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Acupuncture for Cancer-Related Fatigue in Patients With Breast Cancer: A Pragmatic Randomized Controlled Trial


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PURPOSEWe aimed to assess the effectiveness of acupuncture for cancer-related fatigue (CRF) in patients with breast cancer. PATIENTS AND METHODS We conducted a pragmatic, randomized controlled trial comparing acupuncture with enhanced usual care. Three hundred two outpatients with breast cancer participated. We randomly assigned 75 patients to usual care and 227 patients to acupuncture plus usual care (random assignment of 1:3 respectively) with minimization controlling for baseline general fatigue and maintenance treatment. Treatment was delivered by acupuncturists once a week for 6 weeks through needling three pairs of acupoints. The usual care group received a booklet with information about fatigue and its management. Primary outcome was general fatigue at 6 weeks, measured with the Multidimensional Fatigue Inventory (MFI). Other measurements included the Hospital Anxiety and Depression Scale, Functional Assessment of Cancer Therapy-General quality-of-life scale, and expectation of acupuncture effect. Analyses were by intention to treat.ResultsTwo hundred forty-six of 302 patients randomly assigned provided complete data at 6 weeks. The difference in the mean General Fatigue score, between those who received the intervention and those who did not, was -3.11 (95% CI, -3.97 to -2.25; P < .001). The intervention also improved all other fatigue aspects measured by MFI, including Physical Fatigue and Mental Fatigue (acupuncture effect, -2.36 and -1.94, respectively; both at P < .001), anxiety and depression (acupuncture effect, -1.83 and -2.13, respectively; both at P < .001), and quality of life (Physical Well-Being effect, 3.30; Functional Well-Being effect, 3.57; both at P < .001; Emotional Well-Being effect, 1.93; P = .001; and Social Functioning Well-Being effect, 1.05; P < .05). CONCLUSION Acupuncture is an effective intervention for managing the symptom of CRF and improving patients' quality of life.
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Acupuncture for Cancer-Related Fatigue in Patients With
Breast Cancer: A Pragmatic Randomized Controlled Trial
Alexander Molassiotis, Joy Bardy, Jennifer Finnegan-John, Peter Mackereth, David W. Ryder,
Jacqueline Filshie, Emma Ream, and Alison Richardson
See accompanying editorial on page 4449
Alex Molassiotis and Joy Bardy, School
of Nursing, Midwifery, and Social Work,
University of Manchester; Peter Mack-
ereth and David W. Ryder, Christie
National Health Service (NHS) Founda-
tion Trust, Manchester; Jennifer
Finnegan-John and Emma Ream, Flor-
ence Nightingale School of Nursing and
Midwifery, King’s College London;
Jacqueline Filshie, The Royal Marsden
Hospital NHS Foundation Trust,
London; and Alison Richardson, Univer-
sity of Southampton, Southampton,
United Kingdom.
Submitted January 4, 2012; accepted
July 26, 2012; published online ahead
of print at on October 29,
Supported by a grant from Break-
through Breast Cancer.
Authors’ disclosures of potential con-
flicts of interest and author contribu-
tions are found at the end of this
Clinical trial information: NCT00957112.
Corresponding author: Alexander
Molassiotis, RN, PhD, Professor of
Cancer and Supportive Care, University
of Manchester, School of Nursing,
University Place, Manchester M13
9PL, United Kingdom; e-mail: alex
© 2012 by American Society of Clinical
DOI: 10.1200/JCO.2012.41.6222
We aimed to assess the effectiveness of acupuncture for cancer-related fatigue (CRF) in patients
with breast cancer.
Patients and Methods
We conducted a pragmatic, randomized controlled trial comparing acupuncture with enhanced
usual care. Three hundred two outpatients with breast cancer participated. We randomly
assigned 75 patients to usual care and 227 patients to acupuncture plus usual care (random
assignment of 1:3 respectively) with minimization controlling for baseline general fatigue and
maintenance treatment. Treatment was delivered by acupuncturists once a week for 6 weeks
through needling three pairs of acupoints. The usual care group received a booklet with
information about fatigue and its management. Primary outcome was general fatigue at 6
weeks, measured with the Multidimensional Fatigue Inventory (MFI). Other measurements
included the Hospital Anxiety and Depression Scale, Functional Assessment of Cancer
Therapy–General quality-of-life scale, and expectation of acupuncture effect. Analyses were by
intention to treat.
Two hundred forty-six of 302 patients randomly assigned provided complete data at 6 weeks.
The difference in the mean General Fatigue score, between those who received the
intervention and those who did not, was 3.11 (95% CI, 3.97 to 2.25; P.001). The
intervention also improved all other fatigue aspects measured by MFI, including Physical
Fatigue and Mental Fatigue (acupuncture effect, 2.36 and 1.94, respectively; both at P
.001), anxiety and depression (acupuncture effect, 1.83 and 2.13, respectively; both at P
.001), and quality of life (Physical Well-Being effect, 3.30; Functional Well-Being effect, 3.57;
both at P.001; Emotional Well-Being effect, 1.93; P.001; and Social Functioning
Well-Being effect, 1.05; P.05).
Acupuncture is an effective intervention for managing the symptom of CRF and improving
patients’ quality of life.
J Clin Oncol 30:4470-4476. © 2012 by American Society of Clinical Oncology
Persistent cancer-related fatigue (CRF) is a signifi-
cant problem in as many as 40% of disease-free
patients with breast cancer, who experience moder-
ate to severe levels of fatigue even several years after
impacting quality of life. Evidence to
underpin its management is scarce. Patients with
cancer often display an interest in complementary
and a systematic review showed that
acupuncture is promising in the management of
with further supporting evidence from can-
and noncancer studies.
These preliminary
studies had small sample sizes and methodologic
limitations. Our feasibility trial assessed the effects of
acupuncture in a mixed sample of fatigued patients
with cancer (n 47) randomly assigned to receive
six sessions of acupuncture, daily self-acupressure,
or daily sham self-acupressure over 2 weeks.
eral fatigue improved by 36% at the end of the
2-week intervention in the acupuncture group
(compared with 19% in the acupressure group and
0.6% in the sham acupressure group); however, the
effect decreased a month later (22%, 15%, and 7%
improvement, respectively), suggesting that patients
may have been undertreated. The aim of this study
4470 © 2012 by American Society of Clinical Oncology
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was to assess the effectiveness of a course of acupuncture for managing
CRF in a sample of patients with breast cancer who had completed
adjuvant chemotherapy.
A two-group, randomized controlled trial design was used, with partic-
ipants receiving either enhanced usual care or acupuncture. A computer pro-
gram allocated patients to groups and used minimization with a random
element over the margins of the following two factors: baseline Multidimen-
sional Fatigue Inventory (MFI) General Fatigue score (16, 17 or 18, or 19 or
20) and maintenance therapy (none, biologic [trastuzumab], and/or hor-
monal [tamoxifen, goserelin]). The allocation ratio was 3:1 to the acupuncture
and control groups, respectively.
Sample and Settings
Patients with breast cancer experiencing persistent fatigue of at least a
moderate level were the focus of the study. Patients were screened for fatigue
through a single-item 10-point scale (where 0 is not fatigued at all and 10 is
extremely fatigued) to identify patients with significant fatigue (ie, those with
score 5), who were then assessed for eligibility to participate in the study. We
have validated this single item compared with a fatigue scale, and correlations
were r0.75.
Recruitment took place at two specialist cancer hospitals in the
United Kingdom, four cancer centers, and three treatment centers of a na-
tional voluntary breast cancer organization.
Eligible patients had a diagnosis of stage I, II, or IIIA breast cancer; had
completed chemotherapy at least 1 month and up to 5 years previously (to
recruit those with persistent/long-term fatigue); had not planned to receive
chemoradiotherapy during the study; had a score 5ona0to10screening
scale; and were willing to participate and be randomly assigned to one of the
study groups. Patients with previous local recurrence were eligible, but not
patients with distant metastasis.
Exclusion criteria included the following: needle phobia; low platelet
count (50,000/
L); comorbidity with a bleeding disorder or thyroid dys-
function; pregnancy; hemoglobin less than 10 g/dL; hematocrit less than 30%;
active treatment for anemia with erythropoietin or blood transfusions; corti-
costeroid use; and a life expectancy less than 6 months. In addition, the
ipsilateral arm of patients who had undergone axillary dissection was excluded
from needling, as were lymphedematous limbs.
All trial patients received usual care. Because there is no recognized
standard care for fatigue, all patients were offered a fatigue information book-
let. In addition, the intervention group was offered six acupuncture sessions
over 6 weeks. On the basis of the Standards for Reporting Interventions in
Clinical Trials of Acupuncture recommendations for reporting acupuncture
patients received a standardized 20-minute acupuncture session nee-
dling bilaterally or unilaterally three points (ST36, SP6, and LI4), with some
flexibility in case points could not be punctured (eg, in case of lymphedema).
Alternative points were selected by therapists at their discretion to maintain an
equal dose of treatment. These points could include GB34 and SP9.
approach mimics current acupuncture practice and ensured replicability of
the technique across therapists, which was assessed through regular audits of
the therapists’ records. Patients were observed for 18 weeks. Points were
punctured perpendicularly, with a depth of 0.5 to 1 inch,
depending on
patients’ size, sensitivity, and health state. Needles were manufactured by
Seirin (Kyoto, Japan) with guide tubes for single use (size, 36 gauge; point, 16
to 30 mm). No flicking or rotation of the needle took place once inserted. Each
session was based on a strict protocol, and conversation between acupunctur-
ists and patients was kept to minimum. Immediately after each session, ther-
apists completed a form verifying the exact treatment given and any issues that
needed to be reported (eg, adverse effects). These forms were checked regularly
by the investigators for consistency across therapists. No other complementary
therapy use was recommended during the course of acupuncture (although
any such use was documented). Therapists (n 12) were educated in acu-
puncture to degree level, were registered with a professional body, and had a
minimum of 2 years of clinical experience.
The control group received enhanced usual care. In the absence of any
guidelines about how to manage fatigue and the limited available research
evidence, usual care inevitably varied and depended on the clinicians treating
patients with breast cancer at the study sites. To control this current practice,
we chose to enhance usual care by providing all patients with a detailed
information booklet about coping with fatigue developed by Macmillan/Can-
cerBackup (London, United Kingdom), which included details about fatigue
and cancer; causes and effects of fatigue; coping with fatigue at work; diet,
exercise, and sleep; planning the day; and management of fatigue.
The ratio of patients in the experimental and control groups was 3:1,
respectively, to allow us to randomly assign acupuncture patients again at the
end of treatment to one of three groups to test the effectiveness of self-
acupuncture/self-needling as a maintenance therapy (not reported here).
The study received ethical approval from a research ethics committee
and all hospitals and centers involved. Patients were referred by clinicians
or health professionals; were self-referred after responding to media pub-
licity, Web site information, or posters displayed within the hospitals and
satellite centers; were referred directly by researchers during outpatient
visits; or responded to mailshot. Patients willing to participate signed a
consent form and were randomly assigned after completion of baseline
data. Researchers telephoned a central service (hospital clinical trials unit),
and operators there used a bespoke computer system to obtain the alloca-
tions. Stratification took place based on main center. Patients in the acu-
puncture group visited the treatment setting to receive the intervention
weekly. Trial participants’ travel expenses were reimbursed. Assessments
were completed at baseline and at the end of 6, 10, and 18 weeks after
baseline (data for 10- and 18-week follow-ups are reported elsewhere). The
trial was monitored by a trial steering/data monitoring committee that
included independent members and a patient representative.
Outcome Measures
The primary outcome measure was the difference in general fatigue, as
self-reported by patients with the MFI
at 6 weeks (treatment completion).
The MFI is a brief 20-item well-validated scale measuring general fatigue and
the dimensions of physical and mental fatigue, activity, and motivation. Sec-
ondary outcomes included mental fatigue, activity, and motivation (using the
MFI); anxiety and depression using the 14-item Hospital Anxiety and Depres-
sion Scale (HADS)
; and quality of life using the Functional Assessment of
Cancer Therapy–General and the Functional Assessment of Cancer Therapy–
Breast Cancer (FACT-B) module.
Sociodemographic and treatment characteristics were obtained at base-
line from patients’ records and patients themselves. Use of complementary
therapies in the past and during the study participation was recorded with a
self-report questionnaire at 6 weeks. Patients were asked about their treatment
expectations, how much they believed this method would help them alleviate
fatigue, and how much faith they have in acupuncture, using three 10-point
scales. Patients completed the questionnaires at home, and these were mailed
back to the researchers using prepaid envelopes. We monitored adverse events
by patient reports and review of therapists’ records.
Sample Size
Our earlier study
was used to inform the sample size calculation. The
planned sample size was 320 patients, randomly assigned at a ratio of 3:1 with
240 patients in the experimental group and 80 patients in the control group,
unbalanced to allow for 80% power for the second part of the trial (another
random assignment of acupuncture patients to maintenance therapy with
self-needling, not reported here, for which we needed 192 patients). A 20%
attrition rate was anticipated. With this sample size, there would be in excess of
95% power to detect a half standard deviation (SD) difference in fatigue
change scores. The power was for a two-tailed test of equal mean change scores
at the 5% level of significance. The SD was anticipated to be approximately 4,
and thus, the study was planned to have high power to detect a 2-unit differ-
ence in change scores. Recruitment stopped at 302 patients because the target
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numbers for the second phase of the trial (n 192) had been achieved, with
sample power (90%) for the first random assignment.
Data Analysis
Descriptive statistics were used to summarize the data. A simple ttest was
applied to fatigue change scores (week 6 baseline), but the primary analysis
was an analysis of covariance (ANCOVA) of week 6 fatigue scores with the
baseline fatigue score as a covariate and trial arm as grouping factor. Similar
analyses were performed for secondary outcomes (ie, subscales from the MFI,
HADS, and FACT-B). A last value carried forward approach was used as a
sensitivity analysis for patients missing the primary outcome. Sample sizes
were adequate to justify ttests (the sampling distribution of the mean tends to
normality irrespective of the distribution of the observations by the central
limit theorem). Intent-to-treat analysis was performed. Normality assump-
tions in the data were assessed using residual plots against fitted values and a
quantile-quantile plot of the residuals.
Sociodemographic and Clinical Characteristics
Three hundred two patients were enrolled and randomly as-
signed, 227 to acupuncture and 75 to usual care (Fig 1). The sample
was predominantly white, married, and with college or higher educa-
tion. The mean age of the enhanced usual care group was 53 years
(range, 25 to 80 years), and the mean age of the acupuncture group
was 52 years (range, 30 to 75 years). Time since diagnosis was 20.5
months for both groups, with a range of 6 to 84 months in the usual
care group and 5 to 161 months in the acupuncture group. The mean
duration of fatigue was 18 months (range, 4 to 58 months) in the usual
care arm and 15 months (range, 2 to 69 months) in the acupuncture
arm. Other details are listed in Table 1.
Primary Outcome Analysis
Fifty-six (18.5%) of 302 patients were missing the primary out-
come, 46 (20.3%) of 227 patients in the acupuncture arm and 10
(13.3%) of 75 patients in the control arm. The trial arm effect was
highly significant (P.001), with an estimated difference in week 6
score (acupuncture control) given equal baseline scores of 3.11
(95% CI, 3.97 to 2.25; Fig 2).
An assumption of no improvement for patients missing the
6-week general fatigue score (ie, baseline value carried forward) was
postulated, providing a conservative sensitivity analysis for the pri-
mary outcome. On fitting such a model, the magnitude of the acu-
puncture effect was reduced to 2.49 (95% CI, 3.29 to 1.69), but
this remained highly significant (P.001; Table 2). ANCOVA for the
primary outcome is presented in Table 3.
Assessment of a center effect was performed with the addition of
two random effects (an intercept and trial arm contrast) within each of
the 11 centers. This extended mixed-effects model was fitted and
found not to significantly improve the fit (P.39). Under the ex-
tended model, the mean treatment contrast was 2.99, with an esti-
mated SD of the random effect of 0.30.
Primary analysis yielded a treatment contrast of 3.11 fitted to
246 patients. Adding additional covariates of baseline FACT-B,
HADS-Anxiety, and HADS-Depression in an ANCOVA model
yielded a treatment contrast of 2.93 fitted to 221 patients (missing
data in 25 patients), which was similar to the estimate without the
covariates and highly significant (P.001).
ANCOVA regression models were fitted for MFI, HADS, and
FACT-B subscales. In each case, the week 6 value was the response and
the baseline value was used as covariate. The key results are listed in
Table 3, showing that the acupuncture intervention had beneficial
effects on all secondary outcomes assessed.
Subgroup analyses were carried out with regard to the screen-
ing fatigue score (5 to 6 [moderate fatigue] v7 to 10 [severe
fatigue]), age (median cutoff point of 52 years), and whether
patients were receiving or not receiving maintenance hormone
therapies. Significance was assessed by adding appropriate interac-
tion terms to ANCOVA. None of the results were significant (test
of heterogeneity, 0.23, 0.23, and 0.34 for fatigue score, age, and
receipt of hormone therapy, respectively).
Participants were asked before random assignment how much
they expected acupuncture to help them alleviate fatigue. Expectation
of effect did not relate to outcome, as the Spearman rank correlations
were r
⫽⫺0.18 (n 62, P.15) in the control group and r
(n 175, P.74) in the acupuncture group.
Random Allocation 3:1
(N = 302)
Control arm (enhanced standard care; n = 75)
Received allocated intervention (n = 75)
)722 = n( mra erutcnupucA
Received allocated intervention (n = 218)
Did not receive allocated intervention (n = 9)
Withdrew before treatment (n = 6)
Withdrawn by researcher (n = 3)
Received at least one session but < six (n = 53)
)25 = n( eciohc tneitaP
Withdrawn by researcher (n = 1)
)56 = n( dezylanA
Excluded from analysis (n = 10)
(did not return the primary
outcome data at 6 weeks)
)181 = n( dezylanA
Excluded from analysis (n = 46)
(did not return the primary
outcome data at 6 weeks)
Fig 1. Flow of participants through each
stage of the trial.
Molassiotis et al
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This study determined that women with breast cancer and CRF re-
ported significant improvements in overall fatigue, physical and men-
tal fatigue, activity, motivation, psychological distress, and all domains
of quality of life after 6 weeks of acupuncture. To our knowledge, this
is the first large multisite trial of its kind and provides some evidence of
the effects of acupuncture.
This trial confirms preliminary and promising evidence obtained
from an uncontrolled single-arm trial
and our own pilot study.
Although the magnitude of the improvement in the current trial in
absolute numbers was lower than previous preliminary studies, it is
nevertheless both statistically and clinically important. The approach
used in this study not only improved physical fatigue and physical and
functional quality of life, but also improved mental fatigue, which has
Table 1. Sociodemographic and Clinical Characteristics of the
Patient Sample
Usual Care
(n 75)
(n 227)
No. of
Patients %
No. of
Patients %
Marital status
Single 17 23 47 21
Married 46 61 124 55
Divorced or separated 8 11 49 22
Widowed 4 5 7 3
Living arrangements
Living alone 15 20 51 22
Living with husband or partner 51 68 140 63
Other 9 12 36 16
Educational attainment
Secondary school 13 17 64 28
College/diploma 25 33 81 36
University/degree 23 31 45 20
Postgraduate 14 19 36 16
Missing 0 0 1 1
Race or ethnicity
White 71 95 212 93
Black 1 1 3 1
Asian/Chinese 0 0 9 4
Mixed 3 4 2 1
Missing 0 0 1 1
Religious affiliation
Christian 57 76 173 76
Muslim 0 0 5 2
Hindu 0 0 2 1
None 16 21 36 16
Prefer not to say 0 0 3 1
Other 2 3 8 4
Occupational status
Employed full-time 19 25 59 26
Employed part-time 21 28 74 33
Retired 19 25 30 13
Unemployed 0 0 5 2
Casual worker 1 1 0 0
Not working because of ill health 10 13 39 17
Housewife 3 4 12 5
Other 0 0 8 4
Missing 2 3 0 0
Cancer treatment
Surgery and chemotherapy 12 16 45 20
Chemotherapy and radiotherapy 1 1 2 1
Surgery, chemotherapy, and radiotherapy 62 83 180 79
Chemotherapy type
CMF 1 1 4 2
Anthracyclines 32 43 99 44
Taxanes 8 11 16 7
CMF and anthracyclines 10 13 44 19
Anthracyclines and taxanes 20 27 48 21
CMF, anthracyclines, and taxanes 0 0 2 1
Missing 4 5 14 6
Baseline General Fatigue score
16 36 48 113 50
17 or 18 24 32 68 30
19 or 20 15 20 46 20
(continued in next column)
Table 1. Sociodemographic and Clinical Characteristics of the Patient
Sample (continued)
Usual Care
(n 75)
(n 227)
No. of
Patients %
No. of
Patients %
Question rating
Faith in acupuncture
Median 7 7
Range 0-10 0-10
No. of patients with missing data 2 8
Expectations of acupuncture in general
Median 7 7
Range 0-10 0-10
No. of patients with missing data 2 7
Expectations of acupuncture with fatigue
Median 7 7
Range 0-10 0-10
No. of patients with missing data 3 8
Abbreviation: CMF, cyclophosphamide, methotrexate, and fluorouracil.
MFI: General Fatigue (week 6-baseline)
-5-10-15 0 105
Fig 2. Change in Multidimensional Fatigue Inventory (MFI): General Fatigue
scores from baseline to 6 weeks.
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been a difficult area in the past in which to demonstrate an improve-
The improvements in psychological distress and emotional
adjustment are also interesting, particularly because fatigue has been
shown to be part of symptom clusters alongside anxiety and depres-
and acupuncture could be an approach to manage clusters of
symptoms rather than only single symptoms.
The evidence around the role of acupuncture for supportive care
in cancer is increasing, and positive trials exist for the management of
hot flushes, aromatase inhibitor–induced arthralgia, chemotherapy-
induced nausea and vomiting, and xerostomia.
Why acupuncture
helps to reduce fatigue is not known, and this should be the focus of
future work. However, we know acupuncture has an effect on inflam-
matory cytokines, T lymphocytes, and various peptides,
and recent
results suggest that cytokines and tumor necrosis factor
signaling are
contributing factors in the development of fatigue.
Although it is acknowledged that a placebo effect in an acupunc-
ture trial may be possible, a sham acupuncture needling method was
not included because of debate surrounding sham methods. It is
increasingly believed a sham controlled trial is only appropriate when
two acupuncture interventions are compared. In addition, sham acu-
puncture designs cannot detect the whole placebo effect, may generate
false-negative results,
and may introduce ethical and practical
Experimental and clinical studies have also shown that
minimal or sham acupuncture used as placebo control is not neces-
sarily inert from a physiologic perspective, and its relevance as placebo
acupuncture must be questioned,
even when it is not used as per
acupuncture principles.
Instead of reducing bias, sham designs
may introduce bias against the treatment being tested.
To regard
placebo acupuncture as a universally effective super placebo would be
inappropriate, and results should be interpreted with care.
We followed a pragmatic design focusing on effectiveness rather
than efficacy that best reflects the likely clinical response in practice,
but we acknowledge that acupuncture may have a placebo effect.
enhanced usual care by providing participants with a booklet about
fatigue management options, therapists in the acupuncture group
communicated and stayed with patients only to facilitate treatment,
and there was no evidence of expectancy in the results; these facts
partly control for placebo effects as a result of increased contact and
expectation. Future acupuncture trials should include an active con-
trol arm, such as attention control, educational intervention, or exer-
cise, alongside a no treatment arm or wait-list arm, so nonspecific and
placebo effects of acupuncture can be assessed more appropriately.
Findings need to be set in context of the study’s limitations.
Because of self-referral and the multiplicity of sites involved in recruit-
ment, it was not possible to obtain data on how many patients were
approached for participation; hence, we do not know whether our
Table 3. Difference in Outcomes at Week 6 for Fatigue, Quality of Life, Anxiety, and Depression
Scale Score Range No. of Patients Missing Data Equal Slopes PTrial Arm PAcupuncture Effect
SE 95% CI
GF 0-20 56 .23 .001 3.11 0.44 3.97 to 2.25
GF (LVCF) 0-20 0 .35 .001 2.49 0.44 3.29 to 1.69
PF 0-20 56 .40 .001 2.36 0.45 3.25 to 1.47
RA 0-20 61 .68 .001 2.29 0.41 3.10 to 1.48
RM 0-20 60 .93 .001 2.02 0.40 2.82 to 1.22
MF 0-20 61 .14 .001 1.94 0.44 2.81 to 1.07
Anxiety 0-21 70 .94 .001 1.83 0.44 2.69 to 0.97
Depression 0-21 67 .67 .001 2.13 0.36 2.85 to 1.41
PWB 0-28 63 .006 .001 3.30 0.57 2.17 to 4.43
SFWB 0-28 63 .08 .05 1.05 0.54 0.01 to 2.11
EWB 0-24 62 .04 .001 1.93 0.49 0.96 to 2.90
FWB 0-28 85 .29 .001 3.57 0.61 2.38 to 4.76
NOTE. Analysis of covariance was used with baseline values as covariate and trial arm as grouping factor. For conciseness, only the trial arm estimates are
given here.
Abbreviations: EWB, Emotional Well-Being; FACT-B, Functional Assessment of Cancer Therapy–Breast Cancer; FWB, Functional Well-Being; GF, General Fatigue;
HADS, Hospital Anxiety and Depression Scale; LVCF, last value carried forward; MF, Mental Fatigue; MFI, Multidimensional Fatigue Inventory; PF, Physical Fatigue;
PWB, Physical Well-Being; RA, Reduced Activity; RM, Reduced Motivation; SFWB, Social/Family Well-Being.
Estimated difference in week 6 score (acupuncture– control) given equal baseline scores.
Table 2. Fatigue Change Scores Analyses
Complete Patients
(n 246) LVCF (n 302)
Mean score (GF.6–GF.0), SC 0.62 0.53
Mean score (GF.6–GF.0), Acu 3.72 2.96
Difference (Acu–SC) in mean change in
GF (GF.6–GF.0) 3.10 2.43
95% CI 3.98 to 2.23 3.19 to 1.67
P.001 .001
Covariance model estimates for GF
Baseline GF
Estimate 0.47
SE 0.07
Estimate 3.11
SE 0.44
Abbreviations: Acu, acupuncture arm; GF, General Fatigue; GF.0, General
Fatigue at baseline; GF.6, General Fatigue at 6 weeks; LVCF, last value carried
forward; SC, standard care.
Molassiotis et al
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sample is highly selected or whether it differs from those who were
ineligible. One of the difficulties in recruitment was to identify women
with moderate or severe fatigue levels; despite the literature showing
high incidence of CRF, much of the fatigue reported by patients in our
study was of low severity, and we needed to screen many hundreds of
patients to identify those with at least moderate CRF. It is also impor-
tant to emphasize that acupuncture is not just a simple needling
technique eliciting specific physiologic effects, but wide improve-
ments in patient-reported outcomes may indicate nonspecific placebo
effects. We also need to recognize that improvements in outcome
variables in an unblinded trial may be susceptible to assessment bias,
although the secondary patient-reported outcomes we have used are
well known to co-occur with fatigue and impact on quality of life.
There was a 20% missing data rate (which was expected and incorpo-
rated at the time of sample size calculations), which was partly ad-
dressed through sensitivity analysis; however, a 7% difference in
missingness between the two arms, although not statistically signifi-
cant, needs to be considered when results are interpreted. Also, the
trial was powered for the primary outcome analysis; all other analyses
on secondary outcomes need to be considered corroborative or hy-
pothesis generating rather than definitive. Finally, lack of blinding
may be a concern, but in the absence of credible controls for an
acupuncture trial, we chose a pragmatic trial design. Inclusion of
objective physiologic data in future trials will provide stronger evi-
dence of effect in acupuncture trials.
The trial shows that patients in the intervention group reported
better fatigue, anxiety, depression, and quality-of-life scores, but the
design of the trial does not allow the specific effect of acupuncture to
be distinguished from other elements and effects of the intervention.
Although this trial provides some evidence of effectiveness, further
effectiveness trials using appropriate controls, where hypotheses and
study design are formulated based on conditions in routine practice,
and outcomes essential for clinical decisions are warranted before
recommending widespread use of acupuncture in patients with breast
cancer. Acupuncture could be a treatment option for CRF, although
its availability may be an issue in many health care services and patients
may not be able to afford private costs. Future research should con-
centrate on cost-effectiveness of acupuncture, because potentially ex-
pensive acupuncture treatments may be offset by reduced societal
costs and health care utilization in those suffering significant and
protracted fatigue after treatment. Future studies should collect long-
term outcome data for fatigue that could make results more convinc-
ing. The use of acupuncture should also be tested in other cancer
diagnostic groups.
The author(s) indicated no potential conflicts of interest.
Conception and design: Alexander Molassiotis, Peter Mackereth, David
W. Ryder, Jacqueline Filshie, Alison Richardson
Administrative support: David W. Ryder
Provision of study materials or patients: Peter Mackereth,
Jacqueline Filshie
Collection and assembly of data: Joy Bardy, Jennifer Finnegan-John,
Peter Mackereth, Emma Ream
Data analysis and interpretation: Alexander Molassiotis,
David W. Ryder
Manuscript writing: All authors
Final approval of manuscript: All authors
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... Numerous studies have investigated various interventions to target CRF and sleep disturbances related to HT. [33][34][35][36][37] The most prominent of these interventions discussed within the literature is exercise. ...
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Background Breast cancer is the most common type of cancer, accounting for 15% of all new cases. Hormone therapy (HT) is extremely effective in reducing breast cancer recurrence. However, adherence to HT medication is often poor due to negative side effects such as fatigue and sleep disturbances. Physical activity has been identified as a possible intervention to improve quality of life and reduce side effects of HT. Objective The objective of this systematic review was to summarise evidence of exercise interventions for women being treated with HT for breast cancer. Method Electronic searches were conducted from inception to March 2022 using Medline, SPORTdiscus, Embase, Scopus, PsycINFO and Web of Science databases. Searches included a combination of terms related to breast cancer, exercise, sleep disturbances, fatigue and HT. Results Ten eligible papers were identified, and their quality was assessed. Type, frequency, duration and intensity of exercise interventions varied. Exercise types included aerobics, strength/resistance training, walking and yoga. Heterogeneity of data made it difficult to draw conclusions. However, aerobic exercise interventions provide clear improvements in fatigue and sleep disturbances. Conclusions This review identified a lack of consistency in exercise recommendations for women being treated for breast cancer. It identifies that aerobic exercise can successfully improve fatigue and sleep disturbances, consistent with existing literature. Exercise has a range of benefits for this population, including improving psychological well‐being and quality of life. Clinicians should strongly advocate for engagement in exercise to promote overall physical and psychological well‐being in women being treated for breast cancer.
... Some studies have shown that acupuncture treatment can markedly improve the fatigue of patients with breast cancer after chemotherapy (Zhang et al. 2018). For example, a study enrolled 302 patients with breast cancer experiencing fatigue following chemotherapy revealed that the fatigue level of patients that received acupuncture treatment was lower than that of patients who did not receive acupuncture treatment (Molassiotis et al. 2012). In addition, a meta-analysis including 25 studies enrolled 2524 patients with breast cancer indicated that the acupuncture treatment group had lower fatigue than the nonacupuncture treatment group, and the incidence of side effects due to acupuncture was extremely low, with no serious side effects observed (Yuzhu et al. 2021). ...
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Chemotherapy-induced fatigue reduces not only the quality of life of patients but also effect their recurrence-free survival rate. Although electroacupuncture can relieve fatigue, it has limited affect on some patients. Therefore, appropriate biomarkers are needed to help screen patients who can benefit from electroacupuncture treatment of fatigue. We conducted this study to explore the predictive ability of SNPs on the efficacy of electroacupuncture in the treatment of fatigue in patients with breast cancer after adjuvant chemotherapy. Our study included breast cancer patients with fatigue after receiving paclitaxel and/or anthracycline based adjuvant chemotherapy. The patients were divided into the electroacupuncture group and the control group. The electroacupuncture treatment group received adjuvant chemotherapy and electroacupuncture treatment, while the control group only received adjuvant chemotherapy, and then compared the fatigue relief degree of two groups. In addition, we used NCBI dbSNP and PharmGKB databases to select fatigue related genes and their SNPs. We collected peripheral blood from the included patients for SNPs typing, and recorded the efficacy of electroacupuncture to analyzed the correlation between different SNPs and therapeutic efficacy. The side effects of electroacupuncture treatment were also recorded. 76 patients in the electroacupuncture group and 48 patients in the control group were enrolled. In the electroacupuncture group, 63 patients (82.9%) experienced moderate to severe fatigue (BFI score > 3). After electroacupuncture treatment, the number of patients with a BFI score of > 3 was 46 (60.5%). Therefore, the fatigue symptoms of 26.9% patients were significantly improved (P < 0.05). In the control group, which did not receive electroacupuncture treatment, 40 of 48 patients had a BFI score of > 3. Following the same observation time used in the electroacupuncture group, 36 patients had a BFI score of > 3 points. Thus, fatigue was not significantly relieved in the control group (83.3% vs. 75.0%, P > 0.05). We included 56 patients in our analysis of the correlation between SNPs and electroacupuncture treatment effects. We divided the patients into an effective group and ineffective group according to therapeutic effects. Our results indicated that the effective rate of electroacupuncture treatment with IL1A rs3783550 AC and CC genotypes was higher than that with other genotypes (AC: 84.6%, CC: 81.8%, AA: 33.0%, P < 0.05). Similarly, the effective rate of electroacupuncture treatment with HTR1A rs6295 GG and CC genotypes was higher than that with other genotypes (GG: 63.0%, CC: 55.6%, GC: 18.2%, P < 0.05). However, no other genotypes were related to the effect of electroacupuncture treatment on fatigue. Our result showed that electroacupuncture has therapeutic effect on fatigue after adjuvant chemotherapy for breast cancer and the side effects are tolerable. In addition, IL1A rs3763550 and HTR1A rss6295 can predict the therapeutic effect of electroacupuncture on fatigue after adjuvant chemotherapy in breast cancer, which helps to better screen patients who can benefit from electroacupuncture treatment.
... Sham acupuncture also has some limitations including latent ethics issues brought by unnecessary transportation costs for the sham acupuncture group, uncertain effect of inert control [54,55], and the lack of consensus on approaches. For these reasons, more and more trials did not include a sham-acupuncture control group [48,56]. We agree with the opinion of Molassiotis A. and colleagues that shifting the focus from placebo-related issues to those with clinical meanings is appropriate [57]. ...
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Background Patients with local gastric cancer experience a decline of Health-related quality of life (HRQOL) during adjuvant chemotherapy following gastrectomy. Our previous pilot study has indicated the potential of acupuncture to improve HRQOL and control cancer-related symptoms burden. This full-scale trial will focus on confirming the effect of acupuncture for patients with gastric cancer. Methods A multicenter, open-label, three-arm randomized controlled trial with 249 patients will be conducted in China. Patients will be randomly assigned, in a ratio of 1:1:1, to receive high-dose acupuncture (HA, 7 times each chemo-cycle for 3 cycles), low-dose acupuncture (LA, 3 times each chemo-cycle for 3 cycles), or no acupuncture. The acupoints prescription consisted of bilateral ST36, PC6, SP4, DU20, EX-HN3, and selected Back-shu points. Patients-reported Functional Assessment of Cancer Therapy-Gastric (FACT-Ga) and modified Edmonton Symptom Assessment Scale (mESAS) during the therapy will be recorded. Area under curve (AUC, 21 days/cycle × 3 cycles) and average trajectory of FACT-Ga and mESAS will be calculated. The primary outcome will be the differences in AUC of the FACT-Ga Trial Outcome Index (TOI) between HA and LA versus control groups. Secondary outcomes include AUCs and average trajectory of other FACT-Ga subscales and mESAS scores. Discussion This study aims to assess the effect of acupuncture and to compare the difference between LA and HA groups on HRQOL and symptom burden controlling in gastric cancer patients by an adequately powered trial. Trial registration This study was approved by the Ethics Committee of the Guangdong Provincial Hospital of Traditional Chinese Medicine (approval number: BF2018-118) with registration at (identifier: NCT04360577).
... Research evidence has implicated that acupoint stimulation produced both specific and non-specific effects (placebo effects) (Tan et al., 2015(Tan et al., , 2022b. As such, it is recommended to simultaneously use both active (attention control) and inert controls (no treatment at all) in clinical trials to differentiate between the non-specific and specific effects of an intervention (Molassiotis et al., 2012). Our study findings showed that both the true SA group and sham SA group had improvements in FSDSC at cluster level and single symptom level as well as the QoL. ...
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Objective: To evaluate the feasibility of the somatic acupressure (SA) for managing the fatigue-sleep disturbance-depression symptom cluster (FSDSC) among breast cancer (BC) survivors and its preliminary effects. Methods: In this Phase II randomized controlled trial (RCT), 51 participants were randomised evenly into the true SA group, sham SA group, and usual care group. All the participants received usual care. The two SA groups performed additional true or sham self-acupressure daily for seven weeks. The primary outcomes related to the assessment of participants' recruitment and compliance with study questionnaires and interventions. Clinical outcomes assessed the preliminary effects of SA on fatigue, sleep disturbance, depression, and quality of life. Semi-structured interviews were undertaken to capture participants' experiences of participating in this study. The statistical effects of the intervention on the outcomes were modelled in repeated measures ANOVA and adjusted generalized estimating equations. Results: Forty-five participants completed the SA intervention. No adverse events were reported. Over 85% of the participants could sustain for 25 days or more and 15 min or more per session, but the adherence to the intervention requirement was yet to improve. The group by time effect of the FSDSC and depression were significant (p < 0.05). Qualitative findings showed that participants positively viewed SA as a beneficial strategy for symptom management. Conclusions: The SA intervention protocol and the trial procedures were feasible. The results demonstrated signs of improvements in targeted outcomes, and a full-scale RCT is warranted to validate the effects of SA on the FSDSC.
Fatigue is a reversible change in biological, physical and psychic functions, resulting from the imbalance of the organism. In patients with head and neck cancer (HNC), fatigue has been cited as one of the most frequent symptoms, especially in individuals with metastasis. It can significantly limit daily activities in order to be considered as a chronic condition, in particular, when associated with painful symptoms. The objective of this studt was to report the occurrence of fatigue and pain in patients with HNC. This was a series of prospective clinical cases describing the clinical history of four patients with HNC submitted to radio chemotherapeutic treatment, users of a public oncology service. To assess the degree of fatigue, the Brief Fatigue Inventory questionnaire was applied at five different moments during the antineoplastic treatment and pain analysis, an analog pain scale was used. The analysis of the questionnaires showed that fatigue was a frequent complaint and intensified with the advance of antineoplastic therapy. Its occurrence was also related to the difficulty performing daily activities. Painful symptomatology has been reported by patients to varying degrees. The occurrence of fatigue and pain in patients with HNC presents variability due to the individual's own experience, reflected by their socioeconomic and cultural context and their personal perception of the illness process. Keywords: Head and Neck Neoplasms. Quality of Life. Cancer Pain. Resumo A fadiga é uma alteração reversível das funções biológicas, físicas e psíquicas, proveniente do desequilíbrio do organismo. Em pacientes com câncer de cabeça e pescoço (CCP), a fadiga tem sido citada como um dos sintomas mais frequentes, principalmente em indivíduos com metástase. Pode limitar de forma significativa as atividades diárias, de modo a ser considerada uma condição crônica, em especial, quando associada à sintomatologia dolorosa. Este trabalho objetiva relatar a ocorrência de fadiga e dor em pacientes com CCP. Tratou-se de uma série de casos clínicos, de caráter prospectivo, que descreve a história clínica de quatro pacientes com CCP submetidos ao tratamento radioquimioterápico, usuários de um serviço de oncologia público. Para avaliação do grau de fadiga, foi aplicado o questionário Brief Fatigue Inventory em cinco momentos distintos, durante o tratamento antineoplásico e para a análise da dor, foi utilizada uma escala analógica de dor. A análise dos questionários demonstrou que a fadiga foi uma queixa frequente e se intensificou com o avanço da terapia antineoplásica. Sua ocorrência também esteve relacionada à dificuldade de execução de atividades cotidianas. A sintomatologia dolorosa foi relatada pelos pacientes em diferentes graus. A ocorrência de fadiga e dor em pacientes com CCP apresenta variabilidade em razão da experiência vivida pelo próprio indivíduo refletida pelo seu contexto socioeconômico e cultural e a sua percepção pessoal acerca do processo de adoecimento. Palavras-chave: Neoplasias de Cabeça e Pescoço. Qualidade de Vida. Dor do Câncer.
A 4-year prospective cohort study on patients with lung, gastric, hepatic, colorectal, breast, uterine, and ovarian cancer was conducted at the East-West Cancer Center (EWCC) of Daejeon Korean Medicine Hospital in Daejeon, Korea. We divided patients into 2 groups based on how long they had been receiving TKM oncotherapy and compared event-free survival (EFS), telomere length change, and quality of life (QoL). The study collected data on 83 patients from October 2016 to June 2020 and discovered no statistical differences in EFS based on the duration of TKM oncotherapy. In the analysis of changes in QoL outcomes, there were no statistically significant group differences between the groups. After controlling for covariates that could affect telomere length, the long-term TKM oncotherapy group had a higher daily telomere attrition rate. The study of the relationship between telomere length and prognostic factors discovered that patients with advanced N stage at the time of diagnosis and who had previously received radiotherapy had shorter telomere length. When examining associations between SNP genotype and percentile score of telomere length, this study was able to confirm an association between telomere length and rs4387287. This study is significant because it is the first to assess the effects of TKM oncotherapy and investigate telomere length-related factors. To assess the effects of TKM oncotherapy on cancer patients' survival and QoL, a longer-term observational study with a larger sample size is required.
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Purpose: To provide evidence-based recommendations to health care providers on integrative approaches to managing anxiety and depression symptoms in adults living with cancer. Methods: The Society for Integrative Oncology and ASCO convened an expert panel of integrative oncology, medical oncology, radiation oncology, surgical oncology, palliative oncology, social sciences, mind-body medicine, nursing, methodology, and patient advocacy representatives. The literature search included systematic reviews, meta-analyses, and randomized controlled trials published from 1990 through 2023. Outcomes of interest included anxiety or depression symptoms as measured by validated psychometric tools, and adverse events. Expert panel members used this evidence and informal consensus with the Guidelines into Decision Support methodology to develop evidence-based guideline recommendations. Results: The literature search identified 110 relevant studies (30 systematic reviews and 80 randomized controlled trials) to inform the evidence base for this guideline. Recommendations: Recommendations were made for mindfulness-based interventions (MBIs), yoga, relaxation, music therapy, reflexology, and aromatherapy (using inhalation) for treating symptoms of anxiety during active treatment; and MBIs, yoga, acupuncture, tai chi and/or qigong, and reflexology for treating anxiety symptoms after cancer treatment. For depression symptoms, MBIs, yoga, music therapy, relaxation, and reflexology were recommended during treatment, and MBIs, yoga, and tai chi and/or qigong were recommended post-treatment. Discussion: Issues of patient-health care provider communication, health disparities, comorbid medical conditions, cost implications, guideline implementation, provider training and credentialing, and quality assurance of natural health products are discussed. While several approaches such as MBIs and yoga appear effective, limitations of the evidence base including assessment of risk of bias, nonstandardization of therapies, lack of diversity in study samples, and lack of active control conditions as well as future research directions are discussed.Additional information is available at
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Background: Cancer-related fatigue (CRF) has an enormous adverse impact on quality of life and subsequent therapy of cancer patients. Complementary and alternative medicine (CAM) is reported to improve CRF in many systematic reviews (SRs), but the effects are controversial because of variations in the quality and outcomes. Methods: Thirteen databases were searched from inception to September 2022. Only SRs of randomized controlled trials (RCTs) were included. We assessed the quality of included SRs with the AMSTAR-2 tool, the strength of evidence with the GRADE system, the risk of bias with the ROBIS tool, and the integrity of SRs with the PRISMA checklist. Results: We included 30 eligible SRs (27 meta-analyses). Based on the AMSTAR-2 tool, 29 SRs were rated as "critically low" quality, and only one was rated as "low" quality. With the ROBIS tool, 19 SRs demonstrated a low risk of bias. According to the PRISMA checklist, no SRs reported all the items, and 10 SRs sufficiently reported over 70%. Based on the GRADE system, 7 outcomes were assessed as high-quality evidence. Conclusion: This overview demonstrates promising evidence for the effectiveness of CAM interventions in the treatment of CRF in adults. The roles of qigong, music, auricular point therapy, and dietary supplements in CRF need further evaluation. Although findings are mixed, it is recommend to select appropriate CAM to manage cancer-related fatigue under the guidance of physicians. More studies with rigorous methodological designs and sufficient sample sizes are needed.
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The STandards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) were published in five journals in 2001 and 2002. These guidelines, in the form of a checklist and explanations for use by authors and journal ed-itors, were designed to improve reporting of acupuncture trials, particularly the interventions, thereby facilitating their interpretation and replication. Subsequent reviews of the application and impact of STRICTA have highlighted the value of STRICTA as well as scope for improvements and revision. To manage the revision process a collaboration between the STRICTA Group, the CONSORT Group, and the Chinese Cochrane Centre was developed in 2008. An expert panel with 47 participants was convened that provided electronic feedback on a revised draft of the checklist. At a subsequent face-to-face meeting in Freiburg, a group of 21 par-ticipants further revised the STRICTA checklist and planned dissemination. The new STRICTA checklist, which is an official extension of CONSORT, includes six items and 17 sub-items. These set out reporting guidelines for the acupuncture rationale, the details of needling, the treatment regimen, other components of treat-ment, the practitioner background, and the control or comparator interventions. In addition, and as part of this revision process, the explanations for each item have been elaborated, and examples of good reporting for each item are provided. In addition, the word "controlled" in STRICTA is replaced by "clinical," to indicate that STRICTA is applicable to a broad range of clinical evaluation designs, includ-ing uncontrolled outcome studies and case reports. It is intended that the revised STRICTA, in conjunction with both the main CONSORT Statement and extension for nonpharmacologic treatment, will raise the quality of reporting of clinical trials of acupuncture.
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Fatigue, depression, and sleep disturbance are common adverse effects of cancer treatment and frequently co-occur. However, the possibility that inflammatory processes may underlie this constellation of symptoms has not been examined. Women (N = 103) who had recently finished primary treatment (ie, surgery, radiation, chemotherapy) for early-stage breast cancer completed self-report scales and provided blood samples for determination of plasma levels of inflammatory markers: soluble tumor necrosis factor (TNF) receptor II (sTNF-RII), interleukin-1 receptor antagonist, and C-reactive protein. Symptoms were elevated at the end of treatment; greater than 60% of participants reported clinically significant problems with fatigue and sleep, and 25% reported elevated depressive symptoms. Women treated with chemotherapy endorsed higher levels of all symptoms and also had higher plasma levels of sTNF-RII than women who did not receive chemotherapy (all P < .05). Fatigue was positively associated with sTNF-RII, particularly in the chemotherapy-treated group (P < .05). Depressive symptoms and sleep problems were correlated with fatigue but not with inflammatory markers. This study confirms high rates of behavioral symptoms in breast cancer survivors, particularly those treated with chemotherapy, and indicates a role for TNF-α signaling as a contributor to postchemotherapy fatigue. Results also suggest that fatigue, sleep disturbance, and depression may stem from distinct biologic processes in post-treatment survivors, with inflammatory signaling contributing relatively specifically to fatigue.
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Acupuncture has become a popular complementary treatment in oncology, particularly as patients seek non-pharmacological alternatives to provide symptom control. A considerable body of evidence suggests that acupuncture modulates neurological processes to bring about its effects. This basic research is supported by an increasing number of positive clinical studies of varying quality. Lower quality studies have hampered the widespread acceptability of acupuncture, with some deeming the inter-personal skills of the practitioner to be more powerful than the needle or its equivalent. More recent randomised control trials (RCTs) have sought to settle this controversy, with mixed results. The literature was searched to identify, where possible, RCTs involving acupuncture and various common cancer symptoms. A potential role for acupuncture was found in the following cancer symptoms: pain, nausea and vomiting, xerostomia, hot flushes, fatigue, anxiety, depression and insomnia. Acupuncture is safe with minimal side-effects, and is clinically effective for the management of these symptoms. Continuing research using validated methodology is essential. In the interim, health professionals should be open to explore the use of acupuncture with their cancer patients.
ABSTRACT– A self-assessment scale has been developed and found to be a reliable instrument for detecting states of depression and anxiety in the setting of an hospital medical outpatient clinic. The anxiety and depressive subscales are also valid measures of severity of the emotional disorder. It is suggested that the introduction of the scales into general hospital practice would facilitate the large task of detection and management of emotional disorder in patients under investigation and treatment in medical and surgical departments.
Breast cancer is the most commonly diagnosed cancer in women. Insomnia is a significant problem in breast cancer patients, affecting between 20% to 70% of newly diagnosed or recently treated cancer patients. Pain, fatigue, anxiety, and depression are also common conditions in breast cancer and often co-occur with insomnia in symptom clusters, exacerbating one another, and decreasing quality of life (QOL). There have been no clinical trials of drugs for sleep in cancer. Cognitive behavioral psychotherapies on the other hand, have shown some of the most positive results in alleviating the distressing symptoms that often accompany the breast cancer experience, but even these studies have not targeted the symptom cluster. Pharmacological as well as non-pharmacological treatments need to be explored. It might be that a combined pharmacological and behavioral treatment is most efficacious. In short, substantially more research is needed to fully understand and treat the symptom cluster of insomnia, fatigue, pain, depression and anxiety in breast cancer.
Many challenges remain in the evaluation of the clinical efficacy of acupuncture: for example, how to define the particular form of acupuncture used, when there are so many varieties of practice that can be called ‘acupuncture’ and how to choose the control method appropriate to that particular form of acupuncture.1 Perhaps we are still some distance from closing the gap between the rigour of a study (internal validity) and its generalisability and real-world applicability (external validity). In this issue of Acupuncture in Medicine , two reports are presented on the validity of two sham acupuncture methods. In sincere appreciation of the efforts of Takakura et al 2 3 and Tan et al ,4 in this difficult area, we would like to offer a few general points concerning the validation of acupuncture sham control and to comment on the two studies. While it is established that the two main objectives of a validation study of a sham control procedure are to test whether it is indistinguishable from the real acupuncture, and to investigate its relative inertness, how much information needs to be disclosed during the informed consent process is crucial, but has not generally been agreed. Tan et al 4 told the study participants: ‘this study will investigate whether people can tell the difference between a real acupuncture needle and a fake acupuncture needle with a blunt tip, using a small device….’ This question seems to be inviting participants to look out for a fake needle with a blunt tip, and thus raises excessive suspicions …
A growing body of literature supports the use of acupuncture in the oncology clinic for the relief of symptoms caused by cancer treatments. Several clinical trials are currently supported by the National Institutes of Health to assess the efficacy of such treatments, as evidenced by the listings in the National Institutes of Health Computer Retrieval of Information on Scientific Projects (CRISP) database. However, little is known about the mechanisms of action behind the effects of acupuncture. A biomedical database search for articles in the English-language literature revealed studies examining the effect of acupuncture on fibroblast cells, a decrease of inflammatory cytokines, an increase of T-lymphocytes, and increasing adenosine, neuropeptides, opioid peptides, peptide hormones, and stem cells. This limited review attempts to reveal some possible mechanisms of action for the effects of acupuncture for symptom relief in the oncology setting.
The aim of the present study was to scrutinize the evidence on the use of acupoint stimulation for managing therapy-related adverse events in breast cancer. A comprehensive search was conducted on eight English and Chinese databases to identify clinical trials designed to examine the efficacy of acupressure, acupuncture, or acupoint stimulation (APS) for the management of adverse events due to treatments of breast cancer. Methodological quality of the trials was assessed using a modified Jadad scale. Using pre-determined keywords, 843 possibly relevant titles were identified. Eventually 26 papers, 18 in English and eight in Chinese, satisfied the inclusion criteria and entered the quality assessment stage. The 26 articles were published between 1999 and 2008. They assessed the application of acupoint stimulation on six disparate conditions related to anticancer therapies including vasomotor syndrome, chemotherapy-induced nausea and vomiting, lymphedema, post-operation pain, aromatase inhibitors-related joint pain and leukopenia. Modalities of acupoint stimulation used included traditional acupuncture, acupressure, electroacupuncture, and the use of magnetic device on acupuncture points. Overall, 23 trials (88%) reported positive outcomes on at least one of the conditions examined. However, only nine trials (35%) were of high quality; they had a modified Jadad score of 3 or above. Three high quality trials revealed that acupoint stimulation on P6 (NeiGuang) was beneficial to chemotherapy-induced nausea and vomiting. For other adverse events, the quality of many of the trials identified was poor; no conclusive remarks can be made. Very few minor adverse events were observed, and only in five trials. APS, in particular acupressure on the P6 acupoint, appears beneficial in the management of chemotherapy-induced nausea and vomiting, especially in the acute phase. More well-designed trials using rigorous methodology are required to evaluate the effectiveness of acupoint stimulation interventions on managing other distress symptoms.
To examine the symptom cluster of fatigue, pain, anxiety, and depression and its effect on the quality of life (QOL) of women receiving chemotherapy or radiotherapy for breast cancer. Descriptive. Oncology outpatient sections of four public hospitals in Hong Kong. 215 ethnic Chinese women who were midway through treatment for breast cancer. Chinese versions of the Brief Fatigue Inventory, Hospital Anxiety and Depression Scale, Brief Pain Inventory, Functional Assessment of Chronic Illness Therapy for Breast Cancer, and Medical Outcomes Study Social Support Survey were used. Spearman rho correlation and structural equation modeling were used to examine the relationships among the study variables. Breast cancer, fatigue, pain, anxiety, depression, and QOL. Most participants reported mild-to-moderate levels of fatigue and pain. Twenty-one percent and 36% of patients might have had an anxiety or depression disorder, respectively. Significant correlations among the four symptoms supported the existence of the symptom cluster. The participants receiving chemotherapy had inadequate social support, experienced higher levels of symptoms, and were more likely to have a poorer QOL. The findings supported the existence of the symptom cluster that had detrimental effects on QOL. This study shed light on a contemporary approach of grouping several related symptoms together. The findings enhance nurses' clinical sensitivity when identifying patients in high-risk groups and provide useful information for designing and prioritizing symptom-management strategies to meet patients' needs.