NEWS & VIEWS

News & Views Editor Mary Desmond Pinkowish

Acupressure and Acupuncture for Side Effects of Radiotherapy

“Many symptoms of cancer patients, including pain, nausea, treatment than the control group that did not receive the
and dry mouth, are significantly different in an objective sense educational intervention (J Pain Symptom Manage. 2008;35:
than in a subjective sense,” says Peter Johnstone, MD, Wil- 381–387).
liam A. Mitchell Professor and chair of Radiation Oncology
at the Indiana University School of Medicine. “We have The investigators’ explanation of these results was that either
evidence now proving that a disconnect often exists between the expectation of nausea is not truly related to its subsequent
a patient’s reported symptoms and objective evidence of those occurrence and perception, or that the intervention’s effect on
symptoms,” says Dr. Johnstone, who is also past president of expectation was not strong enough to influence subsequent
the Society for Integrative Oncology. He made his comments nausea. In the second study, patients who were about to start
in response to 2 recent studies regarding the effects of acu- chemotherapy were randomized to receive an acupressure
pressure/acupuncture on nausea and xerostomia (dry mouth) band or an acustimulation band, both of which stimulated the
in patients receiving radiotherapy for cancer. P6 point on the inner wrist, an acupuncture point that has
been reported to be associated with nausea relief. A control
Nausea is a common problem for patients undergoing group received no intervention. Among the patients in this
cancer therapy. Several lines of research have documented study, those who used acupressure bands and who reported
that expectation of nausea before the administration of that they expected them to be effective were found to have
chemotherapeutic drugs influences the development of significantly less nausea than people with acupressure bands
nausea during and after treatment. A group of investiga- who did not expect them to be effective, patients who re-
tors based at the James P. Wilmot Cancer Center recently ceived acustimulation bands, and patients who received no
set out to determine whether acupressure bands, which bands, suggesting that expectation was 1 factor that played a
previously were shown to reduce chemotherapy-related strong role in determining efficacy (J Pain Symptom Manage.
nausea, also reduce radiation-induced nausea (J Pain 2003;26:731–742).
Symptom Manage. 2009 March 27. [Epub ahead of print]).
They also tested the hypothesis that an informational Patients were eligible for the current study if they had re-
manipulation designed to enhance expectations regarding ceived a minimum of 2 radiation treatments and had expe-
the efficacy of acupressure bands would, in fact, enhance rienced nausea/vomiting (NV) after at least 1 radiation ses-
the efficacy of the bands. sion. Patients were asked to wear the acupressure band (Sea–
Bands; Sea–Band Ltd, Hinckley, Leicestershire, UK) for 1
This group of investigators previously conducted 2 similar minute. Investigators explained that 2 things were being
studies. In the first study, patients starting chemotherapy investigated: the efficacy of the bands and the way in which
received educational ma- information about the bands was delivered to patients. After
terial designed to dispel wearing the bands for 1 minute, patients took them off and
common misconceptions completed a quality-of-life (QOL) measure and a question-
regarding chemotherapy- naire that included questions related to expected efficacy.
induced nausea. The in- Patients did not take the acupressure bands home, but they
tervention was successful were given a take-home diary in which to record NV after
in reducing the expecta- their next 2 radiation treatments; this served as a baseline
tion of nausea in the pa- measure of NV. Study subjects were unaware of the study’s
In 1 study, patients who used acupres- tients randomized to re- primary hypothesis that expectations would influence percep-
sure bands and who reported that they ceive the educational tions of efficacy.
expected them to be effective had sig-
nificantly less nausea than people with materials, but these pa-
acupressure bands who did not expect tients did not appear to When patients returned the diary of baseline NV symp-
them to be effective.
Credit: Psi Bands have less nausea during toms, they were randomized to 1 of 3 groups:

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• Arm 1: Standard care. compared with a 4.8% decrease in the control group
• Arm 2: Standard care plus acupressure bands plus in- (P ⫽ .01). However, there were no differences noted be-
formation regarding the bands that was not intended to tween patients using bands and those not using the bands
enhance expectations about the efficacy of the bands. with regard to change scores of QOL (P ⫽ .93), changes
Patients were informed about the investigators’ prior in the daily amount of antiemetic medication used
acupressure/acustimulation study, with the explanation (P ⫽ .78), or changes in the occurrence of vomiting
that although patients who used the acupressure/ (P ⫽ .17). Nonetheless, satisfaction with the bands was
acustimulation bands experienced less nausea than pa- high, with most patients reporting that they would rec-
tients who did not get the bands, the difference “was ommend the bands to others undergoing radiotherapy.
probably due only to a placebo effect.” Visual material
was printed on a gray scale. The investigators did not find a difference in expected
• Arm 3: Standard of care plus acupressure bands plus band efficacy between Arms 2 and 3 (P ⫽ .56). One ex-
information regarding the bands that was intended to planation they suggested is that information that the in-
enhance expectations about the efficacy of the bands. vestigators believed was neutral was actually perceived by
Patients were presented with the results of both prior the patients as positive. In particular, patients may not
studies printed in full color, with an emphasis on pos- have recognized that calling the effect of the acupressure
itive results regarding the efficacy of acupressure for bands “just a placebo response” was dismissive and nega-
nausea induced by chemotherapy. For example, they tive. In a follow-up study, Joseph A. Roscoe, PhD, re-
were told “Only 3 patients wearing Sea–Bands had search associate professor in the Department of Radiation
nausea compared to 15 patients not wearing Sea– Oncology at the University of Rochester Medical Center
Bands” and “Patients wearing Sea–Bands had less se- and the other investigators plan to simply thank patients in
vere nausea on the day they received their chemother- Arm 2 for their participation rather than attempting to
apy than patients not wearing Sea–Bands.” present them with neutral educational information. “We
think the difference [between neutral and positive infor-
The patients in Arms 2 and 3 were instructed to wear 1 or mation] in this context is just too subtle,” he says.
both bands at their discretion over the next 5 days, during
which time they received 5 radiation treatments. Anti- Among the 59 patients who used bands, the expected
emetic medications and other treatments for NV were efficacy was not found to be correlated with the change in
permitted for patients in all 3 arms and were not standard- nausea (P ⫽ .61) or vomiting (P ⫽ .56). “It is possible, ”
ized. Patients continued to record NV in a 5-day diary and the investigators wrote, “that the acupressure bands were
completed a QOL questionnaire before going to bed after effective in our study for reasons not related to
the fifth treatment. expectancy…that the acupressure bands are indeed effica-
cious, as suggested by a growing body of literature showing
NV were assessed with a patient report diary, in which that stimulation of acupuncture points can indeed reduce
patients reported on the severity and number of episodes of nausea. It has, after all, been a staple of Chinese medicine
NV in the morning, afternoon, evening, and night of each for centuries. While our data support this interpretation,
radiation treatment. Investigators also assessed the amount of we are reluctant to accept it at face value because of other
antiemetic medication taken by each patient. Each patient’s reports in the literature, including our own, linking the
expectation of nausea was assessed by a questionnaire. QOL efficacy of acupressure bands to expectancy/placebo ef-
was measured with the Functional Assessment of Cancer fects.”
Therapy Scale–General (FACT–G), a well-characterized
and validated, 28-item scale. The investigators planned to “It appears that the acupressure bands are helpful in many
determine the change in average nausea between baseline and patients, but not everyone,” says Dr. Roscoe. He noted
after treatment using analysis of variance. A total of 99 that once nausea is established in patients, as it was in this
patients were randomized, and 88 (89%) provided usable group, it is hard to remedy it. “But that’s what happened
data. The baseline differences in nausea between the 3 treat- here—established nausea was improved. It is preferable to
ment arms were significant and required the use of change prevent nausea in the first place,” he added.
scores in all subsequent analyses.
“Some antinausea medications are very expensive, so a low-
Patients who used the bands (Arms 2 and 3 combined) cost intervention like acupressure bands would be great for
had a 23.8% reduction in the self-reported nausea score patients who need nausea relief,” Dr. Johnstone says. The only

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caveat, says Dr. Roscoe, is that patients with lymphedema before the acupuncture intervention and then repeated at
should be careful not to use the band on the affected arm. Weeks 1, 2, 3, 4, 5, and 8.

Xerostomia occurs as both a chronic and acute complication In these patients, the XI and PBQ scores were found to be
of radiation administered in the treatment of head and neck significantly improved by acupuncture at Weeks 4 and 8
cancer. In addition to mouth pain and difficulty speaking compared with baseline (XI: P ⫽ 0004 and P ⫽ .0001,
resulting from xerostomia, alterations in taste and difficulty respectively; and PBQ: P ⫽ .0004 and P ⫽ .0011, respec-
swallowing can compromise nutritional status, and changes tively). The FACT–H&N total scores were found to be
in the oral flora can lead to dental caries and even jaw significantly (P ⫽ .03) improved at Week 8. The authors
infections. Investigators at The University of Texas M. D. concluded that acupuncture could improve the subjective
Anderson Cancer Center in Houston conducted a pilot study symptoms of dry mouth and that these effects persisted for
to evaluate the effect of acupuncture on radiation-induced, at least 1 month after acupuncture treatment. Despite
self-reported xerostomia and, as a secondary objective, the these subjective improvements, the investigators found no
effect of acupuncture on salivary flow (Head Neck. 2009 April change in the SSFR or UWSFR in these patients.
17. [Epub ahead of print]). Xerostomia tends not to resolve
spontaneously, and the currently available methods used to Dr. Garcia explained the difficulty in taking the salivary flow
manage the condition, including oral pilocarpine, electrical findings at face value: “Both basal and stimulated salivary flow
stimulation of oral tissue, and hyperbaric oxygen therapy, rates vary significantly among individuals. UWSFR have
have limited efficacy and limited acceptance by patients. been reported to range from 0.08 to 1.83 mL/minute, a
Early studies have suggested that acupuncture might stimu- difference of more than 20-fold. SSFR vary even more, from
late saliva production in people with xerostomia induced by 0.2 to 5.7 mL/minute. Within this wide range of flow rates,
radiotherapy, which led this research team in Houston to subjective perception of dry mouth and objective signs of
conduct their study. salivary gland dysfunction do not correlate,” she says.

Nineteen patients participated; all had completed a course Given the wide range of flow rates among patients with
of bilateral, external-beam radiotherapy (⬎4000 centi- normal oral function, the assessment of salivary gland
grays) at least 4 months before enrollment and had devel- function without individual subject baselines is difficult,
oped xerostomia afterward. The intervention consisted of Dr. Garcia says. “Subjective sensations of oral dryness are
acupuncture treatment given twice a week for 4 weeks. not reliable indicators of flow rate; impaired salivary gland
Five standard acupuncture sites were selected based on function can exist without xerostomia, which can, con-
efficacy suggested by earlier studies with xerostomia. versely, exist with normal salivary gland function. A diffi-
culty lies in the fact that there is no definitive threshold of
Patients also completed a Xerostomia Inventory (XI) and a increased saliva output that results in a clear clinical ben-
Patient Benefit Questionnaire (PBQ). “Both questionnaires efit. Thus, the only benefit currently recognized by the
assess symptoms related to dry mouth. They are scored dif- FDA [US Food and Drug Administration] for approval of
ferently, however, ” says M. Kay Garcia, DrPH, MSN, a xerostomia therapies is the subjective response,” she adds.
clinical nurse specialist and study coauthor. “For the XI, a
high score indicates worse xerostomia and for the PBQ, a low “Acupuncture is a relatively low-cost intervention that is
score indicates worse xerostomia. We used both instruments more widely available than people generally assume,” says Dr.
in order to be sure we were measuring what we intended to Johnstone, who echoed Dr. Garcia’s observations that objec-
measure and ensure validity of the assessment.” Patients also tive data regarding xerostomia are difficult to obtain, making
completed The Functional Assessment of Cancer Therapy the patient’s subjective reports the ones that really count.
Scale–Head and Neck (FACT–H&N) scale. “This QOL
instrument asks some questions related to dry mouth, but it “It’s how the patient feels that counts,” says Dr. Johnstone.
also assesses symptoms related to pain, fatigue, nausea, and “For many symptoms of cancer treatment—pain, dry
the impact these have on functional, emotional, and social mouth, nausea, and others—management involves a richer
well-being,” Dr. Garcia explained. canvas than we’ve seen before.”

The investigators also assessed the unstimulated whole Dr. Johnstone adds that “Acupuncture and acupressure
salivary flow rate (UWSFR) and stimulated salivary flow represent low-cost, but highly engaging mechanisms for
rate (SSFR). Baseline determinations were made 1 week potential relief of many cancer patients’ symptoms. Al-

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though proper controls often are difficult in clinical trials creasing number of physicians are aware of appropriate
investigating such integrative therapies, well-designed community resources. Guidelines are available from the
studies are ongoing in many centers. Society for Integrative Oncology for patients who are
interested in using integrative therapies for cancer symp-
Patients should discuss such nontraditional therapies with tom control.”
their oncologists prior to investigating them, but an in- doi:10.3322/caac.20034

Human Papillomavirus Genotype Distributions Inform Screening

and Vaccination Policy
Interventions for cancer prevention are typically divided into analyses of immunogenetic risk factors that are currently not
2 broad categories: primary prevention involves preventing feasible in other racial/ethnic groups. The cases included in
the disease before it develops and secondary prevention in- the study were 1,213 women with in situ cervical cancer who
volves the detection and treatment of precursor lesions and were diagnosed between 1985 and 1999 and 808 women
presymptomatic cancer. Prevention of cervical cancer has with invasive cervical cancer who were diagnosed between
largely emphasized the Papanicolaou test for secondary pre- 1980 and 1999, and for whom archival paraffin– embedded
vention, with the combination of cytology plus testing for
carcinogenic human papillomavirus (HPV) types recently
added as an option. The recent availability of a vaccine
against 2 carcinogenic HPV subtypes has made the primary
prevention of most cervical cancer a possibility. HPV vacci-
nation is expected to substantially change the prevalence of
infection with carcinogenic HPV subtypes among individuals
who receive the vaccine and, to a lesser degree, within the
entire population. But how will these changes influence the
future of secondary prevention programs?

With this question in mind, investigators based at the

University of New Mexico Health Sciences Center in
Albuquerque used data from the New Mexico Surveil-
lance, Epidemiology, and End Results (SEER) registry to
conduct a case–control study of HPV infection and cervi-
cal cancer risk (J Natl Cancer Inst. 2009;101:475– 487).
More specifically, they described cervical cancer risk ac-
cording to HPV genotype and patient age.

“Our goal with this study was to examine what was happen-
ing in the population over time prior to the HPV vaccine
being administered as a point of reference. Then we could
look back to see what had been changed by the vaccine as we
go forward,” says coauthor Cosette M.Wheeler, PhD, pro-
fessor in the Department of Molecular Genetics and Micro-
biology at the School of Medicine at the University of New
Mexico Health Sciences Center in Albuquerque.
Because exposure is very common within the first few years of the onset of
Inclusion was limited to Hispanic and non-Hispanic white sexual activity, we would only recommend delayed onset of screening in girls
who were vaccinated as young adolescents.— Debbie Saslow, PhD, American
women because of the insufficient sample size of some Cancer Society
other groups and because follow-up studies will include Credit: Cathysbellimage|Dreamstime.com

280 CA: A Cancer Journal for Clinicians

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tissue was available for analysis. The controls were 4,007 “This study provides baseline data that will be helpful for
women ages 18 to 40 years who underwent routine cervical monitoring the impact of vaccination,” says Debbie
screening from 1996 through 2000 and had portions of their Saslow, PhD, director of Breast and Gynecologic Cancer
cellular samples frozen in transport medium. The presence at the American Cancer Society in Atlanta. She points out
and genotype of HPV in samples from cases and controls that other data, mostly taken from modeling studies, sup-
were determined by polymerase chain reaction– based meth- port the recommendation that the onset of screening can
ods. The relative risks for cervical cancer were calculated, and be safely delayed for women who have received the HPV
investigators assessed the factors linked with age at diagnosis vaccine. The data from this study confirm that HPV–16
and the prevalence of HPV genotypes. and HPV–18 are associated with cervical cancers at a
younger age, which provides reassurance about delayed
In invasive cancers, the most common HPV type found screening after vaccination, Dr. Saslow says.
was HPV–16 (53.2%); other types included HPV–18
“The American Cancer Society and other groups are poised
(13.1%) and HPV– 45 (6.1%). In situ cancers most fre-
to develop screening recommendations for vaccinated women
quently contained DNA from HPV–16 (56.3%), HPV–31
once data—not just baseline, but monitoring data including
(12.6%), and HPV–33 (8.0%).
that from the vaccine clinical trials—are available,” Dr.
Saslow says. “For the time being, however, there is agreement
Women whose invasive cancers were positive for other
that vaccinated women should follow the same guideline as
carcinogenic HPV types (not types 16 or 18) were diag-
unvaccinated women because the vaccine has only been avail-
nosed at a mean age of 52.3 years (95% confidence interval
able for 2 years and is only effective in women who have not
[95% CI], 50.0 –54.6 years), whereas those with invasive been previously exposed to HPV–16 and –18. Because ex-
cancer who were positive for HPV-16 or HPV–18 were posure is very common within the first few years of the onset
significantly younger at the time of diagnosis: 48.1 years of sexual activity, we would only recommend delayed onset of
(95% CI, 46.6 – 49.6 years) and 45.9 years (95% CI, 42.9 – screening in girlswho were vaccinated as young adolescents.
49.0 years), respectively. And those girls have not yet reached the earliest age to begin
screening,” Dr. Saslow explains.
“It is clear that HPV–16-related cancers occur at a younger
age than other cervical cancers,” Dr. Wheeler says. An editorial by Lauri E. Markowitz, MD, and colleagues
“HPV–16 and –18 are more carcinogenic than other HPV from the Centers for Disease Control and Prevention in
types. They do their job faster,” she says. Atlanta (J Natl Cancer Inst. 2009;101:439 – 440) notes
that, “…screening recommendations have been debated
“We know based on observation that few cervical cancers even without considering HPV vaccine issues. Guidelines
occur in women aged younger than 25 years in unvacci- from national organizations promote the initiation of
nated populations,” Dr. Wheeler says. In fact, the rate is screening at age 21 years or 3 years after the onset of
approximately 2 in 100,000. As Dr. Wheeler and her vaginal sex and recommend lengthening of the screening
colleagues noted in their discussion, the HPV vaccine intervals; however, most providers still screen women an-
could reduce that rate by 50%, a rate similar to that for nually starting at age 18 years or below. Clearly, more
vaginal cancer, a malignancy for which no screening is education and policy interventions are required to translate
conducted. “This could allow us to raise the age of screen- evolving guidelines into best public health practice.”
ing for cervical cancer, as other countries have done,” she
doi:10.3322/caac.20035
said. Screening currently begins at age 21 years, or within
3 years of the onset of sexual activity. In the United
Kingdom, in contrast, screening typically begins at age 25 For additional information, see the American Cancer
years; in the Netherlands, most women are screened start- Society screening guidelines for the early detection
ing at age 30 years. of cervical neoplasia and cancer at: http://caonline.
amcancersoc.org/cgi/content/full/52/6/342 and
Dr. Wheeler also stresses the importance of putting a clear those regarding the use of the HPV vaccine
message out for patients: the current HPV vaccine does not at: http://caonline.amcancersoc.org/cgi/content/
protect against all carcinogenic viruses. “Regardless of a wom- full/57/1/7
an’s vaccine status, she must get screened,” she says.

VOLUME 59 ⱍ NUMBER 5 ⱍ SEPTEMBER/OCTOBER 2009 281