients receiving nonoperative head and neck cancer treatment should be engaged in swallowing therapy prior to start of treatment.
In addition to performance of swallowing exercises for prevention of dysphagia, there is growing evidence that maintenance of oral intake during treatment has a positive impact on swallowing outcomes. In Langmore et al.'s article [22▪],‘Does PEG cause dysphagia in head and neck cancer patients?’, posttreatment diet level was significantly associated with oral intake during treatment in that those who maintained some oral intake had significantly more advanced diet levels following treatment. Further, this study demonstrated that those receiving a prophylactic percutaneous endoscopic gastrostomy (PEG) did not lose less weight than those with no PEG or therapeutic PEG. These findings raise concerns regarding the common practice of automatic prophylactic PEG placement. If the rationale behind prophylactic PEG is maintenance of weight, this study suggests that this intervention may not accomplish this aim. Further, prophylactic PEG may be associated with poorer swallowing outcomes. Additional evidence concerning feeding tube use and posttreatment dysphagia was provided by Hutcheson et al.[23▪▪]. Perhaps one of the most important studies published in the last year, it demonstrated that eating and exercising swallowing musculature during CRT provides protective benefit for maintenance of diet following end of treatment. For individuals not eating and not exercising, return to a normal diet was only enjoyed by 65% of patients. For those who both ate and exercised during treatment, 92% returned to a normal oral diet after treatment completion. These studies together suggest the need to reevaluate the practice of prophylactic PEG placement. Although some patients may require supplemental nutrition, we have found in our practice that with adequate management of acute toxicities, most patients are able to maintain an oral diet without need for prophylactic PEG.
Patient adherence to treatment recommendations requires that patients be active participants in their care. HNCA treatment can be complicated and patient understanding of treatment recommendations can be lacking. Increasing patient comprehension of the importance of swallowing intervention is critical for improving adherence to recommendations. Recent reports [24▪] have demonstrated that adherence to therapy recommendations is poor with only 45% of patients at least partially adhering to treatment recommendations. This work shows that head and neck care teams need to determine strategies that facilitate patient adherence. Our work has shown that inclusion of the speech pathologist in the multidisciplinary head and neck team has a positive impact on patient attendance at and participation in swallowing therapy . Several factors may influence this relationship. We believe the ability to establish a clinical relationship between the patient and the swallowing therapist from the time of diagnosis assists in the patient's familiarity and comfort with that individual provider. Establishing this relationship may have a positive impact on the patient's adherence with recommendations made by the therapist. Inclusion of the swallowing therapist as part of the team evaluation also supports their legitimacy on the team, and we suspect that the emphasis on the importance of swallowing therapy during the multidisciplinary clinic is more salient to patients than an isolated recommendation by the oncology team. Another key to facilitation of adherence is management of acute treatment toxicities. In unpublished work by Carnaby-Mann and Lagorio , pain and fear of pain were cited as primary reasons why patients did not adhere to their recommended swallowing exercise treatment plan. Further, patients who have pain or fear of pain may be more likely to rely on tube feedings. Thus, pain and fear of pain have the potential to significantly impact long-term swallowing. Our team has been investigating the role of gabapentin in the treatment of pain during radiation therapy. We have demonstrated that prophylactic administration of gabapentin (2700 mg/day) during radiation is associated with decreased total narcotic analgesics, time to use of narcotic analgesics, and weight loss despite the decreased use of prophylactically placed PEG [27▪]. During multivariate analysis of factors associated with PEG use, prophylactic gabapentin use was associated with an 85% risk reduction for the use of a prophylactically placed PEG [28▪]. Further, we found that when comparing patients treated prophylactically with gabapentin with historical controls, short-term swallowing outcomes on VFSS and posttreatment diet level were more favorable in those receiving gabapentin [29▪▪]. Patients receiving radiation therapy are known to experience both neuropathic and nociceptive pain. This series of work demonstrates there may be a role for gabapentin in controlling neuropathic pain, which is known to be unresponsive to narcotic analgesics. Investigations regarding optimal use and timing of gabapentin, the role of low-dose narcotics analgesics, and long-term outcomes continue in our study group.
Reducing treatment toxicity may also positively impact swallowing outcomes. It has been demonstrated that treatment factors such as radiation dose and volume influence swallowing outcomes [30–33]. These investigations suggest that radiation doses exceeding 50Gy to the swallowing musculature and the pharyngeal constrictors specifically are associated with poorer swallowing outcomes. Our recent work demonstrated that radiation dose to the floor of mouth musculature involved in laryngeal elevation was significantly related to laryngeal penetration and aspiration . It is clear that techniques that may allow for dose reduction may have a positive impact on swallowing outcomes. With a rising epidemic of HNCA associated with human papilloma virus (HPV) and the favorable oncologic outcomes associated with this disease [35,36], de-intensification treatment efforts have appeared more feasible. Treatment de-intensification is particularly attractive given that despite better oncologic outcomes, patients with HPV-associated HNCA do not appear to have reduced risk of developing dysphagia . Three treatment approaches are currently under investigation and show promise for reducing long-term swallowing toxicities. One approach, de-intensifying radiation after induction chemotherapy, is under investigation in ECOG-1308. This protocol allows for reduction of radiation from a target dose of 69 to 54 Gy after completion of induction chemotherapy. Our research group at Johns Hopkins is also studying radiation de-intensification, specifically in the HPV population. In JHU-0988, patients with HPV-associated HNCA receiving radiation therapy have dose reduction from 70 to 63 Gy with the primary goal of reducing radiation dose and damage to the muscles of deglutition. Finally, the addition of transoral surgeries to debulk the primary tumor may allow the radiation oncologist to plan radiation to lower doses to surrounding musculature such as the pharyngeal constrictors. Further, more thorough tumor and lymph node staging through surgical intervention may result in the ability to avoid concurrent chemotherapy, which has also been associated with increased dysphagia [37,38]. Although these strategies hold promise for reducing swallowing toxicity, data are still pending regarding their impact on swallowing physiology. It is critical that as such new treatment approaches are investigated, thorough assessment of their multidimensional impact on swallowing is conducted. This would include not only PEG dependence rates and quality of life measures, but also physiologic swallowing data. Only by understanding how these interventions impact function and patient perception of function can we understand how different treatments compare.
Dysphagia is a too common consequence of HNCAs and the treatments employed to eradicate the disease. The importance of the swallowing therapist on the team for pretreatment assessment, administration of preventive dysphagia therapy, and provision of rehabilitative strategies cannot be overemphasized in this population. Further, the importance of maintenance of oral diet during radiation therapy has been established, suggesting that prophylactic PEG placement may be better suited for selected individuals at highest risk, such as those with pretreatment dysphagia. Future investigations of adaptation of current treatment strategies are of paramount importance, particularly in the era of HPV-associated disease. Such investigations must include assessment of functional outcomes and should involve close collaboration with the swallowing therapist.
Conflicts of interest
There are no conflicts of interest.
REFERENCES AND RECOMMENDED READING
Papers of particular interest, published within the annual period of review, have been highlighted as:
- ▪ of special interest
- ▪▪ of outstanding interest
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epub ahead of print
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19▪. Kotz T, Federman AD, Kao J, et al. Prophylactic swallowing exercises in patients with head and neck cancer undergoing chemoradiation: a randomized trial. Arch Otolaryngol Head Neck Surg. 2012; 138:376–382.
This is a randomized trial demonstrating the positive dietary benefits in the months following completion of chemoradiotherapy when prophylactic exercises are administered.
20. van der Molen L, van Rossum MA, Burkhead LM, et al. A randomized preventive rehabilitation trial in advanced head and neck cancer patients treated with chemoradiotherapy: feasibility, compliance, and short-term effects. Dysphagia. 2011; 26:115–170.
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This is the first randomized, placebo controlled trial of preventive dysphagia therapy in HNCA which looked at multidimensional aspects of swallowing outcomes including physiology, diet level, and quality of life. It provides strong evidence for the importance of prophylactic swallowing therapy.
22▪. Langmore S, Krisciunas GP, Miloro KV, et al. Does PEG cause dysphagia in head and neck cancer patients? Dysphagia. 2012; 27:251–259.
This is first article to raise the question whether prophylactic PEG is harmful or helpful.
23▪▪. Hutcheson KA, Bhayani MK, Beadle BM, et al. Eat and exercise during radiotherapy or chemoradiotherapy for pharyngeal cancers. Use it or lose it. JAMA Otolaryngol Head Neck Surg. 2013; 139:1127–1134.
Thorough investigation regarding the role of oral intake and prophylactic swallowing exercises.
24▪. Shinn EH, Basen-Engquist K, Baum G, et al. Adherence to preventive exercises and self-reported swallowing outcomes in postradiation head and neck cancer patients. Head and Neck. 2013; 35:1707–1712.
This is an important article showing that patient adherence to treatment recommendations is not optimal. It raises questions regarding how to optimize patient adherence during treatment.
25. Starmer HM, Sanguineti G, Marur S, Gourin CG. Multidisciplinary head and neck cancer clinic and adherence with speech pathology. Laryngoscope. 2011; 121:2131–2135.
26. Carnaby-Mann G, Lagorio L. Preventing dysphagia in head and neck cancer. Paper presented at American Speech Language and Hearing Association (ASHA) Annual Convention. Atlanta, GA, November 15-17, 2012.
27▪. Raval RR, Richardson ML, Yang WY, et al. Gabapentin therapy for prevention and management of the pain syndrome in oropharyngeal carcinoma patients treated with radiation. Paper presented at the American Society for Radiation Oncology (ASTRO) Annual Meeting. Boston MA, October 28-31, 2012.
This is the first presentation looking at the impact of prophylactic gabapentin for pain control during chemoradiotherapy.
28▪. Yang WY, Madanikia S, Kumar R, et al. Predictive factors for prophylactic percutaneous endoscopic gastrostomy (PEG) tube placement and use in Intensity Modulated Radiation Therapy (IMRT) treated head and neck patients: concordance, discrepencies, and the role of gabapentin. Paper presented at the American Head and Neck Society (AHNS) meeting, Orlando FL, April 10-11, 2013.
This article demonstrated significant risk reduction for use of prophylactic PEG if pain is well managed with gabapentin.
29▪▪. Starmer HM, Yang WY, Raval R, et al. Effect of gabapentin on swallowing during and after chemoradiation for oropharyngeal squamous cell cancer. Dysphagia. 2014; (in press)
This article demonstrated that control of pain during radiation therapy using gabapentin resulted in improved swallowing outcomes in contrast to a historical cohort who did not receive gabapentin and had poorer pain control. It showed that patients receiving gabapentin did not require supplemental PEG feedings as often, therefore were able to maintain oral diets more regularly. It provides physiologic data regarding swallowing outcomes.
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