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Summary: Follow-up in patients treated for head and neck cancer (HNC) is aimed at early detection of recurrence, metastases and second primary tumours. Various modalities for the routine follow-up of patients with HNC have been proposed and studied in the literature. Consequently, practising head and neck surgeons and oncologists all over the world use different guidelines and protocols to follow-up their patients. These guidelines involve follow-up intervals of varying intensity and schedule an assortment of investigations that may be neither logical nor practical. This follow-up process may be difficult to administrate, cause unnecessary discomfort and morbidity to the patient and can have serious cost-implications to the healthcare system. This review summarises strategies for follow-up, imaging modalities and key investigations in the literature published between 1980 and 2009. In this structured review, we have assessed studies in the literature that have addressed follow-up intervals, imaging tests, tumour markers, endoscopy and thyroid function tests as a part of the routine post-treatment surveillance in HNC patients. Studies analysing the cost benefit of such surveillance have also been addressed. Based on the evidence presented, we have compiled definitive recommendations for effective surveillance/post-treatment follow-up in patients with HNC. [Copyright &y& Elsevier]

Summary: Dysphagia is an important symptom of head and neck cancer (HNC), as well as representing a significant complication of its treatment. The treatment of HNC can result in neuromuscular and sensory damage affecting any stage of the swallow. The protective mechanisms during swallowing afforded by the structures in the pharynx are also affected in HNC. This article reviews the effect of the various treatment modalities in HNC on the swallowing mechanism. Various interventions which may play in role in relieving this dysphagia are also discussed. Due stress has been laid on the need for a multi-disciplinary approach for an optimal outcome in rehabilitating a patient’s swallow after treatment for HNC. [Copyright &y& Elsevier]

Summary: The TNM system of staging cancers is a simple and effective method to map the extent of tumours. It had traditionally strived to maintain a balance between being simple and user-friendly on one hand and comprehensive on the other. A number of revisions have taken place over the years with the goal of improving utility. However, numerous controversies surround the TNM system. There is a school of thought that contends that patient co-morbidity and specific tumour-related factors should be incorporated to add further prognostic capabilities in the TNM system, but this raises concerns that such an approach may unnecessarily complicate the system. This review highlights some controversies that surround the TNM system and suggests prognostic indicators that may be added to make it more useful in guiding treatment decisions and predicting outcomes. [Copyright &y& Elsevier]

Summary: Oral and oropharyngeal cancers are amongst the commonest cancers worldwide and present a major health problem. Owing to their critical anatomical location and complex physiologic functions, the treatment of oral and oropharyngeal cancers often affects important functions, including speech. The importance of speech in a patient’s life can not be overemphasized, as its loss is often associated with severe functional and psychosocial problems and a poor quality of life. A thorough understanding of the speech problems that are faced by these patients and their timely management is the key to providing a better functional quality of life, which must be one of the major goals of modern oncologic practice. This review summarises key methods of evaluation and outcome of speech functions in the literature on oral and oropharyngeal cancer published between January 2000 and December 2008. Speech has been generally overlooked and poorly investigated in this group of patients. This review is an attempt to fill this gap by conducting the first speech-specific review for oral and oropharyngeal cancer patients. We have proposed guidelines for better understanding and management of speech problems faced by these patients in their day-to-day life. [Copyright &y& Elsevier]

Summary: Quality of life (QOL) is by definition a multi-dimensional global construct that has become an increasingly important outcome measure in cancer treatment. The impact of a head and neck cancer (HNC) diagnosis on the person and the consequences of its treatment cross multiple functional domains that have a clear and direct influence on one’s post-treatment well-being and associated QOL. The evaluation of QOL and performance outcome in cancer is critical to optimal patient care, comprehensive evaluation of treatment alternatives, and the development of informed rehabilitation and patient education services. Despite the difficulties of going from concept to quantification of patient perceptions, the number of instruments available to measure QOL psychometrically has increased rapidly. Assessments can now be made in a variety of distinctive ways using both specific and generic measures. There is no gold-standard questionnaire and the choice is based on psychometric properties, research objectives and study design. QOL assessment has evolved over the years into an organised scientific discipline, such that useful insights can be obtained by a review of the current literature. However, more work needs to be done to improve the applicability and clinical utility of QOL assessment. Most importantly, QOL studies should be reported in such a way as to provide clinically meaningful data to physicians and surgeons, in order to link research to clinical practice. Further attention should be paid to the development of newer theoretical models, minimalist approaches, development of more sensitive and specific instruments and the effective use of modern technology to achieve this objective. [Copyright &y& Elsevier]

Summary: To optimize tracheoesophageal (TO) speech after total laryngectomy, it is vital to have a robust tool of assessment to help investigate deficiencies, document changes, and facilitate therapy. We sought to evaluate and validate electroglottography (EGG) as an important tool in the multidimensional assessment of TO speech. This study is a cross-sectional study of the largest cohort of TO speakers treated by a single surgeon. A second group of normal laryngeal speakers served as a control group. EGG analysis of both groups using connected speech and sustained vowels was performed. Two trained expert raters undertook perceptual evaluation using two accepted scales. EGG measures were then analyzed for correlation with treatment variables. A separate correlation analysis was performed to identify EGG measures that may be associated with perceptual dimensions. Our data from EGG analysis are similar to data obtained from conventional acoustic signal analysis of TO speakers. Sustained vowel and connected speech parameters were poorer in TO speakers than in normal laryngeal speakers. In perceptual evaluation, only grade (G) of the GRBAS scale and Overall Voice Quality appeared reproducible and reliable. T stage, pharyngeal reconstruction and method of closure, cricopharyngeal myotomy, and postoperative complications appear to be correlated with the EGG measures. Five voice measures—jitter, shimmer, average frequency, normalized noise energy, and irregularity—correlated well with the key dimensions of perceptual assessment. EGG is an important assessment tool of TO speech, and can now be reliably used in a clinical setting. [Copyright &y& Elsevier]

Summary: Francis and colleagues reported an association between blood transfusion and worsened cancer prognosis. Since then there has been much debate over whether there is in fact such an association. We propose a possible mechanism which could explain much of the conflicting clinical and experimental evidence, and which can be readily tested experimentally. It is suggested that the extracellular accumulation of bioactive factors in blood transfusion products can directly and indirectly cause tumour growth and hence a worsening of prognosis. This theory can be applied both in vitro and in vivo. Two separate UK studies have shown that perioperative blood transfusion is associated with worsened prognosis in head and neck squamous cell cancer patients. Furthermore, pilot experiments have shown that as blood ages, endothelial growth factors are leached from the metabolically compromised red cell. We believe that we have provided a rationale to explain the conflicting findings of research to date in this area. That red cells should store endothelial reparative growth factors would seem logical, as would the release of any factors as the metabolic processes of the anucleate red cell decline over time. As a result, leuco-depletion should be promoted and blood transfusion should be avoided if possible. [Copyright &y& Elsevier]

Summary: The objective of this study was to assess the difference in voice quality as defined by acoustical analysis using sustained vowel in laryngectomized patients in comparison with normal volunteers. This was designed as a retrospective single center cohort study. An adult tertiary referral unit formed the setting of this study. Fifty patients (40 males) who underwent total laryngectomy and 31 normal volunteers (18 male) participated. Group comparisons with the first three formant frequencies (F 1, F 2, and F 3) using linear predictive coding (LPC) (Laryngograph Ltd, London, UK) was performed. The existence of any significant difference of F 1, F 2, and F 3 between the two groups using the sustained vowel /i/ and the effects of other factors namely, tumor stage (T), chemoradiotherapy, pharyngectomy, cricothyroid myotomy, closure of pharyngoesophageal segment, and postoperative complication were analyzed. Formant frequencies F 1, F 2, and F 3 were significantly different in male laryngectomees compared to controls: F 1 (P <0.001, Mann-Whitney U test), F 2 (P <0.001, Student''s t test), and F 3 (P =0.008, Student''s t test). There was no significant difference between females in both groups for all three formant frequencies. Chemoradiotherapy and postoperative complications (pharyngocutaneous fistula) caused a significantly lower formant F 1 in men, but showed little effect in F 2 and F 3. Laryngectomized males produced significantly higher formant frequencies, F 1, F 2, and F 3, compared to normal volunteers, and this is consistent with literature. Chemoradiotherapy and postoperative complications significantly influenced the formant scores in the laryngectomee population. This study shows that robust and reliable data could be obtained using electroglottography and LPC in normal volunteers and laryngectomees using a sustained vowel. [Copyright &y& Elsevier]

c-erbB receptor signalling induces pleiotropic responses and influences several biological functions involved in the pathogenesis and progression of HNSCC. Aberrant expression of multiple c-erbB receptors and ligands is frequently observed in tumour cells. EGFR appears to be a dominant factor controlling the malignant phenotype in HNSCC at least in part via regulation of molecules involved in invasive and angio-/lymphangiogenic processes. Although c-erbB-2 is an orphan receptor, the formation of heterodimer complexes appears to be an important mechanism for inter-receptor activation and synergistic signal transduction. The roles of c-erbB-3 and c-erbB-4 in HNSCC progression are less clear. However, their ability to form heterodimers with other c-erbB family members enhances proliferation and invasion in HNSCC cells. At least two major downstream signalling pathways, MAPK and PI3K, are involved in the transcriptional regulation of proteases and cytokines implicated in invasion and angiogenesis. Studies using clinical specimens confirmed experimental data that co-operative signalling of c-erbB receptors may play a significant role in the pathogenesis of HNSCC. Most therapeutic studies in HNSCC so far have focused on the strategies targeting of EGFR. Due to the complexity of the system both at the receptor and ligand levels and the integrated biological functions of the c-erbB family in HNSCC, the effect of combined c-erbB blockade (or their downstream signalling pathways) on HNSCC progression should be explored. [ABSTRACT FROM AUTHOR]

Primary liposarcoma of the thyroid gland is extremely rare with only two previous reports in the literature. We report two further cases, both patients presenting with rapid airways compression. Patient 1 had clinical, radiographic, and biopsy appearances suggesting benign goiter. Patient 2 had a long-term history of benign goiter, a previous partial thyroidectomy, and more recent biopsies showing liposarcoma. The management of such rare conditions is always challenging. [Copyright &y& Elsevier]

Summary: We undertook a service evaluation to establish how oropharyngeal dysphagia is managed in head and neck cancer patients receiving radiotherapy in the United Kingdom. A web-based survey including 23 open and closed questions was distributed to Speech and Language Therapy (SLT) teams via a national network of Royal College of Speech and Language Therapists (RCSLT) special interest groups with members involved in head and neck cancer care. Forty-six teams responded to the survey and 89% completed the questionnaire fully. Fifty percent (n =21/42) of the SLT teams reported routinely seeing patients prior to commencing radiotherapy. Baseline oromotor assessment (85.7% (n =36/42)), clinical dysphagia assessment (90.5% (n =38/42)) and information provision on the potential treatment effects on swallowing (97.6% (n =41/42)) and communication ability (85.7% (n =36/42)) were the most common components of initial evaluation. In keeping with expert opinion and emerging evidence, prophylactic swallowing exercises were administered by 71.4% (n =30/42) of teams targeting specific aspects of swallowing, although the nature, intensity and duration of programmes varied. A range of measures are used to monitor progress during treatment. Our survey highlighted that resource limitations affect service provision with some teams managing the consequences of treatment rather than proactive multidisciplinary intervention prior to and during treatment. Cancer- and treatment-related dysphagia can impact significantly on a broad range of outcomes following radiotherapy. There is variability in dysphagia service provision to patients before, during and following treatment. Comprehensive evaluation of swallowing function prior to treatment and proactive management can yield benefits for patients, inform multidisciplinary case management and support those involved in clinical trials to accurately determine treatment effects. [Copyright &y& Elsevier]

Summary: The aim of this study was to explore post-treatment speech impairments using English version of Speech Handicap Index (SHI) (first speech-specific questionnaire) in a cohort of oral cavity (OC) and oropharyngeal (OP) cancer patients. Sixty-three consecutive OC and OP cancer patients in follow-up participated in this study. Descriptive analyses have been presented as percentages, while Mann–Whitney U-test and Kruskall–Wallis test have been used for the quantitative variables. Statistical Package for Social Science-15 statistical software (SPSS Inc., Chicago, IL) was used for the statistical analyses. Over a third (36.1%) of patients reported their speech as either average or bad. Speech intelligibility and articulation were the main speech concerns for 58.8% and 52.9% OC and 31.6% and 34.2% OP cancer patients, respectively. While feeling of incompetent and being less outgoing were the speech-related psychosocial concerns for 64.7% and 23.5% OC and 15.8% and 18.4% OP cancer patients, respectively. Worse speech outcomes were noted for oral tongue and base of tongue cancers vs. tonsillar cancers, mean (SD) values were 56.7 (31.3) and 52.0 (38.4) vs. 10.9 (14.8) (P <0.001) and late vs. early T stage cancers 65.0 (29.9) vs. 29.3 (32.7) (P <0.005). The English version of the SHI is a reliable, valid and useful tool for the evaluation of speech in HNC patients. Over one-third of OC and OP cancer patients reported speech problems in their day-do-day life. Advanced T-stage tumors affecting the oral tongue or base of tongue are particularly associated with poor speech outcomes. [ABSTRACT FROM AUTHOR]

Summary: Head and neck squamous cell cancer (HNSCC) is the sixth most common cancer in the world. Effective therapeutic modalities such as surgery, radiation, chemotherapy and combinations of each are used in the management of this disease. Efforts are ongoing throughout the world to improve early detection and prevention of HNSCCs. Often, treatment fails to obtain total cancer cure and this is more likely with advanced stage disease. In recent years it appears that one of the key determinants of treatment failure may be the presence of cancer stem cells (CSC) that ‘escape’ currently available therapies. CSCs form a minute portion of the total tumour burden but may play a disproportionately important role in determining outcomes. Molecular mechanisms which underlie the genesis of CSCs are yet not fully understood and their detection within the total tumour bulk remains a challenge. Specific markers like Aldehyde dehydrogenase 1 (ALDH1), CD44 and Bmi-1 have shown early promising results both in CSC detection and in guiding treatment protocols. CSCs have been shown to be relatively resistant to standard treatment modalities. It is hoped that developing robust in vitro and in vivo experimental models of CSCs might provide a means of devising more effective therapeutic strategies. [ABSTRACT FROM AUTHOR]

Purpose: A systematic review to establish what evidence is available for swallowing outcomes following IMRT for head and neck cancer.Methods: Online electronic databases were searched to identify papers published in English from January 1998 to December 2009. Papers were independently appraised by two reviewers for methodological quality, method of swallowing evaluation and categorized according to the World Health Organisation's International Classification of Health Functions. The impact of radiation dose to dysphagia aspiration risk structures (DARS) was also evaluated.Results: Sixteen papers met the inclusion criteria. The literature suggests that limiting the radiation dose to certain structures may result in favourable swallowing outcomes. Methodological limitations included variable assessment methods and outcome measures and heterogeneity of patients. There are only limited prospective data, especially where pre-treatment measures have been taken and compared to serial post-treatment assessment.Conclusions: Few studies have investigated the impact of IMRT on swallow function and the impact on everyday life. Initial studies have reported potential benefits but are limited in terms of study design and outcome data. Further well designed, prospective, longitudinal swallowing studies including multidimensional evaluation methods are required to enable a more comprehensive understanding of dysphagia complications and inform pre-treatment counselling and rehabilitation planning. [ABSTRACT FROM AUTHOR]

Summary: The invasion of robotic technology in surgical fields cannot be ignored. Its success in various surgical disciplines especially in urology, cardiology, and gynaecology has set its own benchmarks. Extrapolation of similar results in head and neck is still in experimental stages and long term results are still eagerly awaited to truly establish its efficacy beyond awe and reality. Nonetheless, its future role in this area is inevitable given the encouraging results obtained so far. This article covers the inception to current application to speculation of robotic technology in complex area of head and neck surgery. [Copyright &y& Elsevier]

Summary: Secondary tumours of small intestine account for 10% of all small bowel cancers. The most common sites of primary tumour metastasizing to small bowel are uterus, cervix, colon, lung, breast and melanoma. The majority of these metastatic tumours come from adenocarcinoma primaries; squamous cell carcinoma constitutes a very small proportion of all metastatic small intestinal lesions. Metastasis to small bowel by head and neck squamous cell carcinoma is extremely rare and carries an unfavourable prognosis. Owing to the limited number of published studies, its characteristic features, clinical presentation and outcomes are poorly described. This work aims at specifying these characteristics by reviewing, compiling, analysing and reporting all published cases in the published literature on small bowel metastasis secondary to head and neck squamous cell carcinoma. To the best of our knowledge, this is the first comprehensive review article on the small intestinal metastasis from head and neck squamous cell carcinoma. [Copyright &y& Elsevier]

Purpose: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive cancers, and the current protocol of hyperfractionated accelerated radiotherapy was initiated to improve survival while limiting toxicities. Methods and Materials: All patients with ATC from 1991 to 2002 were accrued and received megavoltage radiotherapy from the mastoid processes to the carina up to 60 Gy in twice-daily fractions of 1.8 and 2 Gy, 6 hours apart. Results: Thirty-one patients were accrued with a median age of 69 years, and 55% were women. Debulking was performed in 26%, and total thyroidectomy, in 6%, whereas 68% received radical radiotherapy alone. Local control data were available for 27 patients: 22% had a complete response, 26% had a partial response, 15% showed progressive disease, and 37% showed static disease. Median overall survival for all 31 patients was 70 days (95% confidence interval, 40–99). There was no significant difference in median survival between patients younger (70 days) and older than 70 years (42 days), between men (70 days) and women (49days), and between patients receiving postoperative radiotherapy (77 days) and radical radiotherapy alone (35 days). Grade III or higher skin erythema was seen in 56% patients; desquamation in 21%; dysphagia in 74%; and esophagitis in 79%. Conclusion: The current protocol failed to offer a significant survival benefit, was associated with severe toxicities, and thus was discontinued. There is a suggestion that younger patients with operable disease have longer survival, but this would require a larger study to confirm it. [Copyright &y& Elsevier]

Purpose: Hypoxia in patients with head-and-neck cancer (HNC) is well established and known to cause radiation resistance and treatment failure in the management of HNC. This study examines the role of parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and perfusion computed tomography (CT) as surrogate markers of intratumoral hypoxia, defined by using the exogenous marker of hypoxia pimonidazole and the endogenous marker carbonic anhydrase 9 (CA9). Methods and Materials: Patients with HNC underwent preoperative DCE-MRI, perfusion CT, and pimonidazole infusion. Imaging parameters were correlated with pimonidazole and CA9 staining. The strength of correlations was tested by using a two-tailed Spearman''s rank correlation coefficient. Results: Twenty-three regions of interest were analyzed from the 7 patients who completed the DCE-MRI studies. A number of statistically significant correlations were seen between DCE-MRI parameters (volume transfer between blood plasma and extracellular extravascular space [EES], volume of EES, rate constant between EES and blood plasma, time at arrival of contrast inflow, time to peak, average gradient, and time to onset) and areas with a pimonidazole score of 4. In the case of CA9 staining, only a weak correlation was shown with wash-in rate. There were no significant correlations between perfusion CT parameters and pimonidazole staining or CA9 expression. Conclusion: Intratumoral hypoxia in patients with HNC may be predicted by using DCE-MRI; however, perfusion CT requires further investigation. [Copyright &y& Elsevier]

Abstract: Background and purpose: To measure voice outcomes following accelerated hypofractionated radiotherapy for larynx cancer. Materials and methods: Twenty-five patients with T1/T2 glottic cancer underwent serial electroglottographic and acoustic analysis (sustained vowel/i/ and connected speech) before radiotherapy and 1, 6 and 12 months post-treatment. Twenty-five normal subjects served as a reference control population. Results: Pre-treatment measures were significantly worse for larynx cancer patients. Median jitter (0.23% vs 0.97%, p =0.001) and shimmer (0.62dB vs 0.98dB, p =0.05) and differences in data ranges reflected greater frequency and amplitude perturbation in the larynx cancer patients. Pre-treatment Mean Phonation Time (MPT) was significantly reduced (21s vs 14.8s, p =0.002) in larynx cancer patients. There was a trend towards improvement of jitter, shimmer and normalized noise energy at 12 months post-treatment. MPT improved but remained significantly worse than for normal subjects (21s vs 16.4s, p =0.013). Average fundamental frequency resembled normal subjects, including improvement of the measured range (91.4–244.6Hz in controls vs 100–201Hz in post-treatment larynx cancer patients). Conclusions: This non-invasive technique effectively measures post-treatment vocal function in larynx cancer patients. This study demonstrated improvement of many key parameters that influence voice function over 12 months after radiotherapy. [Copyright &y& Elsevier]

Purpose: To conduct prospective electroglottographic analyses of voice outcomes after radical chemoradiotherapy for locally advanced laryngopharyngeal cancers and to compare them with patients who have undergone total laryngectomy (TL). Patients and Methods: Twenty-one patients (19 male, 2 female, median age [range] 65 [50–85] years) with Stage III/IV laryngopharyngeal cancer received induction chemotherapy followed by radical chemoradiotherapy. Electroglottography, using the sustained vowel /i/ and connected speech, was performed before treatment and 1, 6, and 12 months after treatment. In addition, single voice recordings were taken from 21 patients (16 male, 5 female, aged 65 [50–84] years) who had undergone TL and surgical voice restoration and from 21 normal controls (18 male, 3 female, aged 65 [33–80] years). Results: Before treatment the vocal measures for the chemoradiotherapy patients were significantly different from normal controls in jitter (p = 0.02), maximum phonation time (MPT) (p = 0.001), and words per minute (WPM) (p = 0.01). At 12 months after treatment MPT and WPM had normalized, but jitter and normalized noise energy were significantly worse than in normal controls. Comparison of voice outcomes at 12 months for chemoradiotherapy patients revealed superiority over the TL group in all parameters except MPT (18.2 s vs. 10.4 s, p = 0.06). Analysis of the recovery of voice up to 12 months after treatment revealed progressive improvement in most electroglottographic measures. Conclusions: This prospective study demonstrates significantly better outcome for patients treated with chemoradiotherapy as compared with TL. Progressive normalization of many voice parameters occurs over the 12 months following chemoradiotherapy. [Copyright &y& Elsevier]

Abstract: Background: Treatment of extensive recurrent cervical lymph node metastases from previously irradiated head and neck cancer represents a difficult clinical challenge. We report the results of an approach of maximal surgical debulking and manually after-loaded intra-operative brachytherapy. Patients and methods: Seventy-four procedures were carried out at the Royal Marsden Hospital between 1979 and 2003. All patients had previously been treated with radical radiotherapy or chemoradiation. Patients underwent maximal surgical debulking, followed by brachytherapy to the tumour bed with low-dose rate 192Ir to a dose of 60Gy to the reference isodose using the Paris system. Results: Overall and disease specific survival rates were 31% and 28% at two years and 23% and 17% at five years. Corresponding Loco-regional control rates were 37% and 23%, respectively. Fifty per cent of patients developed metastatic disease within 5 years of treatment. Best results were obtained with surgical excision, brachytherapy and reconstruction of the skin defect using a vascularised myo-cutaneous flap with in-field control rates of 72% at two years and 66% at 5 years. Nine per cent of patients developed fistulae, 4% had haemorrhage and 8% wound breakdown/infection. Conclusions: Maximal surgical debulking, including removal of overlying skin, and brachytherapy to the surgical tumour bed provides high levels of local control, and can be achieved with acceptable morbidity. Only a minority of patients achieve long-term survival because of the high risk of systemic relapse. [Copyright &y& Elsevier]

Summary: Impairment of swallowing function is a common multidimensional symptom complex seen in 50–75% of head and neck cancer (HNC) survivors. Although there are a number of validated swallowing-specific questionnaires, much of their focus is on the evaluation of swallowing-related quality of life (QOL) rather than swallowing as a specific function. The aim of this study was to validate the Sydney Swallow Questionnaire (SSQ) as a swallowing-specific instrument in HNC patients. Fifty-four consecutive patients in follow-up for oral and oropharyngeal cancer completed the SSQ and MD Anderson Dysphagia Inventory (MDADI). Thirty-one patients completed both questionnaires again four weeks later to address test–retest reliability. Internal consistency and test–retest reliability was assessed using Cronbach’s α and Spearman’s correlation coefficient, respectively. Construct validity (including group validity) and criterion validity were determined using Spearman’s correlation coefficient and Mann–Whitney U-test. Internal consistency, test–retest reliability, construct validity, group validity and criterion validity of the SSQ was found to be significant (P <0.01). We were able to demonstrate the reliability and validity of the SSQ in HNC patients. The SSQ is a precise, reliable and valid tool for assessing swallow in this patient group. [Copyright &y& Elsevier]