Authors
- Jeffs, Eunice RGN, BSc, MSc, PGDipEd (Nurs)
- Bick, Debra RM, BA, MMedSci, PhD
Abstract
Review question/objective: The objective of this review is to identify the effectiveness of decongestive lymphedema treatment to reduce excess limb volume or improve patient-centered outcomes for women presenting within 12 months of developing a swollen arm due to breast cancer-related lymphedema.
More specifically, the objectives are to identify:
1) The most effective combination of treatment elements
2) The optimal duration of treatment.
Background: Lymphedema is a common sequelae of breast cancer treatment, affecting around 20% of women following axillary node dissection.1 Although lymphedema is more likely to develop within the first 24 months following axillary surgery,1 instances of lymphedema are also reported many years after the original surgery,2,3 for example, it is likely that of the 50,000 cases of breast cancer diagnosed in the UK in 2011,4 around 7000 women will already have developed arm swelling.
The physical and psycho-social consequences of breast cancer-related lymphedema (BCRL) affecting the ipsilateral arm and associated quadrant of the trunk are significant and wide ranging: increased size, altered appearance of arm, difficulty finding clothes to fit, heaviness, discomfort or pain in the affected arm,3,5 reduced upper body function,3,6 challenges with work,7-9 social and leisure activities,7,10 psychological distress and altered body image.7,11 Individuals may experience financial impacts regarding treatment, which could include traveling to appointments, time off work, and in some countries a requirement to personally pay for certain aspects of treatment;12 some women may even need to adjust their employment or find alternative work.8 The economic consequences on health service provision are likely to be significant, although there is limited evidence for health resource use. These costs may include provision of specialist and long-term lymphedema treatment, management of poorly controlled symptoms, or supportive social care when appropriate lymphedema treatment is not available.13-15
The internationally accepted gold standard treatment for lymphedema is generally considered to be complex decongestive therapy (CDT), also known as decongestive lymphedema treatment (DLT),16-20 which is a two-phase treatment program. The recommended first phase of treatment is an intensive therapist-led decongestive phase (I), designed to reduce size and extent of swelling, which is followed by a maintenance phase (II) where the patient undertakes daily self-management to retain treatment benefits long-term. A systematic review of the evidence for lymphedema treatment (2004-2010) undertaken by the American Lymphedema Framework Project concluded that there is evidence for the efficacy of CDT to treat varying degrees of lymphedema, whether recent onset or chronic, mild, moderate or severe; however, the level of evidence was only moderately strong due to the limited number of adequately controlled studies, variation in protocols for intervention and measurements, and limited follow-up period.18
A wide range of reported CDT/DLT protocols exist, which combine graduated compression, the usage of bandages or hosiery, manual lymph drainage (MLD), exercise and skin care, and may also include intermittent pneumatic compression (IPC) as an adjunct.16,18,19,21 Phase I decongestive treatment is generally applied five to seven days per week for three to eight weeks to arrest development and reverse the effects of chronic swelling. Reported benefits include reduced limb size, softened skin and subcutaneous tissues, reduction in recurrent infections, and improved quality of life and function.22
It is thought that early application of decongestive treatment in the months immediately following development of BCRL will significantly reduce lymphedema at the time when it is likely to be most responsive to treatment (before tissues changes become established), thus increasing the possibility of long-term successful management of BCRL. However, recent studies have questioned whether traditional CDT is more effective than self-care measures to reduce lymphedema of less than one year duration, although Hwang et al.25 concluded that early application of CDT prevents subsequent deterioration in lymphedema over time.23,24
Lymphedema management does not always follow the internationally recognized two-phase DLT program, largely due to financial challenges and limited availability of trained practitioners, and because hosiery does achieve some lymphedema reduction.26,27,28,29 For example, in Turkey, intensive phase I treatment is not available through the national health service and patients must individually pay for this aspect of treatment. In the UK, most women presenting with mild-moderate BCRL are taught self-care measures and given compression hosiery which represents phase II maintenance treatment, with the intensive decongestive phase reserved for the more severe cases and those who have access to private health care.12,15,19,30 However, women who present with mild swelling are at risk of developing moderate to severe swelling with associated increased healthcare costs, and there is a high risk that self-care measures alone will cause the lymphedema to worsen, resulting in thickened skin and subcutaneous tissues, increasing the complexity of swelling and reducing the effectiveness of treatment.3,17
Despite recent advances in breast cancer treatment, BCRL continues to be a problem for many women. Treatment for BCRL is required life-long and the lymphedema caseload increases year-on-year causing greater pressure on finite health care resources. Early and effective treatment will lessen the impact of BCRL and its treatment for the individual, prevent long-term complications, and reduce the need for long-term specialist treatment. More effective treatment could enable quicker discharge from specialist services, less complex lymphedema could require less expensive compression garments and associated specialist treatments, and the risk of infection and associated costs of treatment could be lowered. With more effective treatment it may be possible for those with mild lymphedema to return to the latent phase, that is, with no visible or palpable lymphedema. In short, the long-term cost of managing BCRL could be lessened by reducing the size and complexity of the lymphedema caseload.
This review seeks to establish the best available evidence for treatment to decongest BCRL of the upper limb in women. Although there have been recent systematic reviews addressing individual treatment modalities applied to BCRL,31-35 the most recent systematic review specifically addressing the management of breast cancer-related lymphedema was published in 2010.36 There are gaps in knowledge and further studies have been published in the intervening years. No review has addressed the impact of the duration of lymphedema on treatment outcome. The optimal decongestive lymphedema treatment package is still not known: protocols include variations in the elements of treatment, particularly with respect to whether compression should be applied through bandaging, hosiery, or intermittent pneumatic compression pump. The optimal duration of treatment is unknown, although a recent study,37 reported programs vary in length from two to eight weeks, and recommended that the program should not be shorter than two weeks. The optimal time for the intensive phase of decongestive treatment is unknown, with apparently conflicting evidence from recently published studies.23,24
This systematic review will focus on the evidence for the effectiveness of decongestive lymphedema treatment for the early management of BCRL within 12 months of the development of lymphedema symptoms. The findings will be used to inform effective management of BCRL, particularly for women newly presenting with arm swelling.
Article Content
Inclusion criteria
Types of participants
This review will consider studies that include women with unilateral breast cancer-related lymphedema (BCRL) of the arm, who have received lymphedema treatment within 12 months of developing arm swelling.
As many studies have included participants with chronic swelling, this review will consider studies where the average duration of swelling is no more than nine months. It is believed that this will maximize the inclusion of relevant studies while limiting the number of participants with chronic lymphedema (i.e. > 12 months duration).
Studies which include participants with other forms of lymphedema (e.g. leg lymphedema) will be included only where data is separately reported for BCRL of the arm.
Studies which include truncal/breast lymphedema, bilateral lymphedema, individuals who are "at risk" of developing BCRL or receiving concurrent cancer treatment will be excluded from the review.
Types of intervention(s)
This review will consider studies that evaluate any decongestive lymphedema treatment delivered with the purpose of reducing arm lymphedema, within 12 months of development of arm swelling, whether as lymphedema therapist-treatment or patient self-management. This will include, but not be limited to, the combination of treatments known as Decongestive Lymphedema Treatment (DLT) or Complete/Complex Decongestive Treatment (CDT); compression therapy, whether bandaging, garments or pneumatic compression pump; exercise, such as resistance training, hydrotherapy; low level laser therapy; manual lymph drainage or lymphatic massage.
The review will be as inclusive as possible. Relevant experimental studies may compare outcomes to another form of lymphedema treatment (whether patient or lymphedema therapist administered), or to placebo or to no treatment.
However, studies relating to prevention of BCRL, describing the lymphedema population and lymphedema treatment given, surgical or drug therapy interventions, treatment of progressive lymphedema due to uncontrolled active cancer, safety assessment, evaluation of a single session of treatment (such as compression bandaging or hosiery, manual lymph drainage or exercise), or comparative assessment techniques will be excluded from the review.
Types of outcomes
This review will consider studies that include the following clinical or patient-centered outcome measures:
Clinical outcome of interest is the change in excess limb volume. Studies will be sought which expressed the outcome as a relative change in excess limb volume as compared to the non-swollen limb, and may be measured by perometry, water displacement or circumference measurements to calculate limb volume. In the absence of relative change in excess limb volume, the relative change in tissue fluid as measured by bioimpedance or tissue dieletric constant will be considered.
Patient-centered outcomes of interest are: health-related quality of life, sensation of heaviness in the swollen arm, limb function, patient-perceived benefit or satisfaction with treatment. Studies which used an appropriate validated assessment tool will be sought; in the absence of a validated tool, studies which used a visual analogue scale will be considered.
Studies which do not report on the relative change to arm size/tissue fluid volume, or psychosocial or patient self-report outcome measure or patient value of treatment will be excluded from the review.
Studies with limb size monitored only by circumference measures without calculating excess limb volume, or reporting absolute volume of only the affected arm, would be included only if a patient-centered outcome was also reported.
A request for clarification of data will be sent to the corresponding author of any study, published in the past 10 years (2004-2014), with insufficient detail regarding the outcome(s) of interest to determine eligibility for the review; it is assumed that authors of studies published prior to 2004 will no longer have access to the original study data, and therefore these studies will be excluded.
Types of studies
This review will consider experimental study designs including randomized controlled trials, non-randomized controlled trials, quasi-experimental, and before and after studies for inclusion.
Search strategy
The search strategy aims to find both published and unpublished studies. All databases will be searched from inception to current date (31 December 2014) using a three-step search strategy. An initial limited search of MEDLINE and CINAHL will be undertaken followed by an analysis of the text words contained in the title and abstract, and of the index terms used to describe article. A second search using all identified keywords and index terms will then be undertaken across all included databases. Thirdly, the reference list of all identified reports and articles will be searched for additional studies. Studies published in any language will be considered for inclusion in this review.
A request for clarification of data will be sent to the corresponding author of any study, published in the past 10 years (2004-2014), with insufficient detail regarding the population of interest to determine eligibility for the review; it is assumed that authors of studies published prior to 2004 will no longer have access to the original study data, and therefore these studies will be excluded. The databases to be searched include:
Allied and Contemporary Medicine (AMED)
Biomed Central
BIOSIS
British Nursing Index
CINAHL
Cochrane Library
Embase
HMIC
Medline (Ovid)
Physiotherapy Evidence database (PEDro)
PsycARTICLES
PsycINFO
PubMed
Scopus
Turning Research into Practice (TRIP)
Web of Science
WorldCat
Four specialist journals will be hand-searched: Lymphology, Journal of Lymphoedema, European Journal of Lymphology, Journal of Phlebology and Lymphology.
The search for unpublished studies will include:
Centre for Reviews & Dissemination (CRD) and PROSPERO
UK Clinical Research Network (UKCRN), ClinicalTrials.gov (USA), Controlled Trials Register, and International Clinical Trials Registry Platform (ICTRP)Conference proceedings citations index (Web of Science), WorldCat ArticleFirst, WorldCat PapersFirst, WorldCat ProceedingsFirst (OCLC)
Evidence NHS UK (NICE)
Grey Literature Report: http://www.greylit.org/ and http://www.opengrey.eu
HTA website
National Guideline Clearing House (USA)
WorldCat Dissertations.
Initial keywords to be used will be:
lymph*edema, breast cancer, breast carcinoma, breast tumo*r, breast malignancy, breast neoplasm, mastectomy, review.
These terms will be combined as follows:
1. lymphoedema OR lymphedema OR lymphoedemas or lymphedemas - in title, abstract, subject heading or keyword
2. breast AND (cancer OR carcinoma OR tumour OR tumor OR malignancy OR neoplasm OR mastectomy) - in title, abstract, subject heading or keyword
3. 1 AND 2
4. (lymphoedema OR lymphedema OR lymphoedemas or lymphedemas) AND 'review', in the title only
5. 3 OR 4.
Assessment of methodological quality
Papers selected for retrieval will be assessed by two independent reviewers for methodological validity prior to inclusion in the review using standardized critical appraisal instruments from the Joanna Briggs Institute Meta Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI) (Appendix I ). Any disagreements that arise between the reviewers will be resolved through discussion, or with a third reviewer.
Data collection
Data will be extracted from papers included in the review using the standardized data extraction tool from JBI-MAStARI (Appendix II ). The data extracted will include specific details about the interventions, populations, study methods and outcomes of significance to the review question and specific objectives.
Data synthesis
Quantitative data will, where possible be pooled in statistical meta-analysis using JBI-MAStARI. All results will be subject to double data entry. Effect sizes expressed as odds ratio (for categorical data) and weighted mean differences (for continuous data) and their 95% confidence intervals will be calculated for analysis. Heterogeneity will be assessed statistically using the standard Chi-square and also explored using subgroup analyses based on the different study designs included in this review. Where statistical pooling is not possible the findings will be presented in narrative form including tables and figures to aid in data presentation where appropriate.
Two subgroup comparisons will be made on available data:
1. Previous lymphedema treatment, yes or no
2. Severity of swelling, whether mild or moderate-severe, where reported and as defined within the study.
Conflicts of interest
There are no conflicts of interest.
Acknowledgements
This protocol is part of independent research supported by the National Institute for Health Research (NIHR/HEE Clinical Doctoral Research Fellowship, Ms Eunice Jeffs, CDRF-2013-04-023). The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health.
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Appendix I: Appraisal instruments
MAStARI appraisal instrument[Context Link]
Appendix II: Data extraction instruments
MAStARI data extraction instrument[Context Link]
Keywords: Lymphoedema; breast cancer; decongestive lymphoedema treatment (DLT)