Dysphagia in Head and Neck Cancer Patients Treated ... - Springer Link

Dysphagia (2010) 25:139–152 DOI 10.1007/s00455-009-9247-7

REVIEW ARTICLE

Dysphagia in Head and Neck Cancer Patients Treated with Chemoradiotherapy Nele Platteaux Æ Piet Dirix Æ Eddy Dejaeger Æ Sandra Nuyts

Received: 22 April 2009 / Accepted: 31 July 2009 / Published online: 27 August 2009 Ó Springer Science+Business Media, LLC 2009

Abstract Dysphagia is a very common complaint of head and neck cancer patients and can exist before, during, and after chemoradiotherapy. It leads to nutritional deficiency, weight loss, and prolonged unnatural feeding and also has a major potential risk for aspiration. This has a significant negative impact on the patient’s entire quality of life. Because treatment of dysphagia in this setting is rarely effective, prevention is paramount. Several strategies have been developed to reduce dysphagia. These include swallowing exercises, treatment modification techniques such as intensity-modulated radiotherapy, selective delineation of elective nodes, reducing xerostomia by parotid-sparing radiotherapy, and adding of radioprotectors. However, more research is needed to further decrease the incidence of dysphagia and improve quality of life. Keywords Radiotherapy Head and neck cancer Dysphagia Intensity-modulated radiotherapy Deglutition Deglutition disorders

Introduction Head and neck cancer (HNC) is the sixth most common malignancy worldwide, representing about 6% of all tumors and accounting for an estimated 650,000 new cases and N. Platteaux (&) P. Dirix S. Nuyts Department of Radiation Oncology, Leuven Cancer Institute, University Hospitals Leuven, Campus Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium e-mail: [email protected] E. Dejaeger Department of Geriatrics, Leuven Cancer Institute, University Hospitals Leuven, Campus Gasthuisberg, Leuven, Belgium

350,000 deaths every year [1]. Radiotherapy (RT) and surgery are the main treatment modalities, although there is an increasing role for chemotherapy. The choice of modality depends on patient factors, primary site, clinical stage, and resectability of the tumor. Approximately 3040% of patients present with early-stage disease, which is treated by surgery or primary radiotherapy. Around 60% of patients are diagnosed with a locally advanced stage, which is associated with a poor prognosis [1]. Standard treatment for locally advanced HNC has been surgery followed by postoperative RT. Several trials focusing on organ preservation showed a similar outcome for these patients using chemoradiotherapy (CRT) [2–4]. Therefore, concurrent radiation therapy with chemotherapy is nowadays accepted as an organ-preserving approach [4–7]. Primary radiotherapy for HNC is conventionally given to a total dose of 70 Gy in once daily fractions of 2 Gy, 5 fractions a week, over 7 weeks [1]. Altered (hyperfractionation and/or acceleration) fractionation schedules and the use of concomitant chemotherapy have both been tested and proven to improve locoregional control and overall survival [5–11]. However, these intensified schedules come at the cost of more acute and chronic side effects [1, 6, 7, 9]. The most common acute side effects of CRT for HNC are mucositis, pain, dermatitis, xerostomia, loss of taste, hoarseness, weight loss, myelosuppression, nausea, and dysphagia. The most frequent late side effects are xerostomia, loss of taste, fibrosis, trismus, and dysphagia. Dysphagia is a common, multifactorial, and potentially life-threatening side effect of CRT, with a potential for aspiration and death due to aspiration pneumonia [12–14]. It also results in nutritional deficiency leading to weight loss and the need for prolonged feeding by a percutaneous endoscopic gastrostomy (PEG) tube. This has a significant negative impact on the global quality of life (QOL) of

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potentially cured patients, causing anxiety and depression [13, 15]. This article focuses on the incidence of dysphagia in HNC patients treated with CRT and provides an overview of methods to prevent this important side effect.

Physiology of Swallowing and Pathophysiology Normal swallowing is a complex process in which a large number of cranial nerves and muscles are involved in carrying food from the mouth through the pharynx into the esophagus and stomach. Swallowing consists of three phases [oral (oral preparatory), pharyngeal, and esophageal], with the voluntary oral preparatory and oral phases followed by an involuntary reflex that must be triggered. This process implies a rapid and precise coordination between sensory input and motor function [16–18]. Swallowing involves controlling the food in the mouth, largely with the oral part of the tongue, to enable tasting and chewing to occur. The oral tongue moves the food onto the teeth to crush the food, collects the food from around the mouth after chewing, brings it together to form a bolus, and propels it backward out of the mouth. Thereafter, the pharyngeal stage of swallowing is triggered and a number of necessary motor activities occur: (1) hyoid movement, (2) closure of the entrance to the nose, the velopharyngeal port, by elevation of the soft palate to prevent food from entering the nose, (3) closure of the airway to prevent food from entering the lungs, (4) opening of the upper esophageal sphincter by relaxation of the cricopharyngeal muscles and by movement of the larynx anteriorly and superiorly to enable the bolus to pass into the esophagus, (5) epiglottic inversion, and (6) pharyngeal contraction to push the food through the pharynx and the esophagus. All these actions occur in the pharynx within 1 s and must be appropriately coordinated for the swallow to be safe and efficient [17, 18]. Pathophysiology of Swallowing Disorders Post-RT swallowing disorders are due to primarily neuromuscular fibrosis and radiation-induced edema [19, 20]. RT induces hyperactivation through hydroxyl radicals of transforming growth factor-b1 (TGF-b1) which plays a role in collagen deposition and degradation. This leads to fibrosis and the resulting abnormal motility of deglutition muscles as impaired pharyngeal contraction and laryngeal elevation responsible for dysphagia, aspiration, and stenosis [21]. Second, sensory changes in the oral cavity and the pharynx also play a role in post-RT swallowing disorders by changing the patient’s perception of swallowing [17, 22]. There are hypotheses that CRT can have an effect on innervation of the larynx and pharynx, causing loss of laryngeal sensation, motor function, and normal peristalsis [18]. Obviously,

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xerostomia after RT due to the inclusion of salivary glands in the radiation field contributes to swallowing problems. Xerostomia is associated with difficulties in mastication and delayed initiation of the swallowing reflex because of decreased bolus lubrication due to the lack of saliva [17]. It also negatively affects the patient’s overall perception of swallowing quality and comfort of eating [19, 22].

Incidence of Dysphagia Pretreatment Dysphagia and Aspiration Rate (Table 1) Dysphagia can exist before treatment as a result of the extent of the tumor which can involve the motility of structures that contribute to swallowing. Dysphagia rate and severity therefore depend on tumor stage and localization, with the most severe complaints in more advanced locoregional stages [23]. Laryngeal and hypopharyngeal cancer patients aspirate most frequently before treatment which is reflected by the high degree of pharyngeal and esophageal impairment [24–26]. Post-Treatment Dysphagia (Table 2) The severity of post-RT swallowing disorders is dependent on several factors: total radiation dose, fraction size, fractionation schedule, target volumes, interfraction interval, treatment techniques such as the use of intensity-modulated radiotherapy treatment (IMRT), addition of concurrent chemotherapy, smoking during and after RT, PEG tube feeding or prolonged ([1–2 weeks) nil per os, depression, and poor mental health [17, 27–30]. The meta-analysis of Machtay et al. [29] showed that older age, advanced tumor stage, larynx/hypopharynx primary site, and neck dissection after concurrent CRT are the main risk factors for severe late toxicity. An average rate of 50% dysphagia in advanced-stage HNC after CRT is reported [31]. However, it should be noted that the incidence of dysphagia is perhaps underreported in trials because clinical judgment often underestimates the severity [32]. Little is known about the evolution of swallowing problems after CRT, but dysphagia and aspiration can begin or significantly worsen years after treatment. This is probably due to submucosal effects such as fibrosis and vascular and nerve (sensory and motor) injury [19]. Nguyen et al. [32] reported that the severity of dysphagia decreased in 32%, remained unchanged in 48%, and worsened in 20% of their patients 1 year or more following HNC treatment. Goguen et al. [33] described dysphagia as slowly but only partly resolving after 6–12 months following CRT for advanced HNC. In another study on nasopharyngeal cancer


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Table 1 Overview from literature of pretreatment dysphagia Tumor stage/site

No. of patients (N)

% Dysphagia

T2 or more, oral, pharyngeal, and laryngeal cancer

352

Oral: 28.2%, pharyngeal: 50.9%, laryngeal: 28.6%

Stage III–IV, HNC

79

Oral cavity: 14%, oropharyngeal: 30%, laryngeal: 67%, hypopharyngeal: 80% VFS

Stenson et al. [26]

Stage II–IV, HNC

63

17% MBS

Nguyen et al. [14]

Stage IV, HNC

22

14% VFS

Eisbruch et al. [12]

Stage III–IV, HNC

27

41% VFS (45% silent–55% overt)

Rosen et al. [83]

Stage III–IV, oropharyngeal, nasopharyngeal cancer

36

8% VFS

Feng et al. [78]

All tumor stages/sites

236

% Aspiration

Refs. Pauloski et al. [25]

Grade 3–7: T1–T2: 20%, T3–T4: 31%, oral cavity: 5%, laryngeal: 29%, oropharyngeal: 33%, hypopharyngeal: 52% VFS

Nguyen et al. [23]

HNC head and neck cancer, VFS videofluoroscopy, MBS modified barium swallow

Table 2 Overview from literature of post-treatment dysphagia Tumor stage/site

Therapy

N

Stage II–IV, HNC

CRT

63

% Dysphagia

% Aspiration

Refs.

59% overall/ 33%

Nguyen et al. [14]

MBS Locally advanced HNC Stage IV, HNC

CRT CRT

55

45% severe

36% grade 6–7

39% grade 4–5

MBS

20

65% early (1–3 months)

Nguyen et al. [21] Eisbruch et al. [12]

62% late (6–12 months) VFS Stage III–IV, oropharyngeal, nasopharyngeal cancer

CRT

All stages, oropharyngeal cancer Stage III–IV, oral cavity, oropharynx, hypopharynx

(C)RT CRT

Nasopharyngeal cancer

RT

36

44% early

Feng et al. [77, 78]

8% strictures VFS 81 10

23% grade 3–4 13% early

Levendag et al. [68] Smith et al. [19]

VFS 31

41.9% silent

Wu et al. [84]

FEES HNC head and neck cancer, VFS, videofluoroscopy, MBS modified barium swallow, FEES functional endoscopic evaluation of swallowing, (C)RT (chemo)radiotherapy, RT radiotherapy

patients treated with RT, a continuous deterioration of swallowing function over time was seen [34] (Table 3).

Measuring and Reporting Dysphagia Subjective Scoring Several scoring systems are available to measure and report dysphagia.

Patient-reported dysphagia can be assessed by qualityof-life (QOL) questionnaires like the European Organization for Research and Treatment of Cancer (EORTC) global Q30 and Head and Neck (H&N35) [31, 35]. The latter is a specific questionnaire for HNC patients and scores xerostomia, swallowing, and eating [35, 36]. Two other commonly used questionnaires for subjective assessment are the Performance Status Scale for HNC patients (PSS-H&N) and the MD Anderson Dysphagia Inventory (MDADI). The PSS is a rapid, clinician-rated

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Table 3 Overview from literature of chronic dysphagia Tumor stage/site

Therapy

All stages and tumor sites

CRT/surgery ± RT

N

% Dysphagia

74

% Aspiration

Refs.

49%

Nguyen et al. [85]

MBS Locally advanced HNC

CRT/surgery ± RT

25

Stage III–IV, oral cavity, oropharynx, hypopharynx cancer

CRT

10

Locally advanced HNC

Induction chemotherapy ? CRT

32%

Nguyen et al. [32]

VFS 30%

Smith et al. [19]

VFS 122

38.5% severe

Caudell et al. [27]

MBS


RT

49


RT

71

22% silent

Hughes et al. [86]

VFS 71.8% VFS

Chang et al. [34]

HNC head and neck cancer, VFS videofluoroscopy, MBS modified barium swallow, (C)RT, (chemo)radiotherapy, RT radiotherapy

instrument consisting of three subscales: normalcy of diet, public eating, and understandability of speech. Ratings range from 0 to 100, with higher scores representing closerto-normal functioning [37, 38]. The MDADI is a validated, dysphagia-specific QOL instrument and consists of 20 questions with global, emotional, functional, and physical subscales. It is patient-friendly and easy to understand and complete by patients [39, 40]. Another cancer-specific QOL instrument reported in literature is the Functional Assessment of Cancer Therapy for head and neck (FACTG& H&N). This questionnaire is completed by the patient and yields a global QOL score (FACT-G: range 0–120 points) comprising six subscales: physical, social, relationship with doctor, emotional and functional well-being, and H&N concerns [37, 38, 41]. Observer-based dysphagia can be assessed by recording acute toxicity during the first 3 months after RT using Common Terminology Criteria for Adverse Events (CTCAE) [42] and by recording late toxicity using the Radiation Therapy Oncology Group (RTOG)/ EORTC Late Radiation Morbidity Scale [43, 44]. Objective Scoring For objective assessment of swallowing function a videofluoroscopy [VF; often known as modified barium swallow (MBS)] can be performed (Fig. 1). It is a validated standard method, developed by Logemann, that allows viewing and recording of the structures and dynamics of the swallowing process [45, 46]. The whole assessment focuses on bolus manipulation, bolus control, and bolus passage including cohesion, motility, and timing [12, 17]. The findings of each patient are scored using the Swallowing Performance Scale (SPS) (Table 4). This is a validated and accurate assessment of dysphagia severity by combining

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Fig. 1 Normal swallowing function on videofluoroscopy

clinical and radiographic information. The severity of dysphagia is graded on a scale of 1–7 [12, 14, 17]. Pathological Features Seen on Videofluoroscopy Abnormal swallowing can be defined in terms of the amount and incidence of aspiration and penetration,


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Table 4 The Swallowing Performance Scale (SPS) Grade 1: normal Grade 2: within functional limits—abnormal oral or pharyngeal stage but able to eat a regular diet without modifications or swallowing precautions Grade 3: mild impairment—mild dysfunction in oral or pharyngeal stage; requires a modified diet without need for therapeutic swallowing precautions Grade 4: mild-to-moderate impairment with need for therapeutic precautions—mild dysfunction in oral or pharyngeal stage; requires a modified diet and therapeutic precautions to minimize aspiration risk Grade 5: moderate impairment—moderate dysfunction in oral or pharyngeal stage, aspiration noted on exam; requires a modified diet and swallowing precautions to minimize aspiration risk Grade 6: moderate-severe dysfunction—moderate dysfunction of oral or pharyngeal stage, aspiration noted on exam; requires a modified diet and swallowing precautions to minimize aspiration risk; needs supplemental enteral feeding support Grade 7: severe impairment—severe dysfunction with significant aspiration or inadequate oropharyngeal transit to esophagus, nothing by mouth; requires primary enteral feeding support

laryngeal sensation (response to penetrant/aspirate), and residue/pooling after the swallow [12]. Also, abnormal timing or duration of each swallowing phase can be evaluated as beyond the range found in normal controls [12, 17, 25]. The most frequently found VF abnormalities after CRT are (1) reduced inversion of the epiglottis, (2) reduced laryngeal elevation and closure resulting in poor airway protection and promoting penetration and aspiration, (3) reduced base-of-tongue retraction resulting in reduced tongue base contact with the posterior pharyngeal wall, (4) delay in triggering the pharyngeal swallow, (5) pharyngeal hypocontractility, (6) incomplete relaxation of cricopharyngeal muscles leading to reduced cricopharyngeal opening which results in pooling of residue in the piriform sinuses and valleculae [12, 17, 24, 47] (Fig. 2). VF can ideally be combined with manometry (manofluoroscopy), first developed by Mc Connel [48]. Manometry involves measurement of the pressures in the pharynx, upper esophageal sphincter, and esophagus. It is most often used to look at the relaxation and the contraction of the esophageal musculature. Ideally, it can be performed by using a solid-state catheter. Manofluoroscopy permits correlation of motion of anatomic structures with the resulting intraluminal pressures [49]. A second objective tool to evaluate swallowing dysfunction is functional endoscopic evaluation of swallowing (FEES), first described by Langmore [50]. It visualizes the pharynx from above by placing an endoscopic tube, without anesthesia, transnasally such that the end of the tube hangs over the end of the soft palate. The anatomy and function of the soft palate, tongue base, pharynx, and

Fig. 2 Aspiration and pharyngeal hypocontraction on videofluoroscopy

larynx are assessed during speech, spontaneous movements, dry swallowing, and swallowing of various consistencies of liquid and food. Sensitivity of the pharynx is assessed by light touch with the tip of the endoscope. Premature leakage of food or fluid from the mouth into the pharynx before a voluntary swallow can be assessed. Residue in vallecula epiglottica, aryepiglottic region, and piriform sinus can be assessed together with laryngeal penetration and aspiration. The patients’ reaction to residues or aspiration can be noted [51]. FEES can be combined with sensory testing (FEESST). The sensory-testing procedure includes air pulse stimuli delivered to the mucosa innervated by the superior laryngeal nerve through a port in the flexible endoscope [52]. When MBS and FEES are compared, the principal advantage of the FEES seems to lie in the detection of aspiration and for MBS in the dynamic evaluation of the oral and esophageal phases of swallowing. FEES is easier and it can be performed bedside without radiation exposure using portable equipment. It also can frequently be repeated and is more cost-effective than VF [53, 54]. Disadvantages of FEES are that it provides only indirect information about oral cavity function, the moment of swallowing itself, and esophageal disease and that it is more observer dependent [50]. Thus, FEES is often used as an adjunct to MBS rather than an alternative [55].

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Third, direct endoscopy under anesthesia can be used to visualize strictures in the inferior pharyngeal muscles at the postcricoid level of the hypopharynx [56]. Finally, CT scans can be used to evaluate the thickness of several swallowing structures like the pharyngeal constrictor muscles, the supraglottic larynx, and the glottic larynx, which is usually increased after RT [56]. Correlation Between Subjective and Objective Scoring There is considerable discrepancy in the literature concerning the correlation between objective and subjective swallowing evaluation. For instance, from a study of 132 HNC patients, Pauloski et al. [57] reported excellent correlation between patients’ perception of dysphagia and their actual swallowing function measured with VF. Patients with complaints of dysphagia had lower oropharyngeal swallow efficiency, longer oral and pharyngeal transit times, more oral and pharyngeal residue, more aspiration, took less nutrition by mouth, and were less able to eat all food consistencies. It appears that pharyngeal function has a greater impact on swallowing perception than oral function. In contrast, from a study of 116 HNC patients, Jensen et al. [58] found little correlation between patient-assessed symptom severity and observer-based toxicity scoring. The observer-based rating of side effects underestimated the patient-scored side effects using QOL questionnaires.

Impact on Quality of Life Swallowing dysfunction has a clear negative impact on the global QOL of HNC patients. Dysphagia leads to longer eating times, inability to eat different types of food, and fear or inability to eat in public, which in turn results in social isolation and depression [13]. Obviously, prolonged unnatural feeding may induce major psychological distress because it causes discomfort and distorts the patient’s selfimage [13]. Nguyen et al. [13] showed that the severity of dysphagia correlates with a compromised QOL, anxiety, and depression. Murry et al. [59] described that swallowing and QOL are often compromised in advanced HNC before

treatment, they further decrease during CRT, and they begin to improve shortly after treatment with a marked improvement 6 months after treatment. They also showed that QOL generally follows a two-stage recovery: first the psychological aspects improve, followed by the physical aspects associated with swallowing [59]. The best predictor of 12month global QOL seems to be the pretreatment global QOL [38, 60]. Langendijk et al. [15] also described that the effect of late radiation-induced toxicity, particularly on swallowing function and salivary gland function, has a significant impact on the more general dimensions of health-related (HR) QOL, such as physical, social, and mental health. They further described that the impact of radiation-induced swallowing dysfunction is greatest in the first 12 months after completion of RT and gradually decreases at 18 and 24 months [15]. Abendstein et al. [61] evaluated long-term QOL 5 years after treatment and noted an improvement in global HRQOL in 40%, deterioration in 25%, and no change in 35% of patients. Dysphagia also leads to prolonged tube feeding dependence as described above. Time dependence for tube feeding ranges in the literature from 4 to 21 months with a median of 9 months [6, 21].

Treatment of Swallowing Disturbances Management of swallowing disorders resulting from HNC treatment includes both compensatory treatment procedures and specific rehabilitation programs. Obviously, a truly multidisciplinary team approach is needed, consisting of the treating oncologist, a speech-language pathologist, a dietician, and sometimes a gastroenterologist for dilatation [17]. Compensatory Treatment Procedures The purpose of the compensatory treatment procedure is to improve bolus flow and reduce aspiration. These procedures should be introduced during MBS to evaluate the immediate results. The following compensatory treatment procedures are generally used: postural techniques, increasing sensory input prior to or during the swallow, modification of bolus size/volume and consistency of food, and deletion of

Table 5 Overview from literature of the results of swallowing therapy Tumor stage/site

Therapy

N

Treatment

Results

Refs.


CRT (n = 24)

41

Swallowing therapy for aspiration

32% improvement dysphagia

Nguyen et al. [87]

36% improvement aspiration

Super-supraglottic swallow

Elimination (1) – reduction of aspiration (2)

Postoperative RT (n = 17) All stages, oral cavity, pharyngeal-laryngeal cancer

CRT

9

HNC head and neck cancer, (C)RT (chemo)radiotherapy

123

Logemann et al. [88]

Trachea Upper border of trachea

7. Upper esophageal sphincter (UES) ? m.cricopharyngeus

8. Esophagus

Upper border of trachea At the level of the cricoid cartilage

Lower edge of cricoid cartilage

6. Glottic larynx (GL)

First 2 cm of esophagus

Cervical vertebra Subglottic larynx

Anterior tip of the thyroid cartilage

Posterior third of the tongue

Top of the piriform sinus and aryepiglottic fold 5. Supraglottic larynx (SGL)

Lower edge of cricoid cartilage Upper edge of hyoid bone Lower edge of hyoid bone Below soft palate

Lower edge of hyoid bone Upper edge of hyoid bone

3. Inferior PC (IPC) muscles 4. Base of tongue (BOT)

Upper edge of the cricoid cartilage

Cervical vertebra or prevertebral muscles Widest diameter of rhinopharynx, base of tongue, hyoid bone, and larynx Upper edge of hyoid bone

Anterior border Inferior border

2. Middle PC muscles (MPC)

Radioprotector amifostine (WR2721) is a cytoprotective agent. It is a thiol compound that protects normal tissues against radiation through the binding of the sulfhydryl group with hydroxyl radicals. It has been tested for mucosal protection and prevention of late dysphagia following RT for HNC with mixed results [69]. In HNC

Caudal tip of pterygoid plates (hamulus)

Radioprotectors

1. Superior pharyngeal constrictor (SPC) muscles

As described above, dysphagia has a significant impact on QOL and prevention of this serious late side effect is of paramount importance [68]. The three main approaches are described below.

Superior border

Prevention of Dysphagia

OAR

In the case of pharyngoesophageal strictures, it is sometimes necessary to perform a pharyngeal and cervical esophageal dilatation [18]. Ahlawat et al. [67] reported that endoscopic dilatation of proximal esophageal strictures gives adequate dysphagia relief in 84% of their treated HNC patients.

Table 6 UZ Leuven guidelines to delineate the dysphagia-aspiration-related structures

Dilatation of Strictures

Posterior border

specific food consistencies as the last resort [17, 62, 63]. Postural changes (like head positioning) are effective 75– 80% of the time in eliminating aspiration of at least one bolus volume introduced by MBS [17, 62, 63]. Rehabilitation therapy procedures are designed to improve the range of motion (ROM) of oral and pharyngeal structures and sensory-motor integration. These therapy procedures include therapy exercises and swallow maneuvers [17, 63]. Therapy exercises are exercises that strengthen the tongue to increase the oral tongue and tongue base volume and function. There are also ROM exercises that should improve bolus transit and clearance from the oral cavity and pharynx [17, 63]. So-called Shaker exercises diminish upper esophageal sphincter (UES)related dysphagia by improving the duration and width of the UES opening [64, 65]. Swallow maneuvers such as supraglottic swallow, super-supraglottic swallow, Mendelsohn maneuver, effortful swallow, and tongue hold are voluntary controls that can be used during swallow to change selected aspects of neuromuscular control [17, 63, 64]. Logemann et al. [18] suggests that function at 6 months after treatment predicts long-term function. It is therefore reasonable to maximize swallowing recovery by 6 months after CRT. Waters et al. [66] also showed less benefit to delayed swallowing therapy. A few results from literature are given in Table 5.

Cervical vertebra

145 Cornu of the thyroid cartilage


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146

patients treated with concomitant CRT ± amifostine, given before each chemotherapy cycle and less than 45 min before RT, less acute nonhematologic (mucositis, Fig. 3 Delineation of swallowing structures on CT slices. (Color figure online)

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xerostomia, dysphagia, loss of taste, and dermatitis) and hematologic side effects and less chronic side effects like radiation-induced xerostomia are observed [69–71].

28 96 53

All stages, nasopharyngeal cancer, IMRT

All stages, HNC, IMRT ± CT


Late dysphagia/QOL

Acute grade 3 dysphagia/ feeding tube duration

EORTC QOL

Aspiration/stricture MBS

FEES variables

(3) Reduced laryngeal elevation, epiglottic inversion

(2) Strictures

(1) Aspiration VFS

Total FEES score

Objective

Mean doses and V50 of MPC/IPC/ supraglottic larynx

V50 larynx, V50 IPC

Mean pharyngoesophageal dose

DVH of supraglottic region

(4) mean PC dose, mean esophageal dose,

(3) mean PC dose, mean GSL dose

(2) PC V70 [ 50%

(1) Mean SPC & MPC doses [ 60 Gy, PC V65 [ 50%, GSL V50 [ 50%

SPC dose

Mean SPC dose

(2) Doses to the aryepiglottic folds

Mean SPC-MPC doses: steep doseeffect relationship (1) Doses to the aryepiglottic folds, false vocal cords, lateral pharyngeal walls

DVH parameters

Dirix et al. [91]

Caglar et al. [76]

Fua et al. [90]

Jensen et al. [51]

Feng et al. [77, 78]

Teguh et al. [20]

Teguh et al. [54]

Dornfeld et al. [89]

Levendag et al. [66]

Refs.

HNC head and neck cancer, RT radiotherapy, CT chemotherapy, IMRT intensity-modulated radiotherapy, QOL quality of life, EORTC European Organization for Research and Treatment of Cancer, PC pharyngeal constrictor muscles (S superior, M middle, I inferior), GSL glottic supraglottic larynx, PEG percutaneous endoscopic gastrostomy, VFS videofluoroscopy, MBS modified barium swallow, FEES functional endoscopic evaluation of swallowing, DVH dose volume histogram

35

Advanced stage, pharynx cancer, RT

(4) Worsening patient-reported liquid swallowing

(1) Worsening patient-reported solid swallowing and observer-rated swallowing scores

Swallowing-related QOL

132

36

Swallowing-related QOL

(2) Weight loss

Severe grade 3–4 dysphagia/ dysphagia QOL (1) Patient report diet and PEG tube persistence at 1 year

Subjective

67 (24)

Stage III–IV, oropharyngeal, nasopharyngeal cancer, CT IMRT

All stages, oropharyngeal cancer, (CT) RT (IMRT) All stages, oropharyngeal, nasopharyngeal cancer, (CT) RT (IMRT)

81

All stages, oropharyngeal cancer, RT (IMRT), chemo Locally advanced HNC, (CT) IMRT 27

N

Tumor stage/site/therapy

Table 7 Correlation between subjective and objective swallowing function, QOL, and DVH parameters

N. Platteaux et al.: Dysphagia in Chemoradiotherapy Patients 147

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N. Platteaux et al.: Dysphagia in Chemoradiotherapy Patients b Fig. 4 Plan of patient with laryngeal cancer cT3N0 treated with

IMRT. Delineation of following structures a tongue base (blue), clinical and planning target volume (CTV and PTV) of elective nodes (red), superior pharyngeal muscles (light blue), submandibular glands (yellow, left; orange, right). b Gross tumour volume (GTV) (red), CTV boost (red) and PTV boost (orange), CTV and PTV of elective nodes (red), inferior constrictor pharyngeus (green) lying in the high dose region ([65 Gy). c PTV boost (orange), CTV and PTV of elective nodes (red–red), m. cricopharyngeus (blue) lying in the high dose region 70 Gy. (Color figure online)

alleviate dysphagia so they should be carefully evaluated in prospective clinical trials. Radiation Modifications

However, the risk of tumor cell protection by amifostine is an issue that needs to be addressed [72]. Currently there is no good level I evidence to suggest that radioprotectors can

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As we know from the literature, there is a relationship between xerostomia and dysphagia after CRT for HNC [22]. The reduction of xerostomia by preserving the salivary gland function can possibly decrease dysphagia. This can be done by using parotid gland-sparing conformal RT or by using IMRT [73, 74]. IMRT modulates the intensity of the radiation beam to decrease the doses to normal structures without compromising the doses to the target. A parotid gland mean dose of 26 Gy or less should be the goal in order to spare gland function and reduce xerostomia and dysphagia [75]. We also know from the literature that dysphagiaaspiration-related structures (DARS), damage to which causes dysphagia and aspiration, are the superior, middle, and inferior pharyngeal constrictor muscles (scm, mcm, icm), cricopharyngeal muscles, esophagus, the glottic larynx, and the supraglottic larynx [56, 68, 76] (Table 6; Fig. 3). IMRT can be used to reduce the doses to DARS by applying dose constraints to them in an attempt to decrease dysphagia [74, 77, 78]. Numerous retrospective studies show a correlation between either subjective or objective assessment of dysphagia and dose volume parameters of anatomic swallowing structures (Table 7). These correlations suggest the reduction of the mean doses and the volumes of the DARS structures that receive 50 Gy or more (V50) in an attempt to reduce swallowing difficulties [51, 68, 76–78]. Partial sparing of the pharyngeal constrictors is expected to confer a benefit if primary distal motor or sensory neural deficits and primary muscle dysfunction play a role in dysphagia [56]. Another way to decrease dysphagia is by more selective delineation of elective nodal volumes. To spare the parotid gland we can start to delineate the elective neck nodes of level II at the contralateral, uninvolved neck on the subdigastric level. We know from the literature that there are no recurrences in these nodes in selected patients [79]. This technique leads to a decrease in xerostomia which has an impact on swallowing. We can also delineate only the


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Table 8 Studies on pretreatment swallowing exercises Tumor stage/site

Therapy

N

Exercises

Results

Advanced stage, oropharynx, hypopharynx, larynx cancer

CRT

18 Mendelsohn maneuver, tongue hold, Improvement in postCarroll et al. [64] tongue resistance, effortful swallow, treatment function on VFS Shaker exercises

T2-T4, oropharynx, hypopharynx, RT/CRT 37 Pretreatment swallowing exercises larynx cancer

Improvement in QOL

Refs.

Kulbersh et al. [39]

CRT chemoradiotherapy, RT radiotherapy, QOL quality of life, VFS videofluoroscopy

lateral retropharyngeal neck nodes (medial from carotid artery and lateral to the longus colli and capitis muscles) while sparing the medial ones. The lateral retropharyngeal neck nodes are involved mostly in metastasis sites, except for the posterior pharyngeal wall where the medial nodes also are involved [79–81]. These modifications can facilitate partial sparing of the pharyngeal constrictors and the upper parts of the glottic and supraglottic regions by using IMRT [77–79, 81]. Not only better definition of the elective nodal volumes but also reduction of the PTV margins can have an impact on the doses to the swallowing structures. Nowadays, the use of online imaging and correction of setup deviations can lead to a reduction of the PTV margins from 5 to 3 mm [78]. Knowing the correlation between the doses to swallowing structures and dysphagia and presuming the highest relapse rates in the therapeutic target volumes, we hypothesize that we can reduce the doses to the elective nodal volumes. A Belgian phase III multicenter trial that randomizes HNC patients to receive 40 or 50 Gy to the elective nodal volumes is ongoing. This trial aims to decrease the severity and rate of swallowing disturbances without compromising locoregional control (Fig. 4). Being aware that sparing swallowing structures leads to steeper dose falloff near the target in the vicinity of these structures, we hope to reach the same locoregional disease control [56]. Exercises Exercise programs are designed to improve swallow physiology and possibly prevent or decrease the severity of swallowing disorders before they develop. These exercises were easily learned by the patients through instructions from the speech pathologists [17]. ROM exercises and resistance exercises are available for the tongue, lips, larynx, and hyoid-related structures. The most frequently performed pretreatment swallowing exercises are the Mendelsohn maneuver, tongue hold, tongue resistance, effortful swallow, and Shaker exercise. These exercises are performed five times a day and are started 2 weeks before RT [39]. The literature has few studies that

show an improvement in post-treatment swallowing function and QOL from performing pretreatment swallowing exercises (Table 8). Avoidance of nothing-by-mouth periods can help to diminish difficulty swallowing after treatment. Patients should be encouraged to swallow throughout the course of their RT or CRT in an attempt to prevent long-term deterioration in swallowing function [18, 27, 82].

Conclusion Dysphagia is a common and serious side effect in HNC patients. It can exist before treatment due to tumor site and stage and/or be a sequel of treatment strategies such as surgery and chemoradiotherapy. It has a significant impact on the QOL because eating is impaired and this has a major impact on social well-being. There are subjective and objective scoring systems to measure dysphagia severity and its impact on QOL. Treatment of swallowing disorders by compensatory and rehabilitation treatment procedures is rarely effective, thus prevention is paramount. Preventing or diminishing dysphagia can be achieved by treatment modification by using IMRT to try to spare or decrease the doses to the dysphagia-aspiration-related structures and the salivary glands without compromising locoregional disease control. Other ways to prevent or diminish dysphagia can be adding radioprotectors or performing exercises before RT. Diminishing dysphagia by these techniques could potentially ameliorate the QOL of HNC patients. However, considerable research remains to be done. Acknowledgments This work was supported by grants from the Flemish League Against Cancer (VLK) and the Clinical Research Fund (KOF) from the University Hospitals Leuven. Piet Dirix is a research assistant (aspirant) of the Research Foundation-Flandres (FWO).

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Nele Platteaux MD Piet Dirix MD Eddy Dejaeger MD, PhD Sandra Nuyts MD, PhD