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Risk Reduction in the News – Response from the NLN Medical Advisory Committee

2012 Conference featured in Oncology Times

Clinical Trials - Patient Participation

NLN Position Papers: Risk Reduction, Risk Reduction Summary, Diagnosis and Treatment, Exercise, Training, Breast Cancer-Related Lymphedema, Supplement BC-Related LE

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Featured Articles from LymphLink

Utilizing Complete Decongestive Therapy to Treat Lymphedema: Evidence from Contemporary Literature

By: Kathryn McKillip Thrift, BS, CLT-LANA and DeCourcy Squire, PT
Dallas, TX; CLT Courses, Decatur, GA

Introduction
A “Systematic Review of the Evidence for Complete Decongestive Therapy in the Treatment of Lymphedema from 2004 to 2011” was commissioned as part of the American Lymphedema Framework Project’s (ALFP) review of literature concerning 13 various aspects of lymphedema management.

Publications from the 11 major medical indices and from the authors own reference articles were reviewed with the goal of critically analyzing current literature regarding the management of lymphedema (LE) with all the components of Complete Decongestive Therapy (CDT) both singularly and in combination. The Best Practice for the Management of Lymphoedema from the International Lymphedema Framework Project (ILFP) was used as the guide for search terms related to articles to be reviewed. Inclusion and exclusion criteria were established for the 99 articles reviewed. Of these, 26 met the inclusion criteria. In addition, 14 review articles and two consensus articles were reviewed. One case study, which did not meet the inclusion criteria, was included as it was a unique case study on genital edema.

Once the articles to be reviewed were determined, the authors categorized the study evidence using the Oncology Nursing Society Putting Evidence into Practice (PEP) guidelines. A consensus of the authors was used to determine not only inclusion/exclusion but also where each article fell within the PEP guideline ratings.

There were several challenges faced by the authors, such as a lack of a uniform definition of what constitutes LE. Many studies did not have control groups or randomization, well-controlled interventions, agreement on the correct dosage of CDT, and the blinding of assessors. Most studies were small in size, and the few having follow-up assessments had a high dropout rate.

Additionally, it was difficult to determine which of the separate aspects of CDT (Manual lymph drainage [MLD], compression bandaging/compression garment [CB/CG], exercise, skin care) were responsible for the success of the therapy.

Some of the studies also incorporated intermittent pneumatic pumps as part of their CDT treatment plans or did not include the exercise component.
These limitations explain why there was only moderately strong evidence for the use of CDT in the treatment of LE.

While CDT has been used successfully in Europe and the United States and Canada for more than 30 years, the “evidence-based medicine” standards have been lacking. It was the purpose of this systematic review to determine the strengths and weaknesses concerning the levels of evidence on CDT as a treatment modality for lymphedema and to guide future research efforts to support the continued use of CDT as a best practice in lymphedema management.

Results
A report on the 26 articles meeting inclusion criteria plus the one unique case study (for a total of 27 studies) follows.

Fifteen articles were rated as “likely to be effective.” They included seven randomized controlled trials (RCTs), four retrospective studies, three prospective studies, and one unique case-controlled study.

Breast-cancer related lymphedema (BCRL) was the most common among the studies, with twelve studies focusing on this aspect of utilizing CDT for patients with LE. Three studies included both upper and lower extremities.

Differing types of measurements were utilized to determine the volume of the lymphedematous limb. Circumference measurement with a tape measure was most common, with nine studies using this method, while two used perometry, five volumetry or a combination of volumetry and circumference. One study used ultrasound and calipers to measure tissue thickness, and one measured the pressure under the compression bandaging.

Studies reviewed had a range of subjects from 29 to 537 participants. Of these studies, nine reported no follow-up, two had a 24-hour follow-up, one had a 6-month follow-up and three had 12-month follow-up.

In 14 of the 15 studies, assessors were not blinded to the intervention. Only two studies measured how lymphedema impacted their quality of life (QOL).

Two studies were judged to be “benefits balanced with harm.” Volume change was the focus of one study with BCRL. It included 31 subjects who had their volume change with exercise alone or in combination of exercise and wearing compression garments. Unfortunately, this study only had a 24-hour follow-up. The other was a prospective study with 57 participants with lower extremity LE. These subjects received between two and four weeks of MLD combined with CB and exercise. There was a one-month follow-up. Measurements were taken circumferentially. Neither study blinded the assessors, but both studies assessed the impact of intervention on the QOL.

“Effectiveness not established” was scored for the remaining ten articles with seven being prospective, two retrospective, and one the single unique case study. Once again, BCRL was the primary focus in six studies while three included lower extremity LE. The one unique case study was included as it reported on genital lymphedema.

Of these ten studies, eight measured volume reduction by circumference, one by volumetry, and one by lymphoscintigraphy. Three studies assessed QOL. Subject size ranged from 1 to 82 participants. Follow-up was reported: four studies, none; one for three months; one for 6 months and one for 12 months. Only one study blinded the assessors.

CDT
Perhaps the 2009 review by Devoogdt et al.1 best summed up what those in the field treating LE know: “CDT is an effective therapy of lymphedema but the role of each component is unclear. . .” Leal et al.2 wrote in their review of treatment modalities that “within the therapeutic modalities used for LE treatment, CDT undoubtedly has the strongest scientific support.”

Most authors agreed the methodology for teasing out the effectiveness of the various aspects of CDT resulted in less than stellar studies. Part of the difficulty in determining the effectiveness of each component is the synergistic effect of combining MLD with CB. MLD was never intended to be the sole treatment modality of LE. It was designed to be used in conjunction with CB since once the edematous fluid has been moved out of the tissues, fluid would quickly return without the external support of bandages replacing the tissue pressure.

One study in 2005 by Karadibak et al.3 attempted to isolate the effects of MLD within the CDT treatment in a RCT of BCRL in 53 cancer survivors. One group of 27 received the standard CDT, which included MLD while the control group of 26 received CDT without MLD. The group who did not receive MLD as part of their protocol, received a reduction in their lymphedema by 36% while the group who received MLD achieved a 56% reduction. This greater reduction with MLD does show the contribution of MLD within the context of CDT.

A cross-over RCT study was done by Williams et al.4 in 2002. In this study, 16 participants with more severe, chronic lymphedema received MLD daily compared to a group of 15 who did self-MLD. After six weeks, the groups switched interventions. In this study, MLD compared to self-MLD led to greater reductions in swelling in both the arm and in the trunk.

In another RCT cross-over study of 42 women with mild or early onset BCRL, Andersen et al.5 found that compared to compression alone, MLD was not a significant factor in reducing volume. However, McNeely et al.6 conducted an RCT study with 50 BCRL participants and found MLD with compression bandaging was more beneficial than the use of compression bandages alone.

A difference in study protocols may be the primary reason for contradictory findings in some of the studies, which points to the need for more research. As an example, MLD was done for 30 minutes, 45 minutes, or 60 minutes a session. Treatments were once a week, 2-3 times a week or 5 times a week, (one study did it twice a day 5 days a week). The course of treatment lasted anywhere from 2 weeks to 6 or more weeks; some were a set length while others went until patient’s volume loss plateaued. During treatment, some protocols used compression bandaging, while others used compression garments. The exercises used were not described and a few protocols did not include exercises in the treatment.

Acute and long-term management of lymphedema with CDT
Most of the articles available for review dealt with the use of CDT or some of its elements or abridged protocols of CDT for the intensive phase of treatment. Only a few articles looked at long-term management of lymphedema.

In spite of the differences in methodology and protocol, the clear outcome in most studies was an immediate improvement in limb volume whether using CDT or a variant.

The limb reductions achieved in the different studies covered a range: Jeffs7 reported 70% reduction. Yamamoto et al.8 reported 59% for patients with arm LE and 73.5% for patients with leg LE. McNeely et al.9 reported 44-46% reduction; Kim et al.10 reported 43.6% reduction; Vignes et al.11 reported 36-38% reduction; Pinell et al.12 reported 22% reduction (this included patients with active tumors).

The long-term results of CDT were harder to determine. Only a few studies included follow-up.

Johnstone et al.13 had a median follow-up of 7.5 months, but a very small sample size (11 patients returned for follow-up out of an initial 82 patients). Of these, the 7 who reported adherence to their home program had continued to reduce and the 4 who didn’t had begun to increase in limb volume again. Kim et al.14 had a 6 month follow-up and found that 42% of the subjects had regressed to just being 15% below where they had started. Mondry et al.,15 with a 12 month follow-up, also noted limb size increasing during follow-up. Vignes et al.16 had the largest number of patients (426) of whom 356 were available for 12 month follow-up. These patients had a home program of wearing compression garments daily and bandaging 3 nights a week (and having MLD 1-3 times a week). There were continued reductions of more than 10% in 28% of these patients.

These studies were consistent with previous follow-up studies (Boris et al.17 and Ko et al.18) which also found that adherence to a home program of compression is important to maintaining results and following active self-care, such as decongestive exercises/self-MLD can lead to continued reductions.

Quality of life (QOL)
Quality of life and improved function are two important results of treatment, but they were examined in only a few of the studies. The general outcome was that after lymphedema treatment, quality of life improved, even if the results of treatment (i.e., limb reduction) were not fully maintained.

Williams et al.19 found treatment that included MLD improved emotional function and decreased sleep disturbance, while using self-MLD instead did not have this effect. Kim et al.20 found that for people with either leg or arm lymphedema, the increased size of their limb led to a decreased QOL and the decreased limb volume from treatment led to an increase in QOL, measured at 6 month follow-up. Mondry et al.21 found that QOL gradually increased during treatment and at 3 month, 6 month and 12 month follow-up, even if limb size began to increase again.

Compression bandaging
Badger et al.22 conducted a RCT using compression bandaging, followed by compression garments after reduction compared to using only compression garments as the tool for reduction. This study showed using compression bandaging first was twice as effective in reducing lymphedema as using only compression garments.

Damstra et al.23 compared the effectiveness of low pressure (20-30 mm Hg) and high pressure (44-58 mm Hg) bandages on people with BCRL. They found no significant difference in outcome and the lower pressure bandages were better tolerated. In another study, Damstra et al.24 found that the sub-bandage pressures dropped significantly after a few hours and by 24 hours were 55-63% less. This makes it important to reapply compression bandages daily when possible.

Lympho-venous disorders

There were two articles related to this topic: one a 2008 consensus document by an international panel of experts on this issue (Partsch et al.25 which reviewed the literature on compression treatment for venous and lymphatic disorders and the other by Shrubb et al.26 reviewing the literature on general management of DVTs (blood clots) to apply it specifically to people with lymphedema who develop DVTs. The recommendations from these articles were the following:

Differential Impact of CDT
A number of studies tried to determine what factors affected the effectiveness of CDT. Among the factors examined were the presence of active cancer; age; weight/BMI; the original amount of swelling; the length of time swelling had been present; and the length of treatment/number of sessions.

Pinell et al.27 found even in patients with active tumors, CDT worked to reduce swelling, but the results took longer to achieve.

Yamamoto et al.28 found while amount of swelling was correlated with age, the effectiveness of treatment was not; Liao et al.29 also found age did not correlate with effectiveness of treatment.

Vignes et al.30 found the weight of the patient did not affect the effectiveness of treatment.

Liao et al.31 found the amount of swelling did not correlate with the percent of reduction, although an earlier study by Ramos et al.32 had found a correlation.
Yamamoto et al.,33 Liao et al.,34 and Vignes et al.35 all found although the duration of the lymphedema correlated with more swelling, it did not affect the amount of reduction in treatment.

Liao et al.36 and Yamamoto et al.37 also both found the length of treatment/number of sessions was not correlated with amount of reduction. Yamamoto et al.38 also found the maximum reduction (about a 50% decrease in swelling) was generally achieved in the first few days, after which the rate of reduction began to taper off.

Discussion
There was a clear and definite trend indicating CDT, even watered down, led to improvements in the patients’ otherwise progressive condition. There was evidence the results were possible to maintain if patients adhered to their home program.

It was still not clear how much of a role each component of CDT plays in the outcome and how the interaction among the components affects the outcome.

Among the areas needing more research are the following:

  1. What is the most effective home program for patients to maintain/improve their results and what are ways to optimize patients’ ability to adhere to this?
  2. What are the effects of BMI, co-morbidities, onset/duration, and other factors on the effectiveness of treatment?
  3. What are the effects of CDT on improved function and QOL and how can these been further enhanced?
  4. What are effective ways to assess and treat genital, facial, truncal and breast lymphedema? (There was a real dearth of material on this!)
  5. What is the evidence for the current risk reduction strategies in helping people keep their lymphedema under control?
  6. What are effective ways to address issues such as radiation fibrosis?
  7. Is there an optimum CDT protocol?

Conclusion
Based on clinical observations CDT is considered the gold standard in treatment and management of lymphedema, but more research with more uniform standards of measurements need to be conducted. This includes RCTs with control groups, blinded assessors, objective measurements of volume, function and/or mobility, larger group sizes with longer follow-up periods, more consistent protocols, with more standard dosing of CDT components. The authors felt a more universal definition of lymphedema also needs to be established.

The authors recognized with the various etiologies of lymphedema (primary and secondary) and with the varying protocols of treatment, it is difficult to state with absolute certainty the effectiveness of each component of CDT. What is recognized, universally among therapists, is CDT, the most effective tool available to clinicians for the treatment and management of lymphedema. The authors also acknowledge better and more comprehensive research is required to understand the varying aspects confounding the successful treatment of lymphedema. These include the effects of BMI, patient adherence during treatment and afterwards to maintain reduction achieved during therapy, co-morbidities, as well as a greater understanding of the lymphatic system and how alteration of it – whether due to birth abnormalities or trauma or surgical intervention -- can influence the transport capacity leading to lymphedema. While limb lymphedema can be successfully managed with CDT, special areas of concern for treatment including breast, truncal, genital, and facial edema which need to be addressed.

Until further research is conducted and analyzed, CDT remains the best option not only for the physical needs, but also for quality of life issues for patients with lymphedema.

REFERENCES:

  1. Devoogdt N, Van Kampen M, Geraerts I, Coremans T, Christiaens MR.Different physical treatment modalities for lymphoedema developing after axillary lymph node dissection for breast cancer: A review. Eur J Obstet Gynecol Reprod Biol 2009;149:3-9.
  2. Leal NF, Carrara HH, Vieira KF, Ferreira CH. Physiotherapy treatments for breast cancer-related lymphedema: A literature review. Rev Lat Am Enfermagem 2009;17:730-736.
  3. Karadibak D, Ufuk YS, Serdar S, Zumre A. The comparison of two different physiotherapy methods in treatment of lymphedema after breast surgery. Breast Cancer Res Treat 2005;93:49-54.
  4. Williams AF, Vadgama A, Franks PJ, Mortimer PS. A randomized controlled crossover study of manual lymphatic drainage therapy in women with breast cancer-related lymphoedema. Eur J Cancer Care 2002;11:254-261.
  5. Andersen L, Hojris I, Erlandsen M, Andersen J. Treatment of breast cancer-related lymphedema with or without manual lymphaticdrainage: A randomized study. Acta Oncol 2000;39:399-405.
  6. McNeely ML, Magee DJ, Lees AW, Bagnall KM, Haykowsky M, Hanson J. The addition of manual lymph drainage to compression therapy for breast cancer related lymphedema: A randomized controlled trial. Breast Cancer Res Treat 2004;86:95 106.
  7. Jeffs E. Treating breast cancer-related lymphoedema at the London Haven: Clinical audit results. Eur J Oncol Nurs 2006;10:71 79.
  8. Yamamoto R, Yamamoto T. Effectiveness of the treatment-phase of two-phase complex decongestive physiotherapy for the treatment of extremity lymphedema. Int J Clin Oncol 2007;12:463-468.
  9. McNeely ML, Magee DJ, Lees AW, Bagnall KM, Haykowsky M, Hanson J. The addition of manual lymph drainage to compression therapy for breast cancer related lymphedema: A randomized controlled trial. Breast Cancer Res Treat 2004;86:95-106.
  10. Kim S, Park Y. Effects of complex decongestive physiotherapy on the oedema and the quality of life of lower unilateral lymphoedema following treatment for gynecological cancer. Eur J Cancer Care 2008;17:463-468.
  11. Vignes S, Porcher R, Champagne A, Dupuy A. Predictive factors of response to intensive decongestive physiotherapy in upper limb lymphedema after breast cancer treatment: A cohort study. Breast Cancer Res Treat 2006;98:1-6.                                                                                                             
  12. Pinell XA, Kirkpatrick SH, Hawkins K, Mondry TE, Johnstone PA. Manipulative therapy of secondary lymphedema in the presence of locoregional tumors. Cancer 2008;112:950-954.
  13. Johnstone PA, Hawkins K, Hood S. Role of patient adherence in maintenance of results after manipulative therapy for lymphedema. J
    Soc Integrat Oncol 2006;4:125-129.
  14. Kim SJ, Yi CH, Kwon OY. Effect of complex decongestive therapy on edema and the quality of life in breast cancer patients with unilateral
    lymphedema. Lymphology 2007;40:143-151.
  15. Mondry TE, Riffenburgh RH, Johnstone PAS. Prospective trial of complete decongestive therapy for upper extremity lymphedema after
    breast cancer therapy. Cancer J 2004;10:42-48.
  16. Vignes S, Porcher R, Arrault M, Dupuy A. Long-term management of breast cancer-related lymphedema after intensive decongestive physiotherapy.
    Breast Cancer Res Treat 2007;101:285-290.
  17. Boris M, Weindorf S, Lasinski B. Persistence of lymphedema reduction after noninvasive complex lymphedema therapy. Oncology (Williston
    Park) 1997;11:99-109.
  18. Ko DSC, Lerner R, Klose G, Cosimi AB. Effective treatment of lymphedema of the extremities. Arch Surg 1998;133:452-458.
  19. Williams AF, Vadgama A, Franks PJ, Mortimer PS. A randomized controlled crossover study of manual lymphatic drainage therapy in
    women with breast cancer-related lymphoedema. Eur J Cancer Care 2002;11:254-261.
  20. Kim SJ, Yi CH, Kwon OY. Effect of complex decongestive therapy on edema and the quality of life in breast cancer patients with unilateral
    lymphedema. Lymphology 2007;40:143-151.
  21. Mondry TE, Riffenburgh RH, Johnstone PAS. Prospective trial of complete decongestive therapy for upper extremity lymphedema after
    breast cancer therapy. Cancer J 2004;10:42-48.
  22. Badger CM, Peacock JL, Mortimer PS. A randomized, controlled, parallel-group clinical trial comparing multilayer bandaging followed by hosiery versus hosiery alone in the treatment of patients with lymphedema of the limb. Cancer 2000;88:2832-2837.
  23. Damstra RJ, Partsch H. Compression therapy in breast cancer-related lymphedema: A randomized, controlled comparative study of relation
    between volume and interface pressure changes. J Vasc Surg 2009;49: 1256-1263.
  24. Damstra RJ, Brouwer ER, Partsch H. Controlled, comparative study of relation between volume changes and interface pressure under short stretch bandages in leg lymphedema patients. Dermatol Surg 2008;34:773-779.
  25. Partsch H, Flour M, Smith PC. Indications for compression therapy in venous and lymphatic disease consensus based on experimental data and scientific evidence. Under the auspices of the IUP. Int Angiol 2008;27:193-219.
  26. Shrubb D, Mason W. The management of deep vein thrombosis in lymphoedema: A review. Br J Community Nurs 2006;11:292-297.
  27. Pinell XA, Kirkpatrick SH, Hawkins K, Mondry TE, Johnstone PA. Manipulative therapy of secondary lymphedema in the presence of locoregional tumors. Cancer 2008;112:950-954.
  28. Yamamoto R, Yamamoto T. Effectiveness of the treatment-phase of two-phase complex decongestive physiotherapy for the treatment of extremity lymphedema. Int J Clin Oncol 2007;12:463-468.
  29. Liao SF, Huang MS, Li SH, et al. Complex decongestive physiotherapy for patients with chronic cancer-associated lymphedema. J Formos Med Assoc 2004;103:344-348.
  30. Vignes S, Porcher R, Champagne A, Dupuy A. Predictive factors of response to intensive decongestive physiotherapy in upper limb lymphedema after breast cancer treatment: A cohort study. Breast Cancer Res Treat 2006;98:1-6.
  31. Liao SF, Huang MS, Li SH, et al. Complex decongestive physiotherapy for patients with chronic cancer-associated lymphedema. J Formos Med Assoc 2004;103:344-348.
  32. Ramos SM, O’Donnell LS, Knight G. Edema volume, not timing, is the key to success in lymphedema treatment: Evolution of the complex decongestive techniques. Am J Surg 1999;178:311-315.
  33. Yamamoto R, Yamamoto T. Effectiveness of the treatment-phase of two-phase complex decongestive physiotherapy for the treatment of extremity lymphedema. Int J Clin Oncol 2007;12:463-468.
  34. Liao SF, Huang MS, Li SH, et al. Complex decongestive physiotherapy for patients with chronic cancer-associated lymphedema. J Formos Med Assoc 2004;103:344-348.
  35. Vignes S, Porcher R, Champagne A, Dupuy A. Predictive factors of response to intensive decongestive physiotherapy in upper limb lymphedema after breast cancer treatment: A cohort study. Breast Cancer Res Treat 2006;98:1-6.
  36. Liao SF, Huang MS, Li SH, et al. Complex decongestive physiotherapy for patients with chronic cancer-associated lymphedema. J Formos Med Assoc 2004;103:344-348.
  37. Yamamoto T, Todo Y, Kaneuchi M, Handa Y, Watanabe K, Yamamoto R. Study of edema reduction patterns during the treatment phase of complex decongestive physiotherapy for extremity lymphedema. Lymphology 2008;41:80-86.
  38. Yamamoto T, Todo Y, Kaneuchi M, Handa Y, Watanabe K, Yamamoto R. Study of edema reduction patterns during the treatment phase of complex decongestive physiotherapy for extremity lymphedema. Lymphology 2008;41:80-86.

 


Exercise in Patients with Lymphedema: Evidence from the Contemporary Literature and How to Apply the Evidence Today (Vol 25, No 2, 2013)

By: Joy C. Cohn, PT, CLT- LANA, Penn Therapy and Fitness, Good Shepherd Penn Partners, Philadelphia, PA
Marilyn L. Kwan, PhD, Division of Research, Kaiser Permanente, Oakland, CA

Introduction
The American Medical Association has teamed with the American College of Sports Medicine (ACSM) for an initiative called “Exercise is Medicine”.1 One of the primary recommendations of this initiative is that 150 min of physical activity each week is important to gain health benefits for all individuals. But for many individuals with lymphedema, this recommendation is difficult to understand and follow due to lack of information about whether exercise is safe for those diagnosed with or at risk for this condition. In addition, some of the common co-morbidities associated with lymphedema, for example, obesity and diabetes, are also conditions for which exercise is an important component of managing the condition. For cancer patients, the majority of whom are at lifetime risk for/or have lymphedema, there is a growing body of literature to encourage exercise throughout their treatment and subsequent survivorship. Due to all of these issues, the question of whether exercise is safe is important.


The International Lymphoedema Framework (ILF) published a Best Practice document in 2006 based upon a review of the literature through 2004. This document and subsequent publications have been written to provide guidance for the management of lymphedema patients and for individuals at risk. The American Lymphedema Framework Project (ALFP), established in the United States in 2008, was subsequently charged to continue the systematic review of the available medical evidence and collaborate with the ILF in updating the best practice documents. Groups of clinicians, researchers, and advocates with expertise in lymphedema were invited to participate in systematically reviewing the literature for publication on many topics related to lymphedema management. The systematic review of surgery in lymphedema was discussed in LymphLink in a previous issue (Vol. 24 No. 2, pp 3).2 A systematic review of the literature from 2004 to 2010 examining the evidence of exercise in individuals with lymphedema was completed and published in 2011.3

Publications with the appropriate search terms were retrieved from 11 major medical index databases.3 Articles were reviewed using inclusion criteria by lymphedema experts, yielding 35 articles for final inclusion as evidence related to exercise. Study evidence was classified using the ‘Putting Evidence into Practice’ (PEP) classification system described by the Oncology Nursing Society.4 Details of study design and objectives, number of participants, study outcomes, intervention used, results, and strengths and weaknesses were tabulated and presented for subsets grouped by the major type of exercise studied. The subsets were: Resistance Exercise, Combined Aerobic and Resistance Exercise, and Other. Please see the article for specific details of the PEP classification and tabulated details of each study.3

Resistance Exercise

There were seven studies representing 599 participants included for resistance (primarily weight lifting) exercise. The evidence from these studies were classified as ‘Likely to be Effective’ by the PEP criteria. The PAL Trial included in this series by Schmitz et al. represents the largest randomized clinical trial published to date with the longest follow-up at one year which evaluated progressive weight lifting in women with a unilateral breast cancer.5, 6 Half (n=141) of the women had a diagnosis of lymphedema and the other half (n=154) were at risk for lymphedema. A control group was identified for each arm of the study, and each group was asked to not change their exercise habits during the course of the study. The intervention groups were instructed in an exercise program including a warm-up, flexibility, core exercises and progressive weight lifting exercises for the upper and lower body. The women with a lymphedema diagnosis were fitted with a custom compression arm sleeve and glove to wear during the exercise sessions. The exercises were taught in a group setting in community fitness centers led by a trainer who had been educated about the intervention and how to monitor for lymphedema symptoms. This setting was chosen in anticipation of possible dissemination of the exercise regimen, if found effective and safe. The participants exercised twice per week for six months with supervision by the trainers.

The main outcome was a change in volume of the hand and arm at one year, with an absolute increase in volume of 5% in comparison of the affected and unaffected limbs. Other outcomes reported were lymphedema symptoms, muscle strength, and exacerbations of lymphedema. Any participant who reported a change in arm symptoms that lasted for more than one week (the definition of a potential exacerbation) was evaluated by a lymphedema therapist with treatment provided, if indicated. In this group of women with lymphedema who exercised, weight lifting did not increase the severity of their limb lymphedema. Instead, the exercise decreased the number and severity of reported symptoms; increased their strength; and reduced the number of exacerbations of lymphedema, as compared with the non-exercising control group.5

The PAL Trial also investigated the effects of the same exercise intervention in women at risk for lymphedema, and the results were even more striking.6 The exercise group did not have an increased risk in the onset of lymphedema: 11% (8/72) in the weight-lifting group as compared to 17% (13/75) in the control group experienced BCRL onset during the study period. (p=0.04). In a separate analysis, in the subgroup of women who had ≥5 lymph nodes removed, only 7% of the exercise group (3/45) versus 22% (11/49) of the control group experienced BCRL onset (p=0.003). The two reported arms of PAL Trial both demonstrate that weight lifting is a safe intervention in breast cancer survivors with or at risk for lymphedema.

The Weight Training for Breast Cancer Survivors trial looked at the effect of a weight training program in 45 breast cancer survivors at risk for lymphedema due to an axillary node dissection as part of their cancer treatment.7 Half of the women (23/45) met twice weekly over six months for resistance exercise. The other half (22/45) were asked to not change their exercise level during the study. Women in the study were not required to wear compression garments, but did so if previously given medical advice to do so. The results again demonstrated that there was no difference in arm circumferential measurements or reported symptoms of lymphedema.

Another large randomized clinical trial including 204 women with breast cancer and had axillary node dissection compared two programs of rehabilitation.8 One group was instructed to restrict their activities of daily living (ADLs) while the other group made no changes in their ADLs and lifted weights for increased strength. The “no restrictions group” participated in a clinic-based program of moderate resistance exercise 2-3 times/week for six months. The “restrictions group” was asked to restrict their ADLs by avoiding heavy or strenuous activities and participating in a ‘usual care’ physical therapy program once per week for the same six-month time frame which was not described further. Arm volumes increased over time in both groups in both at risk and unaffected limbs. There was no significant difference, however, in comparing arm volumes between the restrictions and no restrictions groups.

Several small studies investigated resistance exercise interventions using free weights or Theraband resistance bands.9-11 These studies also demonstrated no adverse effects related to lymphedema symptoms and significant improvements associated with resistance exercise in symptoms and strength. In one study with 19 participants who had lymphedema , the participants all followed an unsupervised exercise program of range of motion (ROM) and light resistance exercises, but one half of the participants wore a compression garment.11 In the group wearing a compression garment, significant decreases in measurements in the distal part of the arm at several timepoints were observed. In the non-compression group, a significant decrease was seen in the upper arm, but only at the initial measurement.

Combined Aerobic and Resistance Exercise

There were seven studies representing 318 participants that examined the effects of aerobic and resistance exercise.12-18 The studies reviewed were small in size with the exception of one RCT with 242 participants, or were literature reviews. The preponderance of evidence was classified as ‘Benefits balanced with harm.’

The Supervised Trial of Aerobic versus Resistance Training represented the largest study.19 It was conducted with 242 breast cancer patients in Canada during their adjuvant chemotherapy treatment. This was a multicenter RCT with participants assigned to one of three possible interventions: Usual Care (82/242), supervised weightlifting (82/242), or supervised aerobic exercise (78/242). The intervention continued throughout planned chemotherapy treatment. The primary outcomes of this study were quality of life, fatigue, depression, and anxiety. Lymphedema was reported as a secondary outcome and did not occur in any group studied during or post-intervention when assessed up to six months after chemotherapy.
The systematic reviews uniformly stated that there was no evidence to suggest that exercise was the cause of lymphedema in those at risk or caused an exacerbation in those studies including participants with primarily BCRL. One review included 38% of participants who had prostate cancer or other cancer20. A literature review of 218 articles to assess effective interventions in the treatment of lymphedema concurred in classifying combined exercise interventions as ‘Benefits balanced with harm’ using the PEP criteria.21

Other Exercise Interventions

This group of five studies that primarily studied standard post-operative physical therapy interventions included, but were not limited to, exercise in generally the immediate post-operative period.22-26 These studies were uniformly small, represented varied treatment programs that included but were not limited to exercise, had short follow up periods, and were not designed to assess lymphedema as the primary outcome. ROM of the shoulder girdle, pain, and function were the major study outcomes. One 2010 study examined lymphedema as the primary outcome, but the intervention included manual lymphatic drainage, scar mobilization, and exercise.26 The control group did have a higher reported incidence of lymphedema at one year follow-up.

Compression Garments During Exercise

It was noted that, other than the PAL Trial in women with diagnosed BRCL, none of the reviewed studies commented specifically on the necessity for compression garments during exercise. Some studies notes that if recommended, some participants wore compression during the studied interventions. Other studies did not mention compression usage. During treatment of lymphedema by complete decongestive therapy as described by the NLN in their Position Paper on treatment, remedial exercises are prescribed with compression on the limb to enhance the musculoskeletal pump leading to greater decongestion of the limb.27 The NLN Position Paper on exercise currently states that “most experts in the field of lymphedema advise the use of compression during vigorous exercise for people with a confirmed diagnosis of lymphedema”. The NLN Medical Advisory Committee (MAC) noted, as we did in this review, that the evidence is not available to definitively recommend compression during exercise. The MAC recommends compression class 1 garments (20-30 mmHg) at minimum for the upper extremity and noted that lower extremity or more severe lymphedema of any type would require higher levels of compression garments. They also recommend that compression garments should be fitted by trained individuals, and specifically in the upper extremity, should provide compression
to the hand as well as the arm.

Summary of the Systematic Review and Recommendations

The evidence in the more recent medical literature is strong regarding the safety of guided exercise in the breast cancer population without increasing the risk of developing or increasing lymphedema. However, most of the published studies are in the breast cancer population and therefore provide less guidance to individuals who are at risk for or have a diagnosis of lymphedema from other etiologies. A roundtable on exercise convened by the ACSM published exercise guidelines specifically for cancer survivors.28 The strongest recommendation of this panel is to “Avoid inactivity,” and this recommendation is made for all periods of cancer survivorship, beginning at diagnosis.

“Physical Activity” is the broader term used in the medical literature to describe any and all forms of movement that is the opposite of inactivity. Studies on physical activity and its benefits have been described for many illnesses/diseases, as well as for simply sedentary individuals. The study results apply to all of us and argue for incorporating exercise into our daily regimes, no matter what other conditions we might have. The exercise programs reported in this systematic review have several themes in common. They recommend a slow, progressive approach to increase repetitions and weight (or other forms of resistance), regular exercise sessions performed 2-3 times per week, and monitoring of increase in symptoms that might indicate the onset or increase in lymphedema. The PAL Trial, in particular, educated patients to not ignore any change in symptoms that lasted more than seven days.
The health benefits of physical activity are strongly associated with: coronary artery disease, diabetes, hypertension, colon cancer, mental health, bone health, strength, flexibility, endurance for daily activities, and obesity.29 A recent review of ‘exercise therapy’ states that, “It is now undeniable that sedentary lifestyles are one of the most significant public health problems of the 21st century.”30 As a society, we do less physical labor at work and home, we travel more often by car, and our entertainment consists of far more sedentary activities such as TV
and digital entertainment in all of its many forms!

Many individuals consider ‘exercise’ a complicated undertaking that requires equipment, a gym membership, or spandex shorts. At Penn Therapy and Fitness, our often-stated mantra is that ‘Asphalt is free.’ Beginning an exercise program by a simple walk each day, with the goal of increasing the time spent in uninterrupted walking to 30 minutes, five days per week over a month or two, meets the AMA/ACSM guideline of 150 minutes per week of physical activity. This is a goal that all individuals can meet, with medical guidance, if needed. With regards to lymphedema, seeking advice regarding treatment or a compression strategy is indicated if symptoms of achiness, heaviness, or an increase in swelling are experienced with exercise. Exercise, as part of an effective weight loss program, can assist in reducing lymphedema symptoms in individuals who are overweight. Occasionally, other simple forms of physical activity can be substituted for walking if necessary. Many exercise professionals, including therapists and trainers, can assist in developing a program individualized to your needs. Therefore, it is ultimately possible for every one of us, regardless of health status, to be physically active.

References Cited

  1. http://exerciseismedicine.org [accessed January 14, 2013].
  2. Schmitz KH: Exercise for Breast Cancer Survivors: Prevention, Treatment, and attenuation of Persistent Adverse Effects of Treatment….Including Lymphedema? LymphLink Vol 24(1) p.3-4,33.
  3. Kwan ML, Cohn JC, Armer JM, Stewart BR, Cormier JN: Exercise in patients with lymphedema: a systematic review of the contemporary literature. J Cancer Surviv 2011; 5: p320-336.
  4. Mitchell SA, Friese CR:ONS PEP (Putting Evidence into Practice) http://www.ons.org/Research/media/ons/docs/research/outcomes/weight-of-evidence-table.pdf accessed 1/14/13.
  5. Schmitz KH, Ahmed RL et al. Weight Lifting in women with breast-cancer-related lymphedema N Engl J Med 2009;361(7):664-73.
  6. Schmitz KH, Ahmed RL et al. Weight lifting in women at risk for breast-cancer-related lymphedema: A randomized trial. JAMA 2010;304(24):2699-705.
  7. Ahmed RL, Thomas W et al. Randomized controlled trial of weight training and lymphedema in breast cancer survivors. J Clin Oncol. 206;24(18):2765-72.
  8. Sagen A, Karesen R et al; Physical therapy for the affected limb and arm lymphedema after breast cancer surgery. A prospective, randomized trial with two years followup. Acta Oncol. 2009;48(8):1102-10.
  9. Kilbreath, S.L., K.M. Refshauge, J.M. Beith, L.C. Ward, J.M. Simpson,R.D. Hansen, Progressive resistance training and stretching following surgery for breast cancer: study protocol for a randomised controlled trial. BMC Cancer, 2006. 6: p. 273.
  10. Irdesel, J.,S. Kahraman Celiktas, Effectiveness of exercise and compression garments in the treatment of breast cancer related lymphedema. Turkiye Fiziksel Tip ve Rehabilitasyon Dergisi, 2007. 53(1): p. 16-21.
  11. Irdesel J, Kahraman Celiktas S. Effectiveness of exercise and compression garments in the treatment of breast cancer related lymphedema. Turkiye Fiziksel Tip ve Rehabilitasyon Dergisi. 2007;53(1):16-21.
  12. Courneya, K.S., R.J. Segal, J.R. Mackey, K. Gelmon, R.D. Reid, C.M. Friedenreich, et al., Effects of aerobic and resistance exercise in breast cancer patients receiving adjuvant chemotherapy: a multicenter randomized controlled trial. J Clin Oncol, 2007. 25(28): p. 4396-404.
  13. Bicego, D., K. Brown, M. Ruddick, D. Storey, C. Wong,S.R. Harris, Exercise for women with or at risk for breast cancer-related lymphedema. Phys Ther, 2006. 86(10): p. 1398-405.
  14. De Backer, I.C., G. Schep, F.J. Backx, G. Vreugdenhil,H. Kuipers, Resistance training in cancer survivors: a systematic review. Int J Sports Med, 2009. 30(10): p. 703-12.
  15. Poage, E., M. Singer, J. Armer, M. Poundall,M.J. Shellabarger, Demystifying lymphedema: development of the lymphedema putting evidence into practice card. Clin J Oncol Nurs, 2008. 12(6): p. 951-64.
  16. Hayes, S.C., H. Reul-Hirche,J. Turner, Exercise and secondary lymphedema: safety, potential benefits, and research issues. Med Sci Sports Exerc, 2009. 41(3): p. 483-9.
  17. Portela, A.L., C.L. Santaella, C.C. Gomez,A. Burch, Feasibility of an Exercise Program for Puerto Rican Women who are Breast Cancer Survivors. Rehabil Oncol, 2008. 26(2): p. 20-31.
  18. Cheema, B., C.A. Gaul, K. Lane,M.A. Fiatarone Singh, Progressive resistance training in breast cancer: a systematic review of clinical trials. Breast Cancer Res Treat, 2008. 109(1): p. 9-26.
  19. Courneya KS, Segal RJ et al. Effects of Aerobic and resistance exercise in breast cancer patients receiving adjuvant chemotherapy: a multicenter randomized controlled trial J Clin Oncol. 2007;25(28):4396-404.
  20. De Backer, I.C., G. Schep, F.J. Backx, G. Vreugdenhil,H. Kuipers, Resistance training in cancer survivors: a systematic review. Int J Sports Med, 2009. 30(10): p. 703-12.
  21. Poage, E., M. Singer, J. Armer, M. Poundall,M.J. Shellabarger, Demystifying lymphedema: development of the lymphedema putting evidence into practice card. Clin J Oncol Nurs, 2008. 12(6): p. 951-64.
  22. Kilgour, R.D., D.H. Jones,J.R. Keyserlingk, Effectiveness of a self-administered, home-based exercise rehabilitation program for women following a modified radical mastectomy and axillary node dissection: a preliminary study. Breast Cancer Res Treat, 2008. 109(2): p. 285-95.
  23. Moseley, A.L., N.B. Piller,C.J. Carati, The effect of gentle arm exercise and deep breathing on secondary arm lymphedema. Lymphology, 2005. 38(3): p. 136-45.
  24. Beurskens, C.H., C.J. van Uden, L.J. Strobbe, R.A. Oostendorp,T. Wobbes, The efficacy of physiotherapy upon shoulder function following axillary dissection in breast cancer, a randomized controlled study. BMC Cancer, 2007. 7: p. 166.
  25. de Rezende, L.F., R.L. Franco, M.F. de Rezende, P.O. Beletti, S.S. Morais,M.S. Gurgel, Two exercise schemes in postoperative breast cancer: comparison of effects on shoulder movement and lymphatic disturbance. Tumori, 2006. 92(1): p. 55-61.
  26. Torres Lacomba, M., M.J. Yuste Sanchez, A. Zapico Goni, D. Prieto Merino, O. Mayoral del Moral, E. Cerezo Tellez, et al., Effectiveness of early physiotherapy to prevent lymphoedema after surgery for breast cancer: randomised, single blinded, clinical trial. BMJ, 2010. 340: p. b5396.
  27. http://www.lymphnet.org/pdfDocs/nlntreatment.pdf [Accessed February 5, 2013].
  28. Schmitz KH, Courneya KS et al: American College of Sports Medicine Roundtable on Exercise Guidelines for Cancer Survivors Med Sci Sports Exerc 2010;42(7):1409-26.
  29. Brown WJ, Burton NW, Rowan PJ: Updating the Evidence on Physical Activity and Health in Women Am J Prev Med 2007;33(5) p. 404-411.
  30. Blair SN, Sallis RE, Hutber A, Archer E: Exercise therapy- the public health message Scand J Med Sci Sports 22:e24-e28.


Joy.Cohn@uphs.upenn.edu;
Marilyn.L.Kwan@lcp.org

 

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