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This article was downloaded by: [Saba Taj] On: 17 April 2012, At: 08:22 Publisher: Taylor & Francis Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK Biological Rhythm Research Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/nbrr20 Temporal profiles of physical activity and energy expenditure in cancer in- patients Saba Taj a , Vivek Choudhary b & Arti Parganiha a a School of Life Sciences, Pt. Ravishankar Shukla University, Raipur, 492010, India b Regional Cancer Center, Pt. J.N.M. Medical College, Dr. B.R. Ambedkar Hospital, Raipur, 492001, India Available online: 21 Feb 2012 To cite this article: Saba Taj, Vivek Choudhary & Arti Parganiha (2012): Temporal profiles of physical activity and energy expenditure in cancer in-patients, Biological Rhythm Research, DOI:10.1080/09291016.2012.667979 To link to this article: http://dx.doi.org/10.1080/09291016.2012.667979 PLEASE SCROLL DOWN FOR ARTICLE Full terms and conditions of use: http://www.tandfonline.com/page/terms-and- conditions This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. The publisher does not give any warranty express or implied or make any representation that the contents will be complete or accurate or up to date. The accuracy of any instructions, formulae, and drug doses should be independently verified with primary sources. The publisher shall not be liable for any loss, actions, claims, proceedings, demand, or costs or damages whatsoever or howsoever caused arising directly or indirectly in connection with or arising out of the use of this material.
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Page 1: Temporal profiles of physical activity and energy expenditure in cancer in-patients

This article was downloaded by: [Saba Taj]On: 17 April 2012, At: 08:22Publisher: Taylor & FrancisInforma Ltd Registered in England and Wales Registered Number: 1072954 Registeredoffice: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK

Biological Rhythm ResearchPublication details, including instructions for authors andsubscription information:http://www.tandfonline.com/loi/nbrr20

Temporal profiles of physical activityand energy expenditure in cancer in-patientsSaba Taj a , Vivek Choudhary b & Arti Parganiha aa School of Life Sciences, Pt. Ravishankar Shukla University,Raipur, 492010, Indiab Regional Cancer Center, Pt. J.N.M. Medical College, Dr. B.R.Ambedkar Hospital, Raipur, 492001, India

Available online: 21 Feb 2012

To cite this article: Saba Taj, Vivek Choudhary & Arti Parganiha (2012): Temporal profiles ofphysical activity and energy expenditure in cancer in-patients, Biological Rhythm Research,DOI:10.1080/09291016.2012.667979

To link to this article: http://dx.doi.org/10.1080/09291016.2012.667979

PLEASE SCROLL DOWN FOR ARTICLE

Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions

This article may be used for research, teaching, and private study purposes. Anysubstantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,systematic supply, or distribution in any form to anyone is expressly forbidden.

The publisher does not give any warranty express or implied or make any representationthat the contents will be complete or accurate or up to date. The accuracy of anyinstructions, formulae, and drug doses should be independently verified with primarysources. The publisher shall not be liable for any loss, actions, claims, proceedings,demand, or costs or damages whatsoever or howsoever caused arising directly orindirectly in connection with or arising out of the use of this material.

Page 2: Temporal profiles of physical activity and energy expenditure in cancer in-patients

Temporal profiles of physical activity and energy expenditure in cancer

in-patients

Saba Taja, Vivek Choudharyb and Arti Parganihaa*

aSchool of Life Sciences, Pt. Ravishankar Shukla University, Raipur 492010, India; bRegionalCancer Center, Pt. J.N.M. Medical College, Dr. B.R. Ambedkar Hospital, Raipur 492001, India

(Received 25 December 2011; final version received 8 February 2012)

Fifty-three cancer in-patients (37 males and 16 females) were randomly selectedfrom the Regional Cancer Center, Pt. J.N.M. College, Dr. B.R. AmbedkarHospital, Raipur, India. Rhythms in physical activity (PA) and energyexpenditure (EE) were studied non-invasively using Actical (Mini Mitter Co.Inc., USA) and compared with 24 apparently healthy subjects (11 males and 13females). Data were gathered at 1-min epoch length for at least three to fourconsecutive days and were analyzed using several statistical techniques, such asCosinor rhythmometry, ANOVA, Duncan’s multiple-range test, and t-test. Mostof the cancer in-patients and all control subjects exhibited a statisticallysignificant circadian rhythm in PA and EE. However, the rhythm detection ratiowas low among cancer in-patients. Patients had significantly lower 24-h average,lower amplitude, and an earlier acrophase in PA and EE rhythms. Further,significant effect of factor disease was discerned on total activity count (TAC) andtotal energy expenditure (TEE). TAC and TEE were significantly lower in cancerin-patients as compared to control subjects, irrespective of gender. In addition, agradual decrement in PA intensity levels from sedentary to vigorous was validatedin patients. From the present findings, it can be concluded that the factor diseasemight alter the temporal profiles of the PA and EE. However, further intensivestudies involving more patients are required to reinforce the above conclusion.

Keywords: Actical; physical activity; energy expenditure; circadian rhythm; cancerin-patients; PA intensity level

1. Introduction

The cancer patients showed altered temporal organization along the 24 h-time scale.The rhythm characteristics of a number of variables, such as melatonin, cortisol,lymphocytes, and rest-activity undergo alterations in cancer patients (Mormont et al.2002; Pati et al. 2006, 2007). The changes involve: (1) lowering of 24-h average andamplitude; (2) phase advance/delay of the peak; and (3) suppression of one or morecircadian outputs (Touitou et al. 1995; Mormont and Levi 1997; Pati et al. 2006,2007). The disruption of the circadian timing system (CTS) accelerates cancer growthin tumor-bearing rodents (Filipski et al. 2002, 2004) and dampens circadian rest-activity rhythm in patients with metastatic colorectal cancer (Levi 1997, 2001;

*Corresponding author. Email: [email protected]

Biological Rhythm Research

2012, 1–17, iFirst article

ISSN 0929-1016 print/ISSN 1744-4179 online

� 2012 Taylor & Francis

http://dx.doi.org/10.1080/09291016.2012.667979

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Mormont et al. 2000, 2002; Mormont and Levi 2003; Rich et al. 2005; Innominatoet al. 2009; Levi et al. 2010). The chances of survival were found to be poor inmetastatic colorectal cancer patients with altered circadian rhythm in rest-activity(Innominato et al. 2007). In humans, the rest–activity rhythm is considered as aconfirmed biomarker of the central pacemaker (Mormont and Levi 2003). Mormontand Waterhouse (2002) suggested that the rest–activity rhythm could be an indicatorof quality of life (QoL) in cancer patients. In recent times, this biomarker is widelyused as a reference for administration of chronotherapeutics in cancer patients.

Further, it has been documented that the physical activity (PA) is associated withlower risk of cancer (Lee 2003). Reduction in the incidence of specific cancer, i.e.colon, rectum, breast, prostate, and lung was found to be associated with routine PA(Shephard and Futcher 1997; Lee 2003; Warburton et al. 2006). However, theseeffects can vary according to the intensity, mode, and duration of PA. It has beendocumented that the PA enhances the dose–response in physically active cancerpatients as compared to sedentary patients (Lee 2003). Physical activity may reducethe probability of tumor recurrence, reduce fatigue, and increase survival of cancerpatients (Godlee 2000).

Moreover, knowledge of energy expenditure (EE) is paramount for severaldiseases, like cancer, diabetes, and obesity. It may be helpful in understanding of thepathophysiology of wasting associated with disease (Nelson et al. 1994; Elia 1995).Presently, the techniques used to assess total EE are either quite expensive andrequire huge place (doubly labeled water and indirect calorimetry) or inaccurate(prediction equations or questionnaires). Thus, the use of activity monitors, i.e.Actical, is useful to estimate the EE. Such estimation can be useful for the patients toprovide nutritional support. A proper nutrition management can be provided on thebasis of studies and the energy wasted in a disease condition can be compensated(Nelson et al. 1994; Elia 1995).

In India, information on circadian rhythms in PA and EE in cancer patients aremeager. In this study, therefore, we examined the CTS of PA and EE in cancer in-patients who were admitted to receive chemotherapy.

2. Materials and methods

2.1. Subjects

Fifty-three cancer patients (median age: 33 years; range: 18–65 years) consisting of37 males and 16 females were selected randomly from the indoor cancer ward of theRegional Cancer Center, Pt. J.N.M. Medical College, B.R. Ambedkar Hospital,Raipur, Chhattisgarh, India. Fourteen patients were suffering from cancer in theregion of reproductive organs, 11 in the blood, 9 in the head and neck, 6 in the lung,and the remaining 13 in other organs. Biographical measurements and clinicalcharacteristics including date of diagnosis of primary tumor (PT), site and stage ofPT, treatment (chemotherapy), medications (drugs and dose), and performancestatus (PS) were recorded for each patient. The PS was rated according to the criteriaof Eastern Cooperative Oncology Group (ECOG; Oken et al. 1982). Patients in poorgeneral condition, i.e. PS above two were not included in the study. All patientsreceived chemotherapy during the tenure of this study. Chemotherapy consistedof a combination of two or three of the following medications: paclitaxel (200–260 mg/m2), cisplatin (50–180 mg/m2), oxaliplatin (110 mg/m2), leucovorin (200 mg/m2), docetaxel (100–150 mg/m2), carboplatin (450–600 mg/m2), etoposide

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(100–200 mg/m2), 5-fluorouracil (500–900 mg/m2), daunorubicin (40–70 mg/m2),gemcitabine (1600 mg/m2), and doxorubicin (70–90 mg/m2). Twenty-four apparentlyhealthy human subjects (median age: 30 years; age range: 22–52 years) consisting of11 males and 13 females were also studied for comparison. The biographical andclinical characteristics of the cancer in-patients and apparently healthy subjects aresummarized in Table 1. The study obtained approval of the Institutional EthicsCommittee on Human Research of the Pt. J.N.M. Medical College, Raipur, India.Both patients and healthy subjects, who participated voluntarily in the study, gavetheir written informed consent.

2.2. Evaluation of the circadian rhythms in physical activity and energy expenditure

Circadian rhythms in PA and EE were monitored non-invasively using an electronicdevice – the Actical (Mini Mitter Co., Inc., USA). ‘‘Activity count, a device-specificarbitrary unit, represents the frequency and amplitude of acceleration eventsoccurring over a user-defined measurement epoch’’. Actical also converts movement(activity counts) into energy units (calories). This yields the total kilocalories thesubject expended during the time span as a result of their activity above the restingmetabolic rate. The EE values for a given time span are summed and multiplied bythe subject’s weight in kilograms.

Patients wore Actical on the wrist of their non-dominant hand, when they wereadmitted to receive the chemotherapy. Data were gathered at 1-min epoch for atleast three to four consecutive days, which is the recommended duration forevaluating circadian rhythm in rest–activity (Littner et al. 2003; Morgenthaler et al.2007). During the study period, either the patients themselves or their attendantsrecorded the sleep log, such as bed time, sleep start time, and awakening time ondaily basis. Apparently, healthy subjects also wore the Actical for at least four to

Table 1. Biographical and clinical characteristics of cancer inpatients and control subjects.

Attribute Description

Number of cancer inpatients (M/F) 53 (37/16)Age (years), median/range 33/18–65BSA (m2) 1.52+0.02*BMI (kg/m2) 20.73+0.50Primary tumor site Head and neck (n ¼ 9), reproductive organs (n ¼ 14),

blood (n ¼ 11), lung (n ¼ 6), and other organs(n ¼ 13)

ECOG performance status 1-PS (23), and 2-PS (30)Treatment ChemotherapyCycles of chemotherapy received

before Actigraphy1 (22), 2 (12), 3 (7), 4 (4), 5 (3), 6 (4), 46 (1)

Drugs used for chemotherapy Paclitaxel, cisplatin, oxaliplatin, leucovorin, docetaxel,carboplatin, etoposide, 5-fluorouracil, daunorubicin,gemcitabine, doxorubicin

Number of control subjects (M/F) 24 (11/13)Age (years), median/range 30/22–52BSA (m2) 1.61+0.03BMI (kg/m2) 21.43+0.60

Note: *M+SE.

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seven days. The data were transferred from the Actical to a personal computer usingthe Actical reader.

2.3. Statistical analyses

Data on PA and EE were analyzed using specific Actical software (Version 2.12). PAand EE are expressed in activity count per minute (AC min71), and kilocalories perhour per kilogram of subject’s body weight (Kcal kg71 h71), respectively. The dataconsisting of PA and EE were log-transformed to minimize variance and weresubjected to further statistical analyses. Rhythm detection in PA and EE wereanalyzed with the help of Cosinor rhythmometry (Nelson et al. 1979; Gupta and Pati1992) at two fixed windows (t ¼ 24 h and t ¼ 12 h). Rhythm parameters, such as24-h average/Mesor (M, rhythm-adjusted mean), amplitude (A, half of the differencebetween the highest and the lowest value of the best fitting cosine function), andacrophase/peak (Ø, the timings of the highest value with reference to midnight) werecomputed. Harmonic means were computed for M, A, and Ø obtained at bothwindows. Rhythm detection ratio was also calculated for both the variables. Thet-test was employed to compare the averages of M, A, and Ø of EE and PA betweencancer in-patients and healthy subjects. A two-way ANOVA followed by theDuncan’s multiple-range test was employed to estimate the effects of gender (maleversus female) and disease (cancer versus control) on total activity count (TAC) andtotal energy expenditure (TEE). Data on TAC and TEE of each subject were takenon daily basis for the analysis. Further, PA was categorized into four differentintensities, such as sedentary (e.g. sleep and rest), light (e.g. shorting cards andwriting letter), moderate (e.g. vacuuming and dusting), and vigorous (e.g. treadmillwalking and treadmill jogging) based on existing accelerometer thresholds. Thedefault threshold for light–moderate (0.031) and moderate–vigorous (0.083) PA wasused for the comparison between cancer in-patients and healthy subjects. Thestatistical software, SPSS (version 10.0) was used for analysis of the data.

3. Results

3.1. Actogram

Figure 1 shows illustrative examples of actograms that depict patterns of PA and EEin cancer in-patients (Figure 1(a, c)) and control subjects (Figure 1(b, d)). Themagnification of the ordinate was kept similar for plotting actograms for both cancerin-patients and control subjects. The apparently healthy subjects, irrespective ofgender, exhibited higher level of activity during the daytime (Figure 1(b, d)). Inaddition, both female and male controls showed day-to-day consistency andregularity in their day–night pattern of PA and EE (Figure 1(b, d)). However, thecancer in-patients, irrespective of gender, displayed greatly reduced activity. Inaddition, the consistency and regularity in day–night patterns of EE and PA werediminished (Figure 1(a, c)).

3.2. Rhythm detection ratio in physical activity and energy expenditure

Statistically significant circadian rhythms in PA and EE were validated in all controlsubjects and most of the cancer in-patients. However, the rhythm detection ratio was oflow magnitude in cancer in-patients, especially with reference to EE (Table 2). In control

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Figure 1. Illustrative examples of PA and EE profiles (actogram) in cancer in-patients (a andc) and apparently healthy subjects (b and d). Abscissa depicts clock hour. Each row represents24 h span, i.e., for a given day. The height of the black marks in each row indicates the level ofactivity (counts per minute) and the green bar shows EE (Kcal/per hour) for the correspondingtime in the abscissa.

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subjects, the rhythm detection ratio in PA was one, irrespective of computation window,i.e. t ¼ 24 h or t ¼ 12 h.

3.3. Twenty-four-hour average/Mesor

Twenty-four-hour averages of PA and EE, of each subject, obtained at the fixedwindows of 24 h or 12 h were averaged separately and presented in Tables 3 and 4,respectively. Harmonic means of PA and EE were also presented in Tables 3 and 4.Twenty-four-hour average of PA was significantly lower in cancer in-patients ascompared to the control subjects, irrespective of the computation window (Table 3).Comparable difference was also observed for the harmonic mean of PA. Twenty-four-hour average of EE exhibited the similar trend as that of PA (Table 4). Figure2(a) depicts differences in harmonic mean of PA with reference to gender. Harmonicmean of PA was statistically significantly declined in both male and female cancerin-patients than those of their respective controls. Results obtained for EE supportthe findings of PA and depicted lower harmonic mean of EE in cancer in-patients,irrespective of gender (Figure 3(a)).

Table 2. Rhythm detection ratio in physical activity (PA) and energy expenditure (EE) atfixed windows with t ¼ 24 h or t ¼ 12 h in cancer inpatients and control subjects.

Cancer in-patients Control subjects

PA EE PA EE

t ¼ 24 h t ¼ 12 h t ¼ 24 h t ¼ 12 h t ¼ 24 h t ¼ 12 h t ¼ 24 h t ¼ 12 h

Male 0.97 0.97 0.76 0.59 1 1 1 0.73Female 1 1 0.81 0.56 1 1 1 0.85All 0.98 0.98 0.77 0.58 1 1 1 0.79

Table 3. Summary of the characteristics of circadian rhythm in physical activity (PA) ofcancer inpatients and control subjects.

Variable Cancer in-patients Control subjects t value; df; p value

Rhythm parameter at t ¼ 24 h24-h average (M) 00.79+ 0.04* 01.45+ 0.06 08.30; 75; 5 0.001Amplitude (A) 00.30+ 0.02 00.78+ 0.05 10.22; 75; 5 0.001Acrophase (Ø in h) 13.34+ 0.46 14.72+ 0.59 01.73; 75; 0.09

Rhythm parameter at t ¼ 12 h24-h average (M) 00.80+ 0.04 01.45+ 0.07 08.29; 75; 5 0.001Amplitude (A) 00.20+ 0.02 00.45+ 0.04 06.78; 75; 5 0.001Acrophase (Ø in h) 08.01+ 0.32 08.97+ 0.25 01.89; 75; 0.06

Rhythm parameter (Harmonic mean)24-h average (M) 00.79+ 0.04 01.45+ 0.06 08.31; 75; 5 0.001Amplitude (A) 00.24+ 0.02 00.52+ 0.04 08.10; 75; 5 0.001Acrophase (Ø in h) 09.63+ 0.37 10.96+ 0.41 02.17; 75; 0.03

Note: *Values are mean+ 1 SEM. Rhythm parameters were computed at fixed windows with t ¼ 24 h ort ¼ 12 h. The harmonic means of each parameter obtained at t ¼ 24 h and t ¼ 12 h were also calculated.

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3.4. Amplitude

Likewise, decrement in circadian amplitudes of PA and EE was observed in cancerin-patients than control subjects (Tables 3 and 4). The harmonic means computedfor amplitudes of PA and EE rhythms were significantly lower in patients than thoseobtained for the control subjects, irrespective of the gender (Figures 2(b) and 3(b)).

3.5. Acrophase/peak

A significant advancement of acrophase of PA occurred for harmonic mean only incancer in-patients than controls (Table 3). However, the acrophase of EE occurredsignificantly earlier in patients than that of controls, irrespective of computationwindow (Table 4). Further, harmonic mean of the circadian acrophase of PAoccurred significantly earlier in male patients only as compared with their healthycounterparts (Figure 2(c)). On the other hand, harmonic mean of acrophase of EEoccurred significantly earlier in both male and female cancer in-patients than theirrespective group of controls (Figure 3(c)).

3.6. Role of factors – disease and gender on physical activity and energyexpenditure

The results of two-way ANOVA revealed a statistically significant effect of the factordisease on TAC (p 5 0.001) and TEE (p 5 0.001). However, factor gender did notproduce any significant effect on these variables. Further, interaction of both thefactors disease and gender also produced significant effect on TAC (p 5 0.001) andTEE (p 5 0.001) (Table 5).

The results of Duncan’s multiple-range test depict that cancer in-patients hadsignificantly lower TAC and TEE as compared to control subjects (Figures 4 and 5).Interestingly, TAC and TEE were always significantly higher in males than theirrespective group of females (Figures 4 and 5).

Table 4. Summary of the characteristics of circadian rhythm in energy expenditure (EE) ofcancer inpatients and control subjects.

Variable Cancer in-patients Control subjects t value; df; p value

Rhythm parameter at t ¼ 24 h24-h average (M) 00.92+0.04* 01.33+0.04 5.92; 75; 5 0.001Amplitude (A) 00.19+0.01 00.39+0.02 8.63; 75; 5 0.001Acrophase (Ø in h) 12.88+0.43 14.66+0.24 2.69; 75; 0.01

Rhythm parameter at t ¼ 12 h24-h average (M) 00.92+0.04 01.34+0.04 6.03; 75; 5 0.001Amplitude (A) 00.15+0.01 00.24+0.02 4.98; 75; 5 0.001Acrophase (Ø in h) 07.67+0.22 08.54+0.26 2.38; 75; 0.02

Rhythm parameter (Harmonic mean)24-h average (M) 00.92+0.04 01.33+0.04 5.98; 75; 5 0.001Amplitude (A) 00.15+0.01 00.29+0.02 7.59; 75; 5 0.001Acrophase (Ø in h) 09.27+0.23 10.77+0.27 3.85; 75; 5 0.001

Note: *Values are mean+1 SEM. Rhythm parameters were computed at fixed windows with t ¼ 24 h ort ¼ 12 h. The harmonic means of each parameter obtained at t ¼ 24 h and t ¼ 12 h were also calculated.

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3.7. Intensity of physical activity

Figure 6 (a, b, c, d) shows illustrative examples of different PA intensity levels on thebasis of accelerometer thresholds in cancer in-patients (Figure 6(a, c)) and controlsubjects (Figure 6(b, d)). In cancer in-patients, the intensity of PA was below the

Figure 2. Twenty-four-hour average based on harmonic means (a), amplitude based onharmonic means (b), and acrophse based on harmonic means (c) of the circadian PA rhythmof control subjects and cancer in-patients. Statistically significant (*p 5 0.05, ***p 5 0.001)differences were discerned between cancer in-patients and control subjects for all threecircadian rhythm characteristics.

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moderate level, irrespective of gender and time of the day (Figure 6(a, c)). However,in apparently healthy male and female subjects the activity levels were above themoderate intensity during the day time (Figure 6(b, d)). This visual observation was

Figure 3. Twenty-four-hour average based on harmonic means (a), amplitude based onharmonic means (b), and acrophse based on harmonic means (c) of the circadian EE rhythmof control subjects and cancer in-patients. Statistically significant (**p 5 0.01, ***p 5 0.001)differences were discerned between cancer in-patients and control subjects for all threecircadian rhythm characteristics.

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digitized and compared between patients and controls using the Student t-test.Statistically significant differences in all the PA intensity levels were witnessedbetween both the groups (Figure 7(a, b, c, d)). Intensity of activity under sedentarycondition was significantly higher in patients (p 5 0.05), whereas other intensities,such as light (p 5 0.001), moderate (p 5 0.001), and vigorous (p 5 0.001) werelower in patients as compared to their control counterparts (Figure 7(a, b, c, d)).

4. Discussion

This study was designed to investigate the temporal profiles of PA and EE in cancerin-patients. In this study, a marked difference in 24-h PA and EE rhythms has beendocumented between cancer in-patients and control subjects. The normal day–nightpattern and day-to-day consistency in PA and EE were absent in cancer in-patients.On the other hand, control subjects exhibited more activity during day time and veryless or no activity during night time. In addition, they exhibited day-to-dayconsistency in their PA and EE rhythms. These results could be favorably compared

Table 5. Effects of factors, disease (cancer versus control) and gender (male versus female)on total activity count and energy expenditure (TAC d71 and TEE kcal d71).

ANOVA summary

Factor F-value Degree of freedom p value

TACDisease 579.43 1325 50.001Gender 2.75 1325 0.098Disease6gender 49.50 1325 50.001

TEEDisease 399.37 1325 50.001Gender 0.32 1325 0.57Disease6gender 71.03 1325 50.001

Figure 4. Effects of disease (cancer versus control) and gender (male versus female) on totalactivity count (TAC). TAC of each subject obtained on daily basis was pooled separately.Means bearing the same letter are not significantly different from each other at p 5 0.05(based on Duncan’s multiple-range test).

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with the findings of earlier studies in that the researchers documented lessdemarcation between day-time and night-time activity in cancer patients sufferingfrom breast cancer (Roscoe et al. 2002), metastatic colorectal cancer (Mormont et al.2000; Mormont and Waterhouse 2002; Chevalier et al. 2003), lung cancer (Levinet al. 2005), and head and neck cancer (Pati et al. 2006). It has been reported thatrest–activity rhythm altered in early stage, which get disturbed later in moreadvanced stages in patients suffering from prostate cancer (Bartsch et al. 1994).

We observed a statistically significant circadian rhythm in PA and EE in cancerin-patients and control subjects, although rhythm detection ratio was declined inpatients. The findings are in agreement with the earlier reports in which a significantcircadian rhythm in rest activity, melatonin, and cortisol has been demonstrated incancer patients and control subjects (Mormont et al. 2000, 2002; Pati et al. 2006).Raida et al. (2002) also reported maintenance of the serum cortisol rhythm inpatients with advanced gastrointestinal carcinomas. Granda and Levi (2002)explained that circadian rhythm in rest–activity is usually maintained in slowgrowing and early stage tumor. It seems that a statistically significant circadianrhythm may persist even with disturbed sleep-activity pattern.

At the same time, in this study, alterations in the rhythm characteristics of EEand PA have been reported in patients. Lower level of activity, decreased amplitude,and shifting of the acrophase for both the studied variables has been documented incancer in-patients as compared to apparently healthy subjects, irrespective of gender.Pati et al. (2006, 2007) also reported a drastic alteration in the circadian rest–activityrhythm parameters in cancer patients. They emphasized that ‘‘these alterations couldbe attributed to disease, irrespective of variability due to gender and site of primarytumor’’.

The findings of this study also showed significant decline in TAC and TEE incancer in-patients than those of their control counterparts. Likewise, reduction hasbeen observed in cachectic patients with advanced pancreatic cancer (Moses et al.2004) and small-cell lung cancer (Gibney et al. 1997). Moses et al. (2004) explainedthe reduction in PA in terms of adaptive response that may keep a balance betweentotal energy intake and EE. However, an increase in the resting energy expenditure

Figure 5. Effects of disease (cancer versus control) and gender (male versus female) on totalenergy expenditure (TEE). TEE of each subject obtained on daily basis was pooled separately.Means bearing the same letter are not significantly different from each other at p 5 0.05(based on Duncan’s multiple-range test).

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Figure 6. Illustrative examples of actograms representing different PA intensity levels, whichare categorized on the basis of accelerometer thresholds, in cancer in-patients (a and c), andcontrol subjects (b and d). Abscissa depicts clock hour. Each row represents 24 h span, i.e. fora given day. The upper line shows the cutpoint for the moderate to vigorous activity (0.083)and the lower line shows cutpoint for light to moderate activity (0.031). Actograms of cancerin-patients reveal lower activity level than the controls.

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(REE) has been documented in patients with pancreatic cancer (Falconer et al. 1994;Moses et al. 2004) and gastrointestinal tumors (Bosaeus et al. 2002). These authorsemphasized that increased REE is on account of hypermetabolic rates because oftumor burden and host tumor competition. Increased metabolic rate is a significantcomponent behind weight loss in cancer disease. Thus, the decreased level of EEinfluences nutritional status and day-to-day functional abilities of cancer patients.

Figure 7. Comparison of different PA intensity levels (total activity count), namelySedentary (a), Light (b), Moderate (c), and Vigorous (d) between cancer in-patients andcontrol subjects.

Figure 6. (Continued).

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Energy balance represents the difference between energy intake by eating and EEthrough PA. However, in this study, we did not determine the REE, though it is animportant parameter that may be helpful in preventing weight loss of cancer patients.Further, in this study, gender as an independent factor did not produce any significanteffect on TAC and TEE. However, the Duncan’s multiple range tests showed that TACand TEE were significantly higher in males than their female counterparts in bothcontrols and patients. Ferraro et al. (1992) also reported higher 24-h EE in healthymales as compared to healthy females. Results of ANOVA, in this study, can beexplained in terms of masking effect of the factor disease on gender.

A noticeable low level of PA has been witnessed in cancer in-patients. Thepatients were admitted to receive chemotherapy, therefore, they spent more time insedentary condition, although they were ambulatory within and outside the ward inthe premises of the hospital. Under such circumstances a decreased level of activitymay be apparent. A previous study also demonstrated a similar pattern of decreasedactivity in small-cell lung cancer patients (Gibney et al. 1997). Courneya andFriedenreich (1999) and Irwin and Ainsworth (2004) reported that PA has positiveeffect on biological and physiological processes. Nowadays greater attention is beingpaid to the research by considering PA for treatment of cancer. It has beendocumented that PA plays an important role to reduce fatigue, improve physicalfunctioning, and improve QoL in cancer patients during and after cancer treatment(Luctkar-Flude et al. 2007). Slattery (2004) and Meyerhardt et al. (2009) showed thatgreater PA was associated with lower risk of colorectal cancer and overall mortality.About 30–60 min of moderate to vigorous PA per day is needed to protect againstcolon cancer. Physical activity was also found to be associated with better QoL andprolonged survival in female patients with breast cancer (Ogunleye and Holmes2009). On the basis of above findings we should also integrate the PA as a part of thetreatment along with the drug therapy given to cancer patients of this region.

Furthermore, it has been reported that overall level of PA and EE decreasedsignificantly when patients received chemotherapy (Demark-Wahnefried et al. 1997).They suggested that chemotherapy may aggravate the changes in the metabolism ofbody, which eventually affect the energy balance. This could be another possibleexplanation for lowering of the activity level in patients in this study.

With reference to PA intensity levels a gradual reduction from sedentary tovigorous has been witnessed in cancer in-patients. Activity count under sedentarycondition was significantly higher in patients as compared to controls. It seems thatpatients had more restlessness during their sleep period. Similarly, Irwin et al. (2003)found a significant decrease in total, moderate-intensity and vigorous-intensity PAafter the diagnosis of breast cancer. However, there is a paucity of peer studies insupport of the present findings.

To conclude, the findings of this study indicate disruption of the CTS of PA andEE characterized by the lower mean value, lower amplitude, and advancement ofpeak timings. However, further intensive studies involving more patients arerequired to strengthen the above conclusion.

Acknowledgements

Financial assistance from University Grants Commission (UGC), New Delhi, India isgratefully acknowledged. We are very much thankful to Dr. A.K. Pati, Professor and Head,School of Life Sciences, Pt. Ravishankar Shukla University, Raipur, who read the draftversion of this article and offered valuable suggestions, and for providing us with the adequate

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research facilities. We are grateful to the cancer in-patients and control subjects for theirvoluntary participation in this study.

References

Bartsch C, Bartsch H, Fluchter SH, Mecke D, Lppert TH. 1994. Diminished pineal functioncoincides with disturbed circadian endocrine rhythmicity in untreated primary cancerpatients. Consequence of premature aging or of tumor growth? Ann NYAcad. 31:502–525.

Bosaeus I, Daneryd P, Lundholm K. 2002. Dietary intake, resting energy expenditure, weightloss and survival in cancer patients. J Nutr. 132:3465S–3466S.

Chevalier V, Mormont MC, Cure H, Chollet P. 2003. Assessment of circadian rhythms byactimetry in healthy subjects and patients with advanced colorectal cancer. Oncol Rep.10:733–737.

Courneya KS, Friedenreich CM. 1999. Physical exercise and quality of life following cancerdiagnosis: a literature review. Ann Behav Med. 21:171–179.

Demark-Wahnefried W, Hars V, Conaway MR, Havlin K, Rimer BK, McElveen G, WinerEP. 1997. Reduced rates of metabolism and decreased physical activity in breast cancerpatients receiving adjuvant chemotherapy. Am J Clin Nutr. 65:1495–1501.

Elia M. 1995. Changing concepts of nutrient requirements in disease: implications for artificialnutritional support. Lancet. 345:1279–1284.

Falconer JS, Fearon KCH, Plester CE, Ross JA, Carter DC. 1994. Cytokines, the acute-phaseresponse, and resting energy expenditure in cachectic patients with pancreatic cancer. AnnSurg. 219:325–331.

Ferraro R, Lillioja S, Fontvieille MA, Rising R, Bogardus C, Ravussin E. 1992. Lowersedentary metabolic rate in women compared with men. J Clin Invest. 90:780–784.

Filipski E, Delaunay F, King MV, Wu WM, Claustrat B, Cassiau GA, Guettier C, HastingsMH, Levi F. 2004. Effects of chronic jet lag on tumor progression in mice. Cancer Res.64:7879–7885.

Filipski E, King VM, Li X, Granda TG, Mormont MC, Liu X, Claustrat B, Hastings MH,Levi F. 2002. Host circadian clock as a control point in tumor progression. J Natl CancerInst. 94:690–697.

Gibney E, Elia M, Jebb SA, Murgatroyd P, Jennings G. 1997. Total energy expenditure inpatients with small-cell lung cancer: results of a validated study using the bicarbonate-ureamethod. Metabolism. 46:1412–1417.

Godlee F. 2000. Does physical activity prevent cancer? [editorial]. BMJ. 321:1424–1425.Granda T, Levi F. 2002. Tumor-based rhythms of anticancer efficacy in experimental models.

Chronobiol Int. 19:21–41.Gupta S, Pati AK. 1992. Data analysis methodology in chronobiological studies. J Parasitol

Appl Anim Bio. 1:151–163.Innominato PF, Bjarnason GA, Garufi C, Focan C, Moreau T, Gorlia T, Waterhouse J,

Giacchetti S, Levi F. 2007. Altered circadian rhythm in rest and activity (CircAct):independent prognostic value for survival in patients (pts) with metastatic colorectalcancer (MCC). ASCO Ann Meeting Proc Part I. J Clin Oncol. 23:14573.

Innominato PF, Focan C, Gorlia T, Moreau T, Garufi C, Waterhouse J, Giacchetti S,Coudert B, Iacobelli S, Genet D, et al. 2009. Circadian rhythm in rest activity: a biologicalcorrelate of quality of life and a predictor of survival in patients with metastatic colorectalcancer. Cancer Res. 69:4700–4707.

Irwin ML, Ainsworth BE. 2004. Physical activity interventions following cancer diagnosis:methodologic challenges to delivery and assessment. Cancer Invest. 22:30–50.

Irwin ML, Crumley D, McTiernan A. 2003. Physical activity levels before and after adiagnosis of breast carcinoma: the health, eating, activity, and lifestyle (HEAL) Study.Cancer. 97:1746–1757.

Lee I-M. 2003. Physical activity and cancer prevention – data from epidemiologic studies. MedSci Sports Exerc. 35:1823–1827.

Levi F. 1997. Chronopharmacology of anticancer agents. In: Rern PH, Lemmer B, editors.Handbook experimental pharmacology: physiology and pharmacology of biologicalrhythms. Berlin: Springer Verlag. p. 299–331.

Levi F. 2001. Circadian chronotherapy for human cancers. Lancet Oncol. 2:307–314.

Biological Rhythm Research 15

Dow

nloa

ded

by [

Saba

Taj

] at

08:

22 1

7 A

pril

2012

Page 17: Temporal profiles of physical activity and energy expenditure in cancer in-patients

Levi F, Okyar A, Dulong S, Innominato PF, Clairambault J. 2010. Circadian timing in cancertreatments. Annu Rev Pharmacol Toxicol. 50:377–342.

Levin RD, Daehler MA, Grutsch JF, Quiton J, Lis CG, Peterson C, Gupta D, Watson K,Layer D, Huff-Adams S, et al. 2005. Circadian function in patients with advanced non-small-cell lung cancer. Brit J Cancer. 93:1202–1208.

Littner M, Kushida CA, Anderson WM, Bailey D, Berry RB, Davila DG, Hirshkowitz M,Kapen S, Kramer M, Loube D, et al. 2003. Practice parameters for the role of actigraphyin the study of sleep and circadian rhythms: an update for 2002. Sleep. 26:337–341.

Luctkar-Flude MF, Groll DL, Tranmer JE, Woodend K. 2007. Fatigue and physical activityin older adults with cancer: a systematic review of the literature. Cancer Nurs. 30:E35–E45.

Meyerhardt JA, Giovannucci EL, Ogino S, Kirkner GJ, Chan AT, Willett W, Fuchs CS.2009. Physical activity and male colorectal cancer survival. Arch Intern Med. 169:2102–2108.

Morgenthaler TI, Chiong TL, Alessi C, Friedman L, Aurora RN, Boehlecke B, Brown T,Chesson AL, Kapur V, Maganti R, et al. 2007. Practice parameters for the clinicalevaluation and treatment of circadian rhythm sleep disorders. Sleep. 30:1445–1459.

Mormont MC, Langouet AM, Claustrat B, Bogdan A, Marion S, Waterhouse J, Touitou Y,Levi F. 2002. Marker rhythms of circadian system function: a study of patients withmetastatic colorectal cancer and good performance status. Chronobiol Int. 19:141–155.

Mormont MC, Levi F. 1997. Circadian system alterations during cancer processes: a review.Int J Cancer. 70:241–247.

Mormont MC, Levi F. 2003. Cancer chronotherapy: principles, applications, and perspectives.Cancer. 97:155–169.

Mormont MC, Waterhouse J. 2002. Contribution of the rest–activity circadian rhythm toquality of life in cancer patients. Chronobiol Int. 19:313–323.

Mormont MC, Waterhouse J, Bleuzen P, Giacchetti S, Jarni A, Bodgan A, Lellouch J, MissetJL, Touitou Y, Levi F. 2000. Marked 24-h rest/activity rhythms are associated with betterquality of life, better response and longer survival in patients with metastatic colorectalcancer and good performance status. Clin Cancer Res. 6:3038–3045.

Moses AW, Slater C, Preston T, Barber MD, Fearon KC. 2004. Reduced total energyexpenditure and physical activity in cachectic patients with pancreatic cancer can bemodulated by an energy and protein dense oral supplement enriched with n-3 fatty acids.Brit J Cancer. 90:996–1002.

Nelson KA, Walsh D, Sheehan FA. 1994. The cancer anorexia-cachexia syndrome. J ClinOncol. 12:213–225.

Nelson W, Tong YL, Lee JK, Halberg F. 1979. Methods of Cosinor-rhythmometry.Chronobiologia. 6:305–323.

Ogunleye AA, Holmes MD. 2009. Physical activity and breast cancer survival [commentary].Breast Cancer Res. 11:106.

Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP. 1982.Toxicity and response criteria of the eastern cooperative oncology group. Am J ClinOncol. 5:649–655.

Pati AK, Parganiha A, Kar A, Soni R, Roy S, Choudhary V. 2006. Implications of the studyof rest–activity circadian rhythm in head and neck cancer patients. Biol Rhythm Res.37:497–505.

Pati AK, Parganiha A, Kar A, Soni R, Roy S, Choudhary V. 2007. Alterations of thecharacteristics of the circadian rest–activity rhythm of cancer in-patients. Chronobiol Int.6:1179–1197.

Raida M, Kliche KO, Schwabe W, Haulser P, Clement JH, Behnke D, Hoffken K. 2002.Circadian variation of dihydropyrimidine dehydrogenase mRNA expression in leucocytesand serum cortisol levels in patients with advanced gastrointestinal carcinomas comparedto healthy controls. J Cancer Res Clin Oncol. 128:96–102.

Rich T, Innominato PF, Boerner J, Mormont MC, Iacobelli S, Baron B, Jasmin C, Levi F.2005. Elevated serum cytokines correlated with altered behavior, serum cortisol rhythm,and dampened 24 hour rest–activity patterns in patients with metastatic colorectal cancer.Clin Cancer Res. 11:1757–1764.

16 S. Taj et al.

Dow

nloa

ded

by [

Saba

Taj

] at

08:

22 1

7 A

pril

2012

Page 18: Temporal profiles of physical activity and energy expenditure in cancer in-patients

Roscoe JA, Morrow GR, Hickok JT, Bushunow P, Matteson S, Rakita D, Andrews PLR.2002. Temporal interrelationships among fatigue, circadian rhythm and depression inbreast cancer patients undergoing chemotherapy treatment. Support Care Cancer. 10:329–336.

Shephard RJ, Futcher R. 1997. Physical activity and cancer: how may protection bemaximized? Crit Rev Oncog. 8:219–272.

Slattery ML. 2004. Physical activity and colorectal cancer. Sports Med. 34:239–252.Touitou Y, Levi F, Bogdan A, Benavides M, Bailleul F, Misset JL. 1995. Rhythm alteration in

patients with metastatic breast cancer and poor prognostic factors. J Cancer Res ClinOncol. 121:181–188.

Warburton DER, Nicol CW, Bredin SSD. 2006. Health benefits of physical activity: theevidence. CMAJ. 174:801–809.

Biological Rhythm Research 17

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by [

Saba

Taj

] at

08:

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