Current Oncology Reports

© Springer Science+Business Media New York 2014

10.1007/s11912-014-0418-9
Integrative Care (C Lammersfeld, Section Editor)

Acupuncture for Symptom Management in

Cancer Care: an Update
M. Kay Garcia1 , Jennifer McQuade1 , Richard Lee1 , Robin Haddad1 , Michael Spano1 and
Lorenzo Cohen1
(1)
Department of General Oncology, Integrative Medicine Program, The University of Texas
MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 0462, Houston, TX 77030,
USA

M. Kay Garcia (Corresponding author)

Email: kaygarcia@mdanderson.org

Jennifer McQuade
Email: jmcquade@mdanderson.org

Richard Lee
Email: rtlee@mdanderson.org

Robin Haddad
Email: rhaddad@mdanderson.org

Michael Spano
Email: mrspano@mdanderson.org

Lorenzo Cohen
Email: lcohen@mdanderson.org
Published online: 18 October 2014
Abstract
In a previous systematic review of the worldwide literature of randomized controlled trials
(RCTs) involving needle insertion into acupuncture points for symptom management in
cancer patients, we identified only one high-quality RCT that was deemed to have a low risk
of bias. Medline, Embase, CINAHL, Cochrane (all databases), Scopus, and PubMed were
searched from inception through December 2011 with no language limits applied. A total of
41 RCTs met all inclusion criteria and were rated. In the current review, we examined 18
trials published since our last report. The purpose of this update was to emphasize important
recent findings and discuss how concerns such as blinding, separating non-specific placebo
effects from specific needling effects, determining biologic mechanisms and dosing
parameters, evaluating determinants of response such as expectation, controlling for sources
of bias, and the lack of standardization in treatment and study methods may affect the
interpretation of study results.
Keywords
Acupuncture Cancer Integrative medicine Complementary medicine Symptom management
Pain Fatigue Peripheral neuropathy Lymphedema Hot flashes
This article is part of the Topical Collection on Integrative Care

Introduction
Determining whether acupuncture should be added to a patient’s cancer treatment plan can be
perplexing; high-quality clinical trials of acupuncture were not conducted until recently, and
the dearth of large studies with a high degree of scientific rigor has made it difficult to draw
meaningful conclusions based on evidence. Because of its complexity as an intervention,
acupuncture presents unique challenges for researchers [1]. Blinding, parsing out placebo
effects from specific needling effects, determining biologic mechanisms and dosing
parameters, evaluating determinants of response such as expectation, controlling for sources
of bias, and standardizing treatment and study methods are all key issues that can make
acupuncture studies more complex than drug trials.
In an effort to synthesize what was known about the use of acupuncture for symptom
management in cancer populations, we previously conducted a systematic review of the
worldwide literature [2••]. Medline, Embase, CINAHL, Cochrane (all databases), Scopus, and
PubMed were searched from inception through December 2011, with no language limits
applied. Risk of bias [3] was evaluated for 41 randomized, controlled trials (RCTs) that
investigated the use of acupuncture (with needle insertion) for symptom management among
cancer patients. Of those studies, only one [4] investigating acupuncture to control
chemotherapy-induced nausea and vomiting was determined to have a low risk of bias.
Although 9 of 11 RCTs evaluating acupuncture for pain control found positive benefits, none
were classified with low risk of bias owing to problems with study design or reporting
deficits. Our conclusions were that acupuncture is an appropriate adjunctive treatment for
chemotherapy-induced nausea/vomiting, but additional studies are needed, and efficacy
remains undetermined for other symptoms.
Although our past review and others [2••, 5] have found that the quality of reporting in RCTs
of acupuncture was weak, clearly, acupuncture can be beneficial as an adjunct to symptom
management for many patients [6•]. The purpose of this update was to emphasize the most
important findings from studies of acupuncture for cancer-related symptom management
conducted since our previous report [2••] and to discuss how the difficulties associated with
acupuncture research may impact the interpretation of study results. We identified 18 clinical
trials in cancer patients with new findings (since December 2011) involving seven symptoms
as follows: aromatase inhibitor-associated arthralgias, chemotherapy-induced peripheral
neuropathy, cancer-related fatigue, hot flashes, lymphedema, radiation-induced xerostomia,
and postoperative ileus (Table 1).
Table 1
Recent trials of acupuncture for symptom management in cancer patients
Author/ Primary Study Interventi Primary Results/conclusi
Limitations
year objective design on outcome ons
Aromatase inhibitor-related joint pain
Compare Semi-fixed Significant Not powered
RCT
pain (manualize reduction for pain to detect
Mao (EA vs Pain
severity d) severity in favor significant
2014 [9•, SA vs severity per
between 10 of EA vs WLCs differences
21] WLC) BPI
EA and treatments at week 8 and between EA
N = 67
WLC at the over lasting through and SA
Author/ Primary Study Interventi Primary Results/conclusi
Limitations
year objective design on outcome ons
end of 8 weeks follow-up at
treatment with 1 month
follow-up (P < 0.0001)
at 1 month
Alternating
No serious AEs
fixed
and no significant
Evaluate treatments
group
feasibility, 12 Small pilot
RCT differences;
safety, and treatments study with no
Oh 2013 (EA vs Safety and however, positive
initial over usual care
[10] SA) feasibility trends were seen
efficacy of 6 weeks comparison
N = 32 in stiffness and
EA for AI with group
physical function
arthralgia follow-up
in favor of EA at
at
week 12
1.5 months
Significant
Compare Fixed group
RA with 8 Differences imbalances in
SA for RCT treatments in change baseline HAQ-
No significant
Bao 2013 AIMSS and (RA vs over scores of DI scores
differences
[11, 33] explore SA) 8 weeks HAQ-DI (P = 0.047)
between groups
potential N = 47 with and VAS and no usual
mechanism follow-up pain rating care
s at 1 month comparison
group
Chemotherapy-induced peripheral neuropathy
No serious AEs
reported;
Examine Fixed
significant Single-arm
safety, 10 sessions
Single- improvement in pilot study
feasibility, over
Bao 2014 arm pilot Safety and mean with small
and initial 10 weeks
[13] study feasibility FACT/GOG-Ntx sample size
efficacy of with
N = 27 scores at weeks and no long-
RA in follow-up
10 and 14 term follow-up
CIPN at 1 month
(P < 0.0001 for
both)
No serious AEs
Fixed reported;
Examine
20 significant Single-arm
safety,
Single- treatments improvement in pilot study
feasibility,
Garcia arm pilot over Safety and mean with small
and initial
2014 [14] study 9 weeks feasibility FACT/GOG-Ntx sample size
efficacy of
N = 19 with scores at 1 month and no long-
EA in
follow-up follow-up term follow-up
BIPN
at 1 month (P = 0.0002);
moderate effect
Author/ Primary Study Interventi Primary Results/conclusi
Limitations
year objective design on outcome ons
size seen on week
4 with the largest
at week 9
(Cohen’s
d = 1.43)
Short
Change in
Fixed treatment
Compare RCT severity of
9 sessions period; sample
multiple (EA vs neuropathic
over No significant size
Rostock modalities HB vs symptoms
3 weeks differences calculations
2013 [15] for VitB vs from day 0
with between groups based on
treatment PC) to day 21
follow-up patients with
of CIPN N = 60 (per 0–10
at 9 weeks more severe
NRS)
CIPN
Fatigue
Pragmatic
Compare design
RA with Semi-fixed Mean general (without
enhanced RCT (pragmatic fatigue score blinding) that
Molassiot usual care (RA vs ) General difference does not allow
is 2012 (fatigue UC + 6 fatigue per between groups evaluation of
[18] information booklet) treatments the MFI was significant in specific effects
booklet) in N = 246 over favor of RA of acupuncture
a pragmatic 6 weeks (P < 0.001) needling; no
design long-term
follow-up
No significant
RCT
Fixed with differences
(RA
self- between groups;
with
Assess needling; however, a non- Unable to
self-
maintenanc semi-fixed significant trend determine
Molassiot needling General
e of RA by in CRF treatment
is 2013 vs RA fatigue per
with self- therapist improvement was compliance in
[19] by the MFI
needling 4 seen at the end of self-needling
therapist
for CRF treatments 4 weeks in the group
vs no
over combined
RA)
4 weeks acupuncture
N = 197
groups (P = 0.07)
Fixed Limited by
Compare 6 number of
RA with RCT treatments patients lost to
No significant
Deng SA for (RA vs over Changes in follow-up;
differences
2013 [20] post-chemo SA) 6 weeks BFI scores short treatment
between groups
chronic N = 74 with period; no
fatigue follow-up usual care
at 1 week comparison;
Author/ Primary Study Interventi Primary Results/conclusi
Limitations
year objective design on outcome ons
no long-term
follow-up
Baseline pain
Evaluate interference was
Semi-fixed
EA for associated with
(manualize
fatigue, fatigue The study was
d)
sleep, and RCT (Pearson’s not powered to
10
Mao psychologic (EA vs r = 0.75; detect
treatments BPI
2014 [9•, al distress SA vs P < 0.001), and significant
over BFI
21] in breast WLC) significant differences
8 weeks
cancer N = 67 improvement in between EA
with
survivors fatigue was seen and SA
follow-up
with AI in favor of EA vs
at 1 month
arthralgia WLCs
(P = 0.0095)
Determine
feasibility Feasibility
Pilot study
and criteria were met
RCT Semi-fixed with small
acceptabilit with significant
(RA vs 6 Feasibility sample size,
Smith y of RA for improvement in
SA vs treatments and initial short treatment
2013 [22] CRF and CRF in favor of
WLC) over efficacy period, and no
well-being RA vs controls at
N = 30 8 weeks long-term
in breast 6 weeks
follow-up
cancer (P = 0.05)
survivors
Hot flashes
16 patients
(52 %) of RA
Fixed group had
Primary
5 significant
Determine outcome based
RCT treatments reduction in HF
the effect of on subjective
(RA vs over distress compared
Bokmand RA on HF patient report
SA vs 5 weeks HF distress with seven
2013 [30] in breast of HF distress
WLC) with patients (24 %) in
cancer per logbook;
N = 94 follow-up the sham group
patients HF frequency
at (P < 0.05), which
not reported
3 months lasted through the
3 month follow-
up visit
Assess if Fixed Both RA and SA The study was
RA 8 were associated not powered to
RCT
improves treatments NSABP with detect
Bao 2013 (RA vs
PROs in over HFRDI improvement in differences
[11, 33] SA)
breast 8 weeks HFDD HF but no between RA
N = 47
cancer with significant and SA in
patients follow-up differences were improving
Author/ Primary Study Interventi Primary Results/conclusi
Limitations
year objective design on outcome ons
taking an at 1 month found between PROs like HF.
adjuvant AI groups. Racial Also, the
differences in points used
response warrant were designed
further study to treat
AIMSS,
although many
overlap with
points used for
HF
Lymphedema
Mean reduction
in arm
circumference
difference was
Mean
Fixed significant from
reduction in
Evaluate 8 baseline to end of
arm
the safety treatments treatment (P 
Single- circumferen Small pilot
and over < 0.0005), and 11
Cassileth arm pilot ce study with no
potential 4 weeks patients (33 %)
2013 [34] study difference comparison
efficacy of with had a reduction
N = 33 between group
acupunctur follow-up ≥30 %. No
affected and
e for BCRL at serious adverse
unaffected
6 months events,
arms
infections, or
severe
exacerbations
were reported
Xerostomia
Determine
feasibility
of
conducting Fixed Significant
a sham- 18 improvement in
Feasibility
controlled RCT treatments XQ XQ scores were
study with
Meng trial of (RA vs over MDASI-HN found in favor of
small sample
2012 [35] acupunctur SA) 6 weeks USFR RA (P < 0.001).
and no long-
e for N = 23 with SSFR No significant
term follow-up
prevention follow-up changes in saliva
of at 1 month flow were found
radiation-
induced
xerostomia
Evaluate CT (RA Fixed Dry mouth Improved Non-
Braga
effectivenes vs NA) 16–20 symptoms salivary flow randomized,
2012 [36]
s of RA in N = 24 treatments per VAS rates in favor of unblinded
Author/ Primary Study Interventi Primary Results/conclusi
Limitations
year objective design on outcome ons
minimizing over 8– (0–10) RA (P < 0.001) convenience
severity of 10 weeks USFR and decreased sample
radiation- SSFR xerostomia-
induced related symptoms
xerostomia (P < 0.05)
Significant
reductions in
favor of RA were
reported for
severe dry mouth
Fixed
(P = 0.031) sticky
Examine RCT 8 sessions
saliva Follow-up data
the efficacy (crossov over QLQC30
(P = 0.048), at 6 months
Simcock of RA for er of RA 8 weeks H&N-35
needing to sip were available
2013 [37] radiation- vs oral with USFR
fluids to swallow for only 68
induced care) follow-up SSFR
food (P = 0.011), participants
xerostomia N = 144 at
and in waking up
6 months
at night to drink
(P = 0.013). No
significant
changes in saliva
flow were found
Prolonged postoperative ileus
Sample size
and power
may not be
adequate to
detect
Significant
Determine differences in
reductions were
efficacy of all parameters
found in favor of
EA in measured
EA over NA and
reducing Time to between the
SA for duration
postoperati RCT defecate EA and SA;
Fixed of postoperative
ve ileus and (EA vs Time to duration of
Ng 2013 4 ileus (P < 0.001
hospital SA vs ambulate hospital stay
[39•] treatments and P = 0.007,
stay after NA) Length of may have been
over 4 days respectively).
laparoscopi N = 165 hospital affected by
Length of
c surgery stay psychosocial
hospital stay was
for issues instead
also shorter for
colorectal of
EA than NA
cancer symptomatolo
(P = 0.007)
gy; study
population
represented a
select group of
patients
Author/ Primary Study Interventi Primary Results/conclusi
Limitations
year objective design on outcome ons
After
uncomplicated
elective
laparoscopic
resection of
colonic and
upper rectal
cancer
EA electro-acupuncture, WLC wait list control group, RCT randomized controlled trial, SA
sham acupuncture, BPI Brief Pain Inventory, AI aromatase inhibitors, AEs adverse events,
AIMSS aromatase inhibitor-related musculoskeletal symptoms, RA real acupuncture (also
called true, active, or verum acupuncture), HAQ-DI Health Assessment Questionnaire
Disability Index, VAS visual analog score, CIPN chemotherapy-induced peripheral
neuropathy, HB hydroelectric baths, VitB vitamin B1/B6 capsules (300/300 mg daily), PC
placebo capsules, NRS numeric rating scale, BIPN bortezomib-induced peripheral
neuropathy, FACT/GOG-Ntx Functional Assessment of Cancer Therapy/Gynecologic
Oncology Group–Neurotoxicity questionnaire, UC usual care, MFI Multidimensional Fatigue
Inventory, CRF cancer-related fatigue, BFI Brief Fatigue Inventory, HF hot flashes, PROs
patient-reported outcomes, NSABP National Surgical Adjuvant Breast and Bowel Project
menopausal symptoms questionnaire, HFRDI Hot Flash-Related Daily Interference Scale,
HFDD hot flash daily diary, BCRL breast cancer-related lymphedema, CT controlled trial
(i.e., not randomized), USFR unstimulated saliva flow rate, SSFR stimulated saliva flow rate,
QLQC30 European Organisation for Research and Treatment of Cancer Quality of Life
Questionnaire, H&N-35 head and neck subscale, XQ Xerostomia Questionnaire, MDASI-HN
MD Anderson Symptom Inventory-Head and Neck, NA no acupuncture

Aromatase Inhibitor-Associated Joint Pain

Joint pain is a frequent side effect of the aromatase inhibitors (AIs) used to treat hormone
receptor-positive breast cancer patients. Nearly half of AI users report arthralgias, and up to
15 % of patients discontinue AIs because of this side effect [7, 8]. Three trials were published
in the past year examining the effect of acupuncture on AI-associated joint pain. One [9•]
reported a positive impact on pain reduction from acupuncture compared to wait list controls
(primary aim) but no significant differences compared to sham acupuncture (secondary aim).
Two other smaller trials [10, 11] found no significant differences between real and sham
acupuncture for treating AI-related joint pain.
In the largest trial to date of acupuncture in AI-related joint pain [9•], Mao and colleagues
randomized 67 patients with stages I–III breast cancer who were receiving an AI and reported
having had AI-associated joint pain for at least 3 months to receive electro-acupuncture (EA),
sham acupuncture (SA), or be placed in the wait list control (WLC) group. The trial design
was informed by a prior feasibility trial [12]. Patients in the EA arm received low-frequency
electrical stimulation to the needles for 30 min twice weekly for 2 weeks and then weekly for
6 more weeks, with acupuncture points based on a manualized protocol adapted for the
patient’s most painful joint and constitutional symptoms. SA was performed using
Streitberger placebo needles, which, like stage daggers, are designed to touch the skin and
then retract into the handle. The study reported a greater reduction in pain severity in the EA
group than in the WLC group at week 8 (−2.2 vs 0.2, P = 0.0004) and week 12 (−2.4 vs −0.2,
P  < 0.0001) and concluded that EA is both effective and durable at reducing AI joint pain (as
effects were sustained 4 weeks after completion of therapy). Also, Brief Pain Inventory (BPI)
interference scores decreased more in the EA group than in the WLC group at week 8 (−2.0
vs 0.2, P = 0.0006) and week 12 (−2.1 vs −0.1, P  = 0.0034). Additionally, 57.1 % of patients
in the EA group reported that their arthralgia was “much improved” or “very much improved”
compared with 4.6 % of WLC group patients (P  < 0.001). The SA group showed a
statistically significantly greater decrease in BPI severity compared with the WLC group at
both week 8 (−2.3, P < 0.001) and week 12 (−1.7, P = 0.0036), but significant differences
between the EA and SA groups were not found.
In a smaller trial, which closed early due to futility [11], Bao and colleagues reported on 47
breast cancer patients with AI-related joint pain who were randomized to real acupuncture
(RA) vs SA. This trial reported no significant differences in the reduction of Health
Assessment Disability Index (HAQ-DI) or pain visual analog scores between the two groups.
Interestingly, 58 % of patients in the SA group and 35 % of patients in the RA group reached
a minimally clinically important change in HAQ-DI score (greater than 0.22-unit reduction),
but limitations of this trial mentioned by the authors included significant imbalances in the
baseline HAQ-DI scores (median 1.12 in RA group vs 0.62 in SA group, P =  0.047) and the
lack of a standard of care comparison group. The study also included exploratory examination
of the effect of acupuncture on serum hormones and pro-inflammatory cytokines that may
play a role in AI joint pain and found significant reductions in interleukin-17 concentrations
compared to baseline in both groups.

Chemotherapy-Induced Peripheral Neuropathy

Three recent studies [13–15] evaluating the use of acupuncture for the management of
chemotherapy-induced peripheral neuropathy (CIPN) deserve mentioning. In two trials [13,
14], acupuncture was used to treat bortezomib-induced peripheral neuropathy in patients with
multiple myeloma. One study [13] used manual stimulation of the needles, while the other
[14] applied electro-stimulation to needles inserted into the acupuncture points. Although both
were single-arm pilot studies (N = 27 and N  = 19 patients, respectively), similar results were
seen in terms of symptom improvement. Participants in both trials reported a reduction in pain
as well as in numbness and tingling, with minimal changes in nerve conduction. Garcia and
colleagues [14] found the greatest improvement occurred after the first month of treatment
(i.e., after 12 sessions). In the third study, Rostock and colleagues [15] also applied electrical
stimulation to the needles in a randomized trial, but they did not find statistically significant
differences between groups and concluded that the effect of acupuncture in chemotherapy-
induced peripheral neuropathy remains unclear. Large randomized trials with long-term
follow-up that are adequately powered to detect group differences are needed.

Fatigue

Two reviews published in 2013 [16, 17] reported that deficits in the quality and quantity of
trials evaluating acupuncture for cancer-related fatigue makes it difficult to draw meaningful
conclusions. Several recent studies [18–22], however, should be mentioned. In 2012, a
pragmatic RCT conducted by Molassiotis and colleagues [18] compared usual care plus
acupuncture (N = 227) to usual care alone (N  = 75) in breast cancer patients with cancer-
related fatigue. All patients also received an information booklet about fatigue. At 6 weeks,
the difference in the general fatigue mean score (per the Multidimensional Fatigue Inventory)
between those who received acupuncture vs those who did not was −3.11 (95 % CI −3.97 to
−2.25; P < 0.001). Improvement was also seen for both physical and mental aspects of fatigue
(−2.36 and −1.94, respectively; both at P < 0.001). Participants were then re-randomized in a
second trial [19] to receive four weekly sessions delivered by an acupuncturist (N = 67), four
self-administered weekly acupuncture sessions (N = 67), or no acupuncture (N  = 65). A non-
significant trend toward further improvement in fatigue was seen at the end of the additional
4 weeks in the combined acupuncture arms (P = 0.07), but no differences were found between
self-administered and therapist-delivered treatment.
A randomized, blinded, sham-controlled trial conducted by Deng and colleagues [20] did not
find true acupuncture to be more effective than SA for reducing post-chemotherapy chronic
fatigue in a general oncology population. However, the Mao RCT of acupuncture for AI-
related joint pain [9•] also found [21] EA significantly improved fatigue (P = 0.0095) and
depression (P = 0.015) compared to WLCs in breast cancer survivors taking AIs and reported
SA did not result in significant reductions in fatigue but did improve depression compared to
the wait list group (P = 0.0088).

Hot Flashes and Sleep Disturbance

Although large RCTs with long-term follow-up are needed to confirm findings, a recent
systematic review [23] of acupuncture for vasomotor symptoms found positive benefits
lasting at least 3 months after the end of treatment for both breast cancer and prostate cancer
patients. Based on analysis of six identified studies (N = 172) [24–29], the average reduction
of hot flashes from baseline to the end of acupuncture treatment (range 5 to 12 weeks of
treatment) was 43.2 %. At follow-up (mean 5.8 months; range 3–9 months after the end of
treatment), the weighted reduction of hot flashes from baseline was 45.6 % in 89 % of
patients.
Additionally, in a double-blinded (patient and investigator) RCT in breast cancer patients,
Bokmand and colleagues [30] reported 52 % of patients in the acupuncture treatment group
experienced a significant reduction in hot flashes compared with 24 % of patients in the sham
group (N = 23; P  < 0.05). This effect was seen after two treatments and lasted through
12 weeks of follow-up. A positive effect was also reported in the acupuncture vs sham group
for sleep disturbance (P < 0.03), a finding consistent with studies in non-cancer populations
[31, 32]. Bao and colleagues also reported a positive effect of acupuncture on hot flashes
(secondary outcome) in breast cancer patients with AI-related joint pain [11, 33]. As
mentioned previously, although the trial was stopped early due to futility for the primary
measures, hot flash severity and frequency improved significantly from baseline in the active
treatment arm (N = 47; P = 0.006 and P  = 0.011, respectively), an effect not found in the SA
group. Interestingly, the authors reported that African American patients benefited more from
RA than SA compared with non-African American participants in the reduction of hot flash
severity (P < 0.001) and frequency (P < 0.001).

Lymphedema

In 2013, Cassileth and colleagues [34] reported the results from a single-arm pilot study (N 
= 37) that evaluated the safety and initial efficacy of acupuncture for the treatment of upper
limb lymphedema in breast cancer patients. Women diagnosed with breast cancer-related
lymphedema 6 months to 5 years previously who had an affected arm circumference ≥2 cm
larger than the unaffected arm circumference were evaluated before and after acupuncture
sessions given twice weekly for 4 weeks. Response was defined as a ≥30 % reduction in
circumference difference between the affected and unaffected arms. Monthly follow-up was
performed for 6 months after treatment ended. The mean reduction in arm circumference
difference was 0.90 cm (95 % CI 0.72–1.07; P  < 0.0005). Eleven patients (33 %) had a
reduction of ≥30 %. No serious adverse events were noted, including infections or
exacerbations of lymphedema, after 255 treatments and 6 months of follow-up interviews.
The authors concluded that acupuncture appears to be safe and may reduce arm circumference
in this population, an important finding for women who have no other treatment options,
although further research is needed before formal clinical recommendations can be made.

Radiation-Induced Xerostomia

Three recent studies investigating the use of acupuncture for radiation-induced xerostomia
deserve mention [35–37]. In addition to our own previous findings in favor of acupuncture
over usual care for the prevention of radiation-induced xerostomia [38], Braga and colleagues
[36] reported positive findings in a small prevention trial (N = 24). In their study, patients who
received acupuncture had higher unstimulated and stimulated salivary flow rates (P < 0.001
for both) and less severe xerostomia-related symptoms (per visual analog scale, P  < 0.05)
than that in patients who received no acupuncture, although the authors reported that
acupuncture treatment did not completely prevent xerostomia from occurring in most patients.
After our earlier positive findings [38] in favor of acupuncture vs usual care for the prevention
of radiation-induced xerostomia, we also reported results from a small sham-controlled trial
(RA vs SA; N = 23) [35] in which patients received treatment three times per week during
their full course (6–7 weeks) of radiotherapy and were followed for 1 month after treatment
ended. Patient-reported xerostomia symptom scores were significantly lower in the RA group
than in the SA group at week 3 of radiotherapy and at the 1-month follow-up visit (P < 0.006
and P < 0.001, respectively). Group differences in saliva flow rates were not significant in this
study.
A randomized, multicenter trial of acupuncture vs oral care for radiation-induced xerostomia
conducted by Simcock and colleagues [37] found eight sessions of weekly group acupuncture
provided significantly greater relief of symptoms from radiation-induced xerostomia than
group oral care education. The study involved 145 patients with chronic radiation-induced
xerostomia who were recruited from seven cancer centers in the UK. A randomized crossover
design was utilized with participants receiving two group sessions of oral care education and
eight acupuncture treatments. As compared with oral care education, acupuncture produced
significant reductions in severity of symptoms as follows: dry mouth (OR = 2.01, P = 0.031),
sticky saliva (OR = 1.67, P = 0.048), needing to sip fluids to swallow food (OR = 2.08,
P = 0.011), and waking up at night to drink (OR = 1.71, P = 0.013). There were no significant
differences in saliva flow rates.

Ileus

Ng and colleagues [39•] found that EA reduced the duration of postoperative ileus after
laparoscopic surgery for colorectal cancer in a sham-controlled trial (N  = 165). Patients were
randomized to receive EA, SA, or no acupuncture. Treatments were given daily starting on
postoperative day 1 and ending on postoperative day 4. Patients who received EA had a
shorter time to defecate than that of patients who received no acupuncture (85.9 ± 36.1 vs
122.1 ± 53.5 h; P < 0.001) as well as a shorter hospital stay (6.5 ± 2.2 vs 8.5 ± 4.8 days; P 
= 0.007). In multiple linear regression analysis, an absence of complications and EA were
associated with a shorter duration of postoperative ileus and hospital stay after surgery.
Patients who received EA also had a shorter time to defecate than that of patients who
received SA (85.9 ± 36.1 vs 107.5 ± 46.2 h; P  = 0.007), and EA was more effective than no
acupuncture or SA in reducing postoperative analgesic requirements and time to ambulate.
Discussion
In the current review, we found 18 acupuncture clinical trials in cancer patients with new
findings (since December 2011) that involve seven symptoms (AI-associated arthralgias,
CIPN, cancer-related fatigue, hot flashes, lymphedema, radiation-induced xerostomia, and
postoperative ileus). Small sample sizes, lack of appropriate comparison groups, and lack of
statistical power were common problems, but the seemingly conflicting conclusions are also
indicative of the many difficulties inherent in designing a rigorous acupuncture study with
adequate controls and treatment methods.
For example, the three trials on acupuncture for AI joint pain highlight the ongoing
controversy over what constitutes an appropriate comparator in trials of acupuncture (i.e.,
usual care controlled vs sham controlled). Bao et al. and Oh et al. [10, 11] both utilized a
sham-controlled design and found no significant differences between groups, but both noted
significant improvements in pain scores over baseline within groups, even though the Oh trial
was a feasibility study and not powered to detect between group differences. The Mao trial
[9•] similarly did not find a statistically significant difference between EA and SA (a
secondary aim that the trial was not powered to detect) but did find clinically meaningful
reductions in pain score when comparing EA to the WLC group. These findings are in line
with a large individual patient-level data meta-analysis of 29 trials involving 14,597 patients
with non-malignant chronic pain treated with acupuncture published by Vickers and the
Acupuncture Trialists’ Collaboration in 2012 [6•] which found significantly better pain
control with RA as compared to no acupuncture (50 vs 30 %, P < 0.001) as well as RA
compared to SA, though to a lesser degree (50 vs 42.5 %, P < 0.001).
There are two possible explanations for the finding that SA is of intermediate utility in the
treatment of pain, with slightly reduced benefit compared to RA but greater benefit compared
to usual care. First, the SA technique may not be a truly inert placebo and could activate the
endogenous opioid system and local inflammatory and immune responses as RA has been
shown to do. Second, most of the positive analgesic effects associated with acupuncture
treatment may be due to non-specific factors, such as conditioning, expectations, self-
empowerment effects, and placebo effects. In a placebo-controlled drug trial, the placebo
treatment must be both physiologically inert and indistinguishable from the active medication.
In a placebo-controlled acupuncture trial, however, sham comparators are less physiologically
active than the real treatment but may not be inert and may be distinguishable to participants
who have received previous acupuncture. Although placebo needle devices have made patient
blinding easier to achieve, one cannot obtain the same level of blinding assurance as in a drug
trial. Therefore, the same effect size difference between sham and active acupuncture should
not be expected to equal the effect size difference between a placebo pill and an active drug.
In acupuncture trials, sham comparators may increase bias against the active treatment and
lead to false-negative findings [18]. Interestingly, no known studies in cancer patients have
reported a sham acupuncture treatment that was more effective than an active acupuncture
treatment; yet, one would expect an equal proportion of studies to report such a finding if
there was no specific biologic effect above and beyond placebo caused by needling.
Other potential sources of bias are common to acupuncture trials that are not issues in drug
trials. For example, in a drug study, the provider can be blinded as to group assignment, but in
an acupuncture study, although patients and assessors can be blinded, the individual who
provides the treatment cannot. Kaptchuk and colleagues [40] found that the patient-
practitioner relationship is the most robust component of a placebo effect. Therefore, studies
where a single acupuncturist provides all treatments to both active and inactive groups may
unintentionally introduce a high degree of bias. Although feasibility issues may dictate the
necessity of a single provider, study methods and proper training of participating
acupuncturists must be incorporated to control for this possibility.
Further research is needed to untangle the mechanisms of action for the various forms of
acupuncture (i.e., active, sham, and electro-acupuncture) and to parse-out the multiple
components of dosing, such as number of needles used, needle size and level of insertion,
intensity and type of needle stimulation, retention time, and frequency of treatments.
Equivocal findings from studies published to date are not surprising considering the
heterogeneity in treatment approaches and study methods common to acupuncture trials.
Although studies with pragmatic designs are becoming more common in an attempt to
evaluate benefits of acupuncture as delivered in actual clinical practice, such designs are
difficult to replicate, cannot identify specific effects of needling, and are limited in the type of
research questions that can be addressed. A major shortcoming in acupuncture research is the
continued lack of understanding about the potential relationship between defined syndromes
(i.e., symptom clusters) within Traditional Chinese Medicine and disease. The distribution of
TCM syndromes within different types of cancer is unknown, and having a better
understanding of the basic epidemiology involved could make an important contribution
toward improving patient outcomes after acupuncture treatment.
The use of acupuncture as an adjunct for symptom control in oncology patients is important to
consider. Findings from multiple reviews [2••, 41] indicate it is an appropriate referral option
for chemotherapy-induced nausea and vomiting. Although additional studies are needed to
better understand how it works and which patients might benefit most. For other symptoms,
the specific effects of acupuncture remain undetermined primarily because of weaknesses in
research methods or reporting deficits. As a low-risk, cost-effective treatment option,
however, may be helpful when combined with conventional care for patients suffering from
uncontrolled treatment-related side-effects or in those for whom other treatment approaches
have failed.
Compliance with Ethics Guidelines
Conflict of Interest
M. Kay Garcia, Jennifer McQuade, Richard Lee, Robin Haddad, Michael Spano, and Lorenzo
Cohen declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of
the authors.
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