Acupuncture and breast cancer-related lymphedema: Quackademia strikes again

Lymphedema is a complication of breast cancer surgery that all surgeons who do breast surgery detest. Patients, of course, detest it even more. The limb swelling that is the primary symptom of lymphedema comes about because surgery on the axillary lymph nodes (the lymph nodes under the arm) that is part and parcel of surgery for breast cancer can interrupt lymph vessels and cause backup of lymph fluid in the affected arm. This backup has consequences, including skin changes, a tendency towards infections, and, in extreme cases, elephantiasis (which is, fortunately, rarely seen these days as a result of breast cancer surgery). Unfortunately, lymphedema is incurable, and the risk of developing it never goes away after breast surgery.

Lymphedema used to be much more of a problem back in the old days (say, more than 10-15 years ago), when surgery for breast cancer routinely involved an axillary dissection, or removal of most of the lymph nodes under the arm. (For surgery geeks, in breast surgery level 1 and 2 lymph nodes out of three levels, unless, of course, leven 3 nodes are grossly involved with tumor, in which case they’re taken too.) Frequently radiation therapy was needed as well, and the combination of axillary dissection and radiation therapy could produce a risk of lymphedema as high as 50%. Of course, in recent years, sentinel lymph node biopsy, which involves removing many fewer nodes (usually 1-3) has supplanted axillary dissection for most cases of breast cancer, and, consistent with fewer nodes being taken, the risk of lymphedema from sentinel lymph node biopsy is much lower. However, none of this means that lymphedema isn’t still a problem after breast surgery; it’s just less of a problem.

There are only a few basic strategies for treating lymphedema, sometimes called decongestive lymphatic therapy. For the most part, these treatments involve physical therapy, compression sleeves to “squeeze” the fluid out of the affected limb, and sometimes the use of mechanical compression stockings that “milk” the fluid back. It’s all very inconvenient and unpleasant, and there’s no doubt that this particular complication can take a major toll on a patient’s quality of life and sometimes even lead to hospitalizations for infection. It might be less of a problem than it was in years past, thanks to less invasive surgery, but it’s still a problem, and it needs better treatments.

Acupuncture is not one of them.

Not that proponents of acupuncture don’t try to convince people that acupuncture is a treatment for lymphedema. To be honest, knowing the mechanism by which lymphedema develops, I can never quite figure out why anyone would think that acupuncture would do anything for lymphedema. How, pray tell, would sticking needles into the body, often in areas of the body not involved by lymphedema, be expected to cause lymphedema to get better? Yet, acupuncturists keep claiming that acupuncture can be used to effectively treat lymphedema. Indeed, if there’s one image that causes me to cringe when I see it, it’s the image of needles being stuck into a lymphedematous arm, often with the acupuncturist not wearing gloves. In any case, just yesterday there appeared news of the publication of a study out of Memorial Sloan-Kettering Cancer Center (MSKCC) examining acupuncture as a treatment for breast cancer surgery-associated lymphedema in the ASCO Post:

Arm lymphedema affects approximately 30% of breast cancer survivors, with rates increasing with longer follow-up and cases presenting well beyond the active treatment period. Lymphedema is observed even with use of less-invasive surgical techniques for staging, and risk is further increased by such factors as radiation therapy, positive lymph node status, increased tumor burden, postoperative seroma or infection, obesity, and increased age. Current treatments for lymphedema after breast cancer treatment are expensive and require ongoing intervention. As reported by Barrie R. Cassileth, MS, PhD, of the Integrative Medicine Service at Memorial Sloan-Kettering Cancer Center and colleagues in Cancer, acupuncture may be an effective treatment.

The study appeared in the journal Cancer and was entitled Acupuncture in the treatment of upper-limb lymphedema: Results of a pilot study. It’s as fine an example of quackademia as I’ve ever seen, its lead investigator being our old friend Barrie Cassileth, the director of the integrative medicine department at MSKCC. Just put her name in the search box of this blog, and you’ll see that, although Dr. Cassileth is very much against cancer quackery like laetrile, shark cartilage, Entelev/Cantron, various oxygen therapies (such as hyperbaric oxygen or various means of administering hydrogen peroxide), and even “energy therapies,” which Cassileth admits have no evidence to support them. Of course, acupuncture is an “energy therapy.” It does, after all, postulate that inserting fine needles into pathways in the body called “meridians” somehow alters the flow of magical, mystical life force energy known as qi, to curative intent. Yet Cassileth really loves acupuncture, so much so that she’s conducted quite a few studies on acupuncture in cancer patients. For example, there was this one on acupuncture for hot flashes a few years ago.

So this time around, it’s acupuncture for lymphedema. Truly, acupuncture is the therapy that can do anything, which is consistent with its being quackery. Certainly, no one has ever postulated a mechanism by which acupuncture can do all the things claimed for it, including (but not limited to) relieving pain, relieving hot flashes, treating infertility, improving asthma symptoms, and, of course, treating lymphedema. What’s the common unifying biological mechanism that could explain therapeutic effects in all these diseases and conditions? There is none, at least none that any acupuncturist has ever been able to explain convincingly to me, nor was any claimed in the ClinicalTrials.gov entry for this.

So what does this study purport to show? It’s a pilot study involving 33 patients with breast cancer-related lymphedema for at least six months but not longer than five years. This time period was chosen to make sure that the subjects were all out of the immediate postoperative period but not so many years out that they started to develop skin complications from chronic lymphedema. These patients all underwent twice weekly 30 minute acupuncture sessions for four weeks as follows:

Alcohol swabs were applied prior to insertion of sterile single-use filiform needles (32-36 gauge; 30-40 mm in length, Tai Chi brand, made in China and distributed by Lhasa OMS, Weymouth, MA) that penetrate 5-10 mm into the skin. A total of 14 needles were inserted: 4 in both affected and unaffected limbs, 2 in acupuncture points on both legs, and 2 in unilateral points on the torso. Selected acupuncture points (Fig. 1) were stimulated manually by gentle rotation of the needles with lift and thrust. The acupuncturists did not intentionally seek to achieve a de qi sensation.

Specific acupuncture points used in this study were determined on the basis of historical context, the published literature, and the consensus of our experienced group of MSKCC staff acupuncturists.[18-20, 34, 37] Many of these acupoints are used to treat pain, weakness, and motor impairment; others are traditionally used to drain “dampness,” a TCM concept similar to edema.

Did I just read what I thought I read? Seriously? The rationale for choosing these points was based on their being related to traditional Chinese medicine concepts to drain “dampness”? This is utter nonsense, the sort of silliness in which quackademic medicine corrupts academic medicine with concepts that have nothing to do with science. Just read about “dampness” in TCM:

In nature, dampness soaks the ground and everything that comes in contact with it, and stagnation results. Once something becomes damp, it can take a long time for it to dry out again, especially in wet weather. The yin pathogenic influence of dampness has similar qualities: It is persistent and heavy, and it can be difficult to resolve. A person who spends a lot of time in the rain, lives in a damp environment, or sleeps on the ground may be susceptible to external dampness.

Similarly, a person who eats large amounts of ice cream, cold foods and drinks, greasy foods, and sweets is prone to imbalances of internal dampness. Dampness has both tangible and intangible aspects. Tangible dampness includes phlegm, edema (fluid retention), and discharges. Intangible dampness includes a person’s subjective feelings of heaviness and dizziness. A “slippery” pulse and a greasy tongue coating usually accompany both types of dampness. In general, symptoms of dampness in the body include water retention, swelling, feelings of heaviness, coughing or vomiting phlegm, and skin rashes that ooze or are crusty (as in eczema).

As I said, none of this has anything to do with science.

So, based on a TCM concept of “dampness” being tortuously related to lymphedema, quackademics at MSKCC subjected patients to acupuncture and measured their limb circumferences. There are a few ways to measure lymphedema. One is water displacement, in which the subject puts her arm into a cylinder of water, and the volume displaced is measured. This method isn’t used much anymore because it’s messy and inconvenient to do, although it is arguably the most accurate. In most cases, lymphedema is measured by comparing the circumference of each arm at different locations defined by anatomy. Generally, this is done in four locations, the metacarpal-phalangeal joints, the wrist, 10 cm distal to the lateral epicondyles, and 15 cm proximal to the lateral epicondyles. Differences of 2 cm or more at any point compared with the contralateral arm are considered by some experts to be clinically significant. The authors used a two-point technique performed by trained research assistants 10 cm above (upper arm) and 5 cm below (lower arm) the olecranon process using nonstretch tape measures, which is said to be as sensitive and specific as any other methods. The median age of subjects was 55, and they were a mean of 3.9 years out from surgery. They were on the obese side, with a mean BMI of 30.4, which is above 30 and thus in the obese range.

The results were as follows. A 30% or greater decrease in arm circumference was observed in 11 patients (33%) and 18 had a reduction of at least 20%, a reduction reported to be across the whole range of severity of lymphedema. One notes that 31 subjects (94%) used other standard therapies during the study, although 30 reported no change in their standard regimen. Now here’s where how you present the data makes all the difference in the word. These percentages seem huge, but you have to remember that the way they were calculated was in terms of the difference between the two arms in circumference, normalized to the pre-treatment difference. If the pre-treatment difference is small, then it doesn’t take much of a decrease in lymphedema to produce a large percentage. That’s why the really telling figure comes from Table 3, which shows that the mean difference between pre-treatment and post-treatment arm circumference was 0.9 cm (95% confidence interval 0.72 to 1.07 cm). That is spectacularly unimpressive, particularly in a population that skews obese. It sure sounds a hell of a lot more impressive.

Of course, the biggest problem with this pilot study is that it was uncontrolled. There is no control group. So we have no idea whether acupuncture had anything to do with the modest decrease in lymphedema reported. I will give Dr. Cassileth credit in that she does acknowledge this in the paper:

Whether acupuncture alone was responsible for this reduction was not evaluable in this pilot study. Our focus was on safety and potential efficacy, as current clinical practice to protect the lymphedematous arm prohibits needling.

Yet she also concludes, unfortunately:

The therapeutic and cost-reduction potential of acupuncture for lymphedema may yield an important tool in the arsenal of lymphedema management. Although randomized clinical trial results await, including our ongoing study, acupuncture can be considered to treat this distressing problem confronted by many women with no other options for sustained reduction in arm circumference.

And in a press release, she says:

“We have shown that acupuncture as a treatment for lymphedema is safe and well tolerated,” says Dr. Cassileth. “Furthermore, this study demonstrated reductions in lymphedema for the patients treated, providing strong impetus for the randomized controlled trial that is now under way to prove that the effect is real.”

Actually, no it doesn’t. This study is not good evidence that acupuncture works for lymphedema. There is no reason from a standpoint of prior plausibility informed by biology to think that acupuncture would do anything for lymphedema. On a Bayesian basis, exceedingly low prior probability plus an equivocal result (and, yes, this result is equivocal) equals a very high likelihood that the effect observed is a false positive. Even worse, the randomized clinical trial being carried out isn’t one that is likely to provide much of an answer. It’s a phase 2 clinical trial comparing immediate acupuncture to wait list for six weeks, after which wait listed subjects will cross over and receive acupuncture for six weeks. In other words, everyone in the study will receive acupuncture. I mean, really. Why are they even bothering? This study is unlikely to provide strong evidence that acupuncture works. Most likely, it will be another equivocal acupuncture trial. Of course, the ironic thing is that the crossover design was probably necessitated by the seemingly “positive” result of Cassileth’s currently reported trial. The IRB probably wouldn’t approve a no acupuncture arm in light of that, because then there wouldn’t be clinical equipoise.

Oh, the ironies of quackademic medicine, when the inevitable false positives that occur when treatments of low prior probability are tested in clinical trials complicate the next steps! It’s just infuriating how much time and resources are being wasted on studies that are so highly unlikely ever to produce useful results.