Association of Tongue Strength and Maximum Incisal Opening with Oral Intake in Persons with Head and Neck Cancer Treated with Radiotherapy: A Retrospective Study.

Persons treated with radiotherapy (RT) for cancer of the head and neck (HNC) may experience limited oral intake at treatment completion. The purpose of this retrospective study was to examine the contributions of tongue strength and maximum incisal opening (MIO) to oral intake in a cohort of veterans treated for HNC. Medical records of veterans diagnosed with HNC treated with RT who were seen by the Speech Pathology Service prior to and throughout treatment per usual care were reviewed for this study; eighty-two records met the inclusion criteria for analysis. Tongue strength in kPa, MIO in mm, feeding tube status at completion of RT, and food and liquid consistencies consumed at completion of RT were among the data abstracted from the records. Most veterans (67%) did not have a feeding tube present at the completion of RT and reported drinking thin liquids (84.2%) at treatment completion. Eighteen percent reported including all food consistencies in their diet at the end of treatment. Both MIO and tongue strength decreased after treatment. Greater tongue strength during RT and larger MIO at the completion of RT were predictive of improved functional outcomes for oral intake at the end of treatment. This study provides evidence of the importance of increasing tongue strength and MIO during treatment with RT, and supports an important focus for intervention by speech-language pathologists.

A translation and validation of the French version of the Gothenburg Trismus Questionnaire 2 (F-GTQ-2).

BACKGROUND: Limitation of mouth opening, widely known as trismus, is a major symptom altering quality of life in individuals presenting from temporomandibular joint disorder or head and neck cancer. A French-language instrument addressing jaw opening limitation following treatment for head and neck cancer (HNC) or temporomandibular joint disorder (TMD) is lacking. OBJECTIVE: The aim of this study was to translate and validate the Gothenburg Trismus Questionnaire-2 (GTQ-2) into French. METHODS: A French translation of the GTQ-2 was performed according to established international guidelines, leading to the French-GTQ-2 (F-GTQ-2). The validation study included 154 participants with trismus (minimum interincisal opening of ≤35 mm) following treatment for TMD or HNC and 149 age-matched participants without trismus. All participants completed the F-GTQ-2 and participants with trismus completed additional health-related quality of life questionnaires to allow for analysis of convergent validity. RESULTS: The F-GTQ-2 demonstrated retained psychometric properties with Cronbach's alpha values above 0.70 for the domains, jaw-related problems, eating limitations, facial pain and somewhat lower for muscular tension (0.60). Mainly moderate correlations were found when comparing the F-GTQ-2 to other instruments, which was in line with the pre-specified hypotheses, indicating satisfactory convergent validity. Discriminant validity was found with statistically significant differences in all domains of the F-GTQ-2 between trismus and non-trismus participants. CONCLUSION: The F-GTQ-2 can be considered a reliable and valid instrument to assess jaw-related difficulties in individuals with trismus due to HNC or TMD.

m7G-related genes-NCBP2 and EIF4E3 determine immune contexture in head and neck squamous cell carcinoma by regulating CCL4/CCL5 expression.

Aberrant N7 -methylguanosine (m7G) levels closely correlate with tumor genesis and progression. NCBP2 and EIF4E3 are two important m7G-related cap-binding genes. This study aimed to identify the relationship between the EIF4E3/NCBP2 function and immunological characteristics of head and neck squamous cell carcinoma (HNSCC). Hierarchical clustering was employed in classifying HNSCC patients into two groups based on the expressions of NCBP2 and EIF4E3. The differentially expressed genes were identified between the two groups, and GO functional enrichment was subsequently performed. Weighted gene co-expression network analysis was conducted to identify the hub genes related to EIF4E3/NCBP2 expression and immunity. The differential infiltration of immune cells and the response to immunotherapy were compared between the two groups. Single-cell sequence and trajectory analyses were performed to predict cell differentiation and display the expression of EIF4E3/NCBP2 in each state. In addition, quantitative real-time PCR, spatial transcriptome analysis, transwell assay, and western blotting were conducted to verify the biological function of EIF4E3/NCBP2. Here, group A showed a higher EIF4E3 expression and a lower NCBP2 expression, which had higher immune scores, proportion of most immune cells, immune activities, expression of immunomodulatory targets, and a better response to cancer immunotherapy. Besides, 56 hub molecules with notable immune regulation significance were identified. A risk model containing 17 hub genes and a prognostic nomogram was successfully established. Moreover, HNSCC tissues had a lower EIF4E3 expression and a higher NCBP2 expression than normal tissues. NCBP2 and EIF4E3 played a vital role in the differentiation of monocytes. Furthermore, the expression of CCL4/CCL5 can be regulated via EIF4E3 overexpression and NCBP2 knockdown. Collectively, NCBP2 and EIF4E3 can affect downstream gene expression, as well as immune contexture and response to immunotherapy, which could induce "cold-to-hot" tumor transformation in HNSCC patients.

Cytoplasmic IGF2BP2 Protein Expression in Human Patients with Oral Squamous Cell Carcinoma: Prognostic and Clinical Implications.

Oral squamous cell carcinoma (OSCC) is particularly prevalent in Taiwan. The goal of this study was to determine the clinicopathological role of insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) proteins as an indicator of clinical outcomes in OSCC patients. In this study, immunohistochemical (IHC) analysis was used to examine IGF2BP2 protein expression in 244 OSCC patients. We investigated the relationships among IGF2BP2 expression, clinicopathological variables, and patient survival. Our results showed that IGF2BP2 cytoplasmic protein expression was significantly correlated with lymph node metastasis, cancer stage, and patient survival. Kaplan-Meier survival curves revealed that elevated cytoplasmic IGF2BP2 expression levels in OSCC patients were associated with poor overall survival. Moreover, multivariate cox proportional hazard models revealed that cytoplasmic IGF2BP2 expression, T status, and lymph node metastasis were independent prognostic factors for survival. In conclusion, IGF2BP2 protein was found to be a helpful predictive marker for OSCC patients, as well as a possible therapeutic target for OSCC treatment.

Distinct nitrogen isotopic compositions of healthy and cancerous tissue in mice brain and head&neck micro-biopsies.

BACKGROUND: Cancerous cells can recycle metabolic ammonium for their growth. As this ammonium has a low nitrogen isotope ratio (15N/14N), its recycling may cause cancer tissue to have lower 15N/14N than surrounding healthy tissue. We investigated whether, within a given tissue type in individual mice, tumoral and healthy tissues could be distinguished based on their 15N/14N. METHODS: Micro-biopsies of murine tumors and adjacent tissues were analyzed for 15N/14N using novel high-sensitivity methods. Isotopic analysis was pursued in Nude and C57BL/6 mice models with mature orthotopic brain and head&neck tumors generated by implantation of H454 and MEERL95 murine cells, respectively. RESULTS: In the 7 mice analyzed, the brain tumors had distinctly lower 15N/14N than healthy neural tissue. In the 5 mice with head&neck tumors, the difference was smaller and more variable. This was at least partly due to infiltration of healthy head&neck tissue by tumor cells. However, it may also indicate that the 15N/14N difference between tumoral and healthy tissue depends on the nitrogen metabolism of the healthy organ in question. CONCLUSIONS: The findings, coupled with the high sensitivity of the 15N/14N measurement method used here, suggest a new approach for micro-biopsy-based diagnosis of malignancy as well as an avenue for investigation of cancer metabolism.

Differential Wnt-ß- catenin pathway activation in HPV positive and negative oral epithelium is transmitted during head and neck tumorigenesis: clinical implications.

The aim of this study is to understand the association of HPV infection and wnt-ß-catenin self-renewal pathway in development of head and neck squamous cell carcinoma (HNSCC). For this reason, the molecular profiles (methylation/deletion/expression) of antagonists (SFRP1/2 and DKK1), agonists (FZD7 and LRP6) and effector protein ß-catenin of the pathway were analyzed in HPV positive/negative oral epithelium at first, followed by its changes during development of the tumor along with correlations with different clinico-pathological parameters. HPV infection alone or in combination with tobacco habit could activate p- ß-catenin expression in basal/parabasal layers of oral epithelium through high expression of FZD7 and significant down regulation of SFRP1/2 through promoter hypermethylation due to over expression of DNMT1 with ubiquitous down regulation of DKK1 and up-regulation of LRP6. This phenomenon has been seen in respective HPV positive and negative HNSCC tumors with additional deletion/microsatellite size alterations in the antagonists. Overall alterations (methylation/deletion) of SFRP1/2, DKK1 gradually increased from Group I (HPV-/Tobacco-) to Group IV(HPV+/Tobacco+) tumors, leading to the worst prognosis of the patients. Thus, the transmission of differentially activated wnt-ß-catenin pathway from HPV positive/negative basal/parabasal layers of oral epithelium to HNSCC tumors determines differences in molecular pathogenesis of the disease.

Glia and Orofacial Pain: Progress and Future Directions.

Orofacial pain is a universal predicament, afflicting millions of individuals worldwide. Research on the molecular mechanisms of orofacial pain has predominately focused on the role of neurons underlying nociception. However, aside from neural mechanisms, non-neuronal cells, such as Schwann cells and satellite ganglion cells in the peripheral nervous system, and microglia and astrocytes in the central nervous system, are important players in both peripheral and central processing of pain in the orofacial region. This review highlights recent molecular and cellular findings of the glia involvement and glia-neuron interactions in four common orofacial pain conditions such as headache, dental pulp injury, temporomandibular joint dysfunction/inflammation, and head and neck cancer. We will discuss the remaining questions and future directions on glial involvement in these four orofacial pain conditions.

SIP SMART: a parallel group randomised feasibility trial of a tailored pre-treatment swallowing intervention package compared with usual care for patients with head and neck cancer.

BACKGROUND: Dysphagia or difficulty in swallowing affects quality of life for most patients with head and neck cancer. SIP SMART - [Swallowing Intervention Package: Self-Monitoring, Assessment, Rehabilitation Training] aims to improve post-treatment swallowing outcomes through a targeted and tailored pre-treatment intervention. This feasibility study assessed 1) recruitment and retention, 2) patient acceptability of randomisation and participation, 3) patient adherence, and 4) sought to identify a suitable primary outcome for a definitive trial, including sample size estimation. METHODS: This two-arm parallel group non-blinded randomised feasibility trial took place within a head and neck centre at a teaching hospital in London, UK. Patients newly diagnosed with stage III/IV head and neck cancer were recruited and underwent 6-month follow-up. Patients were randomised to SIP-SMART or usual care via an online web-based system. SIP SMART comprised two 45-min consultations including a baseline clinical and instrumental swallowing assessment, relevant educational information, targeted swallowing exercises, and specific behaviour change strategies to increase exercise adherence. Usual care comprised a single session including a baseline clinical assessment and generic information about the likely impact of treatment on swallowing. RESULTS: A total of 106 patients were identified at pre-screening, 70 were assessed for eligibility. Twenty-six patients did not meet eligibility criteria [0.37, 95% CI 0.27 to 0.49]. Five of 44 [0.11, 95% CI 0.05 to 0.24] eligible patients were not approached by researchers during clinic. Seven [0.18, 95% CI 0.08 to 0.33] of the 39 approached declined participation. Target recruitment (32 consented patients) was achieved within the timeframe. At 6-months 29/32 [0.91, 95% CI 0.76 to 0.97] patients remained in the trial. Acceptability of randomisation and participation in the intervention was favourable, and adherence to the exercises exceeded the pre-defined 35% minimum criterion. The MD Anderson Dysphagia Inventory swallow related quality of life measure was selected as the most suitable primary outcome for sample size estimation. No adverse effects arose from the intervention, or study participation. CONCLUSIONS: A definitive trial of the SIP SMART intervention compared to usual care is feasible and can be undertaken with patients with head and neck cancer treated within the NHS. TRIAL REGISTRATION: ISRCTN40215425, registered retrospectively.

Demographic, clinical and lifestyle-related correlates of accelerometer assessed physical activity and fitness in newly diagnosed patients with head and neck cancer.

Introduction: Objective measurements of levels of physical activity and fitness in patients with head and neck cancer (HNC) are lacking. Furthermore, demographic, clinical and lifestyle-related correlates of low levels of physical activity and fitness in patients with HNC are unknown. This study aims to investigate the levels of accelerometer that assessed physical activity and fitness in patients with HNC and to identify their demographical, clinical and lifestyle-related correlates.Methods: Two hundred and fifty-four patients who were recently diagnosed with HNC and participated in the NETherlands QUality of life and Biomedical cohort studies In head and neck Cancer (NET-QUBIC) study were included. Physical activity (accelerometer), cardiorespiratory fitness (Chester Step Test), hand grip strength (hand dynamometer) and lower body muscle function (30-second chair-stand test) were assessed. Multivariable linear regression analyses with a stepwise forward selection procedure were used.Results: Patients spent 229 min/d in physical activity of which 18 min/d in moderate-to-vigorous physical activity. The mean predicted VO2max was 27.9 ml/kg/min, the mean hand grip strength was 38.1 kg and the mean number of standings was 14.3. Patients with lower educational level, more comorbidity and higher tumor stage spent significantly less time in physical activity. Older patients, females and patients with a higher tumor stage had significantly lower cardiorespiratory fitness levels. Older patients, females, patients with more comorbidity, patients with normal weight and patients who have never smoked had significantly lower hand grip strength. Older patients, patients with lower educational level, smokers and patients with more comorbidity had a significantly lower function of lower body muscle.Conclusions: Pre-treatment levels of physical activity, cardiorespiratory fitness and lower body muscle function are low in patients with HNC. Based on this study, exercise programs targeted and tailored to patients with low levels of physical activity and fitness can be developed.

Health-Related Quality of Life and Patient-Reported Outcomes in Radiation Oncology Clinical Trials.

OPINION STATEMENT: The importance of assessing health-related quality of life (HRQoL) and patient-reported outcomes (PROs) is now well recognized as an essential measure when evaluating the effectiveness of new cancer therapies. Quality of life measures provide for a multi-dimensional understanding of the impact of cancer treatment on measures ranging from functional, psychological, and social aspects of a patient's health. Patient-reported outcomes provide for an assessment of physical and functional symptoms that are directly elicited from patients. Collection of PROs and HRQoL data has been shown to not only be feasible but also provide for reliable measures that correlate with established outcomes measures better than clinician-scored toxicities. The importance of HRQoL measures has been emphasized by both patients and clinicians, as well as policy makers and regulatory bodies. Given the benefits associated with measuring HRQoL and PROs in oncology clinical trials, it is increasingly important to establish methods to effectively incorporate PROs and HRQoL measures into routine clinical practice.

Evaluation of a speech pathology service delivery model for patients at low dysphagia risk during radiotherapy for HNC.

PURPOSE: There are no evidence-based guidelines informing which patients with head and neck cancer (HNC) require regular speech pathology (SP) support during radiation treatment (RT). Hence, some services use a "one-size-fits-all" model, potentially over-servicing those patients at low risk for dysphagia. This study evaluated the clinical safety and efficiency of an interdisciplinary service model for patients identified prospectively as "low risk" for dysphagia during RT. METHODS: A prospective cohort of 65 patients with HNCs of the skin, thyroid, parotid, nose, and salivary glands, receiving curative RT, were managed on a low-risk pathway. Patients with baseline dysphagia (functional oral intake score ≤ 5) were excluded. The model involved dietitians conducting dysphagia screening at weeks 3, 5, and 6/7 within scheduled appointments. Patients at risk of dysphagia were referred to SP for assessment, then management if required. To validate the model, SP assessed swallow status/toxicities at week 5/6/7 during RT and confirmed dysphagia status at weeks 2 and 6 post RT. RESULTS: Most (89.3%) patients did not require dysphagia support from SP services. Of the 18 patients identified on screening, only 7 (10.7%) had sufficient issues to return to SP care. Week 5/6/7 SP review confirmed low levels of toxicity. No post-treatment dysphagia was observed. There was an incremental benefit of A$15.02 for SP staff costs and a recovery of 5.31 appointments per patient. CONCLUSION: The pathway is a safe and effective service model to manage patients with HNC at low risk for dysphagia during RT, avoiding unnecessary SP appointments for the patient and service.

Oral examination findings, taste and smell testing during and following head and neck cancer therapy.

PURPOSE: Diet and nutrition are critical in health and disease and are highly impacted by the presence and treatment for head and neck cancer (HNC). The purpose of this paper is to present oral examination findings and taste and smell test results in patients during and following HNC. METHODS: Patients with HNC were evaluated during and following radiation therapy with/without chemotherapy. Oral examination findings including mucositis, saliva, oral hygiene (plaque levels, gingivitis), and taste and smell testing was completed on all subjects. NCI Common Terminology Criteria for Adverse Events (CTCAE) 4.0, and the Scale of Subjective Total Taste Acuity (STTA) were used to provide patient report of symptoms. RESULTS: Mucositis and pain affected oral diet during therapy and improved in follow-up. Weight loss of 5% during and 12% following treatment was identified. Tobacco use was associated with increased severity of mucositis and increased weight loss. The subjects maintained excellent oral hygiene as reflected in plaque levels and gingivitis. Spicy/pungent perception was the most strongly disliked of testing stimuli. Umami and fat taste perception were reported of highest intensity during HNC treatment and rated as moderate in intensity after treatment. These results suggest improvement in these taste functions over time following treatment. Salt taste was of high intensity and associated with strong dislike in follow-up. CONCLUSIONS: In HNC patients, oral status and taste change occurs throughout the cancer trajectory and represent potential concerns in cancer survivorship. Taste change (as evaluated by taste testing) occurred in all HNC patients, whereas olfactory changes occurred in 30% of cases. Management of oral changes and symptoms should be considered in all HNC patients in addition to dietary and nutritional guidance in patient care to promote oral intake. Continuing study of taste changes may further define this problem and support dietary and nutritional guidance and product development.

Safety of radiotherapy for hemodialysis patients with cancer.

BACKGROUND: The number of hemodialysis (HD) patients is increasing worldwide, and they are at a higher risk of cancer than the general population. Because HD patients are more likely to have inflammation, radiotherapy (RT)-induced adverse effects (AEs) are theoretically expected to be worse for HD patients. Since only a few reports have been published on this subject, we aimed to evaluate the tolerability of RT in HD patients. METHODS: We retrospectively analyzed AEs related to RT for HD patients. Our study included patients from three institutions treated between January 2007 and July 2017. The patient eligibility criteria were (i) receipt of maintenance HD 2-3 times per week for end-stage renal disease prior to the start of RT and (ii) pathologically confirmed malignancies. The endpoints were acute and late non-hematologic AEs. RESULTS: The study included 56 patients. The most common histology was head and neck cancer (23%), followed by lung cancer (14%) and prostate cancer (11%). The median radiation dose was 60 (range, 12-93.8) Gy at an equivalent dose in 2-Gy fractions (EQD2). The RT completion rate was 96%. Patients had a median follow-up period after RT of 9.1 (range 0.5-98.1) months. Grade 3 or worse acute and late AEs were noted in 6 (11%) and 3 (7%) patients, respectively. In the acute phase, 2 patients had grade 5 AEs, both of which were infections. CONCLUSION: Our results suggest that RT for HD patients is clinically tolerable. However, some patients can experience severe infections related to treatment.

Living with cancer of the head and neck: A qualitative inquiry into the experiences of South African patients.

OBJECTIVE: To describe the experiences of South African patients living with head and neck cancer. METHODS: We used a qualitative descriptive design and conducted unstructured interviews with 18 (n = 18) purposive selected participants. Data saturation determined the sample size. Qualitative content analysis was used to analyse the data. RESULTS: The majority of the sample were Black males; on average, 50.8 years (SD ± 13.6) old. Two themes and eight subthemes arose from the data. The themes were living with the consequences of the illness and treatment, and coping with a changed life. The lives the participants knew before becoming sick changed and became a living hell; pain was a major problem as was eating and for some, communicating. The participants were stigmatised, ridiculed and rejected which added to their suffering. Receiving support from family and friends and their faith in God assisted them to cope with their changed lives. CONCLUSION: Our study poses various challenges to clinical practice. Pain management is of the utmost importance; the nutritional status of these patients should be monitored and best practices in terms of management applied. Raising awareness of cancer and its complications could improve knowledge and decrease blame, stigmatisation and rejection and improve patient outcomes.

Fear of recurrence: A mediator of the relationship between physical symptoms and quality of life in head and neck cancer patients.

OBJECTIVE: Head and neck cancer (HNC) patients suffer from symptoms and fear of recurrence (FoR), which both affect their quality of life (QoL). Based on a self-regulation model, the purpose of the study was to examine patients' FoR as a mediator of the relation between symptoms and QoL, and to identify which symptoms may trigger FoR. METHODS: A cross-sectional study was conducted, using convenience sampling. Structured questionnaires were used to collect data at a medical centre in Northern Taiwan. The analytic methods included descriptive statistics, structural equation modelling and linear regression. RESULTS: A total of 103 participants were recruited. Patients experienced a medium level of symptom severity and QoL but a moderate to high level of FoR. Symptom severity, FoR and QoL were significantly correlated. FoR was a significant partial mediator between symptom severity and QoL. The significant factors of the overall FoR and the subscale of health worry were "pain in general" and "pain in the mouth, throat or neck." "Pain in general" was a significant factor for the subscale of cancer worry. CONCLUSIONS: This theory-driven study supports a mediation model of FoR among HNC patients and provides a more comprehensive understanding of the antecedents and consequences of FoR.

Patients with head and neck cancer: Are they frailer than patients with other solid malignancies?

OBJECTIVE: We aimed to compare frailty status between patients with head and neck cancer (HNC) and other solid malignancies. METHODS: Data collection was prospective, and the following were compared between cohorts at baseline: patient and tumour characteristics, Charlson Comorbidity Index (CCI), Groningen Frailty Indicator (GFI), Mini Mental State Examination (MMSE), Activities of Daily Living (ADLs), Instrumental ADLs (IADLs), Timed Up and Go (TUG) and Quality of Life (QoL). Univariate and multivariate logistic regression analyses were performed, and odds ratios (ORs) with their 95% confidence intervals (95% CIs) were estimated. RESULTS: In total, 242 patients with HNC and 180 with other oncology diagnoses were enrolled, of whom 32.6% and 21.8% were frail according to the GFI respectively. Comorbidity scores were not significantly different between the cohorts (7.4% vs. 13.1%; OR 0.54; 95% CI 0.28-1.02). In the univariate analysis, the GFI was significantly worse in the HNC cohort (OR 1.74; 95% CI 1.11-2.71). However, in the multivariate analysis, the MMSE, TUG and global QoL were significantly worse in the HNC cohort, with ORs of 20.03 (95% CI 2.44-164.31), 11.56 (95% CI 1.86-71.68) and 0.98 (95% CI 0.97-1.00) respectively. CONCLUSION: Patients with HNC appear to be frailer than patients with other solid malignancies despite comparable levels of comorbidity.

Neuromuscular function and fatigability in people diagnosed with head and neck cancer before versus after treatment.

PURPOSE: Treatment for head and neck cancer is associated with multiple side effects, including loss of body mass, impaired physical function and reduced health-related quality of life. This study aimed to investigate the impact of treatment (radiation therapy ± concurrent chemotherapy) on (i) muscle strength, muscle cross-sectional area and patient-reported outcomes, and (ii) central and peripheral alterations during a whole-body exercise task. METHODS: Ten people with head and neck cancer (4 female; 50 ± 9 years) completed a lab visit before and after (56 ± 30 days) completion of treatment. Participants performed a neuromuscular assessment (involving maximal isometric voluntary contractions in the knee extensors and electrical stimulation of the femoral nerve) before and during intermittent cycling to volitional exhaustion. Anthropometrics and patient-reported outcomes were also assessed. RESULTS: From before to after treatment, maximal isometric muscle strength was reduced (P = 0.002, d = 0.73), as was potentiated twitch force (P < 0.001, d = 0.62), and muscle cross-sectional area (e.g., vastus lateralis: P = 0.010, d = 0.64). Exercise time was reduced (P = 0.008, d = 0.62) and peripheral processes contributed to a reduction in maximal force due to cycling. After treatment, the severity of self-reported fatigue increased (P = 0.041, r = - 0.65) and health-related quality of life decreased (P = 0.012, r = - 0.79). CONCLUSION: Neuromuscular function was impaired in patients with head and neck cancer after treatment. Whole-body exercise tolerance was reduced and resulted in predominantly peripheral, rather than central, disturbances to the neuromuscular system. Future research should evaluate strength training after treatment for head and neck cancer, with the overall aim of reducing fatigue and improving health-related quality of life.

Quantification of Tumor Oxygenation Based on FMISO PET: Influence of Location and Oxygen Level of the Well-Oxygenated Reference Region.

Tumor hypoxia may play a fundamental role in determining the radiotherapy outcome for several cancer types. Functional imaging with hypoxia specific radiotracers offers a way to visualize and quantify regions of increased radioresistance, which may benefit from dose escalation strategies. Conversion of the uptake in positron emission tomography (PET) images into oxygenation maps offers a way to quantitatively characterize the microenvironment. However, normalization of the uptake with respect to a well-oxygenated reference volume (WOV), which should be properly selected, is necessary when using conversion functions. This study aims at assessing the sensitivity of quantifying tumor oxygenation based on 18F-fluoromisonidazole (FMISO) PET with respect to the choice of the location and the oxygenation level of the WOV in head and neck cancer patients. WOVs varying not only in shape and location but also with respect to the assigned pO2 level were considered. pO2 values other than the standard 60 mmHg were selected according to the specific tissue type included in the volume. For comparison, the volume which would be considered as hypoxic based on a tissue-to-muscle ratio equal to 1.4 was also delineated, as conventionally done in clinical practice. Hypoxia mapping strategies are found highly sensitive to selection of the location of well-oxygenated region, but also on its assigned oxygenation level, which is crucial for hypoxia-guided adaptive dose escalation strategies.

Association of Neck Range of Motion and Skin Caliper Measures on Dysphagia Outcomes in Head and Neck Cancer and Effects of Neck Stretches and Swallowing Exercises.

To date, there is a paucity of information in the literature regarding the association between cervical range of motion (CROM) and skin caliper measures (SCM) and swallowing outcomes in post-RT individuals with head and neck cancer. Also lacking in the literature are reports of the effect of swallowing exercises and neck stretches on changes in CROM and SCM and their associations with swallowing outcomes. The aim of this study was to assess the associations between CROM and SCM before initiation of a neck stretching and swallowing exercise program and to determine if 12 weeks of twice daily practice changes in CROM and SCM were associated with changes in swallowing outcomes in a cohort of 119 head and neck cancer survivors. Primary results revealed that at baseline, greater right and left CROM were associated with lower penetration aspiration scale (PAS) scores (r = - 0.321, p = < 0.001; r = - 0.203, p = 0.026, respectively). Improved skin pliability revealed lower PAS scores (r = - 0.210, p = 0.022). After 12 weeks, there were no significant correlations between changes in CROM and SCM and PAS scores. Changes in left CROM and CROM extension had positive associations with the Head and Neck Cancer Inventory eating score (r = 0.210, p = 0.026; r = 0.245, p = 0.009, respectively). Findings appear to indicate that any improvement was not associated with changes in swallowing outcomes. Head and neck cancer survivors may perceive improved diet and swallowing skills through exercise, with respect to improved CROM extension.

Impaired Movement Scaling and Reduced Synchrony with Vestibule Closure Characterize Swallowing in Severe Dysphagia.

The contribution of hyoid and laryngeal movement deficits to penetration or aspiration in dysphagia is unclear, partly due to large variations in normal hyolaryngeal kinematics for swallowing. In healthy volunteers, laryngeal and hyoid kinematics relate to the requirements for laryngeal vestibule closure suggesting a central schematic control of movement magnitude and patterning for airway protection. Our first aim was to determine if patients with severe dysphagia showed evidence of an impaired swallowing schema, by examining if their kinematic measures were related to their hyolaryngeal space before swallow onset, and if hyolaryngeal movement synchrony for vestibule closure was disrupted. Our second aim was to determine the kinematic measures that predicted bolus penetration and aspiration in dysphagia. The methods included two-dimensional measures of the hyoid and laryngeal anterior and superior displacement and velocity, and the change in laryngeal vestibule area made from videofluoroscopic swallow recordings of 21 healthy volunteers and 21 patients with dysphagia on tube feeding secondary to the stroke or head and neck cancer. The results demonstrated that the patients did not adapt their hyolaryngeal movements during swallowing to their initial hyolaryngeal space. Further, none of the patients' measures of hyoid or laryngeal peak velocity timing were synchronized with vestibule closure, demonstrating a disorganized movement patterning. Laryngeal elevation peak velocity independently predicted penetration and aspiration. In conclusion, the central schema for swallowing patterning was disturbed, impairing the integration of kinematic actions for airway protection in severe dysphagia, while laryngeal peak elevation velocity predicted penetration and aspiration on patient swallows.