BioMed Research International

BioMed Research International / 2016 / Article

Review Article | Open Access

Volume 2016 |Article ID 6086894 | https://doi.org/10.1155/2016/6086894

B. J. Heijnen, R. Speyer, B. Kertscher, R. Cordier, K. W. J. Koetsenruijter, K. Swan, H. Bogaardt, "Dysphagia, Speech, Voice, and Trismus following Radiotherapy and/or Chemotherapy in Patients with Head and Neck Carcinoma: Review of the Literature", BioMed Research International, vol. 2016, Article ID 6086894, 24 pages, 2016. https://doi.org/10.1155/2016/6086894

Dysphagia, Speech, Voice, and Trismus following Radiotherapy and/or Chemotherapy in Patients with Head and Neck Carcinoma: Review of the Literature

Academic Editor: Kenneth W. Altman
Received27 May 2016
Accepted01 Aug 2016
Published19 Sep 2016

Abstract

Introduction. Patients with head and neck cancer suffer from various impairments due to the primary illness, as well as secondary consequences of the oncological treatment. This systematic review describes the effects of radiotherapy and/or chemotherapy on the functions of the upper aerodigestive tract in patients with head and neck cancer. Methods. A systematic literature search was performed by two independent reviewers using the electronic databases PubMed and Embase. All dates up to May 2016 were included. Results. Of the 947 abstracts, sixty articles met the inclusion criteria and described one or more aspects of the sequelae of radiotherapy and/or chemotherapy. Forty studies described swallowing-related problems, 24 described voice-related problems, seven described trismus, and 25 studies described general quality of life. Only 14 articles reported that speech pathologists conducted the interventions, of which only six articles described in detail what the interventions involved. Conclusion. In general, voice quality improved following intervention, whereas quality of life, dysphagia, and oral intake deteriorated during and after treatment. However, as a consequence of the diversity in treatment protocols and patient characteristics, the conclusions of most studies cannot be easily generalised. Further research on the effects of oncological interventions on the upper aerodigestive tract is needed.

1. Introduction

Head and neck oncological patients suffer from various functional, physical, and emotional impairments due to both the primary illness and the secondary consequences of the tumor treatment [1]. The oncological treatment of head and neck tumors depends on the location and the stage of the tumor, as well as the treatment preferences of the individual patient. Head and neck oncological treatment can include surgery, radiotherapy, chemotherapy, or combinations of these. The impact of head and neck oncological treatments on the anatomical structures, organ function, and the quality of life (QoL) should not be underestimated [2]. For instance, the implications of loss of function for people treated nonsurgically for head and neck cancer (HNC) and its detrimental effects on functioning and QoL are well documented [3].

In order to assist people with dysphagia to adjust to and live successfully with the sequelae of the primary condition, speech pathologists managing this caseload need to ensure posttreatment services are available [4] that address not only the physical but also the emotional and psychosocial needs. A qualitative study by Nund et al. [5] exploring dysphagia management by speech pathologists suggests that care givers generally feel ill-prepared for their role. Furthermore, this study suggests that clinicians should provide adequate and timely training and support to carers. Furthermore, Krisciunas et al. [6] concluded that within speech pathology there is no standardised therapy for HNC patients and scant evidence to support any particular protocol. As a result, institutions and individual speech pathologists need to develop their own protocols based on “standard” practices or anecdotal evidence.

Evidence-based practice (EBP) is hailed to be paramount in the practice of speech pathology [7]. The American Speech-Language-Hearing Association (ASHA) defines evidence-based practice as “…an approach in which current, high-quality research evidence is integrated with practitioner expertise and client preferences and values, into the process of making clinical decisions” [8]. Essentially, EBP involves moving the foundation for clinical decisions from clinical protocols centered solely on expert opinion to the integration of clinical expertise, the best current research evidence, and individual client values. To facilitate EBP in healthcare, clinical practice guidelines can be developed to summarise clinically relevant evidence [9].

Several reviews have been published about the outcomes after radiotherapy and/or chemotherapy in HNC patients (e.g., Frowen and Perry [10]; Jacobi et al. [11]; van der Molen et al. [12]; Paleri et al. [13]; Roe et al. [14]). Most of the reviews focused on selected functional domains in populations with HNC: health-related QoL [15], swallowing [13, 14, 16], and voice and speech [11]. Only the review by van der Molen et al. [12] covered a wider range of functional outcomes in patients with advanced HNC, including swallowing, mouth opening, nutrition, pain, and QoL. Further, the purpose of some studies was to provide evidence-based clinical guidelines (e.g., Paleri et al. [13]) and they did not perform systematic literature searches in line with the PRISMA guidelines [17]. As such, even though a number of reviews have been published over the last ten years, a comprehensive updated systematic review is needed that includes all functional domains affected by radiotherapy and/or chemotherapy in patients with head and neck carcinoma.

A systematic review was conducted to describe the effects of radiotherapy and/or chemotherapy on functions of the upper aerodigestive tract in patients with HNC and examined the evidence of interventions by speech pathologists.

2. Methods

A systematic literature search was performed by two independent reviewers. The electronic biomedical databases PubMed and Embase were used (search period from start of database until 5 May 2016). The searches were limited to English language publications. In PubMed the MeSH terms larynx or hypopharynx were combined with all MeSH terms related to head and neck neoplasms (Table 1). Next, the results were linked to all MeSH terms for chemotherapy or radiotherapy, after which the outcome was combined with all MeSH terms found for dysfunctions of the upper aerodigestive tract and limited with adults +19 years. The exact syntax of the literature search is presented in Table 1.


Database and search termsLimitsNumber of records

Subject headingsEmbase: (larynx/OR pharynx/OR hypopharynx/) AND (neoplasm/OR larynx disorder/OR pharynx disorder/OR larynx cancer/OR larynx carcinoma/OR pharynx cancer/OR pharynx carcinoma/)
AND (radiotherapy/OR chemotherapy/OR chemoradiotherapy/OR adjuvant therapy/OR drug therapy/)
AND (speech sound disorder OR speech/or speech disorder/OR swallowing/OR dysphagia/OR dysphonia/OR voice disorder/OR aphonia/OR speech intelligibility/OR xerostomia/OR dysarthria/OR esophagus speech/OR larynx prosthesis/OR trismus/OR “quality of life”/)
English201

Subject headingsPubMed: (“Larynx”[Mesh] OR “Pharynx”[Mesh] OR “Hypopharynx”[Mesh]) AND (“Neoplasms”[Mesh] OR “Head and Neck Neoplasms”[Mesh] OR “Neoplasms, Second Primary”[Mesh] OR “Pharyngeal Neoplasms”[Mesh] OR “Oropharyngeal Neoplasms”[Mesh] OR “Tonsillar Neoplasms”[Mesh] OR “Nasopharyngeal Neoplasms”[Mesh] OR “Mouth Neoplasms”[Mesh] OR “Laryngeal Neoplasms”[Mesh] OR “Tongue Neoplasms”[Mesh] OR “Thyroid Neoplasms”[Mesh] OR “Salivary Gland Neoplasms”[Mesh] OR “Jaw Neoplasms”[Mesh] OR “Lip Neoplasms”[Mesh] OR “Thyroid Carcinoma, Anaplastic”[Mesh] OR “Neoplasms, Squamous Cell”[Mesh] OR “Neoplasms, Basal Cell”[Mesh] OR “Otorhinolaryngologic Neoplasms”[Mesh] OR “Hypopharyngeal Neoplasms”[Mesh] OR “Laryngeal Diseases”[Mesh] OR “Pharyngeal Diseases”[Mesh]) AND (“Radiotherapy”[Mesh] OR “Radiotherapy, Adjuvant”[Mesh] OR “Radiotherapy, High-Energy”[Mesh] OR “Radiotherapy, Image-Guided”[Mesh] OR “Radiotherapy, Intensity-Modulated”[Mesh] OR “Radiotherapy, Conformal”[Mesh] OR “Radiotherapy, Computer-Assisted”[Mesh] OR “Radiotherapy Planning, Computer-Assisted”[Mesh] OR “Radiotherapy Dosage”[Mesh] OR “Brachytherapy”[Mesh] OR “Radiosurgery”[Mesh] OR “Radiation Oncology”[Mesh] OR “Dose-Response Relationship, Radiation”[Mesh] OR “Consolidation Chemotherapy”[Mesh] OR “Induction Chemotherapy”[Mesh] OR “Maintenance Chemotherapy”[Mesh] OR “Chemotherapy, Adjuvant”[Mesh] OR “Chemotherapy, Cancer, Regional Perfusion”[Mesh] OR “Drug Therapy”[Mesh] OR “Drug Therapy, Combination”[Mesh] OR “Radiotherapy”[Mesh] OR “Radiation Dosage”[Mesh]) AND (“Articulation Disorders”[Mesh] OR “Speech”[Mesh] OR “Speech Sound Disorder”[Mesh] OR “Speech, Esophageal”[Mesh] OR “Speech, Alaryngeal”[Mesh] OR “Speech Intelligibility”[Mesh] OR “Speech Disorders”[Mesh] OR “Deglutition Disorders”[Mesh] OR “Deglutition”[Mesh] OR “Dysphonia” [Mesh] or “Voice Disorders” [Mesh] or “Hoarseness” [Mesh] or “Aphonia” [Mesh] OR “Xerostomia”[Mesh] OR “Dysarthria”[Mesh] OR “Larynx, Artificial”[Mesh] OR “Speech, Esophageal”[Mesh] OR “Trismus”[Mesh] OR “Quality of Life”[Mesh])Adult: 19+ years
English
304

Free textEmbase: (larynx or pharynx OR hypopharyn OR laryngo OR larynge) AND (cancer OR cancers OR neoplasm OR tumour OR tumor OR tumors OR carcinoma) AND (radiation OR radiotherap OR chemotherap OR adjuvant therap OR radiochemotherap) AND (deglut OR swallow OR dysphag OR speech OR voic OR hoarse OR aphon OR rough OR articulat OR dysphon OR (quality AND life) OR xerostom OR dysarthr OR anarthr OR trismus)Publication date: last year397

Free textPubMed: As per Embase Free TextPublication date:
from 2015/05/05 to 2016/05/05
148

In Embase the thesaurus terms larynx or hypopharynx were linked to neoplasm and radiotherapy or chemotherapy. Next, the search outcome was combined with the following terms: dysphagia, speech, speech disorder, voice, dysphonia, xerostomia, quality of life, dysarthria, or trismus (see Table 1).

To identify the most recent publications, the search was complemented by free text words in PubMed and Embase (for the period after April 2015 until May 2016). Truncation symbols and wildcards were used to search for variant forms of words or word extensions: Laryn, pharyn or hypopharyn were combined with cancer, neoplasm, tumour or carcinoma. Furthermore, these free text words were combined with radiation, radiotherap, chemotherap, adjuvant therap or radiochemotherap and, finally, combined with deglut, swallow, dysphag, speech, voic, articulat, dysphon, quality of life, xerostom, dysarthr or anarthr.

Only articles presenting both pre- and postintervention data of the upper aerodigestive tract functions of the participants were included. Review articles and studies with a population sample of less than 20 patients were excluded, as well as experiments on animals or articles not published in English. Furthermore, studies published before 1990, case reports, expert opinions, and articles describing combinations of therapy including surgical interventions were excluded.

Final decisions on inclusion were made based on the original articles by consensus between two expert reviewers in accordance with the PRISMA statement [17]. The reference lists of all the included articles were searched for additional literature. Next, the standard quality assessment QualSyst as described by Kmet et al. [18] was performed in order to evaluate the methodological strength and weaknesses of the included studies. All ratings were performed by two independent reviewers. After consensus, studies with poor methodology scores (<50%) were excluded. All included articles were classified according to the Australian National Health and Medical Research Council (NHMRC) Evidence Hierarchy [19]. Data were retrieved from all studies and tabulated; further details on selected speech pathology interventions were summarised separately.

3. Results

Using MeSH or thesaurus terms, 304 articles were located in PubMed and 201 in Embase. Free text word searches resulted in another 148 articles in PubMed and 397 in Embase. The combination of these searches, without overlap, yielded 947 articles. Figure 1 outlines the PRISMA reviewing process according to Moher et al. [20]. Sixty articles met all inclusion criteria.

Table 2 shows the outcomes of the QualSyst critical appraisal tool by Kmet et al. [18]. As all studies had sufficient methodological quality, no further studies were excluded; the overall methodological quality ranged from adequate to good with 0 studies ranked as poor, 3 studies as adequate, 3 studies as good, and 54 studies as strong. Based on the NHMRC Evidence Hierarchy [19], 6 studies were classified as level II evidence and 54 studies as level III evidence.


ReferenceKmet score (%)Methodological qualityNHMRC level of evidence

Aaltonen et al. 2014 [21]25/28 (89%)StrongII
Ackerstaff et al. 2009 [22]22/28 (79%)GoodII
Agarwal et al. 2009 [23]19/24 (79%)GoodIII-2
Agarwal et al. 2011 [45]17/20 (85%)StrongIII-3
Akst et al. 2004 [46]17/20 (85%)StrongIII-3
Al-Mamgani et al. 2012 [24]19/20 (95%)StrongIII-3
Al-Mamgani et al. 2012 [47]21/22 (95%)StrongIII-3
Al-Mamgani et al. 2013 [25]21/22 (95%)StrongIII-3
Al-Mamgani et al. 2015 [26]21/22 (95%)StrongIII-3
Bansal et al. 2004 [27]14/24 (58%)AdequateIII-3
Bibby et al. 2008 [28]18/22 (82%)StrongIII-2
Bottomley et al. 2014 [78]24/28 (86%)StrongII
Buchbinder et al. 1993 [48]14/26 (54%)AdequateIII-1
Caudell et al. 2010 [49]21/22 (95%)StrongIII-3
Christianen et al. 2015 [50]21/22 (95%)StrongIII-3
Cohen et al. 2006 [51]19/20 (95%)StrongIII-3
Dornfeld et al. 2007 [29]17/22 (77%)StrongIII-3
Dijkstra et al. 2007 [52]19/22 (86%)StrongIII-3
Feng et al. 2007 [53]19/22 (86%)StrongIII-3
Feng et al. 2010 [54]20/20 (100%)StrongIII-3
Frowen et al. 2010 [16]22/22 (100%)StrongIII-2
Haderlein et al. 2014 [55]17/20 (85%)StrongIII-3
Hutcheson et al. 2014 [56]18/20 (90%)StrongIII-3
Jacobi et al. 2016 [30]17/18 (94%)StrongIII-3
Karlsson et al. 2015 [31]26/28 (93%)StrongII
Karlsson et al. 2016 [32]18/20 (90%)StrongIII-3
Kazi et al. 2008 [33]17/20 (85%)StrongIII-2
Kerr et al. 2015 [34]19/20 (95%)StrongIII-2
Kotz et al. 2012 [57]24/28 (86%)StrongII
Kraaijenga et al. 2014 [35]19/20 (95%)StrongIII-3
Kumar et al. 2014 [58]19/20 (95%)StrongIII-2
Lazarus et al. 2014 [36]19/20 (95%)StrongIII-3
List et al. 1999 [59]15/18 (83%)StrongIII-3
McLaughlin et al. 2010 [60]19/20 (95%)StrongIII-3
Mittal et al. 2001 [37]16/20 (80%)StrongIII-3
Murry et al. 1998 [61]11/20 (55%)AdequateIII-3
Niedzielska et al. 2010 [38]17/20 (85%)StrongIII-2
Nourissat et al. 2010 [62]23/26 (88%)StrongIII-3
Ottoson et al. 2014 [63]19/22 (86%)StrongIII-3
Pauli et al. 2013 [64]19/22 (86%)StrongIII-3
Pauloski et al. 2006 [65]18/20 (90%)StrongIII-3
Rademaker et al. 2003 [66]17/20 (85%)StrongIII-3
Remmelts et al. 2013 [39]18/20 (90%)StrongIII-3
Salama et al. 2008 [67]17/20 (85%)StrongIII-3
Sanguineti et al. 2014 [40]19/20 (95%)StrongIII-3
Scrimger et al. 2007 [68]18/20 (90%)StrongIII-3
Spector et al. 1999 [41]17/22 (77%)GoodIII-3
Starmer et al. 2014 [69]18/20 (90%)StrongIII-3
Stenson et al. 2010 [70]16/20 (80%)StrongIII-3
Strigari et al. 2010 [71]17/20 (85%)StrongIII-3
Tuomi et al. 2015 [42]18/20 (90%)StrongIII-2
Urdaniz et al. 2005 [77]18/20 (90%)StrongIII-2
Vainshtein et al. 2015 [72]20/24 (83%)StrongIII-3
van der Molen et al. 2011 [73]24/26 (92%)StrongII
van der Molen et al. 2012 [44]16/20 (80%)StrongIII-3
van der Molen et al. 2013 [74]19/20 (95%)StrongIII-3
Verdonck-de Leeuw et al. 1999 [43]18/20 (90%)StrongIII-2
Verdonck-de Leeuw et al. 2014 [79]16/20 (80%)StrongIII-2
Vlacich et al. 2014 [75]18/20 (90%)StrongIII-3
Wilson et al. 2011 [76]18/20 (90%)StrongIII-3

Methodological quality: strong > 80%; good 60–79%; adequate 50–59%; poor < 50%.
NHMRC evidence hierarchy designates the following hierarchy: level I (evidence obtained from a systematic review of all relevant RCTs), level II (evidence obtained from at least one properly designed RCT), level III-1 (evidence obtained from well-designed pseudo-RCTs [alternate allocation or some other method]), level III-2 (evidence obtained from comparative studies with concurrent controls and allocation not randomised [cohort studies], case control studies, or interrupted time series with a control group), level III-3 (evidence obtained from comparative studies with historical control, two or more single-arm studies, or interrupted time series without a parallel control group), and level IV (evidence obtained from case series, either posttest or pretest and posttest).

All 60 studies focused on different functions of the upper aerodigestive tract following radiotherapy and/or chemotherapy for HNC. The following constructs were evaluated across the different studies: communication (voice and speech), functions of the digestive tract (oral intake, weight loss, dysphagia, trismus, xerostomia, and tube dependency), QoL, and overall survival rates.

Table 3 provides a summary of the 60 retrieved observational and intervention studies that met the inclusion criteria. The first column presents the reference of the author(s). The second column represents the number of subjects, the third column represents the etiology of the head and neck malignancies, and the 4th column displays the staging of the malignancies. The 5th column shows whether voice and/or speech, digestive tract, and QoL were studied. The 6th and 7th columns show the evaluation techniques and the treatment, respectively. The 8th column presents the follow-up and the last column describes the author’s key findings.


ReferenceSubjectsCarcinomaStagingTopicEvaluation techniqueTreatment(s)Follow-upKey findings/author’s conclusions

Aaltonen et al. 2014 [21]Glottic = 56 (100%)T1a = 56 (100%)VVideolaryngostroboscopy
Expert rating (GRBAS)
Patient self-rating (VAS) hoarseness and impact on everyday life
Group 1: laser surgery ()
Group 2: RT ()
6, 24 monthsSimilar overall voice quality for both groups. Laser surgery yielded more breathiness compared to RT

Ackerstaff et al.
2009 [22]
Oral cavity = 40 (19%)
Oropharyngeal = 129 (62%)
Hypopharyngeal = 38 (19%)
T3 = 65 (31%)
T4 = 142 (69%)
V
D
QoL
EORTC QLQ-C30
EORTC QLQ-H&N35
Trial-specific questionnaires
Group 1: intra-arterial cisplatin 4 weekly () + RT
Group 2: intravenous cisplatin 3 weekly () + RT
7 weeks; 3 months; 1, 2, 5 yearsBoth groups showed improved oral intake and voice quality, at 1-year follow-up often better compared to baseline

Agarwal et al.
2009 [23]
Glottic = 50 (100%)T1 = 33 (66%)
T2 = 17 (34%)
VVoice analysis
Acoustic parameters: frequency, intensity, perturbation
Patient-reported improvement in voice quality
RT3–6 monthsA trend for improvement in voice quality following RT was found

Agarwal et al.
2011 [45]
Oropharyngeal
Hypopharyngeal
Laryngeal
(No details provided)
T1
T2
T3
T4
(No details provided)
DVideofluoroscopy
PSS-HN
CRT2, 6, 12 monthsSignificant impairment of swallowing was found: most frequently residue and aspiration

Akst et al.
2004 [46]
Oral cavity = 12 (6%)
Base of tongue = 41 (21%)
Tonsil = 41 (21%)
Other oropharyngeal =
15 (8%)
Hypopharyngeal = 34 (17%)
Laryngeal = 50 (26%)
Unknown = 3 (1%)
T1 = 15 (8%)
T2 = 42 (21%)
T3 = 65 (33%)
T4 = 70 (36%)
Unknown = 4 (2%)
DPresence of feeding tube
Presence of tracheotomy
Level of oral diet
CRT3, 6, 12, 24 monthsA majority of patients did not need a tracheotomy but need a feeding tube during treatment. At 1-year follow-up most patients had a (nearly) normal oral intake. Patients with tumor stage IV and age ≥ 60 had prolonged feeding tube use and slower recovery

Al-Mamgani et al.
2012 [24]
Supraglottic = 121 (71%)
Glottic = 49 (29%)
T3 = 170 (100%)V
QoL
EORTC QLQ-C30
EORTC QLQ-H&N35
VHI
Group 1: CRT ()
Group 2: RT ()
2, 4, 6 weeks; 3, 6, 12 monthsAdding chemotherapy to RT did not diminish QoL or voice handicap

Al-Mamgani et al.
2012 [47]
Hypopharyngeal = 176 (100%)T1 = 18 (10%)
T2 = 55 (31%)
T3 = 56 (32%)
T4a = 35 (20%)
T4b = 12 (7%)
D
QoL
Tube dependency
EORTC QLQ-C30
EORTC QLQ-H&N35
Group 1: CRT ()
Group 2: RT ()
2, 4, 6 weeks; 3, 6 months; 1, 2 yearsCRT significantly improved functional outcome. Acute toxicity increased but late radiation side effects did not increase

Al-Mamgani et al.
2013 [25]
Glottic = 1050 (100%)T1a = 551 (52%)
T1b = 168 (16%)
T2a = 209 (20%)
T2b = 122 (12%)
V
QoL
EORTC QLQ-C30
EORTC QLQ-H&N35
VHI
RT4, 6 weeks; 3, 6, 12, 18, 24, 36, 48 monthsExcellent outcome with good QoL and VHI scores

Al-Mamgani et al.
2015 [26]
Glottic = 30 (100%)T1a = 30 (100%)VLaryngoscopy
VHI
Single vocal cord RT4, 6, 12 weeks; 6, 12, 18 monthsSingle vocal cord RT showed better voice quality compared to whole larynx RT

Bansal et al.
2004 [27]
Base of tongue = 20 (44%)
Tonsil = 10 (22%)
Unknown = 15 (33%)
Stage III = 17 (38%)
Stage IV = 23 (51%)
Not reported = 5 (11%)
V
QoL
Acute and late morbidity scoring of skin, oropharyngeal mucosa, salivary glands, larynx, and oesophagus (LENT/SOMA)
EORTC QLQ-C30
RT1, 4 monthsDuring RT a decline in all QoL domains was found. QoL improved after 1 month but did not reach pre-RT levels

Bibby et al.
2008 [28]
Glottic = 30 (100%)T1 = 21 (70%)
T2 = 9 (30%)
V
QoL
Voice analysis
Patient self-rating voice quality
VR-QoL
RT3, 6, 12 monthsAfter RT expert-rated perceptual auditory outcomes, patient self-rated VAS and all subscales of VR-QoL showed significant improvement

Bottomley et al.
2014 [78]
Laryngeal
Hypopharyngeal
(No details provided)
T2
T3
T4
(No details provided)
QoLEORTC QLQ-C30
EORTC QLQ-H&N35
Group 1: sequential CRT ()
Group 2: alternating CRT ()
6, 12, 18, 24, 36, 48 monthsThe HRQoL scores of the majority of patients returned to baseline after therapy. No group differences were found

Buchbinder et al.
1993 [48]
No details providedNo details providedDMIOGroup 1: RT + unassisted exercise
Group 2: RT + stacked tongue depressors combined + unassisted exercise
Group 3: RT + TheraBite® system combined + unassisted exercise
2, 4, 6, 8, 10 weeksThe highest increase in MIO was reached in group 3

Caudell et al.
2010 [49]
Nasal cavity = 3 (4%)
Nasopharyngeal = 7 (8%)
Oral cavity = 1 (1%)
Oropharyngeal = 44 (53%)
Hypopharyngeal = 6 (7%)
Laryngeal = 17 (21%)
Unknown = 5 (6%)
Tx-2 = 28 (34%)
T3-T4 = 55 (66%)
DVideofluoroscopy
PEG dependency
Group 1: CRT ()
Group 2: RT ()
12 monthsMean dose to the larynx greater than 41 Gy and a receiving volume greater than 24% showed association with increased PEG dependency and aspiration

Christianen et al.
2015 [50]
Nasopharyngeal = 8 (3%)
Oral cavity = 11 (5%)
Oropharyngeal = 71 (30%)
Hypopharyngeal = 12 (5%)
Laryngeal = 136 (57%)
T1-T2 = 161 (68%)
T3-T4 = 77 (32%)
DGrade of swallowing dysfunction according to the RTOG/EORTC Late Radiation Morbidity Scoring CriteriaGroup 1: conventional RT ()
Group 2: accelerated RT ()
Group 3: CRT ()
6, 12, 18, 24 monthsPatterns of swallowing dysfunction may be caused by radiobiological mechanisms of radiation induced damage and recovery. No group differences were found

Cohen et al.
2006 [51]
Oral cavity = 14 (26%)
Oropharyngeal = 11 (21%)
Hypopharyngeal = 3 (6%)
Laryngeal = 9 (17%)
Supraglottic = 13 (24%)
Unknown = 3 (6%)
T0 = 3 (6%)
T1 = 3 (6%)
T2 = 17 (32%)
T3 = 30 (56%)
D
QoL
PSS-HN
Head and Neck RT Questionnaire (selected questions)
FACT-H&N
CRT3, 6, 12, 18, 24, 36, 48, 60 monthsMost patients returned to pretreatment function (QoL and performance) by 12 months

Dornfeld et al.
2007 [29]
Oral cavity = 1 (4%)
Oropharyngeal = 16 (59%)
Hypopharyngeal = 1 (4%)
Laryngeal = 6 (22%)
Unknown = 3 (11%)
Tx = 2 (7%)
T1 = 6 (22%)
T2 = 7 (26%)
T3 = 5 (19%)
T4 = 7 (26%)
V
D
QoL
Weight
Type of diet
Type of speech
Presence of PEG tube
HNCI
CRT1 yearSpeech, diet, and QoL outcomes showed an inverse relationship with the delivered radiation dose to the larynx

Dijkstra et al.
2007 [52]
Parotid = 4 (14%)
Maxilla = 4 (14%)
Gingiva = 2 (7%)
Floor of mouth = 3 (10%)
Trigonum retromolare = 4 (14%)
Oropharyngeal = 8 (27%)
Other localization = 4 (14%)
No details providedDMIORT12–48 weeksIncrease in mouth opening was significantly less in the group of patients with trismus related to head and neck cancer and is difficult to treat with exercise therapy

Feng et al.
2007 [53]
Base of tongue = 19 (53%)
Tonsil = 12 (33%)
Nasopharyngeal = 5 (14%)
T1 = 2 (5%)
T2 = 11 (31%)
T3 = 9 (25%)
T4 = 14 (39%)
D
QoL
Videofluoroscopy
Esophagogram
HNQoL
UWQoL
EORTC Late Radiation Morbidity Scale
CRT3 monthsStatistically significant dose-volume effect relationships for dysphagia and aspiration were found. Reducing the doses to the swallowing structures may improve swallowing

Feng et al.
2010 [54]
Base of tongue = 38 (52%)
Tonsil = 35 (48%)
T1 = 9 (12%)
T2 = 29 (40%)
T3 = 17 (23%)
T4 = 18 (25%)
DVideofluoroscopy
UWQoL (swallowing question)
HNQoL (eating domain)
Observer rated dysphagia
CRT3, 6, 12, 18, 24 monthsLong-term measures of swallowing were slightly worse than pretherapy measures

Frowen et al.
2010 [16]
Base of tongue = 19 (24%)
Soft palate = 2 (2%)
Tonsil = 26 (32%)
Supraglottic = 8 (10%)
Hypopharyngeal = 8 (10%)
Laryngeal = 18 (22%)
T1 = 11 (14%)
T2 = 27 (33%)
T3 = 31 (38%)
T4 = 12 (15%)
DVideofluoroscopyGroup 1: CRT ()
Group 2: CT ()
3, 6 monthsSwallowing in both groups was best at baseline; a decline at 3 months and an improvement at 6 months after therapy were shown. Baseline levels were not reached. Predictors for swallowing outcome were intoxications, tumor size, RT technique, and baseline level of swallowing. Patients who received conformal RT had a very low risk of penetration and aspiration of liquids by 6 months after treatment

Haderlein et al.
2014 [55]
Oropharyngeal = 3 (7%)
Hypopharyngeal = 18 (40%)
Laryngeal = 24 (53%)
T2 = 15 (33%)
T3 = 17 (38%)
T4 = 13 (29%)
D
QoL
PEG dependency
EORTC QLQ-C30
CRT3–6- month intervalsAlmost 50% of patients had deterioration of swallowing function after CRT

Hutcheson et al.
2014 [56]
Nasopharyngeal = 1 (2%)
Oral cavity = 1 (2%)
Oropharyngeal = 41 (88%)
Hypopharyngeal = 2 (4%)
Supraglottic = 2 (4%)
T1 = 16 (34%)
T2 = 14 (30%)
T3 = 12 (25%)
T4 = 5 (11%)
DVideofluoroscopy
PSS-HN
MDADI
Group 1: RT ()
Group 2: CRT ()
Group 3: surgery ()
6, 12, 24 monthsTwo years after therapy, mild deterioration of swallowing without chronic aspiration was found

Jacobi et al.
2016 [30]
Nasopharyngeal = 6 (18%)
Oral cavity/oropharyngeal = 15 (44%)
Hypopharyngeal = 13 (38%)
T1 = 6 (18%)
T2 = 13 (38%)
T3 = 11 (32%)
T4 = 4 (12%)
VSpeech analysisCRT10 weeks; 1 yearReceived dose to tongue and velopharynx were most relevant for speech and voice quality

Karlsson et al.
2015 [31]
Laryngeal = 74 (100%)T0 = 1 (1%)
T1 = 44 (60%)
T2 = 22 (30%)
T3 = 6 (8%)
T4 = 1 (1%)
V
QoL
EORTC QLQ-C30
EORTC QLQ-H&N35
S-SECEL
Group 1: CRT + voice rehabilitation ()
Group 2: CRT only ()
1, 6 monthsPatients treated with voice rehabilitation experienced benefits of therapy on communication and HRQoL

Karlsson et al.
2016 [32]
Laryngeal = 40 (100%)Tis = 2 (5%)
T1 = 20 (50%)
T2 = 13 (33%)
T3 = 5 (12%)
V
QoL
EORTC QLQ-C30
EORTC QLQ-H&N35
S-SECEL
Perceptual and acoustic voice analysis
RT (1 subject received concomitant chemotherapy)1, 6, 12 monthsOne year after treatment most outcomes showed no significant improvements compared to baseline measurements

Kazi et al.
2008 [33]
Hypopharyngeal = 8 (38%)
Laryngeal = 10 (48%)
Supraglottic = 3 (14%)
Stage III
Stage IV
No details provided
VVoice analysis
Electroglottography
CRT1, 6, 12 monthsPatients treated with CRT had a better voice quality compared to patients after total laryngectomy

Kerr et al.
2015 [34]
Tongue base = 77 (38%)
Tonsil/soft palate = 123 (62%)
T0-T1 = 42 (21%)
T2 = 72 (36%)
T3 = 48 (24%)
T4 = 38 (19%)
V
D
KPS
ECOG toxicity and response criteria scale
PSS-HN
RBHOMS
VHI-10
Edmonton Self-Assessment Scale (Self-rated Xerostomia)
Group 1: 3DCRT ()
Group 2: IMRT ()
3, 6, 12, 24 monthsIMRT showed better functional outcomes compared to 3DCRT, both 3–6 and 12–24 months after treatment

Kotz et al.
2012 [57]
Nasopharyngeal = 1 (4%)
Tongue base = 11 (42%)
Tonsil = 11 (42%)
Oropharyngeal = 1 (4%)
Glottic = 1 (4%)
Unknown = 1 (4%)
T2 = 1 (4%)
T3 = 5 (19%)
T4 = 20 (77%)
DPSS-HN (eating in public and normalcy of diet)
FOIS
Group 1: CRT + prophylactic swallowing therapy ()
Group 2: CRT ()
3, 6, 9, 12 monthsProphylactic swallowing therapy improves swallowing at 3 and 6 months; later there were no group differences

Kraaijenga et al.
2014 [35]
Nasopharyngeal = 4 (18%)
Oral cavity/
oropharyngeal = 10 (46%)
Hypopharyngeal/
laryngeal = 8 (36%)
T1 = 5 (23%)
T2 = 9 (41%)
T3 = 7 (32%)
T4 = 1 (4%)
V
D
QoL
Videofluoroscopy
Acoustic analysis
Presence of feeding tube
FOIS
Pain (VAS)
Trismus
QoL aspects (based on EORTC QLQ-C30 and EORTC QLQ-H&N35)
SWAL-QoL
VHI
CRT2, 6 yearsFunctional swallowing and voice problems at 6 years after treatment were minimal, possibly due to preventive swallowing rehabilitation programs

Kumar et al.
2014 [58]
Tonsil = 19 (41%)
Base of tongue = 22 (47%)
Pharyngeal wall = 3 (7%)
Unknown = 2 (5%)
T0 = 2 (4%)
T1 = 15 (33%)
T2 = 14 (30%)
T3 = 12 (26%)
T4 = 3 (7%)
DVideofluoroscopyCRTFrom <6 to >18 monthsAspiration and penetration were associated with dose and volume delivered to the floor of mouth muscles

Lazarus et al.
2014 [36]
Nasopharyngeal = 3 (10%)
Oropharyngeal = 18 (63%)
Pharyngeal = 1 (3%)
Hypopharyngeal = 1 (3%)
Laryngeal = 5 (18%)
Unknown primary = 1 (3%)
Stage I = 2 (7%)
Stage II = 1 (4%)
Stage III = 5 (17%)
Stage IVa = 21 (72%)
D
V
QoL
Tongue strength, jaw ROM, and tongue ROM
Saliva weight
Eating Assessment Tool
MDADI
Speech Handicap Index
EORTC QLQ-H&N35
PSS-HN (normalcy of diet, eating in public, and understandability of speech)
KPS
CRT3, 6 months
Patients performed worse in oral outcomes, performance status, and QoL after treatment

List et al.
1999 [59]
Nasopharyngeal = 1 (2%)
Oral cavity = 6 (9%)
Oropharyngeal = 34 (53%)
Hypopharyngeal = 10 (16%)
Laryngeal = 9 (14%)
Other = 4 (6%)
Stage III = 4 (6%)
Stage IV = 60 (94%)
D
QoL
KPS
PSS-HN
McMaster University Head and Neck RT Questionnaire (selected questions)
FACT-H&N
CRT1, 3, 6, 9, 12 monthsDecline of QoL and functional aspects resolved 1 year after treatment; however, oral intake stayed restricted

McLaughlin et al.
2010 [60]
Nasopharyngeal = 9 (10%)
Oral cavity = 19 (21%)
Oropharyngeal = 32 (35%)
Hypopharyngeal = 7 (8%)
Laryngeal = 12 (13%)
Unknown = 4 (4%)
Other = 8 (9%)
Stage II = 1 (1%)
Stage III = 21 (23%)
Stage IV = 69 (76%)
DWeight loss
Aspiration
Overall nutritional status
Duration G-tube placement
Treatment-related complications
CRT6, 12 monthsPatients treated with CRT could be managed without nutritional support via G-tube. Dysphagia at baseline and advanced tumor stage are associated with increased risk of longer G-tube dependency

Mittal et al.
2001 [37]
Nasopharyngeal = 4 (10%)
Oropharyngeal = 17 (44%)
Hypopharyngeal = 7 (18%)
Laryngeal = 5 (13%)
Unknown = 6 (15%)
Stage III = 5 (13%)
Stage IV = 34 (87%)
D
V
Videofluoroscopy
Saliva production
PSS-HN
FACT-H&N
Fisher-Logemann Test of Articulation Competence
Group 1: CRT with TDC ()
Group 2: CRT without TDC ()
3 monthsPatients treated with TDC had better oral intake, swallowing function, and articulation

Murry et al. 1998 [61]Oropharyngeal = 19 (52%)
Hypopharyngeal = 6 (16%)
Laryngeal = 12 (32%)
T3
T4
(No details provided)
DHNRQ
Questionnaire on swallowing
CRT6 monthsDuring treatment QoL and swallowing function decreased acutely and significantly. Six months after therapy QoL exceeded pretreatment level. Recovery was site-specific: oropharyngeal tumor patients had poorest outcome, whereas hypopharyngeal tumor patients showed most rapid recovery. Physical recovery followed psychosocial recovery. Organ preservation treatment may improve swallowing after treatment

Niedzielska et al.
2010 [38]
Laryngeal = 45 (100%)T1 = 24 (53%)
T2 = 21 (47%)
VVideolaryngostroboscopy
Acoustic analysis
RT1–3 yearsAll irradiated patients showed reduced vibration of the vocal cords. Except for some of the acoustic parameters, most data were comparable to a healthy control group ()

Nourissat et al.
2010 [62]
Oral cavity = 63 (12%)
Oropharyngeal = 17 (3%)
Hypopharyngeal = 8 (1%)
Supraglottic = 100 (19%)
Glottic = 347 (65%)
T1 = 329 (61%)
T2 = 206 (39%)
D
QoL
Weight
KPS
EORTC QLQ-C30
Structured general questionnaire
RTDirect posttherapyThe occurrence of adverse effects of RT appeared to be one of the main reasons for weight loss. Correlations were found between genetic factors associated with the adverse effects of cancer treatments

Ottoson et al.
2014 [63]
Oral cavity = 20 (20%)
Oropharyngeal = 62 (61%)
Hypopharyngeal = 8 (8%)
Laryngeal = 11 (11%)
T1 = 11 (10%)
T2 = 16 (16%)
T3 = 28 (28%)
T4 = 46 (46%)
DVideofluoroscopy
BMI
RT5 yearsDysphagia with aspiration was related to unintentional weight loss and a lower BMI

Pauli et al.
2013 [64]
Sinus, nose = 6 (8%)
Salivary gland = 10 (13%)
Gingiva, buccal = 6 (8%)
Tongue, floor of mouth = 15 (20%)
Tonsil = 24 (32%)
Base of tongue, oropharyngeal = 11 (15%)
Other = 3 (4%)
T0 = 5 (7%)
T1 = 13 (17%)
T2 = 29 (39%)
T3 = 9 (12%)
T4 = 18 (24%)
Unknown = 1 (1%)
D
QoL
MIO
Patient-reported outcome
Gothenburg Trismus Questionnaire
EORTC QLQ-C30
EORTC QLQ-H&N35
HADS
Group 1: surgery ()
Group 2: surgery + RT ()
Group 3: surgery + CRT ()
Group 4: RT ()
Group 5: CRT ()
Group 6: no treatment ()
3, 6, 12 monthsTrismus was a major side effect of the treatment of head and neck cancer and deteriorates HRQoL

Pauloski et al.
2006 [65]
Nasopharyngeal = 8 (5%)
Oral cavity = 15 (9%)
Oropharyngeal = 80 (47%)
Hypopharyngeal = 14 (8%)
Laryngeal = 42 (25%)
Unknown = 11 (6%)
Stage IV = 122 (72%)
Other = 48 (28%)
DVideofluoroscopy
Oral intake
Group 1: CRT ()
Group 2: RT ()
Unknown ()
1, 3, 6, 12 monthsIn both groups limitations in oral intake and diet after cancer treatment were significantly related to reduced laryngeal elevation and reduced cricopharyngeal opening due to treatment

Rademaker et al.
2003 [66]
Nasopharyngeal = 13 (5%)
Oral cavity = 25 (10%)
Oropharyngeal = 118 (46%) Hypopharyngeal = 22 (9%)
Laryngeal = 59 (23%)
Unknown = 18 (7%)
Stage II = 16 (6%)
Stage III = 48 (19%)
Stage IV = 187 (73%)
Unknown = 4 (2%)
DPercentage of oral intake
Food consistencies
CRT1, 3, 6, 12 monthsEating ability decreased during treatment and improved 12 months after treatment to near pretreatment levels

Remmelts et al.
2013 [39]
Glottic = 248 (100%)Tis = 26 (10%)
T1a = 103 (42%)
T1b = 42 (17%)
T2 = 77 (31%)
VVHI (physical subscale)
5-item questionnaire
Group 1: RT ()
Group 2: laser surgery ()
12 monthsVHI scores were comparable for both groups. Regarding laryngeal preservation surgery is the treatment of first choice

Salama et al.
2008 [67]
Nasopharyngeal = 4 (4%)
Oral cavity = 8 (9%)
Oropharyngeal = 49 (52%)
Hypopharyngeal = 5 (5%)
Laryngeal = 22 (23%)
Other = 7 (7%)
Tx = 7 (7%)
T1 = 15 (16%)
T2 = 19 (20%)
T3 = 16 (17%)
T4 = 38 (40%)
DVideofluoroscopy
SPS
CRT1-2 monthsImprovement of swallowing ability compared to baseline was associated with advanced tumor stage

Sanguineti et al.
2014 [40]
Base of tongue = 54 (43%)
Soft palate = 2 (2%)
Tonsil = 59 (48%)
Pharyngeal wall = 1 (1%)
Unknown = 8 (6%)
T0 = 8 (6%)
T1 = 37 (30%)
T2 = 49 (40%)
T3 = 14 (11%)
T4 = 16 (13%)
VCTCAE
FACT-HN (items HN4 and HN10)
Group 1: CRT ()
Group 2: RT ()
3, 6, 12, 18, 24, 36, 48, 60 monthsMild voice changes were common and strictly correlated to mean dose to larynx and should be kept under 50 Gy

Scrimger et al.
2007 [68]
Nasopharyngeal = 10 (21%)
Oral cavity = 20 (43%)
Oropharyngeal = 9 (19%)
Hypopharyngeal/
laryngeal = 6 (13%)
Unknown primary = 2 (4%)
T0 = 2 (4%)
T1 = 7 (15%)
T2 = 20 (42%)
T3 = 12 (26%)
T4 = 6 (13%)
D
QoL
Mouth saliva flow
UW-QoL
RTOG late-toxicity scale
XQoL
Group 1: RT ()
Group 2: CRT ()
Group 3: surgery + RT ()
3, 6, 12 monthsNonsurgery resulted in better QoL questionnaire scores compared to surgery. Patients with good saliva production did not exhibit better QoL after RT than patients with less saliva production

Spector et al.
1999 [41]
Glottic = 659 (100%)T1 = 659 (100%)VVoice preservationGroup 1: low-dose RT ()
Group 2: high-dose RT ()
Group 3: conservation surgery ()
Group 4: endoscopic resection ()
5 yearsGroups 2–4 had similar unaided laryngeal voice preservation rates; however group 1 had significant lower unaided laryngeal voice preservation

Starmer et al.
2014 [69]
Oropharyngeal = 71 (100%)T1 = 24 (34%)
T2 = 19 (27%)
T3 = 13 (18%)
T4 = 12 (17%)
Unknown = 3 (4%)
DVideofluoroscopy
FOIS
Group 1: CRT ()
Group 2: RT ()
1–18 monthsPatients undergoing nonsurgical treatment for oropharyngeal tumors were at risk for posttreatment dysphagia

Stenson et al. 2010 [70]Buccal = 4 (3%)
Alveolus/gingivae = 7 (6%)
Floor of mouth = 32 (29%)
Tongue = 50 (45%)
Palate/oral cavity NOS = 4 (4%)   
Trigonum retromolare = 13 (12%)
Unknown = 1 (1%)
T1 = 9 (8%)
T2 = 15 (14%)
T3 = 20 (18%)
T4 = 67 (60%)
DVideofluoroscopy
SPS
Group 1: CRT ()
Group 2: surgery + CRT ()
2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36 monthsNinety-two percent of all patients were able to maintain weight via oral route.
Both groups showed comparable overall survival. Ninety-two percent of all patients had a sufficient oral intake

Strigari et al.
2010 [71]
Nasopharyngeal = 44 (70%)
Floor of mouth/oral cavity = 2 (3%)
Oropharyngeal = 11 (17%)
Hypopharyngeal = 4 (7%)
Unknown primary = 2 (3%)
T1-T2 = 17 (23%)
T3-T4 = 46 (73%)
DSaliva flow
Xerostomia related questionnaires
RTOG late-toxicity scale
RT3, 6, 12, 18, 24 monthsThe mean score on the xerostomia related questionnaire increased (worsened) after RT and decreased (improved) over time in all patients

Tuomi et al.
2015 [42]
Supraglottic = 13 (19%)
Glottic = 54 (81%)
Tis = 2 (3%)
T1 = 41 (61%)
T2 = 17 (25%)
T3 = 6 (9%)
T4 = 1 (2%)
V
D
QoL
Acoustic analysis
EORTC QLQ-C30
EORTC QLQ-H&N35
S-SECEL
RT1 monthPatients treated for supraglottic tumors experienced more problems in eating and swallowing prior to therapy compared to glottic tumors and demonstrated significant HRQoL reduction after treatment. In contrast, glottic tumors presented with inferior voice quality

Urdaniz et al.
2005 [77]
Paranasal sinuses = 3 (5%)
Nasopharyngeal = 3 (5%)
Oral cavity = 2 (3%)
Oropharyngeal = 25 (42%)
Hypopharyngeal = 9 (15%)
Laryngeal = 18 (30%)
T2 = 2 (3%)
T3 = 20 (33%)
T4 = 38 (64%)
QoLEORTC QLQ-C30
EORTC QLQ-H&N35
Group 1: hyperfractionated concomitant boost RT + cisplatin ()
Group 2: hyperfractionated conventional RT + cisplatin ()
1 monthQoL in both groups was relatively good. QoL improved in the follow-up period

Vainshtein et al.
2015 [72]
Base of tongue = 18 (45%)
Tonsil = 22 (55%)
T1 = 8 (20%)
T2 = 20 (50%)
T3 = 8 (20%)
T4 = 4 (10%)
D
QoL
HNQoL
UWQoL
XQoL
CRT1, 3, 6, 12, 18, 24 monthsAt 6.5 years after therapy patients showed a stable or improved HRQoL in most domains comparable with baseline and 2 years after therapy

van der Molen et al.
2011 [73]
Nasopharyngeal = 7 (14%)
Oral cavity/
oropharyngeal = 24 (49%)
Hypopharyngeal/
laryngeal = 18 (37%)
T1 = 8 (16%)
T2 = 15 (31%)
T3 = 19 (39%)
T4 = 7 (14%)
DVideofluoroscopy
MIO
BMI
FOIS
VAS pain
Group 1: standard rehabilitation ()
Group 2: experimental rehabilitation ()
10 weeks(Preventive) rehabilitation
in head and neck cancer patients was feasible and improved functional outcomes after therapy

van der Molen et al.
2012 [44]
Nonlaryngeal = 36 (65%)
Laryngeal = 19 (35%)
T1 = 8 (15%)
T2 = 15 (27%)
T3 = 21 (38%)
T4 = 11 (20%)
V
QoL
Acoustic analysis
Study-specific QoL questionnaire
CRT10 weeks; 1 yearCRT effects 10 weeks after therapy were worse than 1 year after therapy, and both were worse than baseline

van der Molen et al.
2013 [74]
Nasopharyngeal = 7 (13%)
Oral cavity/
oropharyngeal = 29 (53%)
Hypopharyngeal/
laryngeal = 19 (34%)
T1 = 8 (15%)
T2 = 15 (27%)
T3 = 21 (38%)
T4 = 11 (20%)
DVideofluoroscopy
MIO
Study-specific structured questionnaire
CRT10 weeks; 1 yearA correlation between doses and structures was found for dysphagia and trismus

Verdonck-de Leeuw et al.
1999 [43]
Glottic = 60 (100%)T1 = 60 (100%)VVideolaryngostroboscopy Voice quality rating
Self-rating of vocal performance and quality
RT0.5–10 yearsVoice and its characteristics improved after treatment but did not reach pretreatment levels in half of the patients

Verdonck-de Leeuw et al.
2014 [79]
Oral/oropharyngeal = 95 (58%)
Hypopharyngeal/
laryngeal = 69 (42%)
No details providedQoLEORTC QLQ-C30
EORTC QLQ-H&N35
CRT6 weeks; 6, 12, 18, 24 monthsSignificant difference in HRQoL between survivors and nonsurvivors in favor of survivors was found

Vlacich et al.
2014 [75]
Sinus/nasal cavity = 2 (1%)
Nasopharyngeal = 12 (9%)
Oral cavity = 5 (4%)
Oropharyngeal = 82 (58%)
Hypopharyngeal = 6 (4%)
Laryngeal = 30 (21%)
Unknown = 4 (3%)
Stage III = 42 (30%)
Stage IVa = 81 (57%)
Stage IVb = 18 (13%)
DPEG requirementCRT12 monthsIMRT dose to the inferior constrictor correlated with persistent dysphagia requiring prolonged PEG use

Wilson et al.
2011 [76]
Nasopharyngeal = 5 (3%)
Oropharyngeal = 66 (39%)
Hypopharyngeal = 21 (13%)
Laryngeal = 63 (38%)
Unknown primary = 12 (7%)
T1 = 37 (22%)
T2 = 37 (22%)
T3 = 37 (22%)
T4 = 44 (27%)
Unknown = 12 (7%)
D
QoL
MDADI
UWQoL
Group 1: CRT ()
Group 2: RT ()
3, 6, 12 monthsHRQoL deteriorated significantly after treatment. Little improvement may be expected 3 to 12 months after treatment

3DCRT: 3D conformal radiotherapy; BMI: body mass index; CRT: chemoradiotherapy; CTCAE: common terminology criteria for adverse events; D: digestive tract; ECOG: Eastern Cooperative Oncology Group; EORTC QLQ-C30: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire; EORTC QLQ-H&N35: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Module Head and Neck Cancer; FACT-HN: functional assessment of cancer therapy-head and neck; FOIS: functional oral intake scale; GRBAS: grade, roughness, breathiness, asthenia, strain scale; HADS: hospital anxiety and depression scale; HNCI: head and neck cancer inventory; HNQoL: head and neck quality of life; HNRQ: head and neck radiotherapy questionnaire; HRQoL: health-related quality of life; IMRT: intensity-modulated radiation therapy; KPS: Karnofsky performance status scale; LENT/SOMA: late effects normal tissue-subjective, objective, management, analytic scales; MDADI: MD Anderson dysphagia inventory; MIO: maximum incisal opening; NOS: not otherwise specified; PEG: percutaneous endoscopic gastrostomy; PSS-HN: performance status scale for head and neck cancer patients; QoL: quality of life; RBHOMS: Royal Brisbane Hospital outcome measure for swallowing; ROM: range of motion; RT: radiotherapy; RTOG: Radiation Therapy Oncology Group; S-SECEL: Swedish version of the self-evaluation of communication experiences after laryngeal cancer; SPS: swallowing performance status scale; TDC: tissue/dose compensation; UWQoL: University of Washington Quality of Life Questionnaire; V: voice and/or speech; VAS: visual analog scale; VHI: voice handicap index; VHI-10: voice handicap index-10; VR-QoL: voice-related quality of life; XQoL: xerostomia questionnaire.
3.1. Voice and/or Speech Function

Twenty-four studies evaluated voice and/or speech function [2143] with a follow-up time ranging from 1-month follow-up [42] to ten-year follow-up [43]. Most studies included patients with laryngeal tumors only; however 11 studies [22, 27, 29, 30, 3337, 44] also included nonlaryngeal tumors. Seventeen studies [21, 23, 25, 26, 28, 3032, 3436, 3843] included patients with low-grade tumors (i.e., T1 and T2) and 15 studies included patient with advanced tumors [22, 24, 27, 2937, 40, 42, 44].

Nine studies [23, 28, 30, 32, 33, 35, 38, 42, 44] used acoustic analysis to evaluate voice quality, six studies [2426, 34, 35, 39] used the Voice Handicap Index, and three studies [21, 38, 43] used videolaryngostroboscopy. In several studies, either descriptions of how voice quality was evaluated were missing or nonvalidated tools were used (e.g., patients self-reporting or trial-specific questionnaires). Only four studies [23, 31, 40, 44] reported whether the patient received any voice therapy.

All the studies reported good to excellent outcomes for voice quality at long-term follow-up. Some studies specifically reported pre- to posttreatment improvements of voice or speech quality following radiotherapy and/or chemotherapy [22, 23, 28]. However, other studies [36, 40, 42, 44] reported a deterioration after therapy at long-term follow-up. Al-Mamgani et al. [26] found a better voice outcome in case of single vocal cord irradiation compared with irradiation of the whole larynx. Mittal et al. [37] concluded that radiation with tissue/dose compensation (TDC) improved articulatory outcome compared to radiation without TDC.

3.2. Functions of the Digestive Tract

Forty studies [16, 22, 29, 3437, 42, 4576] describe the effects of radiotherapy and/or chemotherapy on the functions of the digestive tract and used a variety of outcome measures. Of these 40 studies, 16 studies [16, 35, 37, 45, 49, 53, 54, 56, 58, 63, 65, 67, 69, 70, 73, 74] used videofluoroscopy to measure physiological changes in swallowing function. Eight studies [29, 35, 46, 47, 49, 55, 60, 75] used feeding tube dependency as a (dichotomous) outcome, whereas seven studies [35, 46, 57, 65, 66, 69, 73] described the level of oral intake in more detail. Only four studies [35, 36, 56, 76] used a condition specific validated measure for swallowing disorders (e.g., MDADI).

With regard to nutritional status, five studies [29, 60, 62, 63, 73] used the body mass index as an outcome or reported specifically on weight gain or loss. Seven studies [35, 36, 48, 52, 64, 73, 74] used the presence of trismus as an outcome by reporting on the maximum distance of mouth opening. Saliva flow (as a measure of xerostomia) was used in four studies [36, 37, 68, 71].

Follow-up times in these studies range from immediately after therapy [62] to 6 years after therapy [35], describing both low stage tumors and more advanced tumors. Thirty-two studies used the TNM-classification system, stage was described in six other studies, and the remaining two studies did not report on tumor stage or grade. However, it was unclear whether the clinical TNM-score or the pathological TNM-score was used to describe the severity of the disease. Eight studies [16, 35, 46, 48, 52, 56, 57, 69, 73, 74] described whether the patients received functional treatment (by a speech pathologist); the remainder of the articles did not mention whether the patient received any additional treatment.

Nine studies reported impaired swallowing function following radiotherapy and/or chemotherapy [36, 45, 50, 5456, 69, 75, 76].

Five studies [16, 51, 59, 61, 66] showed that swallowing was least affected at baseline, worst immediately following posttreatment (0–3 months after treatment), and improved by 6–12 months after treatment and later. However, swallowing usually did not return to pretreatment functioning level. In four studies [49, 53, 58, 74], a relation between dose-volume, dysphagia, and aspiration was found. Caudell et al. [49] showed that a mean radiation dosage >41 Gy with >24% volume of the larynx being radiated was associated with increased percutaneous endoscopic gastrostomy (PEG) dependency and aspiration. Akst et al. [46] correlated advanced tumor stage and age >60 years with a deterioration of swallowing.

Ackerstaff et al. [22] demonstrated improved oral intake postradiotherapy and/or chemotherapy. Stenson et al. [70] stated that weight remained unchanged after treatment (via oral route), whereas Nourissat et al. [62] described a mean weight loss of 2.2 kg posttreatment.

3.3. QoL

Twenty-five studies [22, 24, 25, 2729, 31, 32, 35, 36, 42, 44, 47, 51, 53, 55, 59, 62, 64, 68, 72, 7679] described the short- and long-term effects of treatment for HNC on patients’ general QoL. The European Organization for Research and Treatment of Cancer (EORTC) C30-questionnaire was used in fifteen studies [22, 24, 25, 27, 31, 32, 35, 42, 47, 55, 62, 64, 7779] and the more HNC specific EORTC H&N35 was used in thirteen studies [22, 24, 25, 31, 32, 35, 36, 42, 47, 64, 7779]. Other questionnaires that were used included the University of Washington QoL Questionnaire (UWQoL) [53, 68, 72, 76], the Head and Neck QoL or HNQoL [53, 72], and the Xerostomia related QoL or XQoL [68, 72]. Follow-up time for QoL was up to six years after treatment [35], including patients with tumors that were early staged and patients with advanced tumors.

Although three studies [28, 72, 77] demonstrated improvements in QoL, four studies [22, 36, 42, 54] reported a decrease in general QoL as a result of radiotherapy and/or chemotherapy. Bansal et al. [27] found a significant decline in physical, social, and emotional functioning as well as in global health scores following a course of radiotherapy. However, the patients’ functional scores improved one month after treatment but did not reach pretreatment levels. The health-related QoL (HRQoL) scores of the majority of patients in the Bottomley et al. [78] study returned to baseline at 48-month follow-up. These findings support the findings of Ackerstaff et al. [22], Cohen et al. [51], Karlsson et al. [32], List et al. [59], and Wilson et al. [76], who suggested that HRQoL deteriorates significantly immediately after treatment, with variable degrees of improvement 3–72 months after treatment.

3.4. Reported (Efficacy of) Speech Pathology Interventions

We assessed the speech pathology interventions against the following criteria: (a) whether a detailed description of the intervention was provided; (b) whether the authors provided a description of treatment duration and intensity; and (c) what the speech pathology intervention outcomes were. The reported efficacy of 14 speech pathology intervention studies aimed at addressing problems in dysphagia, speech, voice, and trismus is summarised in Table 4.


ReferenceTopicGeneral description of intervention and treatment intensity/durationDescription of specific exercisesConclusions specific to therapy

Agarwal et al.
2009 [23]
VoiceAll patients received counseling and voice therapy by a trained speech pathologist
No specific data provided on treatment frequency/intensity
No description of exercises providedForty-seven of 50 patients showed compliance to the therapy. No specific conclusions of influence of provided therapy on primary outcomes described

Akst et al.
2004 [46]
SwallowingSwallowing evaluation and intervention when clinically indicatedNo description of exercises providedNo specific conclusions of influence of provided therapy on primary outcomes described

Buchbinder et al.
1993 [48]
TrismusSix to 10 exercise sessions per day for a 10-week periodGroup 1: unassisted exercises: reach maximum MIO and closing, jaw motion to left, right, and protrusively
Group 2: unassisted exercises: reach maximum MIO and closing, jaw motion to left, right, and protrusively. Stacked tongue depressors, to mechanically increase MIO (5 × 30 seconds per session)
Group 3: unassisted exercises: reach maximum MIO and closing, jaw motion to left, right, and protrusively. Combined with the TheraBite System (5 × 30 seconds per session)
The first four weeks no differences between groups were found. After week 4 minimal improvements in groups 1 and 2 were found and group 3 still improved. The highest increment in MIO was reached in group 3

Dijkstra et al.
2007 [52]
TrismusPhysical therapy for trismus, median of 4 sessionsPhysical therapy consisting of
(i) Active range of motion
(ii) Hold and relax
(iii) Manual stretching
(iv) Joint distraction
Following therapeutic tools are used in described cohort:
(i) Rubber plugs
(ii) Tong blades
(iii) Dynamic bite opener
(iv) TheraBite System
MIO increases significantly after physical therapy. History of HNC decreases the effect of physical therapy, compared to other trismus patients

Frowen et al.
2010 [16]
SwallowingAll patients were seen by a speech pathologist as an aspect of regular careNo description of exercises providedNo specific conclusions of influence of provided therapy on primary outcomes described

Hutcheson et al.
2014 [56]
SwallowingAll patients received prophylactic swallowing therapy to avoid nothing by mouth periods during treatment
No specific data provided on treatment frequency/intensity
Targeted swallowing exercisesNo specific conclusions of influence of provided therapy on primary outcomes described

Karlsson et al.
2015 [31]
VoiceGroup 1: voice therapy group received 10 × 30-minute sessions over 10 weeks
Group 2: vocal hygiene group: 1 session for vocal hygiene advice
Group 1: voice therapy consisting of relaxation, respiration, posture, and phonation exercises
Group 2: vocal hygiene advice
Patients treated with voice therapy experienced greater improvements compared to patients that only received vocal hygiene advice. Group 1 showed a significant better functional communication and HRQoL

Kotz et al.
2012 [57]
SwallowingGroup 1: weekly treatment by speech pathologist and daily 3 × 10 home sessions of exercises. Group 2: swallowing assessment and treatment if necessary after treatmentGroup 1: prophylactic swallowing therapy consisting of effortful swallow, tongue base retraction exercises, super supraglottic swallow, and the Mendelssohn maneuver
Group 2: control group only receive symptomatic dysphagia treatment
Prophylactic swallowing therapy improves swallowing at 3 and 6 months; later there were no group differences found

Kraaijenga et al.
2014 [35]
Swallowing and voiceDaily practice from the start of the treatment until 1 year after treatmentTwo combined groups: TheraBite System and standard logopedic swallowing exercises (the same cohort as van der Molen et al. 2011 [73])Minimal voice and swallowing difficulties were found 60 months after treatment in patients treated with prophylactic swallowing exercises

Sanguineti et al.
2014 [40]
Voice75.8% of the patients received speech therapy. No therapy was provided to 30 patients
No specific data provided on treatment frequency/intensity
No description of exercises providedNo specific conclusions of influence of provided therapy on primary outcomes described

Starmer et al.
2014 [69]
SwallowingPatients received prophylactic swallowing and trismus exercisesNo description of exercises providedNo specific conclusions of influence of provided therapy on primary outcomes described

van der Molen et al.
2011 [73]
SwallowingPatients received instructions in advance of their oncological treatment. Three times daily exercisesGroup 1: range-of-motion exercises and three strengthening exercises, that is, the effortful swallow, the Masako maneuver, and the super supraglottic swallow. Stretch holding for 10–30 seconds at a point of mild discomfort
Group 2: stretch of the mouth using the TheraBite System and a strengthening exercise: swallowing with the tongue elevated to the palate while maintaining mouth opening at 50% of its maximum. Stretch holding for 10–30 seconds at a point of mild discomfort
Similar outcomes in both groups were found. Preventive rehabilitation can improve early posttreatment functional outcomes

van der Molen et al.
2012 [44]
VoiceNo specific speech or voice therapyN/AN/A

van der Molen et al.
2013 [74]
Swallowing and trismusStudy was aimed at describing dose-effect relationships in two treatment groups described in earlier study. References to other published study where treatment regime is describedGroup 1: standard exercises
Group 2: experimental exercises
Any possible difference between the two included treatment groups is not described, nor possible influence of the respective treatments

HNC: head and neck cancer; HRQoL: health-related quality of life; MIO: maximum incisal opening; ROM: range of motion.

Of the 60 articles included in this review, 14 studies [16, 23, 29, 31, 35, 40, 44, 46, 48, 56, 57, 69, 73, 74] reported whether there was any treatment for the sequelae of radiotherapy and/or chemotherapy. Of these intervention studies, five focused on voice-related problems [23, 31, 35, 40, 44], two focused on trismus [48, 52], seven focused on swallowing disorders [16, 35, 46, 56, 57, 69, 73], and one study reported on both swallowing disorders and trismus [74].

The three studies that investigated the treatment of trismus [48, 52, 74] presented the most detailed information on what the interventions involved. The study by Dijkstra et al. [52] described a wide variety of trismus-specific therapies, suggesting that most patients received a combination of therapies. The patients in the van der Molen et al. [44] and Kraaijenga et al. [35] studies did not receive any speech therapy. The remainder of the studies reported that patients received speech therapy; however, most of these studies did not provide specific data on treatment duration or intensity. None of the voice-related studies provided information on the specific exercises prescribed to patients except Karlsson et al. [31].

Of the eight studies on swallowing disorders, only Kotz et al. [57] and van der Molen et al. [73] described the prescribed exercises in detail. The aim of the latter study was to compare the effectiveness of experimental rehabilitation to standard rehabilitation in 49 advanced HNC patients. The authors concluded that preventive rehabilitation is feasible and effective in reducing the extent and/or severity of various functional short-term effects of chemoradiotherapy [74]. This finding is supported by the 6-year follow-up study by Kraaijenga et al. [35]. Kotz et al. [57] described a temporary improvement. These are the only studies that provided detailed information about the speech pathology intervention and reported on the effectiveness of the intervention.

4. Discussion

In total, 60 studies met the inclusion criteria. The studies described the effects of radiotherapy and/or chemotherapy on the functions of the upper aerodigestive tract in patients with HNC. The articles yielded by this systematic review vary in their findings regarding tumor characteristics and treatment modalities. As a result of this variability, no statistical pooling was possible. We also set out to investigate the involvement of speech pathologists in treating patients with HNC.

When considering treatment outcomes, voice quality worsened at the start of radiotherapy and/or chemotherapy but eventually improved after therapy finished. Dysphagia can be a major side effect of HNC and its treatment. The high incidence of dysphagia in this study population can cause serious secondary consequences, such as malnutrition, dehydration, an increased risk of aspiration, and, at worst, death [80]. As dysphagia is a common sequela to oncological treatment, early detection and treatment are needed to avoid or minimise serious secondary complications [81].

The general description of the study population in Table 3 shows that there was great variability in both the location of the tumor and the grading/staging, making comparisons of these studies difficult. As the follow-up times varied in each study, the outcomes may be noncomparable. Thus, this review shows that there is a need for more standardised approaches to research in this field.

Additionally, a large range of outcome measures were used, some of which are not validated. This calls into question the reliability of results reported in some of the studies. The use of validated and standardised assessments in future research would provide more robust findings.

When considering the functional outcomes of radiotherapy and/or chemotherapy, one of the most important factors is whether the patient had received voice or swallowing therapy. Interestingly, only 14 of the 60 included studies reported whether the patients received any speech therapy. Thus, in 46 articles functional results, such as voice quality, are presented with no specification of whether the patient received therapy. As some of these studies have a follow-up of >2 years, it is fair to assume that patients sought help for voice or swallowing problems. Therefore, the involvement of speech therapy may be underreported, suggesting that the presented outcomes in these studies are biased and raise questions about their reliability.

When information was provided about treatment, only six articles [31, 48, 52, 57, 73, 74] described in detail the treatment intensity as the actual treatment. Furthermore, these studies are the only five that include conclusions about the efficacy of speech therapy in this specific population. In the context of EBP, this finding demonstrates the need for more research into the efficacy of speech pathology interventions for patients with HNC receiving radiotherapy and/or chemotherapy.

To enable the objective reporting of the effectiveness of radiation and/or chemotherapy, baseline measurements of different aspects of voice quality and swallowing are required. To manage expectations, healthcare professionals and patients need to be made aware that some aspects of both voice and swallowing commonly do not recover to the level prior to the oncological intervention [16]. Regarding effectiveness of voice treatments, the following multidimensional assessment is recommended [82]: a videolaryngostroboscopy recording of the laryngeal structures and the vocal fold vibration; an acoustic and a perceptual analysis of voice; a voice-related questionnaire on QoL (e.g., the Voice Handicap Index) [83]; and a functional health status questionnaire. Such a protocol would be in line with the recommendations for functional assessment of voice pathology as described by the Committee on Phoniatrics of the European Laryngological Society [84].

When describing aspects of swallowing function, both fiber optic endoscopic evaluation of swallowing and videofluoroscopy are considered to be the gold standard in dysphagia assessment [85]. In addition to these tools, questionnaires on HRQoL and functional health status are recommended and should be integrated in the overall swallowing assessment protocol. Repeated measurements of outcome measures should be performed in order to monitor any side effects of the oncological intervention, to detect spontaneous recovery, and to measure the effects of the speech pathology interventions. Apart from baseline measurements, posttreatment and follow-up measurements should be used to monitor functional and QoL outcomes.

Additional research is needed to develop clinical practice guidelines to support evidence-based practice in the area of dysphagia, speech, voice, and trismus following radiotherapy and/or chemotherapy in patients with head and neck carcinoma. These practice guidelines should bring together the best available current evidence within a specific clinical area, formulating evidence-based recommendations for clinicians and present choices between different interventions that have an impact on health and use of resources [86]. This systematic review summarised the effects of radiotherapy and/or chemotherapy on the function of the upper aerodigestive tract in patients with head and neck cancer. However, because of the marked variation in treatment protocols and patient characteristics, outcome data from the included studies cannot be easily generalised. Recommendations for future studies advocate the use of a multidimensional assessment protocol, using well-validated measures and standardised pretreatment, posttreatment, and follow-up measurements, thus allowing for future meta-analysis of homogeneous outcomes.

5. Conclusion

The studies included in this systematic review described a wide variety of outcomes in patients with HNC following radiotherapy and/or chemotherapy. The findings about the long-term functional implications of radiotherapy and/or chemotherapy in patients with HNC are inconclusive as a result of the wide range of outcome measures used and the possible influence of underreported speech therapy.

Future researchers need to consider targeting more homogeneous groups using standardised treatment protocols to improve the treatment outcomes, thereby decreasing the side effects of the oncological treatments. Findings of these studies need to inform the decision-making process in the treatment of HNC so complications can be better predicted with due consideration of the possible negative side effects to the upper aerodigestive tract. Although the main objective of most studies was to determine curing rates, the importance of the functional implications of the side effects of oncology treatments should not be overlooked, particularly their impact on QoL. Finally, more research is needed to gain a full understanding of the complexity and variety in the effects of radiotherapy and/or chemotherapy on the functions of the upper aerodigestive tract following HNC.

Competing Interests

All authors declare no competing interests or financial disclosures.

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