14q22.3 duplication including OTX2 in a girl with medulloblastoma: A case report with literature review.

Orthodenticle homeobox 2 (OTX2) is a known oncogenic driver of medulloblastoma. Germline duplication of 14q22.3 including OTX2 is a rare condition reported in patients with combined pituitary hormone deficiency, oculo-auriculo-vertebral spectrum, and hemifacial microsomia. There has been one previously published case of a patient carrying a 14q22.3 duplication that included OTX2 with hemifacial microsomia who also developed medulloblastoma. Here, we present a case of a 6-year-old girl with a history of delayed development who was diagnosed with medulloblastoma. Genetic evaluations revealed that she inherited a germline duplication of 14q22.3, which included OTX2. This genetic alteration was passed down from her mother, who also had a history of delayed development. Results from other genetic testing, including exome sequencing, fragile X syndrome, and mtDNA testing, were negative/normal. This is the second report of a 14q22.3 duplication that included OTX2 in a patient with medulloblastoma. Further studies are necessary to establish a clear association.

Nutrition outcomes and treatment toxicities in patients with head and neck cancer receiving helical intensity-modulated radiotherapy.

BACKGROUND: Helical intensity-modulated radiotherapy (H-IMRT) provides excellent limitation of dose to tissues not requiring treatment, although acute toxicity still occurs. The present study aimed to determine how treatment-related acute toxicities affect nutrition outcomes in patients with head and neck cancer. METHODS: A prospective observational study was conducted in 194 patients undergoing curative intent H-IMRT with or without other treatment modalities. Weight outcomes (kg) and acute toxicity and dysphagia data were collected during treatment using Common Toxicity Criteria for Adverse Effects (CTCAE), version 4.0. RESULTS: Significant weight loss (> 10%) was observed in 30% of high nutritional risk patients and 7% of low nutritional risk patients. Nausea, adjusted for baseline dysphagia, in high nutritional risk patients and nausea, dysphagia and pharyngeal mucositis in low nutritional risk patients were significant factors in explaining the percentage loss in baseline weight to treatment completion. CONCLUSIONS: Significant weight loss remains an issue during treatment, despite improvements in radiotherapy technology and high-level multidisciplinary care.

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.

Radiotherapy for cutaneous head and neck cancer and parotid tumours: a prospective investigation of treatment-related acute swallowing and toxicity patterns.

PURPOSE: Reports of acute treatment-related dysphagia and toxicities for patients with parotid tumours or cutaneous head and neck cancer (HNC) are limited. This study aimed to describe the severity and timing of dysphagia and related toxicities experienced during radiotherapy for cutaneous HNC and parotid tumours, to inform the nature of future speech pathology (SP) service models required during treatment. METHODS: Prospective study of 32 patients with parotid tumours and 36 with cutaneous HNC undergoing curative non-surgical management. Dysphagia and acute toxicity data was collected weekly during treatment and at 2, 4 and 12 weeks post-treatment using the Functional Oral Intake Scale, diet descriptors and CTCAE v4.0. RESULTS: In both groups, minimal treatment toxicities (grades 0-1) were observed. Xerostomia and dysgeusia were the most frequently reported grade 2 toxicities. Only 3% of parotid patients and 6% with cutaneous HNC experienced grade 3 dysphagia. Full or soft texture diets were maintained by > 70% of patients in both groups. Symptoms peaked in the final week of treatment and rapidly improved thereafter. Apart from xerostomia < 10% of patients had any grade 2 toxicity at 12 weeks post-treatment. CONCLUSION: Patients in these subgroups of HNC experienced minimal treatment-related toxicity during radiotherapy. As such, the need for supportive symptom management by SP is low. Models that involve interdisciplinary surveillance of symptoms with referral to SP only when required may be best suited for these individuals to ensure issues are identified whilst minimising patient burden created by unnecessary routine SP appointments.

Enteral nutrition support and treatment toxicities in patients with head and neck cancer receiving definitive or adjuvant helical intensity-modulated radiotherapy with concurrent chemotherapy.

BACKGROUND: Enteral nutrition (EN) is often required in patients with head and neck cancer (HNSCC); however, initiation criteria is limited or inconsistent. This study aimed to describe the relationship of treatment toxicities and requirement for EN and investigate toxicity and baseline characteristics association with EN duration. METHODS: Acute toxicities and baseline characteristics were collected from patients with HNSCC (n = 110) undergoing H-IMRT. Percentage EN contributing to estimated requirements and EN duration were measured. RESULTS: The threshold for patients needing ≥50% of estimated requirements via EN increased from week 3 to 4 for grade ≥2 oral/pharyngeal mucositis, dysgeusia, thick saliva and nausea, and for grade 3 dysphagia. Patients with grade 2-3 dysphagia had a reduced risk of ceasing EN compared to those with grade 0-1 dysphagia. CONCLUSIONS: Using acute toxicities in clinical practice may be a useful tool to inform prompt initiation of EN prior to decline in nutritional status and anticipate EN duration.

Micronutrient deficiency risk in long-term enterally fed patients: A systematic review.

BACKGROUND AND AIMS: The micronutrient status of those receiving long-term enteral nutrition (EN) is poorly characterised. This systematic review was undertaken to determine prevalence of micronutrient deficiency in those receiving EN; the impact of the route of feeding; whether underlying disease or clinical factors were associated with micronutrient status; and the efficacy of interventions utilised to treat identified micronutrient deficiency. METHODS: Electronic databases (CINAHL, Embase, PubMed, Web of Science) were searched to June 2021 for publications of primary investigation of micronutrient status in adults or children (>5yrs) receiving EN for >2 months in their usual residence. Independent assessment of compliance with inclusion criteria (Covidence®), data extraction of predefined data points, assessment of basis (Academy of Dietetics Quality Checklist) and certainty of evidence (GRADE) was assessed by at least two authors. (PROSPERO Registration: CRD42021261113). RESULTS: Thirty-one studies (n = 744) met inclusion criteria. Deficiency was reported for copper, zinc, selenium, beta-carotene, and vitamins A, D and E: Only copper, zinc and selenium were associated with physical/haematological manifestations of deficiency. Jejunal feeding was associated with the development of copper deficiency and often required gastric or parenteral replacement to resolve the issue. Circumstances leading to deficiency included receiving feed products formulated with inadequate amounts of the implicated nutrient, low feed product volumes in the context of low macronutrient requirements, and nutritional decline prior to commencement of EN. Potential confounding factors such as inflammation were rarely accounted for. No studies investigated the contribution of underlying clinical condition on micronutrient status, and no other clinical or demographic features appeared to impact outcomes. Reported methods for treating identified deficiencies were usually successful in reversing deficiency symptoms. The certainty of evidence is very low, and the level of bias moderate to high. CONCLUSION: While the evidence is very uncertain about the effect of long-term enteral feeding on the development of micronutrient deficiencies, clinicians should be alert to the possibility of micronutrient deficiency developing in long-term EN fed patients. Those who may be at increased risk are those receiving nutrition into the jejunum, those who meet macronutrient requirements in low volumes of EN product, and those commencing EN in a nutritionally deplete state. Further research and surveillance of micronutrient status with contemporary EN products and practices is required.

Evaluation of a novel pre-treatment model of nutrition care for patients with head and neck cancer receiving chemoradiotherapy.

AIMS: Weight loss and malnutrition occur frequently in patients with head and neck cancer and are associated with reduced survival. This pragmatic study aimed to determine the effect of a novel pre-treatment model of nutrition care on nutrition outcomes for patients with head and neck cancer receiving chemoradiotherapy. METHODS: This health service evaluation consisted of an evaluation of the new model of care implementation (Phase 1) and an evaluation of patient outcomes (Phase 2) in pre- and post-implementation cohorts (n = 64 and n = 47, respectively). All Phase 2 patients received a prophylactic gastrostomy. The new model of care consisted of dietary counselling and commencement of proactive supplementary enteral nutrition via a prophylactic gastrostomy, in addition to normal oral intake, prior to treatment commencement. Nutrition outcomes were collected at baseline (pre-treatment) and 3 months post-radiotherapy completion. RESULTS: The new model of care was successfully incorporated into practice with high referral (96.5%) and attendance (91.5%) rates to the counselling session, and high adherence rates to proactive tube feeding (80.9%). Patients in the post-implementation cohort had less weight-loss (1.2%; p = 0.338) and saw less of a decline in nutritional status compared to patients in the pre-implementation cohort (23% vs. 30%, respectively; p = 0.572), deemed clinically important. However, patients still experienced critical weight loss overall (mean 9.9%). CONCLUSION: Pre-treatment nutrition care was feasible in standard clinical practice and demonstrated clinically relevant outcome improvements for patients. Future high-quality research is warranted to investigate further multidisciplinary strategies to attenuate weight-loss further, inclusive of patient-reported barriers and enablers to nutrition interventions.

Assessing the Concurrent Validity and Interrater Reliability of Patient-Led Screening Using the Malnutrition Screening Tool in the Ambulatory Cancer Care Outpatient Setting.

BACKGROUND: The prevalence of malnutrition in cancer patients is reported as high as 65%; however, malnutrition screening is often substandard. The Malnutrition Screening Tool (MST) has been validated for use by health care professionals to detect at-risk patients; however, there is a gap in the literature regarding validation of patient-led MST screening. OBJECTIVE: The aim of the study was to assess the concurrent validity of patient-led MST against the Subjective Global Assessment (SGA) and the interrater reliability of patient-led MST against dietitian-led MST in patients attending ambulatory cancer care services for chemotherapy or supportive treatments. DESIGN/PARTICIPANTS: A single-site diagnostic accuracy study of 201 patients between May and June 2017 attending the ambulatory cancer care setting at an Australian metropolitan tertiary hospital in Queensland. MAIN OUTCOME MEASUREMENTS: The primary outcome measures were concurrent validity and interrater reliability of MST scores as determined by patients (patient-MST), dietitians (dietitian-MST), and SGA as completed by the dietitian. STATISTICAL ANALYSIS: Concurrent validity of patient-led MST scores against the SGA was determined using specificity, sensitivity, positive predictive values, and negative predictive values. Interrater reliability of patient-MST and dietitian-MST was assessed using κ coefficient. RESULTS: The ability of the patient-led MST scores (0 to 1 vs 2 to 5) to indicate nutrition status was found to have a sensitivity of 94% (95% CI 81% to 99%), a specificity of 86% (95% CI 79% to 91%), and an area under the receiver operating characteristic curve of 0.93 (95% CI 0.89 to 0.96). The positive predictive value was 59% (95% CI 45% to 71%), and the negative predictive value was 99% (95% CI 95% to 100%). A weighted κ of 0.83 (95% CI 0.82 to 0.87) between patient-MST and dietitian-MST was found. CONCLUSION: Patient-led MST screening is a reliable and valid measure that can accurately identify ambulatory cancer care patients as at risk or not at risk of malnutrition.

Outcomes of radiologically inserted gastrostomy versus percutaneous endoscopic gastrostomy.

INTRODUCTION: Gastrostomy insertion either via radiological (radiologically inserted gastrostomy, RIG) or endoscopic (percutaneous endoscopic gastrostomy, PEG) approaches are widely practiced throughout Australia. The purpose of this study was to compare outcomes of inserted tubes and cost evaluation by both methods. METHODS: A retrospective cohort study conducted on all-cause gastrostomy insertions at a quaternary Australian Hospital, Royal Brisbane and Womens' Hospital (RBWH) between January 2012 and August 2015. Current referral pattern is first-line gastrostomy and second-line radiological insertion. RESULTS: A total of 402 gastrostomy tubes were inserted with a total of 307 PEG tubes and 95 RIG tubes, with follow-up to one calendar year. Mean patient age was 61 years ± 14.2 years with 76% male patients. A total of 84% of patients were head and neck cancer patients; major indications for insertion include prophylaxis (58%), dysphagia (32%) and NBM (2.5%). Patient groups were heterogeneous with varied indications for insertion including prophylaxis, dysphagia, decompression, NBM and treatment side effects. Outcomes measured included the following: complications, premature tube failure prior to expected removal and, overall tube outcome/ disposition. A lower incidence of minor complications was observed with the RIG group than the PEG group without differences in major complications over time. Tube failure due to either blockage or dislodgement was assessed. Multivariate analysis of all-cause dislodgement found 'method of insertion' a predictor of dislodgement with RIG 5.4(OR) times more likely to be dislodged than PEG. Competing risk analysis demonstrates equipment as a significant cause of dislodgement occurring more commonly with RIG than PEG tubes. Tubes were removed more often in the PEG group because a large volume were prophylactic. Tubes were replaced more often in the RIG group, with tube blockage and equipment as causes for tube replacement in this group. Replacements occur either in suite or bedside. Costing data were limited with only 94 patients' costing data qualifying for a limited unit cost evaluation, with radiologically inserted tubes marginally more expensive than tubes inserted endoscopically. CONCLUSIONS: Both are safe procedures, with improved techniques; radiologically inserted gastrostomies have an improved profile with respect to dislodgement rates than previously reported in the literature. Radiological tubes remain limited by equipment factors with balloon failure an ongoing issue. Cost analysis was hindered by poor documentation; however, the opportunity cost remains an important advantage of radiological insertion at peripheral sites, increasingly relevant for health service delivery in our geographically vast state.

Reliability of Patient-Led Screening with the Malnutrition Screening Tool: Agreement between Patient and Health Care Professional Scores in the Cancer Care Ambulatory Setting.

BACKGROUND: The prevalence of malnutrition in patients with cancer is reported as high as 60% to 80%, and malnutrition is associated with lower survival, reduced response to treatment, and poorer functional status. The Malnutrition Screening Tool (MST) is a validated tool when administered by health care professionals; however, it has not been evaluated for patient-led screening. OBJECTIVES: This study aims to assess the reliability of patient-led MST screening through assessment of inter-rater reliability between patient-led and dietitian-researcher-led screening and intra-rater reliability between an initial and a repeat patient screening. DESIGN/PARTICIPANTS: This cross-sectional study included 208 adults attending ambulatory cancer care services in a metropolitan teaching hospital in Queensland, Australia, in October 2016 (n=160 inter-rater reliability; n=48 intra-rater reliability measured in a separate sample). MAIN OUTCOME MEASUREMENTS: Primary outcome measures were MST risk categories (MST 0-1: not at risk, MST ≥2: at risk) as determined by screening completed by patients and a dietitian-researcher, patient test-retest screening, and patient acceptability. STATISTICAL ANALYSIS: Percent and chance-corrected agreement (Cohen's kappa coefficient, κ) were used to determine agreement between patient-MST and dietitian-MST (inter-rater reliability) and MST completed by patient on admission to unit (patient-MSTA) and MST completed by patient 1 to 3 hours after completion of initial MST (patient-MSTB) (intra-rater reliability). RESULTS: High inter-rater reliability and intra-rater reliability were observed. Agreement between patient-MST and dietitian-MST was 96%, with "almost perfect" chance-adjusted agreement (κ=0.92, 95% CI 0.84 to 0.97). Agreement between repeated patient-MSTA and patient-MSTB was 94%, with "almost perfect" chance-adjusted agreement (κ=0.88, 95% CI 0.71 to 1.00). Based on dietitian-MST, 33% (n=53) of patients were identified as being at risk for malnutrition, and 40% of these reported not seeing a dietitian. Of 156 patients who provided feedback, almost all reported that the MST was clear (92%), questions were easy to understand (95%), and completion time was ≤5 minutes (99%). CONCLUSION: Patient-led screening with the MST is reliable and well accepted by patients. Patient-led screening in the cancer care ambulatory setting has the potential to improve patient autonomy and screening completion rates.

Helical intensity-modulated radiotherapy with concurrent chemotherapy for oropharyngeal squamous cell carcinoma: A prospective investigation of acute swallowing and toxicity patterns.

BACKGROUND: Conformal radiotherapy modalities may minimize treatment toxicities. The purpose of this study was to document the extent and timing of dysphagia and related toxicities during helical intensity-modulated radiotherapy (IMRT) with chemotherapy for oropharyngeal squamous cell carcinoma (SCC). METHODS: We conducted a prospective study of 76 patients with oropharyngeal SCC undergoing helical IMRT with chemotherapy. Dysphagia and acute toxicity data were collected weekly during treatment and at 2, 4, and 12 weeks posttreatment using the Functional Oral Intake Scale, diet descriptors, and Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. RESULTS: Patients experienced maximum incidence of grade 3 dysphagia (61%), mucositis (30%), and thick saliva (38%), with grade 2 xerostomia (87%) and dysgeusia (97%). Only 14.5% were nil-by-mouth. Symptoms peaked in week 7 and improved thereafter. Grade 3 dysphagia was twice as common for T3 to T4 tumors compared with T2. CONCLUSION: Results confirm that patients with oropharyngeal SCC undergoing helical IMRT with chemotherapy continue to experience incidences of acute toxicities comparable with other conformal techniques, and need supportive cares.

Home-based telehealth service for swallowing and nutrition management following head and neck cancer treatment.

Introduction Following (chemo)radiotherapy (C/RT) for head and neck cancer (HNC), patients return to hospital for regular outpatient reviews with speech pathology (SP) and nutrition and dietetics (ND) for acute symptom monitoring, nutritional management, and swallowing and communication rehabilitation. The aim of the current study was to determine the feasibility of a home-based telehealth model for delivering SP and ND reviews, to provide patients with more convenient access to these appointments. Methods Service outcomes, costs, and consumer satisfaction were examined across 30 matched participants: 15 supported via the standard model of care (SMOC), and 15 via the home-based telehealth model of care (TMOC). Results All patients were successfully managed via telehealth. The TMOC was more efficient, with a reduced number ( p < 0.003) and duration ( p < 0.01) of appointments required until discharge. Significant patient cost savings ( p = 0.002) were reported for the TMOC due to decreased travel requirements. While staff costs were reduced, additional telehealth equipment levies resulted in a lower but non-significant overall cost difference to the health service when using the TMOC. High satisfaction was reported by all participants attending the TMOC. Discussion The findings support the feasibility of a home-based telehealth model for conducting SP and ND reviews post C/RT for HNC.

Patterns of dysphagia and acute toxicities in patients with head and neck cancer undergoing helical IMRT±concurrent chemotherapy.

BACKGROUND: There is limited prospective data reporting the extent of treatment related toxicities associated with helical Intensity Modulated Radiotherapy (H-IMRT) for head and neck cancer (HNC). The study aim was to investigate severity, peak incidence and recovery patterns of dysphagia and related toxicities in patients undergoing H-IMRT±chemotherapy to examine when patients are experiencing symptoms requiring supportive clinical care. METHODS: Prospective study of 212 patients undergoing H-IMRT. Dysphagia and associated acute toxicities were monitored weekly during treatment and at weeks 2, 4 and 12 post treatment using the CTCAE v4, Functional Oral Intake Score and National Dysphagia Diet Descriptors. RESULTS: 75% experienced Grade 2-3 dysphagia. Over 70% had grade 2-3 dysguesia, xerostomia, and thick saliva, and >50% experienced grade 2-3 pharyngeal mucositis, oral mucositis, and nausea. 13% patients declined to NBM requiring complete enteral nutrition, 25% required enteral nutrition but maintained some form of oral intake. Symptoms peaked in final week of treatment, consistently improving thereafter, with the majority better than baseline by 12 weeks post-treatment. Concurrent chemotherapy at least doubles the odds of experiencing most symptoms excepting xerostomia, taste and fluid level. CONCLUSION: Despite advancements in radiation techniques, results confirm a high proportion of HNC patients experience dysphagia and related toxicities requiring supportive care during H-IMRT. Patients receiving H-IMRT alone experience a lower incidence of symptoms compared with those receiving concurrent chemotherapy. The data confirms the ongoing need for active on treatment monitoring with implications for the timing and intensity of patient support services.