Clinical practice guidelines on nutrition management in head and neck cancer: a systematic quality appraisal using the Appraisal of Guidelines for Research and Evaluation 2nd edition instrument.

OBJECTIVE: Several guidelines have been produced for the management of nutrition in patients with head and neck cancer. However, no systematic evaluation of the quality of these guidelines has been performed to date. METHOD: A comprehensive search was conducted up to August 2020. The quality of guidelines was assessed by four independent reviewers using the Appraisal of Guidelines for Research and Evaluation, 2nd edition. RESULTS: Nine guidelines were assessed for critical evaluation. Only two guidelines were classified as 'high quality'. The 'scope and purpose' domain achieved the highest mean score (75.5 ± 17.0 per cent), and the lowest domain mean score was 'applicability' (37.6 ± 23.0 per cent). CONCLUSION: These findings highlight the variability in the methodological quality of guidelines for the management of nutrition in head and neck cancer. These results may help to improve the reporting of future guidelines and guide the selection for use in clinical practice.

Green Salad Intake Is Associated with Improved Oral Cancer Survival and Lower Soluble CD44 Levels.

Deficiencies in fruit and vegetable intake have been associated with oral cancer (oral cavity and oropharyngeal). Salivary rinses contain measurable biomarkers including soluble CD44 (solCD44) and total protein, which are known markers of oral cancer risk. This study investigates the effect of nutritional factors on solCD44 and protein levels to evaluate oral cancer risk and survival. We evaluated solCD44 and protein levels from 150 patients with oral and oropharyngeal squamous cell carcinoma and 150 frequency-matched controls. We subsequently characterized the effect of food group consumption and these biomarkers on progression-free survival (PFS) and overall survival (OS). Patients reported eating fewer servings of salad (p = 0.015), while controls reported eating fewer servings of potatoes (p < 0.001). Oral cancer patients who consumed at least one serving per week of green salad were found to have significantly lower CD44 levels than those who ate salad less frequently (mean of log2[solCD44]1.73 versus 2.25, p = 0.014). Patients who consumed at least one serving per week of "salad or other vegetables" had significantly longer PFS (median 43.5 versus 9.1 months, p = 0.003, adjusted hazard ratio (HR) = 0.39 p = 0.014) and OS (median 83.6 versus 10 months, p = 0.008, adjusted HR = 0.04 p = 0.029). These findings suggest that dietary factors, namely greater green salad and vegetable intake, may be associated with lower CD44 levels and better prognosis in oral cancer patients.

Impact of early nutrition counseling in head and neck cancer patients with normal nutritional status.

BACKGROUND: Nutritional counseling is frequently overlooked in cancer patients with normal nutritional status. This study aimed to evaluate the impact of nutritional counseling in head and neck cancer (HNC) patients with normal nutritional status prior to concurrent chemoradiotherapy (CCRT). METHODS: A total of 243 patients with pretreatment normal nutritional status and locally advanced HNC receiving concurrent chemoradiotherapy (CCRT) at three medical centers were enrolled. All patients were retrospectively allocated into the early (≤ 2 weeks, n = 105, 43.2%), late (> 2 weeks, n = 102, 42.0%), and no nutritional counseling groups (n = 36, 14.8%) according to the time interval between the date of CCRT initiation and the first date of nutritional counseling for comparison. RESULTS: The 1-year overall survival rates were 95.0%, 87.5%, and 81.3% in the early, late, and no nutritional counseling groups (p = 0.035), respectively. The median body weight changes at end of CCRT were - 4.8% (range, - 13.3 to 8.7%), - 5.6% (range, - 21.9 to 5.6%), and - 8.6% (range, - 20.3 to 2.4%) in patients in the early, late, and no nutritional counseling groups, respectively. The early termination of chemotherapy rates and the incompletion rates of planned radiotherapy were 1.9% and 1.9%, 2.9%, and 2.0%, 13.9%, and 19.4% in patients in the early, late, and no nutritional counseling groups, respectively. CONCLUSIONS: Our findings strongly suggest that while some HNC patients may have pretreatment normal nutritional status, early nutritional counseling is nevertheless essential for the improvement of treatment tolerance and survival outcome.

A prospective nutritional assessment using Mini Nutritional Assessment-short form among patients with head and neck cancer receiving concurrent chemoradiotherapy.

BACKGROUND: No gold standard of nutritional assessment is established among patients with head and neck cancer (HNC) receiving concurrent chemoradiotherapy (CCRT). This study aimed to evaluate the clinical significance of pre-treatment nutritional status using the Mini Nutritional Assessment-short form (MNA-SF) among HNC patients receiving CCRT. METHODS: A total of 461 consecutive patients with newly diagnosed HNC treated with definitive CCRT at three medical institutes were prospectively enrolled. Nutritional status was assessed using MNA-SF within 7 days before CCRT initiation. Patients were classified as having normal nutrition, at risk of malnutrition, and malnourished groups according to MNA-SF for comparison. RESULTS: The 1-year overall survival rates were 89.8%, 76.8%, and 67.7% in the normal nutrition, at risk of malnutrition, and malnourished groups, respectively. Patients with normal nutrition had significantly lower rates of uncompleted radiotherapy and chemotherapy (4.5% and 4.1%, respectively) compared with patients at risk for malnutrition (14.1% and 11.5%, respectively) and those malnourished (11.1% and 11.1%, respectively). Patients with normal nutrition had significantly lower treatment-related complication rates regarding emergency room visits, hospital admission, and need for tubal feeding than those with at risk of malnutrition and malnourished. Patients with normal nutrition had significantly fewer severe hematologic toxicities (p = 0.044) and severe non-hematologic toxicities (p = 0.012) of CCRT than those malnourished. CONCLUSION: Pre-CCRT nutritional status identifies HNC patients vulnerable to treatment interruption and treatment complications. We suggest that nutritional assessment with MNA-SF should be incorporated in pre-CCRT evaluation for all HNC patients.

Tratamiento oncológico y estado nutricional del cáncer de cabeza y cuello / Cancer treatment and nutritional status of head and neck cancer

Introducción: la desnutrición es un factor negativo en el manejo del paciente con cáncer. Objetivo: evaluar la influencia del tratamiento oncológico en la evolución del estado nutricional del paciente diagnosticado con cáncer de cabeza y cuello. Métodos: estudio descriptivo, longitudinal, prospectivo y correlacional. Muestra de 36 pacientes, mediante técnica no probabilística a conveniencia. Se utilizó un instrumento con variables demográficas, clínicas, antropométricas, presencia de complicaciones y vía de alimentación; se aplicó estadístico descriptivo con media, desviación estándar, frecuencias y porcentaje. Como estadística inferencial se utilizó la técnica de Fisher, con significancia del valor p < 0,05. Resultados: Se tuvieron 36 pacientes. De los cuales 19 (52,7%) fueron del sexo masculino. No hay correlación significativa entre IMC y el tratamiento oncológico, p=0,074; tampoco entre IMC y vía de alimentación, p=0,796. No hay correlación significativa entre la albúmina sérica y las complicaciones durante el tratamiento oncológico, p=0,278; y las complicaciones después del tratamiento oncológico, p=0,877. Discusión: En los datos de Varila et al. 25, se obtiene la vía oral como la vía de alimentación predominante, en menor medida la sonda. Según Huata Vilca 28, existe algún grado de correlación entre la albúmina sérica y la aparición de alguna complicación postoperatoria, estos resultados son en el vólvulo del sigmoides. Conclusiones: No hay una correlación significativa entre IMC y el tratamiento oncológico, tampoco entre el IMC y la vía de alimentación. Entre la albúmina sérica no hay una correlación significativa con las complicaciones durante y después del tratamiento oncológico. (AU)

Introduction: malnutrition is a negative factor in the management of patients with cancer. Objective: to evaluate the influence of cancer treatment on the evolution of the nutritional status of the patient diagnosed with head and neck cancer. Methods: descriptive, longitudinal, prospective and correlational study. Sample of 36 patients, using a convenience non-probabilistic technique. An instrument with demographic, clinical, anthropometric variables, presence of complications and feeding route was used; Descriptive statistics were applied with mean, standard deviation, frequencies and percentage. Fisher’s technique was used as inferential statistics, with significance of p <0,05. Results: There were 36 patients. Of which 19 (52,7%) were male. There is no significant correlation between BMI and cancer treatment, p = 0,074; nor between BMI and food route, p = 0,796. There is no significant correlation between serum albumin and complications during cancerb treatment, p = 0,278; and complications after cancer treatment, p = 0,877. Discussion: The oral route is obtained as the predominantroute of feeding, to a lesser extent the tube. There is some degree of correlation between serum albumin and the appearance of some postoperative complication; these results are in sigmoid volvulus. Conclusions: There is no significant correlation between BMI and cancer treatment, nor between BMI and diet. There is no significant correlation between serum albumin with complications during and after cancer treatment. (AU)

Drinking Ice-Cold Water Reduces the Severity of Anticancer Drug-Induced Taste Dysfunction in Mice.

Taste disorders are common adverse effects of cancer chemotherapy that can reduce quality of life and impair nutritional status. However, the molecular mechanisms underlying chemotherapy-induced taste disorders remain largely unknown. Furthermore, there are no effective preventive measures for chemotherapy-induced taste disorders. We investigated the effects of a combination of three anticancer drugs (TPF: docetaxel, cisplatin and 5-fluorouracil) on the structure and function of mouse taste tissues and examined whether the drinking of ice-cold water after TPF administration would attenuate these effects. TPF administration significantly increased the number of cells expressing apoptotic and proliferative markers. Furthermore, TPF administration significantly reduced the number of cells expressing taste cell markers and the magnitudes of the responses of taste nerves to tastants. The above results suggest that anticancer drug-induced taste dysfunction may be due to a reduction in the number of taste cells expressing taste-related molecules. The suppressive effects of TPF on taste cell marker expression and taste perception were reduced by the drinking of ice-cold water. We speculate that oral cryotherapy with an ice cube might be useful for prophylaxis against anticancer drug-induced taste disorders in humans.

Nutritional outcomes in head and neck cancer patients: is intensive nutritional care worth it?

OBJECTIVE: This study aimed to compare nutritional outcomes before and after implementation of weekly dietetic counseling (intensive nutritional care) in head and neck cancers patients. METHODS: A retrospective study with all head and neck patients, who received radiotherapy between January 2010 and December 2017 were performed. The main outcome was significant weight loss. Compliance to caloric and protein recommendations were also evaluated. RESULTS: In all, 472 patients were included. Weight loss was not different between before and after implementation (-6.7%; IQ -10.5/-1.9 vs -5.0%; IQ -9.8/-0.7;p=0.06).There were no significant difference in terms of meeting the recommended intake. Higher baseline body mass index and oral nutritional support predicted significant weight loss. CONCLUSION: Implementation of intensive nutritional care did not have an impact on weight loss and energy and protein intake in head and neck cancer patients. Further research would be of value to determine the appropriate service-delivery model to achieve optimal patient outcomes.

Effects of a Multidisciplinary Residential Nutritional Rehabilitation Program in Head and Neck Cancer Survivors-Results from the NUTRI-HAB Randomized Controlled Trial.

Head and neck cancer survivors frequently experience nutritional challenges, and proper rehabilitation should be offered. The trial objective was to test the effect of a multidisciplinary residential nutritional rehabilitation programme addressing physical, psychological, and social aspects of eating problems after treatment. In a randomized controlled trial, 71 head and neck cancer survivors recruited through a nationwide survey were randomized to the program or a wait-list control group. Inclusion was based on self-reported interest in participation. The primary outcome was change in body weight. Secondary outcomes included physical function, quality of life, and symptoms of anxiety and depression. Differences between groups at the 3-month follow-up were tested. No significant differences were seen in body weight change, but there were overall trends towards greater improvements in physical function (hand grip strength: p = 0.042; maximal mouth opening: p = 0.072) and quality of life ("Role functioning": p = 0.041; "Speech problems": p = 0.040; "Pain": p = 0.048) in the intervention group. To conclude, a multidisciplinary residential nutritional rehabilitation program had no effect on body weight in head and neck cancer survivors with self-reported interest in participation, but it may have effect on physical function and quality of life. Further research on relevant outcomes, inclusion criteria, and the program's effect in different subgroups is needed.

Home Enteral Nutrition in Adults-Nationwide Multicenter Survey.

Home enteral nutrition (HEN) is an important part of the health care system, with a growing population of patients around the world. The aim of our study was to analyze one of the largest cohorts of HEN patients to provide the most recent data available in European literature. A multicenter, nation-wide survey in the period of 1 January 2018-1 January 2019 was performed in Poland. Data concerning adult patients on HEN in 2018 during 1 year of observation time were analyzed: demographic characteristics, primary disease, technique of enteral feeding, diet formulation and amount of energy provided. A total of 4586 HEN patients (F: 46.7%, M: 53.3%) were included in the study. The primary diseases were: 54.5% neurological (17.4%-neurovascular, 13.7%-neurodegenerative), 33.9% cancer (20.2%-head and neck, 11.7%-gastrointestinal cancer), 2.5%-gastroenterology, 1.5%-inherited diseases. Of new registrations in 2018-cancer patients 46.3%, neurological patients 45.1%. The median age overall was: 64 yr., BMI-20.2 kg/m2, NRS 2002 score-4.28. A total of 65% of patients were treated with PEG, 11.6% with surgical gastrostomy, 14.3% with naso-gastric tube and 7% with jejunostomy. Boluses were the most common method of feeding (74.4%). Gravity flow was used in 17.6% and peristaltic pump was used in 8% patients. The median energy provision was 1278 kcal/day and 24 kcal/kg/day. The most commonly used diets were: isocaloric (28.1%), protein-enriched isocaloric (20%) and protein-enriched hypercaloric (12%). The median overall duration of HEN was 354 days, 615 days for neurological and 209 days for cancer patients. A number of new registrations of cancer patients was significant and long duration of HEN in this group is encouraging. A developing spectrum of enteral formulas available enables more specified nutritional interventions.

Meta-analysis of the association between dietary inflammatory index (DII) and upper aerodigestive tract cancer risk.

BACKGROUND: Epidemiological studies have reported an inconsistent relationship between dietary inflammatory index (DII) and upper aerodigestive tract (UADT) cancer risk. However, no systematic review or meta-analysis has been reported up to now. To quantify the association between DII and UADT cancer risk, we performed this meta-analysis. METHODS: The PubMed, EMBASE, Web of Science and Cochrane Library database were searched for relevant studies from inception December 2018. All case-control studies investigating the association between DII and UADT cancer risk were selected. RESULTS: A total of 9 case-control studies were identified, involving 13,714 participants. The adjusted pooled OR of UADT cancer for the highest (the most pro-inflammatory diet) vs lowest (the most anti-inflammatory diet) DII categories were 2.27 (95% CI: 1.89-2.73). Subgroup analysis showed that individuals with the highest category of DII score were independently associated with esophagus cancer (OR = 2.53, 95% CI: 1.74-3.68), oral cavity cancer (OR = 2.23, 95% CI: 1.73-2.86), pharyngeal cancer (OR = 2.02, 95% CI: 1.54-2.64), and laryngeal cancer (OR = 2.05, 95% CI: 0.85-4.93). CONCLUSION: This meta-analysis suggested that the most pro-inflammatory diets (the highest DII scores) are associated with increased UADT cancer risk. However, the association between DII and laryngeal cancer risk need to be further investigated.

Safety of Prophylactic Gastrostomy Tube Placement and Gastrostomy Tube Usage in Patients Treated by Radio(chemo)therapy for Head and Neck Cancer.

BACKGROUND: A gastrostomy feeding tube is one method for long-term feeding support in patients undergoing radio(chemo)therapy for head and neck cancer (HNC). The aim of this study was to analyze the safety of prophylactic gastrostomy tube placement and usage in HNSCC patients. PATIENTS AND METHODS: HNC patients undergoing percutaneous endoscopic gastrostomy (PEG) or radiological percutaneous gastrostomy (RPG) tube placement prior to radio(chemo)therapy from 2010-2014 were retrospectively reviewed regarding procedural and long-term gastrostomy tube-related complications, usage of PEG/RPG, weight profile, pretreatment and posttreatment body mass index. RESULTS: A total of 212 patients underwent prophylactic feeding tube placement (71% RPG, 27% PEG and 2% surgical jejunostomy). A total of 173 patients utilized their gastrostomy tubes for either total or supplemental nutrition support. Despite this, 157 patients (74%) lost weight during therapy (mean weight loss=8 kg). The rate of severe tube-related complications (peritonitis/incorrect placement) was low and similar in both groups (PEG 2.7% vs. RPG 3.4%). CONCLUSION: Although a very high proportion of patients used their PEG/RPG during radio(chemo)therapy there was a high mean weight loss. Serious complications of tube placement were rare.

Postoperative enteral immunonutrition in head and neck cancer patients: Impact on clinical outcomes / Uso de inmunonutrición enteral en el postoperatorio de pacientes con cáncer de cabeza y cuello: impacto en los resultados clínicos

Background: Head and neck cancer patients have a high rate of complications during the postoperative period that could increase their morbidity rate. Arginine has been shown to improve healing and to modulate inflammation and immune response. The aim of our study was to assess whether use of arginine-enriched enteral formulas could decrease fistulas and length of stay (LoS). Methods. A retrospective study was conducted in patients who had undergone head and neck cancer surgery and were receiving enteral nutrition through a nasogastric tube in the postoperative period between January 2012 and May 2018. The differences associated to use of immunoformula vs. standard formulas were analysed. Sociodemographic, anthropometric, and nutritional intervention variables, as well as nutritional parameters, were recorded during the early postoperative period. Occurrence of complications (fistulas), length of hospital stay, readmissions, and 90-day mortality were recorded. Results: In a univariate analysis, patients who received nutritional support with immunonutrition had a lower fistula occurrence rate (17.91% vs. 32.84%; p = 0.047) and a shorter mean LoS [28.25 (SD 16.11) vs. 35.50 (SD 25.73) days; p = 0.030]. After adjusting for age, energy intake, aggressiveness of surgery and tumour stage, fistula occurrence rate and LoS were similar in both groups irrespective of the type of formula. Conclusions: Use of arginine-enriched enteral nutrition appears to decrease the occurrence of fistulas in the postoperative period in patients with head and neck cancer, with a resultant reduction in length of hospital stay. However, the differences disappeared after adjusting for age, tumour stage, or aggressiveness of the surgery

Introducción: El postoperatorio de los pacientes con cáncer de cabeza y cuello presenta una alta tasa de complicaciones. Esta circunstancia podría aumentar la morbilidad en estos pacientes. La arginina ha demostrado mejorar la curación y modular la inflamación y la respuesta inmune. Nuestro planteamiento es valorar si el uso de fórmulas de alimentación enteral enriquecidas con arginina podría reducir la aparición de fístulas y la duración de la estancia hospitalaria. Métodos: Estudio retrospectivo en pacientes intervenidos de cáncer de cabeza y cuello que recibieron nutrición enteral a través de una sonda nasogástrica en el periodo postoperatorio entre enero de 2012 y mayo de 2018. Se analizaron las diferencias asociadas a la utilización de inmunofórmula vs. fórmulas estándar. Se recogieron variables sociodemográficas, antropométricas, de intervención nutricional y de parámetros nutricionales durante el postoperatorio inmediato, así como la aparición de complicaciones (fístulas), la duración de la estancia hospitalaria, los reingresos y la mortalidad a 90 días. Resultados: En el análisis univariante los pacientes que recibieron apoyo nutricional con inmunonutrición presentaron menor tasa de aparición de fístulas (17,91 vs. 32,84%; p = 0,047) y menor estancia hospitalaria (28,25 [DE 16,11] vs. 35,50 [DE 25,73] días; p = 0,030). Después de ajustar por edad, aporte calórico, agresividad de la cirugía y estadio del tumor, la incidencia de fístula y la estancia hospitalaria fueron similares entre los grupos, independientemente del tipo de fórmula. Conclusiones: El uso de nutrición enteral enriquecida con arginina en pacientes con cáncer de cabeza y cuello intervenidos podría reducir el desarrollo de la fístula y la duración de la estancia hospitalaria; sin embargo, las diferencias observadas desaparecen después de ajustar por edad, estadio tumoral o agresividad de la cirugía

"Eat to Live"-Piloting a Culinary Medicine Program for Head & Neck Radiotherapy Patients.

BACKGROUND: Head and neck radiotherapy (H&N RT) patients are at risk for malnutrition following treatment due to dysphagia and alterations in taste quality. This project studied feasibility of a food skills intervention strategy support food preparation, cooking confidence, and individualized dietary choices to support nutritional status in this patient population. METHODS: We piloted a monthly cooking class (called "Eat to Live") from November 2018 to January 2019. Every class included cooking and nutrition domains, organized around a specific meal of the day (i.e., breakfast, lunch, or dinner). Seven participants (4 patients, 3 caregivers) attended at least one class, with four participants (3 patients, 1 caregiver) completing all three classes. Pre- and post-study measures (self-administered questionnaires) assessed changes in cooking behavior, dietary choices, and taste sensation before and after the intervention. RESULTS: Healthful eating scores increased modestly from start to finish of the class (1.5 to 1.7 on a 3-point scale), with averaged patient preference scores for healthy foods increasing incrementally. This took place despite physical taste scores declining across the 3-month study. After completing the class, participants were more likely to select fresh fruits and vegetables, grains, lean cuts of meat, and dairy products. Patients also adopted positive behavioral modifications to their diets, such as eating out at restaurants less often and baking/grilling foods instead of frying. CONCLUSIONS: To our knowledge, this is the first published report on feasibility and patient acceptance of an evidence-based culinary medicine intervention in H&N RT patients. We observed objective improvements in dietary choices and cooking confidence in a small cohort of patient/caregiver dyads. This pilot work justifies follow-on development of a more comprehensive intervention optimized for patient convenience and longitudinal support.

Repercusión de la radioterapia sobre la situación nutricional del paciente oncogeriátrico. ¿Puede el oncólogo radioterápico minimizar el impacto de la radioterapia sobre el estado nutricional del enfermo mayor? / Nutritional impact of radiotherapy in oncogeriatric patients. Can radiation oncologists minimize the radiotherapy impact on the nutritional status of the elderly patient?

El cáncer en pacientes ancianos representa un reto de salud a escala mundial debido al aumento de su incidencia y su mortalidad asociada. En nuestro país es la segunda causa de muerte en mayores de 65 años. En años venideros el problema irá en aumento, con un pronóstico de personas mayores de 65 años del 35% en el año 2050. La radioterapia supone una parte fundamental del tratamiento multidisciplinar del cáncer en los pacientes ancianos, donde unas veces se plantea como primera opción terapéutica y otras, como alternativa a la cirugía y/o la quimioterapia si estas plantean demasiado riesgo. El desarrollo tecnológico de la Oncología Radioterápica en los últimos años ha permitido optimizar los tratamientos y disminuir las toxicidades en los pacientes de edad avanzada, que suelen presentar mayor incidencia de comorbilidades. Es fundamental que los profesionales implicados en el tratamiento multidisciplinar del cáncer conozcan la posible toxicidad y su manejo en los pacientes oncogeriátricos, ya que, de lo contrario, disminuyen las probabilidades de que pacientes con indicación adecuada de este tratamiento lo reciban. En este sentido, es imprescindible el reconocimiento de aquellos pacientes que puedan sufrir desnutrición o estén en riesgo de sufrirla, para iniciar una intervención nutricional que minimice una pérdida de peso que altere o incluso haga suspender el tratamiento planificado

Cancer in elderly patients represents a global health challenge due to the increase in its incidence and its associated mortality. In our country it is the second leading cause of death in people over 65 years. In the coming years, the problem will increase, with a prognosis of people over 65 years of 35% in 2050. Radiotherapy is an essential part of the multidisciplinary treatment of cancer in elderly patients, where sometimes it is considered as the first therapeutic option and others, as an alternative to surgery and/or chemotherapy if they pose too much risk. The technological development of Radiation Oncology in recent years has allowed optimizing treatments and reducing side effects in elderly patients, who tend to have a higher incidence of comorbidities. It is essential that professionals involved in the multidisciplinary treatment of cancer know the possible toxicity and its management in oncogeriatric patients; otherwise, the percentage of patients who do not receive radiotherapy despite of an adequate indication will not decrease. In this sense, it is necessary to recognize those patients who may suffer from malnutrition or are at risk of suffering it, to initiate a nutritional intervention that minimizes weight loss that alters or even causes the suspension of the planned treatment

Aconselhamento Nutricional em Pacientes com Câncer de Cabeça, Pescoço e Esôfago em Tratamento (Quimio)Radioterápico / Nutritional Cousenling in Patients with Head, Neck and Esophagus Cancer in (Chemo)Radiotherapy / Asesoramiento Nutricional en Pacientes com Cáncer de Cabeza, Cuello y Esófago em Tratamiento (Quimio)Radioterápico

Introdução: A presença de um nutricionista no setor de radioterapia objetiva a recuperação e a manutenção do estado nutricional dos pacientes. Objetivo: Comparar os resultados do aconselhamento nutricional diário com o aconselhamento nutricional semanal em pacientes com câncer de cabeça, pescoço e esôfago em tratamento radioterápico. Método: Foram selecionados 29 pacientes para o estudo e separados aleatoriamente em dois grupos. O grupo intervenção recebeu aconselhamento nutricional diariamente. O grupo padrão recebeu aconselhamento nutricional semanalmente. De ambos os grupos, foram aferidos peso corporal, circunferência braquial ou de panturrilha, avaliação subjetiva global produzida pelo próprio paciente (ASG-PPP) e cálculo do recordatório alimentar diário. Resultados: A maioria dos participantes era do sexo masculino (80%), com média de idade de 62,7 ± 26 anos. A terapia nutricional oral foi necessária para 48% dos indivíduos e, ao final do tratamento, 60% estavam em uso de nutrição enteral. A perda de peso média no grupo intervenção foi de 1,89 ± 2,58 Kg comparada à perda média de peso no grupo padrão de 9,92 ± 6,68 Kg (p=0,017). Metade dos pacientes do grupo intervenção, que iniciaram o tratamento categorizados pela ASG-PPP em A, finalizou o tratamento nessa mesma categoria (41,7%). Mais de 40% dos pacientes do grupo intervenção alcançaram as necessidades calóricas durante cinco semanas do tratamento. Conclusão: Encontraram-se resultados significativos para menor perda de peso em pacientes com aconselhamento nutricional diário que podem futuramente ser precursores de diretrizes que orientem e direcionem profissionais a condutas específicas aos pacientes com esse perfil.

Introduction: The presence of a nutritionist in the radiotherapy sector intends to recover and maintain the nutritional status of the patients. Objective: To compare the results of daily nutritional counseling with weekly nutritional advising for patients with head, neck and esophagus cancer in radiotherapy treatment. Method: 29 patients were assigned to the study and randomly divided into two groups. The intervention group received nutritional advice daily. The standard group received weekly nutritional counseling. For both groups, body weight, calf or calf circumference, global subjective evaluation produced by the patient (ASG-PPP) and calculation of the daily dietary recall were measured. Results: The majority of the participants were male (80%), mean age 62.7 ± 26 years. Oral nutrition therapy was required treatment 60% were in use of enteral nutrition. The mean weight loss in the intervention group was 1.89 ± 2.58 kg compared to the mean weight loss in the standard group of 9.92 ± 6.68 kg (p <0.001). Half of the patients in the intervention group who began treatment categorized by ASG-PPP in A, finished treatment in the same category (41.7%). More than 40% of patients in the intervention group achieved caloric needs during five weeks of treatment. Conclusion: This study found significant results for lower weight loss in patients with daily nutritional counseling. These results may in the future be precursors of guidelines that steer and direct professionals to specific conducts to patients with this profile.

Introducción: La presencia de un nutricionista en el sector de radioterapia intenciona la recuperación y mantenimiento del estado nutricional de los pacientes. Objetivo: Comparar los resultados del asesoramiento nutricional diario con el asesoramiento nutricional semanal en pacientes con cáncer de cabeza, cuello y esófago en tratamiento radioterápico. Método: Fueron seleccionados 29 pacientes para el estudio y separados aleatoriamente en dos grupos. El grupo de intervención recibió asesoramiento nutricional diariamente. El grupo estándar recibió asesoramiento nutricional semanalmente. De ambos grupos se evaluaron peso corporal, circunferencia braquial o de pantorrilla, evaluación subjetiva global producida por el propio paciente (ASG-PPP) y cálculo del recordatorio alimentario diario. Resultados: La mayoría de los participantes eran del sexo masculino (80%), con una media de edad de 62,7 ± 26 años. La terapia nutricional oral fue necesaria para el 48% de los individuos y al final del tratamiento el 60% estaban en uso de nutrición enteral. La pérdida de peso media en el grupo de intervención fue de 1,89 ± 2,58 Kg comparada con la pérdida media de peso en el grupo estándar de 9,92 ± 6,68 Kg (p<0,001). La mitad de los pacientes del grupo intervención que iniciaron el tratamiento categorizados por la ASG-PPP en A, finalizaron el tratamiento en esa misma categoría (41,7%). Más del 60% de los pacientes del grupo de intervención alcanzaron las necesidades calóricas durante cinco semanas del tratamiento. Conclusión: Este estudio encontró resultados significativos para una menor pérdida de peso en pacientes con asesoramiento nutricional diario. Estos resultados pueden en el futuro ser precursores de pautas que orientan y dirigen profesionales a conductas específicas a los pacientes con este perfil.

Dietary-phytochemical mediated reversion of cancer-specific splicing inhibits Warburg effect in head and neck cancer.

BACKGROUND: The deregulated alternative splicing of key glycolytic enzyme, Pyruvate Kinase muscle isoenzyme (PKM) is implicated in metabolic adaptation of cancer cells. The splicing switch from normal PKM1 to cancer-specific PKM2 isoform allows the cancer cells to meet their energy and biosynthetic demands, thereby facilitating the cancer cells growth. We have investigated the largely unexplored epigenetic mechanism of PKM splicing switch in head and neck cancer (HNC) cells. Considering the reversible nature of epigenetic marks, we have also examined the utility of dietary-phytochemical in reverting the splicing switch from PKM2 to PKM1 isoform and thereby inhibition of HNC tumorigenesis. METHODS: We present HNC-patients samples, showing the splicing-switch from PKM1-isoform to PKM2-isoform analyzed via immunoblotting and qRT-PCR. We performed methylated-DNA-immunoprecipitation to examine the DNA methylation level and chromatin-immunoprecipitation to assess the BORIS (Brother of Regulator of Imprinted Sites) recruitment and polII enrichment. The effect of dietary-phytochemical on the activity of denovo-DNA-methyltransferase-3b (DNMT3B) was detected by DNA-methyltransferase-activity assay. We also analyzed the Warburg effect and growth inhibition using lactate, glucose uptake assay, invasion assay, cell proliferation, and apoptosis assay. The global change in transcriptome upon dietary-phytochemical treatment was assayed using Human Transcriptome Array 2.0 (HTA2.0). RESULTS: Here, we report the role of DNA-methylation mediated recruitment of the BORIS at exon-10 of PKM-gene regulating the alternative-splicing to generate the PKM2-splice-isoform in HNC. Notably, the reversal of Warburg effect was achieved by employing a dietary-phytochemical, which inhibits the DNMT3B, resulting in the reduced DNA-methylation at exon-10 and hence, PKM-splicing switch from cancer-specific PKM2 to normal PKM1. Global-transcriptome-analysis of dietary-phytochemical-treated cells revealed its effect on alternative splicing of various genes involved in HNC. CONCLUSION: This study identifies the epigenetic mechanism of PKM-splicing switch in HNC and reports the role of dietary-phytochemical in reverting the splicing switch from cancer-specific PKM2 to normal PKM1-isoform and hence the reduced Warburg effect and growth inhibition of HNC. We envisage that this approach can provide an effective way to modulate cancer-specific-splicing and thereby aid in the treatment of HNC.

Adherencia a la dieta mediterránea: comparación entre pacientes con cáncer de cabeza y cuello y población sana / Adherence to Mediterranean diet: A comparison of patients with head and neck cancer and healthy population

Antecedentes y objetivo: La dieta mediterránea (DM) tradicional se asocia a un menor riesgo de padecer numerosos cánceres. Sin embargo, pocos estudios han analizado la relación de la DM con el riesgo de padecer cáncer de cabeza y cuello (CCyC). Se lleva a cabo un estudio de casos y controles en el que se compara la adherencia a la DM en pacientes diagnosticados de CCyC y población sana. Pacientes y método: Mediante el cuestionario Mediterranean Diet Adherence Screener (MEDAS), de 14 ítems, empleado en el estudio PREDIMED, se evalúa el nivel de adherencia a la DM tanto en casos obtenidos de pacientes diagnosticados de CCyC en el hospital 12de Octubre de Madrid, como en controles obtenidos de población sana de un centro de salud del Área, estratificando dicha adherencia en función de la puntuación: baja (≤7puntos), media (8-9puntos) y alta (≥10puntos). Se calcula el odds ratio (OR) para desarrollar CCyC en base a diferentes factores. Resultados: Se analiza una muestra de 168 individuos: 100 controles y 68 casos. El hábito tabáquico (OR: 2,98 [IC95%: 1,44-6,12]; p=0,003) y el consumo de alcohol (OR: 2,72 [IC95%: 1,39-5,33]; p=0,003) demuestran ser factores de riesgo para desarrollar CCyC. Sin embargo, la adherencia media-alta a la DM se asocia a menor riesgo de CCyC (OR: 0,48 [IC95%: 0,20-1,07]; p=0,052). Conclusiones: La adherencia media-alta a la DM se asocia a menor riesgo para desarrollar CCyC

Background and objective: The traditional Mediterranean diet (MD) is associated to a lower risk of suffering multiple tumors. However, few studies have analyzed the relationship between MD and the risk of developing head and neck cancer (HNC). A case-control study comparing adherence to MD was conducted in patients diagnosed with HNC and healthy population. Patients and methods: The level of adherence to MD was assessed using the 14-item MEDAS (Mediterranean Diet Adherence Screener) questionnaire, used in the PREDIMED study, in patients diagnosed with HNC at 12de Octubre Hospital in Madrid (cases) and in healthy subjects enrolled in a nearby primary health care center (controls). Adherence was stratified based on the score as low (≤7points), medium (8-9points), and high (≥10points). The odds ratio (OR) for developing HNC was estimated based on different factors. Results: A sample of 168 subjects (100 controls and 68 cases) was analyzed. Smoking (OR, 2.98 [95%CI: 1.44-6.12]; P=.003) and alcohol consumption (OR, 2.72 [95%CI: 1.39-5.33], P=.003) were strongly associated to HNC. However, medium-high adherence to MD was associated to a lower risk of developing HNC (OR, 0.48 [95%CI: 0.20-1.07], P=.052). Conclusions: Consistent medium-high adherence to MD contributes to decrease the risk of developing HNC

Feasibility Outcomes of a Pilot Randomized Clinical Trial to Increase Cruciferous and Green Leafy Vegetable Intake in Posttreatment Head and Neck Cancer Survivors.

BACKGROUND: Higher intakes of cruciferous vegetables (CVs) and green leafy vegetables (GLVs) in observational studies are associated with improvements in survival and cancer-related biomarkers in patients diagnosed with head and neck cancer (HNC). These results have yet to be corroborated in a randomized clinical trial (RCT). OBJECTIVE: Determine the feasibility of implementing a 12-week RCT to increase CV and GLV intake in posttreatment HNC survivors. DESIGN AND PARTICIPANTS: This was a two-arm RCT conducted among 24 posttreatment HNC survivors. Survivors were recruited from a southeastern, National Cancer Institute-designated Comprehensive Cancer Center between January 2015 and September 2016. INTERVENTION: There were two groups: (1) an experimental group (n=12) receiving weekly 15- to 30-minute telephone dietary counseling from a registered dietitian nutritionist stressing 2.5 cups per week CVs and 3.5 cups per week GLVs, and (2) an attention control group (n=12) receiving weekly 15- to 30-minute telephone dietary counseling from a registered dietitian nutritionist focusing on general healthy eating for cancer survivors. Participants completed a baseline survey, three 24-hour dietary recalls, phlebotomy, and anthropometric measures prior to randomization and at the end of the 12-week study period. The experimental group also completed weekly vegetable record recalls. MAIN OUTCOME MEASURES: Primary outcomes included feasibility, recruitment, retention, adherence, and safety. Secondary outcomes included inflammatory markers and carotenoids. STATISTICAL ANALYSES PERFORMED: Descriptive statistics were generated for demographic, epidemiological, and clinical variables as well as the primary feasibility outcomes. Between- and within-group comparisons of mean serum cytokine and carotenoid levels were performed using appropriate statistical tests depending on their respective distributions for the purpose of generating preliminary effect sizes. RESULTS: Overall, 350 incident HNC cases were screened for eligibility, and 98 were eligible for study participation. Reasons for ineligibility and exclusion included deceased (n=93); wrong or inactive telephone numbers, or unable to be reached, or lost to follow-up (n=93); not meeting inclusion criteria (n=39); and too ill to participate (n=27). Of the 98 eligible HNC cases, 24 agreed to participate, for an enrollment rate of 25%. The most common reason for nonparticipation was distance (n=48), as participants were asked to report for two on-site assignments. The retention rate was 96%. Mean intervention adherence rates for weekly goals were 67% CV, 74% GLV, and 71% overall. Completion rate of weekly counseling calls was 90%. The experimental group reported an overall mean increase of 5.5 cups GLV and 3.5 cups CV per week from baseline intake, respectively. No significant between- or within-arm differences were observed for inflammatory markers or carotenoids. CONCLUSION: A posttreatment intervention aimed at increasing CV and GLV intake in HNC survivors is feasible. A larger RCT is needed to assess the efficacy of this intervention on disease outcomes.

Eating As Treatment (EAT): A Stepped-Wedge, Randomized Controlled Trial of a Health Behavior Change Intervention Provided by Dietitians to Improve Nutrition in Patients With Head and Neck Cancer Undergoing Radiation Therapy (TROG 12.03).

PURPOSE: Malnutrition in head and neck cancer (HNC) treatment is common and associated with poorer morbidity and mortality outcomes. This trial aimed to improve nutritional status during radiation therapy (RT) using a novel method of training dietitians to deliver psychological techniques to improve nutritional behaviors in patients with HNC. METHODS AND MATERIALS: This trial used a stepped-wedge, randomized controlled design to assess the efficacy of the Eating As Treatment (EAT) program. Based on motivational interviewing and cognitive behavioral therapy, EAT was designed to be delivered by oncology dietitians and integrated into their clinical practice. During control steps, dietitians provided treatment as usual, before being trained in EAT and moving into the intervention phase. The training was principles based and sought to improve behavior-change skills rather than provide specific scripts. Patients recruited to the trial (151 controls, 156 intervention) were assessed at 4 time points (the first and the final weeks of RT, and 4 and 12 weeks afterward). The primary outcome was nutritional status at the end of RT as measured by the Patient-Generated Subjective Global Assessment. RESULTS: Patients who received the EAT intervention had significantly better scores on the primary outcome of nutritional status at the critical end-of-treatment time point (ß = -1.53 [-2.93 to -.13], P = .03). Intervention patients were also significantly more likely than control patients to be assessed as well-nourished at each time point, lose a smaller percentage of weight, have fewer treatment interruptions, present lower depression scores, and report a higher quality of life. Although results were not statistically significant, patients who received the intervention had fewer and shorter unplanned hospital admissions. CONCLUSIONS: This trial is the first of its kind to demonstrate the effectiveness of a psychological intervention to improve nutrition in patients with HNC who are receiving RT. The intervention provides a means to ameliorate malnutrition and the important related outcomes and consequently should be incorporated into standard care for patients receiving RT for HNC.

Nutritional Intervention for Nonsurgical Head and Neck Cancer Patients Treated with Radiation Therapy: Results from a Prospective Stepped-Wedge Clinical Protocol.

AIM: To evaluate the impact on weight loss (WL) of a standardized nutritional stepped-wedge protocol on consecutive head and neck cancer (HNC) patients treated with curative radiotherapy (RT). METHODS: We prospectively collected data of patients followed by a trained dietitian and treated according to a pre-defined stepped-wedge protocol. Patients with swallowing defect at the baseline and WL >10% 3 months prior to the beginning of RT were excluded from the analysis. Nutritional status was assessed at the baseline and weekly during the course of RT. Fluid and caloric intake were assessed through a 24-h recall. RESULTS: Between May 2010 and March 2011, 42 patients treated were evaluated. Median overall treatment time was 52.5 days. WL per CTCAE 4.03 was G0, G1 and G2 in 23 (55%), 14 (33%) and 5 (12%) patients, respectively. Thirty-five (83%) patients did not require enteral nutrition. About 90% of patients completed RT without interruption of oral feeding. CONCLUSIONS: Despite the high toxicity profile of curative RT in HN, we proposed a standardized stepped-wedge protocol allowing to prevent severe WL in most of our patients. Further larger prospective studies are warranted to validate our approach and to achieve consensus on nutritional intervention in this subset of patients.