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Dysphagia in Solid Tumors Outside the Head, Neck or Upper GI Tract: Clinical Characteristics

Open AccessPublished:September 01, 2022DOI:https://doi.org/10.1016/j.jpainsymman.2022.08.019

      Abstract

      Context

      Dysphagia is common in cancer, but underlying pathophysiology and manifestations within patients are unknown.

      Objectives

      To examine dysphagia characteristics in those with solid malignancies outside the head, neck and upper gastrointestinal tract.

      Methods

      Seventy-three individuals with dysphagia (46 male, 27 female, aged 37-91) were recruited from a parent trial conducted in two acute hospitals and one hospice. Cranial nerve function, Oral Health Assessment Tool (OHAT), Mann Assessment of Swallowing Ability (MASA) and Functional Oral Intake Scale (FOIS) evaluated swallow profile.

      Results

      Only 9/73 (12%) had documented dysphagia prior to study enrollment. MASA risk ratings found n=61/73 (84%) with dysphagia risk and n=22/73 (30%) with aspiration risk. Food texture modification was required for n=34/73 (47%), fluid texture modification for n=1/73 (1%). Compensatory strategies for food were needed by n=13/73 (18%) and for fluids by n=24/73 (33%). Cranial nerve deficits were present in n=43/73 (59%). Oral health problems were common, with xerostomia in two-thirds. Worse dysphagia on MASA was associated with disease progression, affecting hospice, and palliative care the most. Worse performance status was indicative of poorer MASA raw score (P<0.001, OR 2.2, 95% CI 1.5–3.4), greater risk of aspiration (P=0.005, OR 2.1, 95% CI 1.3-3.6) and lower FOIS (P=0.004, OR 2.0, 95% CI 1.2–3.2).

      Conclusion

      Dysphagia management in those with cancer requires robust assessment to uncover clinically important needs like food texture modification and safe swallowing advice. Better assessment tools should be developed for this purpose. Oral health problems should be routinely screened in this population since they exacerbate dysphagia.

      Key Words

      Key message

      This is study used swallow evaluation to examine characteristics and implications of dysphagia in those with solid cancers outside the head, neck and upper GI tract. Dysphagia was associated with oral health difficulties, cranial nerve problems and disease progression. Patients required advice on how to safely and efficiently swallow food.

      Introduction

      Dysphagia in cancer is usually associated with head, neck or esophageal cancers. Recent research revealed it is common in cancers outside anatomic swallow regions. Kenny et al.
      • Kenny C
      • Regan J
      • Balding L
      • et al.
      Dysphagia prevalence and predictors in cancers outside the head, neck, and upper gastrointestinal tract.
      used multimodal swallow examination in 385 individuals with primary solid malignancies outside the head, neck and upper gastrointestinal tract (GI) tract, where dysphagia prevalence was 19%. Those under palliative care (PC), in hospice, or with worse overall performance status were most at risk. Dysphagia was also associated with poorer overall quality of life. Frowen et al.
      • Frowen J.
      Dysphagia in patients with non-head and neck cancer.
      conducted a similar study with patient-reported swallowing difficulties as a diagnostic criterion. They identified a prevalence of 49% for solid tumors outside swallow regions.
      Multiple potential mechanisms for dysphagia in this population have been hypothesized. Radiotherapy may exacerbate dysphagia in radiosensitive organs of the upper aerodigestive tract from fibrosis, mucositis, and xerostomia.
      • Raber-Durlacher JE
      • Brennan MT
      • Verdonck-de Leeuw IM
      • et al.
      Swallowing dysfunction in cancer patients.
      ,
      • King SN
      • Dunlap NE
      • Tennant PA
      • Pitts T.
      Pathophysiology of radiation-induced dysphagia in head and neck cancer.
      These organs are usually spared during radiotherapy for cancers outside anatomic swallow regions, except perhaps lung cancer, where proximity of the esophagus may increase risk.
      • Raber-Durlacher JE
      • Brennan MT
      • Verdonck-de Leeuw IM
      • et al.
      Swallowing dysfunction in cancer patients.
      ,
      • Gong B
      • Jiang N
      • Yan G
      • et al.
      Predictors for severe acute esophagitis in lung cancer patients treated with chemoradiotherapy: a systematic review.
      Chemotherapy induces mucositis, which may cause a painful swallow and is associated with anorexia, dehydration and malnutrition.
      • Denaro N
      • Merlano MC
      • Russi EG
      Dysphagia in head and neck cancer patients: pretreatment evaluation, predictive factors, and assessment during radio-chemotherapy, recommendations.
      ,
      • Brown CG
      • Wingard J.
      Clinical consequences of oral mucositis.
      Both radio- and chemotherapy are also associated with dysgeusia (altered taste) and dysosmia (altered smell).
      • Raber-Durlacher JE
      • Brennan MT
      • Verdonck-de Leeuw IM
      • et al.
      Swallowing dysfunction in cancer patients.
      ,
      • Belqaid K
      • Tishelman C
      • McGreevy J
      • et al.
      A longitudinal study of changing characteristics of self-reported taste and smell alterations in patients treated for lung cancer.
      ,
      • Haxel BR
      • Berg S
      • Boessert P
      • Mann WJ
      • Fruth K.
      Olfaction in chemotherapy for head and neck malignancies.
      While these may not directly cause dysphagia, chemosensory input modulates swallow responsiveness, with increased sensory input providing better swallow response.
      • Scarborough DR
      • Pelletier C.
      The role of chemosenses in swallowing disorders across the lifespan.
      Targeted (or biological) therapies refer to drugs that interfere with carcinogenesis and tumor growth.
      • Watson MS
      Oncology.
      Their impact on swallow function is unknown, though they cause taste changes to a greater extent than other treatment modalities.
      • Di Meglio J
      • Dinu M
      • Doni L
      • et al.
      Occurrence of dysgeusia in patients being treated for cancer.
      Oropharyngeal colonization by candida is highly prevalent amongst those undergoing anti-tumor treatment. One study
      • Gligorov J
      • Bastit L
      • Gervais H
      • et al.
      Prevalence and treatment management of oropharyngeal candidiasis in cancer patients: results of the French CANDIDOSCOPE study.
      found an overall prevalence of almost 10%; rates were highest for chemoradiation, or those on two or more cytotoxic agents. Candida induced odynophagia, taste changes, and xerostomia, which adversely affected swallow efficiency, enjoyment, and safety.
      Some specific tumor locations may directly interfere with swallow function, such as lung cancer, which may induce dysphagia through various mechanisms like interruption of the breath/swallow cycle, esophageal compression, tracheoesophageal tumor invasion or vagus nerve compression.
      • Camidge DR.
      The causes of dysphagia in carcinoma of the lung.
      ,
      • Brady GC
      • Carding PN
      • Bhosle J
      • Roe JW.
      Contemporary management of voice and swallowing disorders in patients with advanced lung cancer.
      Similarly, primary brain tumors or brain metastases may directly interfere with neurological swallow function.
      • Garon BR
      • Sierzant T
      • Ormiston C.
      Silent aspiration: results of 2,000 video fluoroscopic evaluations.
      ,
      • Walbert T
      • Khan M.
      End-of-life symptoms and care in patients with primary malignant brain tumors: a systematic literature review.
      Clinical bedside swallow evaluation is a critical component of dysphagia diagnosis. This comprises a detailed history, general patient status (physical and cognitive evaluation), cranial nerve examination, oral cavity inspection, and direct patient observation when swallowing different food and fluid consistencies.
      • O'Horo JC
      • Rogus-Pulia N
      • Garcia-Arguello L
      • Robbins J
      • Safdar N.
      Bedside diagnosis of dysphagia: a systematic review.
      ,
      • Leslie P
      • Carding PN
      • Wilson JA.
      Investigation and management of chronic dysphagia.
      These items form a ‘core set’ that are routinely evaluated to support a dysphagia diagnosis.
      • McAllister S
      • Kruger S
      • Doeltgen S
      • Tyler-Boltrek E
      Implications of variability in clinical bedside swallowing assessment practices by speech language pathologists.
      This accounts for variations in pathophysiology and diseases which cause swallowing difficulties. A multimodal approach to dysphagia diagnosis is therefore recommended.
      • O'Horo JC
      • Rogus-Pulia N
      • Garcia-Arguello L
      • Robbins J
      • Safdar N.
      Bedside diagnosis of dysphagia: a systematic review.
      • Leslie P
      • Carding PN
      • Wilson JA.
      Investigation and management of chronic dysphagia.
      • McAllister S
      • Kruger S
      • Doeltgen S
      • Tyler-Boltrek E
      Implications of variability in clinical bedside swallowing assessment practices by speech language pathologists.
      While previous studies have screened for dysphagia in those with primary cancers outside the head, neck and upper GI tract, none have diagnosed dysphagia by multimodal assessment nor identified characteristics. We wished to understand the clinical need to assess and manage swallowing difficulties in this complex population. Research objectives were to quantify dysphagia severity, characterize pathophysiological deficits and determine associations between these. This research was novel, so no a priori hypotheses were considered.

      Methods

      Design

      Data collection was completed cross-sectionally, once for each participant and lasted 24 weeks. Data were collected by the first author who is an advanced dysphagia practitioner. STROBE
      • von Elm E
      • Altman DG
      • Egger M
      • et al.
      The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies.
      guided study conduct and reporting. Ethical approval was obtained from the Research Ethics Committees of each recruitment setting. Written informed consent was obtained from participants.

      Recruitment

      Participants were recruited consecutively from two acute hospitals and one hospice under either private or public health care services. Care was led by Medical Oncology (MO), Radiation Oncology (RO), or PC teams, who referred individuals to the study. Participants attended in-patient (IP), out-patient (OP), oncology day ward (DW), or day hospice (DH). Those in DW were receiving anti-tumor treatments. Those in DH received a nurse-led, multidisciplinary rehabilitation service.

      Inclusion/Exclusion

      Participants were adults (≥18) with active primary solid malignancies outside the head, neck or upper GI tract. They were aware of their diagnosis and spoke English. Those deemed by their supervising clinician to be too unwell to participate (e.g. actively dying, acutely distressed) were excluded. Also excluded were individuals with non-solid tumors, or current/past primary cancer of the head, neck or upper GI tract.

      Sample

      Our sample was part of a larger study, which investigated dysphagia prevalence and predictors in adults with solid malignancies outside the head, neck, and upper GI tract.
      • Kenny C
      • Regan J
      • Balding L
      • et al.
      Dysphagia prevalence and predictors in cancers outside the head, neck, and upper gastrointestinal tract.
      That study recruited 385 individuals by consecutive sampling and screened them for dysphagia. Eating Assessment Tool (EAT-10)
      • Belafsky PC
      • Mouadeb DA
      • Rees CJ
      • et al.
      Validity and reliability of the Eating Assessment Tool (EAT-10).
      was chosen for screening because it was validated on a mixed-disease population. A score ≥3 was a positive screen per test instructions. Participants were then asked whether they noticed difficulty chewing or swallowing since their cancer diagnosis, based on a previously validated screening question.
      • Ding R
      • Logemann JA.
      Patient self-perceptions of swallowing difficulties as compared to expert ratings of videofluorographic studies.
      A ‘yes’ to either question was a positive screen, unless the difficulty was historical and fully resolved. In total, n=73/385 (19%) met criteria to proceed to full evaluation and were ultimately included. Of these, n=10/73 (14%) were not identified by EAT-10, but rather the additional screening questions. Participant characteristics were independent variables (Table 1).
      Table 1Participant Demographic and Clinical Characteristics
      Characteristicn=73
      Mean age (SD, range)66 (±13, 37–91)
      Sex, n (%)
       Male46 (63%)
       Female27 (37%)
      Primary cancer site, n (%)
       Colorectal18 (25%)
       Lung15 (21%)
       Kidney9 (12%)
       Prostate10 (14%)
       Pancreas4 (5%)
       Bladder3 (4%)
       Breast3 (4%)
       Mesothelioma3 (4%)
       Other (cervix, gallbladder, mediastinum, melanoma, ovary, sarcoma, testicle, thymus)1 (1%)
      Disease extent, n (%)
       Metastatic47 (64%)
       Locoregional26 (36%)
      Mean time since diagnosis (SD)24 months (±30)
      Health care organization, n (%)
       Public42 (58%)
       Private28 (38%)
       Unknown3 (4%)
      Setting, n (%)
       Hospital49 (67%)
       Hospice24 (33%)
      Patient location, n (%)
       IP41 (56%)
       DW14 (19%)
       OP12 (16%)
       DH6 (8%)
      Primary health care team, n (%)
       MO43 (59%)
       PC27 (37%)
       RO3 (4%)
      Ongoing anti-cancer treatment, n (%)
      Yes53 (73%)
      No20 (27%)

      Screening Phase

      Screening captured participants’ general cognitive, physical and psychological health to identify potential associations with dysphagia severity. Cognitive status was determined by 4AT,
      • Bellelli G
      • Morandi A
      • Davis DH
      • et al.
      Validation of the 4AT, a new instrument for rapid delirium screening: a study in 234 hospitalised older people.
      where scores ≥3 indicate impaired cognition. Performance status was by ECOG-PS,
      • Oken MM
      • Creech RH
      • Tormey DC
      • et al.
      Toxicity and response criteria of the Eastern Cooperative Oncology Group.
      where 0 indicates best and 4 worst physical function. Global quality of life was rated 0 (worst) to 10 (best) on a linear analogue scale.
      • Singh JA
      • Satele D
      • Pattabasavaiah S
      • Buckner JC
      • Sloan JA.
      Normative data and clinically significant effect sizes for single-item numerical linear analogue self-assessment (LASA) scales.
      Aerodigestive and nutritional symptoms were captured because they commonly co-occur with dysphagia
      • Kenny C
      • Regan J
      • Balding L
      • et al.
      Dysphagia prevalence and predictors in cancers outside the head, neck, and upper gastrointestinal tract.
      ,
      • Aktas A
      • Walsh D
      • Hu B
      Cancer symptom clusters: an exploratory analysis of eight statistical techniques.
      and were marked as present or absent within the last week. Height and weight allowed calculation of weight loss and cachexia diagnosis using international consensus guidelines.
      • Fearon K
      • Strasser F
      • Anker SD
      • et al.
      Definition and classification of cancer cachexia: an international consensus.
      If documented height and weight data were available, these were given priority over self-report.
      Each participant's cancer diagnosis and profile, chemistry/hematology results (albumin, c-reactive protein, neutrophil-to-lymphocyte ratio), number of comorbidities and treatment history were captured to reflect overall health. All screening items are in the supplemental file and were independent variables.

      Dysphagia Evaluation

      Those with a positive dysphagia screen were evaluated multimodally. A full list of evaluation items is in the supplemental file. Participants described potential swallowing and food/fluid intake issues using two open questions, similar to a clinical case history.
      • 1)
        Can you tell me about any changes to your eating or drinking habits since you were diagnosed?
      • 2)
        Are you avoiding any particular foods or drinks since you were diagnosed? [If ‘yes’:] Why?
      Responses were transcribed verbatim. These questions yielded large amounts of information about patient experiences and will be reported separately.
      Sensory and motor cranial nerve function were examined with a protocol adapted from two published sources.
      • Talley NJ
      • O'Connor S
      Clinical Examination: A systematic guide to physical diagnosis.
      ,
      • Damodaran O
      • Rizk E
      • Rodriguez J
      • Lee G.
      Cranial nerve assessment: a concise guide to clinical examination.
      Cranial nerves V, VII, IX, X, XII were rated as ‘impaired’ or ‘unimpaired’ and were independent variables.
      Oral health was screened by the Oral Health Assessment Tool (OHAT).
      • Chalmers JM
      • King PL
      • Spencer AJ
      • Wright FA
      • Carter KD
      The oral health assessment tool–validity and reliability.
      OHAT rates severity of oral problems by scoring affected structures and physiology. Scores range from 0 (no problems) to 16 (worst oral health). Since OHAT does not discretely diagnose dry mouth, lingual coating, or mucositis, a schema was developed to identify these dysphagia-related features (see supplemental file). OHAT scores and conditions were independent variables.
      Mann Assessment of Swallowing Ability (MASA)
      • Mann G.
      MASA: The Mann Assessment of Swallowing Ability.
      was used based on a systematic review.
      • Kenny C
      • Gilheaney O
      • Walsh D
      • Regan J
      Oropharyngeal dysphagia evaluation tools in adults with solid malignancies outside the head and neck and upper GI tract: a systematic review.
      MASA generates a score out of 200, where lower scores indicate worse dysphagia. It also allows raters to judge dysphagia and aspiration presence as ‘unlikely’, ‘possible’, ‘probable’, or ‘definite’, by Ordinal Risk Ratings (ORRs). ORRs are based on assessment observations and not self-report. These were dependent variables.
      MASA requires administration of liquid and solid bolus items. The International Dysphagia Diet Standardization Initiative (IDDSI) framework
      • Steele CM
      • Namasivayam-MacDonald AM
      • Guida BT
      • et al.
      Creation and initial validation of the international dysphagia diet standardisation initiative functional diet scale.
      was used to describe textures. Room temperature still water (Irish Spring Water; Dunnes Stores, Dublin, Ireland) was for fluid trials (IDDSI 0). A choice of yoghurt (Petit Filou; Yoplait, Dublin, Ireland) or custard (Deliciously Creamy Custard; Sunny South, Dublin, Ireland) were for purée trials (IDDSI 4). A digestive biscuit (Boland's Digestives; Jacob Fruitfield Food Group, Dublin, Ireland) was for regular trials (IDDSI 7). To avoid excluding those with food intolerances, gluten-free (Gluten Free Digestive; Schär, Burgstall, Italy; IDDSI 7), sugar-free (Sugar Free Digestive Biscuits; Gullón, Palencia, Spain; IDDSI 7), and dairy-free (Simply Plain; Alpro, Ghent, Belgium; IDDSI 4) alternatives were offered and available. All IDDSI 4 items were comparable using spoon tilt testing.

      International Dysphagia Diet Standardisation Initiative. IDDSI Framework Testing Methods 2.0, https://iddsi.org/IDDSI/media/images/Testing_Methods_IDDSI_Framework_Final_31_July2019.pdf (2019, accessed 08/22/2022).

      Participants with difficulties during swallow trials were recommended compensatory swallow strategies involving advice (e.g. a drink to moisten the bolus) or postural adjustments (e.g. chin tuck). Difficulties included overt signs of penetration/aspiration (e.g. coughing), and observed or self-reported problems (e.g. post-swallow pharyngeal residue sensation). If recommendations did not improve swallow safety or efficiency with fluids, they were progressed to more viscous IDDSI consistencies (Nutilis Clear, Nutricia, Amsterdam, Netherlands).
      Functional Oral Intake Scale (FOIS)
      • Crary MA
      • Mann GD
      • Groher ME.
      Initial psychometric assessment of a functional oral intake scale for dysphagia in stroke patients.
      graded participants’ degree of diet modification or restriction. This rates diet from 1 (nil by mouth) to 7 (total oral diet with no restrictions). Scores were based on MASA and self-reported swallow difficulties and were a dependent variable. FOIS scores were unaffected by non-swallow dietary restrictions like food avoidance from nausea.

      Dysphagia Diagnosis

      Any one or more of the following was a positive diagnosis.
      • 1)
        Self-reported swallowing difficulties during open questions (e.g. coughing, choking on intake)
      • 2)
        MASA score ≤177
      • 3)
        MASA dysphagia or aspiration ORR other than ‘unlikely’
      • 4)
        Participant required compensatory swallow strategy
      • 5)
        FOIS <7
      All 73 individuals who screened positively for potential dysphagia were confirmed to have it and included. Of these, n=9/73 (12%) had prior documented dysphagia, n=2/73 (3%) had received swallow assessment and/or management. Median number of diagnostic criteria met was 3 (IQR=2). Diagnosis from self-reported difficulties only was n=4/73 (5%).

      Statistical Analysis

      Statistical analysis was with SPSS 25.0 (IBM Corporation, NY) and Minitab 17 (Minitab Inc., PA). Percentage values were rounded to the nearest whole number (rounding errors apply). Predictors of worse MASA and FOIS were examined by univariate and multivariate ordinal logistic regression. Where data were missing, these were excluded from analysis and reported. All test assumptions were met and significance was α=0.05. A multivariate saturated model was created. Predictors were removed iteratively, the least significant predictor taken out each time. Concordant pairs and Pearson values were examined to improve model fit.

      Results

      Cranial Nerves

      Abnormal cranial nerve function was found in n=43/73 (59%). No participant had sensory trigeminal (CN V) problems, while n=8/73 (11%) had motor difficulties. Motor problems in the facial (CN VII) nerve was present in n=4/73 (5%). Two (3%) had glossopharyngeal (CN IX) sensory issues. Vagus (CN X) motor abnormalities were evident in n=32/73 (44%), hypoglossal (CN XII) motor in n=29/73 (40%).

      Oral Health

      Mean and median Oral Health Assessment Tool (OHAT) scores were 3/16, range 0–11. Dry mouth was observed in n=48/73 (66%), lingual coating n=28/73 (38%), denture use n=25/73 (34%) and mucositis n=18/73 (25%).

      Mann Assessment of Swallowing Ability (MASA)

      Mean MASA score was 190.9 (95% CI 188.8–193), median 194, range 161–200. Chest infection, crepitations or sputum were present in n=27/73 (37%), cough response to bolus administration in n=23/73 (32%). The MASA test manual generated severity ratings and identified impaired swallow phases (Table 2).
      Table 2Mann Assessment of Swallowing Ability Outcomes
      Findingn/73 (%)
      Dysphagia severity rating
       Nil66/73 (90%)
       Mild4/73 (5%)
       Moderate3/73 (4%)
      Aspiration severity rating
       Nil70/73 (96%)
       Mild3/73 (4%)
       Moderate0/73 (0%)
      Dysphagia ORR
       Unlikely12/73 (16%)
       Possible10/73 (14%)
       Probable14/73 (19%)
       Definite37/73 (51%)
      Aspiration ORR
       Unlikely51/73 (70%)
       Possible15/73 (21%)
       Probable4/73 (5%)
       Definite3/73 (4%)
      Swallow stage affected
       Pharyngeal52/73 (71%)
       Oral preparatory41/73 (56%)
       Oral39/73 (53%)
       >1 Phase affected45/73 (62%)

      Post-Assessment Dietary Recommendations

      These were based on multimodal swallow evaluation, including self-reported difficulties from open questions. They included regular (IDDSI 7) foods (n=39/73; 53%), soft and bite-sized (IDDSI 6; n=23/73; 32%), minced and moist (IDDSI 5; n=10/73; 14%) and puréed (IDDSI 4; n=1/73; 1%). One participant required fluid modification to mildly thick (IDDSI 2), all others tolerated thin (IDDSI 0) fluids. Compensatory swallow strategies were required by n=13/73 (18%) for food and n=24/73 (33%) for fluids to improve swallow safety and/or efficiency. Food strategies were: moisten foods (n=8/13; 62%), avoid dry/crumbly foods (n=5/13; 38%), alternate food and fluids to aid clearance (n=4/13; 31%), avoid tough/chewy foods (n=2/13; 15%), chin tuck (n=1/13; 8%), chop food finely (n=1/13; 8%). Fluid strategies were: single, discrete sips (n=15/24; 63%), altering taste or temperature (n=4/24; 17%), chin tuck (2/24; 8%), chin tuck with head turn (1/24; 4%). In total, n=63/73 (86%) required dietary modification, restriction and/or compensatory strategies for swallowing problems. Of the remaining ten participants, n=6/73 (8%) had observable swallow difficulties, n=4/73 (5%) did not. Both groups also self-reported difficulties at home. No specific dietary advice or recommendations could be provided.
      Functional Oral Intake Scale (FOIS) scores were generated by the researcher for those with dysphagia. Scores were also available for the n=312 participants without dysphagia based on self-reported diet (Table 3).
      Table 3Functional Oral Intake Scale Scores for Dysphagic and Non-Dysphagic Individuals
      DysphagicNon-dysphagic
      FOIS<7 indicates dietary restriction for non-swallow reasons e.g. nausea.
      FOISn=%n=%
      719/7326283/31291
      642/735823/3127
      511/73154/3121
      4--2/3121
      31/731--
      a FOIS<7 indicates dietary restriction for non-swallow reasons e.g. nausea.

      Mann Assessment of Swallowing Ability (MASA) Predictors

      Independent variables predicted worse MASA raw score during univariate regression analysis (Table 4). In multivariate analysis, a greater number of cranial nerve deficits was the most significant predictor (P<0.001, OR 6.0, 95% CI 3.3–11.0). This was followed by cough presence (P=0.007, OR=3.4, 95% CI=1.4–8.4), anorexia presence (P=0.015, OR=3.3, 95% CI=1.3–8.5) and being in hospice (P=0.034, OR=2.9, 95% CI=1.1–7.7). Concordant pairs for the model was 80%, Pearson (Goodness of Fit) was 1.000.
      Table 4Independent Variables Associated with Decreasing Mann Assessment of Swallowing Ability raw Score (Univariate)
      PredictorP-valueLevelOdds Ratio95% CI
      ECOG-PS<0.001Worse2.21.5–3.4
      No. of CN deficits<0.001Increasing6.53.7–11.5
      Setting<0.001Hospice6.52.6–16.7
      Team0.002Palliative4.11.7–9.9
      Age0.003Increasing1.11.0–1.1
      Location
      Day Hospice (DH) and In-Patient (IP) participants were significantly more likely than those in Oncology Day Ward (DW) to have higher dysphagia risk. Since only n=6 participants were in DH, results pertaining to this location were unreliable and disregarded.
      0.006IP>DW4.71.6–14.5
      No. of comorbidities0.011Increasing1.21.0–1.5
      Dyspnea0.013Present2.91.3–6.6
      Cough0.016Present2.81.2–6.6
      Anorexia0.020Present2.91.2–7.3
      % Weight loss
      Analysis conducted using participants for whom data were available (%Weight loss: n=46/73; cachexia: n=43/73; albumin: n=63/73) Non-significant predictors available in supplemental file.
      0.022Increasing1.11.0–1.1
      OHAT score0.024Increasing1.21.0–1.4
      EAT-100.026Increasing1.11.0–1.1
      Cachexia
      Analysis conducted using participants for whom data were available (%Weight loss: n=46/73; cachexia: n=43/73; albumin: n=63/73) Non-significant predictors available in supplemental file.
      0.030Present3.41.1–10.0
      Denture use (OHAT)0.030Present2.61.1–6.2
      Albumin
      Analysis conducted using participants for whom data were available (%Weight loss: n=46/73; cachexia: n=43/73; albumin: n=63/73) Non-significant predictors available in supplemental file.
      0.031Normal0.40.2–0.9
      Receiving targeted therapy0.032Present0.30.1–0.9
      Early satiety0.033Present2.51.1–5.8
      Months since diagnosis0.036Decreasing0.980.97–1.0
      Wheeze0.042Present2.41.0–5.5
      a Day Hospice (DH) and In-Patient (IP) participants were significantly more likely than those in Oncology Day Ward (DW) to have higher dysphagia risk. Since only n=6 participants were in DH, results pertaining to this location were unreliable and disregarded.
      b Analysis conducted using participants for whom data were available (%Weight loss: n=46/73; cachexia: n=43/73; albumin: n=63/73)Non-significant predictors available in supplemental file.
      Univariate regression identified the factors that increased dysphagia ordinal risk rating (ORR; Table 5). These were then combined into a multivariate model, where early satiety remained as the only significant predictor of worse dysphagia ORR (P=0.013, OR=3.6, 95% CI=1.3–10.0). Concordant pairs was 78.8%, Pearson (Goodness of Fit) was 0.9. Predictors of worse aspiration ORR by univariate analysis are in Table 6. Multivariate analysis was not possible due to the low number of participants with ratings of ‘probable’ or ‘definite’ aspiration.
      Table 5Independent Variables Associated with Increasing Mann Assessment of Swallowing Ability Dysphagia Ordinal Risk Ratings (Univariate)
      PredictorP-valueLevelOdds Ratio95% CI
      Early satiety0.001Present5.02.0–12.5
      No. of CN deficits0.001Increasing2.71.5–4.8
      Anorexia0.002Present4.81.8–12.5
      OHAT score0.003Increasing1.41.1–1.7
      Setting0.007Hospice4.21.4–11.1
      Team0.016Palliative3.21.3–8.3
      EAT-100.020Increasing1.11.0–1.1
      Wheeze0.025Present2.91.1–7.1
      Age0.031Older1.041.0–1.1
      Vomiting0.032Present3.81.1–12.5
      Denture use (OHAT)0.038Present2.81.5–4.8
      No. of comorbidities0.041Increasing1.21.0–1.5
      NLR
      Analysis conducted using n=63/73 participants for whom data were available. NLR: Neutrophil-to-lymphocyte ratio. Non-significant predictors available in supplemental file.
      0.046High2.61.0–6.7
      Dyspnea0.047Present2.41.0–5.9
      Lingual coating (OHAT)0.048Present2.61.0–6.7
      Health care provider0.049Public2.51.0–6.3
      Mucositis (OHAT)0.049Present3.11.0–9.1
      a Analysis conducted using n=63/73 participants for whom data were available. NLR: Neutrophil-to-lymphocyte ratio.Non-significant predictors available in supplemental file.
      Table 6Independent Variables Associated with Increasing Mann Assessment of Swallowing Ability Aspiration Ordinal Risk Ratings (Univariate)
      PredictorP-valueLevelOdds Ratio95% CI
      No. cranial nerve deficits<0.001Increasing2.91.7–5.0
      Setting<0.001Hospice7.72.6–25.0
      Team0.002Palliative5.61.9–16.7
      ECOG-PS0.005Worse2.11. –-3.6
      Cough0.007Present6.31.7–25.0
      BMI
      Analysis conducted using n=54/73 participants for whom data were available Non-significant predictors available in supplemental file.
      0.020Increasing0.80.7–1.0
      Health care provider0.039Public3.61.1–12.5
      a Analysis conducted using n=54/73 participants for whom data were availableNon-significant predictors available in supplemental file.

      Functional Oral Intake Scale (FOIS) Predictors

      Univariate analysis identified predictors of lower FOIS scores. Worse ECOG-PS was most predictive (P=0.004, OR=2.0, 95% CI=1.2–3.2), followed by anorexia presence (P=0.008, OR=4.2, 95% CI=1.5–12.0), vomiting presence (P=0.015, OR=4.2, 95% CI=1.3–13.3), higher OHAT score (P=0.025, OR=1.2, 95% CI=1.0–1.5) and denture use (P=0.046, OR=2.8, 95% CI=1.0–7.4). Multivariate regression identified that worse ECOG-PS (P=0.008, OR=3.7, 95% CI=1.2–12.1) and presence of self-reported vomiting (P=0.048, OR=3.4, 95% CI=1.0–11.7) were associated with lower FOIS. Concordant pairs was 63.5%, Pearson (Goodness of Fit) was 0.123.

      Discussion

      Our study sought to identify dysphagia severity and associate it with pathophysiology. By Mann Assessment of Swallowing Ability (MASA) raw scores, most participants fell into the ‘Nil’ severity rating for dysphagia and aspiration, with the remainder either mild or moderate. By contrast, ordinal risk ratings (ORRs) found most participants had dysphagia risk, one-third aspiration risk. MASA was developed for stroke disease, so some items (e.g. dysphasia, dyspraxia, dysarthria) were less relevant in our cohort and caused scores to be closer to the normal range. Observed difficulties during swallow trials contributed significantly to ORRs. Most of those with dysphagia had abnormal Functional Oral Intake Scale (FOIS) scores or required a compensatory strategy. This meant MASA raw scores could be near to normal despite observed difficulties. MASA raw scores therefore appear inadequate for identifying dysphagia in this cohort. Instrumental swallow evaluation would be ideal to identify the nature of swallow inefficiencies and more precisely profile aspiration risk. A clinical bedside swallow evaluation more sensitive to the needs of the general cancer population would also be beneficial.
      We identified underlying pathophysiological deficits and their association with dysphagia severity. More than half of participants had deficits in swallow-related cranial nerves. Greater number of deficits predicted worse MASA swallow function, and increased likelihood of dysphagia and aspiration. Neuropathy is not uncommon in cancer and may be associated with anti-cancer treatments.
      • Cleeland CS
      • Farrar JT
      • Hausheer FH.
      Assessment of cancer-related neuropathy and neuropathic pain.
      The vagus nerve is particularly susceptible to chronic inflammation
      • Browning KN
      • Travagli RA.
      Central nervous system control of gastrointestinal motility and secretion and modulation of gastrointestinal functions.
      ,
      • Bonaz B
      • Bazin T
      • Pellissier S.
      The vagus nerve at the interface of the microbiota-gut-brain axis.
      and was the most-affected here. This nerve mediates cough and some autonomic aspects of digestion,
      • Groher ME
      • Crary MA
      Dysphagia: Clinical management in adults and children.
      ,
      • Erman A
      • Kejner A
      • Hogikyan N
      • Feldman E.
      Disorders of cranial nerves IX and X.
      which were abnormal and associated with dysphagia. The cranial nerve examination we employed characterized any weak or hoarse voice as impaired. Such qualities can represent age-related changes
      • Kosztyla-Hojna B
      • Zdrojkowski M
      • Duchnowska E
      Presbyphonia as an individual process of voice change.
      and may have upwardly biased vagus nerve deficit prevalence.
      Oral health was linked with dysphagia. Worse Oral Health Assessment Tool (OHAT) scores predicted worse MASA raw score, higher dysphagia ORR and lower FOIS, but did not affect aspiration risk. Denture use, lingual coating and mucositis were contributory factors to poorer MASA and FOIS, likely because they interfere with preparatory activities like chewing prior to the act of swallowing. Interestingly, xerostomia did not statistically contribute to swallow difficulties despite occurring in two-thirds. Xerostomia can occur without hyposalivation.
      • Millsop JW
      • Wang EA
      • Fazel N
      Etiology, evaluation, and management of xerostomia.
      It may be that participants experienced a sense of difficulty with bolus moistening despite no underlying salivary deficits, but our study did not measure saliva production. Future studies may benefit from discriminating these. Oral health assessment and management should be a priority for clinicians, especially since it diminishes quality of life.
      • Fitzgerald R
      • Gallagher J
      Oral health in end-of-life patients: a rapid review.
      Those with more advanced disease had worse dysphagia. Most prominently, worse ECOG-PS score predicted worse MASA raw score, more likely aspiration and increased diet restriction by FOIS. Other factors that predicted poorer swallow were hospice care, presence of other aerodigestive symptoms (e.g. anorexia, cough, early satiety), more comorbidities, older age and underPC. This supports previous research, which showed that dysphagia manifests when cancer is advanced and especially immediately before death.
      • Chiu TY
      • Hu WY
      • Chen C-Y
      Prevalence and severity of symptoms in terminal cancer patients: a study in Taiwan.
      • Walsh D
      • Donnelly S
      • Rybicki L.
      The symptoms of advanced cancer: relationship to age, gender and performance status in 1,000 patients.
      • Tsai JS
      • Wu CH
      • Chiu TY
      • Hu WY
      • Chen CY.
      Symptom patterns of advanced cancer patients in a palliative care unit.
      • Mercadante S
      • Aielli F
      • Adile C
      • et al.
      Prevalence of oral mucositis, dry mouth, and dysphagia in advanced cancer patients.
      It may be that dysphagia is therefore a sign of overall poorer health, emerges alongside other symptoms and has a potentially multifactorial etiology.
      Hospice and PC services see those with the most severe dysphagia in this population. Those in publicly-funded health care organizations had higher dysphagia and aspiration ORRs than those in private care. The reasons why were not captured, but those who attend public hospitals are older, have riskier lifestyles, and more comorbidities than in private settings.
      • Tynkkynen LK
      • Vrangbaek K.
      Comparing public and private providers: a scoping review of hospital services in Europe.
      People with better health care access, higher educational attainment and higher income seek help for medical problems more readily.
      • van Loenen T
      • van den Berg MJ
      • Faber MJ
      • Westert GP.
      Propensity to seek health care in different health care systems: analysis of patient data in 34 countries.
      Higher socioeconomic status is also associated with better overall health and lower cancer mortality.
      • Atherton IM
      • Evans JM
      • Dibben CJ
      • Woods LM
      • Hubbard G.
      Differences in self-assessed health by socioeconomic group amongst people with and without a history of cancer: an analysis using representative data from Scotland.
      ,
      • Hastert TA
      • Ruterbusch JJ
      • Beresford SA
      • Sheppard L
      • White E
      Contribution of health behaviors to the association between area-level socioeconomic status and cancer mortality.
      It may be that those with private health insurance promptly sought and received health care, reducing dysphagia and aspiration risk. Public health care services could consider patient education and routine screening to capture and manage dysphagia.

      Strengths and Limitations

      This research employed consecutive admissions sampling without seeking to limit itself to any one cancer subpopulation. This was to best represent a typical clinical population and improve ecological validity. However, a large number of people with colorectal, lung, prostate, and renal cancers were sampled due both to disease prevalence and specialist services for these within hospital recruitment settings, which may have biased results. We deliberately used a broad-based diagnostic process to account for problems with either swallow safety or efficiency. Participant-reported difficulties were taken as diagnostic so as not to disregard individuals’ experiences. This was important, because the research was novel and the nature and severity of any potential dysphagia previously unknown. The broad-based approach to diagnosis may however have overestimated dysphagia presence if alternative diagnostic criteria are used. Future studies using instrumental evaluation to supplement bedside evaluation would therefore be useful.
      Qualitative responses from open-ended case history question facilitated appreciation of features not commonly included in dysphagia checklists and tools, including features uncaptured by MASA. These were unreported here because they provided a rich and sizeable account of patient experiences. These data will be reported separately.
      To improve validity and reliability, we used published tools for screening and assessment. This was not without problems, as with MASA, which appeared to represent dysphagia differently by raw scores compared with ORRs. A single investigator carried out all screening and evaluation, which may be a source of bias.

      Clinical Implications

      Only 12% of our dysphagia cohort had documented swallowing difficulties prior to study enrolment. Services should routinely screen and identify potential dysphagia in cancer populations, regardless of primary tumor site. Hospice and PC services should be particularly vigilant, since increasing dysphagia severity was associated with disease progression and poorer overall health. Cachexia and poor nutrition are significant concerns in cancer.
      • Fearon K
      • Strasser F
      • Anker SD
      • et al.
      Definition and classification of cancer cachexia: an international consensus.
      Most of our cohort required diet modification or compensatory swallow strategies. Dysphagia clinicians should work closely with Clinical Nutrition and Dietetics to optimize patients both in terms of nutrition and feeding-related quality of life. This includes promotion of good oral health.

      Research Implications

      Findings from this research were based on clinical observation and should be verified with instrumental evaluation. Our analysis approach was designed to determine associations with underlying pathophysiology, but cannot identify causality. Other designs like case-control or longitudinal studies may help contextualize the evidence. A replicate study with head, neck and esophageal cancer cohorts would be valuable to identify the extent to which dysphagia is site-specific versus due to cancer in general and its treatment.

      Conclusions

      Dysphagia was prevalent and clinically important in solid tumors outside anatomic swallow regions. Most participants were not known to have swallow difficulties prior to the study, placing them at potential risk. Multimodal evaluation was required to capture the nuanced effects of cancer and anti-tumor treatments on swallow. Individual experiences of difficulties with foods or fluids required bespoke clinical advice, particularly in terms of dietary adjustments and compensatory swallow strategies. Those with more advanced cancer, including people under palliative or hospice care had significantly higher dysphagia and aspiration risks. Careful screening and differential diagnosis by clinicians is essential to ensure that swallow, oral health and nutritional needs are identified and met. Swallow assessment tools for this clinical population should be a research priority.

      Disclosures and Acknowledgments

      All authors declare no financial or personal interests which pose a conflict of interest relating to the work contained in this study. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
      The authors thank the study participants for their gracious time.

      Appendix. Supplementary materials

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