- Email: [email protected]
Influence of chemotherapy on total energy expenditure in patients with gastrointestinal cancer: A pilot study
Accepted Manuscript Influence of Chemotherapy on Total Energy Expenditure in Patients with Gastrointestinal Cancer: A Pilot Study M.T. Viggiani, O. Lorusso, F. Natalizio, M. Principi, A. Di Leo, M. Barone PII:
S0899-9007(17)30091-6
DOI:
10.1016/j.nut.2017.05.001
Reference:
NUT 9957
To appear in:
Nutrition
Received Date: 24 January 2017 Revised Date:
6 March 2017
Accepted Date: 8 May 2017
Please cite this article as: Viggiani MT, Lorusso O, Natalizio F, Principi M, Di Leo A, Barone M, Influence of Chemotherapy on Total Energy Expenditure in Patients with Gastrointestinal Cancer: A Pilot Study, Nutrition (2017), doi: 10.1016/j.nut.2017.05.001. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT INFLUENCE OF CHEMOTHERAPY ON TOTAL ENERGY EXPENDITURE IN PATIENTS WITH GASTROINTESTINAL CANCER: A PILOT STUDY Viggiani M.T., Lorusso O., Natalizio F., Principi M., Di Leo A., Barone M.
Gastroenterology Unit,
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Corresponding author: Michele Barone, M.D., Ph.D.
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Dept. of Emergency and Organ Transplantation (D.E.T.O.), University of Bari, Gastroenterology Unit, Bari, Italy
Dept. of Emergency and Organ Transplantation (D.E.T.O.)
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University of Bari
Azienda Universitario-Ospedaliera Policlinico di Bari Piazza G. Cesare 11 70124 Bari, Italy
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Email: [email protected] Tel: +39-080-5593514
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Fax: +39-080-5593177
Keywords: nutrition, cancer patients, resting energy expenditure, physical activity, SenseWear
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Armband
Declaration of interest: All authors disclose any financial and personal relationships with other people or organizations that could inappropriately influence (bias) their work
Abbreviations: resting energy expenditure (REE), physical activity (PA), total energy expenditure (TEE), SenseWear Armband (SWA), metabolic equivalent (MET), fat-free mass (FFM), fat mass (FM), body mass index (BMI), Predicted REE (pREE), measured REE (mREE), Parenteral and Enteral guidelines Nutrition (ESPEN).
ACCEPTED MANUSCRIPT ABSTRACT Objective: Resting energy expenditure (REE) and physical activity (PA) undergo variations during chemotherapy. Herein we assessed, for the first time in patients undergoing chemotherapy, REE,
(SWA)] in order to ensure the appropriate calorie intake.
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total energy expenditure (TEE) and PA changes using a metabolic holter [SenseWear Armband
Research Methods & Procedures: Eight patients with gastrointestinal tumours and a Karnofsky performance status >50, underwent evaluation of the body mass index (BMI), while REE, TEE,
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metabolic equivalent (MET) and sleep efficiency were evaluated by SWA. Fat-free mass (FFM) and fat mass (FM) were measured by bioelectrical impedance analysis, muscle strength by handgrip and
treatment
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dietary intake by food diary. All evaluations were performed before chemotherapy (T0), at mid(T1) and at the end of treatment (T2). A calorie-equivalent diet to the TEE was
recommended to all patients.
Results: At T0, a body weight loss of 15.1 ± 7.2% in the previous 6 months was observed in all
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patients. Two patients did not complete treatment. During chemotherapy, thanks to the nutritional counselling all the remaining patients increased their calorie intake (p=0.006) and no significant change was observed in all the other parameters. The REE calculation measured by SWA was
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correlated to the Harris-Benedict formula (p≤0.002)
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Conclusion(s): Our data exclude significant variations of REE and PA in the course of chemotherapy in patients who do not experience weight loss and have a Karnofsky performance status >50. Nutritional counselling based on SWA measurements is useful to support the nutritional status in cancer patients undergoing chemotherapy.
ACCEPTED MANUSCRIPT INTRODUCTION
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Cancer patients develop malnutrition in 40-80% of cases [1]. The highest incidence of malnutrition
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is found in patients with cancer of the stomach, pancreas, oesophagus and head and neck [2,3].
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Malnutrition leads to impairments of the immune system, performance status, muscle function and
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quality of life. Moreover, in the course of cancer-induced malnutrition, the response to
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chemotherapy is decreased and associated with more frequent complications and severe toxicity;
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survival is reduced. Finally, malnutrition is associated with increased health care costs [4].
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Malnutrition associated with cancer may result from local effects of the tumour, the host response to
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the tumour and the cancer treatments. Although cancer patients often reduce their dietary intake
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(due to systemic effects of the disease, local tumour effects, psychological aspects and adverse
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effects of treatment), the metabolism of nutrients and resting energy expenditure (REE) alterations
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may also contribute to the deterioration of their nutritional status [4].
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It has been reported that chemotherapy can modify REE. In course of chemotherapy, REE measured
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by indirect calorimetry presents the highest levels at the beginning and at the end of the
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chemotherapeutic treatment and lower levels at mid-treatment, giving rise to a "U" curve in
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patients with acute leukaemia, lymphoma non-Hodgkin and head-neck cancers [5-7]. The first half
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of the curve corresponds to the REE reduction, probably due to weight loss [7] or reduction of the
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tumour mass [6], whereas the second half of the curve describes the increase in REE probably due
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to the stress caused by the accumulated effects of chemotherapy [6,7].
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This "U" trend does not occur if the REE is calculated by the Harris-Benedict formula, which shows
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a progressive reduction of REE throughout the period of treatment, due to weight loss [7].
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This means that calculation of the REE Harris-Benedict formula is not reliable in cancer patients
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receiving chemotherapy. In other studies of patients with non-small cell lung cancer the REE was
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reported to remain unchanged before and after chemotherapy treatment, without specifying what
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happened during the course of treatment [8,9].
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ACCEPTED MANUSCRIPT In addition to the modification of REE, chemotherapy can also change the level of physical activity.
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Data in the literature suggest that physical activity, assessed using multi-sensor instruments
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evaluating the metabolic equivalent (MET), is reduced during palliative chemotherapy in patients
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with upper gastrointestinal cancer compared to matched healthy controls [10]. However, in the
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same patients, there are no data on physical activity during chemotherapy.
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Finally, patients non responders to chemotherapy seem to be more prone to weight loss compared to
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responders [11].
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The aim of our study was to evaluate in patients with gastrointestinal tumours: 1) modifications of
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REE and physical activity (measured by a multi-sensor instrument), during a full course of
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chemotherapy; 2) body mass index (BMI), muscle strength, body composition and quality of life
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after administration of a calorie-equivalent diet to the patient’s total energy expenditure (TEE),
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measured by the multi-sensor instrument.
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ACCEPTED MANUSCRIPT MATERIALS AND METHODS
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In this study we enrolled 10 gastrointestinal cancer patients, followed as out-patients by the
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nutritional team of the Gastroenterology Unit, Dept. of Emergency and Organ Transplantation,
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Policlinic University Hospital, Bari. They all received nutritional counselling before starting
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chemotherapy, that was performed at the Internal Medicine Unit "G. Baccelli", Dept. of Biomedical
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Sciences and Human Oncology, of the same hospital.
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The exclusion criteria were: extra intestinal cancers, chemotherapy treatment already underway,
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hypo/hyperthyroidism, and treatment with morphine. The study was approved by the local Ethics
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Committee (Protocol n. 1423/CE).
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At enrolment, for each patient we collected the following data: sex, age, weight and height,
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percentage of weight loss in the last six months, type of tumour, previous surgical treatment of the
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tumour, presence or absence of metastases, Karnofsky index, smoking habit, dominant upper limb.
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In addition, BMI, REE, TEE, MET, quality of life, muscle strength, body composition and daily
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dietary intake were evaluated. All assessments were carried out before chemotherapy (T0), at mid-
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treatment cycle (T1) and at the end of treatment (T2). We also provided patients with a calorie-
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equivalent diet to the TEE measured at T0. The diet was adjusted at T1 and T2, on the basis of the
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TEE measurements.
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Evaluation of REE, TEE, MET and quality of life
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REE, TEE, MET and sleep efficiency were evaluated by the SenseWear Armband (SWA) (SWA;
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BodyMedia, Inc, Pittsburgh, PA), a portable multi-sensor monitor already validated for the study of
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basal and total energy expenditure in cancer patients [12]. The SWA was worn for five days by
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patients at home, and we used the data recorded in the 72 hours from the second until the fourth
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day. All data were analysed using the specific software developed by the manufacturer (Sensewear
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8.1; Copyright © 2001-2013 BodyMedia, Inc.), after entering the required demographic
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characteristics (gender, age, height, weight, smoking habit).
ACCEPTED MANUSCRIPT The measured REE (mREE) was obtained by selecting the energy expenditure during the 10
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minutes closest to awakening. This value was multiplied by 6 to obtain the hourly measure and
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then by 24 to obtain the REE/24h. Predicted REE (pREE) was calculated using Harris-Benedict
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formula to compare it with the mREE. Patients were classified according to the standards of
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Boothby et al. [13] on the basis of the mREE/pREE ratio as hypometabolic (<90%),
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normometabolic (90-110%) or hypermetabolic (>110%). The sleep efficiency measures also
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allowed us to measure the quality of sleep, that was seen to be associated with the quality of life
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[14].
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Evaluation of muscle strength
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Numerous studies have shown that the handgrip strength can be used as a nutritional evaluation
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technique also in the cancer patient [15]. The handgrip dynamometer (Jamar®, Sammons Preston,
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Bolingbrook, IL, USA) was used to determine the isometric force of the forearm. The test procedure
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was carried out as previously described in the literature [16]. Patients repeated the evaluation 3
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consecutive times, for each forearm, and the mean value obtained from the three tests was used.
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Evaluation of body composition
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The measurement of body composition was performed using Bioimpedance (BIA 101, Akern srl,
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Pontassieve (FI), Italy) and the interpretation of the data on resistance and reactance was performed
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by a special software (Pro Bodygram 3.0, Akern srl, Pontassieve (FI), Italy) which provided us with
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the fat mass (FM) and fat-free mass (FFM) of patients expressed as Kg of body weight. The
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execution of the test was performed as reported in the literature [17].
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Elaboration of the diet and evaluation of dietary intake
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The diet was planned by an experienced dietitian with the aid of software (Winfood 3, Medimatica
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Srl, Colonnella (TE), Italy). The software was programmed to process a multi-day diet with a
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ACCEPTED MANUSCRIPT calorie-equivalent quantity to the TEE measured by the SWA and a macro and micro nutrient intake
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based on the Reference Nutrient intake levels for the Italian population (RDAs) [18].
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To assess the actual dietary intake, each patient underwent a structured interview, aimed at
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reconstructing the dietary intake during the previous 7 days (dietary history). A quantitative and
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qualitative dietary survey was conducted by the same dietitian with the aid of the software used to
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plan the diet. The software subsequently processed the data and calculated the correct average daily
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calorie intake.
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Statistical analysis
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Analysis of samples distribution was performed by evaluating the symmetry with the Skewness and
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Kurtosis tests. Continuous variables were expressed as means ± standard deviations. In the case of
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data with a skewed distribution, non-parametric tests were used. The t-test was used to compare 2
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independent samples and the Friedman test to compare more than 2 paired samples. The Bonferroni
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post-hoc test was applied in the case of comparisons among multiple groups. Finally, to analyse the
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correlation between two non-parametric variables, we used the Spearman test. Statistical
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significance was set at p < 0.05. Statistical analysis was performed using SPSS version 21.0
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software.
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ACCEPTED MANUSCRIPT RESULTS This study enrolled 10 patients with gastro-intestinal tumours candidates for chemotherapy. Two of
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the 10 patients discontinued treatment after the first assessment at T0 and were therefore excluded
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from the study. A further 2 patients discontinued chemotherapy treatment after the second
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evaluation at T1, while the remaining six patients completed the study.
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Table 1 summarizes the demographic characteristics of the 8 patients who completed the
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assessments at T0 and T1. Of these 8 patients, 3 underwent neoadjuvant chemotherapy, and 5
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adjuvant chemotherapy. Based on the weight loss over the previous 6 months, 4 patients showed
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mild malnutrition (weight decrease = 5-10%), 2 patients moderate malnutrition (weight loss = 11-
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20%) and 2 patients severe malnutrition (decreased weight >20%). All these patients were self-
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sufficient and their performance status was mainly influenced by malnutrition. Based on REE,
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hypermetabolic, normometabolic and hypometabolic patients represented 25%, 75% and 0%
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respectively, of all patients. They underwent chemotherapy for a period of 6.3 ± 2.5 months.
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Table 2 shows the values of BMI, dietary intake, mREE, mREE / FFM, TEE, physical activity
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(expressed as MET), quality of life (expressed as sleep efficiency), body composition (expressed as
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FM and FFM) and muscle strength occurring before (T0) at mid treatment (T1) and at the end (T2) of
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treatment in the 6 patients who completed the study.
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Based on the TEE measured by SWA, patients were given a personalized diet with a calorie intake
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of 36.6 ± 6.5 kcal/kg at T0, 33.1 ± 8.9 at T1 and 37.5 ± 9.2 at T2. Patients significantly increased
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their dietary intake (p = 0.006) thanks to the use of the oral supplements we recommended (6 of 8
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patients). At T0 (before the nutrition counselling) the dietary intake was significantly reduced as
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compared to the TEE (p = 0.001), while at T1 and T2 this difference was no longer statistically
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significant thanks to the increased intake. None of the patients reached the calorie requirements
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suggested as optimal by the SWA measurements.
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At the end of the study, the weight loss observed in the previous six months was arrested and the
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BMI remained stable over time. The mREE remained stable throughout treatment, even when
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ACCEPTED MANUSCRIPT corrected for FFM. Physical activity, measured in METs, was always of mild intensity (defined as
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MET= 1.1-2.9) and remained constant throughout the treatment. During treatment, there was no
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deterioration in quality of life (measured by sleep efficiency), FFM and muscle strength.
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The two patients who discontinued the study after the second evaluation suspended chemotherapy
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due to adverse effects. They failed to increase their dietary intake after enrolment and underwent a
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weight loss of 4.4% and 9%, respectively, at T1 as compared to T0. When we compared the mREE
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and pREE, we obtained a statistically significant positive correlation between the two methods, with
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a Spearman's rho 0.90 at T0, 0.97 at T1 and 1 at T2 (Figure 1).
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ACCEPTED MANUSCRIPT DISCUSSION Patients with gastrointestinal tumours are known to be the cancer patients exposed to the highest
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risk of malnutrition. Malnutrition is partially due to hypermetabolism, present in 22-51% of these
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patients [19,20], associated with inflammation [20]. In addition, surgical treatment and/or chemo-
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radiotherapy increase the risk of malnutrition in these patients, and consequently the probability of
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an effective chemotherapy. In fact, data in literature suggest that malnourished patients have a
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reduced response to chemotherapy because they do not receive adequate treatment: the dosage of
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chemotherapeutic agents is reduced on the basis of the reduction of body surface; the treatment
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undergoes a further reduction to decrease the toxicity; the duration of treatment is about one month
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shorter compared to non malnourished patients [21]. For all these reasons, cancer patients should
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undergo nutritional counselling at the time of diagnosis and be monitored throughout the treatment
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duration.
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One of the difficulties nutritionists experience in the management of these patients is to establish,
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throughout the course of treatment, the patient's nutritional needs, which are influenced both by
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physical activity and REE. Moreover, cancer itself and the antitumour treatment can influence both
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REE and physical activity [22].
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The European Society for Parenteral and Enteral guidelines Nutrition (ESPEN) suggests a calorie
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intake of 30-35 kcal/kg/day in ambulatory patients and 20-25 kcal/kg/day in bedridden patients
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(estimated TEE) [22]. However, this approach underestimates the calorie needs in severely
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underweight patients.
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The novelty of our study lies in the fact that we evaluated the changes of mREE and physical
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activity during the entire course of chemotherapy, and provided the patient with a diet based on a
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direct measurement of the TEE. In fact, the TEE was measured by the SWA, a device already
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validated for the measurement of TEE in various patients settings (neoplastic, heart disease, COPD,
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rheumatoid arthritis, etc.) that is easy to use in ambulatory care.
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ACCEPTED MANUSCRIPT Our study showed, for the first time, a steady trend of mREE in patients with gastro-intestinal
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cancer receiving chemotherapy. This result seems to be in contrast with other findings reported in
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the literature describing a "U" trend of REE. However, these studies analyzed other type of tumours
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in subjects with significant weight loss during chemotherapy [5-7]. In addition, while in the study
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by Garcia-Peris et al. the pREE was not correlated with the value measured by indirect calorimetry,
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in our study the pREE was correlated with the SWA measurements. This was probably due to the
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weight stability and a BMI > 18.5 kg/m2 in the majority of our patients.
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Another peculiar aspect of our research is that, for the first time, instead of comparing the patient's
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physical activity with that of healthy subjects [10], we compared this parameter in the same patient
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at different treatment stages (T0-T2). Our analysis showed that physical activity, although minor,
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was constant throughout treatment.
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Our nutritional counselling resulted in a significant increase in dietary intakes, which prevented
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weight loss and allowed maintenance of the integrity of muscle mass and strength. However, we
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did not observe a weight gain since patients were unable to achieve a calorie intake higher than the
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TEE measured at T1 and T2.
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In conclusion, our study showed that: 1) the REE and physical activity do not vary during the
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course of chemotherapy in gastro-intestinal cancers when the patient has a Karnofsky index> 50
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and does not lose weight during treatment, 2) the Harris-Benedict formula is reliable for the REE
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calculation when neoplastic patients do not suffer malnutrition during treatment, 3) an accurate
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nutritional follow-up and the use of a device to measure TEE in the course of chemotherapy reduce
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the risk of malnutrition, thus facilitating the response to treatment. These conclusions should,
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however, be confirmed by a clinical trial involving a larger number of patients.
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ACCEPTED MANUSCRIPT Acknowledgments: Barone M, Viggiani M.T. contributed to the conception and design of the study; Lorusso O., Natalizio F. to the generation, collection and assembly of data; Barone M., Viggiani M.T., Principi
All authors approved the final version of the manuscript.
Funding:
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M. to the analysis and interpretation of data; Di Leo A. to drafting and revision of the manuscript.
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This research did not receive any specific grant from funding agencies in the public, commercial, or
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not-for-profit sectors.
ACCEPTED MANUSCRIPT REFERENCES
[1] Vandebroek AJ, Schrijvers D. Nutritional issues in anti-cancer treatment. Ann Oncol. 2008;19:v52-5
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[2] Dewys WD, Begg C, Lavin PT, Band PR, Bennett JM, Bertino JR, et al. Prognostic effect of weight loss prior to chemotherapy in cancer patients. Eastern Cooperative Oncology Group. Am J Med. 1980;69:491-7. [3] Laviano A, Meguid MM, Inui A, Muscaritoli M, Rossi-Fanelli F. Therapy insight: Cancer anorexia-cachexia syndrome--when all you can eat is yourself. Nat Clin Pract Oncol. 2005;2:158-65.
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[4] Van Cutsem E, Arends J. The causes and consequences of cancer-associated malnutrition. Eur J Oncol Nurs. 2005;9:S51-63.
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[5] Lerebours E, Tilly H, Rimbert A, Delarue J, Piguet H, Colin R. Change in energy and protein status during chemotherapy in patients with acute leukemia. Cancer. 1988;61:2412-7. [6] Delarue J, Lerebours E, Tilly H, Rimbert A, Hochain P, Guedon C, et al. Effect of chemotherapy on resting energy expenditure in patients with non-Hodgkin's lymphoma. Results of a sequential study. Cancer. 1990;65:2455-9.
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[7] García-Peris P, Lozano MA, Velasco C, de La Cuerda C, Iriondo T, Bretón I, et al. Prospective study of resting energy expenditure changes in head and neck cancer patients treated with chemoradiotherapy measured by indirect calorimetry. Nutrition. 2005;21:1107-12. [8] Harvie MN, Campbell IT, Thatcher N, Baildam A. Changes in body composition in men and women with advanced nonsmall cell lung cancer (NSCLC) undergoing chemotherapy. J Hum Nutr Diet. 2003;16:323-6.
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[9] Harvie MN, Howell A, Thatcher N, Baildam A, Campbell I. Energy balance in patients with advanced NSCLC, metastatic melanoma and metastatic breast cancer receiving chemotherapy-a longitudinal study. Br J Cancer. 2005;92:673-80. [10] Dahele M, Skipworth RJ, Wall L, Voss A, Preston T, Fearon KC. Objective physical activity and self-reported quality of life in patients receiving palliative chemotherapy. J Pain Symptom Manage. 2007;33:676-85. [11] Jebb SA, Osborne RJ, Dixon AK, Bleehen NM, Elia M. Measurements of resting energy expenditure and body composition before and after treatment of small cell lung cancer. Ann Oncol. 1994;5:915-9. [12] Cereda E, Turrini M, Ciapanna D, Marbello L, Pietrobelli A, Corradi E. Assessing Energy expenditure in cancer patients: a pilot validation of a new wearable device. JPEN J Parenter Enteral Nutr 2007;31:502-7. [13] Boothby WM, Berkson, J, Dunn, HL. Studies of the energy expenditure of normal individuals: a standard for basal metabolism with a nomogram for clinical application. American Journal of Physiology 1936;3:468–83.
ACCEPTED MANUSCRIPT [14] Parker KP, Kutner NG, Bliwise DL, Bailey JL, Rye DB. Nocturnal sleep, daytime sleepiness, and quality of life in stable patients on hemodialysis. Health Qual Life Outcomes 2003;1:68 [15] Norman K, Stobäus N, Gonzalez MC, Schulzke JD, Pirlich M. Hand grip strength: outcome predictor and marker of nutritional status. Clin Nutr. 2011;30:135-42.
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[16] Mathiowetz V. Grip and pinch strength measurements. In: Amundsen LR editor. Muscle Strength Testing: Instrumented and Noninstrumented Systems. New York: ChurchillLivingstone; 1990, p. 163–177. [17] Bedogni G, Battistini NC. Impedenza bioelettrica e composizione corporea. 2th ed. Milano (Italy): EDRA Medical Publishing & New Media; 2001 2014,
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[18] Sinu (società italiana di nutrizione umana). Tabelle LARN http://www.sinu.it/html/pag/tabelle_larn_2014_rev.asp; 2016 [accessed 21.11.16].
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[19] Dempsey DT, Knox LS, Mullen JL, Miller C, Feurer ID, Buzby GP. Energy expenditure in malnourished patients with colorectal cancer. Arch Surg. 1986;121:789-95. [20] Jouinot A, Vazeille C, Durand JP, Huillard O, Boudou-Rouquette P, Coriat R, et al. Resting energy expenditure in the risk assessment of anticancer treatments. Clin Nutr. 2017: S0261-5614(17)30012-2.
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[21] Andreyev HJ, Norman AR, Oates J, Cunningham D. Why do patients with weight loss have a worse outcome when undergoing chemotherapy for gastrointestinal malignancies? Eur J Cancer. 1998;34:503-9.
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[22] Arends J, Bodoky G, Bozzetti F, Fearon K, Muscaritoli M, Selga G, et al. ESPEN Guidelines on Enteral Nutrition: Non-surgical oncology. Clin Nutr. 2006;25:245-59.
ACCEPTED MANUSCRIPT Table 1: Demographical and clinical characteristics of patients at T0
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N. of patients
5/3
M/F Age (mean ± SD)
64.0±9.2
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Diagnosis (N. of pts.)
3
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gastric cancer
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colon cancer
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carcinoma of ampulla of Vater
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Previous surgery (N. of pts.)
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Metastatic disease (N. of pts.)
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Months of the disease (mean ± SD)
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1.8±0.7 5 4
Weight loss in the previous 6 months (media ± DS)
12.9±7.4
Karnofsky performance status (media ± DS)
71.3±12.4
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Hypermetabolic/normometabolic/hypometabolic (N. of pts.)
2/6/0
ACCEPTED MANUSCRIPT Table 2: BMI, dietary intake, REE, REE/FFM, TEE, MET, sleep efficiency, FM e FFM and muscle strength at T0, T1 and T2 in the 6 patients that completed the study. T1
T2
p#
BMI
22.9±5.7
22.6±5.5
23.3±5.1
0.87
dietary intake (kcal)
1132.3±449.7 1729.1±556.9 1915.5±330.9 0.006*
mREE (kcal)
1305.6±195.9 1287.8±186.9 1268.0±224.3 0.73
mREE/FFM (kcal/kg)
33.3±1.8
TEE (kcal)
2177.6±502.2 1897.0±369.7 2204.5±719.2 0.22
MET
1.6±0.3
1.4±0.4
sleep efficiency (%)
77.6±7.3
78.1±11.2
FFM (kg)
40.3±5.1
41.3±5.9
42.5±5.6
0.24
FM (kg)
18.0±11.9
17.2±11.0
17.8±10.1
0.85
muscle strength right hand (kg) 81.9±12.9
75.5±12.7
74.8±15.8
0.51
84.4±18.4
79.7±17.4
76.6±21.5
0.54
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30.9±3.2
0.33
61.3±26.2
0.31
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All values are expressed as mean ± SD. # by Friedman test * T0 vs. T1 p=0.01, T0 vs. T2 p= 0.005, T1 vs. T2 p=0.58 by Bonferroni test.
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0.24
1.6±0.3
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muscle strength left hand (kg)
31.7±2.0
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T0
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Figura 1. Correlation between REE measured by SWA and calculated by Harris-Benedict formula a T0, T1 and T2 Statistical analysis was performed by Sperman correlation (ρs=0.90 and p=0.002 at T0, ρs=0.97 and p<0.00 at T1, ρs=1 at T2)
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ACCEPTED MANUSCRIPT
ACCEPTED MANUSCRIPT HIGHLIGHTS
1) It is known that resting energy expenditure (REE) changes during chemotherapy 2) Also physical activity (PA) changes during chemotherapy
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3) These parameter were never measured during chemotherapy by a metabolic holter 4) REE and PA do not change in general well-being patients during chemotherapy
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5) Counseling based metabolic holter is useful to support the nutritional status
S0899-9007(17)30091-6
DOI:
10.1016/j.nut.2017.05.001
Reference:
NUT 9957
To appear in:
Nutrition
Received Date: 24 January 2017 Revised Date:
6 March 2017
Accepted Date: 8 May 2017
Please cite this article as: Viggiani MT, Lorusso O, Natalizio F, Principi M, Di Leo A, Barone M, Influence of Chemotherapy on Total Energy Expenditure in Patients with Gastrointestinal Cancer: A Pilot Study, Nutrition (2017), doi: 10.1016/j.nut.2017.05.001. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT INFLUENCE OF CHEMOTHERAPY ON TOTAL ENERGY EXPENDITURE IN PATIENTS WITH GASTROINTESTINAL CANCER: A PILOT STUDY Viggiani M.T., Lorusso O., Natalizio F., Principi M., Di Leo A., Barone M.
Gastroenterology Unit,
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Corresponding author: Michele Barone, M.D., Ph.D.
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Dept. of Emergency and Organ Transplantation (D.E.T.O.), University of Bari, Gastroenterology Unit, Bari, Italy
Dept. of Emergency and Organ Transplantation (D.E.T.O.)
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University of Bari
Azienda Universitario-Ospedaliera Policlinico di Bari Piazza G. Cesare 11 70124 Bari, Italy
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Email: [email protected] Tel: +39-080-5593514
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Fax: +39-080-5593177
Keywords: nutrition, cancer patients, resting energy expenditure, physical activity, SenseWear
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Armband
Declaration of interest: All authors disclose any financial and personal relationships with other people or organizations that could inappropriately influence (bias) their work
Abbreviations: resting energy expenditure (REE), physical activity (PA), total energy expenditure (TEE), SenseWear Armband (SWA), metabolic equivalent (MET), fat-free mass (FFM), fat mass (FM), body mass index (BMI), Predicted REE (pREE), measured REE (mREE), Parenteral and Enteral guidelines Nutrition (ESPEN).
ACCEPTED MANUSCRIPT ABSTRACT Objective: Resting energy expenditure (REE) and physical activity (PA) undergo variations during chemotherapy. Herein we assessed, for the first time in patients undergoing chemotherapy, REE,
(SWA)] in order to ensure the appropriate calorie intake.
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total energy expenditure (TEE) and PA changes using a metabolic holter [SenseWear Armband
Research Methods & Procedures: Eight patients with gastrointestinal tumours and a Karnofsky performance status >50, underwent evaluation of the body mass index (BMI), while REE, TEE,
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metabolic equivalent (MET) and sleep efficiency were evaluated by SWA. Fat-free mass (FFM) and fat mass (FM) were measured by bioelectrical impedance analysis, muscle strength by handgrip and
treatment
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dietary intake by food diary. All evaluations were performed before chemotherapy (T0), at mid(T1) and at the end of treatment (T2). A calorie-equivalent diet to the TEE was
recommended to all patients.
Results: At T0, a body weight loss of 15.1 ± 7.2% in the previous 6 months was observed in all
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patients. Two patients did not complete treatment. During chemotherapy, thanks to the nutritional counselling all the remaining patients increased their calorie intake (p=0.006) and no significant change was observed in all the other parameters. The REE calculation measured by SWA was
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correlated to the Harris-Benedict formula (p≤0.002)
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Conclusion(s): Our data exclude significant variations of REE and PA in the course of chemotherapy in patients who do not experience weight loss and have a Karnofsky performance status >50. Nutritional counselling based on SWA measurements is useful to support the nutritional status in cancer patients undergoing chemotherapy.
ACCEPTED MANUSCRIPT INTRODUCTION
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Cancer patients develop malnutrition in 40-80% of cases [1]. The highest incidence of malnutrition
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is found in patients with cancer of the stomach, pancreas, oesophagus and head and neck [2,3].
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Malnutrition leads to impairments of the immune system, performance status, muscle function and
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quality of life. Moreover, in the course of cancer-induced malnutrition, the response to
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chemotherapy is decreased and associated with more frequent complications and severe toxicity;
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survival is reduced. Finally, malnutrition is associated with increased health care costs [4].
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Malnutrition associated with cancer may result from local effects of the tumour, the host response to
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the tumour and the cancer treatments. Although cancer patients often reduce their dietary intake
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(due to systemic effects of the disease, local tumour effects, psychological aspects and adverse
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effects of treatment), the metabolism of nutrients and resting energy expenditure (REE) alterations
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may also contribute to the deterioration of their nutritional status [4].
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It has been reported that chemotherapy can modify REE. In course of chemotherapy, REE measured
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by indirect calorimetry presents the highest levels at the beginning and at the end of the
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chemotherapeutic treatment and lower levels at mid-treatment, giving rise to a "U" curve in
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patients with acute leukaemia, lymphoma non-Hodgkin and head-neck cancers [5-7]. The first half
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of the curve corresponds to the REE reduction, probably due to weight loss [7] or reduction of the
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tumour mass [6], whereas the second half of the curve describes the increase in REE probably due
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to the stress caused by the accumulated effects of chemotherapy [6,7].
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This "U" trend does not occur if the REE is calculated by the Harris-Benedict formula, which shows
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a progressive reduction of REE throughout the period of treatment, due to weight loss [7].
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This means that calculation of the REE Harris-Benedict formula is not reliable in cancer patients
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receiving chemotherapy. In other studies of patients with non-small cell lung cancer the REE was
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reported to remain unchanged before and after chemotherapy treatment, without specifying what
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happened during the course of treatment [8,9].
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ACCEPTED MANUSCRIPT In addition to the modification of REE, chemotherapy can also change the level of physical activity.
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Data in the literature suggest that physical activity, assessed using multi-sensor instruments
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evaluating the metabolic equivalent (MET), is reduced during palliative chemotherapy in patients
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with upper gastrointestinal cancer compared to matched healthy controls [10]. However, in the
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same patients, there are no data on physical activity during chemotherapy.
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Finally, patients non responders to chemotherapy seem to be more prone to weight loss compared to
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responders [11].
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The aim of our study was to evaluate in patients with gastrointestinal tumours: 1) modifications of
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REE and physical activity (measured by a multi-sensor instrument), during a full course of
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chemotherapy; 2) body mass index (BMI), muscle strength, body composition and quality of life
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after administration of a calorie-equivalent diet to the patient’s total energy expenditure (TEE),
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measured by the multi-sensor instrument.
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ACCEPTED MANUSCRIPT MATERIALS AND METHODS
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In this study we enrolled 10 gastrointestinal cancer patients, followed as out-patients by the
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nutritional team of the Gastroenterology Unit, Dept. of Emergency and Organ Transplantation,
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Policlinic University Hospital, Bari. They all received nutritional counselling before starting
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chemotherapy, that was performed at the Internal Medicine Unit "G. Baccelli", Dept. of Biomedical
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Sciences and Human Oncology, of the same hospital.
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The exclusion criteria were: extra intestinal cancers, chemotherapy treatment already underway,
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hypo/hyperthyroidism, and treatment with morphine. The study was approved by the local Ethics
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Committee (Protocol n. 1423/CE).
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At enrolment, for each patient we collected the following data: sex, age, weight and height,
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percentage of weight loss in the last six months, type of tumour, previous surgical treatment of the
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tumour, presence or absence of metastases, Karnofsky index, smoking habit, dominant upper limb.
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In addition, BMI, REE, TEE, MET, quality of life, muscle strength, body composition and daily
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dietary intake were evaluated. All assessments were carried out before chemotherapy (T0), at mid-
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treatment cycle (T1) and at the end of treatment (T2). We also provided patients with a calorie-
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equivalent diet to the TEE measured at T0. The diet was adjusted at T1 and T2, on the basis of the
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TEE measurements.
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Evaluation of REE, TEE, MET and quality of life
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REE, TEE, MET and sleep efficiency were evaluated by the SenseWear Armband (SWA) (SWA;
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BodyMedia, Inc, Pittsburgh, PA), a portable multi-sensor monitor already validated for the study of
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basal and total energy expenditure in cancer patients [12]. The SWA was worn for five days by
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patients at home, and we used the data recorded in the 72 hours from the second until the fourth
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day. All data were analysed using the specific software developed by the manufacturer (Sensewear
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8.1; Copyright © 2001-2013 BodyMedia, Inc.), after entering the required demographic
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characteristics (gender, age, height, weight, smoking habit).
ACCEPTED MANUSCRIPT The measured REE (mREE) was obtained by selecting the energy expenditure during the 10
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minutes closest to awakening. This value was multiplied by 6 to obtain the hourly measure and
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then by 24 to obtain the REE/24h. Predicted REE (pREE) was calculated using Harris-Benedict
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formula to compare it with the mREE. Patients were classified according to the standards of
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Boothby et al. [13] on the basis of the mREE/pREE ratio as hypometabolic (<90%),
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normometabolic (90-110%) or hypermetabolic (>110%). The sleep efficiency measures also
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allowed us to measure the quality of sleep, that was seen to be associated with the quality of life
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[14].
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Evaluation of muscle strength
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Numerous studies have shown that the handgrip strength can be used as a nutritional evaluation
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technique also in the cancer patient [15]. The handgrip dynamometer (Jamar®, Sammons Preston,
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Bolingbrook, IL, USA) was used to determine the isometric force of the forearm. The test procedure
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was carried out as previously described in the literature [16]. Patients repeated the evaluation 3
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consecutive times, for each forearm, and the mean value obtained from the three tests was used.
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Evaluation of body composition
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The measurement of body composition was performed using Bioimpedance (BIA 101, Akern srl,
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Pontassieve (FI), Italy) and the interpretation of the data on resistance and reactance was performed
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by a special software (Pro Bodygram 3.0, Akern srl, Pontassieve (FI), Italy) which provided us with
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the fat mass (FM) and fat-free mass (FFM) of patients expressed as Kg of body weight. The
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execution of the test was performed as reported in the literature [17].
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Elaboration of the diet and evaluation of dietary intake
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The diet was planned by an experienced dietitian with the aid of software (Winfood 3, Medimatica
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Srl, Colonnella (TE), Italy). The software was programmed to process a multi-day diet with a
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ACCEPTED MANUSCRIPT calorie-equivalent quantity to the TEE measured by the SWA and a macro and micro nutrient intake
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based on the Reference Nutrient intake levels for the Italian population (RDAs) [18].
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To assess the actual dietary intake, each patient underwent a structured interview, aimed at
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reconstructing the dietary intake during the previous 7 days (dietary history). A quantitative and
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qualitative dietary survey was conducted by the same dietitian with the aid of the software used to
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plan the diet. The software subsequently processed the data and calculated the correct average daily
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calorie intake.
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Statistical analysis
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Analysis of samples distribution was performed by evaluating the symmetry with the Skewness and
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Kurtosis tests. Continuous variables were expressed as means ± standard deviations. In the case of
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data with a skewed distribution, non-parametric tests were used. The t-test was used to compare 2
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independent samples and the Friedman test to compare more than 2 paired samples. The Bonferroni
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post-hoc test was applied in the case of comparisons among multiple groups. Finally, to analyse the
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correlation between two non-parametric variables, we used the Spearman test. Statistical
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significance was set at p < 0.05. Statistical analysis was performed using SPSS version 21.0
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software.
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ACCEPTED MANUSCRIPT RESULTS This study enrolled 10 patients with gastro-intestinal tumours candidates for chemotherapy. Two of
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the 10 patients discontinued treatment after the first assessment at T0 and were therefore excluded
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from the study. A further 2 patients discontinued chemotherapy treatment after the second
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evaluation at T1, while the remaining six patients completed the study.
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Table 1 summarizes the demographic characteristics of the 8 patients who completed the
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assessments at T0 and T1. Of these 8 patients, 3 underwent neoadjuvant chemotherapy, and 5
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adjuvant chemotherapy. Based on the weight loss over the previous 6 months, 4 patients showed
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mild malnutrition (weight decrease = 5-10%), 2 patients moderate malnutrition (weight loss = 11-
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20%) and 2 patients severe malnutrition (decreased weight >20%). All these patients were self-
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sufficient and their performance status was mainly influenced by malnutrition. Based on REE,
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hypermetabolic, normometabolic and hypometabolic patients represented 25%, 75% and 0%
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respectively, of all patients. They underwent chemotherapy for a period of 6.3 ± 2.5 months.
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Table 2 shows the values of BMI, dietary intake, mREE, mREE / FFM, TEE, physical activity
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(expressed as MET), quality of life (expressed as sleep efficiency), body composition (expressed as
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FM and FFM) and muscle strength occurring before (T0) at mid treatment (T1) and at the end (T2) of
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treatment in the 6 patients who completed the study.
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Based on the TEE measured by SWA, patients were given a personalized diet with a calorie intake
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of 36.6 ± 6.5 kcal/kg at T0, 33.1 ± 8.9 at T1 and 37.5 ± 9.2 at T2. Patients significantly increased
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their dietary intake (p = 0.006) thanks to the use of the oral supplements we recommended (6 of 8
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patients). At T0 (before the nutrition counselling) the dietary intake was significantly reduced as
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compared to the TEE (p = 0.001), while at T1 and T2 this difference was no longer statistically
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significant thanks to the increased intake. None of the patients reached the calorie requirements
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suggested as optimal by the SWA measurements.
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At the end of the study, the weight loss observed in the previous six months was arrested and the
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BMI remained stable over time. The mREE remained stable throughout treatment, even when
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ACCEPTED MANUSCRIPT corrected for FFM. Physical activity, measured in METs, was always of mild intensity (defined as
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MET= 1.1-2.9) and remained constant throughout the treatment. During treatment, there was no
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deterioration in quality of life (measured by sleep efficiency), FFM and muscle strength.
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The two patients who discontinued the study after the second evaluation suspended chemotherapy
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due to adverse effects. They failed to increase their dietary intake after enrolment and underwent a
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weight loss of 4.4% and 9%, respectively, at T1 as compared to T0. When we compared the mREE
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and pREE, we obtained a statistically significant positive correlation between the two methods, with
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a Spearman's rho 0.90 at T0, 0.97 at T1 and 1 at T2 (Figure 1).
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ACCEPTED MANUSCRIPT DISCUSSION Patients with gastrointestinal tumours are known to be the cancer patients exposed to the highest
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risk of malnutrition. Malnutrition is partially due to hypermetabolism, present in 22-51% of these
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patients [19,20], associated with inflammation [20]. In addition, surgical treatment and/or chemo-
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radiotherapy increase the risk of malnutrition in these patients, and consequently the probability of
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an effective chemotherapy. In fact, data in literature suggest that malnourished patients have a
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reduced response to chemotherapy because they do not receive adequate treatment: the dosage of
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chemotherapeutic agents is reduced on the basis of the reduction of body surface; the treatment
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undergoes a further reduction to decrease the toxicity; the duration of treatment is about one month
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shorter compared to non malnourished patients [21]. For all these reasons, cancer patients should
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undergo nutritional counselling at the time of diagnosis and be monitored throughout the treatment
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duration.
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One of the difficulties nutritionists experience in the management of these patients is to establish,
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throughout the course of treatment, the patient's nutritional needs, which are influenced both by
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physical activity and REE. Moreover, cancer itself and the antitumour treatment can influence both
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REE and physical activity [22].
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The European Society for Parenteral and Enteral guidelines Nutrition (ESPEN) suggests a calorie
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intake of 30-35 kcal/kg/day in ambulatory patients and 20-25 kcal/kg/day in bedridden patients
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(estimated TEE) [22]. However, this approach underestimates the calorie needs in severely
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underweight patients.
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The novelty of our study lies in the fact that we evaluated the changes of mREE and physical
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activity during the entire course of chemotherapy, and provided the patient with a diet based on a
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direct measurement of the TEE. In fact, the TEE was measured by the SWA, a device already
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validated for the measurement of TEE in various patients settings (neoplastic, heart disease, COPD,
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rheumatoid arthritis, etc.) that is easy to use in ambulatory care.
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ACCEPTED MANUSCRIPT Our study showed, for the first time, a steady trend of mREE in patients with gastro-intestinal
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cancer receiving chemotherapy. This result seems to be in contrast with other findings reported in
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the literature describing a "U" trend of REE. However, these studies analyzed other type of tumours
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in subjects with significant weight loss during chemotherapy [5-7]. In addition, while in the study
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by Garcia-Peris et al. the pREE was not correlated with the value measured by indirect calorimetry,
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in our study the pREE was correlated with the SWA measurements. This was probably due to the
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weight stability and a BMI > 18.5 kg/m2 in the majority of our patients.
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Another peculiar aspect of our research is that, for the first time, instead of comparing the patient's
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physical activity with that of healthy subjects [10], we compared this parameter in the same patient
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at different treatment stages (T0-T2). Our analysis showed that physical activity, although minor,
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was constant throughout treatment.
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Our nutritional counselling resulted in a significant increase in dietary intakes, which prevented
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weight loss and allowed maintenance of the integrity of muscle mass and strength. However, we
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did not observe a weight gain since patients were unable to achieve a calorie intake higher than the
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TEE measured at T1 and T2.
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In conclusion, our study showed that: 1) the REE and physical activity do not vary during the
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course of chemotherapy in gastro-intestinal cancers when the patient has a Karnofsky index> 50
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and does not lose weight during treatment, 2) the Harris-Benedict formula is reliable for the REE
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calculation when neoplastic patients do not suffer malnutrition during treatment, 3) an accurate
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nutritional follow-up and the use of a device to measure TEE in the course of chemotherapy reduce
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the risk of malnutrition, thus facilitating the response to treatment. These conclusions should,
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however, be confirmed by a clinical trial involving a larger number of patients.
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ACCEPTED MANUSCRIPT Acknowledgments: Barone M, Viggiani M.T. contributed to the conception and design of the study; Lorusso O., Natalizio F. to the generation, collection and assembly of data; Barone M., Viggiani M.T., Principi
All authors approved the final version of the manuscript.
Funding:
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M. to the analysis and interpretation of data; Di Leo A. to drafting and revision of the manuscript.
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This research did not receive any specific grant from funding agencies in the public, commercial, or
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not-for-profit sectors.
ACCEPTED MANUSCRIPT REFERENCES
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[2] Dewys WD, Begg C, Lavin PT, Band PR, Bennett JM, Bertino JR, et al. Prognostic effect of weight loss prior to chemotherapy in cancer patients. Eastern Cooperative Oncology Group. Am J Med. 1980;69:491-7. [3] Laviano A, Meguid MM, Inui A, Muscaritoli M, Rossi-Fanelli F. Therapy insight: Cancer anorexia-cachexia syndrome--when all you can eat is yourself. Nat Clin Pract Oncol. 2005;2:158-65.
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[4] Van Cutsem E, Arends J. The causes and consequences of cancer-associated malnutrition. Eur J Oncol Nurs. 2005;9:S51-63.
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[5] Lerebours E, Tilly H, Rimbert A, Delarue J, Piguet H, Colin R. Change in energy and protein status during chemotherapy in patients with acute leukemia. Cancer. 1988;61:2412-7. [6] Delarue J, Lerebours E, Tilly H, Rimbert A, Hochain P, Guedon C, et al. Effect of chemotherapy on resting energy expenditure in patients with non-Hodgkin's lymphoma. Results of a sequential study. Cancer. 1990;65:2455-9.
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[7] García-Peris P, Lozano MA, Velasco C, de La Cuerda C, Iriondo T, Bretón I, et al. Prospective study of resting energy expenditure changes in head and neck cancer patients treated with chemoradiotherapy measured by indirect calorimetry. Nutrition. 2005;21:1107-12. [8] Harvie MN, Campbell IT, Thatcher N, Baildam A. Changes in body composition in men and women with advanced nonsmall cell lung cancer (NSCLC) undergoing chemotherapy. J Hum Nutr Diet. 2003;16:323-6.
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ACCEPTED MANUSCRIPT [14] Parker KP, Kutner NG, Bliwise DL, Bailey JL, Rye DB. Nocturnal sleep, daytime sleepiness, and quality of life in stable patients on hemodialysis. Health Qual Life Outcomes 2003;1:68 [15] Norman K, Stobäus N, Gonzalez MC, Schulzke JD, Pirlich M. Hand grip strength: outcome predictor and marker of nutritional status. Clin Nutr. 2011;30:135-42.
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[16] Mathiowetz V. Grip and pinch strength measurements. In: Amundsen LR editor. Muscle Strength Testing: Instrumented and Noninstrumented Systems. New York: ChurchillLivingstone; 1990, p. 163–177. [17] Bedogni G, Battistini NC. Impedenza bioelettrica e composizione corporea. 2th ed. Milano (Italy): EDRA Medical Publishing & New Media; 2001 2014,
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[18] Sinu (società italiana di nutrizione umana). Tabelle LARN http://www.sinu.it/html/pag/tabelle_larn_2014_rev.asp; 2016 [accessed 21.11.16].
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[19] Dempsey DT, Knox LS, Mullen JL, Miller C, Feurer ID, Buzby GP. Energy expenditure in malnourished patients with colorectal cancer. Arch Surg. 1986;121:789-95. [20] Jouinot A, Vazeille C, Durand JP, Huillard O, Boudou-Rouquette P, Coriat R, et al. Resting energy expenditure in the risk assessment of anticancer treatments. Clin Nutr. 2017: S0261-5614(17)30012-2.
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[21] Andreyev HJ, Norman AR, Oates J, Cunningham D. Why do patients with weight loss have a worse outcome when undergoing chemotherapy for gastrointestinal malignancies? Eur J Cancer. 1998;34:503-9.
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[22] Arends J, Bodoky G, Bozzetti F, Fearon K, Muscaritoli M, Selga G, et al. ESPEN Guidelines on Enteral Nutrition: Non-surgical oncology. Clin Nutr. 2006;25:245-59.
ACCEPTED MANUSCRIPT Table 1: Demographical and clinical characteristics of patients at T0
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N. of patients
5/3
M/F Age (mean ± SD)
64.0±9.2
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Diagnosis (N. of pts.)
3
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gastric cancer
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colon cancer
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carcinoma of ampulla of Vater
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Previous surgery (N. of pts.)
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Metastatic disease (N. of pts.)
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Months of the disease (mean ± SD)
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1.8±0.7 5 4
Weight loss in the previous 6 months (media ± DS)
12.9±7.4
Karnofsky performance status (media ± DS)
71.3±12.4
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Hypermetabolic/normometabolic/hypometabolic (N. of pts.)
2/6/0
ACCEPTED MANUSCRIPT Table 2: BMI, dietary intake, REE, REE/FFM, TEE, MET, sleep efficiency, FM e FFM and muscle strength at T0, T1 and T2 in the 6 patients that completed the study. T1
T2
p#
BMI
22.9±5.7
22.6±5.5
23.3±5.1
0.87
dietary intake (kcal)
1132.3±449.7 1729.1±556.9 1915.5±330.9 0.006*
mREE (kcal)
1305.6±195.9 1287.8±186.9 1268.0±224.3 0.73
mREE/FFM (kcal/kg)
33.3±1.8
TEE (kcal)
2177.6±502.2 1897.0±369.7 2204.5±719.2 0.22
MET
1.6±0.3
1.4±0.4
sleep efficiency (%)
77.6±7.3
78.1±11.2
FFM (kg)
40.3±5.1
41.3±5.9
42.5±5.6
0.24
FM (kg)
18.0±11.9
17.2±11.0
17.8±10.1
0.85
muscle strength right hand (kg) 81.9±12.9
75.5±12.7
74.8±15.8
0.51
84.4±18.4
79.7±17.4
76.6±21.5
0.54
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30.9±3.2
0.33
61.3±26.2
0.31
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All values are expressed as mean ± SD. # by Friedman test * T0 vs. T1 p=0.01, T0 vs. T2 p= 0.005, T1 vs. T2 p=0.58 by Bonferroni test.
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0.24
1.6±0.3
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muscle strength left hand (kg)
31.7±2.0
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T0
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Figura 1. Correlation between REE measured by SWA and calculated by Harris-Benedict formula a T0, T1 and T2 Statistical analysis was performed by Sperman correlation (ρs=0.90 and p=0.002 at T0, ρs=0.97 and p<0.00 at T1, ρs=1 at T2)
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ACCEPTED MANUSCRIPT HIGHLIGHTS
1) It is known that resting energy expenditure (REE) changes during chemotherapy 2) Also physical activity (PA) changes during chemotherapy
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3) These parameter were never measured during chemotherapy by a metabolic holter 4) REE and PA do not change in general well-being patients during chemotherapy
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5) Counseling based metabolic holter is useful to support the nutritional status