Head and Neck Cancer Early Identification of Malnutrition High Risk Patients and Quality of Life Optimization

Malnutrition in Head and neck cancer (HNC) patients can be present at the moment of diagnosis. The nutritional status is determinant for the treatment success and quality of life of the patients. The nutritional status gradually declines during treatment and the majority of patients undergoing treatment will need nutritional therapy. On the other hand, HNC, like other cancers, can induce a paraneoplastic syndrome that leads to cachexia. This cachexia status is most of the times the cause of death or the cause of treatment failure. So, early identification of malnutrition high risk patients is crucial to start an adequate nutrition support intervention in HNC patients. This study aims to identify HNC patients who present malnutrition or higher risk of malnutrition; to signalize variables that support early identification of high-risk patients of becoming malnourished and to establish a dynamic relationship between malnutrition risk in these patients and Quality of Life (QoL) impacts. For six months consecutive outpatients with HNC admitted at the Head & Neck Unity of Oncology Portuguese Institute—Porto were asked to participate in the research (n = 114). The European Organisation for Research and Treatment of Cancer (EORTC) cancer-specific HRQoL questionnaire-QLQ-C30 high malnutrition risk respectively. Also, Emotional and social functional scales and all symptom scales—including pain, presented significant differences between high and medium risk of malnutrition patients. Fatigue, pain, insomnia, appetite loss and financial difficulties were domains directly related to high risk of malnutrition patients. Pain scores were significantly higher (43.23) in the high-risk patients when compared to medium risk patients (11.67). Nutrition support should be considered at any stage of the pathway —especially in high risk group—in order to optimize tumour treatment results, reduction of adverse effects of therapy and improving both QoL and survival.


Abstract
Malnutrition in Head and neck cancer (HNC) patients can be present at the moment of diagnosis. The nutritional status is determinant for the treatment success and quality of life of the patients. The nutritional status gradually declines during treatment and the majority of patients undergoing treatment will need nutritional therapy. On the other hand, HNC, like other cancers, can induce a paraneoplastic syndrome that leads to cachexia. This cachexia status is most of the times the cause of death or the cause of treatment failure. So, early identification of malnutrition high risk patients is crucial to start an adequate nutrition support intervention in HNC patients. This study aims to identify HNC patients who present malnutrition or higher risk of malnutrition; to signalize variables that support early identification of high-risk patients of becoming malnourished and to establish a dynamic relationship between malnutrition risk in these patients and Quality of Life (QoL) impacts. For six months consecutive outpatients with HNC admitted at the Head & Neck Unity of Oncology Portuguese Institute-Porto were asked to participate in the research (n = 114). The European Organisation for Research and Treatment of Cancer (EORTC) cancer-specific HRQoL questionnaire-QLQ-C30 and Malnutrition Universal Screening Tool, MUST were used. At the moment of first presentation, 32 patients (28.1%) presented high-risk of malnutrition. HNC patients with oral cavity and oropharynx tumour locations, older, with low literacy or with BMI under 18.5 at the moment of diagnosis, represent a high-risk group. When HNC is considered, a dynamic and bi-directional connection between malnutrition and QoL is observed. A significant (p < 0.001) difference in the scores of Global health status/QoL according to the malnutrition risk group was found: 62.96, 53.33, 42.71 for low, medium and

Introduction
Head and neck cancer (HNC) accounts for more than 550,000 cases and 380,000 deaths annually [1]. In the United States 63.000 new cases occur every year while in Europe a higher incidence is seen-250.000 new cases per year. HNC squamous cell carcinoma represents 3% and 6% of all cancer cases respectively [2] [3] [4].
HNC comprehends several locations: the oral cavity, pharynx, larynx, paranasal sinuses and salivary glands and is necessarily related to malnutrition during the disease process and the treatment [5].
Studies reveal that tumour locations, cancer stage, treatment plan, dietary habits, initial weight and body mass index (BMI), lifestyle factors, alcohol and tobacco consumption, oral health performance, social conditions, financial circumstances and cachexia syndrome can guide HNC patients to malnutrition [6] [7] [8]. Early identification of high-risk patients and intervention with nutrition support is crucial in HNC [11].

Objectives
This study aims to: • Identify HNC patients who present malnutrition or higher risk of malnutrition; • Signalize variables that support early identification of high-risk patients of becoming malnourished; • Establish a dynamic relationship between malnutrition risk in HNC patients and QoL impacts.

Ethics
The study was carried out in compliance with the Helsinki Declaration. The method was previously approved by the local research ethical committee and all HNC patients agreed to participate in the research and gave their informed consent. The data were collected for research purposes as part of the routine evaluation.

Patients
For six months, between January and June 2015, consecutive outpatients with HNC admitted at the Head & Neck Unity of Oncology Portuguese Institute-Porto (IPOP) were asked to participate(n = 114).
Socio-demographic data and clinical data-age, gender, education, body mass index (BMI), involuntary weight loss, malnutrition risk (Malnutrition Universal Screening Tool, MUST), and tumour location-were collected from the patient's clinical process and complemented, when needed, in semi structured interviews with patients, proxies or clinical staff. In order to better understand socio-demographic and clinical variables, patients were divided in three groups based on MUST risk (low, medium and high).

Questionnaires and scales
The European Organisation for Research and Treatment of Cancer (EORTC) cancer-specific HRQoL questionnaire-QLQ-C30, were used (Portuguese validated versions).
Questionnaires were completed immediately before consultation as a part of the routine evaluation. Inclusion criteria were: ability to understand written and spoken Portuguese and provision of written consent and physical presence in IPOP for consultation in Head and Neck Unity in the research days.
MUST risk was assessed using three parameters: current BMI, unintentional weight loss and the presence of any acute disease effect that could compromise nutritional intake for >5 days. These parameters are rated 0, 1 or 2 as follows: BMI > 20 kg/m 2 = 0, BMI between 18.5 and 20.0 kg/m 2 = 1 and BMI < 18.5 kg/m 2 = 2; unintentional weight loss in the past 3 -6 months < 5% = 0, weight loss between 5% and 10% = 1 and weight loss > 10% = 2; acute disease absent = 0 or acute disease present = 2. Int. J. Otolaryngology and Head & Neck Surgery The overall risk of malnutrition is defined by the sum of all points allocated to each parameter and is classified as follows: 0 = low-risk; 1 = medium-risk; 2 = high-risk [13].

Analysis Strategies and Statistics
Completed questionnaires were scored according to EORTC instructions. Healthrelated QoL data were analysed by the Statistical Package for Social Sciences (SPSS), version 17 for Windows. Descriptive data are presented with means, standard deviations, medians, ranges, and proportions as appropriate. The chi-squared test was used for testing relationships between the studied variables and to determine whether if there was a significant difference between the expected frequencies and the observed frequencies in the studied variables.

1) HNC Patients' Characteristics
Sociodemographic and clinical characteristics of the studied sample is presented in A relation between education and the risk for malnutrition was detected (Chi-squared = 6.763; degrees of freedom = 3; p = 0.034) as depicted in Table 2.
In fact, higher education (more than 6 schooling years) was associated with a low-risk of malnutrition-this group presented fewer patients than expected with high-risk of malnutrition (ratio 0.63) and more patients than expected in  (5) the low-risk group of malnutrition (ratio 1.30). On the contrary, the less educated group proved to be more vulnerable to malnutrition risk, having more patients than expected both in the high-risk group (ratio 1.12) and in the medium-risk group of malnutrition (1.33).

3) Malnutrition risk in HNC patients and QoL impacts
It was found that the risk of malnutrition has consistent impact on QoL (Table   3).
Patients at high-risk of malnutrition revealed a constant and significantly lower mean score in Global health status and in QoL. A median of 42.71 was found for high-risk patients group significantly lower than de median found low or medium risk groups, with 62.96 and 53.33 respectively.
When we look for all functional scales-and therefore worse QoL and func-  In symptom scales, scores were always higher in the high risk of malnutrition group, revealing to be significantly different from the low risk of malnutrition group except for Diarrhoea and Nausea and vomiting. The major associations were found in Fatigue, Pain, Insomnia, Appetite loss and Financial difficulties symptoms (p = 0.001). Moreover, Fatigue, Pain, Insomnia and Constipation symptom's differences also occurred between high and medium risk patients. A particularly significant difference verified was in Fatigue and Pain scales, with median scores for high-risk patients of 34 Just like in the functional scales, when considering the symptom scales, no differences were found between medium and low risk patients.

Discussion
HNC patient's demographic patterns have been changing over the past 30 yearsthey are more likely to be younger adults in their 40s and 50s who never smoked or had reduced tobacco exposure. It is suggested that 70% -90% of new cancers are oropharyngeal, an evidence of the human papillomavirus (HPV) [14]. The studied sample does not follow such trend since patients are older (63.2% having 46 -65 years old) and the major tumour location was not oropharyngeal but hypopharynx and larynx.
These findings may reflect a limitation of our study because patients were included while they have been presented to first time consultation in our department for a consecutively period of 6 months. So, this study population may not reflect the real incidence of HNC in Portugal when we are looking for some demographic data or incidence according to HNC primary sites.
More than half of the problems influenced by HNC have some connection with nutritional problems. Eating-related problems (oral pain, fit of the dental prostheses, prolonged eating time, reduced eating pleasure, and not being able to eat with family and friends) usually appear early and often even before diagnosis (20% -67% are malnourished or at high risk of becoming malnourished at diagnosis). So, malnutrition high risk in HNC patients can happen at presentation and the nutritional status gradually declines during treatment and most patients undergoing treatment will need nutritional therapy [8] [15] [16] [17].
We found the majority of HNC patients had low risk of malnutrition (63.2%), a clear contrast to values often described in the literature referring up to 80% malnourished because of their lifestyle and the risk factors associated with this disease [18]. Such difference may be explained by the fact that assessment occurred when patients were admitted at the Head & Neck Unity, before any treatment [19] [20].
Nutritional assessment supports and institutional awareness, may favour early nutritional intervention on nutritional status [21] [22]. Awareness of this fact is of major importance when establishing a treatment and follow-up schemes in HNC patients.
HNC are a naturally diverse group of tumours linked by anatomical proximity [4]. HNC patients are commonly associated with low patient health literacy as a result of poor education and socioeconomic status [23] [24]. Indeed, the low patient's literacy level found (only 24.6% completed more than 6 schooling years) reinforces this idea and adds new challenges. Once more the patient recruiting process used in our study can be a limitation when looking to this data because of the possible bias in the population selected.
Certainly, with an aging population and advances in diagnosis and treatment, the number of patients living with the effects of HNC and its treatment continue to rise. Thus, literacy and educational support for both patients and caregivers, particularly in areas of survivorship, are important to optimize well-being [25] [26].
BMI should be always considered when analysing HNC patients in order to follow weight loss described during treatments [27]. An association between BMI and survival has been described [28]. The BMI observed, greater than 18.5 for the vast majority of the studied patients (89.5%) seems thus to constitute a positive prognostic factor. On the other hand, as said before, the recruiting process used in our study may not represent with accuracy the true HNC patients in Portugal. But in this case we don't see this as a limitation of our study because the purpose of the study was to see the relationship of the malnutrition risk in HNC patients and its impact on QoL.
In the present study, patients at high risk of malnutrition revealed a constant and significantly poor QoL in multiple domains. Nutritional status is a strong predictor for HNC patients' QoL before, during and after treatment. Weight loss and malnutrition conduces to nutritional interventions: oral, enteral and parenteral and immune-enhanced nutrition. Tube feeding, usually an invasive procedure, is associated with extended hospitalization, QoL negative impacts and risk of mortality. On the other hand, oral nutritious supplements may introduce several problems: decrease salivary flow and quality, reduce oral clearances, increase bacteria colonization, risk of oral diseases or oral dehydration. QoL domains, such as: swallowing, taste and smell, sticky saliva, mouth pain, speech problems, discouragement or feeling ill, are commonly affected by nutritional interventions. Percutaneous endoscopic gastrostomy, used when long-term tube feeding is necessary, is associated with improved QoL. Quality of nutritious supplements make all difference: the ideal oral supplement should be ready-to-eat, most resemble to regular food (solid like), chewable, moisten, and easy to swallow [15]  Emotional and social functioning scales and all symptom scales presented significant differences between high and medium risk of malnutrition patients. Functional impairments and psychological distress are common in HNC (20% -60% of patients have depressive symptomatology two to three months post-diagnosis).
In the present study, fatigue, pain, insomnia and appetite loss were domains particularly associated to high risk of malnutrition group. There is a dynamic and reciprocal association between QoL domains (depressive and anxiety symptoms, pain, nausea, fatigue, appetite) and weight loss. Pain is considered a robust predictor of poorer QoL in HNC [7] [32] [33].
In this study we can state that pain is the most limitation related to malnutrition. Our data shows that patients in the high-risk group for malnutrition have poorer scores on Pain scale and the impact only occurs in this group (low and medium risk group of patients have similar scores in Pain scale). Future development of this finding could relate QoL evaluation, pain control and analgesics consumption, with nutritional status.
Lifestyle mediation (nutritional and psychosocial support, physical activity orientation) at the moment of diagnosis has been recognized as an important intervention, helping patients to manage side effects and improve their QoL [5].
HNC patients should be subject to a plan contemplating early identification of malnutrition high risk and nutrition interventions. Comprehensive nutritional assessment, documentation, weight loss follow-up and QoL evaluation should be include since admission. It would contribute to identify different needs during the disease trajectory in order to ensure appropriate interventions. Effective nutritional interventions should ultimately aim to improve QoL [16]

Conclusions
HNC patients are a recognized high-risk group for malnutrition and the diagnostic criteria used to define patients as malnourished lacks uniformity. Perform pre-treatment nutrition and QoL assessments allows early identification of highrisk patients representing a fundamental step to identify nutrition status at baseline, in order to improve it during and after treatments.
HNC patients with oral cavity and oropharynx tumour locations, older, with low literacy or with BMI under 18.5 at the moment of diagnosis, represent a highrisk group.
When HNC is considered, a dynamic and bi-directional connection between malnutrition and QoL is observed. Emotional and social functional scales and all symptom scales-including pain, presented significant differences between high and medium risk of malnutrition patients. Fatigue, pain, insomnia, appetite loss Int. J. Otolaryngology and Head & Neck Surgery and financial difficulties were domains directly related to high risk of malnutrition patients.
Nutrition support should be considered at any stage of the pathway-especially in high risk group-in order to optimize tumour treatment results, reduction of adverse effects of therapy and improving both QoL and survival.