We found that many patients were not particularly interested in joining the study. As such, the time to accrue patients became much longer than expected. Even with the reduced criteria for entry, it took 6 years to get enough patients. We were very concerned that the overall reduction in volumes could impact the results. We analyzed the data based on the initial degree of lymphedema and found that this did not impact on our results. Results were similar whether or not patients had mild-moderate or severe lymphedema. Therefore we felt that including patients with 10-20% lymphedema likely had no impact on the findings.
To what do you attribute the poor response to CDT (bandaging), as based on other articles- 29% reduction is much lower than what we would expect? Firstly, many articles examining CDT are based on data collected retrospectively. When physicians go back through their records and report on their patients, it is possible that patients who do not get much benefit from the treatment stop coming and are therefore “lost to follow up”. This means that reports of this nature tend to overestimate the true effect of the treatment. This is a well understood phenomenon when studying any type of treatment. Secondly, even with prospective studies, there may be many small influences on the success of a particular patient’s response to treatment that can never be fully measured or understood. Because of this, it is always difficult to compare results across studies as it is difficult to show that the study groups were exactly the same. The previous two best done studies of CDT reported reductions of approximately 40% (McNeely, 2004) and 43% (Andersen, 2000), which is certainly higher than this study but not as high 50-60% as suggested by some retrospective studies. Of note, the McNeely clinic also enrolled patients on this study. In the article you write: “We estimated that the mean percent reduction in excess arm volume between baseline and week 6 with garments alone would be 40%”. Would you please explain the basis of this estimate? 8 Ly m p h e d e m a p a t h w a y s . c a
When performing a randomized study, estimates must be made to predict how many patients will be needed when drawing up a budget and applying for a grant. To do that, mathematical models are performed to calculate the sample size needed to give a reasonable chance of finding the difference you are looking for. Typically one needs to know the expected benefit of each of the two treatments that are going to be compared, as well as the amount of variability of the benefits within each group. When the study was initiated over a decade ago, we based our estimates on published data that was available at that time.
Another comment: Response to treatment is expected to be poorer if the initial % volume is higher. Would this have an effect on the treatment results as the treatment group had higher volumes? This is answered, in part, in a previous question. I’m not sure there’s much value to giving the same reply. As an observation though, it is interesting that this question suggests that the study may not have shown a difference because the arm volumes were too large while a previous question suggests that same may be true because the arm volumes were too small. Would you comment please on how compressing a limb with only a garment might affect the outcome of a patient in relation to drainage of the adjacent quadrants, protein accumulation and potential fibrotic tissue accumulation in the affected limb? We did not make any measurements with regard to the above outcomes. As such, I’m not sure I’m qualified to comment. However, inherently I’d expect a benefit on those measures with reduced arm volumes, regardless of how the volume was reduced. We received a comment regarding costs. “Advocating the cost saving of approximately $1500 per patient, you suggest that there is little additional benefit from CDT. You place a cost per ml. of volume lost. However this
cost saving must be weighed against long term disadvantages of lack of treatment. Are there not potential costs in patients who do not undergo CDT therapy?” There were no patients on the study who experienced a lack of treatment. All patients had some form of treatment designed to reduce excess arm volumes. We followed patients for a year after treatments and did not find that there were additional costs. Of note, we did ask patients at each visit if they had undergone any additional treatments which were not part of the study. However, at the end of 12 months, excess arm volumes were almost identical between groups, so we had no indication that patients in either group were more or less likely to seek out further treatment. Dr. Dayes, we appreciate the time and care that you took in responding to these comments and questions, and thank you again for your dedication to lymphedema research. LP
References 1. Dayes IS, Whelan TJ, Julian JA, Parpia S, Kathleen I. Pritchard KI, D’Souza DP, Kligman L, Reise D, LeBlanc L, McNeely ML, Manchul L, Wiernikowski J, and Levine MN. Randomized trial of decongestive lymphatic therapy for the treatment of lymphedema in women with breast cancer. Journal of Clinical Oncology Oct 20, 2013:3758-3763 2. H arris SR, Hugi MR, Olivotto IA, et al: Clinical practice guidelines for the care and treatment of breast cancer: 11. Lymphedema. CMAJ 2001;164:191-199, Dr. Ian Dayes is a radiation oncologist at the Juravinski Cancer Centre in Hamilton, Ontario and an associate professor in the Department of Oncology at McMaster University. Following his residency training, he completed a 2-year Master of Science degree in Health Research Methodology, learning how to design and conduct clinical trials. Spring 2014