PERSPECTIVE

published: 21 May 2019

doi: 10.3389/fonc.2019.00401

Late Effects of Organ Preservation

Treatment on Swallowing and Voice;
Presentation, Assessment, and
Screening
J. M. Patterson 1,2*
1
Institute for Health and Society, Newcastle University, Newcastle upon Tyne, United Kingdom, 2 Speech and Language
Therapy Department, City Hospitals Sunderland Foundation Trust, Sunderland, United Kingdom

The prevalence of head and neck cancer (HNC) survivors is on the rise. Treatments
for HNC can have a major deleterious impact on functions such as swallowing and
voice. Poor functional outcomes are strongly correlated with distress, low quality of
life, difficulties returning to work and socializing. Furthermore, dysphagia can have
serious medical consequences such as malnutrition, dehydration, and pneumonia.
A conservative estimate of the percentage of survivors living with dysphagia in the
long-term is between 50 and 60%. Evidence is emerging that functions can worsen
over time, sometimes several years following treatment due to radiation-associated
fibrosis, neuropathy, intractable edema, and atrophy. Muscles lose their strength,
Edited by: pliability, stamina, and range, speed, precision, and initiation of movements necessary
Andreas Dietz,
Leipzig University, Germany
for swallowing and voice functions. Late treatment effects can go unrecognized, and
Reviewed by:
may only be identified when there is a medical complication such as hospitalization for
Susanne Wiegand, aspiration pneumonia. In the routine healthcare setting methods of evaluation include
Leipzig University, Germany
a detailed case history, a thorough clinical examination and instrumental assessments.
Christiane Hey,
Goethe-Universität Frankfurt, Interventions for late treatment effects are limited and it is imperative that patients at
Germany risk are identified as early as possible. This paper considers the role of screening tests in
*Correspondence: monitoring swallowing and detecting aspiration in the long-term. Further work is indicated
J. M. Patterson
joanne.patterson@ncl.ac.uk
for addressing this pressing and increasingly common clinical problem.
Keywords: head and neck cancer, late radiation, function, dysphagia, aspiration, voice, assessment, screening
Specialty section:
This article was submitted to
Head and Neck Cancer,
a section of the journal
INTRODUCTION
Frontiers in Oncology
The prevalence of head and neck cancer (HNC) survivors is on the increase, likely due
Received: 30 January 2019 to improvements in diagnostic technologies, treatment techniques, and a rising number of
Accepted: 29 April 2019
HPV-related oropharyngeal cancers, with patients presenting at a younger age with good survival
Published: 21 May 2019
outcome (1). HNC treatments can result in a multitude of side effects resulting in poor
Citation: function. Post-treatment swallowing and voice difficulties are strongly related to psychosocial
Patterson JM (2019) Late Effects of
problems, poorer quality of life, anxiety, and low mood (2, 3). In addition, dysphagia can pose a
Organ Preservation Treatment on
Swallowing and Voice; Presentation,
serious medical threat, being associated with malnutrition, dehydration, and possibly pneumonia.
Assessment, and Screening. Survivors may therefore live for a long time with significant symptom burden, which can increase
Front. Oncol. 9:401. in severity over time. This paper reports on the presentation, assessment, and potential screening
doi: 10.3389/fonc.2019.00401 tests for late treatment effects on swallowing and voice.

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Patterson Late Radiation Effects on Swallowing and Voice3

THE COMPLEXITY OF SWALLOWING AND poorer quality of life, and is a top priority concern for HNC
VOICE survivors (2, 11, 12)

Swallowing and voice are highly coordinated, specialized Prevalence of Late Effects Dysphagia
functions involving over 25 pairs of muscles under both Little information is published on swallowing outcomes beyond
voluntary and involuntary control. Swallowing is a finely tuned 2 years. In our longitudinal study (n = 146 recruited pre-
process, primarily because the oropharynx is a shared passageway treatment), aspiration rates remained stable between one and 6
for swallowing and respiration. It needs to be executed safely, years following chemoradiotherapy (22–25%), with one half of
avoiding spillage into the airway, and efficiently, to ensure these patients having silent aspiration (13). At 1 year, two patients
adequate nourishment and hydration. Voice is produced by air had a laryngectomy for a dysfunctional larynx and four had a
passing through the vocal folds, causing the edges to vibrate tracheostomy due to airway compromise. By 6 years, five further
rapidly. This sound is amplified by resonating cavities in the patients had a laryngectomy for a dysfunctional larynx (13). An
vocal tract, giving it a distinctive quality. The active articulators Australian study reported a decline in swallowing efficiency over
(tongue, lips and soft palate) modify the voiced sound into speech the same time frame (14). The RTOG 91–11 5 year follow up
via quick and precise movements. identified severe dysphagia in a third of the retained sample (15).
SEER data reported a 49% rate of persistent dysphagia (16, 17),
with older patients following non-surgical treatment being most
LATE TREATMENT EFFECTS ON at risk (18, 19).
FUNCTION
Dysphagia Associated Risk
Surgical treatment for HNC may result in functional impairment, Aspiration is a medical concern as it can lead to repeated
dependent on factors such as tumor site, volume resected, chest infections, poor pulmonary function, and life-threatening
reconstruction, and the subsequent level of edema, scarring, aspiration pneumonia (20). In our 6 year follow up cohort, 28%
and atrophy (4). Radiotherapy can create significant dysfunction reported at least one chest infection, with an increased risk ratio
both acutely and progressively also termed “late effects.” Acute of 6.25 [p = 0.03 CI 1.1–35.7] for aspirators (13). Seven percent
radiotherapy side effects usually include pain, mucosititis, edema, of those initially diagnosed with oropharyngeal cancer had a non-
and xerostomia. For some, this results in mild or short-term functioning larynx, requiring complex, and major reconstructive
dysphagia and dysphonia, resolving by 3 months. This group are surgery (13). SEER data suggests the incidence of aspiration
likely to return to their normal diet with minor limitations. This pneumonia in HNC is 8.7% (95% CI: 8.2–9.1) (17) and it is
is a typical pattern for those treated by low dose radiotherapy estimated that over 80% require hospital admission, half of whom
(2, 5), but may be achieved by a small percentage of patients with transfer to intensive care (20). Case series and cross-sectional
advanced disease treated by intensity-modulated radiotherapy data report alarmingly high rates of aspiration-related deaths
(IMRT) (6). (21–23). For example, the 30-day mortality rate in a series of
nasopharyngeal cancer patients was 51% (24). It is crucial that
we identify those at risk of developing aspiration pneumonia as
DYSPHAGIA early as possible.

Evidence relating to the long-term impact of treatment DYSPHONIA

on swallowing is emerging, with a number of potential
patterns described by Christianen (5). Some patients experience The prevalence of late voice problems are not well-documented.
progressive deterioration in the months and years following Small studies suggest deterioration in patient reports and clinical
treatment, whereas others may have a sudden onset of severe tests of voice up to 7 years post-treatment (25, 26). However,
dysphagia. Causes of these differing trajectories are not well- patients treated with IMRT appear to have better outcomes than
understood. Chronic edema and increased fibroblast formation those treated with conventional radiotherapy, in the long-term
are responsible for the overproduction of collagen, leading (3). A small percentage of patients may require a tracheostomy
to scarring, and fibrosis (7). Consequently, tissues lose their or laryngectomy, significantly altering voice quality (13).
elasticity and movements for adequate functioning are restricted.
Atrophy can alter oropharyngeal anatomical relationships and ASSESSMENT
reduce muscle strength. Furthermore, sensory impairment can
blunt the cough response, should food, or drink enter the airway. Clinical Swallowing and Voice Assessment
Lower cranial nerve palsies (CN IX, X, and XII) have been In the first instance, patients presenting with new symptoms,
noted, probably due to compression or direct nerve damage or deterioration in function should have recurrent or primary
(8). Mandible osteoradionecrosis is a further late complication, disease excluded as a possible cause. A comprehensive clinical
resulting in exposed, non-healing bone (9). This is strongly history of late effects will include details on patients’ perceptions
associated with severe, chronic dysphagia (OR: 4.6, 95% CI: of the onset, trajectory, and symptoms. Clinical information
2.1–10.3), making chewing painful and swallowing less efficient such as co-morbidities, reflux, chest status, oral intake, oral
(10). Dysphagia is strongly associated with psychological distress, hygiene, and weight should be gathered. For older survivors,

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Patterson Late Radiation Effects on Swallowing and Voice3

expected, age-related functional decline i.e., loss of muscle mass Fiberoptic Endoscopic Evaluation of Swallowing (FEES R ) are the
and elasticity, reduced saliva production should be taken into most commonly used instrumental swallow assessments (43). VF
account. An examination will typically include and oral and is a recorded radiographic study of the swallowing structures,
oromotor assessment, palpation of laryngeal structures, voice, their movement and co-ordination. It is usually conducted in the
and speech quality assessment and an observation of eating lateral and anterior-posterior plane. Test boluses are mixed with
and drinking. radio-opaque material to enable visualization. FEES R allows a
There are no agreed standards for long-term voice assessment, direct view of nasolaryngopharyngeal anatomy and physiology
although review papers call for structured, standardized followed by an assessment of swallowing function (44, 45). A
protocols, with measurements taken at baseline and long- range of fluid and food can be given, without requiring radio
term (27, 28). These typically include clinician rated scales, opaque contrast. This may be combined with a voice assessment,
intelligibility rating, and acoustic measures (29). Examples of which also requires a stroboscopic light source to fully assess
scales and measures used in HNC are given in Table 1. vocal fold function and mucosal wave pattern.
The presentation of late treatment effects on instrumental
Patient Reported Outcome Measures assessment constitutes a number of features such as;
Measures of function in HNC should include patient-
reported outcomes both pre- and post-treatment. Swallowing • Excessive external lymphedema, with underlying
questionnaires and symptom report tools capture patients’ tissue hardening.
perspectives of dysphagia, but they are only weakly correlated • Internal edema in critical structures and spaces for functioning
with swallowing impairment and aspiration, the relationship e.g., true vocal folds, epiglottis, pyriform sinuses.
being particularly poor beyond 12 months post-treatment. • Thickening of structures e.g., pharyngo-epiglottic folds
They are therefore not interchangeable with clinical creating a shelf-like barrier to bolus flow.
assessment (36, 37). The most commonly reported swallowing • Muscle thinning e.g., atrophied tongue base and
questionnaires used in HNC care include M.D. Anderson pharyngeal wall.
Dysphagia Inventory (38), SWAL-QOL (39), Sydney Swallow • Palsies of the tongue, vocal fold, soft palate.
Questionnaire (40), and the EAT-10 (41). Examples of patient • Excessively dry laryngopharyngeal muscosa.
reported voice questionnaires include Voice Handicap Index The pathophysiology, safety, and efficiency of swallowing can be
(30), Voice Symptom Scale (32), and the Vocal Performance analyzed and measured using rating scales, a selection of which
Questionnaire (42). are presented in Table 2.
Instrumental Assessment
Instrumental examination(s) is indicated for a thorough MONITORING
investigation of pathophysiology. Videofluoroscopy (VF) and
Cancer surveillance reviews are usually offered up to 5 years
following treatment (1). Swallowing and voice function may
TABLE 1 | Examples of voice outcome measures used in HNC.

Voice measures Description

TABLE 2 | Examples of swallowing rating scales for FEES® and VF.

Patient reported measures Voice handicap index VHI-10 (30). 10 items on 5
point scale
Rating scale Assessment
Voice-related quality of life V-RQOL (31). 10 items, 5
point scale and an overall score FEES VF
Voice symptom scale VoiSS (32). 30 items 3 Penetration Aspiration Scale (49) Yes Yes
subscales impairment-related, emotional, and 8-point scale describing laryngeal penetration and
physical symptoms aspiration and sensory response
Vocal performance questionnaire VPQ (33). 12 The MBS Impairment Scale (50) No Yes
items, 5 point ordinal scale 16-item scale of swallow physiology and residue
Clinician rated measures GRBAS (34) roughness, breathiness, asthenia, Dynamic Image Grade of Swallowing Toxicity No Yes
strain. 4 point scale for each area and overall grade (DIGEST) (51)
Consensus Auditory-Perceptual Evaluation of Voice Summary score for swallow safety and efficiency
(CAPE V) (35). Overall severity, roughness, Oropharyngeal swallow efficiency (52) No Yes
breathiness, strain, pitch, loudness. 6 vocal Combined measure of residue and aspiration
attributes measured on a visual analog scale
Patterson’s Oedema Scale (53) Yes No
Acoustic and aerodynamic Fundamental frequency-vocal fold vibration 4-point scale of laryngopharyngeal structures and
measures frequency spaces
Pertubation-Jitter: irregularities in vocal fold The Boston Residue and Clearance Scale (54) Yes No
frequency, Shimmer: amplitude irregularities. 11-point scale scoring amount, location and
Harmonic to noise ratio-ratio of sound frequencies clearance of residue
to noise energy in the voice Yale Pharyngeal Residue Severity Rating Scale (55), Yes No
Maximum phonation time-glottic efficiency 5-point scale on amount of pharyngeal residue

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Patterson Late Radiation Effects on Swallowing and Voice3

not be routinely tested, unless patients report a problem. One health care costs (57). No such programme exists for HNC
preliminary study proposes four questions that could be used survivors, but the following section reviews candidate screening
as part of a clinical assessment to detect dysphagia i.e., Do you tests for this group.
have difficulties: (1) drinking? (2) eating? (3) swallowing? (4)
Do you cough when eating/drinking? When three or more of Water Swallow Test
these questions were answered affirmatory, the likelihood of A water swallow test (WST) is the most commonly reported
aspiration observed on VF increased (46). Given afore described aspiration screening tool (58). Two systematic reviews report
mortality risks, and the preponderance of sub-clinical aspiration, a range of protocols, predominantly for testing neurological
the immediate clinical challenge is identifying those at risk dysphagia (56, 58–61). Using prescribed amounts of water and
of developing pneumonia, using reliable, repeatable, and cost- recording coughing or a wet voice gave the most accurate
effective tests. results for identifying aspiration (56, 62). Consecutive sips
with large volumes had the best sensitivity (91% CI 89,
Identifying Patients at Risk of Aspiration 93%) while, single sips of water were better at ruling out
Pneumonia aspiration (90% CI 86, 93%) (58). We have reported on
Healthy adults can experience trace aspiration without the timed 100 mLs WST in HNC, recording swallowing
adverse consequences, and not every HNC survivor with performance overtime, as well as a screening test for aspiration
aspiration appears to develop pneumonia. In a series of partial (63). This test was acceptable for identifying aspiration in
laryngectomy patients, 65% were identified with aspiration, early post-operative or chemoradiotherapy patient groups
but without x-ray evidence of pneumonia or infection (47). (63, 64), but its reliability for late effects patients has not
There may be additional factors to be taken into account, been investigated.
when weighing up pneumonia risk. For example, older
adults in a care facility developed pneumonia only when Cough Reflex Test
aspiration co-occurred with poor oral hygiene, dependence This test assesses the cough reflex by introducing a tussive agent
on others for eating, poor dentition and co-morbidities such as citric acid via a facemask and nebulizer and observing
(48). Most HNC studies have explored patient and disease for a responsive cough (65). The outcome is judged on reflexive
characteristics and treatment type as predictors of pneumonia, cough strength and has been used as screening test in Stroke (65),
with no clear pattern emerging (see Table 3). Further work Parkinson’s Disease (66), and post-extubation (67). The absence
on identifying predictor variables for aspiration pneumonia of a cough reflex in neurological patients has a sensitivity of 69%
to be used as part of an algorithm for monitoring purposes (95% CI 55, 81%) and specificity of 71% (95% CI 63, 77%) to
is required. detect aspiration (65). No studies have reported on its use in
HNC, but given that late effects can result in silent aspiration,
Screening Assessments further investigation is warranted.
Instrumental assessments provide a more objective way of
measuring swallowing, but have limited access and high cost, Pulmonary Function
due to the need for specialist equipment and personnel (56). In Many patients elect to eat and drink despite experiencing
Stroke care, early detection of dysphagia by screening reduces aspiration. Assessments to monitor pulmonary function
pulmonary complications, length of hospital stay, and overall such as spirometry and flow-volume loops may be

TABLE 3 | HNC studies reporting predictors of (1) aspiration pneumonia* (2) aspiration pneumonia-related death** 6= Wang et al. (24) only included patients with a
diagnosis of aspiration pneumonia.

Author N T site Tx % AP Predictors of AP Non-predictive

Hunter et al. (69) 72 OPSCC C-IMRT 22% T-stage, patient report, aspiration on CTCAE
VF*
Xu et al. (20) 3513 Mixed Surgery and RT, CRT, RT 16% 1Y 24% 5Y Hypopharynx or NPC, gender, age, Surgery, stage, type of CT, type
co-morbidity, primary RT, care at of RT
non-teaching hospital*
Kawai et al. (70) 305 Mixed CRT 21% Alcohol, sleeping pills, oral hygiene,
hypoalbumemia, presence of other
cancer*
Madan et al. (71) 85 Mixed Surgery & RT, CRT, RT 60% Pharynx cancer, T stage** Age, gender, tx modality,
smoking, co-morbidity, treatment
intent, baseline swallowing
Wang et al. (24) 113 NPC RT +/– CT IMRT 100% 6= age, smoking, weight loss, lower CN
palsy**
O’Hare et al. (72) 206 Mixed RT +/– CT 15% Larynx cancer, dose to cricopharynx** Gender, chemotherapy

NPC, nasopharynx cancer; OPSCC, oropharynx cancer; T, tumor; Tx, treatment; CRT, chemoradiotherapy; RT, radiotherapy; CT, chemotherapy.

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Patterson Late Radiation Effects on Swallowing and Voice3

indicated together with close collaboration with Respiratory • Clinical care pathways for identifying and monitoring late
Physicians to develop mechanisms to detect deterioration in functional effects.
chest status.

CONCLUSION
FUTURE DIRECTIONS
The number of HNC survivors is rising and this trend
There are a number of current trials investigating treatment
is set to continue. Late functional effects of treatment is
modulation to prevent or reduce toxicities without a common, distressing, and potentially life-threatening
compromising survival (68). In the meantime, further work on problem. Assessment and monitoring of HNC survivors
late functional effects is indicated in the following areas. in the long-term is an important step for identifying
• Information on the long-term outcomes for voice and speech. those at risk, as early as possible. Reliable, acceptable, and
• Identification of predictors of significant fibrosis and repeatable screening assessments are needed to address this
exploration of preventative interventions. growing problem.
• Identification of predictor variables for pneumonia in patients
who aspirate. AUTHOR CONTRIBUTIONS
• Reliable screening tests for identifying aspiration and
dysphagia for long-term follow up. The author confirms being the sole contributor of this work and
• Accurate patient information regarding late treatment effects. has approved it for publication.

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68. Patterson JM, Brady GC, JRoe WG. Research into the prevention be construed as a potential conflict of interest.
and rehabilitation of dysphagia in head and neck cancer: a UK
perspective. Curr Opin Otolaryngol Head Neck Surg. (2016) 24:208–14. Copyright © 2019 Patterson. This is an open-access article distributed under the
doi: 10.1097/MOO.0000000000000260 terms of the Creative Commons Attribution License (CC BY). The use, distribution
69. Hunter KU, Lee OE, Lyden TH, Haxer MJ, Feng FY, Schipper M, et al. or reproduction in other forums is permitted, provided the original author(s) and
Aspiration pneumonia after chemo-intensity-modulated radiation therapy of the copyright owner(s) are credited and that the original publication in this journal
oropharyngeal carcinoma and its clinical and dysphagia-related predictors. is cited, in accordance with accepted academic practice. No use, distribution or
Head Neck. (2014) 36:120–5. doi: 10.1002/hed.23275 reproduction is permitted which does not comply with these terms.

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