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ORIGINAL ARTICLES
Acupuncture for Cancer-Related Pain:
An Open Clinical Trial
Ronald M. Glick, MD,
1–3
Mary Matsumoto, MD,
2
Xiaotian Chen, MS,
4
Yu Cheng, PhD,
1,4
Patricia Smith, LAc,
3
Judith L. Balk, MD,
5
Carol M. Greco, PhD,
1,3
and Dana H. Bovbjerg, PhD
1,6
ABSTRACT
Background: Among patients with cancer, pain is common andsignificantly impairs qualityof life. The mainstay of
treatment, opioids, can increase nausea and fatigue. Acupuncture appears to be efficacious for nonmalignant pain
states. Studies of acupuncture for cancer-related pain are mixed, with systematic reviewers calling for further studies.
Materials and Methods: Fifty-seven patients receiving treatment at a university oncology center and who had
significant pain were seen in an open treatment program. A semistructured acupuncture protocol was designed
to target pain, as well as anxiety, depression, fatigue, and nausea. Outcome measures included the Brief Pain
Inventory (BPI) as the primary outcome and Edmonton Symptom Assessment System (ESAS) ratings of current
symptoms. Patients were offered up to 12 sessions of acupuncture, typically over a 3-month period.
Results: Twenty-five patients were considered to be treatment completers, receiving 9 or more sessions of
acupuncture, and the analysis examines the response for these patients. Pain severity on the BPI decreased by
32% from baseline to the last session and pain interference decreased by 40%. Current symptoms on the ESAS
decreased by *50% for pain, nausea, and fatigue, and by 44% for anxiety. Except for nausea, these change
scores were all found to be significant on paired t-tests.
Conclusions: This semistructured acupuncture protocol appeared to be effective for reducing cancer-related
pain and other symptoms. Further study with a larger sample size, an appropriate control, and adequate follow-
up is warranted. It would also be helpful to assess pragmatic outcomes including nausea and pain medication
use and hospital admission for pain.
Key Words: Acupuncture, Cancer, Pain, Nausea, Anxiety
INTRODUCTION
Pain is a common and challenging complication of
cancer. A review from the American Cancer Society
estimates the prevalence of cancer-related pain as 30%
among patients who are newly diagnosed, 30%–50% for
patients undergoing treatment, and 70%–90% for patients
with advanced disease.
1
Other studies show similar figures
with prevalence of cancer-related pain overall *50%.
2,3
One study estimated that 51% of patients report that they are
1
Departments of
1
Psychiatry and
2
Physical Medicine and Rehabilitation, University of Pittsburgh School of Medicine, Pittsburgh, PA.
3
UPMC Center for Integrative Medicine, Shadyside, Pittsburgh, PA.
4
Department of Statistics, University of Pittsburgh School of Medicine, Pittsburgh, PA.
5
Allegheny Health Network, Temple University, Pittsburgh, PA.
6
Departments of Psychology, Behavioral and Community Health Sciences, and Clinical and Translational Science, University of
Pittsburgh School of Medicine, Pittsburgh, PA.
This study was designed as a clinical service project, supported by hospital grant funding.
This study was as an oral presentation at the 11th International Conference of the Society for Integrative Oncology, in Houston, TX,
on October 27, 2014.
MEDICAL ACUPUNCTURE
Volume 27, Number 3, 2015
#Mary Ann Liebert, Inc.
DOI: 10.1089/acu.2015.1100
188
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not receiving adequate relief of pain with current treatment.
4
Cancer pain may be somatic, visceral, or neuropathic, and
may be related to the disease itself or subsequent to chemo-
therapy, radiation, or surgery. Opioid medication, the main-
stay of treatment for significant cancer-related pain, can
worsen the nausea and fatigue that is so common among
patients receiving treatment for cancer. Despite modern ap-
proaches to cancer pain management, particularly in the case
of advanced disease, severe and persistent pain can be quite
interfering with respect to life activities, with resultant in-
creases in anxiety and impairment of quality of life (QoL).
5,6
Among the nonpharmacologic approaches to pain man-
agement, acupuncture has been studied extensively showing
benefits over placebo for nonmalignant conditions.
7
The use
of acupuncture for cancer-related pain has been less well-
studied and results have been mixed. Three systematic
reviews found wide variability in study quality with meth-
odological concerns noted, a trend for more positive results
to come from China, and no significant benefit over placebo
or sham conditions.
8–10
A Cochrane review identified three
randomized, controlled trials of acupuncture for pain caused
by cancer in adults, with only one trial found to be of high
quality, and concluded that there was insufficient evidence
to judge the efficacy of acupuncture.
11
Compared with usual care, two randomized trials found
benefit of acupuncture for pain following surgery. One
hundred and thirty-eight patients were randomized on a 2–1
basis, favoring treatment, to receive massage and acu-
puncture on the 1st and 2nd postoperative days.
12
Patients
receiving usual care had a 0.6-point reduction in their 0–10
pain ratings and the intervention group experienced a 1.4-
point drop. In another study, 58 patients who had previously
undergone head-and-neck dissection surgery were ran-
domized to acupuncture versus usual care.
13
Acupuncture
was provided over 4 weekly sessions, and assessments in-
cluded measures of pain, functioning, and xerostomia. All
measures were essentially unchanged in the control group
and improved significantly in the treatment group.
In an open case series of acupuncture for women with ad-
vanced breast or ovarian carcinoma, Dean-Clower et al. found a
63% reduction in pain severity and a 75% decrease in pain
interference, along with reductions from baseline in anxiety,
depression, and fatigue.
14
In summary, research on acupuncture
for cancer-related pain is mixed and further studies are needed.
MATERIALS AND METHODS
This study was designed as a clinical service project,
supported by a grant from the Shadyside Hospital Founda-
tion. Patients receiving treatment for cancer at a university-
based hospital and clinic, who were experiencing significant
pain, were informed about the program through their on-
cology providers and from flyers. All services were pro-
vided at the Center for Integrative Medicine at UPMC
Shadyside, or at UPMC Shadyside Hospital. This project took
place between 2011 and 2013. Quality Assurance (QA) out-
comes data were collected at baseline and through treatment.
Questionnaires were completed primarily using a tablet com-
puter, to allow direct data entry and avoid data entry errors
and missing data. Institutional review board approval was
granted to allow analysis of the QA data for research purposes.
Patients who enrolled were 18 and older, with a cancer
diagnosis, and experiencing significant pain, based on self-
reporting. They were excluded from this program if they had
risk factors for bleeding or infection, as evidenced by one of
the following: absolute neutrophil count of <1000; platelet
count of <50 K; or therapeutic doses (beyond prophylactic
doses) of an anticoagulant medication. All patients were
able to read and write English. As this was a clinical service
project, there were no specific exclusions for research pur-
poses. All patients continued to receive standard oncologic
and medical care, including pain and nausea medications
and other disease-related and symptomatic treatments.
Patients were offered 12 sessions of acupuncture, to be
spaced out over 2–4 months. While the preferred regimen
was 4 weeks of twice weekly treatment followed by 4
weekly sessions, most individuals stretched their programs
out for reasons, including difficulty with coming in for
frequent sessions, hospital admission, or personal prefer-
ence. Treatment involved a semistructured protocol with
standard points and additional points for specific symptoms.
Points were selected based on analgesia and other qualities
as described in Traditional Chinese Medicine (TCM) texts,
research articles on the treatment of cancer-related pain and
other symptoms, and clinical utility in practice. The proto-
col was designed by consensus of the 3 acupuncturists in-
volved with this program. The acupuncturists had an
average of 15 years of clinical acupuncture experience, of
whom 2 were medical acupuncturists (R.M.G. and J.L.B.)
and 1 was a TCM-trained licensed acupuncturist (P.S.).
Acupuncture was provided by the licensed acupuncturist
who had 7 years of clinical acupuncture experience.
The standard points included: bilateral auricular Shen-
men, PC 6, LI 4, ST 36, and KI 3. For patients who had no
known cardiac arrhythmias or pacemakers, electrical stim-
ulation (E-stim) at 4 Hz at a moderate intensity (below the
pain threshold), was run between needles at LI 4 (positive)
and ST 36 (negative). The Ito ES-130 3 channel electro-
stimulator, manufactured in Japan, was used. Based on
symptoms, additional points were treated as follows:
Anxiety, irritability, and agitation—GV 20, yin tang,
and bilateral auricular tranquilizer point
Depression, despair, and withdrawal—GV 20 and yin
tang, and bilateral HT-7.
For body points, Mac Ultrasmooth Spring Handle
0.22 ·25 mm needles we used; these are made in China. For
auricular points, Seirin J-type 0.16 ·15 mm needles were
used; these are manufactured in Japan. All were single-use
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stainless steel needles placed to a sufficient depth to
elicit De Qi, typically
1
⁄
2
–
3
⁄
4
†
, with auricular needles placed
to a depth sufficient to remain in place securely. For the
body needles not connected to E-stim, gentle manual clock-
wise stimulation was provided on insertion and at one later
point, to elicit De Qi. Clockwise stimulation was provided for
tonification, given the depleted status of the majority of the
patients. Typically, needles were left in place for up to 30
minutes. A maximum of 14 needles was used in any one
treatment session.
The acupuncturist had leeway to individualize treatment,
based on each patient’s circumstances or needs. This in-
cluded omitting treatment for any extremity that was in-
volved in lymphatic surgery. For anyone who was frail or
fatigued, the adjustments included the option to treat fewer
points, limit stimulation, or shorten the session to 20 min-
utes. For patients with more severe pain or whose conditions
were slow to respond, treatment was extended to 40 min-
utes. Also, at the discretion of the acupuncturist, if other
symptoms warranted treatment, modifications to the proto-
col were allowed to treat additional points.
QA measures were collected using self-report question-
naires. As the main target of this protocol was alleviation of
pain, the primary outcome measure was the Brief Pain In-
ventory (BPI)–Short Form, which is a standardized instru-
ment that has been used extensively in cancer-pain
studies.
15,16
This provides an 0–10 numerical rating, as-
sessing pain severity and interference over the prior 24
hours. In addition, current symptoms were assessed using
the Edmonton Symptom Assessment System (ESAS) for
pain and other symptoms.
17
This is also a 0–10-point rating
of symptom severity, with the patient asked to rate the de-
gree of symptoms at the current time. Specific symptoms
assessed by the ESAS included: pain; nausea; fatigue; and
anxiety. The BPI data were obtained weekly through treat-
ment and the ESAS data were obtained before and after each
acupuncture treatment. A side-effect checklist was com-
pleted before each session after the start of treatment.
In addition, patients completed an Intervention Experi-
ence questionnaire (IE), which was obtained after the sixth,
eighth, and twelfth sessions, assessing global satisfaction
and effectiveness of the treatment. Demographic data were
culled from the medical record.
Regarding data analysis, the primary outcome was the
change in scores from baseline to the last treatment session
in the BPI ratings of pain severity and pain interference. For
ESAS the current authors examined change in scores within
each session and change over time from baseline to the last
treatment session. Paired t-tests were used to assess reduc-
tion in pain and other symptoms on the BPI and ESAS. In
addition to the continuous outcome measures, the treatment
response rate was examined, with a benchmark of a 30%
reduction in pain severity or pain interference as a measure
of clinical significance. Analyses were performed using
SAS 9.3.
RESULTS
Fifty-seven patients enrolled in this program with charac-
teristics as follows: 17 (30%) were male and 40 (70%) were
female; 54 (95%) were Caucasian; 2 were African Ameri-
cans; and 1 was Asian descent. The primary organ of in-
volvement varied, but the vast majority of patients had
carcinoma, and the majority had locally invasive or meta-
static disease. The majority of patients were actively receiv-
ing chemotherapy or other treatment, but several patients
were recruited from the Cancer Survivorship Program at the
University of Pittsburgh Medical School, Pittsburgh, PA, and
were beyond any acute disease-related treatment.
Of the 57 patients, 25 completed 9 or more sessions of
acupuncture. Of the 32 patients who completed fewer than 9
sessions, 26 completed 4 or fewer sessions and their par-
ticipation was limited by the acuity of their disease and
difficulty coming for appointments. Eight patients suc-
cumbed to their diseases during the course of the program.
Two patients complained of significant pain from acu-
puncture, leading to their dropping out of treatment. The
most common complaint was mild needle-related soreness
or increase in pain. Other reported adverse effects included
nausea, fatigue, and dizziness, all of which were mild and
transient. There were no serious adverse effects reported.
The mean duration of the program for treatment completers
was 12 weeks, with a range of 6–22 weeks.
This article reports results for the 25 patients who were
considered treatment completers (Table 1). On the BPI,
Table 1. Treatment Outcomes
Instrument Baseline (SD) Last Tx (SD) % Decrease P-value
BPI—Severity 4.74 (1.9) 3.21 (1.9) 32 0.0003
BPI—Interference 4.67 (2.7) 2.82 (2.8) 40 0.0004
ESAS—Pain 4.76 (2.5) 2.33 (2.0) 51 0.0001
ESAS—Nausea 1.48 (2.1) 0.75 (1.2) 49 0.08
ESAS—Fatigue 4.72 (2.5) 1.92 (2.1) 59 0.0001
ESAS— Anxiety 2.52 (2.8) 1.42 (2.4) 44 0.04
SD, standard deviation; Tx, treatment, BPI, Brief Pain Inventory; ESAS, Edmonton Symptom Assessment System.
190 GLICK ET AL.
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mean values of pain severity decreased by 32% between the
first and last treatment (P=0.0003) and pain interference
decreased by 40% (P=0.0004). As seen with the BPI scores
and ESAS, there was a gradual reduction in pain over the 12
sessions, with the greatest response initially (Figs. 1 and 2).
Current symptom scores on the ESAS were obtained prior to
and at the end of each session. For the purposes of tracking
outcome for the full study period, the current symptom re-
port was used prior to the treatment for the first and last
sessions. Mean scores on the ESAS decreased by 51% for
pain, 49% for nausea, 59% for fatigue, and 44% for anxiety,
with all except nausea reaching significance based on the
paired t-test (Fig. 3).
Within each session, average current symptom scores on
the ESAS were reduced after the treatment by 1.5 points for
pain, 1.0 points for nausea, 1.3 points for fatigue, and 1.1
points for anxiety. Fifteen of 25 patients experienced a 30%
reduction in pain severity over the course of treatment and 9
of 25 patients had a 50% reduction. For pain interference, 16
of 25 patients had a 30% reduction and 13 of 25 had a 50%
reduction.
The IE questionnaire reflected high patient satisfaction
and perceived treatment effectiveness. At the eighth treat-
ment session, subjects rated their overall satisfaction with
treatment as 8.95 on a 0–10 scale and effectiveness at 8.4.
To examine the possibility that the individuals who did
not complete 9 or more sessions chose to drop out because
they did not see benefit from the treatment, the change in
ESAS current symptom rating was examined before and
after the first acupuncture session. The results, displayed in
Table 2, show that there was no difference in this response
between treatment completers and noncompleters.
FIG. 1. Brief Pain Inventory scores over the twelve sessions for
treatment completers.
FIG. 2. Current symptoms scores on the Edmonton Symptom
Assessment System over the twelve sessions for treatment com-
pleters. TX, treatment.
FIG. 3. Current symptoms sscores on the Edmonton Symptom
Assessment System at baseline and end of treatment. *P-value
between 0.01 and 0.05. ***P-value <0.001.
Table 2. ESAS Current Symptom Change Score
from Before to After First Acupuncture Session
Symptom %DNon-completers %DCompleters
Pain 49 51
Nausea 57 49
Fatigue 55 59
Anxiety 59 44
ESAS, Edmonton Symptom Assessment System.
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DISCUSSION
Pain is a common, multifactorial, and difficult to treat
complication of cancer and its treatment. Cancer-related
pain is often not adequately treated and may lead to im-
paired functional status and QoL.
2–6
Opioids are considered
the mainstay of cancer-pain therapy. Their use is compli-
cated by side-effects, including constipation, nausea, seda-
tion, cognitive blunting, and respiratory depression. Patients
with cancer are increasingly utilizing complementary and
alternative medicine (CAM) approaches; one study esti-
mated that 83% of patients with cancer had used at least 1
CAM modality.
18
What is cited more commonly is a prev-
alence of CAM usage off *50%.
19–22
Pain commonly leads
individuals to seek complementary therapies.
This study investigated the effect of acupuncture on
cancer-related pain as well as other symptoms, including
nausea, fatigue and anxiety. It was found that these symp-
toms were reduced over a course of treatment involving 9–
12 sessions of acupuncture. Specifically, pain severity and
interference with life activities were significantly reduced
with treatment. There was a more-modest reduction than the
trial by Dean-Clower et al.
14
This difference can be ac-
counted for by 3 factors: (1) their patients all had advanced
disease; (2) they utilized a larger number of acupuncture
points than the current study; and (3) the 12 sessions of
treatment in the Dean-Clower study were completed in 8
weeks. Regarding the latter point, a consensus panel re-
viewed factors to rate the quality of acupuncture trials.
23
While treatment frequency did not make the final cut of the
Delphi process, 59% of the expert panel stated that twice-
weekly acupuncture treatment contributes to a higher-quality
study. The extended duration of the current study, as long as
22 weeks, may have diluted the treatment effect.
The design of this project was dictated by the primary aim
of providing a clinical service. The greatest limitation of an
open trial is the lack of a control or comparison group. Given
the state of current knowledge about acupuncture for cancer-
related pain, it is appropriate to conduct open early phase
research to determine if a program is tolerated and appears to
show a clinical effect. Another weakness is that the analysis
was of treatment completers. This could bias the results to-
wards a Type 1 error, if the individuals who dropped out
were not benefiting or were dissatisfied with treatment. Ex-
cept for the 2 patients who dropped out because of pain from
the acupuncture, the current authors’ impression is that pri-
marily the withdrawals were the result of disease activity and
difficulty with coming into the office for treatment. A similar
reduction in current symptoms was found over the first
acupuncture session, between treatment noncompleters as
with completers, which refutes the idea that these individuals
had a less-robust response to the initial treatment.
An attempt was made to standardize the program to lay
the groundwork for further studies. Future research might
address the impact of acupuncture on use of pain and nausea
medications, readmission to the hospital, and other measures
of cost and QoL. Finally, the question remains if any gains from
a course of acupuncture will be maintained after treatment
ends; follow-up data are needed in a more-definitive study.
CONCLUSIONS
Acupuncture was beneficial for treatment of cancer-
related pain and associated symptoms. We met our a priori
threshold, with 60% of the patients experiencing a clinically
meaningful reduction of 30% in pain severity and interfer-
ence. Acupuncture also resulted in significant improvement
in associated symptoms. This semistructured protocol
should be studied further, with appropriate controls. If well-
designed studies support the benefit of acupuncture for
treating cancer-related pain and show cost savings, this
could make an impact on health insurance coverage and
make this service more widely available to patients.
ACKNOWLEDGMENTS
The authors appreciate the Shadyside Hospital Foundation,
UPMC Shadyside, Pittsburgh, PA, for its generous support
of this program.
DISCLOSURE STATEMENT
None of the authors have any conflicts of interest to
disclose.
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Address correspondence to:
Ronald M. Glick, MD
UPMC Center for Integrative Medicine, Shadyside
Shadyside Place
580 South Aiken Avenue, Suite 310
Pittsburgh, PA 15232
E-mail: glickrm@upmc.edu
ACUPUNCTURE FOR CANCER-RELATED PAIN 193
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