An 8-week exercise study to improve cancer

treatment related fatigue and QOL among

African American breast cancer patients
undergoing radiation treatment: A pilot
randomized clinical trial ✩
Lucile L. Adams-Campbell , Jennifer Hicks , Kepher Makambi , Pamela Randolph-Jackson , Mary Mills ,
Claudine Isaacs, Chiranjeev Dash

INTRODUCTION
Funding: This study is supported by development funds from National Institute
ancer treatment related fatigue (CTRF) is one of

C
of Health/National Cancer Institute grant P30 CA051008; Bioinformatics Shared
Resource is partially supported by National Institute of Health/National Cancer
Institute grant P30 CA051008; and Georgetown-Howard Universities Center for
the most debilitating side effects of RT.1-3 Nearly
Clinical and Translational Science grant UL1TR000101. all breast cancer patients report fatigue as a conse-
✰ Clinical Trial Registration: NCT02117011 quence of treatment,4 , 5 and RT-related fatigue is reported
ABSTRACT: Background: Cancer treatment related fatigue (CTRF) is one of the in up to 80% of patients.1 , 2 , 6-9 Fatigue can limit a patient’s
most debilitating side effects of adjuvant radiation therapy (RT). Several
studies have found that physical activity (PA) may be an effective intervention
ability to care for herself and can decrease her quality of
to decrease fatigue and enhance QOL in cancer survivors. The primary life.10 , 11 of its occurrence may also impact treatment con-
objective of the PEDLAR study is to test the feasibility of an easily administered
8-week structured moderate-intensity PA intervention, delivered concurrently tinuity.5 , 10
with RT, in reducing CTRF and improving health-related QOL among
African-American breast cancer patients. This study is also designed to
The etiology of RT-CTRF is poorly understood.11-14 Ra-
provide pilot data on the acceptability and adherence of PA interventions in diation exposure initiates a programmed response of nor-
African-American women with breast cancer.
mal tissue towards tissue remodeling, of which inflam-
Methods: It is a prospective, 2-arm, 8-week feasibility trial. Participants are
randomized to either a structured, moderate-intensity aerobic training mation is an important component.15-17 Inflammation has
exercise regimen concurrent with radiotherapy or a control group. been hypothesized as a potential cause of treatment-related
Results: Participants in intervention group reported high satisfaction with
exercise and adherence was >75% for exercise sessions.
fatigue11 as inflammatory markers such as cytokines have
Conclusions: African-American breast cancer patients in a moderate-intensity
been positively associated with increases in fatigue during
75 min/wk aerobic exercise intervention had marginally lower fatigue at 8-wk radiation treatment.12 , 18 , 19
follow-up compared to baseline. The control group participants had
marginally higher fatigue at 8-wk follow-up compared to baseline. Several studies have demonstrated that physical activity
Participants in the intervention group reported slightly better quality of life at
8-wk follow-up compared to baseline (P = 0.06).
may be an effective intervention to enhance quality of life
(QOL) in cancer survivors.20-22 and decrease fatigue, anxi-
Keywords: Fatigue  Breast cancer  Randomized controlled trial 
Exercise  Quality of life ety, and depression.23-27 More than one third of the decline
in functional capacity experienced by cancer patients can
be attributed to prolonged physical inactivity.28 Prolonged
Author affiliations: Lucile L. Adams-Campbell Georgetown Lombardi Comprehensive physical inactivity and sedentary lifestyle can lead to rapid
Cancer Center, Georgetown University Medical Center, Washington, D.C, United States;
Jennifer Hicks Georgetown Lombardi Comprehensive Cancer Center, Georgetown
losses in fitness, energy, and physical functioning.29
University Medical Center, Washington, D.C, United States; Kepher Makambi There is evidence that proinflammatory cytokines
Georgetown Lombardi Comprehensive Cancer Center, Georgetown University Medical
Center, Washington, D.C, United States, Georgetown Lombardi Comprehensive Cancer play a key role in the development of CTRF.30 In pa-
Center, Department of Biostatistics, Bioinformatics, and Mathematics, Washington, DC,
United States; Pamela Randolph-Jackson Department of Radiation Oncology, MedStar
tients undergoing RT, aerobic exercise training has been
Washington Hospital Center, Washington, D.C, United States; Mary Mills Georgetown found to reduce CTRF, although the mechanisms are not
Lombardi Comprehensive Cancer Center, Georgetown University Medical Center,
Washington, D.C, United States; Claudine Isaacs Georgetown Lombardi well understood5 , 6 , 31 However, the evidence of the ben-
Comprehensive Cancer Center, Georgetown University Medical Center, Washington, efits of exercise in African Americans, who are more
D.C, United States; Chiranjeev Dash Georgetown Lombardi Comprehensive Cancer
Center, Georgetown University Medical Center, Washington, D.C, United States likely to be obese, is currently lacking. Thus, the primary
Corresponding author at: Office of Minority Health and Health Disparities Research, aim of the PEDLAR study is to test the feasibility of an 8-
Georgetown Lombardi Comprehensive Cancer Center, 1010 New Jersey Ave SE,
Washington, D.C. 20003, United States.email: lla9@georgetown.edu week structured moderate-intensity physical activity (PA)
© 2023 National Medical Association. Published by Elsevier Inc. All rights reserved. intervention, delivered concurrently with RT, in reducing
https://doi.org/10.1016/j.jnma.2023.01.011 CTRF and improving health-related QOL among African

JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION VOL 115, NO 2, APRIL 2023 199
AN 8-WEEK EXERCISE STUDY TO IMPROVE CANCER TREATMENT RELATED FATIGUE AND QOL
American breast cancer patients. The feasibility and ac-
ceptability of the study was based on participants par-
ticipating in at least 75% of the exercise sessions, i.e.,
30 out of 40 exercise days without any adverse events.
METHODS, INCLUDING STATISTICAL
ANALYSIS
Study design
The methods for this study have been published by Dash et
al.32 This RCT targets women with breast cancer stages 0-
IIIA scheduled to receive RT (no T4, N3, or M1 disease).
After obtaining written informed consent, participants
were randomized either to a structured moderate-intensity
aerobic training exercise regimen concurrent with radio-
therapy or to a control group. Endpoints were assessed at
baseline, 4 weeks into the radiation course, and at the 4-
week follow-up visit. In order to minimize loss to follow
up, visits coincided with radiation appointments. Partici-
pants in the structured exercise group were instructed to
use portable stationary pedal exercisers to achieve an exer-
cise goal of 75 min/week of moderate-intensity exercise.
All exercise sessions were supervised and conducted in
the RT facility while patients were waiting for their RT
or after their RT. Radiation therapy was typically adminis-
tered daily, five-tiems per week, allowing patients to exer-
cise 15 min per weekday. Control group participants were
asked to maintain their normal physical activity levels.
Eligibility criteria
Eligibility for the study included the following parame-
ters: (1) women between the ages of 18 and 75 years; (2)
histologically confirmed non-metastatic carcinoma of the
breast (in situ disease or invasive); (3) radiation therapy
naïve; (4) sedentary activity level at baseline, as defined
by less than 60 min per week of modest physical activ-
ity based on 7-day physical activity recall questionnaire
(5) ambulatory; (6) negative serum pregnancy test and not
planning to become pregnant in the next three months;
and (7) able to provide meaningful consent. The exclu-
sion criteria included the following: (1) prior breast, chest,
or pelvic radiotherapy; (2) concurrent chemotherapy; (3)
distant metastases; (4) physical limitations that contraindi-
cate participation in low to moderate intensity exercise; (5)
positive pregnancy test; and (6) currently engaged in mod-
erate to vigorous physical activity. Prior to randomization,
participants were required to complete a physical activity
readiness questionnaire (PAR-Q) that included questions
regarding physical and medical conditions that would pre-
clude safe participation in an exercise program.
200 VOL 115, NO 2, APRIL 2023
Recruitment and randomization
Women with breast cancer stages 0-IIIA, who were sched-
uled to receive RT were recruited from the Department
of Radiation Oncology at Medstar Washington Hospital
Center (MWHC). The patients were invited to partic-
ipate in the study directly by their radiation oncolo-
gist at MWHC and consented. Participants were ran-
domly assigned, in a 1:1 ratio, to an 8-week struc-
tured moderate-intensity aerobic exercise intervention
or control group using a block (n = 4) randomization
scheme.
Intervention
Exercise intervention arm. Participants randomized
to the exercise intervention were required to exercise be-
fore or after each radiation treatment session, on a five-
treatment per week schedule. The exercise intervention
was administered at the RT facility in a room allocated
for the study. The exercise prescription consisted of aer-
obic training utilizing the portable stationary pedal exer-
ciser (Pedlar) which contains two cycling pedals mounted
to a stationary block that allows patients to exercise while
sitting. Pedal tension was adjusted to provide desired re-
sistance. Exercise intensity was self-rated by participants,
instructed that moderate intensity goal will “make you
breathe somewhat harder than normal”. Participants were
required to perform 15 min/day of aerobic exercise us-
ing the Pedlar device on radiation treatment days; during
a standard radiation course, this yielded 75 min/week of
aerobic time.
Control arm. Control group participants were told to
maintain their current daily activities and exercise habits
for the duration of their treatment.
Study adherence and retention
Adherence was defined as the number of exercise ses-
sions a patient initiated over the 8-week intervention.
Participants had flexibility in scheduling daily exercise,
either before or after radiation treatment. Exercise was
recorded in daily participation logs. Logs document par-
ticipant identification, date, and length of time utilizing the
Pedlar device. To increase retention, participants received
a $20 gift card incentive at baseline and at follow-up visits.
Assessments
Three assessments: at baseline, at 4-weeks into radiation
course and at 4-week follow-up visit, were assessed.
Primary outcomes. Feasibility. Feasibility for the in-
tervention was based at least 75% of the participants en-
gaging in at least 75% of the exercise intervention ses-
sions, i.e., 30 out of 40 total exercise days. In addition,
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION
 AN 8-WEEK EXERCISE STUDY TO IMPROVE CANCER TREATMENT RELATED FATIGUE AND QOL

Table 1. Baseline characteristics in the PEDLAR study.

Intervention (n = 15) Control (n = 15)

Variable Mean (SD) % Mean (SD) %
Age, years 63.3 (3.2) 64.5 (3.2)
Education
≤ 12 years 40 27
> 12 years 60 73
2
Current smokers 27 33
Family history of breast cancer in first 13 20
degree relative
Postmenopausal 93 100
Weight, Kg 92.1 (18.4) 96.8 (19.2)
2
BMI, Kg/m 35.9 (7.1) 35.6 (5.2)
Waist circumference, cm 109.0 (13.4) 114.2 (12.9)
Waist to hip ratio 0.90 (0.07) 0.95 (0.08)
Stage
0 33 46
1 33 33
2 33 23
3 – 20
Type
ER+/PR+ 73 80
Her2+ 7 20
Surgery Type
Lumpectomy 40 40
Partial mastectomy 53 33
Mastectomy 7 27

feasibility included the reporting of no adverse events or
injuries.
CTRF was determined using the Functional Assessment
of Chronic Illness Therapy (FACIT-Fatigue) survey instru-
ment.33 The FACIT is a 13-item subscale developed to
identify a finite set of concerns specific to fatigue. The re-
sponses to the 13 items on the FACIT-Fatigue question-
naire are each measured on a 4-point likert scale, with
score ranging from 0 to 52.34 The FACIT-Fatigue scale has
been validated in patients with cancer and showed excel-
lent internal consistency and reliability.
Cancer-related healthcare quality of life (HRQOL)
among participants in the study will be measured using the
Functional Assessment of Cancer Therapy (FACT) system
questionnaires.35 The HRQOL measured four different
domains (physical well-being, functional well-being,
emotional well-being, and social/family well-being).
FACT-B34 is a breast cancer specific module that was
used to reflect patients’ concerns; moreover, they are reli-
able, reproducible, and have been validated in numerous
studies. Higher scores on the FACT questionnaires reflect
higher QOL.
STATISTICAL ANALYSIS
Baseline characteristics were reported as means and stan-
dard deviations for continuous variables and percentages
for categorical variables. Baseline and follow-up fatigue
and HR-QOL scores were compared separately for the in-
tervention and control arms using the paired t-test. The
mean change scores were computed as the difference be-
tween follow-up and baseline scores. These scores were

JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION VOL 115, NO 2, APRIL 2023 201
AN 8-WEEK EXERCISE STUDY TO IMPROVE CANCER TREATMENT RELATED FATIGUE AND QOL
Fig. 1. Consort Diagram.
compared between the two arms using two-sample t-test.
Analysis of covariance (ANCOVA) models were used to
assess group differences in final scores adjusting for base-
line scores.
RESULTS
A total of 30 African American women with breast can-
cer undergoing RT participated in the PEDLAR feasibility
study, as shown in the consort diagram (Fig. 1). The ac-
ceptable adherence rate for the exercise sessions was 75%.
This means that 30 out of the 40 sessions were com-
pleted by the study participants. The characteristics of
the study population are shown in Table 1. The study popu-
lation was comprised primarily of patients with ER+/PR+
breast cancer. The study population is primarily obese
with mean BMIs of 35.9 kg/m2 and 35.6 kg/m2 for the
intervention and control arms, respectively. Also worth
202 VOL 115, NO 2, APRIL 2023
noting is that the majority of the African American
women had completed high school.
Fatigue and QOL means by intervention group at base-
line and at 8 weeks are shown in Table 2. HRQOL, the
emotional well-being domain, showed numerical improve-
ments from baseline to 8-weeks in the Exercise Interven-
tion arm (p<0.06). Similarly, higher FACT-B score ob-
served in the Exercise Intervention Arm reflected higher
QOL after 8 weeks (p<0.06). Among the controls, fa-
tigue showed evidence of worsening, although not sig-
nificant (−1.9, p = 0.60). The change scores between the
Exercise Intervention and Control arms revealed no sta-
tistically significant differences for fatigue or quality of
life measures (Table 3). Table 4 reveals the fatigue and
QOL comparisons between Intervention and control arms
at baseline and 8 weeks. Emotional well- being was the
only marked improvement during this time frame with the
intervention arm having the most benefit compared to con-
trol, (p = 0.07).
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION
 AN 8-WEEK EXERCISE STUDY TO IMPROVE CANCER TREATMENT RELATED FATIGUE AND QOL

Table 2. Fatigue and QOL scores at baseline and 8-wk follow-up by group.

Outcomes Baseline Final Mean change score CI∗∗ P∗

INTERVENTION (n = 15)
Fatigue, mean (SD)
Composite fatigue score 43.3 (8.6) 44.6 (9.2) +1.3 (5.9) (−2.1, 4.8) 0.43
HR-QOL, mean (SD)
Physical well-being 24.0 (3.7) 24.0 (3.7) 0 (2.3) (−1.3, 1.3) 0.91
Emotional well-being 21.6 (4.3) 23.6 (2.1) +2.0 (3.6) (−0.1, 4.1) 0.06
Functional well-being 4.5 (4.4) 5.6 (4.3) +1.1 (3.7) (−1.1, 3.3) 0.29
Social/family well-being 4.5 (4.3) 2.9 (3.1) −1.6 (3.7) (−3.7, 0.6) 0.14
Composite FACT-B score 79.6 (6.0) 83.0 (5.2) +3.4 (8.4) (−0.2, 7.1) 0.07
CONTROL (n = 15)
Fatigue, mean (SD)
Composite fatigue score 36.6 (10.6) 34.7 (12.8) −1.9 (12.4) (−9.7, 6.0) 0.60
HR-QOL, mean (SD)
Physical well-being 22.1 (5.4) 21.4 (6.4) −0.7 (5.9) (−4.2, 2.9) 0.67
Emotional well-being 20.4 (2.8) 20.5 (5.1) +0.1 (5.1) (−3.1, 3.3) 0.98
Functional well-being 9.4 (5.2) 9.0 (5.2) −0.4 (4.1) (−3.0, 2.2) 0.71
Social/family well-being 5.3 (6.8) 5.1 (7.1) −0.2 (2.8) (−1.8, 1.5) 0.80
Composite FACT-B score 80.2 (11.9) 79.7 (16.3) −0.5 (13.6) (−9.1, 8.2) 0.89
∗P values were obtained from paired t-test.
∗∗ CI are the 95% confidence intervals for the mean change score .

Table 3. Fatigue and QOL change scores between intervention and control .

Intervention change score Control change score

Outcomes (8 wk - baseline) (8 wk - baseline) Mean (CI∗∗ ) P∗
Fatigue, mean (SD)
Composite fatigue score +1.3 (5.9) −1.9 (12.4) 3.2 (5.1, 11.5) 0.42
HR-QOL, mean (SD)
Physical well-being 0 (2.3) −0.7 (5.9) 0.7 (−2.9, 4.1) 0.71
Emotional well-being +2.0 (3.6) +0.1 (5.1) 1.9 (−1.6, 5.4) 0.26
Functional well-being +1.1 (3.7) −0.4 (4.1) 1.5 (−1.7, 4.7) 0.32
Social/family well-being −1.6 (3.7) −0.2 (2.8) −1.4 (−3.9, 1.4) 0.29
Composite FACT-B score +3.4 (8.4) −0.5 (13.6) 3.9 (−4.5, 13.1) 0.37
∗P values were obtained from independent samples t-test.
∗∗ CI
are the 95% confidence intervals for the mean difference in mean change scores between intervention and
control (intervention - control).

JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION VOL 115, NO 2, APRIL 2023 203
AN 8-WEEK EXERCISE STUDY TO IMPROVE CANCER TREATMENT RELATED FATIGUE AND QOL

Table 4. Fatigue and QOL adjusted mean scores at 8 wk final follow-up.

LS+ mean score (SE)

Outcomes Intervention Control 95% CI∗∗ P∗
Fatigue
Composite fatigue score 42.5 (2.5) 37.1 (2.7) 5.4 (−2.4, 13.23) 0.17
HR-QOL
Physical well-being 23.4 (1.2) 22.1 (1.2) 1.3 (−2.1, 4.8) 0.45
Emotional well-being 23.5 (1.0) 20.7 (1.1) 2.8 (−0.2, 5.8) 0.07
Functional well-being 7.1 (1.0) 7.2 (1.1) −0.1 (−3.4, 3.3) 0.95
Social/family well-being 3.2 (0.8) 4.8 (0.9) −1.6 (−4.0, 1.0) 0.22
Composite FACT-B score 83.2 (2.7) 79.5 (2.9) 3.7 (−4.4, 12.0) 0.36
+ LS are least squares mean scores and the standard error (SE) obtained from analysis of covariance (ANCOVA) on the difference in
final (8 wk) scores between the intervention and control adjusting for baseline scores.
∗∗ CI are 95% confidence intervals for the group differences between LS means (intervention - control).
∗P values from ANCOVA.

DISCUSSION preliminary findings. Our study only focused on aerobic

The results of this exercise intervention study among
African American women with breast cancer, who were
primarily obese and HER2+ and ER+ undergoing RT,
demonstrated that the study was feasible based on the par-
ticipation rate of 75% coupled with 75% of the exercise
days being completed. In addition, there were no adverse
events or injuries reported by any of the participants ran-
domized to the exercise intervention arm.
After adjusting for baseline scores, both CTRF and
QOL scores at the 8-week follow- up were higher for inter-
vention versus control group, although not statistically sig-
nificant. The “Emotional well-being” domain of the FACT-
B QOL seemed to show the greatest benefit with exercise
in the intervention group compared to the control.
There were several limitations to the study including
the small sample size that restricts statistical power and
may explain why some of the observed changes did not
achieve statistical significance. Also, we did not objec-
tively assess the intensity of the exercise and/or the resis-
tance load selected by the patients. More in-depth mea-
sures of adherence are clearly warranted, than what was
done in this study. Despite the noted limitations, the re-
sults of this pilot clinical trial favor an exercise interven-
tion among breast cancer patients undergoing radiation
treatments, which have the potential to improve QOL and
CTRF intervention for optimizing recovery during radia-
tion therapy for breast and prostate cancers.
Adequately powered randomized, controlled clinical tri-
als are needed to confirm these finding and expand these
exercise and there is a need to better understand the in-
dividual and combined effects of aerobic and resistance
training on QOL and CTRF in this study population. Al-
though not reported, the participants expressed interest in
extending the period of the intervention if they could exer-
cise at home.
CONCLUSIONS
These data expand previous research in an understudied
population of African American women while showing
feasibility and adherence for exercise intervention during
radiation treatments. Furthermore, this intervention is in-
clusive of obese women, which minimizes the exclusion
criteria that is often a barrier. Increasing minority partici-
pation in clinical trials is very important and this type of
study proved to be acceptable.
AUTHOR CONTRIBUTIONS
Lucile Adams-Campbell, Pamela Randolph-Jackson, Chi-
ranjeev Dash, Claudine Isaacs, Mary Mills, and Jennifer
Hicks contributed to the study conception and design. Ma-
terial preparation and data collection were performed by
Mary Mills and Jennifer Hicks. Data analysis were per-
formed by Kepher Makambi and Chiranjeev Dash. The
first draft of the manuscript was written by Lucile Adams-
Campbell and Chiranjeev Dash; all authors commented on
previous versions of the manuscript. All authors read and
approved the final manuscript.

204 VOL 115, NO 2, APRIL 2023 JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION
 AN 8-WEEK EXERCISE STUDY TO IMPROVE CANCER TREATMENT RELATED FATIGUE AND QOL
ETHICS APPROVAL
The study was approved by Georgetown University Insti-
tution Review Board, with study number 2012–1377.
CONSENT TO PARTICIPATE
Informed consent was obtained from all individual partic-
ipants included in the study.
DECLARATION OF COMPETING
INTEREST
The authors have no relevant financial or non-financial in-
terests to disclose.
REFERENCES
1. Fisher B, Jeong JH, Anderson S, et al. Twenty-five-year follow-
up of a randomized trial comparing radical mastectomy, total
mastectomy, and total mastectomy followed by irradiation. N
Engl J Med. 2002;347:567–575. doi:10.1056/NEJMoa020128.
2. Potthoff K, Schmidt ME, Wiskemann J, et al. Randomized
controlled trial to evaluate the effects of progressive resis-
tance training compared to progressive muscle relaxation in
breast cancer patients undergoing adjuvant radiotherapy:
the BEST study. BMC Cancer. 2013;13:162–2407. doi:10.1186/
1471- 2407- 13- 162.
3. Zelefsky MJ, Fuks Z, Hunt M, et al. High-dose intensity modu-
lated radiation therapy for prostate cancer: early toxicity and
biochemical outcome in 772 patients. Int J Radiat Oncol Biol
Phys. 2002;53:1111–1116. S0360301602028572 [pii].
4. Fisher B, Dignam J, Wolmark N, et al. Lumpectomy and ra-
diation therapy for the treatment of intraductal breast can-
cer: findings from national surgical adjuvant breast and bowel
project B-17. J Clin Oncol. 1998;16:441–452. doi:10.1200/JCO.
1998.16.2.441.
5. Bagshaw MA, Kaplan ID, Cox RC. Prostate cancer. Radiation
therapy for localized disease. Cancer. 1993;71:939–952. doi:10.
1002/1097- 0142(19930201)71:3+3.0.co;2- 0.
6. Alcantara-Silva TR, Freitas-Junior R, Freitas NM, et al. Fatigue re-
lated to radiotherapy for breast and/or gynaecological can-
cer: a systematic review. J Clin Nurs. 2013;22:2679–2686. doi:10.
1111/jocn.12236.
7. Steindorf K, Schmidt ME, Klassen O, et al. Randomized, con-
trolled trial of resistance training in breast cancer patients
receiving adjuvant radiotherapy: results on cancer-related
fatigue and quality of life. Ann Oncol. 2014;25:2237–2243.
S0923-7534(19)36769-9 [pii].
8. Dhruva A, Dodd M, Paul SM, et al. Trajectories of fatigue in
patients with breast cancer before, during, and after radia-
tion therapy. Cancer Nurs. 2010;33:201–212. doi:10.1097/NCC.
0b013e3181c75f2a.
9. Jereczek-Fossa BA, Marsiglia HR, Orecchia R. Radiothera-
py-related fatigue. Crit Rev Oncol Hematol. 2002;41:317–325.
S1040842801001433 [pii].
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION
10. Morrow GR, Shelke AR, Roscoe JA, et al. Management
of cancer-related fatigue. Cancer Invest. 2005;23:229–239.
doi:10.1081/cnv-200055960.
11. Mustian KM, Peppone L, Darling TV, et al. A 4-week home-
-based aerobic and resistance exercise program during radia-
tion therapy: a pilot randomized clinical trial. J Support Oncol.
2009;7:158–167.
12. Noal S, Levy C, Hardouin A, et al. One-year longitudinal study
of fatigue, cognitive functions, and quality of life after adju-
vant radiotherapy for breast cancer. Int J Radiat Oncol Biol
Phys. 2011;81:795–803. doi:10.1016/j.ijrobp.2010.06.037.
13. Hickok JT, Roscoe JA, Morrow GR, et al. Frequency, severity,
clinical course, and correlates of fatigue in 372 patients during
5 weeks of radiotherapy for cancer. Cancer. 2005;104:1772–
1778. doi:10.1002/cncr.21364.
14. Ryan JL, Carroll JK, Ryan EP, et al. Mechanisms of
cancer-related fatigue. Oncologist. 2007;12(1):22–34.
Suppl12/suppl_1/22 [pii].
15. Bower JE, Ganz PA, Tao ML, et al. Inflammatory biomarkers and
fatigue during radiation therapy for breast and prostate can-
cer. Clin Cancer Res. 2009;15:5534.
16. Geinitz H, Zimmermann F, Stoll P, et al. Fatigue, serum cytokine
levels, and blood cell counts during radiotherapy of patients
with breast cancer. Int J Radiat Oncol Biol Phys. 2001;51:691.
17. Lundh Hagelin C, Wengstrom Y, Furst CJ. Patterns of fatigue re-
lated to advanced disease and radiotherapy in patients with
cancer-a comparative cross-sectional study of fatigue inten-
sity and characteristics. Support Care Cancer. 2009;17:519–
526. doi:10.1007/s00520- 008- 0502- 5.
18. Larsen A, Bjorge B, Klementsen B, et al. Time patterns of
changes in biomarkers, symptoms and histopathology during
pelvic radiotherapy. Acta Oncol. 2007;46:639–650. 779467586
[pii].
19. Hovdenak N, Fajardo LF, Hauer-Jensen M. Acute radiation
proctitis: a sequential clinicopathologic study during pelvic ra-
diotherapy. Int J Radiat Oncol Biol Phys. 2000;48:1111–1117.
S0360-3016(00)00744-6 [pii].
20. Symon Z, Goldshmidt Y, Picard O, et al. A murine model for
the study of molecular pathogenesis of radiation proctitis. Int
J Radiat Oncol Biol Phys. 2010;76:242–250. doi:10.1016/j.ijrobp.
2009.07.1736.
21. Greenberg DB, Gray JL, Mannix CM, et al. Treatment-related
fatigue and serum interleukin-1 levels in patients during exter-
nal beam irradiation for prostate cancer. J Pain Symptom Man-
age. 1993;8:196–200. 0885-3924(93)90127-H [pii].
22. Christiansen H, Saile B, Hermann RM, et al. Increase of hep-
cidin plasma and urine levels is associated with acute proctitis
and changes in hemoglobin levels in primary radiotherapy for
prostate cancer. J Cancer Res Clin Oncol. 2007;133:297–304.
doi:10.1007/s00432- 006- 0170- 0.
23. Saligan LN, Kim HS. A systematic review of the association be-
tween immunogenomic markers and cancer-related fatigue.
Brain Behav Immun. 2012;26:830–848. doi:10.1016/j.bbi.2012.
05.004.
24. Courneya KS, Mackey JR, Bell GJ, et al. Randomized controlled
trial of exercise training in postmenopausal breast cancer sur-
vivors: cardiopulmonary and quality of life outcomes. J Clin
Oncol. 2003;21:1660–1668. doi:10.1200/JCO.2003.04.093.
VOL 115, NO 2, APRIL 2023 205
AN 8-WEEK EXERCISE STUDY TO IMPROVE CANCER TREATMENT RELATED FATIGUE AND QOL
25. Cuesta-Vargas AI, Buchan J, Arroyo-Morales M. A multimodal
physiotherapy programme plus deep water running for im-
proving cancer-related fatigue and quality of life in breast
cancer survivors. Eur J Cancer Care (Engl). 2014;23:15–21.
doi:10.1111/ecc.12114.
26. Galanti G, Stefani L, Gensini G. Exercise as a prescription ther-
apy for breast and colon cancer survivors. Int J Gen Med.
2013;6:245–251. doi:10.2147/IJGM.S42720.
27. Blanchard CM, Courneya KS, Laing D. Effects of acute exercise
on state anxiety in breast cancer survivors. Oncol Nurs Forum.
2001;28:1617–1621.
28. Byrne A, Byrne DG. The effect of exercise on depression,
anxiety and other mood states: a review. J Psychosom Res.
1993;37:565–574. 0022-3999(93)90050-P [pii].
29. King AC, Taylor CB, Haskell WL. Effects of differing intensities
and formats of 12 months of exercise training on psychologi-
cal outcomes in older adults. Health Psychol. 1993;12:292–300.
doi:10.1037//0278-6133.12.4.292.
30. Wood LJ, Nail LM, Winters KA. Does muscle-derived interleuk-
in-6 mediate some of the beneficial effects of exercise on can-
cer treatment-related fatigue? Oncol Nurs Forum. 2009;36:519.
206 VOL 115, NO 2, APRIL 2023
31. Blumenthal JA, Williams RS, Needels TL, et al. Psychological
changes accompany aerobic exercise in healthy middle-
aged adults. Psychosom Med. 1982;44:529–536. doi:10.1097/
00006842- 198212000- 00004.
32. Dash CR, Isaacs C, Mills M, et al. An exercise trial to reduce can-
cer related fatigue in African American breast cancer patients
undergoing radiation therapy: design, rationale, and meth-
ods. Contemp Clin Trials. 2016;47:153.
33. Webster K, Cella D, Yost K. The Functional Assessment of
Chronic Illness Therapy (FACIT) measurement system: proper-
ties, applications, and interpretation. Health Qual Life Out-
comes Dec. 2003;16:79.
34. Brady MJ, Cella DF, Mo F, et al. Reliability and validity of the
functional assessment of cancer therapy-breast quality-of-life
instrument. J Clin Oncol. 1997;15:974–986. doi:10.1200/JCO.
1997.15.3.974.
35. Cella DF, Tulsky DS, Gray G, et al. The Functional Assessment
of Cancer Therapy scale: development and validation of the
general measure. J Clin Oncol. 1993;11:570–579. doi:10.1200/
JCO.1993.11.3.570.
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION