Title of the project: To assess the correlation between nutritional status and quality of life in Indian adult palliative cancer patients.

Introduction:

            Cancer may be cured if present early stage. But at times, when these cancers become advanced or metastatic, definitive therapy is not feasible. Then these patients require palliative therapy for symptom management.

            Malnutrition in cancer patients: The prevalence of malnutrition among cancer patients is up to 80% (1, 2). As cancer develops, a patient’s nutritional status is progressively affected. The multiple metabolic changes and nutritional depletion may impact body composition, functional status, psychological status and response to cancer treatment (3). Chemotherapeutic agents not only cause cancer cell death but also affect healthy cells of the body, which further leads to gastrointestinal symptoms (like anorexia, nausea and vomiting), deteriorating patients’ nutritional status (4,5). Recent observational study has concluded that advanced cancer patients with significant weight loss were associated with reduced survival (6,7). Weight losing cancer patients have shown reduced mobility, immunity and chemotherapy endurance (8, 9). In a recent study on weight-losing advanced cancer patients, it was shown that along with weight loss and lower mid upper arm circumference (MUAC) these patients had reduced functional abilities (functional ability was defined as walking on the treadmill) (10).

            Nutritional assessment: Patient Generated Subjective Global Assessment (PG-SGA) has been accepted as the standard nutrition assessment tool for patients with cancer (11). PG-SGA is most effective and sensitive tool for assessing and evaluating cancer patients’ nutritional status and validated on Indian cancer patients (12,13,14). Anthropometric parameters such as body mass index (BMI), skin fold thickness and mid upper arm circumference (MUAC) are useful in identifying malnutrition (14).

            Quality of life in cancer patients:  WHO defines quality of life as “individuals perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards and concerns” (15). Apart from clinical indicators, patient’s psychological and social health along with physical functioning is important and categorized as quality of life (QoL) (16,17). Nutrition has an effect on patients’ social aspects of life (18, 19, 20). Research has documented increased prevalence of depression among malnourished cancer patients (21). Observations on malnourished cancer patients suggests decline in quality of life with body weight loss (10, 22). There was a negative correlation between malnutrition status and functioning scales and positive correlation with symptom scales. Well-nourished patients had significantly better quality of life scores in the global, physical, and role function scales (23). Isering et al. 2003, reported that PGSGA score and EORlTC QLQC30 (European Organisation for Research and Treatment of Cancer quality of life questionnaire) score are correlated. Analysis showed that a deterioration in PG-SGA by a score of nine would result in a deterioration in QoL by 17 points. The scored PG-SGA will not only provide information about nutritional status, but also will give an indication to the QoL of the patient (17).

            Quality of life assessment: EORTC QLQC30 is a validated self-assessment instrument used for assessing quality of life in patients with cancer (19, 24, 25). The questionnaire has been validated on Indian population (26, 27, 28, 29).

Lacunae in existing Knowledge: 

·         The impact of nutritional status on quality of life has not been studied in palliative care setting of cancer patients in Indian Population.

Research Question:

·         Is quality of life affected by nutritional status of cancer patients in palliative care setting in Indian Population?

Aim of the study:

·         The aim of study is to assess the prevalence of malnutrition among palliative cancer patients and its impact on their quality of life.

Objectives:

The objectives of the study are:

1. To determine the level of malnutrition in adult palliative cancer patients.

2. To study the correlation between nutritional status and quality of life in adult palliative cancer patients.

Hypothesis:

·         Malnourished adult palliative cancer patients will experience worse quality of life. 

Anticipated result of the project

The result of the project will help institution to:

·         Design nutritional assessment techniques for malnourished palliative cancer patients.

·         Correct their nutritional status via counseling and therapy.

Review of Literature:

            Cancer is one of the main causes of death among developed countries and the second cause of death in developing countries (30). International Agency for Research on Cancer (GLOBOCAN project, 2012) reported approximately 14.1 million new cancer cases and 8.2 million cancer deaths worldwide. Out of these there were a little over 1 million cancer cases and 683,000 cancer deaths in India (31). The incidence and mortality rate are higher in metropolitan cities of India. The National Cancer Registry revealed that the Delhi male (103.0/10,000) and female (113.9/100,000) population had the highest cancer incidence rate  when adjusted for minimum age among all Indian states (32). Neglect of undernourished cancer patients and inappropriate nutritional care may lead them to a cachectic state (33).  

            Cancer cachexia can be described as “a multifactorial syndrome defined by an ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment. Its pathophysiology is characterised by a negative protein and energy balance driven by a variable combination of reduced food intake and abnormal metabolism” (34).  Few tumor sites are widely associated with cachexia (like pancreatic, gastric, head and neck) but the same tumor site may exhibit cachexia of varying degree or be absent in different patients. Nearly 50% of cancer patients progress to cachexic stage (35).

            Weight loss in cachexia is due to wasting of skeletal muscle as well as adipose tissue. In skeletal muscle, due to protein breakdown amino acids are generated, which thereby contribute to fuel hepatic protein and glucose synthesis (36). Reduced immunity and mobility are results of skeletal muscle wasting (37). As weight loss advances to 30% of pre-treatment body weight, death becomes inevitable (35). Cachexia negatively impacts patients’ capability to endure chemotherapy and fight infection (38). Increased energy expenditure and anorexia are key factors among cachexia patients leading to weight loss (39, 40).

            Cachexia is the most common cause of death in advanced cancer. Nutritional status of patients suffering from cachexia is negatively impacted due to tumor induced alterations in metabolism during cancer (41). Pro-cachectic factors including proteolysis inducing factor (PIF) and lipid mobilizing factor (LMF) are produced by the tumor cells whilst the production of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin - 1β (IL-1) and interleukin – 6 (IL-6)  are  the hosts inflammatory tumor presence response. These cytokines inhibit lipoprotein lipase which in turn restricts fatty acid storage by adipocytes. LMF production promotes lipid breakdown from body fat stores (42). PIF and pro-inflammatory cytokines lead to protein breakdown by activating the ATP ubiquitin-proteasome proteolytic pathway contributing to muscle atrophy (43). The body’s response to cytokine-derived inflammation is called acute phase protein response (APPR). During APPR, protein synthesis in the liver is altered as albumin production is substituted by C-reactive protein, fibrinogen, serum amyloid A, 2-macroglobulin and α-1 antitrypsin production. Released cytokines TNF-α and IL-1 are responsible for loss of appetite and anorexia. They act upon the hypothalamic areas of the brain which control food intake. As fat stores are reduced during cachexia, serum leptin levels decrease which lead to suppression of appetite. IL-1 affects food intake by reducing neuropeptide-Y levels (appetite stimulant) in the hypothalamus (42).

Figure 1: Pathogenesis of Cancer Cachexia (44)

            The scored PG-SGA is a valid nutrition assessment tool specifically designed for the assessment of patients with cancer (12). It is an adaptation of subjective global assessment (SGA) (45), which, as well as incorporating three global ratings of nutritional status (well nourished, moderately or suspected of being malnourished and severely malnourished), includes a numerical score (0–35) and additional nutrition impact symptoms (46). PG-SGA questionnaire evaluates variables such as weight losses, variations in food intake, nutrition symptoms, physical activity status, and clinical examination and the resulting scores are used to classify the patients for treatments plans. The SGA has been used in Indian cancer patients to assess nutritional status and proved to be a good predictor (14).

            Cancer and treatment-induced changes in metabolism can lead to alterations in physiological and psychological functions, which, in turn, can reduce a patient’s quality of life by negatively influencing nutritional status (47). QoL will be measured using the European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ-C30 Version 3) (19). The EORTC QLQC30 questionnaire is a validated self-assessment instrument used for assessing quality of life in patients with cancer and is the most widely used tool (24, 25). Translated version in Hindi is available from the official website. The questionnaire has been validated on Indian population (26, 27, 28, 29). The EORT QoL is composed of 30 items, which entails five functional scales (physical, role, emotional, cognitive, and social), three symptom scales (pain, fatigue, nausea and vomiting), six single item scales (dyspnea, insomnia, appetite loss, financial difficulties, diarrhoea, and constipation) and one global quality of life scale. Each item is scored on a 4-point scale, with a score of 1 for "not at all" to a score of 4 "very much", except for the last 2 questions for the global QoL scale, which is scored on a 7-point scale ranging from 1 "very poor" to 7 "excellent". A score will be calculated for all the15 domains.  For the global and the functional scales, a higher score indicates better global and physical functioning; and for the symptom scale, a higher score would indicate worse symptoms (48).

                Nutrition screening is rarely carried out routinely in Indian hospitals. We hereby suggest nutritional status screening for all patients attending palliative care clinic to address malnourishment effectively and except better treatment response. Correcting malnutrition by counselling and nutritional intervention can further improve their quality of life.  

Study design and methodology:

            This prospective observational study will be carried at Pain and Palliative Care Clinic, Dr BRA Institute Rotary Cancer Hospital, AIIMS, New Delhi, India. Eligible cancer patients attending Palliative Care clinic will be recruited. Informed consent form will be signed prior to participation and ‘patient information’ sheet will be distributed and explained to all participants.

Eligibility criteria:

·         Adult, age 18 years and above.

·         Suffering from cancer and receiving palliative care management.

Exclusion criteria:

·         Incapable to provide written consent.

·         Patients with known psychological disorder or having brain tumor or metastasis.

            After enrolment, anthropometric measurements in form of body weight, height (to measure body mass index, BMI), mid upper arm circumference (MUAC) and skin fold thickness measurement will be taken by the investigator. PG-SGA (Appendix 1) and EORTC QLQ C30 questionnaire (Appendix 2) will be filled up by discussions with the patient and caregiver. The 24 Hour dietary recall and food frequency questionnaire (FFQ) will be asked using standard kitchen utensils to understand their dietary pattern.

After successful completion of the study the research variables will be investigated.

Research variables

Anthropometric measurements: Body weight will be taken using bathroom weighing scale and height using a measuring tape against the wall. BMI will be calculated using weight and height measured. MUAC will be measured using a non-stretchable measuring tape. Four site skin fold thickness measurement (i.e. triceps, biceps, subscapular and suprailiac) will be taken by the help of scientific Harpenden Skinfold Caliper (0120 by Baty International) and noted to the nearest 0.2mm reading, to calculate percentage body density. Body fat percentage will be calculated using body density value in Siri equation (50).

Malnutrition assessment: PG-SGA questionnaire to be completed and patient will be categorized according to the level of malnutrition. Questionnaire will be filled by discussing with the patient and caregiver. FFQ and 24 hour dietary recall is an accurate method because patients are asked to record the frequency of consumption of individual foods and can help provide information on eating patterns (Appendix 3 & 4).

Quality of Life assessment: EORTC QLQ C30 questionnaire will be used to analyse patients’ QoL and asked personally by the investigator.

Sample Size and Statistics:

            Sample size for the study has been computed to compare mean global health status (QoL) between normal versus moderate/severe malnourished patients with following assumptions: mean ± SD of global health status (QoL) in normal and moderate/severe group as 69±2.0 and 58±17 respectively; confidence level 95%, and power 90%, we require to enrol 60 patients in each of the two groups (based on nutritional status assessment in 120 patients).(49).

            Data collected from the questionnaire and patients’ anthropometric measurements will be collated and analyzed statistically using SPSS version 20.0 software to study the significance and validity of collected results.

Ethical Considerations

            Throughout the project, confidentiality and anonymity of the patients will be maintained. Participation in the project will be voluntarily and shall take into consideration the welfare of the subjects.   

             Before enrolment, the study will be carefully explained to all participants describing the purpose of the study, the procedures to be followed, and benefits of participation. No adverse effects are expected following the information collection from the patient or hospital staff. The necessary ethical approvals will be obtained from the AIIMS Ethics Committee before implementation of the project.

Project Funding

            The project will receive no funding from any funding body. As it is an observational study in hospital premises no funding will be needed by the investigators to carry on with it.

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