Lymphovenous Canada: Juravinski Cancer Centre studies the effectiveness of decongestive lymphatic therapy

Note to readers: The Juravinski Cancer Centre (formerly known as the Hamilton Regional Cancer Centre), has re-opened their lymphedema clinic. Patients must be referred by their oncologist. For information please contact Margaret Forbes, RN at (905) 387-9495 ext. 64176.

Dr. Ian Dayes: I studied medicine at the University of Toronto and came here in 1995 to do a 5-year residency in radiation oncology. After that I did an 18-month fellowship. The main thrust of that fellowship was a health research methodology program at McMaster University which is essentially how you do clinical studies, the statistics, the ethics of randomizing patients, how to do the correct measurements, etc.

One of the projects I did under that fellowship was a study on the role of massage therapy in lymphedema for breast cancer survivors. That class project expanded out to a grant proposal, which was sent in to the Canadian Breast Cancer Research Initiative (CBCRI), which was officially accepted in March 2002. Since then we have been trying to get things under way in terms of recruiting other centers and the logistical details.

I have been a radiation oncologist on staff here for almost a year. At the moment I am largely seeing patients with breast cancer and GU conditions such as kidney, bladder, testes, etc. I don't have a lot of breast cancer survivorship issues to deal with yet such as lymphedema because my practice is so young. It probably will become so over the next few years as patients move away from their disease and the long-term effects of their treatments start to occur.

Why did I get into this field? Like every other physician you do a rotation with someone who you enjoy - you get an enthusiasm for their work and then before you know it you start thinking about getting into that field. Dr. Tony Fyles at Princess Margaret was that person. He made me feel very interested in going to those clinics.

Jennifer Wiernikowski: I have been a nurse at the Cancer Clinic since 1994. I worked in the primary care practice with Dr. Tim Whelan, a physician at the Hamilton Regional Cancer Centre who is very interested in doing supportive cancer care research. About three years ago I returned to school to get a masters degree and I am now working as an advance practice work nurse.

I have a real interest in women who have been treated for breast cancer who now find themselves in the follow-up phase. We have many clinical trials and guidelines for the treatment of breast cancer, but more and more women are surviving longer and surviving better so I would like to see some trials now that target survivorship issues.

This has been a bit of a focus on my studies during my masters degree. Around the same time Ian did his project for his course, I was also asked to do a project for my course, doing some critical appraisal of randomized studies. I chose to look at studies evaluating lymphedema. It was at this time I started talking to Ian about his study and particular interventions. He told me he was writing up a proposal and I was very enthused about it.

It was just a gift of timing that I had finished my studies and had secured my position here. I had started my own advance practice nursing clinic doing follow-up of breast cancer patients. We were able to make this clinic a place to find patients to be part of the study.

It's a very new clinic which is all about symptom management in the follow up phase after breast cancer. Certainly patients with lymphedema are patients we would see in the clinic along with other problematic symptoms such as menopausal issues, etc.

Jennifer Wiernikowski and Dr. Ian Dayes

Dr. Ian Dayes: As a resident I saw that this was a very frustrating issue for patients. As physicians we are very poorly trained in recognizing lymphedema and how to deal with it.

There had been a couple of Canadian-wide guidelines published on the treatment of breast cancer related lymphedema and each of them called for further randomized studies to be done on the effectiveness of lymphatic massage (manual lymphatic drainage). (Cancer Care Ontario is currently in the process of developing its own guidelines in this area) Everyone was making recommendations that these studies needed to be done but no one seemed to be actually doing them.

During the fellowship I recognized that this was an area many of the Canadian-wide experts clearly identified as an important issue. Everything seemed to be pointing in that direction but no one seemed actively involved so I figured it might as well be me.

I decided to take my project and flesh it out into a true grant proposal. That was when I got in touch with Lyn Kligman, an advanced practice nurse at the London Cancer Regional Centre, who deals with a number of patients with lymphedema at her symptoms clinic and Donna Lue Reise, who is a Vodder-trained therapist in the Hamilton area.

Between Jennifer, Donna and Lyn we pooled our resources together to determine how to approach this. We worked closely with Tim Whelan, Director of the Breast Disease Site Team, Hamilton Regional Cancer Centre who also heads up the Supportive Cancer Care Research (SCCR) Unit at McMaster University. It was under his guidance that the grant proposal was written. The clinical trials methodology group at the Henderson Hospital lent their statistical expertise which also really helped as well in the writing of the proposal.

The study:

The study is taking place in three centers: Toronto Sunnybrook, Hamilton and London Regional Cancer Centres.

At every cancer center there is a physician who is the main point person. Also at every center there is going to be a nurse who will be running a breast cancer symptom clinic. In addition to that there will be a clinical trial nurse to help run the nuts and bolts of the study

The study will look at 100 patients. We are assuming that one third of the patients - about 30 to 35 will come from each center. Any woman who has active breast cancer disease will not be eligible for the trial because the cancer may be responsible for the lymphedema and so that individual may not be positively affected by any treatment and that wouldn't be fair to the study.

So far the entire funding is through CBCRI. The trial is being run through the Supportive Cancer Care Research (SCCR) Unit here in Hamilton as well as the Clinical Trials Methodology Group here in Hamilton.

Why isn't more research being done in this area? There are a lot of patients with lymphedema in the community who aren't being captured by the medical community. They aren't admitted for lymphedema; they aren't seeing their physician for lymphedema. They are often paying out of pocket for treatments to see a massage therapist.

Some patients don't enter into the established health care system. Certainly when I talk to therapists involved in the study they say to me "oh yeah I have patients who have been putting up with this for 5 to 10 years". They've gone around to various clinics trying to get help - it was really on their own initiative that they found something. It's really by word of mouth that I have heard about that.

Jennifer Wiernikowski: All the patients that Ian and I see and all the patients who will be involved in the study already have a diagnosis of breast cancer and so that access to the health care system has already been established.

One thing I am curious about is the number of women with lymphedema. We do not currently document as many cases of lymphedema as the literature suggests we might find.

I found that the rate of lymphedema that we see in our breast cancer patients is less than what's quoted in the breast cancer literature which is anywhere from 10% to 60%. I'd say we have settled on something from around 12-15%. I am only speaking from the perspective of a new advanced practice nurse in Hamilton. There is an advanced practice nurse in Toronto whose practice is filled 90% with patients with lymphedema; there is an advanced practice nurse in London who has a very large lymphedema practice who says she could practice five days a week with patients with lymphedema.

I am very curious to see how this works - the clinic has only been operational for two months. It is very possible that we don't identify lymphedema when it is mild or moderate, only identifying it when it is really obvious. Patients who complain of a heavy arm and tingling may not have been identified as having lymphedema in the absence of obvious arm swelling in the past. One of the challenges for our team in the next few months is to do some education with our colleagues in terms of assessment and how to identify those patients with milder forms of lymphedema.

Ian and I are planning an information session for nurses at the Hamilton Cancer Regional Centre in January and I think we are going to see a lot of referrals after that.

There are lot of women in the community at least three or five years from their treatment who are no longer followed by their oncologist. We've discussed how we re-capture them for this study.

Dr. Ian Dayes: The incidence of lymphedema increases depending on the number of interventions which have taken place and the extent to which they were done. We don't see patients who have had radical mastectomies any more, which were very aggressive surgeries. It was very common about 30 years ago but it's not done now. The rate of lymphedema was apparently very high with them.

In terms of Canada data on the rates of breast cancer-related lymphedema, probably the B.C group is the best. Two major studies came out about four or five years ago, which showed a role for radiation of the nodes in the breast to the collarbone area. I think they quoted a rate of 9%.

I'm not sure that we have any evidence that would suggest that Canadian incidence of lymphedema would be any different than American incidences of lymphedema. The difficulty with that is that they are often reporting on patients who had their breast cancer treatments 10 or 15 years ago when radiation techniques were different, different surgeries were being done. So by the time you get that information published it may not actually be relevant to patients we are seeing now. If we see patients six months after treatment and do measurements we may see different results than if we do that 2 or 3 years after treatment. There are an awful lot of biases that come into play in the data.

Jennifer Wiernikowski: The other difficulty is that lymphedema is defined very differently by different authors. That is why there is no consistency in the data.

Dr. Ian Dayes: We may start seeing more patients with lymphedema because we are finding that at least in certain groups of breast cancer patients radiation to the breast area and to the collar bone area is indicated.

It may actually go up in the future because we are finding more and more indications for giving radiation not just for the breast but under the arm and over the collarbone. That's one reason.

As well there is some data in the surgical literature suggesting that all patients undergoing an axillary node dissection should have a minimum of 10 lymph nodes removed. It is quite likely that the number of lymph nodes removed has some correlation with the likelihood of developing lymphedema. So if you just go in take two or three lymph nodes out it may be good for preventing lymphedema but not be that great in terms of your likelihood for controlling disease in that area.

We don't do as much as we used to because radical mastectomy is no longer performed. Anatomically there are three levels of lymph nodes of which surgeons now only take two. We certainly know through scientific randomized control trials in the U.S. 15 years ago that you are going to do significantly worse if you don't have the lymph nodes removed as opposed to getting the correct procedure done.

Jennifer Wiernikowski: We use the information about the lymph nodes to guide the decisions that are made about treating the patient. When you don't have that very key piece of information it makes treatment decision-making extremely difficult. There is a movement lately to have a CCO guideline on sentinel node biopsy to see if there is a sub-group of people who don't need an axillary node dissection. I think the jury is still out on this issue.

It would be nice to know we could identify those patients but at this point I don't think we can say there are a group of patients with sentinel lymph nodes without cancer who don't need an axillary node dissection to guide the decision making process. We can't really overstate the importance of that, especially for women who are making decisions to have chemotherapy. The choices of chemotherapy for women under the age of menopause are very much geared towards whether those lymph nodes are positive.

There have also been changes in radiation treatment. Modern techniques for planning and giving radiation may make the risk of lymphedema less than it was previously,

I think patients might not understand that when the surgeon does a lymph node dissection, he doesn't take away every lymph node under the arm. I think there is a prevailing understanding that that's the case - that the surgeon goes into that area and takes all the lymph nodes they can find. When in fact they take a piece of fat tissue from under the arm and they really don't know how many lymph nodes they take. It is just one anatomical area and there are often lots of lymph nodes left to pick up the work. As we know it sometimes doesn't work quite that way and lymphedema is the result - but often it does work which is why most women never develop arm swelling.

Dr. Ian Dayes: There may well be patients who we've seen through the cancer center and then there is no evidence of the cancer coming back after five years at which point we generally send them back to their family physician. And there's that second group of patients out there who may have gone to a surgeon, had a mastectomy, and had no need for chemotherapy or radiation afterwards so we would not have ever seen them through the center here. They may have developed lymphedema and may be struggling outside in the community. So we may have to do a bit of local advertising with local surgeons. We certainly don't want to do that right now because we don't want to get overwhelmed by those patient numbers. So I think we will wait a couple of months and if the numbers aren't what we expected we will go around by word of mouth.

We are hoping to recruit patients roughly over a year and a half - although the funding is for two years. Each patient will be followed up to a year. We are hoping to randomize 100 patients - 50 in each group. One group will have conservative management which will involve skin care, exercise, maintenance for body weight and being fitted for elastic gauntlet and sleeve which was the main recommendation of the steering committee in the CMAJ article; the other half of the patients will be randomized for lymphatic drainage so essentially they will be receiving an hours' worth of massage every day, five days a week for four weeks, with bandaging for the intervening 23 hours.

Patients will also be taught self-bandaging so that on the weekends they can re-bandage and an exercise program in addition to everything else the control group will receive. After the four weeks are finished they will then also be fitted for an elastic garment. They will be measured once during the active treatment, once at the end and then at roughly at three months, six months and twelve months.

The primary outcome is full arm volume at roughly two weeks after they are finished their treatment. Measurements are going to be obtained through circumferential measurements not water displacement.

We will be selecting patients for moderate to severe lymphedema. For the moment at least we are not going to be including people who have 20% or less excess arm volume. For one thing many therapists feel that it could be inappropriate for patients who have 10% or less excess volume to use massage therapy. It might just make more reasonable for them to use a sleeve. Patients will have to have had their lymphedema for at least three months because we didn't want include people with temporary edema, which had flared up with their radiation or surgery.

After three months the acute affects of surgery or radiation at least acute affects should be settling down. One of the studies I reviewed suggested that about half of patients who are going develop lymphedema are going to develop it about 12 to 14 months after treatment. And about 4 years after treatment, about 95% of patients who are going to develop lymphedema have developed it. Beyond the four-year mark it is very rare.

Surgery and radiation are local treatments so the complications are usually local. So that if patients are getting swelling in the breast and upper arm than it is fairly reasonable to say that it is a direct part of the surgery and that it may settle down. But if the patient starts to develop swelling in the forearm or the hand than that is more likely to be lymphedema.

In an effort to look at sub-group analysis, we will be looking at persons with lymphedema for less than a year versus patients with lymphedema for more than a year to see if duration of lymphedema affects how treatments work. We are also going to split the more severe edema and the less severe edema to see if one of these groups particularly benefits more from the treatment.

"The main information we are getting from a trial like this is to determine which treatments are best for which patients."

But in addition we are collecting information on patients as they get entered into the study such as age, concurrent medication, smoking status, diabetes status, cardiac history and lots of other information which may not correlate at all but there's one way to find out and that's to look at that information.

With regard to diabetes, many reports suggest that patients with repeated infected are at greater risk of developing permanent lymphedema. Certainly persons with diabetes are more likely to get infections - particularly skin infections - so it is not a great leap of faith to think that patients with diabetes may have more of a higher risk of developing lymphedema. We may not be able to say anything definitive about this with 100 patients - but at least it will help us determine what type of questions would be important to ask and perhaps establish a trend which might support future funding.

Types of massage:

You get into an awful lot of methodological and funding issues once you start having more than two groups in any particular study probably to the point that you would not be able to do it. This is one of the issues that came up earlier in discussions - were we going to include a third group of patients? Then the cost immediately became prohibitive.

We have two reasonable treatments and we can build on that. At the moment we are using therapists who are Vodder trained and Foldie trained. My understanding is that the techniques used by these schools are really quite similar.

Originally we wanted to use Vodder trained therapists only but that could present a bit of a problem for us in terms of which therapists would be available in which towns. We will have the therapists talking to each other so the therapists have standards they all agree upon. I don't think you can ever get any therapy 100% standardized though. If we have the therapists agree to a certain set of rules that is probably a bit more transferable to the patient population after the study is reported.