Body Composition Early Identifies Cancer Patients With Radiotherapy at Risk for Malnutrition

Accepted Manuscript Body Composition Early Identifies Cancer Patients with Radiotherapy at Risk for Malnutrition Pei- Ling Tang, PhD, Hsiu- Hung Wang, PhD, Huey-Shyan Lin, PhD, Wen-Shan Liu, MD, PhD, Lih-Mih Chen, MD, Fan- Hao Chou, PhD PII:

S0885-3924(17)30571-7

DOI:

10.1016/j.jpainsymman.2017.10.005

Reference:

JPS 9608

To appear in:

Journal of Pain and Symptom Management

Received Date: 20 June 2017 Revised Date:

6 October 2017

Accepted Date: 8 October 2017

Please cite this article as: Tang P-L, Wang H-H, Lin H-S, Liu W-S, Chen L-M, Chou F-H, Body Composition Early Identifies Cancer Patients with Radiotherapy at Risk for Malnutrition, Journal of Pain and Symptom Management (2017), doi: 10.1016/j.jpainsymman.2017.10.005. 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.

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ACCEPTED MANUSCRIPT Title Page Title: Body Composition Early Identifies Cancer Patients with Radiotherapy at Risk for Malnutrition Short running head: Body Composition Early Identifies Cancer Patients

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Author Names Pei- Ling Tang1,2,3,†, PhD, Hsiu- Hung Wang3, PhD, Huey-Shyan Lin4, PhD, Wen-Shan Liu5, MD, PhD, Lih-Mih Chen3, MD, Fan- Hao Chou3,*, PhD

Author Affiliations Research Center of Medical Informatics, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan (R.O.C.). (Tang PL) 2 Department of Nursing, Meiho University, Pingtung, Taiwan (R.O.C.). (Tang PL) 3 College of Nursing, Kaohsiung Medical University, Kaohsiung, Taiwan (R.O.C.). (Tang PL, Wang HH, Chen LM, Chou FH) 4 Department of Health-Business Administration, Fooyin University, Taiwan, (R.O.C.). (Lin HS) 5 Radiation Oncology Department, Kaohsiung Veterans General Hospital, Taiwan (R.O.C.). (Liu WS)

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Address correspondence to: Fan-Hao Chou, RN, PhD (E-mail: [email protected]).

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Corresponding author: Fan-Hao Chou, RN, PhD College of Nursing, Kaohsiung Medical University,100, Shih-chuan 1st Road, Kaohsiung 807, Taiwan, (R.O.C.). Tel.: 886-7-3121101 ext 2602 Mail address: [email protected]

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Conflict of interest statement: No Disclosures to Report Ethical review committee statement: This study was approved by the institutional review board of Kaohsiung Veterans General Hospital (IRB VGHKS13-CT11-05).

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ACCEPTED MANUSCRIPT Abstract

Background: The side effects of radiotherapy (RT) and the occurrence of

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comorbidity often result in appetite loss in patients, which leads to serious

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nutritional problems, significantly affecting the patients’ treatment results

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and disease prognosis.

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Objectives: We aimed to investigate changes in the body composition of

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patients with cancer from the time they received RT to 3 months after

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completion of RT.

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Design: A total of 101 cancer patients who received RT, which included

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head or neck cancer, chest or breast cancer, and abdominal or pelvic

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cancer patients. A longitudinal study design was adopted, in which the

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body composition analyzer In Body3.0 was used to obtain patient data at

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six different time points. The data were analyzed through generalized

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estimating equation.

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Results: All patients with cancer had the lowest body mass index at the

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end of RT. For head or neck cancer patients, their total body water and

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muscle mass decreased significantly in the fourth week of RT and at the

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end of RT. For chest or breast cancer patients, their body fat mass changed

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significantly in the second and fourth weeks of RT (β = −0.57, p = .0233;

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β = −3.23, p = .0254). For abdominal or pelvic cancer patients, their total

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body weight and muscle mass decreased significantly in the second week

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of RT and at the end of RT (β = –1.07, p = .0248; β = −5.13, p = .0017; β =

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−1.37, p = .0245; β = −6.50, p = .0016); their body fat mass increased

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significantly in the third month after RT (β = 4.61, p = .0072).

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Conclusions: Body composition analysis can be used to promptly and

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effectively monitor changes in the nutritional status of patients with

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cancer during the cancer treatment period; changes in the body

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composition at different repetitions differ between patients with dissimilar

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cancers.

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Keywords: cancer, radiotherapy, body composition

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Introduction Current cancer treatments primarily involve the use of surgery,

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chemotherapy, and radiotherapy (RT). More than half of all cancer patients

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who are treated for cancer require RT. 1 During the RT stage of cancer

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treatment,

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comorbidity, and the side effects of cancer treatment commonly result in

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the loss of appetite in patients, which leads to serious nutritional problems,

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significantly affecting the patients’ quality of life, treatment results, and

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disease prognosis. 2,

immune

functions,

the

occurrence

of

Weight loss is normally considered an inevitable

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system

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impaired

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consequence of cancer treatment. 4

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decreases patients’ physiological tolerance to cancer treatment, lowering

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their survival rate. 5

However, lean tissue reduction

The composition of the human body is relatively complex: the entire

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body mass (weight) primarily consists of fat mass, muscle mass, body

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water and bone mass. Patients with cancer experience changes in

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metabolism, which inhibit the synthesis of muscle proteins and accelerate

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proteolysis and lipolysis, resulting in the loss of lean tissues and adipose

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tissues. 6 Body composition changes in response to metabolic demand

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changes,

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Therefore, body composition, instead of body weight, can be used as a

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better health assessment indicator and offer more insight into the overall

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effect of diet, nutritional support and treatments among cancer patients

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treatment, and disease on the body during treatment 3 . Some researchers

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had tried to explore the changes of body composition in patients with

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cancer from the onset of appetite loss to the development of cachexia

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physiological

changes,

aging,

and

treatments

for cancer.

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syndrome. However, they focused on detecting patients’ muscle mass

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changes only. 7, 8 Based on the advance of the bioelectricity, we could obtain more

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comprehensive data on the body composition changes in cancer patients.

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Therefore, we tried to investigate the body composition changes among

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patients with all cancer types after receiving RT. Because of the side

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effects of RT generally occur from the time patients receiving RT until 3

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months after completion of the RT, 9,

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patients with cancer were measured at six time points during the same

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period–from the time they received RT to 3 months after completion of RT.

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Study Design

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Methods

the body composition changes of

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There were 140 patients recruited. The participants would be arranged

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an interview to help the participants receive the body composition measure

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at six time points, including before RT start, the second week later since

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the first interview, the fourth week later, the end of RT, the first month

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later after discharge, and the third month later. In addition, the

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demographic characteristics and other information on the participant’s

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physical conditions, especially those related to the cancer and cancer

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treatments including cancer type, cancer stage and prior treatments

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received were also collected in the first interview. Each bioimpedance

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measure done fasting and at the same time of day.

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The inclusion criteria in the study were (1) patients who was

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diagnosed as cancer for the first time and no previous cancer history; (2)

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patients who were indicated to receiving RT; (3) age more than 18 years;

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(4) no cognitive deficit and be able to communicate with researchers.

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Exclusion criteria were (1) the treatment goal of receiving RT is for

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palliative care; (2) patients were provided the nutritional intervention

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during receving RT; (3) patients with relapsed cancer; (4) determined by

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the attending physicians to be unsuitable for participation due to

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unsatisfactory physical conditions.

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Bioelectrical impedance analyses were conducted to obtain the

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physiological measurements required for subsequent body composition

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analysis. Bioelectrical impedance analysis operates on the principle that

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human body fluids are electrically conductive, whereas body fat is not; this

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allows the analysis results to be used to estimate participants’ body

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composition situation. 6, 11, 12 This analyzer measured the participants’ body

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composition data (e.g., body weight, body mass index (BMI), total body

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water (TBW), muscle mass, and body fat mass) and administered a

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segmental, multi-frequency bioelectrical impedance computer analysis.

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Rigorous calibrations and tests were performed to reduce errors. Scholars

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have maintained that bioelectrical impedance analysis features high

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efficiency, reliability, objectivity, and implementability and can be

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considered the optimal body composition analysis in clinical practice. 12

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Statistical Analysis

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The number of participants was calculated using the G power 3.1

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software, repeated measures was employed and the following settings

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were applied: type I error, α = .05; test power, (1-β) power = 0.8;

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two-tailed test; 95% confidence interval; recommended medium effect

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size = .25; six repetitions, and number of group = 1. The calculations

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showed that at least 19 patients were required for each cancer site. Strauss

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et al. has estimated that the patient loss rate while receiving

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13%. 13 This indicated that the minimum number of patients required for

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this study was 66. During the study period, 4 participants interrupted their

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RT courses, 9 participants stated that they were no willing to continue, 3

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participants died,and the data collected from 4 participants were removed

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because of incomplete information. The missing data rate in the study was

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16.52%. In the end, 101 participants completed the study (Figure 1).

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Thereafter, the 101 participants were allocated to 3 groups based on the

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cancer regions: (1) head and neck; (2) chest and breast; (3) abdominal and

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pelvic. Accordingly, data on 101 cancer patients were collected. Both the

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demographically descriptive statistics such as percentage, mean, standard

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error, and the analytical statistics including generalized estimation

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equation were analyzed with SPSS statistical software for Windows,

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Version 20 (IBM, Armonk, NY, USA). Statistically significant is

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considered when p < 0.05.

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RT was

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Results

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Demographic Information and Treatment of Disease

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The study results showed that of the 101 patients with cancer, 57

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(56.43%) and 44 (43.57%) were male and female, respectively; the

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participants were aged between 18 and 82 years (with a mean age and

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standard deviation of 52.83 and ± 11.06 years, respectively); most of them

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(59; 58.42%) were aged more than 50, (64, 63.36%) had lower education

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level, (77, 76.24%) were married, (58, 57.43%) were employed. Of the 101 participants, 32 had head or neck cancer; 45 had chest or

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breast cancer; 24 had abdominal or pelvic cancer. Also, 67 (56.44%)

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received surgery; 57 (56.44%) received chemotherapy; and 58 (57.43%)

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had no other physical co-morbidities (Table 1).

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Body Composition Analysis of Cancer Patients Receiving Radiotherapy

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Body composition analysis included variables such as BMI, TBW,

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muscle mass, and body fat mass. The results showed that all patients with

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cancer had the lowest BMI, TBW, muscle mass and body fat mass at the

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end of RT (Table 2, Figure 2−5).

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Changes in the Patients’ Body Composition Analysis Results at Different

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Repetitions

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Possible confounding variables such as age, sex, cancer stage, prior

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treatments were adjusted using F tests-ANOVA. In addition, the body

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composition analysis data collected at the first time point (before RT) were

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set as the reference to analyze whether significant changes were observed

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in their body compositions at different time points. As Table 3 shown,

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for patients with head or neck cancer, their BMI decreased significantly in

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the first month after RT (β = −0.94, p = .0384), their TBW and muscle

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mass decreased significantly in the fourth week of RT and at the end of RT.

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However, the patients in the head and neck group revealed no significant

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changes on body fat mass. For patients with chest or breast cancer, the BMI

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decreased significantly in the fourth week of RT and at the end of RT (β =

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−1.50, p = .0489; β = −2.10, p = .0077), the TBW and muscle mass did not

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show

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significantly in the second and fourth week of RT (β = -0.56, p = .0280; β =

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-3.22, p = .0259). For patients with abdominal or pelvic cancer, the BMI

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increased significantly in the third month after RT (β = 1.99, p = .0423),

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their TBW and muscle mass decreased significantly in the second week of

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RT and at the end of RT (β = −1.07, p = .0248; β = −5.13, p = .0017; β =

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−1.37, p = .0245; β = −6.50, p = .0016). However, their body fat mass

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increased significantly in the third month after RT (β = 4.61, p = .0072).

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Discussion

changes,

and

the body fat

mass

decreased

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any significant

This study was the first to use the body composition changes as the

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major focus to examine patients with different cancer regions. After

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controlling for factors such as age, sex, cancer stage, and treatments,

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bioelectrical impedance analyses were conducted to analyze patients’ body

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composition indicators including the BMI, TBW, muscle mass, and body

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fat mass. The results showed that the body composition changes differed

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among the patients in different cancer region groups at different measure

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time points during the study. The body composition analysis results

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indicated that the body composition indicators (i.e., TBW, muscle mass,

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body fat mass) changed at different time points, and that the body

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composition changes in cancer patients receiving RT could not be

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effectively monitored by merely measuring their height, weight, and

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BMI. 14, 15

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For patients with head or neck cancer who received RT, the decrease

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of TBW and the muscle mass in the patients with head and neck cancer in

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the fourth week of RT and at the end of RT may reveal the time points

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when nutritional care is to be provided to the patients. For patients with chest or breast cancer, their body fat mass decreased

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in the second and fourth week of RT. Previous studies have shown that

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factors such as age, women’s menstrual state, and chemotherapy drugs

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may explain the reason of body fat mass loss in the cancer group. For

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example, the loss of body fat mass of women with breast cancer changes

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when different chemotherapy drugs are used. 16-18

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Different from other two cancer groups, the BMI showed significant

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increase in the third month after RT among the patients with abdominal or

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pelvic cancer. The TBW and the muscle mass decreased in the second

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week of RT and at the end of RT, however, their body fat mass increased

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significantly in the third month after RT. The result implies that the

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possibility of ignoring cancer patient’s nutrional support if we only

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depended on the BMI changes. Several studies have shown that sarcopenia

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and obesity and overweightness are crucial prognostic factors for patients

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with pancreatic and colorectal cancer. 16,

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studies, Patients with abdominal or pelvic cancer receving RT may have

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higher risk of suffering from both loss of mascle mass and increase body

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fat at the same time.

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Conclusion

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Based on the results of our

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Few empirical studies have investigated the body composition

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changes among patients with cancer during treatment. This study

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indicated that cancer patients may have different nutrition needs at

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different time points and compared with BMI, body composition

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analyses could provide more information while evaluating nutritional

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status of patients with cancer.

7 Ethical Considerations

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This study was approved by the institutional review board of

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Kaohsiung Veterans General Hospital (IRB VGHKS13-CT11-05).

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After an explanation of the researcher, letters of consent were

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obtained from all the patients who agreed to participate in the study.

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Acknowledgments

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The authors’ responsibilities were as follows—PLT, HHW, HSL, WSL, and FHC: designed the research project; PLT, HSL, and FHC: conducted

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the research; PLT, HHW, WSL, and FHC: analyzed the data; PLT and FHC:

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wrote the manuscript and had primary responsibility for the final content of

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the manuscript; and all authors: read and approved the final manuscript.

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None of the authors reported a conflict of interest related to the study.

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J Cancer 2001;93:380-383.

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Isenring EA, Capra S, Bauer JD. Nutrition intervention is beneficial in oncology outpatients receiving radiotherapy to the gastrointestinal or head and

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ACCEPTED MANUSCRIPT TABLE 1 Demographic information (n = 101) Variable

n (%)

12 33

16 8

42(41.58) 59(58.42)

10 22

23 22

9 15

64(63.36) 37(36.64)

22 10

27 18

15 9

24(23.76) 77(76.24)

7 25

10 35

7 17

68(67.33) 33(32.67)

25 7

23 22

20 4

13 19

24 21

6 18

2 30

5 40

1 23

35 (34.65) 18 (17.82) 30 (29.70) 18 (17.82)

9 3 8 12

22 11 7 5

4 4 15 1

16 16

9 36

9 15

44 (43.56) 57 (56.44)

20 12

13 32

11 13

86 (85.15) 15 (14.85)

29 3

33 12

24 0

58 (57.43) 43 (42.57)

21 11

26 19

11 13

Marital status Single Married Main source of income Oneself Family or child Occupation No

43(42.57) 58(57.43)

Yes Residential situation Living alone

3 4 Operation No Yes

34 (33.66) 67 (66.34)

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Chemotherapy No

8 ( 7.92) 93(92.08)

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Living with family

Yes

Other therapy No Yes

Chronic disease No Yes

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University or higher

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50 ≥ Highest level of education High school or low

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29 3

50 <

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Abdominal and pelvic

57(56.43) 44(43.57)

Female Age year

Cancer stage 1

Chest and breast

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Sex Male

Head and neck

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ACCEPTED MANUSCRIPT TABLE 2 Body composition among cancer patients with radiotherapy

Before RT

Time

Mean(SD)

Second Fourth week of RT week of RT Mean(SD)

Mean(SD)

Third First months months after after RT RT Mean(SD) Mean(SD)

Ending of RT Mean(SD)

BMI 24.14(3.72) 24.16(3.96) 23.21(2.29) 22.96(3.46) 23.22(3.88) 23.67(2.45)

Chest and breast

24.85(3.36) 24.69(3.41) 23.40(2.74) 22.70(3.78) 24.45(2.88) 23.93(2.54)

Abdominal and pelvic

23.04(2.66) 23.30(2.96) 23.58(2.29) 22.64(3.28) 23.59(3.13) 25.39(3.37)

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Head and neck

TBW

37.05(6.81) 37.24(5.52) 33.94(4.74) 32.28(6.78) 36.44(5.58) 32.54(7.33)

Chest and breast

33.05(5.89) 32.96(5.80) 32.70(5.65) 31.20(7.07) 32.54(5.76) 32.15(6.40)

Abdominal and pelvic

35.86(5.28) 34.41(5.24) 32.63(4.18) 30.66(4.78) 34.36(4.93) 32.27(5.94)

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Head and neck

Muscle Mass Head and neck

46.88(8.58) 47.12(6.97) 43.03(6.07) 40.86(8.58) 46.05(7.08) 41.21(9.23)

Chest and breast

41.80(7.40) 41.71(7.31) 41.37(7.22) 39.49(8.88) 41.20(7.27) 40.71(8.06)

Abdominal and pelvic

45.40(6.71) 43.54(6.63) 41.32(5.40) 38.82(6.08) 43.45(6.22) 40.93(7.46)

Body Fat Mass

17.16(7.08) 16.80(6.30) 15.43(4.69) 17.64(7.12) 15.64(5.84) 16.84(3.55)

Chest and breast

19.85(6.04) 19.34(6.02) 16.64(5.83) 17.25(7.01) 19.21(5.32) 17.85(4.14)

Abdominal and pelvic

14.54(4.68) 15.45(5.37) 16.90(5.61) 16.52(5.93) 16.29(5.75) 19.83(4.32)

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Head and neck

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SD, standard deviation; RT, radiotherapy; BMI, body mass index; TBW, total body water.

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17 TABLE 3 Generalized estimating equation for change in body composition among cancer patients with radiotherapy (1adjusted)

1

β

β

1.47

16.63 <.0001 33.69

1.79

18.81 <.0001

42.99

-0.05 -1.04 -1.37 -0.94 -0.72 Ref.

0.28 0.9 0.91 0.46 0.9

-0.18 -1.16 -1.5 -2.07 -0.79

0.11 -3.18 -5.14 -0.63 -4.69 Ref.

0.65 1.56 1.76 0.84 2.68

0.17 -2.04 -2.93 -0.74 -1.75

0.13 -3.95 -6.51 -0.86 -5.9 Ref.

22.86

0.88

25.93 <.0001 26.74

1.22

-0.21 -1.50 -2.10 -0.48 -1.00 Ref.

0.16 0.76 0.79 0.43 0.65

-1.31 -1.97 -2.66 -1.11 -1.53

0.24 1.32 1.44 0.54 1.43

-0.94 -0.37 -1.07 -1.09 -0.63

23.43

1.26

18.54 <.0001 35.76

-0.02 0.19 -0.55 0.10 1.99 Ref.

0.23 0.68 1.16 0.41 0.98

-0.10 0.29 -0.47 0.25 2.03

0.9209 0.7756 0.6383 0.8042 0.0423

-0.23 -0.49 -1.54 -0.59 -0.91 Ref.

0.82 1.97 2.21 1.07 3.38

0.16 -2.01 -2.94 -0.81 -1.74

33.95

0.3485 0.7117 0.2849 0.2766 0.5257

2.66

-1.07 -2.97 -5.13 -0.78 -3.09 Ref.

0.48 1.62 1.64 0.83 1.79

β

Body Fat Mass Standard Z score p value Error

16.7

2.7

6.18

<.0001

-0.46 -1.91 0.27 -1.6 -0.79 Ref.

0.91 1.67 1.97 1.09 1.49

-0.5 -1.14 0.13 -1.47 -0.53

0.6181 0.2537 0.8931 0.1411 0.599

1.53

22.21 <.0001 21.74

1.53

14.17

<.0001

-0.27 -0.60 -1.93 -0.70 -1.10 Ref.

0.31 1.67 1.82 0.68 1.80

-0.88 -0.36 -1.06 -1.03 -0.61

-0.56 -3.22 -2.68 -0.86 -2.00 Ref.

0.25 1.44 1.43 0.69 1.12

-2.20 -2.23 -1.87 -1.24 -1.79

0.0280 0.0259 0.0616 0.2149 0.0731

13.45 <.0001

45.24

3.37

13.41 <.0001 16.46

1.64

10.01

<.0001

-2.24 -1.84 -3.13 -0.95 -1.72

-1.37 -3.75 -6.50 -1.03 -3.83 Ref.

0.61 2.07 2.06 1.05 2.27

-2.25 -1.82 -3.15 -0.97 -1.69

0.34 1.31 1.81 0.64 1.71

0.79 1.19 0.86 1.16 2.69

0.4276 0.2325 0.3902 0.2456 0.0072

0.864 0.0409 0.0034 0.4578 0.0804

M AN U

0.1918 0.0489 0.0077 0.2683 0.1272

19.14 <.0001

21.9 <.0001

TE D

0.8604 0.2451 0.1327 0.0384 0.4272

2.25

SC

24.39

Muscle Mass Standard Z score p value Error

RI PT

TBW Standard Z score p value Error

EP

Head and Neck Intercep Time Second week of RT Fourth week of RT Ending of RT First months after RT Third months after RT Before RT Chest and breast Intercep Time Second week of RT Fourth week of RT Ending of RT First months after RT Third months after RT Before RT Abdominal and pelvic Intercep Time Second week of RT Fourth week of RT Ending of RT First months after RT Third months after RT Before RT

β

BMI Standard Z score p value Error

AC C

Variable

0.0248 0.0659 0.0017 0.3421 0.0849

0.8719 0.0449 0.0033 0.4196 0.0812

0.3782 0.7202 0.2875 0.3028 0.5420

0.0245 0.0693 0.0016 0.3298 0.0914

0.27 1.56 1.55 0.74 4.61 Ref.

Adjusted for sex; age; cancer stage; operation and chemotherapy. RT, radiotherapy; BMI, body mass index; TBW, total body water.

18

ACCEPTED MANUSCRIPT Legends for figures Figure 1 Flow Diagram of Protocol Figure 2 Line graphs for changes of body mass index in cancer patients with radiotherapy

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Figure 3 Line graphs for changes of total body water in cancer patients with radiotherapy

Figure 4 Line graphs for changes of muscle mass in cancer patients with radiotherapy

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Figure 5 Line graphs for changes of body fat mass in cancer patients with

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