Recruitment for the trial took place between July 2001 and March 2004 among patients under treatment for advanced lung or breast cancer at Memorial Sloan-Kettering Cancer Center (MSKCC). Patients age 18 or above with subjective complaint of shortness of breath and scoring grade two or higher on the American Thoracic Society Breathlessness Scale were eligible. Patients must have pursued a trial of steroid medication for dyspnea, if indicated, for at least 48 hours. Patients were excluded if any of the following applied: shortness of breath predated cancer diagnosis (e.g. asthma); recent onset of symptoms (< 7 days); anemia (defined as hemoglobin < 8 gm/dl); recent acupuncture; contraindications to acupuncture such as heart valve dysfunction or pancytopenia; planned initiation or change in oncologic therapy or symptomatic management of breathlessness (continuation of any existing management was allowed), or likelihood of patient death during the course of anticipated participation in the trial. Patients were also excluded if the primary cause of dyspnea was thought to be congestive heart failure, sarcoid disease, hypersensitivity pneumonitis, cryptogenic organizing pneumonitis, pneumothorax, chest wall deformity, obesity, neuromuscular disorders, pulmonary vascular disease, hepatomegaly or phrenic nerve paralysis syndrome. If the primary cause of dyspnea was ascites, effusion, pneumonia, large airway obstruction, superior vena cava syndrome or pulmonary embolism, patients were eligible only if they remained short of breath despite conventional therapy administered by their primary oncologist, or if they had refused such therapy.
Eligible consenting patients were randomized by telephone using the MSKCC clinical research database. Randomization used randomly permuted blocks with the cancer diagnosis (lung/breast) and breathless at rest (yes/no) as strata. The use of independent telephone registration and randomization ensured concealment of treatment allocation. Patients, researchers and others involved in patient care were blind to study group; only the acupuncturists and a researcher not associated with the study were aware of which patients received true and which placebo treatment.
Treatment consisted of two phases, acupuncture and acupressure. Patients received either true acupuncture followed by true acupressure, or placebo acupuncture followed by placebo acupressure. The first "acupuncture phase" consisted of a single treatment in which real or placebo needles were applied for 15 minutes at true or sham points, respectively. In the true acupuncture group, the needles used were stainless steel AsiaMed No.16 30 mm × 0.30 mm inserted to the traditional Chinese depth of 0.5 cm – 1.5 cm. Auricular points were needled with stainless steel Seirin D type No. 1 15 mm × 0.16 mm. As is common in traditional acupuncture, practitioners attempted to elicit de qi
to help determine exact point location, but there was no manipulation of needles after placement. Placebo needles consist of a blunted needle that moves up inside its handle instead of into the skin. This technique has previously been demonstrated to be indistinguishable from true acupuncture[12
]. Patients were told that in placebo acupuncture "the needles are placed so that they do not stimulate the correct acupuncture points. However, they do not look or feel any different from real needles." Immediately after insertion of the needles, patients were asked to assess the credibility of their treatment using a previously published scale[13
The point prescription is described in Table . True points were chosen on the basis of the prior case series[11
] and points traditionally used for breathlessness[15
]; sham points were chosen in body areas away from true acupuncture points. The point prescription was modified slightly during the trial (details available on request), primarily to improve patient comfort. Patient outcome was not affected by the prescription used (see Results). Immediately after needle insertion, acupuncturists completed an audit sheet verifying the acupuncture points used. These records were routinely reviewed, and acupuncturists were found to have followed the acupuncture point prescription.
Location of acupuncture points.
One hour after removal of needles, patients started the second "acupressure phase." Stainless steel AcuMedic acupressure studs, sometimes described as "press," "semi-permanent" or "intradermal" acupuncture needles, were used. These consist of a 2 mm × 0.28 mm acupuncture needle attached to a metal ring embedded in surgical tape. When the surgical tape is pressed on the skin, the needle pierces the skin but its diameter is so fine that this sensation is neither painful nor even immediately obvious. Acupressure studs have been used in a number of studies with cancer patients[16
]. Placebo studs have no needle: they were specially designed for research in end-of-life populations by the author of the previous research on acupuncture for cancer related breathlessness[11
To ensure retention of studs and guard against infection, the studs were covered with Tegaderm following application. Patients in the true acupuncture group were treated with true studs at ST36; Sternal points or Ren17; Auricular lung point and Auricular kidney point (see Table ). Placebo patients received placebo studs at sham1, sham2 and ear sham. We thought it possible that patients might remove the studs before the end of the trial and that studs with a visible needle might be more credible than those without. Therefore, we also applied a placebo stud at sham1 to the acupuncture group and a true stud at sham3 to the placebo group. We told patients that some studs had small needles, others did not and that the choice depended on where they were placed on the body. Patients were also told that those in the placebo group received treatment at points not thought to help breathlessness.
Following application of the studs, patients were instructed to apply pressure to the study by making small circular movements with the fingers of the opposite hand, 2 – 3 cycles per second for 1 – 2 minutes per point. As is typical for self-administered acupressure, patients were encouraged to apply acupressure this way on waking, in the early afternoon and during any exacerbation of symptoms. Initial instruction was provided verbally, at which time patients were asked to confirm their understanding by demonstrating the procedure. Patients also were given easy-to-read written materials describing the acupressure procedure.
Study acupuncturists are certified by the National Certification Commission for Acupuncture and Oriental Medicine (NCCAOM) and are licensed to practice acupuncture in New York State. They have used acupuncture in clinical practice for 3 – 25 years. All were employed at MSKCC during the study and had considerable experience in treating cancer patients.
Outcome was measured in two ways. Every 15 minutes for 75 minutes immediately before acupuncture treatment and one hour immediately after, patients rated their current level of breathlessness on a 0 to 10 rating scale. They then completed a dairy daily for seven days, recording their average level of breathlessness through the day with the same 0 to 10 scale, and recorded compliance with acupressure.
The protocol was modified after 16 patients were accrued, as we found that many in-patients had been excluded because changes in management were likely in the subsequent seven days. We therefore modified the protocol so that inpatients did not take part in the acupressure phase. Moreover, many outpatients who complained of breathlessness in everyday life did not record significant breathlessness during the waiting period immediately before acupuncture. Accordingly, we amended the protocol so that outpatients completed the daily breathlessness diary for a week at baseline. Only patients scoring a mean of two or more were eligible. Out-patients who reported no breathlessness at rest were not asked to report on symptoms in the period immediately before and after acupuncture.
Preliminary power calculations on the basis of published data[10
] suggested that a sample of 120–150 patients would be required to provide power to detect a clinically significant difference between groups, defined as a 20% lower follow-up dyspnea score in the acupuncture group compared to placebo. For this pilot we sought a sample of 40–50 patients. We felt that a sample of this size would give us sufficient methodologic experience to conduct an adequate fully powered study. Comparisons between groups were by analysis of covariance (ANCOVA) with baseline score and randomization strata as covariates. Baseline score for the acupressure phase was the one week baseline diary, if available, otherwise the immediate pre-treatment breathlessness score was used. Patients were analyzed in their randomized groups regardless of treatment received. Prespecified sensitivity analyses were to examine the effects of credibility on outcome and to assess outcome for the acupuncture phase only in patients with pre-treatment dyspnea scores greater than two. Statistical analysis was conducted using Stata 8 (College Station, Texas). No interim analyses were planned and the data were not analyzed before study closure.
The study was approved by the institutional review board at MSKCC in accordance with an assurance filed with and approved by the Department of Health and Human Services. Written informed consent was obtained from each participant.